bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of aIF5B in archaeal translation initiation
Authors: Kazan Ramy , Bourgeois Gabrielle , Lazennec-Schurdevin Christine , Larquet Eric , Mechulam Yves , Coureux Pierre-Damien , Schmitt Emmanuelle 
Published: May 2022

ABSTRACTIn eukaryotes and in archaea late steps of translation initiation involve the two initiation factors e/aIF5B and e/aIF1A. In eukaryotes, the role of eIF5B in ribosomal subunit joining is established and structural data showing eIF5B bound to the full ribosome were obtained. To achieve its function, eIF5B collaborates with eIF1A. However, structural data illustrating how these two factors interact on the small ribosomal subunit have long been awaited. The role of the archaeal counterparts, aIF5B and aIF1A, remains to be extensively addressed. Here, we study the late steps of Pyrococcus abyssi translation initiation. Using in vitro reconstituted initiation complexes and light scattering, we show that aIF5B bound to GTP accelerates subunit joining without the need for GTP hydrolysis. We report the crystallographic structures of aIF5B bound to GDP and GTP and analyze domain movements associated to these two nucleotide states. Finally, we present the cryo-EM structure of an initiation complex containing 30S bound to mRNA, Met-tRNAiMet, aIF5B and aIF1A at 2.7 Å resolution. Structural data shows how archaeal 5B and 1A factors cooperate to induce a conformation of the initiator tRNA favorable to subunit joining. Archaeal and eukaryotic features of late steps of translation initiation are discussed.
Impatiens banensp. nov. &I. etugeisp. nov. (Balsaminaceae), threatened lowland species of the Cross-Sanaga Interval, Cameroon
Authors: Cheek Martin , Darbyshire Iain , Onana Jean Michel 
Published: May 2022

SummaryWe describe two range-restricted new species to science from the genusImpatiens(Balsaminaceae), both threatened, from the Cross-Sanaga Interval of western Cameroon. The first,Impatiens banen, appears to be restricted to an open seepage microhabitat on granitic inselbergs in the lowland-submontane forest zone of the Ebo Forest in Littoral Region and is provisionally assessed using the 2012 IUCN standard as Vulnerable. Sharing characters withImpatiens burtoniiandI. mannii, it differs from both, and appears to be unique in Camerooninter alia1) in the bicolored united lateral petals, the upper petals being white, while the lower petals are an intense pink-purple, 2) the hairy, filamentous spur, purple with a white apex, is curved along its length (through nearly 360°), almost describing a circle. Inselberg-specific species are unusual inImpatiens.The second species,Impatiens etugei, of theI. macropteraaggregate, is restricted to rocks in the Mutel River of the Kom Wum Forest Reserve of NorthWest Region and is assessed as Critically Endangered. Having similarities withI. mackeyanaandI. letouzeyi, it differs from other species in the aggregateinter aliaby having opposite leaves (vs always alternate), flower exterior white (vs pink or pink-purple), and in the dorsal petal having a pair of lateral projections (vs projections absent).
A new machine learning based computational framework identifies therapeutic targets and unveils influential genes in pancreatic islet cells
Authors: Turki Turki , Taguchi Y-h. 
Published: May 2022

AbstractPancreatic islets comprise a group of cells that produce hormones regulating blood glucose levels. Particularly, the alpha and beta islet cells produce glucagon and insulin to stabilize blood glucose. When beta islet cells are dysfunctional, insulin is not secreted, inducing a glucose metabolic disorder. Identifying effective therapeutic targets against the disease is a complicated task and is not yet conclusive. To close the wide gap between understanding the molecular mechanism of pancreatic islet cells and providing effective therapeutic targets, we present a computational framework to identify potential therapeutic targets against pancreatic disorders. First, we downloaded three transcriptome expression profiling datasets pertaining to pancreatic islet cells (GSE87375, GSE79457, GSE110154) from the Gene Expression Omnibus database. For each dataset, we extracted expression profiles for two cell types. We then provided these expression profiles along with the cell types to our proposed constrained optimization problem of a support vector machine and to other existing methods, selecting important genes from the expression profiles. Finally, we performed (1) an evaluation from a classification perspective which showed the superiority of our methods against the baseline; and (2) an enrichment analysis which indicated that our methods achieved better outcomes. Results for the three datasets included 44 unique genes and 10 unique transcription factors (SP1, HDAC1, EGR1, E2F1, AR, STAT6, RELA, SP3, NFKB1, and ESR1) which are reportedly related to pancreatic islet functions, diseases, and therapeutic targets.
Light-dependent modulation of protein localization and function in living bacteria cells
Authors: McQuillen Ryan , Yang Xinxing , Bohrer Christopher H. , McCausland Joshua W. , Xiao Jie 
Published: May 2022

AbstractMost bacteria lack membrane-enclosed organelles to compartmentalize cellular processes. In lieu of physical compartments, bacterial proteins are often recruited to macromolecular scaffolds at specific subcellular locations to carry out their functions. Consequently, the ability to modulate a protein’s subcellular location with high precision and speed bears the potential to manipulate its corresponding cellular functions. Here we demonstrate that the CRY2/CIB1 system from Arabidopsis thaliana can be used to rapidly direct proteins to different subcellular locations inside live E. coli cells including the nucleoid, the cell pole, membrane, and the midcell division plane. We further show that such light-induced re-localization can be used to rapidly inhibit cytokinesis in actively dividing E. coli cells. Finally, we demonstrate that the CRY2/CIBN binding kinetics can be modulated by green light, adding a new dimension of control to the system.
Fc-engineered antibodies leverage neutrophils to drive control ofMycobacterium tuberculosis
Authors: Irvine Edward B. , Peters Joshua M. , Lu Richard , Grace Patricia S. , Sixsmith Jaimie , Wallace Aaron , Schneider Matthew , Shin Sally , Karpinski Wiktor , Hsiao Jeff C. , van Woudenbergh Esther , Casadevall Arturo , Bryson Bryan D. , Cavacini Lisa , Alter Galit , Fortune Sarah M. 
Published: May 2022

ABSTRACTNovel vaccination and therapeutic strategies are urgently needed to mitigate the tuberculosis (TB) epidemic. While extensive efforts have focused on potentiating cell-mediated immunity to controlMycobacterium tuberculosis(Mtb) infection, less effort has been invested in exploiting the humoral immune system to combatMtb. Emerging data point to a role for antibodies in microbial control ofMtb, however the precise mechanism(s) of this control remain incompletely understood. Here we took an antibody Fc-engineering approach to determine whether Fc-modifications could improve the ability of antibodies to restrictMtb, and to define Fc-mediated mechanism(s) antibodies leverage for this restriction. Using an antibody specific to the capsular polysaccharide α-glucan, we engineer a panel of Fc variants to augment or dampen select antibody effector functions, rationally building antibodies with enhanced capacity to promoteMtbrestriction in a human whole blood model of infection. Surprisingly, restrictive Fc-engineered antibodies driveMtbcontrol in a neutrophil, not monocyte, dependent manner. Using single cell RNA sequencing, we show that restrictive antibodies promote neutrophil survival and expression of cell intrinsic antimicrobial programs. These data provide a roadmap for exploiting Fc-engineered antibodies as a novel class of TB therapeutics able to harness the protective functions of neutrophils to achieve disease control.
Arc-Expressing Accessory Olfactory Bulb Interneurons Support Chemosensory Social Behavioral Plasticity
Authors: Zuk Kelsey E. , Cansler Hillary L. , Wang Jinxin , Meeks Julian P. 
Published: May 2022

AbstractThe accessory olfactory system (AOS) is critical for the development and expression of social behavior. The first dedicated circuit in the AOS, the accessory olfactory bulb (AOB), exhibits cellular and network plasticity in male and female mice after social experience. In the AOB, interneurons called internal granule cells (IGCs) express the plasticity-associated immediate-early gene Arc following intermale aggression or mating. Here, we sought to better understand how Arc-expressing IGCs shape AOB information processing and social behavior in the context of territorial aggression. We used “ArcTRAP” (Arc-CreERT2) transgenic mice to selectively and permanently label Arc-expressing IGCs following male-male resident-intruder interactions. Using whole-cell patch clamp electrophysiology, we found that Arc-expressing IGCs display increased intrinsic excitability for several days after a single resident-intruder interaction. Further, we found that Arc-expressing IGCs maintain this increased excitability across repeated resident-intruder interactions, during which resident mice increase or “ramp” their aggression. We tested the hypothesis that Arc-expressing IGCs participate in ramping aggression. Using a combination of ArcTRAP mice and chemogenetics (Cre-dependent hM4D(Gi)-mCherry AAV injections), we found that disruption of Arc-expressing IGC activity during repeated resident-intruder interactions abolishes the ramping aggression exhibited by resident male mice. This work shows that Arc-expressing AOB IGC ensembles are activated by specific chemosensory environments, and play an integral role in the establishment and expression of sex-typical social behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior.Significance statementThe accessory olfactory system (AOS) plays a vital role in rodent chemosensory social behavior. We studied experience-dependent plasticity in the accessory olfactory bulb (AOB) and found that internal granule cells (IGCs) expressing the immediate-early gene Arc after the resident-intruder paradigm increase their excitability for several days. We investigated the roles of these Arc-expressing IGCs on chemosensory social behavior by chemogenetically manipulating their excitability during repeated social interactions. We found that inhibiting these cells eliminated intermale aggressive ramping behavior. These studies identify a population of plastic interneurons in an early chemosensory circuit that display physiological features consistent with simple memory formation, increasing our understanding of central chemosensory processing and mammalian social behavior.
Microbiome signatures inAcropora cervicornisare associated with genotypic resistance to elevated nutrients and heat stress
Authors: Palacio-Castro Ana M. , Rosales Stephanie M. , Dennison Caroline E. , Baker Andrew C. 
Published: May 2022

SummaryThe staghorn coral,Acropora cervicornis, was once abundant in the Caribbean, but now is listed as critically endangered. To recoverA. cervicornispopulations, restoration efforts have focused on preserving genetic diversity and increasing coral cover. However, identifying stress-resistant corals can help to increase restoration success, by allocating genotypes to reefs where they are more likely to survive. We assessed the performance (growth, survivorship, and photochemical efficiency) and characterized the microbiome (prokaryotes) of sixA. cervicornisgenotypes that were maintained at control temperatures (~26 °C) and either ambient nutrients or elevated nutrients (elevated NH4, and elevated NH4+ PO4) for > 2 months. We then compared how these parameters changed when the corals were exposed to heat-stress (3-weeks at ~31.5 °C). We found that exposure to elevated nutrients reducedA. cervicornisperformance under control temperatures and heat stress. However, there was a wide range of variation among genotypes, with three genotypes maintaining relatively higher survivorship and growth rates when exposed to nutrients alone, and nutrients followed by heat stress. Heat stress alone changed the microbial composition among genotypes more than elevated nutrients alone, but heat stress also interacted with nutrient pre-exposure to affect microbial communities. The relative abundance ofMidichloriaceaeandSpirochaetaceaevaried by coral genotype and a high abundance of these bacterial taxa was a positive predictor of coral survivorship rate, suggesting a microbial signature that could aid in identifying resistantA. cervicornisgenotypes. Our findings suggest there is significant variation among genotypes in the response ofA. cervicornisto elevated nutrients and temperatures. Resistant genotypes may be identifiable via their microbiomes and prioritized for outplanting at sites characterized by high levels of nutrient pollution. Large-scale microbiome screening may help expedite targeted outplanting and could be tested and extended to facilitate the identification of genotypes with other resistance characteristics.
Characterization and mu opioid receptor sensitivity of neuropeptide Y interneurons in the nucleus accumbens
Authors: Retzlaff Cassandra L. , Rothwell Patrick E. 
Published: May 2022

ABSTRACTInhibitory interneurons represent less than 5% of neurons within the nucleus accumbens, but are critical for proper microcircuit function within this brain region. In the dorsal striatum, neuropeptide Y is expressed by two interneuron subtypes (low-threshold spiking interneurons and neurogliaform interneurons) that exhibit mu opioid receptor sensitivity in other brain regions. However, few studies have assessed the molecular and physiological properties of neuropeptide Y interneurons within the nucleus accumbens. We used a transgenic reporter mouse to identify and characterize neuropeptide Y interneurons in acute nucleus accumbens brain slices. Nearly all cells exhibited electrophysiological properties of low-threshold spiking interneurons, with almost no neurogliaform interneurons observed among neuropeptide Y interneurons. We corroborated this pattern using fluorescent in situ hybridization, and also identified a high level of mu opioid receptor expression by low-threshold spiking interneurons, which led us to examine the functional consequences of mu opioid receptor activation in these cells using electrophysiology. Mu opioid receptor activation caused a reduction in the rate of spontaneous action potentials in low-threshold spiking interneurons, as well as a decrease in optogenetically-evoked GABA release onto medium spiny neurons. The latter effect was more robust in female versus male mice, and when the postsynaptic medium spiny neuron expressed the Drd1 dopamine receptor. This work is the first to examine the physiological properties of neuropeptide Y interneurons in the nucleus accumbens, and show they may be an important target for mu opioid receptor modulation by endogenous and exogenous opioids.
TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity
Authors: Jia Aolin , Huang Shijia , Song Wen , Wang Junli , Meng Yonggang , Sun Yue , Xu Lina , Laessle Henriette , Jirschitzka Jan , Hou Jiao , Zhang Tiantian , Yu Wenquan , Hessler Giuliana , Li Ertong , Ma Shoucai , Yu Dongli , Gebauer Jan , Baumann Ulrich , Liu Xiaohui , Han Zhifu , Chang Junbiao , Parker Jane E. , Chai Jijie 
Published: May 2022

AbstractPlant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/Interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded NADases produce signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR sub-classes. Here we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) via ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of di-ADPR or ADPr-ATP allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A)in vitroandin planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.
The global randomization test: A Mendelian randomization falsification test for the exclusion restriction assumption
Authors: Millard Louise AC , Smith George Davey , Tilling Kate 
Published: May 2022

ABSTRACTMendelian randomization may give biased causal estimates if the instrument affects the outcome not solely via the exposure of interest (violating the exclusion restriction assumption). We demonstrate use of a global randomization test as a falsification test for the exclusion restriction assumption. Using simulations, we explored the statistical power of the randomization test to detect an association between a genetic instrument and a covariate set due to a) selection bias or b) horizontal pleiotropy, compared to three approaches examining associations with individual covariates: i) Bonferroni correction for the number of covariates, and ii) correction for the effective number of independent covariates and iii) an r2 permutation-based approach. We conducted proof-of-principle analyses in UK Biobank, using CRP as the exposure and coronary heart disease (CHD) as the outcome. In simulations, power of the randomization test was higher than the other approaches for detecting selection bias when the correlation between the covariates was low (R2< 0.1), and at least as powerful as the other approaches across all simulated horizontal pleiotropy scenarios. In our applied example, we found strong evidence of selection bias using all approaches (e.g., global randomization test p<0.002). We identified 51 of the 58 CRP genetic variants as horizontally pleiotropic, and estimated effects of CRP on CHD attenuated somewhat to the null when excluding these from the genetic risk score (OR=0.956 [95% CI: 0.918, 0.996] versus 0.970 [95% CI: 0.900, 1.046] per 1-unit higher log CRP levels). The global randomization test can be a useful addition to the MR researcher’ s toolkit.
Craniodental traits predict feeding performance and dietary hardness in a community of Neotropical free‐tailed bats (Chiroptera: Molossidae)
Authors: Villalobos‐Chaves David , Santana Sharlene E. 
Published: May 2022

Abstract

Form–function studies have established a strong link between dental morphology and the mechanical properties of food items, with animals evolving tooth shapes theoretically ideal for their diets. However, information on how teeth perform under natural conditions is rare, which limits the understanding of how dental morphology influences dietary ecology and niche partitioning within animal communities.

Free‐tailed bats (Chiroptera: Molossidae) are a diverse clade of aerial insectivorous mammals that exhibit an outstanding variation in size and craniodental traits, which have been directly related to ecological segregation among sympatric species.

We investigate the mechanisms that allow functional dietary specialization and trophic segregation among sympatric free‐tailed bat species inhabiting a Neotropical forest. To do so, we coupled data on 3D dental topographic metrics, head and skull dimensions, field‐collected feeding performance and dietary hardness measurements.

We found that evolved differences in molar topography and skull size vary in tandem with the mechanical demands of prey items naturally consumed by sympatric molossid species. This may be explained by feeding performance capabilities resulting from both molar shape and the overall size of the feeding apparatus, which seem to allow efficient processing of prey items with specific mechanical properties. For instance, smaller bats with higher molar topographic values (sharper, more complex molars) and more gracile heads mainly feed on softer insects, whereas bigger bats with lower molar topographic values (blunter, less complex molars) and more robust heads mostly feed on tougher insects. Species with a broader range of sizes, craniodental morphologies and insect hardness are also present in the community.

These results illustrate how the morphology and size of feeding structures, and how they perform, may facilitate trophic segregation among sympatric insectivorous bats. Similar mechanisms may help structure other communities of insectivorous mammals, therefore the approaches presented here could be used to generate a better understanding of the ecomorphological traits and processes that underlie their diversity.

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Sparse seismic reflectivity inversion using an adaptive fast iterative shrinkage‐thresholding algorithm
Authors: Li Chuanhui , Liu Xuewei 
Published: May 2022

ABSTRACTSeismic reflectivity inversion using l1‐norm regularization produces sparse solutions by applying an l1‐norm constraint. The fast iterative shrinkage‐thresholding algorithm is one of the most effective methods to solve l1‐norm regularized inversion problems. A large number of iterations are commonly required in the fast iterative shrinkage‐thresholding algorithm because its solution converges slowly towards the sparse solution. To improve its convergence rate, we introduce a modifying strategy for the traditional fast iterative shrinkage‐thresholding algorithm. When implementing the soft‐thresholding operator, the thresholding value is adaptively adjusted by assigning the reciprocal of the solution in the previous iteration as a weight to the thresholding value of the current iteration. In this way, small variables in the solution produce large coefficients applied to the thresholding value, which causes small variables to quickly converge to zero. The adaptive fast iterative shrinkage‐thresholding algorithm shows significantly improved computational efficiency and accuracy compared to the traditional fast iterative shrinkage‐thresholding algorithm. It produces good results for both numerical and field examples of l1‐norm regularized seismic reflectivity inversion.
How effective is rescue therapeutic plasma exchange in treatment of SARS‐Coronavirus‐2?
Authors: Diskin Charles J. , Maldonado Ricardo , Leon Jose , Dansby Linda M. , Carter Thomas B. , Radcliff Lautrec , Diskin Charles D. 
Published: May 2022

AbstractIntroductionAfter the FDA gave emergency approval for the use of therapeutic plasma exchange in treatment for SARS‐Coronoavirus‐2, we analyzed its efficacy in patients who had failed all other known therapies.MethodsThis was a prospective observational study of 42 patients with SARS‐Coronoavirus‐2 who had failed conventional therapy and were treated with therapeutic plasma exchange. Pre‐ and postexchange clinical and laboratory parameters were monitored. The patients were then also compared with a group of 147 patients with SARS‐Coronoavirus‐2 who were referred for stage 3 acute renal failure and dialysis from SARS‐Coronoavirus‐2.ResultsAfter therapeutic plasma exchange, there were significant improvements in some clinical parameters but mortality remained high; although better than the renal failure group (43.9% vs. 50.7%, p = 0.004).ConclusionSARS‐CoV‐2 patients who failed all other therapies had significant mortality with therapeutic plasma exchange; however, their survival was better than SARS‐CoV‐2 patients with stage 3 acute renal failure.