bluuebunny/crossref_metadata_2025 huggingface dataset:
MOF-mediated Histone H4 Lysine 16 Acetylation Governs Mitochondrial and Ciliary Functions By Controlling Gene Promoters
Authors: Wang Dongmei , Li Haimin , Chandel Navdeep S , Dou Yali , Yi Rui
Published: November 2022

Histone H4 lysine 16 acetylation (H4K16ac), governed by the histone acetyltransferase (HAT) MOF, orchestrates critical functions in gene expression regulation and chromatin interaction. However, how does MOF and H4K16ac control cellular function and regulate mammalian tissue development remains unclear. Furthermore, whether the function of MOF is mediated by MSL or NSL, two distinct MOF-containing HAT complexes, have not been determined during mammalian development. Here we show that conditional deletion ofMofbut notKansl1, an essential component of the NSL complex, causes severe defects during murine skin development. In the absence ofMofand H4K16ac, basal epithelial progenitors of mammalian skin fail to establish the basement membrane and cell polarity, causing the failure of self-renewal. Furthermore, epidermal differentiation and hair growth are severely compromised, leading to barrier defects and perinatal lethality. Single-cell and bulk RNA-seq, in combination with MOF ChIP-seq, reveal that MOF regulated genes are highly enriched in mitochondria and cilia. Mechanistically, MOF coordinates with RFX2 transcription factor, which preferentially binds to gene promoters, to regulate ciliary and mitochondrial genes. Importantly, genetic deletion ofUqcrq, a nuclear-encoded, essential subunit for electron transport chain (ETC) Complex III, recapitulates the defects of epidermal differentiation and hair follicle growth observed in MOF cKO. Together, this study reveals the requirement of MOF-mediated epigenetic mechanism for mitochondria and cilia, and demonstrates the important function of the MOF/ETC axis for mammalian skin development.
Multiplexed and scalable cellular phenotyping toward the standardized three-dimensional human neuroanatomy
Authors: Murakami Tatsuya C. , Heintz Nathaniel
Published: November 2022

The advent of three-dimensional histological methods has advanced studies of cellular-resolution anatomy of the brain. The use of whole-mount staining and tissue clearing has advanced systems-level identification of cells underlying brain functions in mouse models. However, application of these methods to studies of human brains has been difficult due to their structural variability and the lack of standardized quantitative metrics. Here we report a rapid and scalable staining/imaging technique, termed mFISH3D, that enables single-cell-resolution imaging of mRNAs of more than ten genes in a large mammalian brain. To apply mFISH3D to postmortem human cerebral cortex, we have reconstructed morphogenic tracks of cortical growth, and used the tracks to provide a framework for quantitative assessment of cytoarchitecture. The workflow enabled the objective quantification of biological heterogeneity among cortical regions. We propose these techniques for standardization of 3D histology of the human cortex to provide reproducible measurements of cell-type-specific neuroanatomy.
Interactions between circuit architecture and plasticity in a closed-loop system
Authors: Payne Hannah L. , Raymond Jennifer L. , Goldman Mark S.
Published: November 2022

Determining the sites of plasticity underlying changes in neural activity and behavior is critical for understanding mechanisms of learning. Identifying such sites from neural recording data can be challenging due to feedback pathways that impede reasoning about cause and effect. We studied interactions between feedback, neural activity, and plasticity in the context of a closed-loop motor learning task for which there is disagreement about the loci and directions of plasticity. We constructed a set of models that differed in the strength of their recurrent feedback. Despite these differences, each model successfully fit a large set of neural and behavioral data. However, the patterns of plasticity predicted by the models fundamentally differed, with the sign of plasticity at a key site changing from depression to potentiation as feedback strength increased. Guided by our analysis, we suggest how such models can be experimentally disambiguated. Our results address a long-standing debate regarding cerebellum-dependent motor learning and demonstrate how learning-related changes in neural activity can appear to contradict the sign of the underlying plasticity when feedback is present.
Consensus Label Propagation with Graph Convolutional Networks for Single-Cell RNA Sequencing Cell Type Annotation
Authors: Lewinsohn Daniel P , Vigh-Conrad Katinka A , Conrad Donald F , Scott Cory B
Published: November 2022

Motivation

Single-cell RNA sequencing (scRNA-seq) data, annotated by cell type, is useful in a variety of downstream biological applications, such as profiling gene expression at the single-cell level. However, manually assigning these annotations with known marker genes is both time-consuming and subjective.

Results

We present a Graph Convolutional Network (GCN) based approach to automate the annotation process. Our process builds upon existing labeling approaches, using state-of-the-art tools to find cells with highly confident label assignments through consensus and spreading these confident labels with a semi-supervised GCN. Using simulated data and two scRNA-seq data sets from different tissues, we show that our method improves accuracy over a simple consensus algorithm and the average of the underlying tools. We also compare our method to a non-parametric neighbor majority approach, showing comparable results. We then demonstrate that our GCN method allows for feature interpretation, identifying important genes for cell type classification. We present our completed pipeline, written in PyTorch, as an end-to-end tool for automating and interpreting the classification of scRNA-seq data.

Availability

Our code for conducting the experiments in this paper and using our model is available athttps://github.com/lewinsohndp/scSHARP

Contact

d_lewinsohn@coloradocollege.edu

Supplementary information

Supplementary data are available atJournal Nameonline.
Caught in the Act: targeted mutagenesis of the herpesvirus fusogen central helix captures transition states
Authors: Zhou Momei , Vollmer Benjamin , Machala Emily , Chen Muyuan , Grünewald Kay , Arvin Ann M. , Chiu Wah , Oliver Stefan L.
Published: November 2022

Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Structure-function studies of the VZV gB DIII central helix were performed targeting residues526EHV528. Critically, a H527P mutation captured gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] were identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.
Progressive neural engagement within the IFG-pMTG circuit as gesture and speech entropy and MI advances
Authors: Zhao Wanying , Li Zhouyi , Li Xiang , Du Yi
Published: November 2022

Semantic representation emerges from distributed multisensory modalities, yet a comprehensive understanding of the functional changing pattern within convergence zones or hubs integrating multisensory semantic information remains elusive. In this study, employing information-theoretic metrics, we quantified gesture and speech information, alongside their interaction, utilizing entropy and mutual information (MI). Neural activities were assessed via interruption effects induced by High-Definition transcranial direct current stimulation (HD-tDCS). Additionally, chronometric double-pulse transcranial magnetic stimulation (TMS) and high-temporal event-related potentials were utilized to decipher dynamic neural changes resulting from various information contributors. Results showed gradual inhibition of both inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) as degree of gesture-speech integration, indexed by MI, increased. Moreover, a time-sensitive and staged progression of neural engagement was observed, evidenced by distinct correlations between neural activity patterns and entropy measures of speech and gesture, as well as MI, across early sensory and lexico-semantic processing stages. These findings illuminate the gradual nature of neural activity during multisensory gesture-speech semantic processing, shaped by dynamic gesture constraints and speech encoding, thereby offering insights into the neural mechanisms underlying multisensory language processing.
Monitoring mouse brain perfusion with hybrid magnetic resonance optoacoustic tomography
Authors: Ren Wuwei , Deán-Ben Xosé Luís , Skachokova Zhiva , Augath Mark-Aurel , Ni Ruiqing , Chen Zhenyue , Razansky Daniel
Published: November 2022

Progress in brain research critically depends on the development of next-generation multi-modal imaging tools that are capable of capturing transient functional events and multiplexed contrasts noninvasively and concurrently. A number of outstanding questions, such as those pertaining to the link between blood-oxygen-level-dependent (BOLD) signaling, oxygen saturation and underlying neural activity, could potentially be addressed by truly integrating several complementary neuroimaging readouts into one hybrid system, thus enabling a holistic view of dynamic eventsin vivo. Here we developed a hybrid magnetic resonance and optoacoustic tomography (MROT) system for murine brain imaging by incorporating an MR-compatible spherical matrix array transducer and fiberbased light illumination into a 9.4T small animal scanner, whilst further designing an optimized radiofrequency coil for whole-brain interrogation. The utility of the system is demonstrated by acquiring complementary angiographic and soft tissue anatomical contrast along with simultaneous dual-modality visualization of contrast agent dynamicsin vivo.
Natural genetic variation in the pheromone production ofC. elegans
Authors: Lee Daehan , Fox Bennett W. , Palomino Diana C. F. , Panda Oishika , Tenjo Francisco J. , Koury Emily J. , Evans Kathryn S. , Stevens Lewis , Rodrigues Pedro R. , Kolodziej Aiden R. , Schroeder Frank C. , Andersen Erik C.
Published: November 2022

From bacterial quorum sensing to human language, communication is essential for social interactions. Nematodes produce and sense pheromones to communicate among individuals and respond to environmental changes. These signals are encoded by different types and mixtures of ascarosides, whose modular structures further enhance the diversity of this nematode pheromone language. Interspecific and intraspecific differences in this ascaroside pheromone language have been described previously, but the genetic basis and molecular mechanisms underlying the variation remain largely unknown. Here, we analyzed natural variation in the production of 44 ascarosides across 95 wildCaenorhabditis elegansstrains using high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS). By cross-analyzing genomes andexo-metabolomes of wild strains, we discovered quantitative trait loci (QTL) that underlie the natural differences in pheromone bouquet composition. Fine mapping of the QTL further uncovered associations between mitochondrial metabolism and pheromone production. Our findings demonstrate how natural genetic variation in core metabolic pathways can affect the production of social signals.
Prediction and diagnosis of chronic kidney disease development and progression using machine-learning: protocol for a systematic review and meta-analysis of reporting standards and model performance
Authors: Chen Fangyue , Kantagowit Piyawat , Nopsopon Tanawin , Chuklin Arisa , Pongpirul Krit
Published: November 2022

Chronic Kidney disease (CKD) is an important yet under-recognized contributor to morbidity and mortality globally. Machine-learning (ML) based decision support tools have been developed across many aspects of CKD care. Notably, algorithms developed in the prediction and diagnosis of CKD development and progression may help to facilitate early disease prevention, assist with early planning of renal replacement therapy, and offer potential clinical and economic benefits to patients and health systems. Clinical implementation can be affected by the uncertainty surrounding the methodological rigor and performance of ML-based models. This systematic review aims to evaluate the application of prognostic and diagnostic ML tools in CKD development and progression.

The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. The systematic review protocol for CKD prediction and diagnosis have been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022356704, CRD42022372378). A systematic search will be undertaken of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the IEEE Xplore digital library. Studies in which ML has been applied to predict and diagnose CKD development and progression will be included. The primary outcome will be the comparison of the performance of ML-based models with non-ML-based models. Secondary analysis will consist of model use cases, model construct, and model reporting quality.

This systematic review will offer valuable insight into the performance and reporting quality of ML-based models in CKD diagnosis and prediction. This will inform clinicians and technical specialists of the current development of ML in CKD care, as well as direct future model development and standardization.
Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community
Authors: Weiss Anna S. , Niedermeier Lisa S. , von Strempel Alexandra , Burrichter Anna G. , Ring Diana , Meng Chen , Kleigrewe Karin , Lincetto Chiara , Hübner Johannes , Stecher Bärbel
Published: November 2022

Microbe-microbe interactions are critical for gut microbiome function. A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Here, we aimed to determine members taking on a keystone role in shaping community ecology of a widely used synthetic bacterial community (OMM12). Using single-species dropout communities and metabolomic profiling, we identifiedBacteroides caecimurisI48,Blautia coccoidesYL58 andEnterococcus faecalisKB1 as major drivers ofin vitrocommunity assembly and elucidated underlying mechanisms of these keystone functions. Importantly, keystone species and bacterial strain relationships were found to strongly vary across different nutritional conditions, depending on the strains’ potential to modify the corresponding environment. Further, gnotobiotic mice transplanted with communities lackingB. caecimurisI48 andB. coccoidesYL58 exhibited morphological anomalies and altered intestinal metabolomic profiles, exposing physiologically relevant functions of these keystone community members. In summary, the presented study experimentally confirms the strong interdependency between bacterial community ecology and the biotic and abiotic environment, underlining the context-dependency and conditionality of bacterial interaction networks.
A simplified, amplicon-based method for whole genome sequencing of human respiratory syncytial viruses
Authors: Dong Xiaomin , Deng Yi-Mo , Aziz Ammar , Whitney Paul , Clark Julia , Harris Patrick , Bautista Catherine , Costa Anna Maria , Waller Gregory , Daley Andrew J , Wieringa Megan , Korman Tony , Barr Ian G.
Published: November 2022

Human Respiratory Syncytial Virus (RSV) infections pose a significant risk to human health worldwide, especially for young children. Whole genome sequencing (WGS) provides a useful tool for global surveillance to better understand the evolution and epidemiology of RSV and provide essential information that may impact on antibody treatments, antiviral drug sensitivity and vaccine effectiveness. Here we report the development of a rapid and simplified amplicon-based one-step multiplex reverse-transcription polymerase chain reaction (mRT-PCR) for WGS of both human RSV-A and RSV-B viruses. The method requires only two reactions for each sample, which significantly reduces the cost and time compared to other commonly used RSV WGS methods. In silico analysis and laboratory testing revealed that the primers used in the new method covered most of the currently circulating RSV-A and RSV-B. Amplicons generated were suitable for both Illumina and Oxford Nanopore Technologies (ONT) NGS platforms. This new method was tested on 200 clinical samples collected in Australia in 2020 and 2021 with RSV Ct values between 10 and 32. A success rate of 88% with a full coverage for the genome of 99 RSV-A and 77 RSV-B was achieved. This assay is simple to set up, robust, easily scalable in sample preparation and relatively inexpensive, and as such, provides a valuable addition to existing NGS RSV WGS methods.
MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells
Authors: Röring Rutger J. , Debisarun Priya A. , Botey-Bataller Javier , Suen Tsz Kin , Bulut Özlem , Kilic Gizem , Koeken Valerie A. C. M. , Sarlea Andrei , Bahrar Harsh , Dijkstra Helga , Lemmers Heidi , Gössling Katharina L. , Rüchel Nadine , Ostermann Philipp N. , Müller Lisa , Schaal Heiner , Adams Ortwin , Borkhardt Arndt , Ariyurek Yavuz , de Meijer Emile J. , Kloet Susan , ten Oever Jaap , Placek Katarzyna , Li Yang , Netea Mihai G.
Published: November 2022

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in γδ T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination.

One-sentence summary

MMR vaccination induces cellular and metabolic reprogramming in γδ T cells towards a more active phenotype.
Reconstruction of Three-Dimensional Trajectories of Honeybees Flying in High-Density Aerial Environments
Authors: Mahadeeswara Mandiyam Yadav , Srinivasan Mandyam V
Published: November 2022

So far, relatively few studies have investigated the flight of insects moving in experimental conditions approximating natural scenes. This is mainly because of the technical difficulties involved in detecting and tracking individual insects in three dimensions in outdoor scenarios, as well as matching views of corresponding insects in stereo images for trajectory reconstruction (the so-called ‘Correspondence Problem’). In this study, we describe the methods we have developed to track and unambiguously reconstruct the trajectories and body orientations of a large number of bees flying in close proximity in a ‘bee cloud’, using just two high-speed video cameras configured as a stereo pair in a semi-outdoor setting. Using these methods, two separate bee clouds were filmed and the data were analysed to reconstruct the three-dimensional trajectories, including the head and tail positions, of a total of 382 bees. This dataset should enable future analysis of the movement characteristics of bees flying in a dense environment, as well as uncover potential strategies for mid-air collision avoidance.
Engineering stringent genetic biocontainment of yeast with a protein stability switch
Authors: Hoffmann Stefan A. , Cai Yizhi
Published: November 2022

Synthetic biology holds immense promise to tackle key problems we are facing, for instance in resource use, environmental health, and human health care. However, comprehensive safety measures are needed to deploy genetically engineered microorganisms in open-environment applications. Here, we describe a genetic biocontainment system based on conditional stability of essential proteins. We used a yeast-adapted destabilizing domain degron, which can be stabilized by estradiol addition (ERdd). Leveraging the yeast GFP collection and lab automation platforms, we ERdd-tagged 775 essential genes and screened for strains with estradiol dependent growth. Three genes,SPC110, DIS3andRRP46, were found to be particularly suitable targets. Respective strains showed no growth defect in the presence of estradiol and strong growth inhibition in its absence.SPC110-ERddoffered the most stringent containment, with an escape frequency of 7.0×10-8, and full growth restoration at 100 nM estradiol. By systematically analyzing the containment escapees, we identified the non-essential C-terminal region ofSPC110as target for escape mutations. Its removal decreased the escape frequency with a single ERdd tag further to 4.3×10-9. CombiningSPC110-ERddwith a second ERdd tag on eitherDIS3orRRP46resulted in escape frequencies below the detection limit of the used assay (<2×10-10). Being based on conditional protein stability, this approach is mechanistically orthogonal to previously reported intrinsic biocontainment systems. It thus can be readily combined with other systems, for instance ones based on transcriptional or translational control of essential gene expression, to achieve multiplexed, extremely stringent control over the survival of engineered organisms.

Significance

Synthetic biology holds enormous potential to tackle key issues humanity is facing and can for instance revolutionize agriculture, bioremediation or health care. In each case, the unchecked spread of engineered organisms in natural environments must be prevented. This is particularly problematic with use cases of engineered microbes in open environments. Intrinsic, genetically encoded biocontainment systems, which control cell survival based on environmental cues, can solve this issue. We have developed such a genetic biocontainment system acting on the stability of essential proteins, leveraging a switchable degron. Through a large-scale screening for suitable essential target genes, we were able to create yeast strains that are strictly dependent on estradiol. Supplied with this small molecule, the engineered cells maintain high fitness and grow as robustly as the unmodified strains.
Optimal clustering for quantum refinement of biomolecular structures: Q|R#4
Authors: Wang Yaru , Kruse Holger , Moriarty Nigel W. , Waller Mark P. , Afonine Pavel V. , Biczysko Malgorzata
Published: November 2022

Quantum refinement (Q|R) of crystallographic or cryo-EM derived structures of biomolecules within the Q|R project aims at usingab initiocomputations instead of library-based chemical restraints. An atomic model refinement requires the calculation of the gradient of the objective function. While it is not a computational bottleneck in classic refinement it is a roadblock if the objective function requiresab initiocalculations. A solution to this problem adopted in Q|R is to divide the molecular system into manageable parts and do computations for these parts rather than using the whole macromolecule. This work focuses on the validation and optimization of the automaticdivide-and-conquerprocedure developed within the Q|R project. Also, we propose an atomic gradient error score that can be easily examined with common molecular visualization programs. While the tool is designed to work within the Q|R setting the error score can be adapted to similar fragmentation methods. The gradient testing tool presented here allowsa prioridetermination of the computationally efficient strategy given available resources for the potentially time-expensive refinement process. The procedure is illustrated using a peptide and small protein models considering different quantum mechanical (QM) methodologies from Hartree-Fock, including basis set and dispersion corrections, to the modern semi-empirical method from the GFN-xTB family. The results obtained provide some general recommendations for the reliable and effective quantum refinement of larger peptides and proteins.
iLID-antiGFP-nanobody is a flexible targeting strategy for recruitment to GFP-tagged proteins
Authors: Mahlandt Eike K. , Toereppel Maarten , Haydary Tayeba , Goedhart Joachim
Published: November 2022

Optogenetics is a fast-growing field, that applies light-sensitive proteins to manipulate cellular processes. A popular optogenetics tool is the improved light-induced dimer (iLID). It comprises two components, iLID and SspB, which heterodimerize upon illumination with blue light. This system is often used to recruit proteins to a specific subcellular location, e.g. by targeting the iLID to the plasma membrane. The targeting requires modification of the iLID with a targeting sequence. To skip the modification of the iLID and use existing GFP fusion as targets, we fuse an antiGFP nanobody to the iLID. We show that the antiGFP nanobody is able to locate iLID to GFP-tagged proteins. Plus, the light-dependent recruitment of SspB to iLID, localized by the antiGFP nanobody to a GFP-tagged protein, is still functioning efficiently. This approach increases flexibility, enabling the recruitment of any GFP-tagged protein, without the necessity of protein engineering.
Recent evolution of a maternally-acting sex-determining supergene in a fly with single-sex broods
Authors: Baird Robert B. , Urban John M. , Mongue Andrew J. , Jaron Kamil S. , Hodson Christina N. , Grewoldt Malte , Martin Simon H. , Ross Laura
Published: November 2022

Sex determination is a key developmental process, yet it is remarkably variable across the tree of life. The dipteran family Sciaridae exhibits one of the most unusual sex determination systems in which mothers control offspring sex through selective elimination of paternal X chromosomes. Whereas in some members of the family females produce mixed-sex broods, others such as the dark-winged fungus gnatBradysia coprophilaare monogenic, with females producing single-sex broods. Female-producing females were previously found to be heterozygous for a large X-linked paracentric inversion (X’), which is maternally inherited and absent from male-producing females. Here we assembled and characterized the X’ sequence. As close sequence homology between the X and X’ made identification of the inversion challenging, we developed a k-mer-based approach to bin genomic reads before assembly. We confirmed that the inversion spans most of the X’ chromosome (approximately 55Mb) and encodes around 3500 genes. Analysis of the divergence between the inversion and the homologous region of the X revealed that it originated very recently (<0.5 mya). Surprisingly, we found that the X’ is more complex than previously thought and is likely to have undergone multiple rearrangements that have produced regions of varying ages, resembling a supergene composed of evolutionary strata. We found functional degradation of around 7.3% of genes within the region of recombination suppression, but no evidence of accumulation of repetitive elements. Our findings provide an indication that sex-linked inversions are driving turnover of the strange sex determination system in this family of flies.
Ultra Low Power, Event-Driven Data Compression of Multi-Unit Activity
Authors: Savolainen Oscar W. , Zhang Zheng , Constandinou Timothy G.
Published: November 2022

Recent years have demonstrated the feasibility of using intracortical Brain-Machine Interfaces (iBMIs), by decoding thoughts, for communication and cursor control tasks. iBMIs are increasingly becoming wireless due to the risk of infection and mechanical failure, typically associated with percutaneous connections. The wireless communication itself, however, increases the power consumption further; with the total dissipation being strictly limited due to safety heating limits of cortical tissue. Since wireless power is typically proportional to the communication bandwidth, the output Bit Rate (BR) must be minimised. Whilst most iBMIs utilise Multi-Unit activity (MUA), i.e. spike events, and this in itself significantly reduces the output BR (compared to raw data), it still limits the scalability (number of channels) that can be achieved. As such, additional compression for MUA signals are essential for fully-implantable, high-information-bandwidth systems. To meet this need, this work proposes various hardware-efficient, ultra-low power MUA compression schemes. We investigate them in terms of their BRs and hardware requirements as a function of various on-implant conditions such as MUA Binning Period (BP) and number of channels. It was found that for BPs ≤ 10 ms, the delta-asynchronous method had the lowest total power and reduced the BR by almost an order of magnitude relative to classical methods (e.g. to approx. 151 bps/channel for a BP of 1 ms and 1000 channels on-implant.). However, at larger BPs the synchronous method performed best (e.g. approx. 29 bps/channel for a BP of 50 ms, independent of channel count). As such, this work can guide the choice of MUA data compression scheme for BMI applications, where the BR can be significantly reduced in hardware efficient ways. This enables the next generation of wireless iBMIs, with small implant sizes, high channel counts, low-power, and small hardware footprint. All code and results have been made publicly available.
Dynamics of methane cycling microbiome during methane flux hot moments from riparian buffer systems
Authors: Obregon Dasiel , Mafa-Attoye Tolulope , Baskerville Megan , Mitter Eduardo , Fonseca de Souza Leandro , Oelbermann Maren , Thevathasan Naresh , Tsai Siu Mui , Dunfield Kari E
Published: November 2022

Riparian buffer systems (RBS) are a common agroforestry practice that consists of keeping a forested boundary adjacent to water bodies in agricultural landscapes, thus helping to protect aquatic ecosystems from adverse impacts. Nevertheless, despite the multiple benefits they provide, RBSs can be hotspots of methane emissions since abundant organic carbon and high-water tables are often found in these soils. In southern Ontario, Canada, the rehabilitation of Washington Creek streambank occurred in 1985. In a recent study, methane (CH4) fluxes were measured biweekly for two years (2017-2018) in four different vegetative riparian areas alongside Washington creek: a rehabilitated tree buffer (RH), a grassed buffer (GRB), an undisturbed deciduous forest (UNF), an undisturbed coniferous forest (CF), and an adjacent agricultural field (AGR) for comparison. Based on methane fluxes in 2018 and hot moments identified, we selected two dates from summer (July 04 and August 15) and use soil sampling from those days to assess the CH4 cycling microbial communities in these RBS. We used qPCR and high-throughput sequencing from both DNA and cDNA to measure the diversity and activity of the methanogen and methanotroph communities. Methanogens were abundant in all riparian soils, including the archaeal genera Methanosaeta, Methanosarcina, Methanomassiliicoccus Methanoreggula, but they were mostly active in UNF soils. Among methanotrophs, Methylocystis was the most abundant taxon in all the riparian sites, except for AGR soils where the methanotrophs community mostly comprised members of rice paddy clusters (RPCs and RPC-1) and upland soil clusters (TUSC and USCα). In summary, these results indicate that differences in CH4 fluxes between RBS at Washington creek are influenced by differences in the presence and activity of methanogens, which were higher in the deciduous forest (UNF) soils during hot moments CH4 flux, likely due to high water content in that soils
retro-Tango enables versatile retrograde circuit tracing inDrosophila
Authors: Sorkaç Altar , A Moșneanu Rareș , Crown Anthony M , Savaş Doruk , Okoro Angel M , Talay Mustafa , Barnea Gilad
Published: November 2022

Transsynaptic tracing methods are crucial tools in studying neural circuits. Although a couple of anterograde tracing methods and a targeted retrograde tool have been developed inDrosophila melanogaster, there is still need for an unbiased, user-friendly, and flexible retrograde tracing system. Here we describeretro-Tango, a method for transsynaptic, retrograde circuit tracing and manipulation inDrosophila. In this genetically encoded system, a ligand-receptor interaction at the synapse triggers an intracellular signaling cascade that results in reporter gene expression in presynaptic neurons. Importantly, panneuronal expression of the elements of the cascade renders this method versatile, enabling its use not only to test hypotheses but also to generate them. We validateretro-Tango in various circuits and benchmark it by comparing our findings with the electron microscopy reconstruction of theDrosophilahemibrain. Our experiments establishretro-Tango as a key method for circuit tracing in neuroscience research.
Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits
Authors: Mohamed Gadisti Aisha , Mahmood Sundis , Ognjenovic Nevena B. , Lee Min Kyung , Wilkins Owen M. , Christensen Brock C. , Muller Kristen E. , Pattabiraman Diwakar R.
Published: November 2022

Abstract/summary

Stratifying breast cancer into specific molecular or histological subtypes aids in therapeutic decision-making and predicting outcomes, however, these subtypes may not be as distinct as previously thought. Patients with luminal-like, Estrogen Receptor (ER)- expressing tumors have better prognosis than patients with more aggressive, triple- negative or basal-like tumors. There is, however, a subset of luminal-like tumors that express lower levels of ER, which exhibit more basal-like features. We have found that breast tumors expressing lower levels of ER, traditionally considered to be luminal-like, represent a distinct subset of breast cancer characterized by the emergence of basal-like features. Lineage tracing of low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that basal marker expressing cells arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics. This plasticity allows tumor cells to gain a new lumino-basal phenotype, thus leading to intratumoral lumino-basal heterogeneity. Single- cell RNA sequencing revealed SOX10 as a potential driver for this plasticity, which is known among breast tumors to be almost exclusively expressed in Triple Negative Breast Cancer (TNBC) and was also found to be highly expressed in low-ER tumors. These findings suggest that basal-like tumors may result from the evolutionary progression of luminal tumors with low ER expression.
Identification of heterokaryon incompatibility genes inAspergillus fumigatushighlights a narrow footprint of ancient balancing selection
Authors: Auxier Ben , Zhang Jianhua , Marquez Francisca Reyes , Senden Kira , van den Heuvel Joost , Aanen Duur K. , Snelders Eveline , Debets Alfons J.M.
Published: November 2022

In fungi, a phenomenon termed heterokaryon incompatibility restricts hyphal fusion to occur within an individual since fusion between individuals leads to cell death. Generally, the genes involved are found to be under balancing selection from negative frequency dependent fitness. Here, we assess this inAspergillus fumigatus, a human pathogenic fungus with an extremely high crossover rate. Using auxotrophic markers we screened sexual progeny for compatibility to identify genes involved in this process, the so-calledhetgenes. In total, 5/148 (3.4%) offspring were compatible with a parent and 166/2142 (7.7%) sibling pairs were compatible, consistent with several segregating incompatibility loci. Genetic mapping resulted in five loci, four of which could be fine mapped to individual genes, of which we tested three through heterologous expression, confirming their causal relationship. Surprisingly, a population-level analysis of two available independent datasets did not show an increase in Tajima’s D near these loci, normally a hallmark of balancing selection. However, analysis of closely related species did show trans-species polymorphisms across >10 million years, and equal allele frequencies withinA. fumigatus. Using availablede novoassemblies, we show that these balanced polymorphisms are restricted to within several hundred base pairs flanking the coding sequence, potentially due to this species’ high crossover rate. In addition to identifying the firsthetgenes in anAspergillusspecies, this work highlights the interaction of long-term balancing selection with a high recombination rate. Future mechanistic work on thesehetgenes may provide novel routes for clinical therapies, as well as opportunities for strain improvement in biotechnology.
RNAlysis: analyze your RNA sequencing data without writing a single line of code
Authors: Teichman Guy , Cohen Dror , Ganon Or , Dunsky Netta , Shani Shachar , Gingold Hila , Rechavi Oded
Published: November 2022

Background

Amongst the major challenges in next-generation sequencing experiments are exploratory data analysis, interpreting trends, identifying potential targets/candidates, and visualizing the results clearly and intuitively. These hurdles are further heightened for researchers who are not experienced in writing computer code, since the majority of available analysis tools require programming skills. Even for proficient computational biologists, an efficient and replicable system is warranted to generate standardized results.

Results

We have developedRNAlysis, a modular Python-based analysis software for RNA sequencing data.RNAlysisallows users to build customized analysis pipelines suiting their specific research questions, going all the way from raw FASTQ files, through exploratory data analysis and data visualization, clustering analysis, and gene-set enrichment analysis.RNAlysisprovides a friendly graphical user interface, allowing researchers to analyze data without writing code. We demonstrate the use ofRNAlysisby analyzing RNA data from different studies usingC. elegansnematodes. We note that the software is equally applicable to data obtained from any organism.

Conclusions

RNAlysisis suitable for investigating a variety of biological questions, and allows researchers to more accurately and reproducibly run comprehensive bioinformatic analyses. It functions as a gateway into RNA sequencing analysis for less computer-savvy researchers, but can also help experienced bioinformaticians make their analyses more robust and efficient, as it offers diverse tools, scalability, automation, and standardization between analyses.
Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein
Authors: Devi Santosh , Garg Dushyant Kumar , Bhat Rajiv
Published: November 2022

Aggregation of neuronal protein α-synuclein is implicated in synucleinopathies, including Parkinson’s disease. Despite abundant in vitro studies, the mechanism of α-synuclein assembly process remains ambiguous. In this work, α-synuclein aggregation was induced by its constant mixing in two separate modes, either by agitation in a 96-well microplate reader (MP) or in microcentrifuge tubes using a shaker incubator (SI). Aggregation in both modes occurred through a sigmoidal growth pattern with a well-defined lag, growth, and saturation phase. The end-stage MP- and SI-derived aggregates displayed distinct differences in morphological, biochemical, and spectral signatures as discerned through AFM, proteinase-K digestion, FTIR, Raman, and CD spectroscopy. The MP-derived aggregates showed irregular morphology with a significant random coil conformation, contrary to SI-derived aggregates, which showed typical β-sheet fibrillar structures. The end-stage MP aggregates convert to β-rich SI-like aggregates upon 1) seeding with SI-derived aggregates and 2) agitating in SI. We conclude that end-stage MP aggregates were in a kinetically trapped conformation, whose kinetic barrier was bypassed upon either seeding by SI-derived fibrils or shaking in SI. We further show that MP-derived aggregates that form in the presence of sorbitol, an osmolyte, displayed a β-rich signature, indicating that the preferential exclusion effect of osmolytes helped overcome the kinetic barrier. Our findings help in unravelling the kinetic origin of different α-synuclein aggregated polymorphs (strains) that encode diverse variants of synucleinopathies. We demonstrate that kinetic control shapes the polymorphic landscape of α-synuclein aggregates, both through de novo generation of polymorphs, and by their interconversion.
Cryo-EM Structure of the 50S-HflX Complex Reveals a Novel Mechanism of Antibiotic Resistance inE. coli
Authors: Wu Damu , Dai Yuhao , Gao Ning
Published: November 2022

Bacterial HflX is a conserved ribosome-binding GTPase involved in splitting ribosomal complexes accumulated under stress condition. However, the atomic details of its ribosomal interaction remain to be elucidated. In this work, we present a high-resolution structure of theE. coli50S subunit bound with HflX. The structure reveals highly specific contacts between HflX and the ribosomal RNA, and in particular, an insertion loop of the N-terminal domain of HflX is situated in the peptidyl transferase center (PTC) and makes direct interactions with PTC residues. Interestingly, this loop displays steric clash with a few PTC-targeting antibiotics on the 50S subunit, such as chloramphenicol. Deletion ofhflXresults in hypersensitivity to chloramphenicol treatment, and a loop residue G154 of HflX is important for the observed chloramphenicol resistance. Overall, our results suggest that HflX could be a general stress response factor that functions in both stalled ribosome splitting and PTC antibiotic displacing.
Systematic review of mobile travel apps and their smart features and challenges
Authors: Sia Phoebe Yueng-Hee , Saidin Siti Salina , Iskandar Yulita Hanum P.
Published: November 2022

Purpose

Mobile travel apps (MTA) smart features were identified based on recent travel application (app) trends and a literature review of MTA smart features. Subsequently, the MTA features that could be prioritised to increase user interest in MTA were determined. The MTA smart feature development challenges that should be mitigated were also identified.

Design/methodology/approach

The app identification and selection were based on the one-stop solution characteristics containing the common function of travel apps and eight MTA smart features. A total of 193 Apple apps and 250 Google apps were identified, where 36 apps that met the inclusion and exclusion criteria based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart were selected for evaluation.

Findings

The high user ratings for apps from both app stores revealed the acceptance of smart technology in the tourism industry. Geolocation tracking services, travel itinerary generators, and real-time personalisation and recommendation were the three major features available in the included MTA. The challenges of MTA with smart features were highlighted from the tourism organisation, app developer and user perspectives.

Practical implications

The findings can guide tourism organisations and app developers on the smart features that MTA should offer for user engagement. Technological organisations could optimise their technology stack by considering the identified smart features. The findings are valuable for scholars in terms of MTA aesthetics and usability to gain acceptability. The development challenges included significant investment in technology, location accuracy and privacy concerns when implementing MTA smart features.

Originality/value

The previous literature mainly focused on evaluating app quality, assessing app functionality, and user ratings using the Mobile Application Rating Scale, and scoping reviews of MTA articles. Contrastingly, this study is among the first in which MTA smart features were examined from a developer-centric perspective. Moreover, it is suggested that MTA includes integrated smart features for better tourism services and market penetration in the tourism industry.
Financial sensitivity analysis of small lodging establishments during COVID-19
Authors: Kizildag Murat , Weinland Jeffrey Thomas , Demirer Ilhan
Published: November 2022

Purpose

The main stance of this paper is to draw an authentic and rigorous outlook in terms of the financial and operational performance of small lodging establishments (SLEs) and put forth achievable and practical economic solutions that demonstrate the relative effectiveness of the adopted measures. This paper also suggests practical solutions to help minimize SLEs' financial vulnerability to long-term crisis and to boost their resilience with relative measures by applying recovery revival strategies for this particular segment of the lodging industry.

Design/methodology/approach

The authors have picked a locally owned resort hotel in Central Florida area and structured a real-life, case study-based inductive approach that is purposeful and offers rich economic outlook and analysis for the entire lodging industry, especially for the resort-hotel type of accommodation facilities. The main reason for why they only focus on one company is that they can fully understand the financial effects of COVID-19 on resort type of hotels and layout countering strategies. To achieve paper objectives, they have implemented cost–benefit (C–B), break-even (B-E) analyses along with a sensitivity testing approach.

Findings

The most striking result was that during the state-mandated shutdown period in 2020, overhead and overall operational costs associated with room sales and revenues were very high during this period that shrank the contribution margin ratio for rooms CMRw (room) and eventually yielded high sales volumes to be achieved at the B-E points vs lower sales volumes with almost the same average daily rate (ADR) levels needed for the B-E levels.

Research limitations/implications

Future studies should specifically delve further into a portfolio of SLEs in the region or state or nation wise because the units comprising the SLEs might be too small to muster the changes required to bounce forward for the entire lodging industry in the world.

Practical implications

The resort's revenue re-optimization focus should center on financial re-benchmarking and business re-viability stress under different levels of shock scenarios. According to the different scenarios and calibrations for the ADRs, room nights, net present values (NPVs) of cash flows and profit margins derived from our main analyses, minimizing expenses and preserving cash would be the best key strategy for financial recovery during an ongoing COVID-19 pandemic.

Originality/value

It is obvious that the lodging, hospitality and tourism industry are the hardest-hit industries by the harsh and adverse effects of COVID-19. The effects of pandemic are differently shaped on operations in different industries and subsectors. Therefore, the operational and financial evaluation for the SLEs as the core and a catalyst in the entire lodging industry can shed a light on the strategic financial recovery procedures with broadly applicable real-life and endogenous capabilities and reasoning.