A stainless steel version similar to Apple's gold Watch band, once worn by Kanye West and Beyoncé, is now available for $349.

Online conversations about Ozempic and similar medications are full of misinformation — and echo decades of flawed teachings on weight management.

Carnival's budget-friendly cruises are a stark contrast from its sister brand Seabourn's luxury voyages.

We've rounded up the best stocking stuffers under $20 that are both fun and functional.

The Lo & Sons Aoyama travel purse is one of its best designs yet. We also compare its totes and weekender bags, which make commuting a lot more comfortable.

Winning the 2024 presidential election is already helping Donald Trump in all four of his criminal cases.

Sirio Pharma Co., Ltd. (Sirio), a global manufacturer of nutritional supplements, launched BloomDays^TM, a postbiotic gummy product featuring EpiCor®, Cargill’s postbiotic ingredient.

Floor Trends reached out to Tressa Samdal, VP of marketing for E.J. Welch Company, for a brief follow-up interview in the wake of the pandemic to see what has changed since we last spoke to her and ask what advice she would give to other women working their way up through the industry. 

Jeolla Province's largest environmental exhibition 'The 13th International Climate & Environment Fair'

Arindam Majumdar, deputy chief risk officer at Bank OZK, ensures compliance with national laws and regulations

In this episode, Dirk talks with David Frankel, resident Metamodeller and MDA expert at SAP Labs LLC, SAP's subsidiary in the Silicon Valley. Dave's extensive experience provides a big picture, from the early days of CORBA all the way to current issues that are bugging most enterprise architects' work with MDA.

this really is a good list of books

The Bermuda Medical Doctors Association elected Dr. Kyjuan H. Brown as President, along with a new executive team, at its Annual General Conference on October 24, 2024. A spokesperson said, “The Bermuda Medical Doctors Association [BMDA] is pleased to announce the election of its new executive team following the Annual General Conference held on October […]

Denzel Washington may have let slip that director Ryan Coogler is working on a third "Black Panther" film, which Marvel has not yet announced.

"I think they say they want autonomy. I think their actions don't say the same thing," Airbnb CEO Brian Chesky recently said in an interview.

Taylor Swift has made a habit of cheering for the Kansas City Chiefs since she began dating NFL star Travis Kelce.

Marilyn Chinitz has worked with celebs like Tom Cruise, Michael Douglas, and Wendy Williams. She has been happily married for 38 years.

It's a British heritage brand driven by royals, including the late Queen Elizabeth. Now new Jaguars won't be on UK car lots until at least 2026.

Too much fluoride can make your teeth brown, but getting a little bit is a dentist's dream. Here's the complete history of fluoridated water.

HMDA and Housing Demand

The adipocyte-derived hormone leptin increases trafficking of KATP and Kv2.1 channels to the pancreatic β-cell surface, resulting in membrane hyperpolarization and suppression of insulin secretion. We have previously shown that this effect of leptin is mediated by the NMDA subtype of glutamate receptors (NMDARs). It does so by potentiating NMDAR activity, thus enhancing Ca2+ influx and the ensuing downstream signaling events that drive channel trafficking to the cell surface. However, the molecular mechanism by which leptin potentiates NMDARs in β-cells remains unknown. Here, we report that leptin augments NMDAR function via Src kinase–mediated phosphorylation of the GluN2A subunit. Leptin-induced membrane hyperpolarization diminished upon pharmacological inhibition of GluN2A but not GluN2B, indicating involvement of GluN2A-containing NMDARs. GluN2A harbors tyrosine residues that, when phosphorylated by Src family kinases, potentiate NMDAR activity. We found that leptin increases phosphorylation of Tyr-418 in Src, an indicator of kinase activation. Pharmacological inhibition of Src or overexpression of a kinase-dead Src mutant prevented the effect of leptin, whereas a Src kinase activator peptide mimicked it. Using mutant GluN2A overexpression, we show that Tyr-1292 and Tyr-1387 but not Tyr-1325 are responsible for the effect of leptin. Importantly, β-cells from db/db mice, a type 2 diabetes mouse model lacking functional leptin receptors, or from obese diabetic human donors failed to respond to leptin but hyperpolarized in response to NMDA. Our study reveals a signaling pathway wherein leptin modulates NMDARs via Src to regulate β-cell excitability and suggests NMDARs as a potential target to overcome leptin resistance.

Vukile Property Fund plans to build more solar farms to power its malls and reduce its reliance on Eskom's power by another 5% by the end of March 2023.

For the Pakistani military, the F-16 sale is tangible proof of the post-9/11 bilateral relationship, and we seriously doubt they will allow it to fail.

Sukanta Majumdar: বিজেপি নেতা রাহুল সিনহা বলেন, নির্বাচন কমিশন যখন কাউকে শো কজ করে তখন স্বাভাবিকভাবেই মন্তব্য করতে চাই না। তবে বলতে চাই কিছু আইপিএসের যে আচরণ তাতে মানুষ তিতিবিরক্ত

Your construction-related queries answered by Green Evolution, a Chennai-based architectural service firm

The other day I had to test an API response based on a file having the incorrect Content-Type of a FormData PUT request. After some digging in cURL I found the -F & --form flag to set the file and its content type. If you don’t specify the content type it will be inferred from … Continue reading "Changing content type of a file in a FormData request with cURL"

In a shocking revelation, senior journalist Rajeev Bhattacharyya’s latest book ‘ULFA : The Mirage of Dawn‘s page no 280 reads that “A former Director General of Assam police hired a surrendered ULFA (SULFA) activist to assassinate editor Anil Mazumdar in Guwahati on 24 March 2009.” The same also added “After two weeks, the police chief […]

The post Journalist Anil Majumdar was Killed By Former DGP of Assam | ULFA : The Mirage of Dawn appeared first on TIMES OF ASSAM by Dhruba Jyoti Deka.

The Indian team delivered a lackluster performance on the field, ultimately resulting in a nine-run loss to defending champions Australia in their must-win game on Sunday (October 14, 2024)

How a jamdani weaving cluster in Srikakulam, established by Hyderabad-based textile designer Gaurang Shah, is helping women learn the heritage craft and weave heirloom-worthy saris

Cash flows will be tight and they may also experience delay in the investment cycle, but this is a temporary phase, says Bhaskar Majumdar, managing partner, Unicorn India Ventures (UIV), a Mumbai-based fund house.

7) Munnaf Ali, have sought for pre-arrest bail in the event of their arrest in connection with Chhaygaon PS Case No. 207/2020, corresponding to GR Case No. 369 (K)/2020, under Sections 143/147/148/447/325/302 IPC.

Heard Mr B Chowdhury, learned counsel for the petitioners. Also heard Mr N Kalita, learned Additional Public Prosecutor for the State of Assam.

Also perused the record and the Case Diary produced.

It is submitted by the learned Additional Public Prosecutor, Mr Kalita that so far as the accused Page No.# 3/3 petitioners, namely, 1) Imdadul Hoque and 2) Bilat Ali are concerned, their sufficient implication have been given by the eyewitnesses, regarding the commission of the offence.

1. The appellant filed an application under the Right to Information Act, 2005 (RTI Act) before the Central Public Information Officer (CPIO), Eastern Railway, DRMO Howrah Division seeking information on two points, including,

a) To provide a copy of S.DPO/HWH Letter No. E/Engg/OC/Policy/Pt.IV/2nd Phase dated 31.07.2015, 07.08.2015, and,

b) To provide a copy of seniority list of Track Maintainer III and IV from 2007 to 2015.

2. The CPIO, vide reply dated 27.04.2020, provided requisite information to the appellant. The appellant filed a first appeal dated 24.04.2018 on the ground of no information furnished by the CPIO. The first appeal was not disposed of by the FAA. Thereafter, the appellant filed a second appeal u/Section 19(3) of the RTI Act before the Commission on the ground of non-receipt of information and requested the Commission to direct the CPIO to provide the information sought for.

The recent developments at microdiffraction X-ray beamlines are making microcrystals of macromolecules appealing subjects for routine structural analysis. Microcrystal diffraction data collected at synchrotron microdiffraction beamlines may be radiation damaged with incomplete data per microcrystal and with unit-cell variations. A multi-stage data assembly method has previously been designed for microcrystal synchrotron crystallography. Here the strategy has been implemented as a Python program for microcrystal data assembly (PyMDA). PyMDA optimizes microcrystal data quality including weak anomalous signals through iterative crystal and frame rejections. Beyond microcrystals, PyMDA may be applicable for assembling data sets from larger crystals for improved data quality.

(California Court of Appeal) - In a stockholder's suit against a company and individual directors, claiming that both the acquisition process, and the common stock arising from the acquisition were unfair, the judgment of the trial court is affirmed in part, reversed in part and remanded where: 1) the doctrine of shareholder ratification does not bar the intervenor's claims; 2) the intervenor's complaint, which consists of a single cause of action states facts sufficient for a cause of action for breach of fiduciary duties as to the individual directors; and 3) trial court's judgment sustaining the demurrer as to the company is affirmed.

[S-Methyl-¹¹C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (¹¹C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. ¹¹C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: ¹¹C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.

The chic sneaks are part of Zappos' massive Cyber Monday sale.

You've got exactly four hours left to take advantage of these heavily discounted prices.

You can save 50% right now. 

This retro style is making a comeback for a reason.

They’re already going out of stock.

M Niethammer
Apr 1, 1996; 16:2157-2163
Articles

Zhengui Xia
Sep 1, 1996; 16:5425-5436
Articles

Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia's pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone.

SIGNIFICANCE STATEMENT NMDAR hypofunction in cortical interneurons has been linked to schizophrenia pathophysiology. How a dysfunction of GABAergic cortical interneurons interacts with maturation during adolescence has not been clarified yet. Here, we demonstrate in vivo that early postnatal ablation of the NMDAR in corticolimbic interneurons results in an overactive but desynchronized PFC before adolescence. Final postnatal maturation during this stage outspreads the impact of the genetic manipulation toward a functional disconnection of the ventral hippocampal-prefrontal pathway, probably as a consequence of an exacerbated propensity toward hippocampal-evoked depotentiation plasticity. Our results demonstrate a complex interaction between genetic and developmental factors affecting cortical interneurons and PFC function.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca²⁺ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b. Both grin1a^–/– and grin1b^–/– zebrafish are viable. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double-mutant fish (grin1a^–/–; grin1b^–/–), which lack all NMDAR-mediated synaptic transmission, survive until ~10 d dpf (days post fertilization), providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double-mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey-capture deficits, and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting that they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.

SIGNIFICANCE STATEMENT Rapid communication between cells in the nervous system depends on ion channels that are directly activated by chemical neurotransmitters. One such ligand-gated ion channel, the NMDAR, impacts nearly all forms of nervous system function. It has been challenging, however, to study the prolonged absence of NMDARs in vertebrates, and hence their role in nervous system development, due to experimental limitations. Here, we demonstrate that zebrafish lacking all NMDAR transmission are viable through early development and are capable of a wide range of stereotypic behaviors. As such, this zebrafish model provides a unique opportunity to study the role of NMDAR in the development of the early vertebrate nervous system.

Structural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength. Here, using two-photon glutamate uncaging to induce plasticity at individual dendritic spines on hippocampal CA1 neurons from mice and rats of both sexes, we demonstrate that p38 MAPK is generally required downstream of non-ionotropic NMDAR signaling to drive both spine shrinkage and LTD. In a series of pharmacological and molecular genetic experiments, we identify key components of the non-ionotropic NMDAR signaling pathway driving dendritic spine shrinkage, including the interaction between NOS1AP (nitric oxide synthase 1 adaptor protein) and neuronal nitric oxide synthase (nNOS), nNOS enzymatic activity, activation of MK2 (MAPK-activated protein kinase 2) and cofilin, and signaling through CaMKII. Our results represent a large step forward in delineating the molecular mechanisms of non-ionotropic NMDAR signaling that can drive shrinkage and elimination of dendritic spines during synaptic plasticity.

SIGNIFICANCE STATEMENT Signaling through the NMDA receptor (NMDAR) is vitally important for the synaptic plasticity that underlies learning. Recent studies highlight a novel role for the NMDAR, independent of ion flow, in driving synaptic weakening and dendritic spine shrinkage during synaptic plasticity. Here, we delineate several key components of the molecular pathway that links conformational signaling through the NMDAR to dendritic spine shrinkage during synaptic plasticity.