bluuebunny/crossref_metadata_2025_split huggingface dataset:
LinAliFold and CentroidLinAliFold: Fast RNA consensus secondary structure prediction for aligned sequences using beam search methods
Authors: Fukunaga Tsukasa , Hamada Michiaki 
Published: June 2022

AbstractRNA consensus secondary structure prediction from aligned sequences is a powerful approach for improving the secondary structure prediction accuracy. However, because the computational complexities of conventional prediction tools scale with the cube of the alignment lengths, their application to long RNA sequences, such as viral RNAs or long non-coding RNAs, requires significant computational time. In this study, we developed LinAliFold and CentroidLinAliFold, fast RNA consensus secondary structure prediction tools based on minimum free energy and maximum expected accuracy principles, respectively. We achieved software acceleration using beam search methods that were successfully used for fast secondary structure prediction from a single RNA sequence. Benchmark analyses showed that LinAliFold and CentroidLinAliFold were much faster than the existing methods while preserving the prediction accuracy. As an empirical application, we predicted the consensus secondary structure of coronaviruses with approximately 30,000 nt in 5 and 76 minutes by LinAliFold and CentroidLinAliFold, respectively. We confirmed that the predicted consensus secondary structure of coronaviruses was consistent with the experimental results. The source code is freely available at https://github.com/fukunagatsu/LinAliFold-CentroidLinAliFold.
Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells
Authors: McQuate Andrea , Knecht Sharmon , Raible David W. 
Published: June 2022

AbstractHair cells of the inner ear are particularly sensitive to changes in mitochondria, the subcellular organelles necessary for energy production in all eukaryotic cells. There are over thirty mitochondrial deafness genes, and mitochondria are implicated in hair cell death following noise exposure, aminoglycoside antibiotic exposure, as well as in age-related hearing loss. However, little is known about the basic aspects of hair cell mitochondrial biology. Using hair cells from the zebrafish lateral line as a model and serial block-face scanning electron microscopy, we have quantifiably characterized a unique hair cell mitochondrial phenotype that includes (1) a high mitochondrial volume, and (2) specific mitochondrial architecture: multiple small mitochondria apically, and a reticular mitochondrial network basally. This phenotype develops gradually over the lifetime of the hair cell. Disrupting this mitochondrial phenotype with a mutation in opa1 impacts mitochondrial health and function. While hair cell activity is not required for the high mitochondrial volume, it shapes the mitochondrial architecture, with mechanotransduction necessary for all patterning, and synaptic transmission necessary for development of mitochondrial networks. These results demonstrate the high degree to which hair cells regulate their mitochondria for optimal physiology, and provide new insights into mitochondrial deafness.
Optimized path planning surpasses human efficiency in cryo-EM imaging
Authors: Li Yilai , Fan Quanfu , Xu Ziping , Lee Emma Rose , Cohn John , Demers Veronique , Lee Ja Young , Yip Lucy , Cianfrocco Michael A. , Vos Seychelle M. 
Published: June 2022

AbstractCryo-electron microscopy (cryo-EM) represents a powerful technology for determining atomic models of biological macromolecules(Kühlbrandt, 2014). Despite this promise, human-guided cryo-EM data collection practices limit the impact of cryo-EM because of a path planning problem: cryo-EM datasets typically represent 2-5% of the total sample area. Here, we address this fundamental problem by formalizing cryo-EM data collection as a path planning optimization from low signal data. Within this framework, we incorporate reinforcement learning (RL) and deep regression to design an algorithm that uses distributed surveying of cryo-EM samples at low magnification to learn optimal cryo-EM data collection policies. Our algorithm - cryoRL - solves the problem of path planning on cryo-EM grids, allowing the algorithm to maximize data quality in a limited time without human intervention. A head-to-head comparison of cryoRL versus human subjects shows that cryoRL performs in the top 10% of test subjects, surpassing the majority of users in collecting high-quality images from the same sample. CryoRL establishes a general framework that will enable human-free cryo-EM data collection to increase the impact of cryo-EM across life sciences research.
O-GlcNAc transferase modulates formation of clathrin-coated pits
Authors: Rahmani Sadia , Ahmed Hafsa , Ibazebo Osemudiamen , Fussner-Dupas Eden , Wakarchuk Warren W. , Antonescu Costin N. 
Published: June 2022

AbstractClathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). These structures recruit specific membrane protein cargo destined for internalization and trigger the generation of membrane curvature that precedes eventual scission of CCPs from the plasma membrane to yield intracellular vesicles. The diversity of cell surface protein cargo thus controlled by CME indicates that CCP formation is regulated to allow cellular adaptation under different contexts. Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. The modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. We examined how the modification of proteins with O-GlcNAc may control CCP formation and thus CME. We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs is controlled by O-GlcNAc protein modification. This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis.
The nucleoporin Nup170 mediates subtelomeric gene silencing through the Ctf18-RFC complex and PCNA
Authors: Kumar Sanjeev , Neal Maxwell L. , Li Song , Navare Arti T. , Mast Fred D. , Rout Michael P. , Aitchison John D. 
Published: June 2022

ABSTRACTThe nuclear pore complex (NPC) physically interacts with chromatin and regulates gene expression. The inner ring nucleoporin Nup170 has been implicated in chromatin organization and the maintenance of gene silencing in subtelomeric regions. To gain insight into how Nup170 regulates this process, we used protein-protein interaction, genetic interaction, and transcriptome correlation analyses to identify the Ctf18-RFC complex, an alternative proliferating cell nuclear antigen (PCNA) loader, as a facilitator of the gene regulatory functions of Nup170. The Ctf18-RFC complex is recruited to a subpopulation of NPCs that lack the nuclear basket proteins Mlp1 and Mlp2. In the absence of Nup170, PCNA levels on DNA are reduced, resulting in the loss of silencing of subtelomeric genes. Increasing PCNA levels on DNA by removing Elg1, which is required for PCNA unloading, rescues subtelomeric silencing defects in nup170Δ. The NPC therefore mediates subtelomeric gene silencing by regulating PCNA levels on DNA.
A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint
Authors: Guay Kevin P. , Ibba Roberta , Kiappes JL , De Benedictis Maria , Zeni Ilaria , Le Cornu James D. , Hensen Mario , Chandran Anu V. , Kantsadi Anastassia L. , Caputo Alessandro T. , Blanco Capurro Juan I. , Bayo Yusupha , Hill Johan C. , Hudson Kieran , Lia Andrea , Vasiljević Snežana , Modenutti Carlos P. , Withers Stephen G. , Martí Marcelo , Biasini Emiliano , Santino Angelo , Hebert Daniel N. , Zitzmann Nicole , Roversi Pietro 
Published: June 2022

The Endoplasmic Reticulum (ER) glycoprotein folding Quality Control (ERQC) machinery aids folding of glycoproteins in the ER. Misfolded glycoprotein recognition and ER-retention is mediated by the ERQC checkpoint enzyme, the 170 kDa UDP-Glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. Towards the generation of selective UGGT inhibitors, we determined the crystal structures of the catalytic domain ofChaetomium thermophilumUGGT (CtUGGTGT24), alone and in complex with the inhibitor UDP-2-deoxy-2-fluoro-D-glucose (U2F). Using theCtUGGTGT24crystals, we carried out a fragment-based lead discovery screen via X-ray crystallography and discovered that the small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds aCtUGGTGT24‘WY’ conserved surface motif that is not present in other GT24 family glycosyltransferases. The 5M-8OH-Q molecule has a 613µM binding affinity for human UGGT1in vitroas measured by saturation transfer difference NMR spectroscopy. The 5M-8OH-Q molecule inhibits both human UGGT1and UGGT2 activity at concentrations higher than 750µM in modified HEK293-6E cells. The compound is toxicin cellulaandin plantaat concentrations higher than 1 mM. A few off-target effects are also observed upon 5M-8OH-Q treatment. Based on anin silicomodel of the interaction between UGGT and its substrateN-glycan, the 5M-8OH-Q molecule likely works as a competitive inhibitor, binding to the site of recognition of the first GlcNAc residue of the substrateN-glycan.Significance StatementWhen a candidate drug target is the product of a housekeeping gene - i.e. it is important for the normal functioning of the healthy cell – availability of inhibitors for tests and assays is of paramount importance. One such housekeeping protein is UGGT, the enzyme that makes sure that only correctly folded glycoproteins can leave the endoplasmic reticulum for further trafficking through the secretory pathway. UGGT is a potential drug target against viruses, in certain instances of congenital rare disease, and against some cancers, but no UGGT inhibitors are known yet. We discovered and describe here a small molecule that binds human UGGT1in vitroand inhibits both isoforms of human UGGTin cellula. The compound paves the way to testing of UGGT inhibition as a potential pharmacological strategy in a number of medical contexts.
Clinical features and outcomes in children with Stevens–Johnson syndrome and toxic epidermal necrolysis
Authors: Chi Min‐Hui , Chung Wen‐Hung , Hui Rosaline Chung‐Yee , Chen Chun‐Bing , Lu Chun‐Wei , Chiu Tsu‐Man , Ma David Hui‐Kang , Wang Chuang‐Wei , Yang Chin‐Yi ,   Taiwan Severe Cutaneous Adverse Reaction Consortium
Published: June 2022

AbstractStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged < 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty‐seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1–17 years); 51.1% were male. Thirty‐three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often‐implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3–42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long‐term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post‐inflammatory hypo‐/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long‐term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long‐term sequelae requiring regular follow‐up.
Challenges and opportunities for using natural history collections to estimate insect population trends
Authors: Davis Courtney L. , Guralnick Robert P. , Zipkin Elise F. 
Published: June 2022

Abstract

Natural history collections (NHC) provide a wealth of information that can be used to understand the impacts of global change on biodiversity. As such, there is growing interest in using NHC data to estimate changes in species' distributions and abundance trends over historic time horizons when contemporary survey data are limited or unavailable.

However, museum specimens were not collected with the purpose of estimating population trends and thus can exhibit spatiotemporal and collector‐specific biases that can impose severe limitations to using NHC data for evaluating population trajectories.

Here we review the challenges associated with using museum records to track long‐term insect population trends, including spatiotemporal biases in sampling effort and sparse temporal coverage within and across years. We highlight recent methodological advancements that aim to overcome these challenges and discuss emerging research opportunities.

Specifically, we examine the potential of integrating museum records and other contemporary data sources (e.g. collected via structured, designed surveys and opportunistic citizen science programs) in a unified analytical framework that accounts for the sampling biases associated with each data source. The emerging field of integrated modelling provides a promising framework for leveraging the wealth of collections data to accurately estimate long‐term trends of insect populations and identify cases where that is not possible using existing data sources.
Subarctic afforestation: Effects of forest plantations on ground‐nesting birds in lowland Iceland
Authors: Pálsdóttir Aldís E. , Gill Jennifer A. , Alves José A. , Pálsson Snæbjörn , Méndez Verónica , Ewing Harry , Gunnarsson Tómas G. 
Published: June 2022

Abstract

Planting forests is a commonly suggested measure to mitigate climate change. The resulting changes in habitat structure can greatly influence the diversity and abundance of pre‐existing wildlife. Understanding these consequences is key for avoiding unintended impacts of afforestation on habitats and populations of conservation concern.

Afforestation in lowland Iceland has been gaining momentum in recent years and further increases are planned. Iceland supports internationally important breeding populations of several ground‐nesting, migratory bird species that mostly breed in open habitats. If afforestation impacts the distribution and abundance of these species, the consequences may be apparent throughout their non‐breeding ranges across Europe and Africa.

To quantify the effects of plantation forests on the abundance and distribution of ground‐nesting birds (in particular waders, Charadriiformes), surveys were conducted on 161 transects (surrounding 118 plantations) perpendicular to forest edges throughout Iceland. The resulting variation in density with distance from plantation was used to estimate the likely changes in bird numbers resulting from future afforestation plans, and to explore the potential effects of different planting configuration (size and number of forest patches) scenarios.

Of seven wader species, densities of five (golden plover Pluvialis apricaria, whimbrel Numenius phaeopus, oystercatcher Haematopus ostralegus, dunlin Calidris alpina and black‐tailed godwit Limosa limosa) in the 200 m surrounding plantations were just under half of those further away (up to 700 m). Redshank Tringa totanus densities were lowest ≤150 m from the plantation edge while snipe Gallinago gallinago densities were 50% higher close to plantations (0–50 m) than further away (51–700 m), and no consistent effects of plantation height, diameter, density or type were identified. Plantations are typically small and widespread, and simulated scenarios indicated that total declines in bird abundance resulting from planting trees in one large block (1,000 ha) could result in only ~11% of the declines predicted from planting multiple small blocks (1 ha) in similar habitats.

Synthesis and application. Planting forests in open landscapes can have severe impacts on populations of ground‐nesting birds, which emphasizes the need for strategic planning of tree‐planting schemes. Given Iceland's statutory commitments to species protection and the huge contribution of Iceland to global migratory bird flyways, these are challenges that must be addressed quickly, before population‐level impacts are observed across migratory ranges.
Occupational therapy in Australian residential aged care facilities: A systematic mapping review
Authors: Calderone Lora , Bissett Michelle , Molineux Matthew 
Published: June 2022

AbstractIntroductionAustralia's population is ageing, resulting in more older adults living in residential aged care facilities. Occupational therapy scope of practice in Australian residential aged care facilities is significantly influenced by the government funding instrument. As the current government funding instrument is administratively inefficient, insufficiently discriminates between residents' care needs and provides perverse incentives, a new funding model is set to be implemented. This creates an opportunity for a review of the current evidence base to support the lobbying of national associations to shape occupational therapy practice. The research question that guided this systematic mapping review was as follows: What is the current state of scholarship about occupational therapy in Australian residential aged care facilities?MethodsA search of four databases (CINAHL, Medline, Embase and Scopus) was conducted and 1,617 papers were identified. All papers were screened through a two‐phase process: (i) title and abstract review and (ii) full text review, using pre‐determined inclusion and exclusion criteria to identify papers relevant to this review. A data extraction tool was designed in Microsoft Excel® and was used to extract data from the included papers.ResultsTwelve Australian articles were published between 1986 and 2020, most frequently authored by an occupational therapist. Included articles were classified into four groups: articles including occupational therapists as participants, articles about occupational therapy practice, articles exploring an occupational perspective of residents and articles with limited exploration of occupational therapy.ConclusionThis review identified that there is a dearth of Australian occupational therapy literature. This creates challenges for occupational therapists seeking evidence to guide their practice to optimise resident health and well‐being and for national associations seeking to lobby for the profession. Consequently, there is a crucial need to develop the evidence base to support the profession within this practice setting and, ultimately, residents.
Rapid changes in coastal ocean microbiomes uncoupled with shifts in environmental variables
Authors: Gronniger Jessica L. , Wang Zhao , Brandt Genevieve R. , Ward Christopher S. , Tsementzi Despina , Mu Han , Gu Junyao , Johnson Zackary I. , Konstantinidis Konstantinos T. , Hunt Dana E. 
Published: June 2022

SummaryDisturbances, here defined as events that directly alter microbial community composition, are commonly studied in host‐associated and engineered systems. In spite of global change both altering environmental averages and increasing extreme events, there has been relatively little research into the causes, persistence and population‐level impacts of disturbance in the dynamic coastal ocean. Here, we utilize 3 years of observations from a coastal time series to identify disturbances based on the largest week‐over‐week changes in the microbiome (i.e. identifying disturbance as events that alter the community composition). In general, these microbiome disturbances were not clearly linked to specific environmental factors and responsive taxa largely differed, aside from SAR11, which generally declined. However, several disturbance metagenomes identified increased phage‐associated genes, suggesting that unexplained community shifts might be caused by increased mortality. Furthermore, a category 1 hurricane, the only event that would likely be classified a priori as an environmental disturbance, was not an outlier in microbiome composition, but did enhance a bloom in seasonally abundant phytoplankton. Thus, as extreme environmental changes intensify, assumptions of what constitutes a disturbance should be re‐examined in the context of ecological history and microbiome responses.
‘More options…less time’ in the ‘hustle culture’ of ‘generation sensible’: Individualization and drinking decline among twenty‐first century young adults
Authors: Burgess Adam , Yeomans Henry , Fenton Laura 
Published: June 2022

AbstractThere has been a dramatic decline in alcohol consumption among younger people, including an increase of conscious moderation and abstinence. Change has a generational character, with different cohorts' drinking changing over time from the heavy, embedded pattern among post‐war ‘boomers’ to the more selective habits initiated by ‘millennials’. This is a surprising development in historical terms and has been cast as indicating the emergence of a moderating ‘generation sensible’. It is also coincident with more negative trends, such as young adults worsening mental health. Informed by the perspective of individualization, we consider the decline in youth drinking in the context of generational changes in the lifecourse. We focus upon how recent generations of young people experience greater choice, pressure and a prolonged adolescence, characterized by more limited autonomy. Explored with conscious young moderators through a survey (N = 517) and focus groups (N = 13), these themes resonated with our sample who appear a self‐conscious generation with significant and open‐ended focus upon maintaining their wellbeing and control. Further, they appear more disembedded from pressure to conform but under greater pressure to perform. The same forces of individualization encouraging moderate drinking may also weigh down upon young people who feel under pressure not only to transform their own lives but feel a burden of responsibility for a damaged, unjust world. The article's originality lies in applying individualization to both generational change and consumption, suggesting this can be usefully done through a focus upon freedom/choice and pressure/performance. It also considers what is regarded as the positive trend of drinking decline alongside, and as related to, negative trends such as greater loneliness and less autonomy among young adults.