apt

BelAmi Online: Callum Dean Fucks Tommy Clapton

Back at the BelAmi “Frisky Summer” ranch, the heat is on. It’s early in the morning and Tommy Clapton is already up and around, so as horny Callum Dean wakes up and decides he needs a bit of morning sex, he has to find his bunk mate and ask if he can lend a hand.... View Article

The post BelAmi Online: Callum Dean Fucks Tommy Clapton appeared first on QueerClick.




apt

Living in the Long Emergency: Global Crisis, the Failure of the Futurists, and the Early Adapters Who Are Showing Us the Way Forward

Hardcover, Kindle, Audiobook – March 3, 2020




apt

The best climate-adaptive watering systems for your garden

If you've grown a garden for a while, you may have noticed that the last few years have been brutal due to climate change-related patterns. One month it's drought and the next it's flooding. What is the best watering system for your home garden and can it help you navigate the climate ups and downs? Here are some great options with the pros and cons so you can decide the right garden irrigation system for your micro climate.[...]




apt

Adapting national parks for wheelchair hiking

The trails through our public lands weren’t designed for wheelchairs, but new wheelchairs are designed for those trails. National Park Service accessibility specialist Quinn Brett wants parks to catch up with wheelchair technology, increasing access to American wilderness.




apt

Scientists capture first-ever image of our galaxy’s supermassive black hole

The Event Horizon Telescope team has captured the first image of Sagittarius A*, the black hole at the center of the Milky Way.




apt

The History of Earth in Five Epic Chapters

The evolution of planet Earth over 4.5 billion years.




apt

'Pedro Páramo' captures the disorientation of Juan Rulfo's timeless novel

Netflix's film is based on a 1955 novel about a man who goes in search of the father he’d never met — only to discover that his father is dead, and the village he inhabited is haunted by ghosts.




apt

£30,000 limit on disabled adaptions grants reviewed

A court challenge means the government will look again at the cap on the Disabled Facilities Grant.




apt

Arsenal captain Odegaard pulls out of Norway squad

Arsenal captain Martin Odegaard says he must "listen to my body" after withdrawing from Norway's squad.




apt

Why Man Utd's forwards will need to 'adapt' under Amorim

Before Ruben Amorim takes over as Manchester United manager, Match of the Day 2's Theo Walcott explains why some of United's attacking players will need to adapt their game under their new boss.




apt

Here's how much more laptops, TVs, and smartphones could cost under Trump's proposed tariffs, consumer group says

Donald Trump's proposed tariffs would hit the consumer tech sector, raising prices on US consumers' favorite gadgets, an October report found.




apt

"Laptop" with full 4090 GPU weighs 15 pounds

There are laptops sold with NVidia's high-end 4090 graphics chip, but it's a power-constrained mobile version appropriate for portable machines. A Chinese-language blogger modded themselves a beast of a machine with a full desktop-class 4090 card. This thing weighs 15 pounds and its battery life is a Borgesian map of nothing (one must plug it in). — Read the rest

The post "Laptop" with full 4090 GPU weighs 15 pounds appeared first on Boing Boing.




apt

Former BLM Chapter Co-Founder Switches To Trump In ’24 … What Changed His Mind?

Mark Fisher was co-founder of the Rhode Island chapter of BLM. He voted for Joe Biden in 2020. Does he have buyers remorse? Yeah, you could say so. His viral video is causing a stir... but there's more to that story.

The post Former BLM Chapter Co-Founder Switches To Trump In ’24 … What Changed His Mind? appeared first on Clash Daily.




apt

Relative and Absolute Quantification of Postsynaptic Density Proteome Isolated from Rat Forebrain and Cerebellum

Dongmei Cheng
Jun 1, 2006; 5:1158-1170
Datasets




apt

How modular renewables can reduce the costs of relying on carbon capture

How modular renewables can reduce the costs of relying on carbon capture Expert comment LToremark

COP29 must raise countries’ ambitions to deploy vastly more low-cost modular renewable technologies to help meet the tripling of renewables target set at COP28 and reduce our reliance on expensive carbon capture systems.

The most important international climate conference is around the corner. COP29 in Baku, Azerbaijan will be especially important because next year countries will submit their five-yearly national climate plans – or Nationally Determined Contributions (NDCs) – as set out under the Paris Agreement.

At COP28 in Dubai last year, the final text was heralded as a last-minute success as – somewhat surprisingly – it was the first ever COP to commit to ‘transition away from fossil fuels in energy systems in a just, orderly and equitable manner’. To support this, over 200 countries also committed to triple renewable capacity by 2030.

Under current NDCs, even if all countries achieve their most ambitious decarbonization plans, the world would still fall 30 per cent short of tripling renewable capacity by 2030. 

At COP29 in November, hosted by a petrostate, additional agreement is needed to operationalize the removal of fossil fuels from the global energy system and set the ambition for those crucial NDCs in 2025. Failing to do so means the opportunity to triple renewables by 2030 will slip away. But the actions of oil producing nations, international oil companies, their associated supply chains and networks of lobbyists have in recent years done their best to disrupt and slow down the energy transition and water down key negotiations during COPs and elsewhere

During the final days of COP28, the Organization of the Petroleum Exporting Countries (OPEC) sent private letters to its 13 members – including COP28 host the United Arab Emirates (UAE) – urging them to ‘proactively reject any text or formula that targets energy, i.e. fossil fuels, rather than emissions’. OPEC members own 80 per cent of global oil reserves.

Due to the startling decline in the cost of renewables and electric vehicles, fossil fuel producers are increasingly concerned. To fight back they are turning to carbon capture and storage (CCS) technologies and carbon removal options, which would enable the continued burning of fossil fuels – and protect their assets and business models.

A key battle ground for oil and gas producers is the difference between abated and unabated fossil fuels.

Abatement is the process of capturing CO2 as fossil fuels are burnt to prevent a proportion of those CO2 emissions from entering the atmosphere, either by using that CO2 in products or storing it in geological formations deep underground in near perpetuity, commonly referred to as CCS.

After COP28 there was optimism that the final agreement was significant and covered all fossil fuels without ambiguity around whether they are unabated or abated. 

But the definition of unabated has not actually been agreed within the COP process. During the 2021 COP26 summit, the Glasgow Climate Pact mentioned unabated in reference to coal. Could a gas power station capturing 51 per cent of the emitted CO2 be considered abated?

And what about the so-called downstream emissions? Downstream emissions from cars, planes, tanker ships and diesel generators etc make up 50–80 per cent of the total emissions from oil – and there are no plans to attach mini-CCS systems to cars.

CCS and engineered carbon removals are also likely to be expensive. Analysis by the Oxford Smith School of Enterprise and the Environment has shown that high CCS pathways to net zero emissions in 2050 would cost at least $30 trillion more than a low CCS pathway with more renewables – roughly $1 trillion more per year.

The rapid cost reductions of solar, wind and batteries are due to their modular nature.

The costs of CCS have also remained the same for the past 40 years, while the costs of renewables like solar, wind and lithium-ion batteries have dropped radically. Solar costs have declined by 90 per cent in the last decade

The rapid cost reductions of solar, wind and batteries are due to their modular nature. Around 70 billion solar cells will be manufactured this year, the majority in China. It is the repetitive modular manufacturing process that has led to rapid efficiency improvements and cost reductions. Each Tesla has around 7,000 lithium-ion battery cells, and the price of these modular batteries fell 14 per cent between 2022 and 2023 alone. 

The modular criteria can help define the technology winners of the future, technologies we should selectively support and accelerate over the coming years. 

While huge industrial power stations, oil rigs and refineries have their benefits, they are not modular in the same way. Their economy of scale is in the large size of each asset. CCS is bolted on to fossil fuel infrastructure but there are less than 50,000 fossil fuel producing assets globally. By contrast, there were 1.5 billion solar panels produced in 2022. The cost of deploying CCS is therefore unlikely to benefit from the rapid cost reductions of modular renewables. Nuclear even less so. There are 440 nuclear power stations in operation today, they take many years to build and remain hugely expensive. 




apt

Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage?

Net Zero and Beyond: What Role for Bioenergy with Carbon Capture and Storage? 23 January 2020 — 8:30AM TO 10:00AM Anonymous (not verified) 6 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

In the context of the feasibility of reducing greenhouse gas emissions to net zero, policymakers are beginning to pay more attention to options for removing carbon dioxide from the atmosphere. A wide range of potential carbon dioxide removal (CDR) options are currently being discussed and modelled though the most prominent among them are bioenergy with carbon capture and storage (BECCS) and afforestation and reforestation.

There are many reasons to question the reliance on BECCS assumed in the models including the carbon balances achievable, its substantial needs for land, water and other inputs and technically and economically viable carbon capture and storage technologies.

This meeting will examine the potentials and challenges of BECCS in the context of other CDR and emissions abatement options. It will discuss the requisite policy and regulatory frameworks to minimize sustainability and socio-political risks of CDR approaches while also avoiding overshooting climate goals.

Attendance at this event is by invitation only.




apt

Climate Change and the Pacific: Impacts and Adaptation

Climate Change and the Pacific: Impacts and Adaptation 27 November 2018 — 8:30AM TO 10:00AM Anonymous (not verified) 14 November 2018 Royal Academy of Arts

Pacific Island leaders have identified climate change as the single greatest challenge facing the region. Warming oceans and the increasing incidence of extreme weather events threaten Pacific peoples and their way of life.
This event will explore the existing impacts of climate change on the South Pacific and what solutions are feasible for the region. This discussion will follow a brief screening of the documentary film, Subject to Change, which looks at the impact of climate change in New Zealand and Fiji and documents the personal stories of a tiny Pacific community faced with rising and acidifying seas, extreme weather conditions, tidal events and social changes. It also looks at New Zealand’s efforts to amplify the voices of its Pacific neighbours and to drive domestic and global action on climate change.
This event is being held in partnership with the New Zealand government.
THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.




apt

‘One-burner’ life - Vybz Kartel credits fiancée for new chapter

Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'...




apt

PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids

Hideaki Kuge
Dec 1, 2020; 61:1747-1763
Research Articles




apt

Problem Notes for SAS®9 - 61815: SAS Episode Analytics 3.1 - Audit table is required in order to capture user interactions with the user interface

SAS  Episode Analytics 3.1 requires the ability to capture user interactions with the user interface for auditing purposes. To support the required functionality a new table has been add




apt

PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids [Research Articles]

The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.




apt

Conserved biophysical features of the CaV2 presynaptic Ca2+ channel homologue from the early-diverging animal Trichoplax adhaerens [Membrane Biology]

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.




apt

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.




apt

The Capture of a Disabled Proteasome Identifies Erg25 as a Substrate for Endoplasmic Reticulum Associated Degradation [Research]

Studies in the yeast Saccharomyces cerevisiae have helped define mechanisms underlying the activity of the ubiquitin–proteasome system (UPS), uncover the proteasome assembly pathway, and link the UPS to the maintenance of cellular homeostasis. However, the spectrum of UPS substrates is incompletely defined, even though multiple techniques—including MS—have been used. Therefore, we developed a substrate trapping proteomics workflow to identify previously unknown UPS substrates. We first generated a yeast strain with an epitope tagged proteasome subunit to which a proteasome inhibitor could be applied. Parallel experiments utilized inhibitor insensitive strains or strains lacking the tagged subunit. After affinity isolation, enriched proteins were resolved, in-gel digested, and analyzed by high resolution liquid chromatography-tandem MS. A total of 149 proteasome partners were identified, including all 33 proteasome subunits. When we next compared data between inhibitor sensitive and resistant cells, 27 proteasome partners were significantly enriched. Among these proteins were known UPS substrates and proteins that escort ubiquitinated substrates to the proteasome. We also detected Erg25 as a high-confidence partner. Erg25 is a methyl oxidase that converts dimethylzymosterol to zymosterol, a precursor of the plasma membrane sterol, ergosterol. Because Erg25 is a resident of the endoplasmic reticulum (ER) and had not previously been directly characterized as a UPS substrate, we asked whether Erg25 is a target of the ER associated degradation (ERAD) pathway, which most commonly mediates proteasome-dependent destruction of aberrant proteins. As anticipated, Erg25 was ubiquitinated and associated with stalled proteasomes. Further, Erg25 degradation depended on ERAD-associated ubiquitin ligases and was regulated by sterol synthesis. These data expand the cohort of lipid biosynthetic enzymes targeted for ERAD, highlight the role of the UPS in maintaining ER function, and provide a novel tool to uncover other UPS substrates via manipulations of our engineered strain.




apt

Transcriptome and secretome analysis of intra-mammalian life-stages of the emerging helminth pathogen, Calicophoron daubneyi reveals adaptation to a unique host environment. [Research]

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.




apt

Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).




apt

Kangaroo captured after three weeks on the loose in Florida

A kangaroo that escaped from its Florida enclosure while fleeing from a bear has been safely returned home three weeks later.




apt

QCT POD- An Adaptive Converged Platform for HPC and AI

Building an integrated workload-driven system with optimized performance is a resource-intensive and time-consuming effort. The QCT Platform on Demand (QCT POD) offers an on-premises HPC/AI converged system, featuring best-practice hardware […]

The post QCT POD- An Adaptive Converged Platform for HPC and AI appeared first on HPCwire.




apt

Why Your Brain Breaks Up Your Day Into ‘Chapters’ (M)

Find out how and why your brain divides your day into meaningful chapters.




apt

5 ways leaders can adapt to shifting geopolitics | Nikolaus S. Lang

What will the world look like in 2030? International business consultant Nikolaus S. Lang predicts the evolution of a multipolar world, with multiple emerging coalitions of countries acting in new ways to achieve their economic, technological and military goals. He dives into what this will mean for the global economy, offering five tips for business leaders to prepare for the coming geopolitical landscape.




apt

Baptist couple ask court to ban book from son's school




apt

Parents Awarded $900K After Hidden Cameras Capture Student Restraint

Parents of a child with autism filed lawsuits against the Clark County, Nev. district, after video evidence showed him being restrained repeatedly.




apt

Maine Teachers Are Trading in Their iPads for Laptops

Teachers felt that iPads "provide no educational function in the classroom" and are often used to play games in class.




apt

Maine Teachers Trade IPads for Laptops

Middle and high schools in Maine are returning their iPads and switching back to laptops after a survey found that 88.5 percent of teachers and 74 percent of students in one district preferred laptops for schoolwork and instruction, reports the Lewiston-Auburn Sun Journal.




apt

Former Predators Captain Shea Weber Inducted Into The Hockey Hall of Fame

Shea Weber gets inducted into the Hockey Hall of Fame after an impressive career.




apt

Did #RedForEd Just Capture Its First Midterm Victory?

In Tuesday night's Republican primary in West Virginia, Robert Karnes, a West Virginia Republican state senator who lashed out at teachers during their nine-day strike, lost to pro-labor candidate Bill Hamilton.




apt

Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type

Guo-qiang Bi
Dec 15, 1998; 18:10464-10472
Articles




apt

Gravin Orchestrates Protein Kinase A and {beta}2-Adrenergic Receptor Signaling Critical for Synaptic Plasticity and Memory

Robbert Havekes
Dec 12, 2012; 32:18137-18149
BehavioralSystemsCognitive




apt

An Implicit Plan Overrides an Explicit Strategy during Visuomotor Adaptation

Pietro Mazzoni
Apr 5, 2006; 26:3642-3645
BRIEF COMMUNICATION




apt

Explicit and Implicit Contributions to Learning in a Sensorimotor Adaptation Task

Jordan A. Taylor
Feb 19, 2014; 34:3023-3032
BehavioralSystemsCognitive




apt

A Systematic Structure-Function Characterization of a Human Mutation in Neurexin-3{alpha} Reveals an Extracellular Modulatory Sequence That Stabilizes Neuroligin-1 Binding to Enhance the Postsynaptic Properties of Excitatory Synapses

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3αA687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.




apt

Synaptotagmin 4 Supports Spontaneous Axon Sprouting after Spinal Cord Injury

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function.




apt

Pre- and Postsynaptic MEF2C Promotes Experience-Dependent, Input-Specific Development of Cortical Layer 4 to Layer 2/3 Excitatory Synapses and Regulates Activity-Dependent Expression of Synaptic Cell Adhesion Molecules

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.




apt

This Captivating Guide Uncovers the History and Mystery of Dinosaurs in 50 Fossils

A paleontologist at the Natural History Museum in London chronicles the age of the famous and fascinating massive reptiles




apt

How NASA Captured Asteroid Dust to Find the Origins of Life

Capturing a piece of an asteroid and bringing it to Earth is even more difficult than it is time-consuming. After four years in space, NASA’s OSIRIS-REx craft made a brief landing on the asteroid Bennu to collect samples of the ancient rock. Six months later, part of the spacecraft began its journey home to Earth, and earlier this fall, that sample collection canister landed, via parachute, in Utah. Scientists will be studying those samples of Bennu for decades in the hope of unlocking the mystery of how life on Earth began — but they’ve already learned enough to get them excited. In this episode, we speak with Linda Shiner, the former editor of Air & Space / Smithsonian magazine, about the challenges and triumphs of the OSIRIS-REx mission, and what scientists hope it will teach us about how life on Earth began. Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz. Music by APM Music.




apt

A Runaway Capybara Is Evading Capture and 'Living Her Best Life' in England

The “beloved” rodent named Cinnamon was spotted this week with help from drones. She has been wandering and eating grass after escaping her zoo enclosure last Friday




apt

Rare Drone Footage Captures Orcas Feeding on Dusky Dolphins

The predatory pod hunts off the coast of Chile and is led by a matriarch called Dakota




apt

Scientists Unveil the First-Ever Complete Map of an Adult Fruit Fly's Brain, Captured in Stunning Detail

The brain diagram, called a connectome, could revolutionize researchers' understanding of the human brain, which has many parallels with a fruit fly's




apt

‘Pride and Prejudice’ Gets a New Adaptation: an Interactive A.I. Avatar

Lizzy, the avatar based on the novel’s Elizabeth Bennet, will hold period-accurate conversations with visitors at Jane Austen’s cottage home




apt

After the Death of Cassius, the World's Largest Captive Crocodile, Scientists Are Trying to Solve the Mystery of His Age

The beloved reptile in Australia died last weekend and was thought to be up to 120 years old, though that age is only an estimate. Research on his bones might reveal a more exact number