Search

Nucleic acid and histone modifications critically depend on the tricarboxylic acid (TCA) cycle for substrates and cofactors. Although a few TCA cycle enzymes have been reported in the nucleus, the corresponding pathways are considered to operate in mitochondria. Here, we show that a part of the TCA cycle is operational also in the nucleus. Using13C-tracer analysis, we identified activity of glutamine-to-fumarate, citrate-to-succinate, and glutamine-to-aspartate routes in the nuclei ofHeLacells. Proximity labeling mass spectrometry revealed a spatial vicinity of the involved enzymes with core nuclear proteins. We further show nuclear localization of aconitase 2 and 2-oxoglutarate dehydrogenase in mouse embryonic stem cells. Nuclear localization of the latter enzyme, which produces succinyl-CoA, changed from pluripotency to a differentiated state with accompanying changes in the nuclear protein succinylation. Together, our results demonstrate operation of an extended metabolic pathway in the nucleus, warranting a revision of the canonical view on metabolic compartmentalization.

Astronomers have been measuring the separations and position angles between the two components of binary stars since William Herschel began his observations in 1781. In 1970, Anton Labeyrie pioneered a method, speckle interferometry, that overcomes the usual resolution limits induced by atmospheric turbulence by taking hundreds or thousands of short exposures and reducing them in Fourier space. Our 2022 automation of speckle interferometry allowed us to use a fully robotic 1.0-meter PlaneWave Instruments telescope, located at the El Sauce Observatory in the Atacama Desert of Chile, to obtain observations of many known binaries with established orbits. The long-term objective of these observations is to establish the precision, accuracy, and limitations of this telescope's automated speckle interferometry measurements. This paper provides an early overview of the Known Binaries Project and provide example results on a small-separation (0.27") binary, WDS 12274-2843 B 228.

Over the past three decades, a rich historiography on nineteenth-century Hawai‘i has argued that too often the islands have been understood as marginal, and their people as passive in the face of American colonialism. This literature recovers the voices of the colonized, stressing the crucial ways in which Hawaiian history is not American history, but rather that of an independent people whose politics and culture were eroded by imperialism. This article offers an overview of this scholarship, asking how it might help scholars of U.S. history understand Hawai‘i as offering a different perspective for viewing the United States, from the outside in.

The study of protein localisation has greatly benefited from high-throughput methods utilising cellular fractionation and proteomic profiling. Hyperplexed Localisation of Organelle Proteins by Isotope Tagging (hyperLOPIT) is a well-established method in this area. It achieves high-resolution separation of organelles and subcellular compartments but is relatively time- and resource-intensive. As a simpler alternative, we here develop Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) and compare this method to the density gradient-based hyperLOPIT approach. We confirm that high-resolution maps can be obtained using differential centrifugation down to the suborganellar and protein complex level. HyperLOPIT and LOPIT-DC yield highly similar results, facilitating the identification of isoform-specific localisations and high-confidence localisation assignment for proteins in suborganellar structures, protein complexes and signalling pathways. By combining both approaches, we present a comprehensive high-resolution dataset of human protein localisations and deliver a flexible set of protocols for subcellular proteomics., Spatial proteomics allows studying cellular protein localisations at system-wide scale. Here, the authors show that combining the previously developed hyperLOPIT method with differential centrifugation yields protein localisation maps at suborganellar resolution while reducing analysis time and input material.

COVID-19 is profoundly affecting almost all aspects of economic and social life globally. Governments have closed borders, banned mass gatherings, and enforced social distancing, generating a new normal for businesses and individual citizens. Measures taken to protect public health have threatened the global economy, necessitating economic stimulus in most countries, and reconfiguring the role of business in society. We ask: Will the role of business in society return to normal after COVID-19, or will it be reconfigured in enduring and impactful ways? We use Alexander’s (2018, 2019) theory of societalization to examine how socially disruptive extreme events affect the role of business in society. To evidence this, we apply societalization to the revelatory example of COVID-19 and evaluate its impacts on society. Our analysis of the societalization of COVID-19 in the United States shows that concern regarding pandemic disease has moved from the governmental inside to the civic outside, placing strain on society, leading to regulatory response, and a significant societal backlash. We discuss three scenarios regarding the long-run impacts of COVID-19 on the role of business in society, suggest that societalization provides useful insights into other socially disruptive extreme events, and identify implications for future business and society research.

This chapter notes the challenges of CVAs, primarily under Section 6 of the 1986 Act. Challenges to a CVAS may come in the forms of jurisdiction or two statutory grounds of challenge under section 6 of the 1986 Act. The basis of challenges varies from unfair prejudice to material irregularity. The challenge under the grounds of unfair prejudice looks into the effect of a CVA's contents on the rights of creditors, while a material irregularity challenge is focused on the circumstances and process by the approval of the CVA. A limit of 28 days is the required observance period when challenging a CVA under the aforementioned grounds.

Large carnivores have long fascinated human societies and have profound influences on ecosystems. However, their conservation represents one of the greatest challenges of our time, particularly where attacks on humans occur. Where human recreational and/or livelihood activities overlap with large carnivore ranges, conflicts can become particularly serious. Two different scenarios are responsible for such overlap: In some regions of the world, increasing human populations lead to extended encroachment into large carnivore ranges, which are subject to increasing contraction, fragmentation, and degradation. In other regions, human and large carnivore populations are expanding, thus exacerbating conflicts, especially in those areas where these species were extirpated and are now returning. We thus face the problem of learning how to live with species that can pose serious threats to humans. We collected a total of 5,440 large carnivore (Felidae, Canidae, and Ursidae; 12 species) attacks worldwide between 1950 and 2019. The number of reported attacks increased over time, especially in lower-income countries. Most attacks (68%) resulted in human injuries, whereas 32% were fatal. Although attack scenarios varied greatly within and among species, as well as in different areas of the world, factors triggering large carnivore attacks on humans largely depend on the socioeconomic context, with people being at risk mainly during recreational activities in high-income countries and during livelihood activities in low-income countries. The specific combination of local socioeconomic and ecological factors is thus a risky mix triggering large carnivore attacks on humans, whose circumstances and frequencies cannot only be ascribed to the animal species. This also implies that effective measures to reduce large carnivore attacks must also consider the diverse local ecological and social contexts., VP was financially supported by the Project PID2020-114181GB-I00 financed by the Spanish Ministry of Science and Innovation, the Agencia Estatal de Investigación (AEI), and the Fondo Europeo de Desarrollo Regional (FEDER, EU).

BACKGROUND: Diagnostic and Statistical Manual (DSM) alcohol use disorder (AUD) criteria are written in broad enough terms to apply to diverse populations. The current analyses evaluate if the endorsement of criteria change with increasing age in individuals with persistent AUDs. METHODS: Data regarding AUDs persisting across three timepoints between average ages of 31 and 43 were gathered about every five years from 318 interviews for 106 San Diego Prospective Study (SDPS) AUD male probands. Similar data regarding persistent AUDs across two timepoints were obtained from 136 interviews with 68 SDPS AUD offspring between average ages of 21 and 27. Changes in endorsement of each AUD criterion were evaluated using Cochran’s Q test. RESULTS: For AUD probands across time significant decreases were observed in the proportions endorsing four criteria (tolerance, withdrawal, failure to fulfill obligations, and using alcohol in hazardous situations). Increased rates of endorsement were documented for three criteria (drinking higher quantities or for longer periods of time, spending a great deal of time regarding alcohol, and continued use despite social or interpersonal problems). Significant increases in rates of endorsements for offspring were seen for spending a great deal of time regarding alcohol and giving up or reducing important activities in order to drink. CONCLUSIONS: These data indicate that the salience of many DSM AUD criterion items changed significantly with age in both SDPS generations among individuals with persistent AUDs. The current results support the need for additional systematic research to determine whether specific criterion items might need to be weighted differently in evaluating older and younger individuals with persistent AUDs.

Protein-RNA interactions regulate all aspects of RNA metabolism and are crucial to the function of catalytic ribonucleoproteins. Until recently, the available technologies to capture RNA-bound proteins have been biased toward poly(A) RNA-binding proteins (RBPs) or involve molecular labeling, limiting their application. With the advent of organic-aqueous phase separation-based methods, we now have technologies that efficiently enrich the complete suite of RBPs and enable quantification of RBP dynamics. These flexible approaches to study RBPs and their bound RNA open up new research avenues for systems-level interrogation of protein-RNA interactions.

Emotional support animals Emotional support animals are not customary pets yet rather they give a mental health advantage to individuals having any sort of physical or mental frailty. In actuality like animals are prepared for express exercises like police association dogs, emotional support animals are prepared to perform comforting undertakings to offer emotional help for mentally steamed people and help them with their deficiencies. Proprietors who own pets that offer emotional or authentic help can get official endorsement to assume their pets any position they go. ESA animals assist individuals with genuine handicaps like visual block, wheelchair progressions and correspondingly give alarms about an individual's sugar level and circulatory strain. ESA pets are incredibly useful in instances of mental disorders like PTSD. ESA pets are comparatively useful in the instances of hypertension and shock management. Likewise get anESA letter for housingthat will assist you with keeping ESA at home. Javanese cat breed Javanese cats are known for their friendly nature towards individuals, certainly, they are incredibly captivated with their proprietors. Javanese cats are especially important for individuals who feel fruitless or weaken, they never let their proprietors be without a doubt follow them all over. On the off chance that you whenever need to talk with somebody the entire day, Javanese is the best other alternative. Friendly and assisting nature and relationship with their proprietors make Javanese cats extraordinary emotional support pets. Individuals who feel that they have nobody in life for emotional support can track down an astonishing friend in Javanese cat taking into account the capacity to regularly helping and prizing their proprietors. On the hand, Javanese cats are ordinarily under which recommends that these cats have the propensity for strolling around their proprietor's feet. Due to being under, Javanese cats are not the best alternative for individuals who use walkers or supports to walk. So we can say that for mental disorders Javanese is the best choice at any rate not for veritable disappointments identified with legs or feet which can be an obstacle in getting anESA Letter. Emotional support animal letter Getting an emotional support letter is a long method several fundamental necessities. Any individual with a mental or genuine handicap can't simply pick a pet for support. Potentially it is fundamental first to get the assessment report of their inability to introduce confirmation that they really need an ESA. After confirmation, attributes of their pets are matched to guarantee that their pet would not hurt others and fill the fundamental need. It has been seen that getting an emotional support dog letter is verifiably more problematic than a cat considering their wild nature. Regardless, concerning cats it is in addition not really straightforward due to the fundamental considered cats which isn't friendly. Right when we talk about Javanese, it is gotten to say that these cats genuinely offer mental help, yet tolerating you need to get theemotional support dog letterfor your pet because of genuine handicap then there is an issue. Which animals fit the bill for ESA? Any neighborhood animal that helps its proprietor in stress and genuine work can be separate as an emotional support animal. Notwithstanding, when an individual doesn't have an analyzed mental issue at any rate once in a while feels low and takes help from its pet can stamp it as ESA. Nonetheless, individuals who need to go with their pets just for the justification support need to get theemotional support animal letter. The most fundamental game plan of broadcasting a pet ESA is that it should not do any damage or upset others. Normally, hypoallergenic cats are a pleasant decision for emotional support animals. There are six fundamental characteristics that should be open in an animal to have every one of the essential characteristics for the letter, these qualities solidify; assembled, friendly, cautious, appreciating, delicate and reliable. Other than these six credits quietness and delicacy in nature comparatively acknowledges a basic part. Useful Resources: ESA Cat Breeds You Would Love to Have | Guide 2021 ESA Cat Breeds You Would Love to Have Useful Guide Towards ESA Cat Breeds You Would Love to Have ESA Cat Breeds You Would Love to Have at Your Home Get an ESA Letter to Get Rid of Your Stress and Anxiety - Guide Get an ESA Letter to Get Rid of Your Stress and Anxiety - Guide 2021

BackgroundA low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session.MethodsData were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway.ResultsContrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures.ConclusionThese data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Deprivation of liberty as part of the criminal process is always a significant step, and arguably even more so when the person so deprived has not yet been convicted of an offence. Remand decision making – that is, granting bail or requiring detention of a defendant prior to trial – in the courts of England and Wales is a common and important part of modern criminal procedure, yet has been under-examined in the last two decades. This article presents some of the findings of the first empirical study of remand law and practice in this jurisdiction in many years. It concludes that, notwithstanding that the rate of pretrial detention is comparatively low and practice is broadly in line with domestic and regional standards, there remain significant issues – particularly in relation to the time spent on such decisions and the information provided to courts when considering remands on bail or in custody.

Tom Scott-Smith is Associate Professor of Refugee Studies and Forced Migration, Fellow of St. Cross College Oxford, and Course Director for the MSc in Refugee and Forced Migration Studies. Previously, he worked as a development practitioner concerned with the education sector in the Middle East and Sub-Saharan Africa.1 The following interview discusses arguments and questions arising from his newest book (2020), historical and currents trends of hunger relief, important players, institutions and gender relations in the humanitarian sector ��� and more. It was conducted by Heike Wieters (Historical European Studies, Humboldt-Universit��t zu Berlin) and Tatjana T��nsmeyer (Contemporary History, Bergische Universit��t Wuppertal) in a back-and-forth conversation via E-Mail.

Transactions of the London and Middlesex Archaeological Society, 2.52, 169-176

Existing high-throughput methods to identify RNA-binding proteins (RBPs) are based on capture of polyadenylated RNAs and cannot recover proteins that interact with nonadenylated RNAs, including long noncoding RNA, pre-mRNAs and bacterial RNAs. We present orthogonal organic phase separation (OOPS), which does not require molecular tagging or capture of polyadenylated RNA, and apply it to recover cross-linked protein–RNA and free protein, or protein-bound RNA and free RNA, in an unbiased way. We validated OOPS in HEK293, U2OS and MCF10A human cell lines, and show that 96% of proteins recovered were bound to RNA. We show that all long RNAs can be cross-linked to proteins, and recovered 1,838 RBPs, including 926 putative novel RBPs. OOPS is approximately 100-fold more efficient than existing methods and can enable analyses of dynamic RNA–protein interactions. We also characterize dynamic changes in RNA–protein interactions in mammalian cells following nocodazole arrest, and present a bacterial RNA-interactome for Escherichia coli. OOPS is compatible with downstream proteomics and RNA sequencing, and can be applied in any organism.

Additional file 1: Bayesian model specification.

Additional file 3: Ethics approval and consent to participate.

Additional file 2: Details of methods and results.

Background Postoperative pulmonary complications (PPCs) are associated with poor outcomes following thoracotomy and lung resection. Video-assisted thoracoscopic surgery (VATS) for lobectomy is now frequently utilised as an alternative to thoracotomy, however patients remain at risk for development of PPC. There is little known of the short-term outcome associated with PPC following VATS lobectomy and if there are any potential risk factors that could be modified to prevent PPC development; our study aimed to investigate this. Methods A prospective observational study of consecutive patients undergoing VATS lobectomy for lung cancer over a 4-year period in a regional centre was performed (2012–2016). Exclusion criteria included re-do VATS or surgery for pulmonary infection. All patients received physiotherapy as necessary from postoperative day 1 (POD1) and PPC was determined using the Melbourne Group Scale. Outcomes included hospital LOS, intensive therapy unit (ITU) admission and hospital mortality. Results Of the 285 patients included in the study, 137 were male (48.1%), the median (IQR) age was 69 (13) years and the mean (±SD) FEV1% predicted was 87% (±19). Patients that developed a PPC (n = 21; 7.4%) had a significantly longer hospital LOS (4 vs. 3 days), higher frequency of ITU admission (23.8% vs. 0.5%) and higher hospital mortality (14.3% vs. 0%) (p

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms.