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Supporting Wildlife with Statistics

Dr. Outi Tervo of Greenland Institute for Natural Resources, shares how mathematics helps recommend speed limits for marine vessels, which benefits narwhals and Inuit culture. Narwhals "can only be found in the Arctic," said Outi Tervo, a senior scientist at GINR. "These species are going to be threatened by climate change more than other species that can live in a bigger geographical area." The collaboration has already lobbied on behalf of the narwhals to reduce the level of sea traffic in their habitat, after using mathematical analysis to identify how noise from passing boats changes the narwhals' foraging behavior.




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Moduli Spaces and Vector Bundles—New Trends

Peter Gothen, Margarida Melo and Montserrat Teixidor i Bigas, editors. American Mathematical Society, 2024, CONM, volume 803, approx. 380 pp. ISBN: 978-1-4704-7296-2 (print), 978-1-4704-7646-5 (online).

This volume contains the proceedings of the VBAC 2022 Conference on Moduli Spaces and Vector Bundles—New Trends, held in honor of Peter...





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Analysis-India's middle class tightens its belt, squeezed by food inflation




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Woman in custody after allegedly stabbing boyfriend in Los Angeles




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A mom’s worst nightmare - East Kingston mother mourns teen son after deadly clash with cops

Kadian Morgan was overwhelmed with grief as she leaned against a wall outside her gate on Jackson Lane, East Kingston, yesterday, tears streaming down her face. Her 19-year-old son, Kayshan 'Bem Bem' Smith, was lying in the morgue after being...




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Police make arrest relating to bags of cash that allegedly fell from Beryllium vehicle

The police have arrested an individual in the probe surrounding two bags of cash that allegedly fell from a Beryllium security vehicle en route to the Norman Manley International Airport in Kingston last week. 




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Landscaper charged for allegedly stealing oranges

The Clarendon police have arrested and charged 25-year-old landscaper Anthony Marshall, of Lamparth district, Trout Hall in the parish for allegedly stealing oranges from a property in his community on Sunday.




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BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells [Signal Transduction]

Bone morphogenetic protein-9 (BMP-9) is a circulating cytokine that is known to play an essential role in the endothelial homeostasis and the binding of BMP-9 to the receptor activin-like kinase 1 (ALK-1) promotes endothelial cell quiescence. Previously, using an unbiased screen, we identified ALK-1 as a high-capacity receptor for low-density lipoprotein (LDL) in endothelial cells that mediates its transcytosis in a nondegradative manner. Here we examine the crosstalk between BMP-9 and LDL and how it influences their interactions with ALK-1. Treatment of endothelial cells with BMP-9 triggers the extensive endocytosis of ALK-1, and it is mediated by caveolin-1 (CAV-1) and dynamin-2 (DNM2) but not clathrin heavy chain. Knockdown of CAV-1 reduces BMP-9–mediated internalization of ALK-1, BMP-9–dependent signaling and gene expression. Similarly, treatment of endothelial cells with LDL reduces BMP-9–induced SMAD1/5 phosphorylation and gene expression and silencing of CAV-1 and DNM2 diminishes LDL-mediated ALK-1 internalization. Interestingly, BMP-9–mediated ALK-1 internalization strongly re-duces LDL transcytosis to levels seen with ALK-1 deficiency. Thus, BMP-9 levels can control cell surface levels of ALK-1, via CAV-1, to regulate both BMP-9 signaling and LDL transcytosis.




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LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

Auguste Dargent
Dec 1, 2020; 61:1776-1783
Research Articles




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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux

Oktawia Nilsson
Nov 17, 2020; 0:jlr.RA120000920v1-jlr.RA120000920
Research Articles




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rHDL modelling and the anchoring mechanism of LCAT activation

Tommaso Laurenzi
Dec 2, 2020; 0:jlr.RA120000843v1-jlr.RA120000843
Research Articles




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Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects

Akemi Kakino
Nov 3, 2020; 0:jlr.RA120000767v1-jlr.RA120000767
Research Articles




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Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects [Research Articles]

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.




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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux [Research Articles]

Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of patients carrying either L75P or L174S ApoA-I amyloidogenic variants a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.




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rHDL modelling and the anchoring mechanism of LCAT activation [Research Articles]

Lecithin:cholesterol-acyl-transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodelling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT func- tionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences. Although several hypotheses were formulated, the exact molecular recognition mechanism between LCAT and HDLs is still unknown. We employed a combination of structural bioinformatics procedures to deepen the insights into the HDL-LCAT interplay that promotes LCAT activation and cholesterol esterification. We have generated a data-driven model of reconstituted HDL (rHDL) and studied the dynamics of an assembled rHDL::LCAT supramolecular complex, pinpointing the conformational changes originating from the interaction between LCAT and apolipoprotein A-I (apoA-I) that are necessary for LCAT activation. Specifically, we propose a mechanism in which the anchoring of LCAT lid to apoA-I helices allows the formation of a hydrophobic hood that expands LCAT active site and shields it from the solvent, allowing the enzyme to process large hydrophobic substrates.




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Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance [Research Articles]

Angiopoietin-like protein (ANGPTL)3 regulates plasma lipids by inhibiting LPL and endothelial lipase (EL). ANGPTL3 inactivation lowers LDL-C independently of the classical LDLR-mediated pathway and represents a promising therapeutic approach for individuals with homozygous familial hypercholesterolemia due to LDLR mutations. Yet, how ANGPTL3 regulates LDL-C levels is unknown. Here, we demonstrate in hyperlipidemic humans and mice that ANGPTL3 controls VLDL catabolism upstream of LDL. Using kinetic, lipidomic, and biophysical studies, we show that ANGPTL3 inhibition reduces VLDL-lipid content and size, generating remnant particles that are efficiently removed from the circulation. This suggests that ANGPTL3 inhibition lowers LDL-C by limiting LDL particle production. Mechanistically, we discovered that EL is a key mediator of ANGPTL3’s novel pathway. Our experiments revealed that, although dispensable in the presence of LDLR, EL-mediated processing of VLDL becomes critical for LDLR-independent particle clearance. In the absence of EL and LDLR, ANGPTL3 inhibition perturbed VLDL catabolism, promoted accumulation of atypical remnants, and failed to reduce LDL-C. Taken together, we uncover ANGPTL3 at the helm of a novel EL-dependent pathway that lowers LDL-C in the absence of LDLR.




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LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients [Research Articles]

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.




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The Insulin Receptor Adaptor IRS2 is an APC/C Substrate That Promotes Cell Cycle Protein Expression and a Robust Spindle Assembly Checkpoint [Research]

Insulin receptor substrate 2 (IRS2) is an essential adaptor that mediates signaling downstream of the insulin receptor and other receptor tyrosine kinases. Transduction through IRS2-dependent pathways is important for coordinating metabolic homeostasis, and dysregulation of IRS2 causes systemic insulin signaling defects. Despite the importance of maintaining proper IRS2 abundance, little is known about what factors mediate its protein stability. We conducted an unbiased proteomic screen to uncover novel substrates of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that controls the abundance of key cell cycle regulators. We found that IRS2 levels are regulated by APC/C activity and that IRS2 is a direct APC/C target in G1. Consistent with the APC/C's role in degrading cell cycle regulators, quantitative proteomic analysis of IRS2-null cells revealed a deficiency in proteins involved in cell cycle progression. We further show that cells lacking IRS2 display a weakened spindle assembly checkpoint in cells treated with microtubule inhibitors. Together, these findings reveal a new pathway for IRS2 turnover and indicate that IRS2 is a component of the cell cycle control system in addition to acting as an essential metabolic regulator.




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Middle East and North Africa

Middle East and North Africa

Research on the Middle East and North Africa region focuses on changes to politics and society, economics, and security issues.

nfaulds-adams… 20 January 2020

This is a turbulent period for the region following the Arab Spring, with conflict in Syria continuing to impact its neighbours, governance in Libya under scrutiny, and increasing pressures on the Gulf monarchies, especially around human rights.   

Key research areas include the Gulf States and the Gulf Cooperation Council (GCC), the future of the state, mapping the region’s war economies, the Yemen conflict, Iraq’s reconstruction, and the influence of Saudi Arabia and Iran.




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The ProteoRed MIAPE web toolkit: A user-friendly framework to connect and share proteomics standards [Technology]

The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/.




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Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Field scout recording desert black rhino data, Save the Rhino Trust, Palmwag, Torra Conservancy, Damaraland, Namibia. Photo: Mint Images/Frans Lanting/Getty Images.

Summary

  • The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
  • In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
  • The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
  • The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.




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First mpox vaccines arrive in Africa as officials work “blindly” to contain outbreaks




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Middle East and great power competition

Middle East and great power competition 28 November 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 25 October 2022 Chatham House and Online

Experts discuss how the Middle East is changing in a fast-moving geopolitical environment.

The war in Ukraine and great power competition define not only global politics but also regional ones. The Middle East is a microcosm for observing how the great power rivalry informs regional affairs.

OPEC+’s decision to reduce oil supply to international markets and many regional states’ balancing act between the West and Russia, for that matter China as well, are only a few recent policy choices that clearly illustrate how the global and regional levels interact with each other.

Plus this is now a region in which the US has downsized its security commitments, whereas Russia has increased its footprint in regional security and China in economy.

This event tries to unpack how the great power rivalry and the war in Ukraine affect regional politics and how the Middle East adjusts itself to this new phase in global politics.




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Turkey's Foreign Policy in the Middle East

Turkey's Foreign Policy in the Middle East 14 May 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 29 April 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey is cooperating closely with Russia to secure its border with Syria and to encourage a long-term political resolution to the Syrian conflict. Its efforts have staved off a humanitarian catastrophe in the northern Syrian province of Idlib and initiated the trilateral ‘Astana Process’ with Russia and Iran as the primary framework to settle the future of Syria.

By contrast, Turkey and the US disagree on a range of important issues including Turkey’s purchase of the Russian-made S-400 air missile defence systems and American support for the PKK-affiliated Peoples’ Protection Units (YPG) in Syria.

In this session, the speaker will outline Turkey’s foreign policy priorities in the Middle East and share his country’s perspectives on the US and Russian policies in that region.

Attendance at this event is by invitation only.




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American woman killed in Budapest allegedly by man she met on vacation

An American woman who was traveling in Hungary was killed in Budapest last week allegedly by a man she met on vacation.




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‘Loopholes’ let warring parties use incendiary weapons in Ukraine, Middle East: HRW

Loopholes in international laws governing the use of incendiary weapons in warfare are allowing warring parties in Ukraine and the Middle East to exploit the use of such weapons without adequately protecting civilians.




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Biden, Israeli President Herzog meet to discuss Gaza, Middle East

President Joe Biden and Israeli President Isaac Herzog met at the White House on Tuesday afternoon to discuss the war against Hamas and Hezbollah and other Middle East concerns.




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Google educates users about the moon cycle with new Doodle game

Google is educating users about the lunar cycle with its latest interactive Doodle released Thursday.




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Why People Are More Bored Than Ever — Despite Endless Online Content (M)

Discover why more content isn’t solving your boredom but making it worse.




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The otters of Singapore — and other unexpected wildlife thriving in cities | Philip Johns

Animal behavior expert Philip Johns introduces us to the vibrant urban environments of Singapore, where city dwellers and skyscrapers coexist with a rich array of other species, including otters, hornbills and lizards — prompting the question: Can we design cities to be wildlife refuges?




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From prison to purpose through wildland firefighting | Royal Ramey

When wildfires rage in California, incarcerated people are often on the front lines fighting the flames. TED Fellow Royal Ramey was one of them. He shares the story of how doing public service in prison inspired him to cofound the Forestry and Fire Recruitment Program, a nonprofit helping formerly incarcerated people become wildland firefighters — and find purpose along the way.




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Don’t Bungle Your Bundles

Does grouping products together into a single-price bundle increase the perception of value? Most of us would answer “yes,” but surprising research shows there is at least one condition where such grouping can actually reduce the apparent value. Here’s the most surprising and counterintuitive part: the bundle may be seen as worth not just less […]

The post Don’t Bungle Your Bundles appeared first on Neuromarketing.




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Call for papers: SJDM, San Francisco, Nov 17-20, 2023. Submission deadline June 22, 2023

Call for papers: SJDM, San Francisco, Nov 17-20, 2023. Submission deadline June 22, 2023




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Virus worries latest hurdle in Florida school shooting case




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Washoe middle, high schools suspending in-class instruction




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Washoe middle, high schools suspending in-class instruction




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Virus worries latest hurdle in Florida school shooting case




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Indiana Educators Race to Renew Teaching Licenses Before Deadline

Thousands of Indiana teachers are scrambling to begin renewing their professional teaching licenses before new rules that state lawmakers approved this spring take effect July 1.




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Oilers Hope Offensive Breakthrough Continues Against Injury-Riddled Islanders

The Oilers look to claw themselves up above .500 against the team that started their memorable turnaround last season.




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Lady Vols rely on best 3-point shooting performance of season to beat Middle Tennessee

Lady Vols basketball relied on its best 3-point shooting night of the season to close out a win over Middle Tennessee State on Tuesday




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Hand-Jaw Coordination as Mice Handle Food Is Organized around Intrinsic Structure-Function Relationships

Rodent jaws evolved structurally to support dual functionality, for either biting or chewing food. Rodent hands also function dually during food handling, for actively manipulating or statically holding food. How are these oral and manual functions coordinated? We combined electrophysiological recording of muscle activity and kilohertz kinematic tracking to analyze masseter and hand actions as mice of both sexes handled food. Masseter activity was organized into two modes synchronized to hand movement modes. In holding/chewing mode, mastication occurred as rhythmic (~5 Hz) masseter activity while the hands held food below the mouth. In oromanual/ingestion mode, bites occurred as lower-amplitude aperiodic masseter events that were precisely timed to follow regrips (by ~200 ms). Thus, jaw and hand movements are flexibly coordinated during food handling: uncoupled in holding/chewing mode and tightly coordinated in oromanual/ingestion mode as regrip–bite sequences. Key features of this coordination were captured in a simple model of hierarchically orchestrated mode-switching and intramode action sequencing. We serendipitously detected an additional masseter-related action, tooth sharpening, identified as bouts of higher-frequency (~13 Hz) rhythmic masseter activity, which was accompanied by eye displacement, including rhythmic proptosis, attributable to masseter contractions. Collectively, the findings demonstrate how a natural, complex, and goal-oriented activity is organized as an assemblage of distinct modes and complex actions, adapted for the divisions of function arising from anatomical structure. These results reveal intricate, high-speed coordination of disparate effectors and show how natural forms of dexterity can serve as a model for understanding the behavioral neurobiology of multi-body-part coordination.




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Coupling of Slow Oscillations in the Prefrontal and Motor Cortex Predicts Onset of Spindle Trains and Persistent Memory Reactivations

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.




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Glucocorticoids Rapidly Modulate CaV1.2-Mediated Calcium Signals through Kv2.1 Channel Clusters in Hippocampal Neurons

The precise regulation of Ca2+ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca2+ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca2+ spikes generated by Kv2.1-organized Ca2+ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and CaV1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K+ currents. In HEK293 cells transfected with CaV1.2 alone, glucocorticoids inhibited CaV1.2 currents but had no effect on the cell surface expression of CaV1.2. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of CaV1.2 channels in HEK293 cells. However, this effect was not observed in the presence of nonclustering Kv2.1S586A mutant channels. Live-cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, Western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly suppress CaV1.2-mediated Ca2+ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.




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See 11 of the Best Wildlife Photographs From Years Past

A new book reveals striking images from six decades of the beloved Wildlife Photographer of the Year competition




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Saving Amphibians From Deadly Fungus

Building captive colonies for eventual re-introduction to the wild, scientists from Atlanta rescue endangered frogs and other amphibians threatened with extinction by a fatal fungus spreading through South American forests




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How a 'Non-Hazardous' NASA Mission Turned Deadly

In 1967, a horrific fire broke out during a routine pre-launch test for the Apollo 1 mission at Cape Kennedy, Florida. It would claim the lives of three NASA astronauts




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Andy Warhol's Headlines

Ever the media gadfly himself, the pop artist was fascinated by newspapers, especially the tabloids, as explored in a new exhibit at the National Gallery of Art. Read more at http://www.smithsonianmag.com/arts-culture/Bringing-Andy-Warhols-Shadows-to-the-Hirshhorn.html




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How Idlewild Courted the Black Middle Class in the 1930s

By the 1930s, the black middle class had arrived, with the purchasing power to match. Sensing an opportunity, developers established Idlewild: a summer resort aimed exclusively at African-Americans.




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The Dark and Deadly History of the Plague

What caused the Plague? And what methods did people use to combat the spread? Learn about its origins, past outbreaks (including the Black Death), and the long-lasting impact of its legacy today. --- For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Digital Editorial Director: Brian Wolly Supervising Producer & Scriptwriter: Michelle Mehrtens Producer: Nicki Marko Producer: Sierra Theobald Video Editor: Natalie Cline Graphic Designer: Kevin Schoenblum