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Innominato - Std Ed |
A Classic Gothic Horror Triumph - Rediscovered! Standard Edition and Limited Edition Hardback (here) Free Sample Chapter 1 - Dr Onofrio "With Innominato, Oleander Press has unearthed a little-known gothic masterpiece." - Full Review
"I don't believe it possible for any man to be endowed with knowledge such as he is reported to have, without trafficking in the powers of darkness; and I have more than once heard that the Innominato is strongly suspected of sorcery..." Touring Europe in the 1840s the author, on reaching this small and breathtakingly beautiful corner of Italy, was intrigued by rumours of the ghost of an ancient sorcerer in the locale of a huge ruined castle. Fortuitously coming across a dead monk's collection of local lore surrounding this figure, he preserved and now presents them for your stimulation. An array of spellbinding tales from a noted author at the height of his powers, this collection marks the eventual return of a lost classic to the ranks of Victorian horror and dark fiction. Compelling Gothic themes, exotic environs and engrossing plots are populated by a range of both pure and evil characters: decaying vampires, beautiful virgins, sinister phantoms, marauding bandits... These and more await in this collection of deliciously ghoulish and macabre stories as well as the Innominato himself: known to have made himself much beloved and yet also a man 'much dreaded for his sanguinary propensities.' Good or Evil? You decide... The author William Gilbert (1804-90), the father of W.S. Gilbert of Gilbert and Sullivan fame, became a well-known and much-respected writer after a career as a naval surgeon. A noted author of various novels and biographies, he also produced short stories for a range of magazines including Argosy. Some of these, all concerning the enigmatic wizard and astrologer, the Innominato, were collected and published in the volume The Wizard of the Mountain in 1867 now incredibly rare. These stories are now collected and reproduced in Oleander's edition Innominato - The Wizard of the Mountain and are once again available to enjoy. |


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side dishes
(3 Recipes) Created by LISASTECINA
Recipes in this Collection
These are great served as a side dish with any meal. Submitted by KEVINKELLY Carbs: 25.1g | Fat: 9.8g | Fiber: 2.7g | Protein: 3.7g | Calories: 200.2
Fresh and juicy during spring and summer months, strawberries are delicious when combined with tender spinach and crunchy toasted almonds. Submitted by CHEF_MEG Carbs: 6.3g | Fat: 15.1g | Fiber: 2.3g | Protein: 2.7g | Calories: 162.2
A low-fat, heart healthy version of this traditional comfort food. Carbs: 11.2g | Fat: 5.9g | Fiber: 2.2g | Protein: 4.2g | Calories: 111.3

subset: commoncrawl


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Former Olympian Bill Rodgers looking forward to scenic Dexter-Ann Arbor Run
Former Olympic marathoner Bill Rodgers took his second-ever run in Ann Arbor Friday morning, a "light" six-mile jog through the city's's neighborhoods, across the University of Michigan campus and along the Huron River.
Pete Cunningham | AnnArbor.com
Rodgers enjoyed the variety along the scenic route, marveling at the vastness of the campus and beauty of the riverside. It's something the 64-year-old Rodgers, who has won the Boston and New York City marathons four times apiece, hasn't always been able to do.
When he runs in the 10K portion of the 39th annual Dexter-Ann Arbor Run, his plans are again to enjoy himself, even if he's not near the front.
"When you get to be an older runner, you look for that a little bit more, stop to smell the roses," Rodgers said. "It's not like when I was 28 years old and I would be coming here to win it."
Rodgers has won plenty of races in his life -- including marathons on five different continents during his prime in the 1970s and 80s -- and was a member of the 1976 U.S. Olympic team. His status in Sunday's run isn't as one of the top contenders, though. He's the celebrity runner.
Rodgers has run in Ann Arbor once before, five years ago as a celebrity runner in a 5K, which included a route along Nichols Arboreteum.
"It's a great place to run," said Rodgers, who checked out the course for Sunday's run on Friday. "(Sunday's race) should be fun, it seemed like a really neat, scenic route."
Rodgers' celebrity runner duties included signing autographs at Running Fit in Ann Arbor off of Jackson Avenue on Friday. He'll speak to children before Saturday's "Kid's Run" at Pioneer High School and run on Sunday with the USATF 10K Masters Championship racers.
His talk at Pioneer will be part of Saturday's Race Expo, where several fitness organizations will have booths and give presentations. Saturday also will be the final chance for late registration as race-day sign-ups are not allowed.
Last year, Rodgers' former racing rival Frank Shorter, who won Olympic gold in the 1972 Games in Munich, was the race's celebrity runner. Though they competed fiercely on the track, Rodgers said he and Shorter remain good friends to this day.
It's an aspect of the sport he loves to observe at events like the Dexter-Ann Arbor Run.
"It's that kind of sport, where everyone seems to get along," Rodgers said. "And everyone's talking about obesity, diabetes and all that. Sunday you'll see the other side, how huge this sport is and it's the ultimate fitness sport.
"It's got something for everyone."
Contact Pete Cunningham at email@example.com or by phone at 734-623-2561. Follow him on Twitter @petcunningham.


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While the World Bank is confident about the region's fiscal health, it warns about the need to implement social reforms.
Billionaire Bidzina Ivanishvili aims to breathe fire into the country's ho-hum economy despite political challenges.
Analysts estimate significant petroleum discoveries in 2013, which could serve as the nation's much-needed economic lifeline.
The government is putting a spotlight on economic recovery efforts despite public uproar over the recent EU-backed election.
Two decades of steady growth has been put at risk by a brewing civil war that analysts say could keep financiers at bay.
Two major pipeline consortiums competing to export Azerbaijan gas to insatiable European markets will find out their fate by June 30.
The USD is gradually losing its magic as countries across the continent turn to the Chinese currency to beef up their forex reserves.
Financial aids to domestic energy consumption are doing more harm than good to the region, according to a recent global report.
Mohammad Morsi's government is running low on options as the country continues to succumb to a worsening economic climate.
The oil-rich country remains buoyant, but analysts express concern that unresolved partisan strife could dampen fiscal growth.


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Truro City suffer humbling eight-nil defeat away at Maidenhead United
5:28pm Saturday 8th September 2012 in Sport
Truro City's week took another bad turn on Saturday as they suffered a humbling 8-0 loss away at Maidenhead United.
Truro, who went into administration on Tuesday, began the day at the foot of the Conference South table on minus two points.
Truro City clipped the crossbar early on, but Reece Tison-Lascaris made it 1-0 as he shot into the bottom corner from Daniel Brown's pass.
Tison-Lascaris then added two further goals at the start of the second half before strikes from Alex Wall and Paul Sem put Maindehead firmly in control.
Bobby Behzadi added a sixth from the penalty spot, before Wall scored again to make it 7-0.
The embarrassing scoreline was completed late on as Lee Barny fired home.
Speaking after the defeat, Truro City boss Lee Hodges, said:
"It was the proverbial game of two halves. The boys had done fantastically well at the start of the season and they could really have done with a break, or at least to have some fresh faces available to come on, but of course we haven't got any.
"They have given it their all, but after the first half at Maidenhead (1-0 at half-time) they just weren't at the races. I think everything caught up with them and their minds were elsewhere, which was disappointing.
"I said to the lads afterwards that if it does turn out to be the last game for some of them it will have been a very disappointing way to sign off.
"I think we will still have some of the first team players available for Saturday, and as I say it is really important now to get as many people as possible in to see that match."
Truro City: Tim Sandercombe; Dan Green, Ben Williams, Jake Ash, Ian Hodges, Cody Cooke, Adam Kelly, Joe Broad, Stewart Yetton, Keiffer Moore, Les Afful. Subs (all used): Andy Watkins, Hall, Danny Carne.


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Some liquids such as water can cause bacteria in wood - made for alcohol use only. We will send instructions on how to keep the keg cured, as well as, the care and cleaning of wood barrels. . Your Big Dawg will be the envy of the neighborhood, lake or beach! And it would look great on any large dog in a Christmas, 4th of July or Memorial Day Parade. This barrel looks great on a Great Pyrenees, Newfoundland, Greater Swiss Mountain, Labrador, Mastiff, Bernese Mountain, Akita, Great Dane, Bull Dog, Retriever, Swissy or any large dog. Our custom leather straps and kegs are a labor of love and we think the buyer will be very pleased with this barrel. It could become a treasured family heirloom. And not to be moroffer, but it can also be used to hold the ashes of your Gentle Giant after he or she passes on to Doggie Heaven. Free Shipping if within the contiguous United States via USPS Priority 2 Day Mail. International buyers are welcome if they are able to pay via Paypal in US dollars. International shipping fee is $42.50 and DOES NOT include custom fees or duties. In most cases, there are no custom fees, but in case they are it will be the sole responsibility of the
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The Undergraduate Medicine Office is responsible for providing invaluable service of work experience to college students who are thinking of pursuing a career in healthcare.
Work Experience and Work Shadowing placements fully booked for 2013. Due to the high volume of application forms already received for both work experience and work shadowing, we are now fully booked for 2013. Please note that we will not acknowledge or process any application submitted on or after the 24th January 2013. If you are thinking of applying to the University to study any course relating to Radiography (X-Ray) and Neuro-physiology, please send in your application form. Please note we are unable to guarantee placement. Please visit this page for regular update on availability.
All students interested in applying for work experience in the Trust must complete both the Work Experience Application Form and the Work Experience Health Screening Form.
The Introduction to the NHS 2013 Please note that this course has now closed and no more applications will be accepted.
UMO opening hours For work experience: Please contact Gold Mendel-Idowu between the hours of 0900 – 1430, Tuesday – Thursday. Useful Documents Useful Information for work experience students:
Useful Links Careers in the NHS:
Careers Advice in Medicine and Nursing:
Royal Society of Medicine
Health Learning and Skills Advice
Key Routes to Society, Health and Development


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Stylewars: Grand Finale: 28 Stairs
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Take a look at the Grand Finale of Stylewars as the annual 28 Stairs comp goes on under the lights.
Stylewars draws to a close as snowboarders take on the annual 28 Stairs competition under lights, and Mark McMorris is crowned new Stylewars Stairmaster. Best Trick goes to Seb Toots (Switch Hardway 270 Boardslide) and Best Aussie Rider is Jye Kearney from NSW.
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The requirement for the annual submission of the Professional Activity Report was abolished by faculty legislation March 29, 2011.
Faculty members are still required to file an updated CV each year. Please submit CV to email@example.com as an email attachment in MSWord or as a .pdf.
If you have recieved a grant, fellowship, or other notable honor, please submit the "Faculty Awards and Honors" form. If you have recently published a book/article or had an artistic production presented/shown, please submit the "Faculty Publications and Artistic Productions " form. Books and articles must be already published, not pending.


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- GLUTEN FREE specialties can be order by items marked with an " * " next to the price. If gluten free items are desired, please indicate this in the Special Instructions field.
- Feel free to write special instructions before placing your order.
We look forward to hearing from you, and will contact you to confirm your order.
Thank you!
Chef Paolo


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Florida State / School of Theatre / Alumni / Alumni News
Alumni News
On Broadway
Two-time Tony Award winning Producer Darren Bagert (c/o 1992) is a Producer behind the recent Broadway revival of Gore Vidal's The Best Man which received a Tony nomination for Best Revival of a Play. Darren has served as Producer for a number of Broadway hits and revivals including The Gershwins' Porgy and Bess, Bonnie and Clyde, Guys and Dolls,Company, Sweeney Todd, and Long Day's Journey Into Night.
Jessica Patty (c/o 2001) is currently performing in the Broadway musical revival of Evita. Prior to Evita, Jessica performed on Broadway in The Addams Family, 9 to 5, The People in the Picture, and A Chorus Line.
Music Theatre graduates Justin Bowen (c/o 2009) and Leslie Flesner (c/o 2008) can be seen in the new Broadway musical Chaplin, which opened on September 10, 2012 at the Ethel Barrymore Theatre. Leslie has performed on Broadway before in Finian's Rainbow and Follies.
Michael Fatica (c/o 2009) is currently performing in the Broadway hit Newsies.
Greg Mills (c/o 1997) is currently performing in the Phantom of the Opera on Broadway.
John Papsidera (c/o 1983) was the Casting Director for the summer blockbuster The Dark Knight Rises, which stars Christian Bale, Michael Caine, and Morgan Freeman. John has won two Emmy Awards for Outstanding Casting and has served as Casting Director on a number of Hollywood blockbusters including Batman Begins, The Prestige, The Dark Knight, Inception, and Enchanted. John is currently casting several new projects including Oz: The Great and Powerful, Gangster Squad, and White House Down.
John Brace (c/o 1984) is the Casting Director behind the hit television shows Grey's Anatomyand Private Practice. John's other credits as Casting Director include Friday Night Lights andPrime Suspect - just to name a few. John has won Emmy Awards for Casting for Grey's Anatomy and Friday Night Lights.
Megan Boone (c/o 2005) was recently seen in the feature film release Step Up Revolution. Megan has appeared in the films Sex and the City 2 and My Bloody Valentine 3D and had a recurring role in the NBC hit-show Law & Order: Los Angeles.
Marc Hester (c/o 1998) can currently be seen in the feature film Lawless and in the upcoming film release of Looper, which stars Joseph Gordon-Levitt and Bruce Willis. Marc is currently filming a new series for Cinemax called Banshee where he will be a recurring character.
Randy Ser (c/o 1975) is currently the Production Designer for ABC's hit-comedy, The Middle. Randy's other credits include Raising Hope, My Name is Earl, and Cinderella which earned him an Emmy Award for Outstanding Art Direction.
Eliza Kiss is co-starring as "Vivian" in the feature film Axeman at Cutter's Creek slated for release in February 2013.
Additional Updates
The School of Theatre currently has a number of alums in National Tours:
Harris Milgrim West Side Story
Max Chucker West Side Story
Andres Acosta West Side Story
Rachel Boone CATS
Amanda LaMotte CATS
Austin Owen Memphis
Johnny Machesko Fiddler on the Roof
Jennifer Swiderski Mama Mia
Susan Gearou Shrek
Annie Petersmeyer Mary Poppins
Joseph Spieldenner Les Miserables
Stephen Anthony Catch Me If You Can
Trevor Leaderbrand Catch Me If You Can
Mike Evariste The Book of Mormon
Hardy Weaver The Book of Mormon


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Family, Friends Search for Tik Yam Lam, Missing Since Nov. 13
Lam, who had recently moved to Philadelphia from New Jersey, hasn't been seen in more than six weeks.
With no access to a car and just the clothes on his back, Tik Yam Lam walked out of his Center City apartment a little more than six weeks ago and seemingly disappeared.
The Philadelphia resident may have been spotted twice since leaving his home Nov. 13, but his family and Philadelphia Police are still searching for the 72-year-old.
Friends of the family say there have only been a few hints at where Lam may have gone following his disappearance—they had a report of an elderly Asian man walking along the shoulder of a highway in the Lower Merion/Tredyffrin area on Nov. 14, more than 13 miles from Lam's apartment.
But a conflicting report from a driver on the Ben Franklin Bridge put an older Asian man walking across the bridge into New Jersey. Despite that, those searching for Lam say it's possible he could've gone in any direction, and given the stress he would've been under, may have been capable of pushing himself a great distance.
Complicating the situation: Lam has dementia and doesn't speak English.
Lam, who is described as about 5-foot-3 and 125 pounds by police, was wearing a flannel shirt and a vest when he left his apartment in November, and had only moved to Philadelphia from New Jersey a few months prior to his disappearance. He was carrying a New Jersey ID card with him when he left the apartment.
Those searching for Lam say they think he could be anywhere within a 150-mile radius of Philadelphia, and are asking anyone who has seen a man fitting Lam's description to contact Philadelphia Police at 215-686-3193.


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In JoVE (1)
Other Publications (22)
- Journal of Neurobiology
- In Vivo (Athens, Greece)
- Brain Research. Developmental Brain Research
- Journal of Veterinary Internal Medicine / American College of Veterinary Internal Medicine
- Cerebellum (London, England)
- Neurobiology of Disease
- Brain Research
- Cerebellum (London, England)
- Neurotoxicity Research
- Journal of Neurobiology
- Brain Research
- Brain Research
- Brain Research
- International Journal of Toxicology
- International Journal of Toxicology
- Toxicology Mechanisms and Methods
- Neurotoxicity Research
- Behavioural Brain Research
- International Journal of Toxicology
- Neurotoxicity Research
- Neuroscience Letters
- Frontiers in Neuroinformatics
Articles by Louise C. Abbott in JoVE
Specimen Preparation, Imaging, and Analysis Protocols for Knife-edge Scanning Microscopy
Yoonsuck Choe1, David Mayerich2, Jaerock Kwon3, Daniel E. Miller1, Chul Sung1, Ji Ryang Chung1, Todd Huffman4, John Keyser1, Louise C. Abbott5
1Department of Computer Science and Engineering, Texas A&M University, 2Beckman Institute for Advanced Science and Technology, University of Illinois, 3Department of Electrical and Computer Engineering, Kettering University, 43Scan, 5Department of Veterinary Integrative Biosciences, Texas A&M University
The full process from brain specimen preparation to serial sectioning imaging using the Knife-Edge Scanning Microscope, to data visualization and analysis is described. This technique is currently used to acquire mouse brain data, but it is applicable to other organs, other species.
Other articles by Louise C. Abbott on PubMed
Decreased Calretinin Expression in Cerebellar Granule Cells in the Leaner Mouse
Journal of Neurobiology. Jun, 2002 | Pubmed ID: 12150506
We investigated calretinin expression in cerebellar granule cells of 30-day-old leaner mice to understand possible changes in calcium homeostasis due to the calcium channel mutation that these mice carry. Quantitative in situ hybridization histochemistry showed decreased calretinin mRNA expression in the leaner cerebellum. Immunohistochemical staining also revealed decreased calretinin immunoreactivity in the leaner cerebellum. To exclude the effect of granule cell loss that occurs in the leaner mouse when comparing cerebellar calretinin expression, the number of granule cells per unit area in the cerebellum was compared to the wild-type cerebellum. Granule cell counts per unit area of cerebellum revealed similar numbers of granule cells present in wild-type and leaner mice. Laser capture microdissection (LCM) was employed to obtain an equal number of granule cells from wild-type and leaner mice. Western blot analysis with LCM-procured cerebellar granule cells showed decreased calretinin expression in leaner granule cells. These results indicate that there is an absolute decrease in calretinin expression in leaner granule cells even when granule cell loss is taken into account. Decreased calretinin expression in leaner granule cells may contribute to altered calcium buffering capacity. This alteration could be an adaptive change due to the calcium channel dysfunction, and may result in abnormal neuronal excitability and gene expression.
A Line of Berlin Druckrey IV Rats Proposed As a New Model for Human Hereditary Ataxia
In Vivo (Athens, Greece). Jul-Aug, 2002 | Pubmed ID: 12224135
An experimental colony of Berlin Druckrey IV (BD IV) rats with inherited, congenital, gradually progressive incoordination and rear limb ataxia was evaluated for clinical signs, gross and microscopic nervous system lesions, and mode of inheritance of the gene defect. Clinical evaluation suggested a lesion in the midbrain or brainstem, with resulting lower motor neuron functional impairment. Gross alterations in affected rats were atrophy of thigh musculature by six months of age and thoracic kyphoscoliosis. Histological evaluation of the nervous system revealed central chromatolysis of neurons within the red nuclei in 20 out of 24 affected rats. Additionally, in six out of 24 affected rats chromatolytic neural cell bodies of this nucleus contained brightly eosinophilic, coarsely granular, cytoplasmic deposits. Special stains (osmium tetroxide, Kinyoun's acid-fast and periodic acid-Schiff) indicated these deposits consisted of lipopolysaccharide. Additional lesions in ataxic rats included qualitative reduction in neuronal cell bodies of the inferior olivary nucleus (10 out of 26 rats) and cerebellar Purkinje cells (5 out of 27 rats). No reduction in the number of spinal cord lower motor neurons was detected. Analysis of intercross pedigrees that were established between ataxic BD IV females and either normal Long Evans or Fisher males indicated a likely autosomal recessive mode of inheritance. The authors propose that this disease accompanying a new variant of the BD IV rat (to be designated "shaker" rat) provides a new and unique research model for ataxia with features in common with some human hereditary ataxias.
Effects of Early Postnatal Ethanol Intubation on GABAergic Synaptic Proteins
Brain Research. Developmental Brain Research. Oct, 2002 | Pubmed ID: 12354645
Fetal alcohol syndrome includes brain damage from aberrant synaptogenesis, altered cell-cell signaling and blunted plasticity in surviving neurons. Distortion of neurotrophic GABA signals by ethanol-mediated allosteric modulation of GABA(A) receptor (GABA(A)R) activity during brain maturation may play a role. In this regard, early postnatal binge-like ethanol treatment on postnatal days (PDs) 4-9 acutely inhibits whole cell GABA(A)R Cl(-) current and subsequently blunts GABA(A)R function in medial septum/diagonal band (MS/DB) neurons and cerebellar Purkinje cells [Dev. Brain Res. 130 (2001) 25-40; Brain Res. 810 (1998) 100-113; Brain Res. 832 (1999) 124-135]. In light of these functional changes, we hypothesized that ethanol treatment also would decrease levels of proteins important for assembly of GABAergic synapses in maturing brain. To test this relationship, binge-like ethanol intubation was administered to rat pups on PDs 4-9 producing peak blood ethanol concentrations in the range of 302.5+/-6.3 mg/dl. GABAergic synaptic proteins were measured in brain tissue on PDs 13-14 when GABA(A)R currents in individual MS/DB neurons are reduced, but those of cerebellar Purkinje neurons are not yet altered [Dev. Brain Res. 130 (2001) 25-40; Brain Res. 810 (1998) 100-113; Brain Res. 832 (1999) 124-135]. Surprisingly, ethanol did not decrease protein levels of GABA(A)R alpha1/beta2 subunits, GAD(67) or gephyrin in MS/DB at this time when whole cell recordings indicate GABA(A)R function is impaired in acutely dissociated individual neurons. However, in cerebellum where ethanol treated Purkinje cell GABA(A)R function remains normal on PDs 13-14 [Brain Res. 832 (1999) 124-135], reduced levels of several GABAergic synaptic proteins including: GAD(67), GABA(A)R alpha1 subunit, ClC-2 a voltage-gated Cl(-) channel, synaptotagmin a synaptic vesicle protein, and N-cadherin, a synapse associated cell adhesion molecule, were found. These results indicate that binge-like ethanol exposure differentially decreases GABAergic synaptic proteins in some brain areas in a pattern that does not parallel reductions in GABA(A)R function of individual neurons that survive this ethanol insult.
Neonatal Cerebellar Ataxia in Coton De Tulear Dogs
Journal of Veterinary Internal Medicine / American College of Veterinary Internal Medicine. Nov-Dec, 2002 | Pubmed ID: 12465765
A neonatal ataxia syndrome was observed in Coton de Tulear dogs. Seven affected pups (32%; 7/22) of both genders came from 5 different litters with phenotypically normal parents. Neurologic examination revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements ("swimming") for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age. No specific abnormalities were identified in routine laboratory screening of blood and urine. Cerebrospinal fluid (CSF) analysis was normal in 1 dog, and a mild increase in protein concentration was observed in a second dog. CSF organic and amino acid concentrations were within normal limits. Magnetic resonance imaging and computed tomography of the brain, electromyography, motor nerve conduction studies, and brain stem auditory-evoked potentials were within normal limits. Postmortem examinations were performed on 5 affected dogs between 2 and 4 months of age. Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells. An autosomal recessive trait affecting development of the cerebellum is suspected.
Homeostatic Compensation Maintains Ca2+ Signaling Functions in Purkinje Neurons in the Leaner Mutant Mouse
Cerebellum (London, England). Apr, 2002 | Pubmed ID: 12882361
Several human neurological disorders have been associated with mutations in the gene coding for the alpha1 subunit of the P/Q type voltage-gated calcium channel (alpha1A/Ca(v)2.1). Mutations in this gene also occur in a number of neurologically affected mouse strains, including leaner (tg(la)/tg(la)). Because the P-type calcium current is very prominent in cerebellar Purkinje neurons, these cells from mice with alpha1 subunit mutations make excellent models for the investigation of the functional consequences of native mutations in a voltage-gated calcium channel of mammalian central nervous system. In this review, we describe the impact of altered channel function on cellular calcium homeostasis and signaling. Remarkably, calcium buffering functions of the endoplasmic reticulum and calcium-binding proteins appear to be regulated in order to compensate for altered calcium influx through the mutant channels. Although this compensation may serve to maintain calcium signaling functions, such as calcium-induced calcium release, it remains uncertain whether such compensation alleviates or contributes to the behavioral phenotype.
Insulin-like Growth Factor-I Improves Cerebellar Dysfunction but Does Not Prevent Cerebellar Neurodegeneration in the Calcium Channel Mutant Mouse, Leaner
Neurobiology of Disease. Nov, 2003 | Pubmed ID: 14572439
The effects of insulin-like growth factor-I (IGF-I) on cerebellar dysfunction and neurodegeneration were investigated in leaner mice, which exhibit cerebellar ataxia and neurodegeneration related to P/Q-type calcium channel mutations. Leaner mice showed significantly reduced serum and cerebellar IGF-I concentrations compared to wild-type mice at postnatal day 30. Behavioral assessment of leaner mice injected with IGF-I subcutaneously for 4 weeks showed partially improved cerebellar function. Histological analysis of IGF-I treated leaner cerebella showed no difference in the number of dying Purkinje cells compared to control leaner cerebella. These results further support potential use of IGF-I as a therapeutic aid for cerebellar ataxia related to calcium channel mutations. Nonetheless, IGF-I administration does not rescue dying cerebellar neurons, which suggests that the beneficial effects of IGF-I may have been achieved through surviving cerebellar neurons.
Altered Neuronal Nitric Oxide Synthase Expression in the Cerebellum of Calcium Channel Mutant Mice
Brain Research. Jul, 2003 | Pubmed ID: 12834873
Tottering, rolling Nagoya, and leaner mutant mice all exhibit cerebellar ataxia to varying degrees, from mild (tottering mice) to severe (leaner mice). Collectively, these mice are regarded as tottering locus mutants because each of these mutant mice expresses a different autosomal recessive mutation in the gene coding for the alpha(1A) calcium ion channel protein, which is the pore forming subunit for P/Q-type high voltage activated calcium ion channels. These mutant mice all exhibit varying degrees of cerebellar dysfunction and neuronal cell death. Nitric oxide (NO) is an important messenger molecule in the central nervous system, especially in the cerebellum, and it is produced via the enzyme, nitric oxide synthase (NOS). We investigated expression of neuronal-NOS (n-NOS) in the cerebella of all three mutant mice, as revealed by NADPH-diaphorase (NADPH-d) histochemical staining, quantitation of n-NOS protein using Western blotting and quantitation of n-NOS mRNA using in situ hybridization. The expression of n-NOS mRNA and protein as well as the NADPH-d histochemical reaction were elevated in tottering and rolling Nagoya cerebella. n-NOS mRNA and the NADPH-d histochemical reaction were decreased in the leaner cerebellum, but the leaner mouse n-NOS protein concentration was not significantly different compared to age- and gender-matched controls. These findings suggest that NO may act as an important mediator in the production of the neuropathology observed in these mutant mice.
Neuronal Nitric Oxide Synthase Expression in Cerebellar Mutant Mice
Cerebellum (London, England). 2004 | Pubmed ID: 15543804
Nitric oxide (NO) is a diffusible, multifunctional signaling molecule found in many areas of the brain. NO signaling is involved in a wide array of neurophysiological functions including synaptogenesis, modulation of neurotransmitter release, synaptic plasticity, central nervous system blood flow and cell death. NO synthase (NOS) activity regulates the production of NO and the cerebellum expresses high levels of nitric oxide synthase (NOS) in granule, stellate and basket cells. Cerebellar mutant mice provide excellent opportunities to study changes of NO/NOS concentrations and activities to gain a greater understanding of the roles of NO and NOS in cerebellar function. Here, we have reviewed the current understanding of the functional roles of NO and NOS in the cerebellum and present NO/NOS activities that have been described in various cerebellar mutant mice and NOS knockout mice. NO appears to exert neuroprotective effects at low to moderate concentrations, whereas NO becomes neurotoxic as the concentration increases. Excessive NO production can cause oxidative stress to neurons, ultimately impairing neuronal function and result in neuronal cell death. Based on their genetics and cerebellar histopathology, some of cerebellar mutant mice display similarities with human neurological conditions and may prove to be valuable models to study several human neurological disorders, such as autism and schizophrenia.
Postnatal Apoptosis in Cerebellar Granule Cells of Homozygous Leaner (tg1a/tg1a) Mice
Neurotoxicity Research. 2004 | Pubmed ID: 15545010
Leaner mice carry a homozygous, autosomal recessive mutation in the mouse CACNA1A gene encoding the Alpha1A subunit of P/Q-type calcium channels, which results in an out-of-frame splicing event in the carboxy terminus of the Alpha1A protein. Leaner mice exhibit severe ataxia, paroxysmal dyskinesia and absence seizures. Functional studies have revealed a marked decrease in calcium currents through leaner P/Q-type channels and altered neuronal calcium ion homeostasis in cerebellar Purkinje cells. Histopathological studies of leaner mice have revealed extensive postnatal cerebellar Purkinje and granule cell loss. We examined the temporospatial pattern of cerebellar granule cell death in the leaner mouse between postnatal days (P) 10 and 40. Our observations clearly indicate that leaner cerebellar granule cells die via an apoptotic process and that the peak time of neuronal death is P20. We did not observe a significant increase in microglial and astrocytic responses at P20, suggesting that glial responses are not a cause of neuronal cell death. We propose that the leaner cerebellar granule cell represents an in vivo animal model for low intracellular [Ca2+]-induced apoptosis. Since intracellular [Ca2+] is critical in the control of gene expression, it is quite likely that reduced intracellular [Ca2+] could activate a lethal cascade of altered gene expression leading to the apoptotic granule cell death in the leaner cerebellum.
Differential Expression of T-type Calcium Channels in P/Q-type Calcium Channel Mutant Mice with Ataxia and Absence Epilepsy
Journal of Neurobiology. Feb, 2005 | Pubmed ID: 15514988
Mutations in P/Q-type calcium channels generate common phenotypes in mice and humans, which are characterized by ataxia, paroxysmal dyskinesia, and absence seizures. Subsequent functional changes of T-type calcium channels in thalamus are observed in P/Q-type calcium channel mutant mice and these changes play important roles in generation of absence seizures. However, the changes in T-type calcium channel function and/or expression in the cerebellum, which may be related to movement disorders, are still unknown. The leaner mouse exhibits severe ataxia, paroxysmal dyskinesia, and absence epilepsy due to a P/Q-type calcium channel mutation. We investigated changes in T-type calcium channel expression in the leaner mouse thalamus and cerebellum using quantitative real-time polymerase chain reaction (qRT-PCR) and quantitative in situ hybridization histochemistry (ISHH). qRT-PCR analysis showed no change in T-type calcium channel alpha 1G subunit (Cav3.1) expression in the leaner thalamus, but a significant decrease in alpha 1G expression in the whole leaner mouse cerebellum. Interestingly, quantitative ISHH revealed differential changes in alpha 1G expression in the leaner cerebellum, where the granule cell layer showed decreased alpha 1G expression while Purkinje cells showed increased alpha 1G expression. To confirm these observations, the granule cell layer and the Purkinje cell layer were laser capture microdissected separately, then analyzed with qRT-PCR. Similar to the observation obtained by ISHH, the leaner granule cell layer showed decreased alpha 1G expression and the leaner Purkinje cell layer showed increased alpha 1G expression. These results suggest that differential expression of T-type calcium channels in the leaner cerebellum may be involved in the observed movement disorders.
Developmental Expression of Neuronal Nitric Oxide Synthase in P/Q-type Voltage-gated Calcium Ion Channel Mutant Mice, Leaner and Tottering
Brain Research. Apr, 2007 | Pubmed ID: 16359645
Nitric oxide (NO) is a diffusible messenger molecule produced primarily by neuronal nitric oxide synthase (nNOS) in the central nervous system. Both nNOS expression and NO production are regulated by calcium ions. Leaner and tottering mice carry a mutation in the pore forming subunit (alpha1A) of P/Q-type voltage-gated calcium ion channels, which decreases calcium ion current through the affected channels and disrupts calcium homeostasis. We have previously shown that nNOS expression is altered in adult leaner and tottering cerebella. In addition, leaner and tottering mice have been shown to have abnormal cerebellar granule cell-Purkinje cell synapses and leaner cerebellar granule cells undergo abnormal apoptosis during early postnatal development. Since NO production has been linked to several developmental roles including neuronal cell death, synaptogenesis and neuronal cell survival, our objective was to evaluate the expression of nNOS in developing leaner and tottering cerebella. Our results show that nNOS is differentially expressed in leaner and tottering cerebella compared to wild type cerebella and compared to each other. In whole cerebella, Western blotting revealed a significant increase in nNOS expression at postnatal day 12 in tottering but not leaner or wild type cerebella. At the cellular level the NADPH-diaphorase marker for nNOS revealed a significant increase in nNOS expression in basket cell interneurons in both mutant mice. nNOS expression in granule cells in the internal granule cell layer in tottering mice was increased at P12, while granule cells of leaner mice exhibited decreased nNOS expression at P20. The changes in nNOS expression at P12 did not correlate with a change in overall NO production, but rather maintained wild type NO concentrations. These findings suggest that changes in nNOS expression in the leaner and tottering cerebella are compensatory in nature with NO most likely functioning as a calcium-regulated neuroprotective/neurotrophic factor in postnatal cerebellar development.
Functional Compensation by Other Voltage-gated Ca2+ Channels in Mouse Basal Forebrain Neurons with Ca(V)2.1 Mutations
Brain Research. Apr, 2007 | Pubmed ID: 16364258
Tottering (tg/tg) and leaner (tg(la)/tg(la)) mutant mice exhibit distinct mutations in the gene encoding the voltage-activated Ca(2+) channel alpha(1A) subunit (CACNA1A), the pore-forming subunit of the Ca(V)2.1 (P/Q type) Ca(2+) channels. These mice exhibit absence seizures and deficiencies in motor control and other functions. Previous work in cerebellar Purkinje neurons has shown that these mutations cause dramatic reductions in calcium channel function. Because Purkinje cell somata primarily express the Ca(V)2.1 channels, the general decrease in Ca(V)2.1 channel function is observed as a profound decrease in whole-cell current. In contrast to Purkinje cells, basal forebrain (BF) neurons express all of the Ca(2+) channel alpha(1) subunits, with Ca(V)2.1 contributing approximately 30% to the whole-cell current in wild-type (+/+) mice. Here, we show that whole-cell Ba(2+) current densities in BF neurons are not reduced in the mutant genotypes despite a reduction in the Ca(V)2.1 contribution. By blocking the different Ca(2+) channel subtypes with specific pharmacological agents, we found a significant increase in the proportion of Ca(V)1 Ca(2+) current in mutant phenotypes. There was no change in tissue mRNA expression of calcium channel subtypes Ca(V)2.1, Ca(V)2.2, Ca(V)1.2, Ca(V)1.3, and Ca(V)2.3 in the tottering and leaner mutant mice. These results suggest that Ca(V)1 channels may functionally upregulate to compensate for reduced Ca(V)2.1 function in the mutants without an increase in Ca(v)1 message. Single-cell reverse transcription polymerase chain reaction (RT-PCR) experiments in a subset of sampled neurons revealed that approximately 90% of the cells could be considered cholinergic based on choline acetyltransferase (ChAT) mRNA expression.
Inherited Tertiary Hypothyroidism in Sprague-Dawley Rats
Brain Research. May, 2007 | Pubmed ID: 17368429
Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.
Coordination Deficits Induced in Young Adult Mice Treated with Methylmercury
International Journal of Toxicology. Mar-Apr, 2007 | Pubmed ID: 17454251
Male and female C57BL/6J mice starting at postnatal (P) day 34 were exposed orally to five divided doses totaling 1.0 or 5.0 mg/kg of methylmercury (MeHg; given as methylmercuric chloride) or sterile deionized water in moistened rodent chow. After a 5-day waiting period, control and MeHg-treated mice were subjected to a standard battery of behavior tests for balance and motor coordination. Latency to falling on the accelerating rota-rod was significantly decreased in 5.0 mg/kg MeHg-exposed mice when compared to control mice. In the open field, horizontal exploration with respect to total distance traveled during the first 5 min on the first test day was significantly reduced in 1.0 mg/kg MeHg-exposed mice when compared to control mice. Rearing activity was not affected by MeHg treatment. In the footprint analysis, angle of foot placement measured in 1.0 mg/kg MeHg-treated mice was significantly greater compared to control mice. Base stance and stride length were unaffected by MeHg treatment. On the vertical pole test, 10 mice from each treatment group fell off the pole during the time the pole was shifted from a horizontal position to a vertical position, whereas none of the control mice fell. These results indicate that short-term, low to moderate doses of MeHg in young adult mice can be detrimental to motor coordination and balance.
Changes in Biochemical Processes in Cerebellar Granule Cells of Mice Exposed to Methylmercury
International Journal of Toxicology. May-Jun, 2007 | Pubmed ID: 17564908
At postnatal day 34, male and female C57BL/6J mice were exposed orally once a day to a total of five doses totaling 1.0 or 5.0 mg/kg of methylmercuric chloride or sterile deionized water in moistened rodent chow. Eleven days after the last dose cerebellar granule cells were acutely isolated to measure reactive oxygen species (ROS) levels and mitochondrial membrane potential using CM-H(2)DCFDA and TMRM dyes, respectively. For visualizing intracellular calcium ion distribution using transmission electron microscopy, mice were perfused 11 days after the last dose of methylmercury (MeHg) using the oxalate-pyroantimonate method. Cytosolic and mitochondrial protein fractions from acutely isolated granule cells were analyzed for cytochrome c content using Western blot analysis. Histochemistry (Fluoro-Jade dye) and immunohistochemistry (activated caspase 3) was performed on frozen serial cerebellar sections to label granule cell death and activation of caspase 3, respectively. Granule cells isolated from MeHg-treated mice showed elevated ROS levels and decreased mitochondrial membrane potential when compared to granule cells from control mice. Electron photomicrographs of MeHg-treated granule cells showed altered intracellular calcium ion homeostasis ([Ca(2+)](i)) when compared to control granule cells. However, in spite of these subcellular changes and moderate relocalization of cytochrome c into the cytosol, the concentrations of MeHg used in this study did not produce significant neuronal cell death/apoptosis at the time point examined, as evidenced by Fluoro-Jade and activated caspase 3 immunostaining, respectively. These results demonstrate that short-term in vivo exposure to total doses of 1.0 and 5.0 mg/kg MeHg through the most common exposure route (oral) can result in significant subcellular changes that are not accompanied by overt neuronal cell death.
Assessment of Mercury Concentrations in Mouse Brain Using Different Routes of Administration and Different Tissue Preparations
Toxicology Mechanisms and Methods. 2007 | Pubmed ID: 20020966
ABSTRACT The objective of this study was to determine the best method for preparing brain tissue for mercury analysis from mice exposed to methylmercury either through subcutaneous (SC) injection or through ingestion. C57BL/6 J mice at postnatal day 29 were exposed to 0.0 or 5.0 mg/kg methylmercuric chloride (MMC) given SC or through food containing MMC. Eighteen mice received vehicle (sodium bicarbonate; SC) and 18 additional mice received 5.0 mg/kg MMC (SC). Whole brain tissue was prepared using one of four tissue preparation methods: rapid freezing, saline perfusion, 4% paraformaldehyde perfusion fixation, or 4% paraformaldehyde immersion fixation. Brains from vehicle-treated mice exhibited minimal levels of mercury (0.0007 to 0.0018 ppm) in all preparation methods. Mercury content in rapidly frozen control brains differed statistically from immersion-fixed control brain tissue. There was no significant difference in mercury content from mice given 5.0 mg/kg MMC (SC) in all preparation methods (0.2660 to 0.3650 ppm). Additional mice were divided into groups of six mice each: single oral dose of 5.0 mg/kg MMC; total oral dose of 5.0 mg/kg MMC divided into five doses; and vehicle only. Forebrain (0.3243 ppm) and hindbrain (0.1908 ppm) mercury content in MMC-treated mice given multiple doses was 10 times higher than in brain tissue from mice given a single 5.0 mg/kg dose. Brain mercury content following administration of 5.0 mg/kg MMC via the oral route (0.5354 ppm) differed statistically from the SC route (0.3430 ppm). In conclusion, different tissue preparation methods do not significantly affect brain mercury content, but route of administration and dosing regimen can influence total brain mercury content.
Analysis of Calcium Ion Homeostasis and Mitochondrial Function in Cerebellar Granule Cells of Adult CaV 2.1 Calcium Ion Channel Mutant Mice
Neurotoxicity Research. Jan, 2008 | Pubmed ID: 18367436
CaV 2.1 voltage-gated calcium channels (VGCC) are highly expressed by cerebellar neurons, and their dysfunction is linked to human disorders including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. Altered calcium homeostasis, due to dysfunctional Ca(V 2.1 VGCC can severely affect mitochondrial function, eventually leading to neuronal cell death. We study leaner and tottering mice, which carry autosomal recessive mutations in the gene coding for the alpha 1A pore-forming subunit of CaV 2.1 VGCC. Both leaner and tottering mice exhibit cerebellar ataxia and epilepsy. Excessive leaner cerebellar granule cell (CGC) death starts soon after postnatal day 10, but it is not known whether the degree of CGC cell death observed in adult leaner mice is significantly different from wild type mice. We used Fluoro-Jade and TUNEL staining to quantify apoptotic cell death in leaner and wild type CGC. We investigated calcium homeostasis, mitochondrial function and generation of reactive oxygen species (ROS) in isolated CGC, using indicator dyes Fura-2AM, TMRM and CMH2DCFDA, respectively. We observed a small but significant increase in number of apoptotic adult leaner CGC. Calcium homeostasis and mitochondrial function also were altered in leaner CGC. However, no significant differences in ROS levels were observed. It is possible that CGC death in leaner mice may be related to mitochondrial dysfunction but may not be directly related to decreased basal intracellular calcium.
Chronic, Low-dose Prenatal Exposure to Methylmercury Impairs Motor and Mnemonic Function in Adult C57/B6 Mice
Behavioural Brain Research. Aug, 2008 | Pubmed ID: 18436314
Methylmercury (MeHg) has cytotoxic effects on animals and humans, and a major target organ for MeHg is the central nervous system (CNS). It is well known that the developing CNS is extremely vulnerable to MeHg-induced changes in comparison to the mature brain. Most studies have concentrated on the direct effects of high levels of prenatal MeHg exposure. Surprisingly, behavioral outcomes found in adult offspring exposed developmentally to the neurotoxic effects of chronic, low-dose mercury more akin to ingestion in humans are not well characterized. The objective of this study was to determine whether such exposure produces deleterious effects on behavior in adult mice, including motor/coordination abilities, overall activity and mnemonic function. Developing mouse fetuses were exposed in utero during gestational days 8-18 by giving pregnant C57Bl/6J female mice food containing MeHg at a daily dose of 0.01 mg/kg body weight. Adult mice prenatally exposed to MeHg exhibited significant deficits in motor abilities, coordination, and overall activity, as measured by rotarod, footprint analysis and open field. In addition, MeHg-exposed mice were impaired with respect to reference memory but not in a visible, cued version of the Morris water maze task. These results indicate that prenatal exposure to the lowest dose of MeHg examined to date can have long-lasting motor and cognitive consequences on adult offspring. These findings have far reaching implications related to putative safe levels of MeHg ingestion, particularly during pregnancy, and increasing rates of cognitive and psychological disorders (e.g. attention hyperactivity deficit disorder, autism) in our society.
Effects of Quillaja Saponin (Quillaja Saponaria) on Early Embryonic Zebrafish (Danio Rerio) Development
International Journal of Toxicology. 2008 | Pubmed ID: 18569168
Although much attention has focused on environmental contamination by heavy metals, pesticides, and polychlorinated biphenyls, potential deleterious effects of naturally occurring organic compounds have received much less consideration. Saponins, which are glycosides found in many plants, are important, environmentally ubiquitous organic compounds. Saponins have both beneficial and deleterious effects in adults, but little is known about how saponins effect early vertebrate embryonic development. The authors tested the toxicity of quillaja saponin using a zebrafish embryo assay. Quillaja saponin, extracted from bark of the tree, Quillaja saponaria, is a common foaming agent used in foods and beverages. At 6 h post fertilization, zebrafish embryos were exposed to five concentrations (0 [negative control], 1, 5, 10 or 20 micro g) of quillaja saponin per milliliter of medium. Zebrafish embryos exposed to 2% ethanol were positive controls (100% embryonic death). Embryos were assessed at 30, 54, and 72 h post fertilization for changes in embryonic development, mortality, time of hatching, and morphological deformities. Embryos exposed to 1 and 5 micro g saponin were healthy, showed no obvious deformities, but exhibited shrinkage of the chorion. Hatching time for zebrafish embryos exposed to 1 and 5 micro g/ml saponin decreased by 18 h compared to unexposed embryos. Zebrafish embryos treated with 5 micro g/ml saponin responded less to touch than embryos treated with 1 micro g/ml saponin or controls. Zebrafish embryos exposed to more than 5 micro g/ml saponin exhibited 100% embryonic mortality. These results indicate that exposure to 5 micro g/ml or less of quillaja saponin acts as a growth promoter, whereas concentrations of 10 micro g/ml or greater are lethal.
Alterations in Intracellular Calcium Ion Concentrations in Cerebellar Granule Cells of the CACNA1A Mutant Mouse, Leaner, During Postnatal Development
Neurotoxicity Research. Jan, 2011 | Pubmed ID: 20043243
Maintaining calcium ion (Ca²+) homeostasis is crucial for normal neuronal function. Altered Ca²+ homeostasis interferes with Ca²+ signaling processes and affects neuronal survival. In this study, we used homozygous leaner and tottering mutant mice, which carry autosomal recessive mutations in the gene coding for the α(1A) pore forming subunit of Ca(V)2.1 (P/Q-type) voltage-gated calcium channels (VGCC). Leaner mice show severe ataxia and epilepsy, while tottering mice are less severely affected. Leaner cerebellar granule cells (CGC) show extensive apoptotic cell death that peaks at postnatal (P) day 20 and continues into adulthood. Intracellular Ca²+ ([Ca²+](i)) concentrations in leaner and tottering mouse Purkinje cells have been described, but [Ca²+](i) concentrations have not been reported for granule cells, the largest neuronal population of the cerebellum. Using the ratiometric dye, Fura-2 AM, we investigated the role of Ca²+ homeostasis in CGC death during postnatal development by demonstrating basal [Ca²+](i), depolarization induced Ca²+ transients, and Ca²+ transients after completely blocking Ca(V)2.1 VGCC. From P20 onward, basal [Ca²+](i) levels in leaner CGC were significantly lower compared to age-matched wild-type CGC. We also compared basal [Ca²+](i) levels in leaner and wild-type CGC to basal [Ca²+](i) in tottering CGC. Potassium chloride induced depolarization revealed no significant difference in Ca²+ transients between leaner and wild-type CGC, indicating that even though leaner CGC have dysfunctional P/Q-type VGCC, Ca²+ transients after depolarization are the same. This suggests that other VGCC are compensating for the dysfunctional P/Q channels. This finding was further confirmed by completely blocking Ca(V)2.1 VGCC using ω-Agatoxin IV-A.
Striatal Expression of Homer1a is Affected by Genotype but Not Dystonic Phenotype of Tottering Mice: a Model of Spontaneously Occurring Motor Disturbances
Neuroscience Letters. Oct, 2011 | Pubmed ID: 21884752
Tottering (tg) mice carry a missense mutation in the gene coding for P/Q-type voltage-dependent Ca(2+) channels (VDCCs). Aberrant functioning of P/Q-type VDCCs results in molecular alterations in Ca(2+) currents and in glutamate and dopamine systems. As a consequence, tottering mice exhibit mild ataxia, spontaneous epilepsy, and paroxysmal dyskinesia. In this study, we evaluated whether the tottering mice genotype (homozygous vs. heterozygous) and abnormal movement phenotype (mice exhibiting paroxysmal dyskinesia vs. mice not exhibiting dyskinesia) may affect the expression of Homer1a. Homer1a is a gene whose expression is modulated by glutamate, dopamine and Ca(2+) concentrations. Over-expression of Homer1a has been described in epilepsy and motor dysfunctions. Thereby, changes in Homer1a expression could take place in tottering mice. Studying the expression profile of this gene may shed light on the molecular events occurring in tottering mice. Moreover, tottering mice may represent a valuable animal model for investigating Homer1a involvement in motor disorders. Homer1a expression was decreased in all striatal subregions, with the exclusion of the dorsolateral caudate-putamen, in heterozygous mice compared to wild-type and homozygous mice. Gene expression was decreased in the core of the accumbens in mice exhibiting paroxysmal dyskinesia compared to wild-type mice and to mice not exhibiting dyskinesia. These results demonstrate that the tottering mouse genotype may affect striatal expression of Homer1a, possibly as a result of imbalance between Ca(2+) channels subtypes or Ca(2+)-related molecules in heterozygous vs. homozygous mice.
Multiscale Exploration of Mouse Brain Microstructures Using the Knife-edge Scanning Microscope Brain Atlas
Frontiers in Neuroinformatics. 2011 | Pubmed ID: 22275895
Connectomics is the study of the full connection matrix of the brain. Recent advances in high-throughput, high-resolution 3D microscopy methods have enabled the imaging of whole small animal brains at a sub-micrometer resolution, potentially opening the road to full-blown connectomics research. One of the first such instruments to achieve whole-brain-scale imaging at sub-micrometer resolution is the Knife-Edge Scanning Microscope (KESM). KESM whole-brain data sets now include Golgi (neuronal circuits), Nissl (soma distribution), and India ink (vascular networks). KESM data can contribute greatly to connectomics research, since they fill the gap between lower resolution, large volume imaging methods (such as diffusion MRI) and higher resolution, small volume methods (e.g., serial sectioning electron microscopy). Furthermore, KESM data are by their nature multiscale, ranging from the subcellular to the whole organ scale. Due to this, visualization alone is a huge challenge, before we even start worrying about quantitative connectivity analysis. To solve this issue, we developed a web-based neuroinformatics framework for efficient visualization and analysis of the multiscale KESM data sets. In this paper, we will first provide an overview of KESM, then discuss in detail the KESM data sets and the web-based neuroinformatics framework, which is called the KESM brain atlas (KESMBA). Finally, we will discuss the relevance of the KESMBA to connectomics research, and identify challenges and future directions.


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Deal will prevent spike in milk prices
WASHINGTON (AP) — A potential doubling of milk prices will be averted as part of the compromise that White House and congressional bargainers reached on wide-ranging legislation to avert the "fiscal cliff," a leading senator said late Monday.
Senate Agriculture Committee Chairwoman Debbie Stabenow, D-Mich., told reporters that negotiators had agreed to extend portions of the expired 2008 farm bill through September. She said that includes language keeping milk prices from rising, but excludes other provisions like energy and disaster aid for farmers.
Stabenow said she considers the slimmed-down extension to be "Mitch McConnell's version of a farm bill." She was referring to the Senate Republican leader from Kentucky, who she said forced bargainers to accept the version of the farm bill that appeared in the deal.
McConnell spokesman Michael Brumas responded: "Sen. McConnell put forward a bipartisan, responsible solution that averted the dairy cliff and provided certainty to farmers for the next year without costing taxpayers a dime."
Just a day earlier, Stabenow said leaders from both parties on the House and Senate agriculture committees had agreed to extend the entire farm bill.
Stabenow and House Agriculture Chairman Frank Lucas, R-Okla., announced Sunday that they had agreed on a last-minute move that would extend the entire farm bill and replace dairy programs that expire at midnight Tuesday. Expiration of those dairy programs could mean higher milk prices at the grocery store within just a few weeks.
But the House GOP had not endorsed the committees' extension agreement.
The nonpartisan Congressional Budget Office estimated Sunday that extending the entire bill through September, including disaster assistance for farmers affected by drought, could cost more than $1 billion this budget year.
House Speaker John Boehner, R-Ohio, has pushed back on passage of a new five-year farm bill for months, saying there were not enough votes to bring it to the House floor after the House Agriculture Committee approved it in July. The Senate passed its version of a farm bill in June. The bill, generally passed every five years, includes food stamps, farm subsidies and other help for rural areas.
But the prospect of higher milk prices prompted some action. Agriculture Secretary Tom Vilsack has said Americans face the prospect of paying $7 for a gallon of milk if the current dairy program lapsed and the government returned to a 1948 formula for calculating milk price supports. Continued...
Extending the entire agriculture bill would have included an overhaul of dairy programs that was included in both the Senate and House committee bills. The new dairy programs include a voluntary insurance program for dairy producers, and those who choose that new program also would have to participate in a market stabilization program that could dictate production cuts when oversupply drives down prices — an idea that hasn't gone over well with Boehner.
In July, he called the current dairy program "Soviet-style" and said the new program would make it even worse. Large food companies that process and use dairy products have backed Boehner, saying the program could limit milk supplies and increase their costs.
One of the reasons Boehner has balked at bringing up a farm bill is disagreement among House Republicans over how much money should be cut from food stamps, which make up roughly 80 percent of the half-trillion-dollar bill's cost over five years. Lucas has unsuccessfully pushed his leadership for months to move on the legislation despite the disagreement over food aid.
Follow Mary Clare Jalonick on Twitter at http://twitter.com/mcjalonick
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Illinois Chapter ASLA – 2013 LARE Review & Prep Session
Location: IIT Campus, Chicago, Illinois
The ILASLA Education Committee is pleased to invite Emerging Professionals and LARE Candidates to participate in a fast moving session for reviewing the content for Section 1 & 2 Friday half day as well as Section 3 and 4 Saturday full day. The format enables candidates to view strength and weakness, to preview problem styles, experience drilling, discover success factors as well as hear an over view of exam content to enhance overall exam performance. The session features slides, allows for discussion and individual questions, plus supplemental handouts and post session follow-up via email. The session uses a proven, affordable format featuring one book of study materials per section published by PPI, Inc. The proven course format has helped over 250 successful candidates since 2008 with instruction by landscape architects Matt Mathes, PLA, ASLA and Erik Sweet, PLA, ASLA.
Section 1 & 2 Sessions Friday Feb 22 (1PM to 3PM, 15 minute break 3:15PM to 5:15PM) includes the following format starting at 1PM for Section 1 and at 3:15PM for Section 2:
Section 3 Session (8AM – Noon, include 15 minute break) includes:
Section 4 Contents (1PM to 5PM, include 15 minute break) includes:
For sign-up and session pricing options, go to: http://il-asla.org/meetinginfo.php?id=80&ts=1359584280
Kenon Boehm, ILASLA Education Committee Chair
Is anyone aware of a Section 4 review class in Colorado this fall?
I still have seats in my Section 1 and 2 class on August 11-12. Accepting applications on Tuesday. I fyou need registration materials or detailed info re the course, please e-mail me at email@example.com
I still have the preparatory materials that I made available in April (see below). Even though the test is changing formats, this material is still sold through the PPI website - don't be fooled by the new packaging...it's the same thing and they haven't yet figured out how to adapt to the new format (see here for a direct comparison of the relevancy of the subject matter http://ppi2pass.com/Docs/PPIInfo/LARE_Cross_Reference_Chart_2012.html
I acknowledge that the price has dropped to $285. Please don't pay that...I'll accept $250 with shipping included O.B.O. Email me today at firstname.lastname@example.com with questions/offers.
I live in Upper Marlboro, MD, and am preparing for Sections 3 & 4 in December. Any DC/Baltimore/NoVa candidates doing the same? I've got all my study books and old vignettes, but it could be nice to know others in the same boat.
Southern California - UCLA- LARE PREP COURSES |
Date/Time: |
April 13, 14, 15 and May 5,6 2012 |
Description: |
California, ALSA Section E 4/13 (Friday) 12pm-7 pm 4/14-15 ( Saturday, Sun) 8am – 5pm Jerry Hastings, RLA CA #1577, Instructor Designed for students and professionals who already possess a basic knowledge of grading and drainage, this course reviews the principles and skills necessary to do grading design and prepare for the grading portion of the LARE Section E: Grading, Drainage, and Storm Water Management Section C 5/5 – 5/6/2012 (Saturday & Sun.) 8am – 5pm Angela Woodward, RLA CA #2126, Instructor Designed for students who are preparing to take the LARE Section C: Planning and Site Design, this course reviews the knowledge and skills associated with the design process of incorporating elements in the natural and built environment in a safe and effective manner. Subcategories of study for this graphic response section include site planning, circulation, and planting design. Instruction focuses on the three essential keys for successfully passing the exam: subject matter mastery, problem-solving ability, and test-taking strategies. Our intensive review courses are taught by working landscape architects - talented professionals who can guide you in preparing for this all-important exam. Review materials will be provided in the sessions. To register go to http://tinyurl.com/LAREUCLA |
Location: |
Location: UCLA Extension, Westwood, California |
Cost: |
Session C: $459 Session E: $599 (10% discount before March 13) |
Contact Details: |
Name: Amanda Wesley, Program Manager |
LARE Preparatory Course
Section E Review
April 20-22, 2012 8:30 am-6:00 pm
CSU Denver Extension
888 East Iliff Avenue
Denver, CO 80210
Subjects Covered
Overview of the exam and Section E
Solving watershed planning problems
Precision requirements of the LARE
Foundation systems and setting finish floors
Interpretation of soil maps and reports
Accessibility requirements
Roadway grading
Grading processes and procedures
Storm drainage and stormwater management principles
Vision cone problem solving
Elements of stormwater ponds and dams
Sizing stormwater basins
Practical techniques for solving vignettes
Exam preparation techniques
Students will complete timed problems covering basic skills required in grading and drainage design. The class takes a programmed approach to Section E, covering necessary skills and developing each subset of this section through the use of a few introductory exercises and building to solving full vignette problems typical of those encountered of the LARE. The instructor will provide tips on how to break problems down and conceptualize a plan of attack for developing solutions. The last two days of the course will be spent on specific task oriented techniques and working and then reviewing timed vignettes typical of those on the exam. A 130 page syllabus and 30 exercises will be provided.
Instructor: Ray Freeman, of Freeman and Jewell Landscape Architecture. He has taught LARE review sessions since 2000. In December 2011, 30 of 45 of Ray's students sitting for section E passed. The national pass rate was 36%.
To obtain a flyer on this class, go to: http://www.aslacolorado.org/calendar/
Any questions should be directed to David Gregory,
Denver Area Director, ASLA Colorado -
Tuition: $300 ASLA Colorado member
$400 non-member
Payment by check or credit card
Please make checks payable to:
ASLA Colorado
Registration Deadline is April 15.
Class size is limited to 25 students
PPI - LARE Complete Review Package Sections A-E. This package is as ordered directly from PPI and includes all of the materials listed on their website (click here to see what is included). They are virtually unmarked as I worked on copies instead of the originals. This package originally sells for $335, but I'm asking $300. A discounted price for you, recovered costs for me.
Anyone living in Southern California taking LARE Sections C or E in June? I've taken & passed sections A, B, & D. Now its time to tackle C & E. I'm in the process of gathering info & looking for study partners. Give me a shout if you're interested in comparing notes.
Hello everyone. I found this searching around and thought someone might be interested in this infomation. LARE Secrets Study Guide and the PPI practice tests for Sections A, D. and C and E.
Link: http://www.ebay.com/itm/180816993658?ssPageName=STRK:MESELX:IT&...
Started by Bri Morrison. Last reply by alland May 9. 9 Replies 2 Likes
Started by Amanda Wesley. Last reply by Sherry Alexander Aug 2, 2012. 1 Reply 0 Likes
© 2013 Created by Andrew Spiering.


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assalamu alaykum
I just want to know if any organisation is collecting clothes for the earthquake victims in Kashmir. If not, what is the best place to donate these clothes so that Muslims benefit?
Thread: Donating Clothes
Results 1 to 13 of 13
- Join Date
- Apr 2003
- Posts
- 212
21-Oct-2005 12:19 PM
21-Oct-2005 01:31 PM
taqwa: a while ago they did collect clothes for pakistan at Doncaster Mosque.
I'm not sure where you could but some options would be contacting Doncaster Mosque as they have been collecting money for the victims. I know other mosques have too but Doncaster has alot more links to that region.
You could also ask the muslim aid organisation if they want clothes for the victims.
21-Oct-2005 01:50 PM
I found it the other day and I been meaning to post it here
is quite helpful because it has many links to the helping sites along with their toll free numbers link here
22-Oct-2005 05:03 AM
Muslims should be careful giving money to non-Muslim agencies, as they keep large parts of the donated money, like up to 75% of it.
23-Oct-2005 06:11 PM
monash uni islamic society is
i know of brothers who have already taken clothing up there
26-Oct-2005 11:27 PM
Auburn mosque did collect clothes but i think they already sent couple of containers
Fe Amaan Allah
رَبَّنَا لاَ تُزِغْ قُلُوبَنَا بَعْدَ إِذْ هَدَيْتَنَا وَهَبْ لَنَا مِن لَّدُنكَ رَحْمَةً إِنَّكَ أَنتَ الْوَهَّابُ -آل عمران -8"Our Lord! Let not our hearts deviate (from the truth) after You have guided us, and grant us mercy from You. Truly, You are the Bestower." (Aali Imran 3:8)
02-Nov-2005 10:43 AM
Is there anywhere in Melbourne, possibly within the northern suburbs thats collecting clothes?
- Join Date
- Aug 2005
- Location
- Melbourne
- Posts
- 222
02-Nov-2005 11:55 PMI hear there is an Op Shop opening soon ... perhaps they can collect those clothes.
Do a search on these forums for Op Shopihsan: "It is to worship Allah as though you are seeing Him, and while you see Him not, yet truly He sees you".
04-Nov-2005 12:16 AM
lol No.. I dont want to give them to an OP shop..
I want to donate them to muslims.
04-Nov-2005 01:26 AM
Jalal is referring to a Muslim op-shop.
- Join Date
- Aug 2005
- Location
- Melbourne
- Posts
- 222
04-Nov-2005 08:58 AMOriginally Posted by aussiemuihsan: "It is to worship Allah as though you are seeing Him, and while you see Him not, yet truly He sees you".
05-Nov-2005 12:14 AM
lol Oh ok.
Sorry i didn't even know they have them here.
Where abouts are they located?
06-Nov-2005 11:42 AM
Its opening soon on 18 Nov. The name of the Muslim Op-Shop is Next to New located in Coburg opposite the Don Bosco Centre. Contact 0423 148 185 for further details."All humans are dead except those who have knowledge... and those who have knowledge are asleep, except those who do good deeds... and those who do good deeds are deceived, except those who are sincere... and those who are sincere are always in a state of worry." -- Imam al-Shafi'i (Rahimahullah)


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If you don't have an account click the "login or signup" tab in the upper right & create one. To make things easy you can quickly create it using your facebook, twitter, or google login. Your real identity & your login credentials for those sites will remain private. Just be sure to choose an alias when you set it up. PS: Even if you haven't been to SFN in years, your old login will still work.
PHOTOSHOP/GIF THREAD - New Eric The Midget Heads From His Latest Video.
Discussion in 'Howard Stern' started by Doctor Ivan, Jun 6, 2012.
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Recently in one of the interview, I faced this tricky question, "What is the advantage for compiling to intermediate code instead of native code directly?"
This is a tricky question. However, i read an article written by .NET team member Eric Lippert about the same topic.
Converting to Intermediate code has few advantages over direct conversion of native code. As so many languages comes under .NET framework, and all source code of these languages has to support conversion into native code in different platforms.
Say, if there are "m" number of languages, and these supports "n" number of platforms, it will take "m"x"n" implementations, if source code is directly converted to native code.
By introducing Intermediate Language concept, it required only "m" + "n" different implementations, as all languages has to implement only conversion to intermediate code. This approach results in less coding effort for language implementer.
Read More..   [255 clicks]
Published under: C# Interview Questions and Answers · · · ·


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Schnack Attack - East Greenwich High School's Best
Mrs. Schnacky has been a teacher for many years at East Greenwich High School, and she continues to keep the same high level and positive energy to every classroom each day. She is a teacher that stands out from others as she greets you with a big smile every day and goes above and beyond in every aspect.
Although her class is very challenging, she makes it top priority for her students to understand. She cares so much for her students that she offers them a 24/7 chemistry hotline with her own home number! She always responds to their questions, taking time out of her personal life. Mrs. Schnacky not only cares for her students and their academic futures, but their personal lives as well. She will listen and give you advice if you're struggling, and will take as much time as she can out of her day to be there as a teacher and mentor. She is brilliant and is talented in so many ways. After school, she rides her horse and feeds all of her pets she adores. She shares her love for animals and her many hobbies to the classroom which creates many icebreakers and fun conversations.
Smiling is the greatest gift you can give Mrs. Schnacky, because she loves to see her students glow. Just like her.


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Addressee Unknown
Another comma goes AWOL
By Merrill Perlman Feb 6, 2012 at 05:52 PM
The Super Bowl is over, thank heavens, so all those incorrectly punctuated signs rooting for one team or another can... More
Appositive Negatives
Some things are not unique
By Merrill Perlman Jun 6, 2011 at 02:38 PM
Last week, we talked about setting a parenthetical description off with commas in the grammatical phenomenon known as an "appositive."... More
Negative Appositives
Phrases set off by commas
By Merrill Perlman May 31, 2011 at 01:40 PM
Commas are wonderful tools. They tell a reader to pause, as this one did. They can also tell a reader... More
'See you on the other side' - Meet Jessica Lum, a terminally ill 25-year-old who chose to spend what little time she had practicing journalism
#Realtalk: This is the best moment to be in journalism - The old stuff isn't coming back, but that's okay
Streams of consciousness - Millennials expect a steady diet of quick-hit, social-media-mediated bits and bytes. What does that mean for journalism?
Sticking with the truth - How 'balanced' coverage helped sustain the bogus claim that childhood vaccines can cause autism
An ink-stained stretch - Can Aaron Kushner save the Orange County Register—and the newspaper industry?
This is the best moment to be in journalism (25)
The WSJ editorial page hits rock bottom (19)
The completist guide to Star Trek
Matt Yglesias watched every Star Trek movie and every episode of every TV show in the franchise
The uncomfortable questions not raised by Benghazi
The press and Congress are asking the wrong questions
Rob Ford in 'crack cocaine' video scandal
A video that appears to show Toronto's mayor smoking crack is being shopped around by a group of Somali men involved in the drug trade
Why the underwear-bomber leak infuriated the Obama administration
The threat of even grander leaks
HD footage from the World Trade Center's new spire
CJR's Guide to Online News Startups
Uptown Messenger – Hyperlocal news for a neighborhood in New Orleans
Who Owns What
The Business of Digital Journalism
A report from the Columbia University Graduate School of Journalism
Questions and exercises for journalism students.


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Maggie Koerth-Baker is the science editor at BoingBoing.net. She writes a monthly column for The New York Times Magazine and is the author of Before the Lights Go Out, a book about electricity, infrastructure, and the future of energy. You can find Maggie on Twitter and Facebook.
Maggie goes places and talks to people. Find out where she'll be speaking next.
MORE: Science
More at Boing Boing
Sativa Joe
When I went to Bella Tempo (a music festival in Minnesota) there were a lot of people selling alleged Molly (MDMA, usually in powder or crystal form) that were mephedrone. I understand drugs are always kinda of a crapshoot for quality and safety, but this was bordering on the ridiculous.
We had two guys die from Mephedrone here in my area
http://abclocal.go.com/wtvd/story?section=news/local&id=7713942 -
I have actually done bath salts, and imo the high is superior to coke. But I wouldn't do them again, they really do make people act crazy if they are on them for an extended time (like any speed really).
Half of all deaths from liver failure in the US every year are from acetaminophen aka paracetamol (brand names Tylenol, etc) overdose.
There have been no medically confirmed deaths from cannabis overdose ever.
One is made from petrochemicals and sold at high profits, which are used to bribe politicians. The other is a natural plant that grows all around the world for free.
So one kills hundreds of thousands of people and is legal. The other makes people feel good for free and is illegal.
The world is run by violent, amoral, profit seeking criminal syndicates but they dress in suits and have ceremonies so even many people that work for them don't realize it.
These articles should really tell us if it's any fun to take rather than how dangerous it is. I'm reliably informed that meow-meow was no fun at all. Which makes me wonder about bath salts. Is it even worth investigating?
That 'august' body The Caves Of Erowid has some interesting information to be found:
I tried some of the "reformulated" Spice while in Madison, WI.
At $15 an gram, it's no cheaper than buying an 8th of genuine weed.The high is closer to the disconnected feeling after breathing too much paint thinner.
The high lasts for 45 minutes followed by a blunt, constant headache.
It's legal. But so is paint thinner.Conclusion: If you're scared to buy or can't get a hold of real weed, Spice is not a good alternative.
I know I stopped listening to warnings about the drug after the British media claimed 5 lives had been lost to 'Meow-Meow' and the government subsequently made it illegal – then it turned out none of those deaths were linked to Meow Meow and in some of the cases people hadn't even taken the drug.
If official bodies want me to take drug control seriously they should start basing their regulations on scientific studies, rather than hearsay.
Incidentally it never appealed to me anyway, and those it appeals to will still take it. So like all drug control it's a bit of a moot point.
If official bodies want me to take drug control seriously they should start basing their regulations on scientific studies, rather than hearsay.
sadly, i recall that some UK politician basically stated that they would not consider scientific inputs when writing UK drug policies…
Self-induced psychosis isn't my idea of recreation.
They can have my MgSO4 when they pry it from my damp wrinkly fingers!
I wonder how many people have actually confused the two? After a bender: "Steve, you feeling anything? Me neither. But sure could take a dump right about now!"
Mephedrone was popular in the UK a couple of years ago.
Some newspapers ran scare stories, including some attributing deaths to mephedrone. Subsequent to this the drug was banned.
After the legislation was introduced, the scare stories were mostly discredited. In particular the one story about a death caused by mephedrone was show to be untrue.
Of course, even though the stories were shown to be untrue, the legislation they helped support has not been repealed.
The truth is that the government doesn't worry about the health impact of this . . . They simply don't want to legalised another way to get high. One reason for this is that they'd be crucified in the press.
Thanks for the de-mythologising post.
The wacky "hey people are tripping on bath salts!" reporting angle on these stories really annoys me. The basic, underlying fact is that these are things that are merely sold as bath salts by some accident of marketing and scene convention. The basic, chemical nature of these stimulant analogues is almost never reported, let alone emphasised.
Karl Stevens
"there is at least one death that can be directly tied to the use of 'bath salts'"
Coincidentally, that's the same number that can be attributed to drinking tap water (although I'm sure there have been more.)
Uh oh, I always mix my bath salts with hot tap water.
You sir, win the internet.
"…experts say the state bans can be thwarted by chemists who need change only one molecule in salts to make them legal again."
Right. By analogy, you could, say, change all the cocaine molecules in cocaine to water molecules and they'd be legal. Those tricky chemists! What will they think of next?
It's sloppy science writing like this drivel from the New York Times that makes me appreciate Boing Boing.
This is why the authorities should look the other way at much more fun and less dangerous drugs like marijuana, psilocybin, and mescaline.
I have no interest in doing "bath salts," but what's the justification for making them illegal? Is that really going to have the desired outcome?
I used to take mephedrone here in the UK. It's intended as an analogue for ecstasy, but you know what ecstasy never did? Put me in the psychiatric hospital for two weeks. I'm still not right a year later.
Come on people pleeeeeasse stop chasing down the next big high. She's already out there and it's called coke! Just stop buying the shit stuff
I recall watching a British documentary on "legal" drugs (mostly just mixtures of chemicals which simulated the high you got from various illegal drugs, then slapped "not for human consumption" on the packet).
One of the more interesting parts was an interview with an ER doctor who basically said "If you come in and you've overdosed on cocaine, well, that's bad, but at least we've seen cocaine. We know how it works, and we know what to do about it. If you come in overdosed on some bizarre concoction of chemicals that we've never seen before, then we're not always sure what to do with you".
Stick with the classics, kids.


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Although the state's Supreme Court chief justice has until early March to name a deciding vote for legislative redistricting, the real drop-dead date for when new legislative maps for county, state, and federal redistricting are due is April 4.
This could mean utter madness for those seeking to run in the June primary for the U.S. House of Representatives, state Senate and Assembly, and even freeholder, because it will give candidates only seven days to gather signatures on nominating petitions.
While this will matter less if the districts maintain more or less the same boundaries, if the boundaries change radically – as they are expected to do in some cases – then incumbents will have to scramble to get signatures from areas they are not accustomed to.
"This is the reason some people are afraid to move too soon," said Assemblyman Jason O'Donnell, who also serves as chairman of the Bayonne Democratic Organization. "If people gather signatures now, they might be gathering them from the wrong areas."
Bayonne Mayor Mark Smith, the Democratic chairman for Hudson County, and Republican Chairman Jose Arango, have radically different maps for freeholder districts. But the real battle will be over all three state legislative districts in Hudson County, which could change radically. It is possible the 31st District, which currently includes all of Bayonne and a large portion of Jersey City, could see a radical shift west, with Bayonne finding itself in the same district as Elizabeth. The 31st District might also expand northward into Hoboken or westward into West Hudson County.
The most significant change will be in North Hudson, where State Sens. Nicholas Sacco and Brian Stack currently serve in adjoining districts. While armchair quarterbacks had hoped for redistricting that would put Sacco in the same district with Stack and ignite a primary battle between two champion teams, most now believe Sacco's district will be moved into southern Bergen County, losing Secaucus and West Hudson while likely picking up West New York and Guttenberg.
At the center of the freeholder redistricting is the Hoboken district, with its 50,000 population, which will likely lose Jersey City Heights. Hoboken could even be split between two freeholder districts.
Letter gets it wrong
An apparent series of mistakes sent a number of long time Hoboken poll workers – most of whom are senior citizens – into a panic last week.
New to the process, Hoboken Councilman Ravi S. Bhalla, who is also chairman of the Hoboken Democratic Party, sent out a letter to District Board Workers on Feb. 18, informing them that it was time for them to submit applications to serve as district board workers for the upcoming municipal elections.
The letter, however, had several errors of fact. It directed applicants to return their applications to the Hoboken City Clerk's office, something that hasn't been done in decades if ever, rather than to the Hudson County Board of Elections in Jersey City. The letter also posted a deadline of March 1, 2011, which was also wrong. The letter also pointed out that school board elections this year will be run on April 27 from 6 a.m. to 9 p.m. Because of Passover, this is a rare Wednesday election. But state laws governing school elections say polls cannot open before 7 a.m.
This last error was generated by a resolution of the Hoboken Board of Education, which set the hours based on a change of state law for regular municipal elections that said polls could open as early as 6 a.m. and close as late as 9 p.m. Although most municipal elections and some school elections around the state generally run from 8 a.m. to 8 p.m., the Hoboken school board amended its elections to run from 7 a.m. to 9 p.m. to be in compliance with state law.
The longer hours, political observers point out, will actually benefit reform candidates, allowing more time for commuting parents to access the polls.
St. Patrick's Parade fundraiser opens political season in Hoboken
The official opening of Hoboken's election season began at the St. Patrick's Day Parade Fundraiser held last week at Our Lady of Grace Hall in Hoboken.
For 25 years, this has been the event where politicians running for office begin to show their faces. This was still true this year, when City Council reform candidates Rami Pinchevsky, Tom Greaney, and Eric Kurta arrived in suits and ties. Normally, this is not a formal affair. On the other side, incumbent candidates Tim Occhipinti and Beth Mason also worked the room.
Mayor Dawn Zimmer, who will be backing the reform ticket in May and mostly likely a slate for school board, also made appearance, as did school board candidates Carmelo Garcia and Frances Rhodes-Kearns.
Assemblyman Ruben Ramos and Freeholder Anthony Romano, both seeking reelection this year, wandered in as well.
The city's parade, slated for March 5, of course has its political overtones, since some residents along the route, particularly in the 5th and 6th wards, may be concerned with the noise.
While Zimmer clearly supports the parade, she is also apparently making moves to keep the noise levels down in two wards where she would like to see her candidates win.
Hoboken Democrats, meanwhile, are holding their annual Lincoln Day event at the Clinton Social Club honoring Ramos, who was supposed to be honored two years ago, but lost the honor due to political infighting. Last year, some reformers boycotted the event when City Clerk James Farina was honored. Hoboken Democrats have held this event since 1986 when they first honored West New York Mayor Anthony DeFino.
Fulop to back school board ticket in Jersey City
Councilman Steve Fulop, an already declared mayoral candidate for the 2013 municipal election, said at his fundraiser at the Beer Garden in Jersey City on Feb. 16 that he will back three candidates for school board this year: Susan Mack, Marvin Adams and Carol Harrison Arnold.