Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y₅ receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons. Repeated treatment of OTCs with NPY followed by an identical treatment with CRF, or vice versa, inhibited or reversed all structural changes in OTCs. These structural responses to NPY or CRF required calcineurin or CaMKII, respectively. Finally, repeated intra-BLA injections of NPY or a Y₅ receptor agonist increased social interaction, a validated behavior for anxiety, and recapitulated structural changes in BLA neurons seen in OTCs, while a Y₅ receptor antagonist prevented NPY's effects both on behavior and on structure. These results implicate the Y₅ receptor in the long-term, anxiolytic-like effects of NPY in the BLA, consistent with an intrinsic role in stress buffering, and highlight a remarkable mechanism by which BLA neurons may adapt to different levels of stress. Moreover, BLA OTCs offer a robust model to study mechanisms associated with resilience and vulnerability to stress in BLA.

SIGNIFICANCE STATEMENT Within the basolateral amygdala (BLA), neuropeptide Y (NPY) is associated with buffering the neural stress response induced by corticotropin releasing factor, and promoting stress resilience. We used a novel organotypic slice culture model of BLA, complemented with in vivo studies, to examine the cellular mechanisms associated with the actions of NPY. In organotypic slice cultures, repeated NPY treatment reduces the complexity of the dendritic extent of anxiogenic BLA principal neurons, making them less excitable. NPY, via activation of Y5 receptors, additionally inhibits and reverses the increases in dendritic extent and excitability induced by the stress hormone, corticotropin releasing factor. This NPY-mediated neuroplasticity indicates that resilience or vulnerability to stress may thus involve neuropeptide-mediated dendritic remodeling in BLA principal neurons.

Perhaps it was not just a massive slice that made Pizza Rat a true New Yorker

Expelled by animals as a waste product, the gas appears to play a crucial role in keeping these bizarre, burrowing rodents safe

Mice, rats, or hamsters are immunized by giving biweekly injections of a purified antigen, cultured cells, or cDNA. For mice, if a pure, soluble protein antigen is being used and is abundant, a dose of 50–100 µg in adjuvant at each immunization is a sensible general recommendation; for rats and hamsters, a dose of 100–200 µg is sufficient. Lower doses can be used for antigens with higher immunogenicity. Adjuvants (Freund's, Ribi, Hunter's TiterMax, ImmunEasy, or Alum) should be mixed with the immunizing antigen for the first two immunizations only; Complete Freund's adjuvant is only used with the first immunization. Subsequent immunizations are performed in phosphate-buffered saline (PBS) or normal saline, with or without Incomplete Freund's adjuvant. The choice of adjuvant is dependent on the subclass of immunoglobulin required. Over the course of the 6-wk immunization schedule, each animal usually receives a total of six injections (three subcutaneous and three intraperitoneal). Once a good titer has developed against the antigen of interest, regular boosts and bleeds are performed to collect the maximum amount of serum. For rats and hamsters, boosts should be spaced every 2–3 wk, and serum samples of 400–500 µL should be collected 10–12 d after each boost. For mice, boosts should be spaced every 2–3 wk, and serum samples of 200–300 µL should be collected 10–12 d after each boost.

State adviser says government was sympathetic to the economic difficulties caused by the on-going lockdown but growth in infections in areas such as the Western Cape are biggest risk to the faster reopening of the economy.

Mardi Gras in New Orleans has always had a gothic element. The voodoo culture dates from the African American diaspora, though it’s now mostly for tourists. But this year there was an authentically macabre dimension to Fat Tuesday.

House Democrats are demanding that companies return federal dollars that they say were intended for smaller businesses

Pressure from progressives for more expansive government assistance programs, especially now during the COVID pandemic, along with concerns over a recent sexual assault allegation and a challenge from a third-party candidate, threaten to fracture that unified support

Opposition to President Donald Trump has consolidated Democratic party...

Bill Maher is rather frustrated with Democrats and the liberal media . In particular, the talk show host and comedian...

While President Donald Trump traveled to the battleground state of Arizona this week, his Democratic opponent for the White House, Joe Biden, campaigned from his basement as he has done throughout the coronavirus pandemic.

Robots made of 3D-printed muscle and rat spines could help us understand conditions like motor neurone disease and the technique may eventually be used to build prosthetic devices

Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine herb Cinnamomum cassia, has been reported to have multipharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell Counting Kit ‎CCK-8 assay was performed to evaluate the cell cytotoxicity. Proinflammatory cytokine expression was evaluated using quantitative polymerase chain reaction and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg per day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histologic examinations. Cin significantly inhibited interleukin (IL)-1β–induced IL-6, IL-8, and tumor necrosis factor-α release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6–induced activation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1), and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1, and STAT3, without affecting NF-B pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion and destruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1β–induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential traditional Chinese medicine–derived, disease-modifying, antirheumatic herbal drug.

Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (A-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized KPR-5714 (N-[(R)-3,3-difluoro-4-hydroxy-1-(2H-1,2,3-triazol-2-yl)butan-2-yl]-3-fluoro-2-[5-(4-fluorophenyl)-1H-pyrazol-3-yl]benzamide), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels. Intravenously administered KPR-5714 inhibited the hyperactivity of mechanosensitive C-fibers of bladder afferents and dose-dependently increased the intercontraction interval shortened by intravesical instillation of acetic acid in anesthetized rats. Furthermore, we examined the effects of KPR-5714 on voiding behavior in conscious rats with cerebral infarction and in those exposed to cold in metabolic cage experiments. Cerebral infarction and cold exposure induced a significant decrease in the mean voided volume and increase in voiding frequency in rats. Orally administered KPR-5714 dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume in these models. This study demonstrates that KPR-5714 improves OAB in three different models by inhibiting exaggerated activity of mechanosensitive bladder C-fibers and suggests that KPR-5714 may provide a new and useful approach to the treatment of OAB.

In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is demonstrable at 24 h, but not 48 h, posttraining. Using this paradigm, pups that showed peppermint preference 30 min posttraining were sacrificed 20 min later for laser microdissection of odor-encoding mitral cells. Controls were given odor only. Microarray analysis revealed that 13 nonprotein-coding mRNAs linked to mRNA translation and splicing and 11 protein-coding mRNAs linked to transcription differed with odor preference training. MicroRNA23b, a translation inhibitor of multiple plasticity-related mRNAs, was down-regulated. Protein-coding transcription was up-regulated for Sec23b, Clic2, Rpp14, Dcbld1, Magee2, Mstn, Fam229b, RGD1566265, and Mgst2. Gng12 and Srcg1 mRNAs were down-regulated. Increases in Sec23b, Clic2, and Dcbld1 proteins were confirmed in mitral cells in situ at the same time point following training. The protein-coding changes are consistent with extracellular matrix remodeling and ryanodine receptor involvement in odor preference learning. A role for CREB and AP1 as triggers of memory-related mRNA regulation is supported. The small number of gene changes identified in the mitral cell input/output link for 24 h memory will facilitate investigation of the nature, and reversibility, of changes supporting temporally restricted long-term memory.

Subtractive immunization is useful for directing the immune response away from dominant epitopes to allow antibodies against less immunogenic antigens to be developed. It is also useful when there is a need to downplay the response to carriers added to peptides and recombinant proteins, such as Gst and Ig, to aid in production and purification. Subtractive immunization protocols also can be helpful if the target protein is part of a mixture (such as a cell lysate) or present on the surface of transfected cells.

The repetitive immunization at multiple sites (RIMMS) protocol capitalizes on the animal's innate immune system, which is genetically preprogrammed to recognize many antigens. By repetitively immunizing the animal, B cells that recognize the antigen are kept continuously expanding until the lymph nodes are harvested for hybridoma generation. This is a good method for making a more diverse repertoire of antibodies or antibodies directed against conformational epitopes.

Robots made of 3D-printed muscle and rat spines could help us understand conditions like motor neurone disease and the technique may eventually be used to build prosthetic devices

What’s going to get Jen first: the discovery of what’s happening in her garage, or the guilt over what she hasn’t told her BFF?

While President Donald Trump traveled to the battleground state of Arizona this week, his Democratic opponent for the White House, Joe Biden, campaigned from his basement as he has done throughout the coronavirus pandemic.

U.S. House of Representatives Speaker Nancy Pelosi on Thursday laid out the broad outlines of the next massive coronavirus-response bill Democrats will seek, with possible votes as soon as next week.

While President Donald Trump traveled to the battleground state of Arizona this week, his Democratic opponent for the White House, Joe Biden, campaigned from his basement as he has done throughout the coronavirus pandemic.

Chief Justice John Roberts on Friday put a temporary hold on the release of secret materials from former special counsel Robert Mueller's investigation to a Democrat-led House committee.

The order stops the clock on a lower court's ruling requiring the Justice Department to turn over confidential grand jury materials underlying ...

Republican lawmakers accused House Speaker Nancy Pelosi of "cowering" from the coronavirus on Friday and said they're ready to get back to work, even as President Trump said he is in "no rush" to negotiate with Democrats over another emergency aid package.

During a meeting at the White House with ...

The closure of cafes and restaurants in Rome due to the coronavirus outbreak means seagulls have had to change their habits and start eating rats, zoologists claim.

Humans can easily forget that the cities and towns they call home and frequently visit are also home to wild animals, writes Sandra E Garcia. In Wales, goats roam the streets, while in San Francisco the Coyotes have come out

McGowan previously called her 'Charmed' co-star Alyssa Milano a 'fraud' for endorsing Biden

The party is downplaying expectations in next week's special election for a congressional seat in the L.A. suburbs.

Two former Inslee campaign staffers have a message for Joe Biden: To unite the Democratic party, prioritize climate policies.

Bernie Sanders, who has criticized Amazon's treatment of its blue-collar workforce, led the field of Democratic presidential hopefuls in donations from Amazon employees, with support from both warehouse workers and software engineers.

Bernie Sanders has been called "selfish" for failing to "get out" of the presidential race but the senator from Vermont has given no indication he is going anywhere.

npj Microgravity, Published online: 24 February 2020; doi:10.1038/s41526-020-0096-x

The recently released infrastructure framework from House Democrats is a broad statement of purpose, not a specific legislative agenda, says Adie Tomer, a sign that it's intended more as a platform for generating productive debate over the details--especially the always-contentious funding question. Tomer explains the wide range of programs covered in the proposal, why Democrats…

The growing unilateralism and weaponization of trade policy by President Trump have turned into the most grievous risk for a rules-based international system that ensures fairness, reciprocity and a level playing field for global trade. If this trend continues, trade policy will end up being decided by interest groups with enough access to influence and…

Why did so many traditionally “blue” communities break for Donald Trump in 2016? Will they do so again in 2020? Looking for answers, Muravchik and Shields lived in three such “flipped” blue communities, finding that these voters still like the Democratic Party, but it’s not the party many of this book’s readers will recognize. In…

U.S. efforts to promote democracy in the Middle East have long been paralyzed by a unique “Islamist dilemma”: We want democracy in theory but fear its outcomes in practice. In this case, the outcomes that we fear are Islamist parties either doing well in elections or winning them outright. If we would like to (finally)…

For more than two weeks now, a stream of current and former U.S. officials, this week including Amb. Bill Taylor, have described to Congressional committees the White House’s sordid effort to outsource American foreign policy to the president’s lawyer, Rudy Giuliani, who sought to advance the personal political interests of Donald Trump. Faced with compelling…

U.S. efforts to promote democracy in the Middle East have long been paralyzed by a unique “Islamist dilemma”: We want democracy in theory but fear its outcomes in practice. In this case, the outcomes that we fear are Islamist parties either doing well in elections or winning them outright. If we would like to (finally)…

The growing unilateralism and weaponization of trade policy by President Trump have turned into the most grievous risk for a rules-based international system that ensures fairness, reciprocity and a level playing field for global trade. If this trend continues, trade policy will end up being decided by interest groups with enough access to influence and…

The economic crisis and pandemic have made it patently clear that US capitalism is not at all exceptional. Like everything else in the universe, American capital’s political system is subject to sharp and sudden changes. After Bernie Sanders handily won the first few contests of the 2020 race for the Democratic nomination, he was seen as an unstoppable threat—prompting every other candidate to immediately fold up their campaigns and close ranks against him. After months of panicking over Bernie’s momentum, the ruling class finally managed to reverse the course of the electoral race—and they did it with unprecedented speed. Now, after an electrifying rollercoaster ride, Bernie Sanders’s campaign for the American presidency is over, and a balance sheet is needed.

Usually, air-dropping over 20 tons of poison from an helicopter on a fragile island ecosystem would be a very bad thing...

The GOP groups are arguing that Democrats are applying a different standard to Biden, who has denied that he assaulted former Senate staffer Tara Reade in 1993, than they did to Justice Brett Kavanaugh.

Democrats are pushing to pass their next coronavirus relief bill, but Republicans have less urgency as they grow wary of taxpayer spending.

Why the rhetoric surrounding wealth inequality is especially acute this election season among Democratic presidential candidates — and will continue to be so.