bluuebunny/crossref_metadata_2025 huggingface dataset:
MRIO: The Magnetic Resonance Imaging Acquisition and Analysis Ontology
Authors: Bartnik Alexander , Serra Lucas M. , Smith Mackenzie , Duncan William D. , Wishnie Lauren , Ruttenberg Alan , Dwyer Michael G. , Diehl Alexander D.
Published: August 2023

Objective

Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition.

Materials and Methods

To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Results

MRIO provides well-reasoned classes and logical axioms for the acquisition of several MRI acquisition types and well-known, peer-reviewed analysis software, facilitating the use of MRI data. These classes provide a common language for the neuroimaging research process and help standardize the organization and analysis of MRI data for reproducible datasets. We also provide queries for automated assignment of analyses for given MRI types.

Discussion

MRIO aids researchers in managing neuroimaging studies by helping organize and annotate MRI data and integrating with existing standards such as Digital Imaging and Communications in Medicine and the Brain Imaging Data Structure, enhancing reproducibility and interoperability. MRIO was constructed according to Open Biomedical Ontologies Foundry principals and has contributed several terms to the Ontology for Biomedical Investigations to help bridge neuroimaging data to other domains.

Conclusion

MRIO addresses the need for a “common language” for MRI that can help manage the neuroimaging research, by enabling researchers to identify appropriate analyses for sets of scans and facilitating data organization and reporting.
YAEL: Your Advanced Electrode Localizer
Authors: Wang Zhengjia , Magnotti John , Zhang Xiang , Beauchamp Michael S.
Published: August 2023

Intracranial electroencephalography (iEEG) provides a unique opportunity to measure human brain function with implanted electrodes. A key step in neuroscience inference from iEEG is localizing the electrodes relative to individual subject anatomy and identified regions in brain atlases. While there are number of workflows for electrode localization, most suffer from one or more limitations. The first limitation is a lack of integration: scientists must install and use different software packages for each localization step. Second, they are inefficient: while most iEEG analysis steps can be automated, electrode localization is still largely a manual process. Third, most current tools are limited to the localization process itself, leaving users without the ability to create high-quality visualizations for clinical and research purposes. We developed YAEL (Your Advanced Electrode Localizer) to overcome these limitations. First, YAEL is completely integrated: a single easy-to-use graphical user interface (GUI) controls every step of the localization process. Second, YAEL uses a flexible 3D viewer and automation tools to make accurate localization of electrodes quick and easy. Third, after localization is complete, YAEL leverages the same viewer to create high-quality visualizations of electrode data including identified brain areas from atlases; the response to experimental tasks measured with iEEG; and clinical measures such as epileptiform activity or the results of electrical stimulation mapping. YAEL contains more than 30,000 lines of code, is free and open source, and can be installed in minutes on Mac, Windows and Linux platforms fromhttps://yael.wiki. User interactions with YAEL occur through a web browser ensuring a familiar user experience and consistent operation across platforms and whether YAEL is used locally or deployed in the cloud.
Progesterone receptor activation regulates sensory sensitivity
Authors: Joshi Suchitra , Williamson John , Moosa Shayan , Kapur Jaideep
Published: August 2023

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. We measured the pain threshold daily for four days in ovariectomized, estrogen-primed animals treated with progesterone. The pain threshold was lower 2 days later and stayed that way for the duration of the testing. A specific progesterone-receptor (PR) agonist, segesterone, promoted pain, and mice lacking PR in the brain (PRKO) did not experience lowered pain threshold when treated with progesterone or segesterone. PR activation increased the cold sensitivity but did not affect the heat sensitivity and had a small effect on light sensitivity. Finally, we evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin (NTG) when administered sequentially, reduced pain threshold but not separately. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain in women.
Tomato Response Evaluation through Fertilization and PGRs application Under Temperature Differentiation in late Winter
Authors: Gomasta Joydeb , Hassan Jahidul , Sultana Hasina , Ozaki Yukio , Alamri Saud , Alfagham Alanoud T. , AL-Humaid Latifah A
Published: August 2023

This study evaluated the exogenous application of PGRs substitute chemical fertilization without compromising the growth and yield of tomato in fluctuated day-night temperature and humidity stressed late winter. Two-factor experiment comprising chemical fertilizers at 100, 110, 90 and 80 % of recommended doses besides control and PGRs of GA3; NAA, 4-CPA and SA @ 50 ppm including control was conducted where treatments were assigned in triplicates. Results revealed no significant variation among the fertilizer doses (80% to 110% of recommendation) regarding growth and yield contributing traits while among the PGRs, GA3@ 50 ppm produced maximum number of flower clusters plant-1(16.85), flowers (8.80) and fruits (5.79) cluster-1, single fruit weight (67.83 g) and fruit yield (6.61 kg plant-1) of tomato that was statistically identical with the findings of SA. But significant reduction in yield was noted in NAA and 4-CPA (1.20 kg and 1.21 kg plant-1, respectively). Interestingly, GA3and SA in combination with any doses of the studied fertilizers maximize the tomato morphological and reproductive traits while fertilizer plus NAA and 4-CPA interaction gave the inferior results. Further, correlation matrix and PCA findings revealed that five fertilizer doses have no distinctiveness whereas GA3and SA has distinct position than other PGRs with the maximum dependent variables those were contributed positively in the total variations. The study findings suggested that 20% fertilizer requirement could be reduced with the substitution of GA3and SA @ 50 ppm for successful cultivation of tomato in late winter having the extreme environmental issues.
IRE1 regulated autophagy and chaperone levels cooperatively modulate acquired thermotolerance inArabidopsis thaliana
Authors: Bajaj Mayur , Allu Annapurna Devi , Rao Basuthkar J
Published: August 2023

Rapidly changing global climatic conditions emphasize the urgent need for the development of heat stress-resilient plants. Priming, a stress-training program that aids in imparting tolerance to subsequent stress(es) emerged as a promising approach to improve stress tolerance. However, molecular mechanisms underlying priming-induced plant stress responses still remain largely elusive. In the current study, the impact of heat stress onArabidopsis thalianaseedlings pre-exposed to elevated temperature (primed) was found to be minimal, compared to naïve (unprimed) seedlings, which failed to survive. Our findings suggest that thermopriming-mediated heat stress tolerance operates through the activation of IRE1-bZIP60 cascade triggering unfolded protein response (UPR). Further, IRE1 activation triggers autophagy response through attenuation of autophagy-negative regulators such asBGLU21, ROSY1andPR-14via RIDD-mediated mRNA degradation. Alongside UPR and autophagy, priming temporally induces HSP levels, rendering plants tolerant to acute heat stress. Contrarily, unprimed seedlings fail to mount such temporally coordinated regulation, thus fail to survive. Moreover, loss of bZIP60 reduces the impact of priming-induced response, suggesting its role in the maintenance of stress memory. Taken together, the current study suggests that priming-mediated regulation of protein homeostasis through the temporal regulation of autophagy in concert with chaperone synthesis promotes heat stress tolerance.
Can Protein Structure Prediction Methods Capture Alternative Conformations of Membrane Proteins?
Authors: Xie Tengyu , Huang Jing
Published: August 2023

Understanding the conformational dynamics of proteins, such as the inward-facing (IF) and outward-facing (OF) transition observed in transporters, is vital for elucidating their functional mechanisms. Despite significant advances in protein structure prediction (PSP) over the past three decades, most efforts have been focused on single-state prediction, leaving multi-state or alternative conformation prediction (ACP) relatively unexplored. This discrepancy has led to the development of highly accurate PSP methods such as AlphaFold, yet their capabilities for ACP remain limited. To investigate the performance of current PSP methods in ACP, we curated a dataset, named IOMemP, consisting of 32 experimentally determined high-resolution IF and OF structures of 16 membrane proteins. We benchmarked 12 representative PSP methods, along with two recent multi-state methods based on AlphaFold, against this dataset. Our findings reveal an escalating bias towards one specific state in deep learning-based methods and a remarkably consistent preference for specific states across various PSP methods. We elucidated how coevolution information in MSAs influences the state preference. Moreover, we showed that AlphaFold, when excluding coevolution information, estimated similar energies between the experimental IF and OF conformations, indicating that the energy model learned by AlphaFold is not biased towards any particular state. Our IOMemP dataset and benchmark results are anticipated to advance the development of robust ACP methods.
Benchmarking computational methods for single-cell chromatin data analysis
Authors: Luo Siyuan , Germain Pierre-Luc , Robinson Mark D. , Meyenn Ferdinand von
Published: August 2023

Single-cell chromatin accessibility assays, such as scATAC-seq, are increasingly employed in individual and joint multi-omic profiling of single cells. As the accumulation of scATAC-seq and multi-omics datasets continue, challenges in analyzing such sparse, noisy, and high-dimensional data become pressing. Specifically, one challenge relates to optimizing the processing of chromatin-level measurements and efficiently extracting information to discern cellular heterogeneity. This is of critical importance, since the identification of cell types is a fundamental step in current single-cell data analysis practices.

We benchmarked 8 feature engineering pipelines derived from 5 recent methods to assess their ability to discover and discriminate cell types. By using 10 metrics calculated at the cell embedding, shared nearest neighbor graph, or partition levels, we evaluated the performance of each method at different data processing stages. This comprehensive approach allowed us to thoroughly understand the strengths and weaknesses of each method and the influence of parameter selection.

Our analysis provides guidelines for choosing analysis methods for different datasets. Overall, feature aggregation, SnapATAC, and SnapATAC2 outperform latent semantic indexing-based methods. For datasets with complex cell-type structures, SnapATAC and SnapATAC2 are preferred. With large datasets, SnapATAC2 and ArchR are most scalable.
Large-scale lensless microscopy with fast acquisition and region-wise focusing
Authors: Zhou You , Song Weizhi , Wu Linyuan , Fan Lin , Wang Junjia , Jiang Shaowei , Ma Zhan , Xiong Bo , Cao Xun
Published: August 2023

The imaging field of view (FOV) of lensless microscope is consistent with the size of image sensor in use, enabling the observation of sample areas larger than 20 mm2. Combined with high-performance and even super-resolution phase retrieval algorithms, micron and sub-micron resolution can be achieved, ultimately realizing wide-field and high-resolution imaging performance simultaneously. However, high-throughput lensless imaging poses significant challenges in terms of rapid data acquisition and large-scale phase retrieval. Additionally, when observing biological samples over a large FOV, the focus plane often exhibits inconsistency among different regions, necessitating further parameter calibration. In this study, we propose a fast acquisition and efficient reconstruction strategy for coherent lensless imaging based on a multi-height imaging model. Multiple measurements are manually modulated using an axial translation stage and continuously captured by an image sensor, facilitating rapid data acquisition within seconds and requiring no hardware synchronization. The efficiency and accuracy of phase retrieval are enhanced through precise parameter calibration algorithms, as well as techniques such as region-wise parallel computing and region-wise auto-focusing. Experimental results demonstrate 7.4×5.5 mm2FOV and 1.55 μm half-pitch resolution imaging of human skin and lung tumor sections with region-wise focusing, requiring only an approximate 0.5-s acquisition time and 44-s reconstruction time. Furthermore, by incorporating the pixel super-resolution principle, the 1.10 μm half-pitch imaging resolution is demonstrated in full-FOV peripheral blood smears without additional data required, beneficial to the identification of hollow shape and segmentation of blood cells.
Methods and techniques enabling multi-kilobase long-range genomic rewrite/replace editing
Authors: Piggott Christopher A , Tjang Laurentia V , Chen Selina , Tatu Utsav , Hirou Hannah , Jaroszewska Antonina , McIntyre Emma , Chen Jocelin , Faybishenko Joelle V , Gavan Richard V , Hackley Chris R
Published: August 2023

CRISPR enabled cell and gene therapies have the potential to revolutionize the field of genetic medicine. However, the vast majority of rare diseases remain untreatable due to the limitations of current tools and techniques. To date, most corrective therapeutic approaches have been restricted to mutation-by-mutation approaches, where either HDR, or newer techniques such as base or prime editing, rewrite small regions of DNA at a time (∼1-100 bp). While these approaches are powerful, short editing windows (relative to the size of human genes) are financially and/or technically incompatible with most rare-disease mutation profiles. Here, we demonstrate for the first time that CRISPR/Cas9 can be used to “rewrite” 7kb+ sections of the human genome simultaneously via a selection-free process we have named “long-range rewriting”. Long-range rewriting approaches are compatible with multiple nucleases, cell types and genomic loci, and can be used with both double-strand break (DSB) and non-DSB based approaches.
Woody plant taxonomic, functional, and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests: environmental filtering and arrival of temperate taxa
Authors: Bañares-de-Dios Guillermo , Macía Manuel J. , Arellano Gabriel , Granzow-de la Cerda Íñigo , Vega-Álvarez Julia , Arnelas Itziar , Espinosa Carlos I. , Salinas Norma , Cayuela Luis
Published: August 2023

Aim

Mountains are paramount for exploring biodiversity patterns and their causes due to the rich mosaic of topographies and climates encompassed over short geographical distances. Biodiversity changes along elevational gradients have traditionally been explored in terms of taxonomic diversity, but other aspects must be considered. For first time, we simultaneously assessed elevational trends in the taxonomic, functional, and phylogenetic diversity of woody plants in Andean tropical montane forests (TMFs) and explored their underlying ecological and evolutionary causing processes.

Location

Tropical Andes

Time period

2011/2012 and 2017/2019

Tropical Andes

Major Taxa

Woody plants

Methods

We investigated taxonomic, functional, and phylogenetic diversity along four transects (traversingca. 2,200 m altitudinal gradients) encompassing 114 0.1 ha plots across a broad latitudinal range (ca. 10°). We used Hill numbers to quantify differences in the abundance-based diversity of 37,869 woody plant individuals with DBH ≥ 2.5 cm.

Results

Taxonomic, functional, and phylogenetic diversity decreased as elevation increased. The decrease was less pronounced for Hill numbers of higher orders. The only exception was a slight increase in phylogenetic diversity when more weight was given to dominant species. These results were consistent between transects.

Main conclusions

The decrease in taxonomic and functional diversity with elevation might be due to an environmental filtering process where the increasingly harsher conditions towards highlands exclude species and functional strategies. Besides, the differences in the steepness of the decrease between Hill orders suggest that rare species contribute disproportionately to functional diversity. The shifting elevational trend in the phylogenetic diversity between Hill orders indicates a greater than previously considered influence in central tropical Andean highlands of species originated in lowlands with strong niche conservatism relative to distantly related temperate lineages. This could be explained by a decreasing presence and abundance of extratropical taxa towards the central Andes relative to northern or southern Andes.

BIOSKETCH

Guillermo Bañares-de-Dios is a plant ecologist with interests in community assembly, biodiversity patterns, and global change. He completed his PhD in 2020 and belongs to “Grupo de Ecología Tropical”, an international network of researchers from different institutions with broad interests in tropical biology (http://www.grupoecologiatropical.com/?lang=en). Currently he works as Project Manager implementing the European Pollinator Monitoring Scheme in Spain.
Somatosensory cortex microstimulation modulates primary motor and ventral premotor cortex neurons with extensive spatial convergence and divergence
Authors: Ruszala Brandon , Mazurek Kevin A. , Schieber Marc H.
Published: August 2023

Intracortical microstimulation (ICMS) is known to affect distant neurons transynaptically, yet the extent to which ICMS pulses delivered in one cortical area modulate neurons in other cortical areas remains largely unknown. Here we assessed how the individual pulses of multi-channel ICMS trains delivered in the upper extremity representation of the macaque primary somatosensory area (S1) modulate neuron firing in the primary motor cortex (M1) and in the ventral premotor cortex (PMv). S1-ICMS pulses modulated the majority of units recorded both in the M1 upper extremity representation and in PMv, producing more inhibition than excitation. Effects converged on individual neurons in both M1 and PMv from extensive S1 territories. Conversely, effects of ICMS delivered in a small region of S1 diverged to wide territories in both M1 and PMv. The effects of this direct modulation of M1 and PMv neurons produced by multi-electrode S1-ICMS like that used here may need to be taken into account by bidirectional brain-computer interfaces that decode intended movements from neural activity in these cortical motor areas.

Significance Statement

Although ICMS is known to produce effects transynaptically, relatively little is known about how ICMS in one cortical area affects neurons in other cortical areas. We show that the effects of multi-channel ICMS in a small patch of S1 diverge to affect neurons distributed widely in both M1 and PMv, and conversely, individual neurons in each of these areas can be affected by ICMS converging from much of the S1 upper extremity representation. Such direct effects of ICMS may complicate the decoding of motor intent from M1 or PMv when artificial sensation is delivered via S1-ICMS in bidirectional brain-computer interfaces.
Tissue-wide scRNA-seq analysis reveals enrichment of imprinted genes in stem and endocrine cell-types in mice
Authors: Higgs Matthew J. , Hill Matthew J. , John Rosalind M. , Isles Anthony R.
Published: August 2023

Enriched expression of imprinted genes may provide evidence of convergent function. Here we interrogated five single-cell RNA sequencing datasets to identify imprinted gene over-representation in the embryonic and adult mouse focusing on tissues including the bladder, pancreas, mammary gland and muscle. We identify a consistent enrichment of imprinted genes in stromal cell and mesenchymal stem cell populations across these tissues, suggesting a role in tissue maintenance. Furthermore, we identify a distinct enrichment in the endocrine islets of the mouse pancreas, over and above the stromal/stem cells from this tissue. Taken together with our previous work examining imprinted gene expression in cell subpopulations of the adult mouse brain and pituitary gland, these data suggest that genomic imprinting influences physiology largely via separate systems of cell populations either involved in hormonal signalling or in stemness and cell-fate co-ordination.
Decoding Visual Spatial Attention Control
Authors: Meyyappan Sreenivasan , Rajan Abhijit , Yang Qiang , Mangun George R , Ding Mingzhou
Published: August 2023

In models of visual spatial attention control, it is commonly held that top-down control signals originate in the dorsal attention network, propagating to the visual cortex to modulate baseline neural activity and bias sensory processing. However, the precise distribution of these top-down influences across different levels of the visual hierarchy is debated. In addition, it is unclear whether these changes in baseline neural activity directly translate into improved performance. We analyzed attention-related baseline activity during the anticipatory period of a trial-by-trial voluntary spatial attention task, using two independent fMRI datasets, and two different analytic approaches. First, as in prior studies, univariate analysis showed that covert attention significantly enhanced baseline neural activity in higher-order visual areas contralateral to the attended visual hemifield, while effects in lower-order visual areas (e.g., V1) were weaker and more variable. Second, in contrast, multivariate pattern analysis (MVPA) revealed significant decoding of attention conditions across all visual cortical areas, with lower-order visual areas exhibiting higher decoding accuracies than higher-order areas. Third, decoding accuracy, rather than the magnitude of univariate activation, was a better predictor of a subject’s stimulus discrimination performance. Finally, the MVPA results were replicated across two experimental conditions, where the direction of spatial attention was either externally instructed by a cue or based on the participants free choice decision about where to attend. Together, these findings offer new insights into the extent of attentional biases in the visual hierarchy under top-down control, and how these biases influence both sensory processing and behavioral performance.

Highlights

Multivariate pattern analysis revealed the presence of top-down attentional biasing signals in all areas of the visual hierarchy whereas univariate analysis was not able to reveal the full extent of attentional biasing in the visual cortex.

The decoding accuracy derived from the MVPA analysis but not the magnitude difference derived from the univariate analysis predicted the subject’s behavioral performance in stimulus discrimination.

The MVPA results were consistent across two experimental conditions where the direction of spatial attention was driven either by external instructions or from purely internal decisions.
Targeted decontamination of sequencing data with CLEAN
Authors: Lataretu Marie , Krautwurst Sebastian , Huska Matthew R. , Marquet Mike , Viehweger Adrian , Braun Sascha D. , Brandt Christian , Hölzer Martin
Published: August 2023

Many biological and medical questions are answered based on the analysis of sequence data. However, we can find contamination, artificial spike-ins, and overrepresented rRNA sequences in various read collections and assemblies. In particular, spike-ins used as controls, as those known from Illumina or Nanopore data, are often not considered as contaminants and also not appropriately removed during analyses. Additionally, removing human host DNA may be necessary for data protection and ethical considerations to ensure that individuals cannot be identified.

We developed CLEAN, a pipeline to remove unwanted sequences from both long- and short-read sequencing techniques. While focusing on Illumina and Nanopore data with their technology-specific control sequences, the pipeline can also be used for host decontamination of metagenomic reads and assemblies, or the removal of rRNA from RNA-Seq data. The results are the purified sequences and sequences identified as contaminated with statistics summarized in a report.

The output can be used directly in subsequent analyses, resulting in faster computations and improved results. Although decontamination seems mundane, many contaminants are routinely overlooked, cleaned by steps that are not fully reproducible or difficult to trace. CLEAN facilitates reproducible, platform-independent data analysis in genomics and transcriptomics and is freely available athttps://github.com/rki-mf1/cleanunder a BSD3 license.

GRAPHICAL ABSTRACT
Microplastics reach the brain and interfere with honey bee cognition
Authors: Pasquini Elisa , Ferrante Federico , Passaponti Leonardo , Pavone Francesco Saverio , Costantini Irene , Baracchi David
Published: August 2023

Scientific research exploring the impact of microplastics (MPs) in terrestrial systems is still at an early stage but has already confirmed that exposure to plastics leads to various detrimental health effects in several organisms. Although recent studies have shown the toxicological effects of single MP polymers on honey bees, the effects of different polymer combinations and their consequences on cognitive and behavioural performance remain unknown. To fill this knowledge gap, we investigated the effects of MPs, both individually and in combination, on the cognitive abilities of the honey beeApis mellifera. We evaluated the acute oral toxicity of Polystyrene (PS) and Plexiglass (PMMA) MPs, as well as a combination of the two (MIX), at three different concentrations (0.5, 5 and 50 mg/L-1) and analysed their effects on sucrose responsiveness and appetitive olfactory learning and memory. We also explored whether these MPs could reach and accumulate in the insect brain using Two-Photon Fluorescence Microscopy (TPFM) in combination with an optimized version of the DISCO clearing technique. The results revealed that PS reduced the responsiveness of foragers to sucrose, whereas PMMA had no significant impact; however, the combination of PMMA and PS had a pronounced negative effect on sucrose responsiveness. In addition, both PMMA and PS, as well as MIX, impaired bee learning formation and memory retrieval, with PS exhibiting the most severe effects. Regarding our brain imaging analysis performed with TFPM, we found that after only three days of oral exposure, MPs could penetrate and accumulate in the brain. These results raise concerns about the potential mechanical, cellular, and biochemical damage that MPs may cause to the central nervous system.
Sex-Specific Developmental Gene Expression Atlas Unveils Dimorphic Gene Networks inC. elegans
Authors: Haque Rizwanul , Kurien Sonu Peedikayil , Setty Hagar , Salzberg Yehuda , Stelzer Gil , Litvak Einav , Gingold Hila , Rechavi Oded , Oren-Suissa Meital
Published: August 2023

Sex-specific traits and behaviors emerge during development by the acquisition of unique properties in the nervous system of each sex. However, the genetic events responsible for introducing these sex-specific features remain poorly understood. In this study, we created a comprehensive gene expression atlas for both sexes of the nematodeCaenorhabditis elegansacross development. By comparing the transcriptome of pure populations of hermaphrodites and males from early larval stages to adulthood, we discovered numerous differentially expressed genes, including neuronal gene families like transcription factors, neuropeptides, and GPCRs. We identified INS-39, an insulin-like peptide, as a prominent male-biased gene expressed specifically in ciliated sensory neurons. We show that INS-39 serves as an early-stage male marker, facilitating the effective isolation of males in high-throughput experiments. Through complex and sex-specific regulation,ins-39plays pleiotropic sexually-dimorphic roles in temperature sensation, survival in cold temperatures, resilience against high hydrogen peroxide levels, and dauer entry, while also playing a shared, dimorphic role in early life stress. This study offers a comparative sexual and developmental gene expression database forC. elegans, which will facilitate research into the genetic regulation of the sexual development of other organisms. Furthermore, it highlights conserved candidate genes that may underlie the sexually-dimorphic manifestation of different human diseases.
Using social information improves individual foraging efficiency in sheep
Authors: Vartparonian Vartan E , Leu Stephan T
Published: August 2023

Knowledge about the environment is fundamentally important to move, find resources and forage efficiently. This information can either be acquired through individual exploration (personal information) or from other group members (social information). We experimentally assessed the use of social information and its influence on foraging efficiency in sheep,Ovis aries. Naïve individuals paired with an informed partner that knew the food patch location, found the patch significantly faster compared to naïve individuals paired with another naïve individual. Similarly, they spent a significantly lower proportion of time exploring areas away from the food patch. We further found that the previous outcome of using social information (success = access to feed vs failure = no access to feed) had no impact and sheep continued to use social information in subsequent foraging trials and foraged similarly efficient. Our results suggest, naïve sheep that are unfamiliar with resource locations, forage more efficiently when informed individuals are present compared to when all individuals are naïve. If informed individuals play a similar role in larger groups, new management practices could be developed to improve foraging efficiency when sheep are moved to new paddocks or in paddocks with heterogenous and dynamic resource distribution.
Dissociation of attentional state and behavioral outcome using local field potentials
Authors: Prakash Surya S , Mayo J Patrick , Ray Supratim
Published: August 2023

Successful behavior depends on attentional state and other factors related to decision-making, which may modulate neuronal activity differently. Here, we investigated whether attentional state and behavioral outcome (i.e., whether a target is detected or missed) are distinguishable using the power and phase of local field potential (LFP) recorded bilaterally from area V4 of monkeys performing a cued visual attention task. To link each trial’s outcome to pairwise measures of attention that are typically averaged across trials, we used several methods to obtain single-trial estimates of spike count correlation and phase consistency. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase in attentional/behavioral discriminability, although single-trial gamma phase consistency provided reasonably high attentional discriminability. Our results suggest a dissociation between the neuronal mechanisms that regulate attentional focus and behavioral outcome.
Feed-forward metabotropic signaling by Cav1 Ca2+channels supports pacemaking in pedunculopontine cholinergic neurons
Authors: Tubert C. , Zampese E. , Pancani T. , Tkatch T. , Surmeier D. J.
Published: August 2023

Like a handful of other neuronal types in the brain, cholinergic neurons (CNs) in the pedunculopontine nucleus (PPN) are lost in the course of Parkinson’s disease (PD). Why this is the case is unknown. One neuronal trait implicated in PD selective neuronal vulnerability is the engagement of feed-forward stimulation of mitochondrial oxidative phosphorylation (OXPHOS) to meet high bioenergetic demand, leading to sustained oxidant stress and ultimately degeneration. The extent to which this trait is shared by PPN CNs is unresolved. To address this question, a combination of molecular and physiological approaches were used. These studies revealed that PPN CNs are autonomous pacemakers with modest spike-associated cytosolic Ca2+transients. These Ca2+transients were attributable in part to the opening of high-threshold Cav1.2 Ca2+channels, but not Cav1.3 channels. Nevertheless, Cav1.2 channel signaling through endoplasmic reticulum ryanodine receptors stimulated mitochondrial OXPHOS to help maintain cytosolic adenosine triphosphate (ATP) levels necessary for pacemaking. Inhibition of Cav1.2 channels led to recruitment of ATP-sensitive K+channels and slowing of pacemaking. Cav1.2 channel-mediated stimulation of mitochondria increased oxidant stress. Thus, PPN CNs have a distinctive physiological phenotype that shares some, but not all, of the features of other neurons that are selectively vulnerable in PD.
Resource-combining costs of being a diet generalist in the super-generalist protist predatorDictyostelium discoideum
Authors: Shreenidhi P. M. , Brock Debra A. , McCabe Rachel I. , Strassmann Joan E. , Queller David C.
Published: August 2023

Consumers lie on a continuum between diet specialization on few resources to being generalist feeders on many resources. Generalism has the clear advantage of having more resources to exploit, but the costs that limit generalism are less clear. We explore two understudied costs of generalism in a super-generalist amoeba predator,Dictyostelium discoideum, feeding on naturally co-occurring bacterial prey. Both involve costs of combining different prey. First, amoebas exhibit a reduction in growth rate when they switch from one species of prey bacteria to another, something we call resource-switching costs. These switching costs typically disappear within a day, indicating adjustment to new prey bacteria. Second, amoebas usually divide more slowly on mixtures of bacteria compared to on single bacteria, something we call resource-mixing costs. Both results support that idea that, although amoebas can consume a huge variety of prey, they must use partially different methods and thus must pay costs to handle multiple prey, either sequentially or simultaneously.

Significance Statement

Perhaps the most fundamental conflict in nature occurs when one organism consumes another. Diet generalists benefit from the advantage of eating many prey but then must deal with many prey defences. We explore costs associated with a broad diet in a protist microbial predator,Dictyostelium discoideum. These predators of bacteria show a delay in growth when switched from one bacteria to another, supporting the hypothesis that they must deploy different strategies. They also experience costs when grown on many bacteria at once, suggesting that the alternative strategies for consuming different prey are partly incompatible with each other. Our findings shed light on the nature of diet generalism and highlight the complexity of predation in the microbial world.
HIV-1 Capsid Shape, Orientation, and Entropic Elasticity Regulate Translocation into the Nuclear Pore Complex
Authors: Hudait Arpa , Voth Gregory A.
Published: August 2023

Nuclear import of the viral capsid is a critical step in the HIV-1 life cycle that serve to transport and release genomic material into the nucleus. Nuclear Pore Complex (NPC) allows passage of intact capsid, though mechanistic details of the process remain to be fully understood. Here we investigate the factors regulating HIV-1 capsid translocation into the NPC central channel using coarse-grained molecular dynamics simulations. We find that successful translocation is contingent on the compatibility of the capsid morphology and channel dimension and the proper orientation of the capsid approach to the channel. The central channel dynamically expands to allow capsid passage, demonstrating the pleomorphic nature of the channel necessary for transporting large cargoes. Structural analysis shows that stress induced by the central channel confinement and uncondensed internal genomic material generates correlated striated patterns of lattice disorder across the viral capsid surface which is an indicator of its lattice “elasticity”. Our results suggest that the “elasticity” can aid the capsid to adapt to the stress and remain structurally intact during translocation.

Teaser

Computer Simulations identify capsid elasticity as a key factor for successful nuclear entry.
Scoping Review of One-Dimension Statistical Parametric Mapping in Lower Limb Biomechanical Analysis
Authors: Yona Tomer , Kamel Netanel , Cohen-Eick Galya , Ovadia Inbar , Fischer Arielle
Published: August 2023

Background

Biomechanics is crucial in enhancing sports performance and preventing injury. Traditionally, discrete point analysis is used to analyze important kinetic and kinematic data points, reducing continuous data to a single point. One-dimensional Statistical Parametric Mapping (spm1d) offers a more comprehensive approach by assessing entire movement curves instead of isolated peak values. Nevertheless, spm1d is still underutilized in various sports and sports-related injuries.

Purpose

To summarize the existing literature on the application of spm1d in sports biomechanics, including the kinetics and kinematics of the hip, knee, and ankle joints, as well as to identify gaps in the literature that may require further research.

Methods

A scoping review was conducted, searching PubMed, Embase, Web of Science, and ProQuest databases. English peer-reviewed studies using SPM to assess lower limb kinetics or kinematics in different sports or sports-related injuries were included. In contrast, reviews, meta-analyses, conference abstracts, grey literature, and studies focusing on non-kinetic or kinematic outcomes were excluded.

Results

The review yielded 129 papers, with an increased number of studies published in the last three years. Of these studies, 81 examined healthy individuals (63%), and 48 focused on injured populations (37%). Running (n=28), cutting (n=21), and jumping/landing (n=14) were the most common activities. The most prevalent sport-related injuries examined were anterior cruciate ligament rupture (n=21), chronic ankle instability (n=16), and hip-related pain (n=9). Research gaps include the underrepresentation of common sports and movements, small sample size, lack of studies in non-laboratory settings and varied active age groups, and absence of evaluations on the effects of protective sports gear other than shoes.

Conclusion

The application of spm1d in sports biomechanics demonstrates diverse uses in sports performance, injury reduction, and rehabilitation. While spm1d shows promise in improving our understanding of sports biomechanics, there are still significant gaps in the literature that present future research opportunities.
Characterizing heterogeneity along EMT and metabolic axes in colorectal cancer reveals underlying consensus molecular subtype-specific trends
Authors: Sehgal Manas , R Soundharya , Vaz Joel Markus , Yogeshwar Raja G , Muralidharan Srinath , Venkatraghavan Sankalpa , Jolly Mohit Kumar
Published: August 2023

Colorectal cancer (CRC) is highly heterogenous with variable survival outcomes and therapeutic vulnerabilities. A commonly used classification system in CRC is the Consensus Molecular Subtypes (CMS) based on gene expression patterns. However, how these CMS categories connect to axes of phenotypic plasticity and heterogeneity remains unclear. Here, we analyze 101 bulk transcriptomic datasets, along with patient tumor samples from TCGA and single-cell RNA sequencing data, to evaluate the extent of variation among CMS subtypes across metabolic plasticity and EMT axes. Our results show that CMS2 and CMS3 samples were relatively more epithelial as compared to CMS1 and CMS4. Single-cell RNA-seq analysis of CMS1 revealed two subpopulations: one close to CMS4 (more mesenchymal) and the other closer to CMS2 or CMS3 (more epithelial), indicating a partial EMT-like behavior. Further, in our meta-analysis and in TCGA data, epithelial phenotype score was positively correlated with scores of glycolysis, OXPHOS and FAO pathways, while mesenchymal scores showed CMS subtype-specific associations with metabolic axes. PD-L1 activity scores, however, consistently correlated positively with mesenchymal signature ones and negatively with epithelial signature ones, across the four CMS categories. Together, our results quantify the patterns of two interconnected axes of phenotypic heterogeneity - EMT and metabolic reprogramming - at a CMS subtype level in CRC.
Revealing Gene Expression Heterogeneity in a Clonal Population ofTetrahymena thermophilathrough Single-Cell RNA Sequencing
Authors: Kojima Hiroki , Kashiwagi Akiko , Ikegami Takashi
Published: August 2023

We performed single-cell RNA sequencing (scRNA-seq) on a population of 5,000Tetrahymena thermophila, using the 10x Genomics 3’ gene expression analysis, to investigate gene expression variability within this clonal population. Initially, we estimated the 3’-untranslated regions (3’ UTRs), which were absent in existing annotation files but are crucial for the 10x Genomics 3’ gene expression analysis, using the peaks2utr method. This allowed us to create a modified annotation file, which was then utilized in our scRNA-seq analysis. Our analysis revealed significant gene expression variability within the population, even after removing the effect of cell phase-related features. This variability predominantly appeared in six distinct clusters. Through gene ontology and KEGG pathway enrichment analyses, we identified that these were primarily associated with ribosomal proteins, proteins specific to mitochondria, proteins involved in peroxisome-specific carbon metabolism, cytoskeletal proteins, motor proteins, and immobilized antigens.
Phonic Tics in a Rat Model of Tourette Syndrome Enable Research on Symptom-Based DBS
Authors: Sagalajev Boriss , Lennartz Lina , Mokhtari Niloofar , Szpak Mikolaj , Schüller Thomas , Baldermann Juan Carlos , Andrade Pablo , Visser-Vandewalle Veerle , Sesia Thibaut
Published: August 2023

The lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a GABA-A antagonist (bicuculline) was previously shown to induce tic-like hyperkinesia in rats and monkeys, while tic-like vocalizations were studied and confirmed only in the latter. We, therefore, assessed whether vocalizations accompany hyperkinesia also in rats and whether they respond to thalamic DBS. Rats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline. Bicuculline in CPu led to the development of hyperkinesia in the form of arrhythmic, myocloniform shoulder jerks sporadically alternating with episodes of dystonic lordosis. Likewise, bicuculline in NAc resulted in hyperkinesia, but at a much smaller dose and in conjunction with nonsensical vocalizations. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia. Also, early results indicate that thalamic DBS attenuates vocalizations, yet the hotspot for stimulation remains to be determined. In conclusion, striatal disinhibition leads not only to the development of hyperkinesia but also vocalizations in rats. The resemblance of hyperkinesia to motor tics and vocalizations to phonic tics is evident in their appearance and susceptibility to DBS. Rats can, therefore, be used to study DBS for symptom-based TS therapy.
Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation
Authors: Alston Jhullian J. , Soranno Andrea , Holehouse Alex S.
Published: August 2023

Intrinsically disordered regions (IDRs) are critical for cellular function, yet often appear to lack sequence conservation when assessed by multiple sequence alignments. This raises the question of if and how function can be encoded and preserved in these regions despite massive sequence variation. To address this question, we have applied coarse-grained molecular dynamics simulations to investigate non-specific RNA binding of coronavirus nucleocapsid proteins. Coronavirus nucleocapsid proteins consist of multiple interspersed disordered and folded domains that bind RNA. We focussed here on the first two domains of coronavirus nucleocapsid proteins, the disordered N-terminal domain (NTD) followed by the folded RNA binding domain (RBD). While the NTD is highly variable across evolution, the RBD is structurally conserved. This combination makes the NTD-RBD a convenient model system to explore the interplay between an IDR adjacent to a folded domain, and how changes in IDR sequence can influence molecular recognition of a partner. Our results reveal a surprising degree of sequence-specificity encoded by both the composition and the precise order of the amino acids in the NTD. The presence of an NTD can – depending on the sequence – either suppress or enhance RNA binding. Despite this sensitivity, large-scale variation in NTD sequences is possible while certain sequence features are retained. Consequently, a conformationally-conserved fuzzy RNA:protein complex is found across nucleocapsid protein orthologs, despite large-scale changes in both NTD sequence and RBD surface chemistry. Taken together, these insights shed light on the ability of disordered regions to preserve functional characteristics despite their sequence variability.