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{alpha}-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate [Membrane Biology]

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson's disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking.




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A potential role for the Gsdf-eEF1{alpha} complex in inhibiting germ cell proliferation: A protein-interaction analysis in medaka (Oryzias latipes) from a proteomics perspective [Research]

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation.




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High-throughput and site-specific N-glycosylation analysis of human alpha-1-acid glycoprotein offers a great potential for new biomarker discovery [Research]

Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.




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Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC

LONDON and TORONTO, Sept. 30, 2024 — Alphawave Semi, a global leader in high-speed connectivity and compute silicon for the world’s technology infrastructure, has unveiled the availability of the industry’s […]

The post Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC appeared first on HPCwire.




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To See or Not to See: Prestimulus {alpha} Phase Predicts Visual Awareness

Kyle E. Mathewson
Mar 4, 2009; 29:2725-2732
BehavioralSystemsCognitive




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Cardiac-Sympathetic Contractility and Neural Alpha-Band Power: Cross-Modal Collaboration during Approach-Avoidance Conflict

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.




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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.




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Google DeepMind Open Sources AlphaFold 3 AI Model to Help Researchers in Drug Discovery

Google DeepMind has silently open-sourced its frontier artificial intelligence (AI) model that can predict the interaction between proteins and other molecules. Dubbed AlphaFold 3, the large language model is the successor of AlphaFold 2, whose research led to the creators of the large language model (LLM) Demis Hassabis and John Jumper getting the Nobel Prize in Chemistry in 2024.




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Wings Alpha Review

Read the in depth Review of Wings Alpha Audio Video. Know detailed info about Wings Alpha configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.




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CYP8B1 Catalyzes 12alpha-Hydroxylation of C27 Bile Acid: In Vitro Conversion of Dihydroxycoprostanic Acid into Trihydroxycoprostanic Acid [Articles]

Sterol 12α-hydroxylase (CYP8B1) is the unique P450 enzyme with sterol 12-oxidation activity, playing an exclusive role in 12α-hydroxylating intermediates along the bile acid (BA) synthesis pathway. Despite the long history of BA metabolism studies, it is unclear whether CYP8B1 catalyzes 12α-hydroxylation of C27 BAs, the key intermediates shuttling between mitochondria and peroxisomes. This work provides robust in vitro evidence that both microsomal and recombinant CYP8B1 enzymes catalyze the 12α-hydroxylation of dihydroxycoprostanic acid (DHCA) into trihydroxycoprostanic acid (THCA). On the one hand, DHCA 12α-hydroxylation reactivity is conservatively detected in liver microsomes of both human and preclinical animals. The reactivity of human tissue fractions conforms well with the selectivity of CYP8B1 mRNA expression, while the contribution of P450 enzymes other than CYP8B1 is excluded by reaction phenotyping in commercial recombinant enzymes. On the other hand, we prepared functional recombinant human CYP8B1 proteins according to a recently published protocol. Titration of the purified CYP8B1 proteins with either C4 (7α-hydroxy-4-cholesten-3-one) or DHCA yields expected blue shifts of the heme Soret peak (type I binding). The recombinant CYP8B1 proteins efficiently catalyze 12α-hydroxylation of both DHCA and C4, with substrate concentration occupying half of the binding sites of 3.0 and 1.9 μM and kcat of 3.2 and 2.6 minutes–1, respectively. In summary, the confirmed role of CYP8B1 in 12α-hydroxylation of C27 BAs has furnished the forgotten passageway in the BA synthesis pathway. The present finding might have opened a new window to consider the biology of CYP8B1 in glucolipid metabolism and to evaluate CYP8B1 inhibition as a therapeutic approach of crucial interest for metabolic diseases.

SIGNIFICANCE STATEMENT

The academic community has spent approximately 90 years interpreting the synthesis of bile acids. However, the 12α-hydroxylation of intermediates catalyzed by CYP8B1 is not completely mapped on the classic pathway, particularly for the C27 bile acids, the pivotal intermediates shuttling between mitochondria and peroxisomes. This work discloses the forgotten 12α-hydroxylation pathway from dihydroxycoprostanic acid into trihydroxycoprostanic acid. The present finding may facilitate evaluating CYP8B1 inhibition as a therapeutic approach of crucial interest for metabolic diseases.




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Inhibitory Actions of Potentiating Neuroactive Steroids in the Human {alpha}1{beta}3{gamma}2L {gamma}-Aminobutyric Acid Type A Receptor [Article]

The -aminobutyric acid type A (GABAA) receptor is modulated by a number of neuroactive steroids. Sulfated steroids and 3β-hydroxy steroids inhibit, while 3α-hydroxy steroids typically potentiate the receptor. Here, we have investigated inhibition of the α1β32L GABAA receptor by the endogenous neurosteroid 3α-hydroxy-5β-pregnan-20-one (3α5βP) and the synthetic neuroactive steroid 3α-hydroxy-5α-androstane-17β-carbonitrile (ACN). The receptors were expressed in Xenopus oocytes. All experiments were done using two-electrode voltage-clamp electrophysiology. In the presence of low concentrations of GABA, 3α5βP and ACN potentiate the GABAA receptor. To reveal inhibition, we conducted the experiments on receptors activated by the combination of a saturating concentration of GABA and propofol to fully activate the receptors and mask potentiation, or on mutant receptors in which potentiation is ablated. Under these conditions, both steroids inhibited the receptor with IC50s of ~13 μM and maximal inhibitory effects of 70–90%. Receptor inhibition by 3α5βP was sensitive to substitution of the α1 transmembrane domain (TM) 2-2' residue, previously shown to ablate inhibition by pregnenolone sulfate. However, results of coapplication studies and the apparent lack of state dependence suggest that pregnenolone sulfate and 3α5βP inhibit the GABAA receptor independently and through distinct mechanisms. Mutations to the neurosteroid binding sites in the α1 and β3 subunits statistically significantly, albeit weakly and incompletely, reduced inhibition by 3α5βP and ACN.

SIGNIFICANCE STATEMENT

The heteromeric GABAA receptor is inhibited by sulfated steroids and 3β-hydroxy steroids, while 3α-hydroxy steroids are considered to potentiate the receptor. We show here that 3α-hydroxy steroids have inhibitory effects on the α1β32L receptor, which are observed in specific experimental settings and are expected to manifest under different physiological conditions.




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Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated G{alpha} in Human Cancer [Minireview]

G protein–coupled receptors (GPCRs) couple to heterotrimeric G proteins, comprised of α and β subunits, to convert extracellular signals into activation of intracellular signaling pathways. Canonically, GPCR-mediated activation results in the exchange of GDP for GTP on G protein α subunits (Gα) and the dissociation of Gα-GTP and G protein β subunits (Gβ), both of which can regulate a variety of signaling pathways. Hydrolysis of bound GTP by Gα returns the protein to Gα-GDP and allows reassociation with Gβ to reform the inactive heterotrimer. Naturally occurring mutations in Gα have been found at conserved glutamine and arginine amino acids that disrupt the canonical G protein cycle by inhibiting GTP hydrolysis, rendering these mutants constitutively active. Interestingly, these dysregulated Gα mutants are found in many different cancers due to their ability to sustain aberrant signaling without a need for activation by GPCRs. This review will highlight an increased recognition of the prevalence of such constitutively activating Gα mutations in cancers and the signaling pathways activated. In addition, we will discuss new knowledge regarding how these constitutively active Gα are regulated, how different mutations are biochemically distinct, and how mutationally activated Gα are unique compared with GPCR-activated Gα. Lastly, we will discuss recent progress in developing inhibitors directly targeting constitutively active Gα mutants.

SIGNIFICANCE STATEMENT

Constitutively activating mutations in G protein α subunits (Gα) widely occur in and contribute to the development of many human cancers. To develop ways to inhibit dysregulated, oncogenic signaling by these mutant Gα, it is crucial to better understand mechanisms that lead to constitutive Gα activation and unique mechanisms that regulate mutationally activated Gα in cells. The prevalence of activating mutations in Gα in various cancers makes Gα proteins compelling targets for the development of therapeutics.




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Posttranslational Modifications of {alpha}-Synuclein, Their Therapeutic Potential, and Crosstalk in Health and Neurodegenerative Diseases [Review Article]

α-Synuclein (α-Syn) aggregation in Lewy bodies and Lewy neurites has emerged as a key pathogenetic feature in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Various factors, including posttranslational modifications (PTMs), can influence the propensity of α-Syn to misfold and aggregate. PTMs are biochemical modifications of a protein that occur during or after translation and are typically mediated by enzymes. PTMs modulate several characteristics of proteins including their structure, activity, localization, and stability. α-Syn undergoes various posttranslational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, O-GlcNAcylation, nitration, oxidation, polyamination, arginylation, and truncation. Different PTMs of a protein can physically interact with one another or work together to influence a particular physiological or pathological feature in a process known as PTMs crosstalk. The development of detection techniques for the cooccurrence of PTMs in recent years has uncovered previously unappreciated mechanisms of their crosstalk. This has led to the emergence of evidence supporting an association between α-Syn PTMs crosstalk and synucleinopathies. In this review, we provide a comprehensive evaluation of α-Syn PTMs, their impact on misfolding and pathogenicity, the pharmacological means of targeting them, and their potential as biomarkers of disease. We also highlight the importance of the crosstalk between these PTMs in α-Syn function and aggregation. Insight into these PTMS and the complexities of their crosstalk can improve our understanding of the pathogenesis of synucleinopathies and identify novel targets of therapeutic potential.

Significance Statement

α-Synuclein is a key pathogenic protein in Parkinson’s disease and other synucleinopathies, making it a leading therapeutic target for disease modification. Multiple posttranslational modifications occur at various sites in α-Synuclein and alter its biophysical and pathological properties, some interacting with one another to add to the complexity of the pathogenicity of this protein. This review details these modifications, their implications in disease, and potential therapeutic opportunities.




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[PERSPECTIVES] {alpha}-Synuclein in Parkinson's Disease: 12 Years Later

α-Synuclein (AS) is a small presynaptic protein that is genetically, biochemically, and neuropathologically linked to Parkinson's disease (PD) and related synucleinopathies. We present here a review of the topic of this relationship, focusing on more recent knowledge. In particular, we review the genetic evidence linking AS to familial and sporadic PD, including a number of recently identified point mutations in the SNCA gene. We briefly go over the relevant neuropathological findings, stressing the evidence indicating a correlation between aberrant AS deposition and nervous system dysfunction. We analyze the structural characteristics of the protein, in relation to both its physiologic and pathological conformations, with particular emphasis on posttranslational modifications, aggregation properties, and secreted forms. We review the interrelationship of AS with various cellular compartments and functions, with particular focus on the synapse and protein degradation systems. We finally go over the recent exciting data indicating that AS can provide the basis for novel robust biomarkers in the field of synucleinopathies, while at the same time results from the first clinical trials specifically targeting AS are being reported.




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«ALPHAS»: le masculiniste Joël McGuirk déplore la décision de le «désinviter» de «Tout le monde en parle»

Joël McGuirk a dénoncé son retrait imprévu du dernier plateau de «Tout le monde en parle», lundi, au micro de Sophie Durocher, à QUB radio.




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DeepMind открыл код AlphaFold 3, AI-системы моделирования структуры белков

Компания Google DeepMind опубликовала исходные тексты системы машинного обучения AlphaFold 3, предназначенной для предсказания трёхмерной структуры белков и моделирования взаимодействия белков с другими типами молекул. За создание алгоритмов машинного обучения, реализованных во второй версии AlphaFold, в этом году присуждена Нобелевская премия по химии. Связанный с AlphaFold 3 инструментарий написан на Python и C++, и распространяется под лицензией CC BY-NC-SA 4.0. Натренированные модели предоставляются на основе пользовательского соглашения. Отдельно запущен сервер, позволяющий экспериментировать с AlphaFold 3 в online-режиме.




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November 13, 2024: Trivia Question: Alpha?

I recently asked the question about which Steve Jackson Games product and game is last alphabetically, which we answered here. In that earlier question, I alluded to the other question. Namely:

• What is the first item alphabetically that is currently available for sale, and . . .

• What is the first item alphabetically that is a complete game and currently available for sale?

This one is trickier for a couple of reasons. As Magesmiley noted on the forums when talking about the "Omega" question, somewhat of a software-sorting question hides here. There's also a bit of an oddity in the second question we're asking today that makes this more challenging. Still, let's see if we can't muddle toward an answer . . .

. . . Which we'll divulge sometime soon. As ever, feel free to share your answers on the forums!

Steven Marsh

Warehouse 23 News: The City Never Sleeps Because Of All The Action

There are a million stories in the city, and they're all exciting! GURPS Action 9: The City shows how you can add GURPS City Stats to your GURPS Action campaigns. It also features six sample cities to use with your own action-packed adventures. Download it today from Warehouse 23!




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Bootstrap 5.3.0-alpha1

It’s a Christmas miracle—Bootstrap v5.3.0-alpha1 has arrived just in time for the holiday break! This release brings new color mode support, an expanded color palette with variables and utilities, and more.

We’re keeping things short and simple in this blog post with deeper dives into the new color modes and more coming in future posts. For now, we want you to enjoy the holiday break and come back next year feeling refreshed and rejuvenated. Keep reading for what’s new and we’ll see you next year!




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Bootstrap 5.3.0-alpha2

Our second alpha release of v5.3.0 has landed with a ton of enhancements and bug fixes for our new color modes! There’s still more to come, but we’ve held off shipping until we ironed out enough issues. Huzzah, we have!

This v5.3.0 release is a monumental update for Bootstrap 5. It’s big enough that it could’ve been a v6 on its own, but we wanted to do right by the community and get color modes out the door without the massive major release upgrade. We’re getting super close now, so bear with us as we continue to chip away at this.




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Bootstrap 5.3.0-alpha3

Hot on the heels of our second alpha, we’re releasing a third (and unexpected) alpha for v5.3.0 today with some fixes for some Node Sass compilation errors. In addition, we’ve added a handful of other updates. We’re still on target to ship our stable release soon!

Once again, if you’re new to the v5.3.0 alpha releases, please read through the Migration guide for the first alpha and last month’s second alpha.

Here’s a look at what’s changed in this quick release:




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UN Peacekeepers Report Severe Violations by Israel on Alpha Line with Syria Amid Ongoing Construction

The UN Disengagement Observer Force warns of severe violations by Israel along the Alpha Line, risking increased tensions with Syria.




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Social Alpha launches programme to support 10 agri start-ups 

Social Alpha to support innovations in precision farming, soil and water management, farm mechanization, post-harvest management, and animal husbandry They need to address critical challenges smallholder farmers face




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Yamaha launches Cygnus Alpha with disc brake




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Inter-{alpha}-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation [Glycobiology and Extracellular Matrices]

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.




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Glycation-mediated inter-protein cross-linking is promoted by chaperone-client complexes of {alpha}-crystallin: Implications for lens aging and presbyopia [Glycobiology and Extracellular Matrices]

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.




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Alpha and Omega Semiconductor Limited (AOSL) CEO Mike Chang on Q3 2020 Results - Earnings Call Transcript




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Eric Schmidt no longer advisor at Alphabet




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Alpha and Omega Semiconductor Limited (AOSL) CEO Mike Chang on Q3 2020 Results - Earnings Call Transcript





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The new general and mining telegraph code ...: alphabetically arranged for the use of mining companies, mining engineers, stockbrokers, financial agents, and trust and finance companies / by C. Algernon Moreing and Thomas Neal

Archives, Room Use Only - HE7677.M6 M67 1907




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The life of James Francis Leonard, the first practical sound-reader of the Morse alphabet / by John Wilson Townsend ; a paper read before the Filson Club at its meeting, October 5, 1908

Archives, Room Use Only - TK5243.L4 T69 1909




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Animals, Insects, etc in alphabetical order (with an image if you wish)




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Alphagories...




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Alpha Ventus: Germany cuts the ribbon on offshore wind

12 shiny new off-shore turbines in Germany are a reminder of just how far behind the U.S. lags in race for clean offshore energy.



  • Research & Innovations

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GRE Alpha Products Featured at Frankfurt Light and Building Fair

GRE Alpha's team brings their modular approach to LED dimming to the Messe Light+Building 2018




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GRE Alpha Launching New DALI-2 Dimming Module

World Leader in LED Driver Manufacturing Breaks New Ground with Advance to DALI-2




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GRE Alpha Announces Participation in the Autumn 2019 Hong Kong International Lighting Fair

The company's leadership in modular LED product development takes center stage at the event




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As Trade War Tensions Rise, GRE Alpha Expands its Manufacturing Presence in Vietnam

GRE Alpha Customers will Remain Unaffected by China Tariffs




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GRE Alpha to Exhibit in 2019 LED+Light Asia Singapore

Next-generation LED dimmers and drivers making their debut




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The SLD-DIM-XG4 has been added to GRE Alpha's Growing Line of High-quality Lighting Control Modules

GRE Alpha expands their popular line of LED power supplies




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GRE Alpha Debuts Next-Generation Dimmers and Drivers in LED+Light Asia 2019

GRE Alpha showcased how unique, modular approach is meeting the demand for smarter building solutions




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GRE Alpha Partners with Setsuyo Astec Corporation to Bring LED Lighting Drivers and Power Supplies to SE Asia

GRE Alpha recently formed a partnership with Setsuyo Astec Corporation




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GRE Alpha Bringing Innovative Dimmers to Light + Building 2020

Collaboration with EnOcean Proves to be a Big Win for Architectural LED Lighting




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How to Manage the Alpha Male

Kate Ludeman and Eddie Erlandson, authors of "Alpha Male Syndrome." Also: Judith Ross on using trust as a strategic management tool.




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Avoiding 5/4-powers on the alphabet of nonnegative integers. (arXiv:2005.03158v1 [math.CO])

We identify the structure of the lexicographically least word avoiding 5/4-powers on the alphabet of nonnegative integers. Specifically, we show that this word has the form $p au(varphi(z) varphi^2(z) cdots)$ where $p, z$ are finite words, $varphi$ is a 6-uniform morphism, and $ au$ is a coding. This description yields a recurrence for the $i$th letter, which we use to prove that the sequence of letters is 6-regular with rank 188. More generally, we prove $k$-regularity for a sequence satisfying a recurrence of the same type.




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Production of alpha, omega-diols

Disclosed herein are processes for preparing an α,ω-Cn-diol, wherein n is 5 or greater, from a feedstock comprising a Cn oxygenate. In one embodiment, the process comprises contacting the feedstock with hydrogen gas in the presence of a catalyst comprising Pt, Cu, Ni, Pd, Pt, Rh, Ir, Ru, or Fe on a WO3 or WOx support. In one embodiment, the process comprises contacting the feedstock with hydrogen in the presence of a catalyst comprising a metal M1 and a metal M2 or an oxide of M2, and optionally a support. In one embodiment, M1 is Pd, Pt, or Ir; and M2 is Mo, W, V, Mn, Re, Zr, Ni, Cu, Zn, Cr, Ge, Sn, Ti, Au, or Co. The Cn oxygenate may be obtained from a biorenewable resource.




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Alpha helix mimetics and methods relating thereto

Alpha-helix mimetic structures and compounds represented by the formula (I) wherein the general formula and the definition of each symbol are as defined in the specification, a chemical library relating thereto, and methods relating thereto, are disclosed. Applications of these compounds in the treatment of medical conditions, e.g., cancer diseases, fibrotic diseases, and pharmaceutical compositions comprising the mimetics are further disclosed.




alpha

Process to make alpha olefins from ethanol

The present invention relates to a process to make alpha olefins comprising: dehydrating ethanol to recover an ethylene stream,introducing said ethylene stream into an oligomerization zone containing an oligomerization catalyst and into contact with said oligomerization catalyst,operating said oligomerization zone at conditions effective to produce an effluent consisting essentially of 1-butene, 1-hexene, optionally heavier alpha olefins and unconverted ethylene if any,introducing the above effluent into a fractionation zone to recover a stream consisting essentially of 1-butene, a stream consisting essentially of 1-hexene, optionally a stream consisting essentially of heavier alpha olefins and an optional ethylene stream. In an advantageous embodiment the 1-hexene or at least one heavier alpha olefins, if any, are isomerized to an internal olefin and subsequently transformed by metathesis with the aid of additional ethylene into different alpha-olefins with even or odd number of carbons. By way of example 1-hexene is isomerized into 2-hexene and by methathesis with ethylene converted to 1-pentene and propylene.In another embodiment the oligomerization zone is only a dimerization zone and butene is produced. 1-butene is isomerized to 2-butene and sent to a methathesis zone in the presence of ethylene to be converted to propylene. In said embodiment the dehydration catalyst is selected in the group consisting of a crystalline silicate having a ratio Si/Al of at least about 100, a dealuminated crystalline silicate, and a phosphorus modified zeolite.




alpha

Isomerized alpha olefin sulfonate and method of making the same

The present invention is directed to an isomerized alpha olefin sulfonate and a method of making the same wherein the isomerized alpha olefin sulfonate is derived from sulfonating an isomerized alpha olefin with sulfur trioxide in the presence of air thereby producing an isomerized alpha olefin sulfonic acid, wherein the isomerized alpha olefin is derived from the isomerization of C12-C20 normal alpha olefins; and neutralizing the isomerized alpha olefin sulfonic acid with a source of an alkali metal or ammonium or substituted ammonium ion.




alpha

Production of glucose from starch using alpha-amylases from Bacillus subtilis

An α-amylase from Bacillus subtilis (AmyE) produces significant amounts of glucose from various carbohydrate substrates, including vegetable starch, maltoheptaose, and maltotriose. Among other things, this advantageous property allows AmyE or variants thereof to be used in a saccharification reaction having a reduced or eliminated requirement for glucoamylase. The reduction or elimination of the glucoamylase requirement significantly improves the efficiency of the production of ethanol or high fructose corn syrup, for example.