bluuebunny/crossref_metadata_2025 huggingface dataset:
Contact bioassay in tandem with HPLC analysis of the active ingredients in LLINs revealed hidden possible causes of the unabated rise in malaria cases
Authors: Kusimo Michael O. , Ibrahim Sulaiman S. , Kusimo Nelly O. , Nwokeoji Alison O. , Yemitan Omoniyi K.
Published: November 2022

Background

The World Malaria Report 2021 revealed that Nigeria accounted for 27% of 241 million malaria cases worldwide and 31% of 602,000 malaria deaths. This WHO report is in sharp contrast to the ambitious goal of the National Malaria Strategic Plan (NMSP) 2014-2020, which aimed to transition Nigeria from malaria control to malaria elimination status by 2020. In this study, we combined contact bioassay with HPLC analysis to investigate how the end users’ treatment of Long-Lasting Insecticide Treated Nets (LLINs) inadvertently contributes to the unabated rise in malaria cases.

Methods

We randomly selected a few LLINs used under normal household conditions in Port-Harcourt and one on sale in Lagos, Nigeria. The continued potency of these LLINs to protect the users against malaria vectors, assuming the local vectors are insecticide-susceptible, was evaluated by exposing laboratory-susceptibleAnopheles gambiaKisumu strain to the nets according to the WHO cone bioassay protocol. After the exposure, the active ingredients (AI) in the LLINs were extracted and analysed using reverse phase HPLC to establish the quantity of the AIs and correlate it to bio-efficacy. The AI loss per wash was also computed based on the information provided by the users.

Results

The labels on the LLINs revealed them to be Royal Sentry, PermaNet 2.0 and DuraNet. The bio-efficacy of these LLINs under household usage is less than two years. AI lost per wash was higher by 2.5-fold in LLIN made of polyethylene nets than polyester nets: 0.35g/Kg/wash and 0.14g/Kg/wash, respectively. The AI lost per wash increased by 31% for net exposed longer to the harsh environmental conditions of this region. The LLIN (ParmaNet) purchased in the open market has the highest AI concentration but only achieved 70.62% mortality, far below the acceptable standard.

Conclusion

The AI in the LLIN bought from the open market was the highest, but of poor quality. This bed net was a counterfeit product, not approved by WHOPES. More importantly, this study revealed that field examination of LLINs under normal household use should be examined per region for policy makers to have informed knowledge of the duration of the bio-efficacy of the LLINs being distributed.
Large-scale Rare Variant Burden Testing in Parkinson’s Disease Identifies Novel Associations with Genes Involved in Neuro-inflammation
Authors: Makarious Mary B. , Lake Julie , Pitz Vanessa , Fu Allen Ye , Guidubaldi Joseph L. , Solsberg Caroline Warly , Bandres-Ciga Sara , Leonard Hampton L. , Kim Jonggeol Jeffrey , Billingsley Kimberley J. , Grenn Francis P. , Jerez Pilar Alvarez , Alvarado Chelsea , Iwaki Hirotaka , Ta Michael , Vitale Dan , Hernandez Dena , Torkamani Ali , Ryten Mina , Hardy John ,   UK Brain Expression Consortium (UKBEC), Scholz Sonja W. , Traynor Bryan J. , Dalgard Clifton L. , Ehrlich Debra J. , Tanaka Toshiko , Ferrucci Luigi , Beach Thomas G. , Serrano Geidy E. , Real Raquel , Morris Huw R. , Ding Jinhui , Gibbs J. Raphael , Singleton Andrew B. , Nalls Mike A. , Bhangale Tushar , Blauwendraat Cornelis
Published: November 2022

Parkinson’s disease (PD) has a large heritable component and genome-wide association studies to date have identified over 90 variants associated with PD, providing deeper insights into the disease biology. However, there have not been large-scale rare variant analyses for PD. To address this gap, we investigated the rare genetic component of PD at minor allele frequencies <1%, using whole genome and whole exome sequencing data from 7,184 PD cases, 6,701 proxy-cases, and 51,650 healthy controls from the Accelerating Medicines Partnership Parkinson’s disease (AMP-PD) initiative, the National Institutes of Health, the UK Biobank, and Genentech. We performed burden tests meta-analyses on protein-altering variants, prioritized based on their predicted functional impact. Our work identified several genes reaching exome-wide significance. While two of these genes,GBAandLRRK2, have been previously implicated as risk factors for PD, we identify potential novel associations forB3GNT3, AUNIP, ADH5, TUBA1B, OR1G1, CAPN10, andTREML1. Of these,B3GNT3andTREML1provide new evidence for the role of neuroinflammation in PD. To date, this is the largest analysis of rare genetic variation in PD.
Astrocytic Gapjinc (TMEM43) modulates gap junction networks by facilitating transjunctional potentials
Authors: Jang Minwoo Wendy , Kim Ki Jung , Lim Jiwoon , Kim Daeun , Park Yongmin Mason , Kim Tai Young , Roh Woo Suk , Han Young-Eun , Won Joungha , Lee Jae-Hun , Shin Eunjin , Han Ah-reum , Kim Ho Min , Han Kyung-Seok , Lee C. Justin
Published: November 2022

TheTMEM43gene has been reported to play supportive but critical roles in human diseases including cancer, arrhythmogenic right ventricular cardiomyopathy (ARVC), and auditory neuropathy spectrum disorder (ANSD). However, direct characterization of the TMEM43 protein itself and its role in the brain remain unexplored. In this study, we demonstrated that TMEM43 confers ion channel activities via the lipid bilayer reconstitution of purified TMEM43 protein and further characterized TMEM43 as a pH-sensing cation channel in the heterologous expression system. TMEM43 was shown to conduct transjunctional potentials between adjacent cells, further facilitating electrical couplings of the gap junctions. In the hippocampus of TMEM43 knockout (KO) mice, we observed a decrease in astrocytic dye diffusion and potassium buffering, an increase in neuronal excitability, and alterations in AMPA/NMDA ratio and LTP. The electrophysiological changes in the KO mice led to a disturbance in memory retrieval which was rescued with TMEM43 overexpression. These results indicate that TMEM43 actively participates in gap junction networks of the hippocampus to prevent neurons from hyperexcitability, which is critical for memory retrieval. Together, our study elucidates the molecular and functional identities of TMEM43 and underscores its role in memory retrieval.
Progress in elementary school reading linked to growth of cortical responses to familiar letter combinations within visual word forms
Authors: Wang Fang , Kaneshiro Blair , Toomarian Elizabeth Y. , Gosavi Radhika S. , Hasak Lindsey R. , Moron Suanna , Nguyen Quynh Trang H. , Norcia Anthony M. , McCandliss Bruce D.
Published: November 2022

Learning to read depends on the ability to extract precise details of letter combinations, which convey critical information that distinguishes tens of thousands of visual word forms. To support fluent reading skill, one crucial neural developmental process is one’s brain sensitivity to statistical constraints inherent in combining letters into visual word forms. To test this idea in early readers, we tracked the impact of two years of schooling on within-subject longitudinal changes in cortical responses to different properties of words (coarse tuning for print, and fine tuning to visual word forms and whole word representations) and their growth in reading skill. Three stimulus contrasts—words versus pseudofonts, words versus pseudowords, pseudowords versus nonwords—were presented while high-density EEG Steady-State Visual Evoked Potentials (SSVEPs, n=31) were recorded. Internalization of abstract visual word form structures over two years of reading experience resulted in a near doubling of SSVEP amplitude, with increasing left lateralization. Longitudinal changes in brain responses to such word form structural information were linked to the growth in reading, especially in rapid automatic naming for letters. No such changes were observed for whole word representation processing and coarse tuning for print. Collectively, these findings indicate that sensitivity to visual word form structure develops rapidly through exposure to print and is linked to growth in reading skill.

Research Highlights

Longitudinal changes in cognitive responses to coarse print tuning, visual word from structure, and whole word representation were examined in early readers.

Visual word form structure processing demonstrated striking patterns of growth with nearly doubled in EEG amplitude and increased left lateralization.

Longitudinal changes in brain responses to visual word form structural information were linked to the growth in rapid automatic naming for letters.

No longitudinal changes were observed for whole word representation processing and coarse tuning for print.
Callose deposition at plasmodesmata suggests a role in viral movement restriction in transgenic tobacco plants during recovery fromTobacco etch virusinfection
Authors: Vargas-Mejía Pablo , Olguín-Lamas Alejandro , Fernandez-Valverde Selene L. , Flores-García Carmen M. , Lund Gertrud , Vielle-Calzada Jean-Philippe , Silva-Rosales Laura
Published: November 2022

Viruses are amongst the most prevalent pathogens that threaten plants. Plants have evolved a sequence-specific defense mechanism against viruses to ensure survival, known as RNA silencing, which includes transcriptional and post-transcriptional gene silencing. After a viral infection, some plants undergo recovery and become further resistant to viral infection. To identify additional mechanisms underlying disease recovery besides the known RNA silencing, we analyzed transgenic tobacco plants expressing a transcript derived from the Nuclear Inclusion “a” protein (NIa) cistron of thetobacco etch virus(TEV), which had recovered from infection three weeks following viral inoculation. Usingin situhybridizations and qRT-PCR, we detected the viral RNA and the transgene-derived transcript in stem sections adjacent to the recovered leaves. To further characterize the silenced and non-silenced conditions, we undertook tissue-specific RNA-Seq and small RNA-Seq analyses in leaf and stem. We found more differentially expressed genes (DEGs) in the recovered leaf, primarily related to defense, silencing, and hormone signaling responses. Finally, we observed differences in plasmodesmata callose deposition and callose-related genes. Overall, our findings suggest that cell-to-cell viral restriction movement also participates in the recovery of TEV infection in transgenic tobacco plants, besides the key function of RNA silencing.
Event-Related Desynchronization induced by Tactile Imagery: an EEG Study
Authors: Yakovlev Lev , Syrov Nikolay , Miroshnikov Andrei , Lebedev Mikhail , Kaplan Alexander
Published: November 2022

It is well known that both the movement of the hand itself and the mental representation of it lead to event-related desynchronization (ERD) of EEG recorded over the corresponding motor areas of the cerebral cortex. Similarly, in somatosensory cortical areas, ERD occurs upon tactile stimulation of the hand, but whether this effect is caused by mental representation of sensations from tactile stimulation remains poorly understood. In the present study, the effects on the EEG of imaginary vibrotactile sensations on the right hand were compared with the effects of real vibrotactile stimulation. Both actual vibrotactile stimulation and mental representation of it have been found to elicit contralateral ERD patterns, particularly prominent in theμ-band and most pronounced in the C3 region. The paper discusses tactile imagery as a part of the complex sensorimotor mental image and its prospects for using EEG patterns of imagery-induced tactile sensations as control signals in BCI circuits independently and when combined with ERD based on movement imagination to improve the efficiency of neurointerface technologies in rehabilitation medicine, in particular, to restore movements after a stroke and neurotrauma.
Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits
Authors: Zhang Jilin , Zhang Ming , Wang Qinrui , Wen Han , Liu Zheyi , Wang Fangjun , Wang Yuhang , Yao Fenyong , Song Nan , Kou Zengwei , Li Yang , Guo Fei , Zhu Shujia
Published: November 2022

N-Methyl-D-Aspartate (NMDA) receptors are essential for many brain functions. These receptors are heterotetramers typically comprising two GluN1 subunits and two GluN2 subunits. The latter could alternate among four subtypes (N2A-N2D) and determine the functional diversity of NMDA receptors1, 2. For example, receptors containing N2C or N2D exhibit 50-fold lower channel open probability (Po) than those containing N2A (ref.3–5). Structures of N2A- and N2B-containing receptors have been extensively characterized, providing molecular basis for understanding NMDA receptor function6–14. Here we report the cryo-EM structures of N1-N2D and N1-N2C di-heterotetramers (di-receptors), and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a resolution up to 3.0 Å. Structural analysis showed that the bilobate N-terminal domain (NTD) in N2D adopted an intrinsic closed conformation, leading to a compact NTD tetramer in N1-N2D receptor. Functional studies further demonstrated that, in di-receptors containing N2D but not N2A or N2B, crosslinking NTD at the tetrameric interface had no effect on channel activity, while crosslinking ligand-binding domain (LBD) of two N1 protomers significantly elevated Po. Surprisingly, we found that the N1-N2C di-receptors spontaneously oscillated between symmetric and asymmetric conformation. The later one occupied a predominant population, whereby two N2C protomers exhibited distinct conformation. This asymmetry, which was also found to a lesser extent in N1-N2A di-receptor10, was further locked by the binding of an N2C-specific allosteric potentiator PYD-106 to a unique binding pocket between NTD and LBD in only one N2C protomer. Finally, N2A and N2C in the N1-N2A-N2C tri-receptor displayed the conformation close to that found in one protomer of N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse functional properties of major NMDA receptor subtypes.
Differential requirement for IRGM proteins during tuberculosis infection in mice
Authors: Wilburn Kaley M. , Meade Rachel K. , Heckenberg Emma M. , Dockterman Jacob , Coers Jörn , Sassetti Christopher M. , Olive Andrew J. , Smith Clare M.
Published: November 2022

Mycobacterium tuberculosis(Mtb) is a bacterium that exclusively resides in human hosts and remains a dominant cause of morbidity and mortality among infectious diseases worldwide. Host protection againstMtbinfection is dependent on the function of immunity-related GTPase clade M (IRGM) proteins. Polymorphisms in humanIRGMassociate with altered susceptibility to mycobacterial disease, and human IRGM promotes the delivery ofMtbinto degradative autolysosomes. Among the three murine IRGM orthologs,Irgm1has been singled out as essential for host protection duringMtbinfections in cultured macrophages andin vivo. However, whether the paralogous murineIrgmgenes,Irgm2andIrgm3, play roles in host defense againstMtbor exhibit functional relationships withIrgm1duringMtbinfection remains undetermined. Here, we report thatIrgm1-/-mice are indeed acutely susceptible to aerosol infection withMtb, yet the additional deletion of the paralogousIrgm3gene restores protective immunity toMtbinfections inIrgm1-deficient animals. Mice lacking all threeIrgmgenes (panIrgm-/-) are characterized by shifted lung cytokine profiles at 4 and 24 weeks post infection, but control disease until the very late stages of the infection, when panIrgm-/-mice display increased mortality compared to wild type mice. Collectively, our data demonstrate that disruptions in the balance betweenIrgmisoforms is more detrimental to theMtb-infected host than total loss ofIrgm-mediated host defense, a concept that also needs to be considered in the context of humanMtbsusceptibility linked toIRGMpolymorphisms.
Pluripotent, germ cell competent adult stem cells underlie cnidarian plant-like life history
Authors: Varley Áine , Horkan Helen R , McMahon Emma T , Krasovec Gabriel , Frank Uri
Published: November 2022

In most animals, pluripotency is irreversibly lost post-gastrulation. By this stage, all embryonic cells have already committed either to one of the somatic lineages (ectoderm, endoderm, mesoderm) or to the germline. The lack of pluripotent cells in adult life may be linked to organismal aging. Cnidarians (corals, and jellyfish) are an early branch of animals that do not succumb to age, but the developmental potential of their adult stem cells remains unclear. Here, we show that adult stem cells in the cnidarianHydractinia symbiolongicarpus(known as i-cells) are pluripotent. We transplanted single i-cells from transgenic fluorescent donors to wild type recipients and followed themin vivoin the translucent animals. Single engrafted i-cells self-renewed and contributed to all somatic lineages and to gamete production, co-existing with and eventually displacing the allogeneic recipient’s cells. Hence, a fully functional, sexually competent individual can originate from a single adult i-cell. Given that some of their cells remain pluripotent beyond embryogenesis and throughout life, we conclude thatHydractiniaembryos never complete gastrulation. Pluripotent i-cells underlie a regenerative, plant-like life history in these animals.
Expanding the molecular and morphological diversity of Apusomonadida, a deep-branching group of gliding bacterivorous protists
Authors: Torruella Guifré , Galindo Luis Javier , Moreira David , Ciobanu Maria , Heiss Aaron A. , Yubuki Naoji , Kim Eunsoo , López-García Purificación
Published: November 2022

Apusomonads are cosmopolitan bacterivorous biflagellate protists usually gliding on freshwater and marine sediment or wet soils. These nanoflagellates form a sister lineage to opisthokonts and may have retained ancestral features helpful to understanding the early evolution of this large supergroup. Although molecular environmental analyses indicate that apusomonads are genetically diverse, few species have been described. Here, we morphologically characterize eleven new apusomonad strains. Based on molecular phylogenetic analyses of the rRNA gene operon, we describe four new strains of the known speciesMultimonas media, Podomonas capensis, Apusomonas proboscideaandApusomonas australiensis, and renameThecamonas oxoniensisasMylnikovia oxoniensisn. gen., n. comb. Additionally, we describe four new genera and six new species:Catacumbia lutetiensisn. gen. n. sp.,Cavaliersmithia chaoaen. gen. n. sp.,Singekia montserratensisn. gen. n. sp.,Singekia franciliensisn. gen. n. sp.,Karpovia croatican. gen. n. sp. andChelonemonas dolanin. sp. Our comparative analysis suggests that apusomonad ancestor was a fusiform biflagellate with a dorsal pellicle, a plastic ventral surface and a sleeve covering the anterior flagellum, that thrived in marine, possibly oxygen-poor, environments. It likely had a complex cell cycle with dormant and multiple fission stages, and sex. Our results extend known apusomonad diversity, allow updating their taxonomy, and provide elements to understand early eukaryotic evolution.
The C-terminal acid phosphatase module of the RNase HI enzyme RnhC controls rifampicin sensitivity and light-dependent colony pigmentation ofMycobacterium smegmatis
Authors: Dupuy Pierre , Glickman Michael S
Published: November 2022

RNase H enzymes participate in various processes that require processing of RNA:DNA hybrids, including DNA replication, transcription, and ribonucleotide excision from DNA. Mycobacteria encode multiple RNase H enzymes and prior data indicates that RNase HI activity is essential for mycobacterial viability. However, the additional roles of mycobacterial RNase Hs are unknown, including whether RNase HII (RnhB and RnhD) excises chromosomal ribonucleotides misincorporated during DNA replication and whether individual RNase HI enzymes (RnhA and RnhC) mediate additional phenotypes. We find that loss of RNase HII activity inM. smegmatis(through combined deletion ofrnhB/rnhD) or individual RNase HI enzymes, does not affect growth, hydroxyurea sensitivity, or mutagenesis, whereas overexpression of either RNase HII severely compromises bacterial viability. We also show that deletion ofrnhC, which encodes a protein with an N terminal RNase HI domain and a C terminal acid phosphatase domain, confers sensitivity to rifampicin and oxidative stress as well as loss of light induced carotenoid pigmentation. These phenotypes are due to loss of the activity of the C terminal acid phosphatase domain rather than the RNase HI activity, suggesting that the acid phosphatase activity may confer rifampicin resistance through the antioxidant properties of carotenoid pigment production.
Radical pair based magnetic field effects in cells: the importance of photoexcitation conditions and single cell measurements
Authors: Woodward Jonathan R. , Ikeya Noboru
Published: November 2022

A recent publication1on the bioRxiv preprint server aims to replicate our observation of magnetic field effects on the autofluorescence of HeLa cells2, but is unable to reproduce the effects described in our original work. Here we examine this new study and demonstrate, based on a model of the reaction photocycle, why the differences in the measurement conditions used render the experiment unlikely to be able to observe the originally reported effect. In addition, we highlight substantial problems in the quality of the data in the replicate study and reiterate the advantages of the direct modulation, single cell measurement approach presented in the original work over a more standard statistical approach.
ConstrastivePose: A contrastive learning approach for self-supervised feature engineering for pose estimation and behavorial classification of interacting animals
Authors: Zhou Tianxun , Hoe Cheah Calvin Chee , Mun Chin Eunice Wei , Chen Jie , Farm Hui Jia , Keow Goh Eyleen Lay , Chiam Keng Hwee
Published: November 2022

In recent years, supervised machine learning models trained on videos of animals with pose estimation data and behavior labels have been used for automated behavior classification. Applications include, for example, automated detection of neurological diseases in animal models. However, there are two problems with these supervised learning models. First, such models require a large amount of labeled data but the labeling of behaviors frame by frame is a laborious manual process that is not easily scalable. Second, such methods rely on handcrafted features obtained from pose estimation data that are usually designed empirically. In this paper, we propose to overcome these two problems using contrastive learning for self-supervised feature engineering on pose estimation data. Our approach allows the use of unlabeled videos to learn feature representations and reduce the need for handcrafting of higher-level features from pose positions. We show that this approach to feature representation can achieve better classification performance compared to handcrafted features alone, and that the performance improvement is due to contrastive learning on unlabeled data rather than the neural network architecture.

Author Summary

Animal models are widely used in medicine to study diseases. For example, the study of social interactions between animals such as mice are used to investigate changes in social behaviors in neurological diseases. The process of manually annotating animal behaviors from videos is slow and tedious. To solve this problem, machine learning approaches to automate the video annotation process have become more popular. Many of the recent machine learning approaches are built on the advances in pose-estimation technology which enables accurate localization of key points of the animals. However, manual labeling of behaviors frame by frame for the training set is still a bottleneck that is not scalable. Also, existing methods rely on handcrafted feature engineering from pose estimation data. In this study, we propose ConstrastivePose, an approach using contrastive learning to learn feature representation from unlabeled data. We demonstrate the improved performance using the features learnt by our method versus handcrafted features for supervised learning. This approach can be helpful for work seeking to build supervised behavior classification models where behavior labelled videos are scarce.
A phloem-localized Arabidopsis metacaspase (AtMC3) improves drought tolerance
Authors: Pitsili Eugenia , Rodriguez-Trevino Ricardo , Ruiz-Solani Nerea , Demir Fatih , Kastanaki Elizabeth , Dambire Charlene , de Pedro Roger , Vercammen Dominique , Salguero-Linares Jose , Hall Hardy , Mantz Melissa , Schuler Martin , Tuominen Hannele , Breusegem Frank Van , Valls Marc , Munné-Bosch Sergi , Holdsworth Michael J. , Huesgen Pitter F. , Rodriguez-Villalon Antia , Coll Nuria S.
Published: November 2022

Increasing drought phenomena pose a serious threat to agricultural productivity. Although plants have multiple ways to respond to the complexity of drought stress, the underlying mechanisms of stress sensing and signalling remain unclear. The role of the vasculature, in particular the phloem, in facilitating inter-organ communication is critical. Here, we investigated the role of AtMC3, a phloem-specific member of the metacaspase family, in osmotic stress responses inArabidopsis thaliana. Overexpression ofAtMC3conferred drought tolerance by enhancing the differentiation of the metaphloem sieve elements and maintaining higher levels of vascular-mediated transportation, whilst plants lacking the protein showed an impaired response to drought and inability to respond effectively to the hormone abscisic acid. Analyses of the proteome in plants with altered AtMC3 levels revealed differential abundance of proteins related to osmotic stress. Overall, our data highlight the importance of AtMC3 and vascular plasticity in fine-tuning early drought responses at the whole plant level without affecting growth or yield.
Long-read genome assemblies reveals acis-regulatory landscape associated with phenotypic divergence in two sisterSinipercafishes
Authors: Tu Guangxian , Chen Qi , Zhang Xinshuang , Jiang Ruirun , Zhang Long , Lai Chengjun , Yan Zhuyue , Lv Yanrong , Weng Shaoping , Zhang Li , He Jianguo , Wang Muhua
Published: November 2022

Background

Dissecting the genetic basis of variation in the regulation of gene expression is essential for understanding phenotypic evolution. Structural variants intersecting thecis-regulatory elements are found to cause gene expression variation in several developmental genes, resulting in morphological divergence between species. Due to the difficulty of identifying structural variants accurately across the genome, a comprehensive study of impacts of structural variants incis-regulatory divergence of closely related species, especially fish species, is still scarce. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remain poorly understood.Siniperca chuatsiandS. scherzeriare two closely related fish species diverge in several phenotypic traits, making them an ideal model to studycis-regulatory evolution in closely related species.

Results

We generated chromosome-level genomes ofS. chuatsiandS. scherzeri. The evolutionary histories ofS. chuatsiandS. scherzeriwere studied by inferring the dynamic changes in the ancestral population sizes. The genetic basis of adaptation inS. chuatsiandS. scherzeriwas dissected by performing gene family expansion and contraction analysis and identifying positively selected genes (PSGs). To investigate the role of SVs incis-regulatory divergence of closely related fish species, we identified high-quality SVs betweenS. chuatsiandS. scherzeri, as well as H3K27ac and H3K4me3 domains. Integrated analysis revealed thatcis-regulatory divergence caused by SVs played an essential role in the differentiation of metabolism, skin pigmentation, and immunity betweenS. chuatsiandS. scherzeri. Additionally, divergent broad H3K4me3 domains were found to mostly associate with cancer-related genes inS. chuatsiandS. scherzeriand contribute to their phenotypic divergence.

Conclusions

Our analysis reveals SVs play an essential role incis-regulatory variation between the two sister fish species, which in turn contributes to their phenotypic divergence. The divergence of broad H3K4me3 domains contributes to phenotypic divergence between closely related species. Additionally, the association of broad H3K4me3 domains and cancer-related genes has an ancient origin.
Cryo-EM structures of kalium channelrhodopsins KCRs
Authors: Zhang Mingfeng , Shan Yuanyue , Xiao Li , Zhao Liping , Pei Duanqing
Published: November 2022

H. catenoideskalium channelrhodopsins (HcKCR1 andHcKCR2) are potassium-selective light-gated ion channels with unique properties for optogenetics. Here we report cryo-electron microscopy (cryo-EM) structures ofHcKCR1 andHcKCR2 with endogenous retinal. Strikingly, one structure of HcKCR1 represents the conducting state with continuous potassium ion flow in the lumen, while another in non-conducting state with discontinuous potassium ion flow. Further electrophysiological studies identified extracellular side of ion permeation region as the major element for channel potassium selectivity and retinal binding region for channel gating. Our results uncover the unprecedented potassium selectivity and light-gating mechanism, and may facilitate the rational design of new optogenetic tools.
Grad-seq analysis ofEnterococcus faecalisandEnterococcus faeciumprovides a global view of RNA and protein complexes in these two opportunistic pathogens
Authors: Michaux Charlotte , Gerovac Milan , Hansen Elisabeth E. , Barquist Lars , Vogel Jörg
Published: November 2022

Enterococcus faecalisandEnterococcus faeciumare major nosocomial pathogens. Despite their relevance to public health and their role in the development of bacterial antibiotic resistance, relatively little is known about gene regulation in these species. RNA–protein complexes serve crucial functions in all cellular processes associated with gene expression, including post-transcriptional control mediated by small regulatory RNAs (sRNAs). Here, we present a new resource for the study of enterococcal RNA biology, employing the Grad-seq technique to comprehensively predict complexes formed by RNA and proteins inE. faecalisV583 andE. faeciumAUS0004. Analysis of the generated global RNA and protein sedimentation profiles led to the identification of RNA-protein complexes and putative novel sRNAs. Validating our data sets, we observe well-established cellular RNA-protein complexes such as the 6S RNA-RNA polymerase complex, suggesting that 6S RNA-mediated global control of transcription is conserved in enterococci. Focusing on the largely uncharacterized RNA-binding protein KhpB, we use the RIP-seq technique to predict that KhpB interacts with sRNAs, tRNAs, and untranslated regions of mRNAs, and might be involved in the processing of specific tRNAs. Collectively, these datasets provide departure points for in-depth studies of the cellular interactome of enterococci that should facilitate functional discovery in these and related Gram-positive species. Our data are available to the community through a user-friendly Grad-seq browser that allows interactive searches of the sedimentation profiles (https://resources.helmholtz-hiri.de/gradseqef/).
Mimicking seasonal changes in light-dark cycle and ambient temperature modulates gut microbiome in mice under the same dietary regimen
Authors: Matsumoto Shoko , Ren Liang , Iigo Masayuki , Murai Atsushi , Yoshimura Takashi
Published: November 2022

To better adapt to seasonal environmental changes, physiological processes and behaviors are regulated seasonally. The gut microbiome interacts with the physiology, behavior, and even the diseases of host animals, including humans and livestock. Seasonal changes in gut microbiome composition have been reported in several species under natural environments. Dietary content significantly affects the composition of the microbiome, and, in the natural environment, the diet varies between different seasons. Therefore, understanding the seasonal regulatory mechanisms of the gut microbiome is important for understanding the seasonal adaptation strategies of animals. Herein, we examined the effects of changing day length and temperature, which mimic summer and winter conditions, on the gut microbiome of laboratory mice. Principal coordinate analysis and analysis of the composition of microbiomes of 16S rRNA sequencing data demonstrated that the microbiomes of the cecum and large intestine showed significant differences between summer and winter mimicking conditions. Similar to previous studies, a daily rhythm was observed in the composition of the microbiome. Furthermore, the phylogenetic investigation of communities by reconstruction of unobserved states predicted seasonal changes in several metabolic pathways. Changing day length and temperature can affect the composition of the gut microbiome without changing dietary contents.
Hybran: Hybrid Reference Transfer and ab initio Prokaryotic Genome Annotation
Authors: Elghraoui Afif , Gunasekaran Deepika , Radecke Sarah M. , Bishop Emma , Valafar Faramarz
Published: November 2022

De novo assembly has become commonplace for microbial organisms, increasing the demand for reliable genome annotation. Ab initio annotation is not an ideal approach for closely related strains due to suboptimal matching of the short or hypervariable genomic features that reference-based annotation transfer can overcome through identification of conserved synteny. At the same time, reference-based annotation methods leave gaps in the annotation where structural variations introduce unique sequence. We present Hybran, a hybrid reference-based and ab initio prokaryotic genome annotation pipeline that transfers features from a curated reference annotation and supplements unannotated regions with ab initio predictions. It builds on existing tools to create initial annotations using both approaches, then compares and resolves them to produce the hybrid annotation. With this pipeline, full advantage is taken of the community’s experimental efforts on reference strains to propagate as many known features as possible without sacrificing best-effort ab initio predictions for the remaining unannotated loci. Genome annotation performed in this way can facilitate comparative genomics and the investigation of evolutionary dynamics in microbial populations.

Hybran is freely available athttps://lpcdrp.gitlab.io/hybran
Sleep-dependent engram reactivation during hippocampal memory consolidation is associated with subregion-specific biosynthetic changes
Authors: Wang Lijing , Park Lauren , Wu Weisheng , King Dana , Medina Alexis Vega , Raven Frank , Martinez Jessy , Ensing Amy , McDonald Katherine , Yang Zhongying , Jiang Sha , Aton Sara J.
Published: November 2022

Post-learning sleep is essential for hippocampal memory processing, including contextual fear memory (CFM) consolidation. We used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons after fear learning. Post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupted reactivation of inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus – with activity-driven transcripts, and those associated with cytoskeletal remodeling, selectively suppressed in the inferior blade. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. These changes suggested an increase in glutamatergic receptor signaling, and a decrease in GABA receptor signaling, during CFM consolidation. Protein abundance across hippocampal subregions was also differentially impacted by learning and sleep, with most alterations to protein expression restricted to DG. Together, these data suggest that the DG is critical for sleep-dependent memory consolidation, and that the effects of sleep loss on the hippocampus are highly subregion-specific, even within the DG itself.
Adaptive preservation of orphan ribosomal proteins in chaperone-stirred condensates
Authors: Ali Asif , Garde Rania , Schaffer Olivia C , Bard Jared A M , Husain Kabir , Kik Samantha Keyport , Davis Kathleen A , Luengo-Woods Sofia , Drummond D Allan , Squires Allison H , Pincus David
Published: November 2022

Ribosome biogenesis is among the most resource-intensive cellular processes, with ribosomal proteins accounting for up to half of all newly synthesized proteins in eukaryotic cells. During stress, cells shut down ribosome biogenesis in part by halting rRNA synthesis, potentially leading to massive accumulation of aggregation-prone “orphan” ribosomal proteins (oRPs). Here we show that during heat shock in yeast and human cells, oRPs accumulate as reversible condensates at the nucleolar periphery recognized by the Hsp70 co-chaperone Sis1/DnaJB6. oRP condensates are liquid-like in cell-free lysate but solidify upon depletion of Sis1 or inhibition of Hsp70. When cells recover from heat shock, oRP condensates disperse in a Sis1-dependent manner, and their ribosomal protein constituents are incorporated into functional ribosomes in the cytosol, enabling cells to efficiently resume growth.

One sentence summary

During stress, molecular chaperones preserve “orphan” ribosomal proteins (RPs) – RPs that are not bound to rRNA – in liquid-like condensates, maintaining the RPs in a usable form and enabling cells to efficiently resume growth upon recovery from stress.
Perception of Rigidity in Three- and Four-Dimensional Spaces
Authors: He Dongcheng , Nguyen Dat-Thanh , Ogmen Haluk , Nishina Shigeaki , Yazdanbakhsh Arash
Published: November 2022

Our brain employs mechanisms to adapt to changing visual conditions. In addition to natural changes in our physiology and those in the environment, our brain is also capable of adapting to “unnatural” changes, such as inverted visual-inputs generated by inverting prisms. In this study, we examined the brain’s capability to adapt to hyperspaces. We generated four spatial-dimensional stimuli in virtual reality and tested the ability to distinguish between rigid and non-rigid motion. We found that observers are able to differentiate rigid and non-rigid motion of tesseracts (4D) with a performance comparable to that obtained using cubes (3D). Moreover, observers’ performance improved when they were provided with more immersive 3D experience but remained robust against increasing shape variations. At this juncture, we characterize our findings as “perception” since, while we show the ability to extract and use 4D information, we do not have yet evidence of a complete phenomenal 4D experience.
Voltage-Seq: all-optical postsynaptic connectome-guided single-cell transcriptomics
Authors: Csillag Veronika , Bizzozzero Marianne Hiriart , Noble Joyce , Reinius Björn , Fuzik János
Published: November 2022

Understanding the routing of neuronal information requires the functional characterization of connections. Neuronal projections recruit large postsynaptic ensembles with distinct postsynaptic response types (PRTs). PRT is probed by low-throughput whole-cell electrophysiology and is not a selection criterion for single-cell RNA-sequencing (scRNA-seq). To overcome these limitations and target neurons based on specific PRTs for soma harvesting and subsequent scRNA-seq we created Voltage-Seq. To test our methodology, we established all-optical voltage imaging and recorded the PRT of 8347 periaqueductal gray (PAG) neurons evoked by the optogenetic activation of ventromedial hypothalamic (VMH) terminals. PRTs were classified and spatially resolved in the entire VMH-PAG connectome. We built an on-site analysis named VoltView to navigate soma harvesting towards target PRTs guided by a classifier which used the VMH-PAG connectome database as a reference. We demonstrated the agility of Voltage-Seq in locating VMH-driven GABAergic neurons in the PAG, solely guided by the on-site classification in VoltView.
Irreversible inactivation of lactate racemase by sodium borohydride reveals reactivity of the nickel-pincer nucleotide cofactor
Authors: Gatreddi Santhosh , Sui Dexin , Hausinger Robert P. , Hu Jian
Published: November 2022

The nickel-pincer nucleotide (NPN) cofactor discovered in lactate racemase fromLactiplantibacillus plantarum(LarALp) is essential for the activities of racemases/epimerases in the highly diverse LarA superfamily. Prior mechanistic studies have established a proton-coupled hydride-transfer mechanism for LarALp, but direct evidence showing that hydride attacks the C4 atom in the pyridinium ring of NPN has been lacking. Here, we show that sodium borohydride (NaBH4) irreversibly inactivates LarALpaccompanied by a rapid color change of the enzyme. The drastically altered ultraviolet-visible spectra during NaBH4titration supported hydride transfer to C4 of NPN, and the concomitant Ni loss unraveled by mass spectrometry experiments accounted for the mechanism-based inactivation. High resolution structures of LarALprevealed a substantially weakened C-Ni bond in the metastable sulfite-NPN adduct where the NPN cofactor is in the reduced state. These findings allowed us to propose a mechanism of LarALpinactivation by NaBH4that provides key insights into the enzyme-catalyzed reaction and sheds light on the reactivity of small molecule NPN mimetics.
Crystal structure of cis(S),trans(O,N
bpy)-(2,2′-bipyridyl-κ2
N,N′)bis(dimethyl sulfoxide-κS)[phenyl(pyridin-2-yl)methanone-κ2
N,O]ruthenium(II) bis(trifluoromethanesulfonate)
Authors: Toyama Mari , Nagao Noriharu
Published: November 2022

The molecular and crystal structures of the title complex, [Ru(C10H8N2)(C12H9NO)(C2H6OS)2](CF3O3S)2 or cis(S),trans(O,N
bpy)-[Ru(bpy)(ppk)(dmso-S)2](OTf)2 {bpy = 2,2′-bipyridine, ppk = phenyl-2-pyridyl ketone [IUPAC nomenclature: phenyl(pyridine-2-yl)methanone], dmso = dimethyl sulfoxide, and OTf− = trifluoromethanesulfonate}, are reported. The Ru2+ ion has a distorted octahedral geometry with two bpy N atoms, the N and O atoms of ppk, and two S atoms of two cis dmso-S ligands. The carbonyl O atom of ppk is trans to bpy, and the N atom of pyridyl is trans to the dmso-S ligand [trans(O,N
bpy) geometry]. One of the trifluoromethanesulfonate anions is disordered over three positions, with occupancies of 0.4, 0.4, and 0.2, respectively, in the refined model. The original disordered and SQUEEZE [Spek (2015). Acta Cryst. C71, 9–18] models were found to be almost equivalent, indicating that both the SQUEEZE and the original disordered model are satisfactory.
Crystal structure of dibenzo[c,e]thiepine-5(7H)-thione
Authors: Brown Loren C. , Ghiassi Kamran B. , Fulton Ashley C. , Thum Matthew
Published: November 2022

The title compound, C14H10S2, was prepared from dibenzo[c,e]oxepine-5(7H)-one and Lawesson's reagent in refluxing toluene. Pink blocks were grown by slow evaporation from petroleum ether. The resulting crystal structure resides in the orthorhombic space group Pbca with Z = 8 and Z′ = 1. The structure is comprised of a network of C—H...S and C—H...π interactions. No π–π interactions between ring moieties were observed, most likely due to the lack of molecular planarity.
Crystal structure of a copper–mefenamate complex solvated with diglyme and water
Authors: Chong Magdalene W. S. , Ottoboni Sara , Martin Alan R. G. , Bowering Deborah , Price Chris J. , Nordon Alison , Oswald Iain D. H. , Ward Martin R.
Published: November 2022

In the copper–mefenamate complex tetrakis[μ-2-(2,3-dimethylanilino)benzoato-κ2
O:O′]bis[aquacopper(II)]–1-methoxy-2-(2-methoxyethoxy)ethane (1/2), [Cu2(C15H14NO2)4(H2O)2]·2C6H14O3, the asymmetric unit comprises a CuII cation coordinated to two mefenamate ligands solvated with a water molecule and a diglyme molecule. The complex adopts a paddlewheel motif and is compared to structural analogues crystallized with dimethylformamide and dimethyl sulfoxide.
Crystal structures of two new carbazole derivatives: ethyl 9-(benzenesulfonyl)-2-(4-fluoro-2-nitrophenyl)-6-methoxy-9H-carbazole-3-carboxylate and 12-(benzenesulfonyl)-12H-quinolino[4,3-b]carbazole
Authors: Madhan S. , NizamMohideen M. , Pavunkumar Vinayagam , MohanaKrishnan Arasambattu K.
Published: November 2022

The title compounds, C28H21FN2O7S (I) and C25H16N2O2S (II), are carbazole derivatives with a benzenesulfonyl group attached to the carbazole moiety at the N atom on both molecules. A fluoro-substituted nitrophenyl ring system in I and a fused isoquinoline ring in II are attached to the respective carbazole moieties. In both compounds, the carbazole ring systems are essentially planar, with maximum deviations of 0.028 (2) and 0.026 (2) Å for carbon atoms in compounds I and II, respectively. The carbazole ring system is almost orthogonal to the benzene ring attached to sulfonyl group, with dihedral angles of 79.7 (2) in I and 88.2 (2)° in II, respectively. The mean planes of the carbazole ring systems make dihedral angles of 66.1 (2) and 1.3 (2)°, respectively, with the nitrophenyl ring in I and the planar isoquinoline moiety [maximum deviation of 0.009 (3) Å for a carbon atom in II, indicating that the ring system in II is essentially planar]. The benzenesulfonyl ring is almost normal to the isoquinoline ring, with a dihedral angle of 87.9 (2)° in II and the nitrophenyl ring forms a dihedral angle of 17.8 (2)° in I. In both compounds, intramolecular C—H...O hydrogen bonds generate S(6) ring motifs with the sulfone group O atoms. In crystals of compound I, the molecules are linked by C—H...O intermolecular weak hydrogen bonds, which generate C(7) and C(10) chains running parallel to [010] and [100], respectively.
A football debate: the future of football accountability research
Authors: Philippou Christina
Published: November 2022

Purpose

The purpose of this paper is to provide commentary on Soccer Society debate that is used to create accountability research agenda.

Design/methodology/approach

The methodology applied is thematic analysis of debate in relation to accountability research gaps.

Findings

The authors found that areas for future football accountability research include refereeing, human rights in event hosting, governance, ownership, networks and club and fan finances.

Originality/value

The study contributes to debate commentary and agenda for football accountability research.