bluuebunny/crossref_metadata_2025 huggingface dataset:
MIADE metadata guidelines: Minimum Information About a Disorder Experiment
Authors: Mészáros Bálint , Hatos András , Palopoli Nicolas , Quaglia Federica , Salladini Edoardo , Van Roey Kim , Arthanari Haribabu , Dosztányi Zsuzsanna , Felli Isabella C. , Fischer Patrick D , Hoch Jeffrey C. , Jeffries Cy M , Longhi Sonia , Maiani Emiliano , Orchard Sandra , Pancsa Rita , Papaleo Elena , Pierattelli Roberta , Piovesan Damiano , Pritisanac Iva , Viennet Thibault , Tompa Peter , Vranken Wim , Tosatto Silvio CE , Davey Norman E
Published: July 2022

An unambiguous description of an experimental setup and analysis, and the subsequent biological observation is vital for accurate data interpretation and reproducible results. Consequently, experimental analyses should be described in a concise, unequivocal, and digestible manner. The aim of minimum information guidelines is to define the fundamental complement of data that can support an unambiguous conclusion on experimental observations. In this document, we present the Minimum Information About Disorder Experiments (MIADE) guidelines to define the minimal fundamental parameters required for non-experts to understand the key findings of an experiment studying intrinsically disordered proteins (IDPs) or intrinsically disordered protein regions (IDRs). MIADE guidelines provide recommendations for data producers to describe the results of their experiments at source, for curators to annotate experimental data to community resources and for database developers maintaining community resources to disseminate the data. We give examples of the application of these guidelines in common use cases and describe the implementation of an update to the DisProt IDP database to allow MIADE-compliant annotation. The MIADE guidelines will improve the interpretability of experimental results for data consumers, facilitate direct data submission, simplify data curation, improve data exchange among repositories and standardise the dissemination of the key metadata on an IDP experiment by IDP data sources.
Unraveling the relationship between cancer and life history traits in vertebrates
Authors: Bulls Stephanie E. , Platner Laura , Ayub Wania , Moreno Nickolas , Arditi Jean-Pierre , Dreyer Saskia , McCain Stephanie , Wagner Philipp , Burgstaller Silvia , Davis Leyla R. , Bruins - van Sonsbeek Linda GR. , Fischer Dominik , Lynch Vincent J. , Claude Julien , Glaberman Scott , Chiari Ylenia
Published: July 2022

Identifying species with unusually low cancer prevalence can provide new insights into cancer resistance. Most studies have focused on mammals, but the genetic, physiological, and ecological diversity among vertebrates can influence cancer susceptibility. We used necropsies from over a thousand species of amphibians, birds, crocodilians, mammals, squamates, and turtles to investigate relationships between cancer prevalence, intrinsic cancer risk, body mass, and lifespan. Previous studies often relied on species averages, leading to inaccurate interpretations. Our innovative statistical approach uses raw cancer data and resampling to improve accuracy. We found remarkably low cancer prevalence in turtles, high prevalence in squamates and mammals, and lower-than-expected prevalence based on lifespan and body mass in multiple groups. Our results show lifespan influences neoplasia and malignancy transformation rates in mammals, while body mass affects neoplasia prevalence in amphibians and squamates. These data reveal a complex relationship between life history traits and cancer risk, identifying vertebrates with potential novel cancer resistance mechanisms.

STATEMENT OF SIGNIFICANCE

Biodiversity is an untapped natural resource for understanding cancer. Our study reveals a wide divergence in cancer prevalence among vertebrate groups, with notably low rates in turtles and high rates in squamates and mammals. These findings can lead to new breakthroughs in understanding the biology of cancer.
Including Phylogenetic Conservatism of Shortgrass Prairie Restoration Species Does Not Improve Species Germinability Prediction
Authors: Chen Yanni , Schwilk Dylan W. , Cox Robert D. , Johnson Matthew G.
Published: July 2022

PREMISE

We investigated whether phylogenetic conservatism can improve the performance of seed germinability prediction models. Previous studies in tallgrass prairie and alpine meadow revealed that seed morphological traits demonstrate phylogenetic conservatism. We hypothesized that phylogenetic conservatism in seed traits could help predict the seed germinability, under the assumption that seed traits contain phylogenetic signals.

METHODS

We measured seed germination percentage and seed morphological traits (seed mass, seed height, and seed surface area) on 34 native species from shortgrass prairie in North America. We supplemented these data with similar data from the literature on 11 more species. We calculated the robustness of the phylogenetic signal of each trait to the number of species sampled. We also compressed the phylogenetic distance matrix to a two-dimensional space, and applied the Akaike information criterion to evaluate the effects of phylogeny on seed germinability prediction models.

KEY RESULTS

We found weak but significant phylogenetic signals in seed mass and seed height in the full data set. These phylogenetic signals were not able to improve seed germinability prediction model performance among shortgrass prairie species. Our robustness tests of phylogenetic signals using random sub-sampling showed that the detection rate of phylogenetic signals in seed mass was increased along with the expansion of species pool, and nearly 100% at 40 species. However, the detection rate of phylogenetic signals in seed height was constantly low, around 20%.

CONCLUSIONS

When the phylogenetic signals are weak, the phylogenetic position does not improve germinability prediction model performance. Therefore, phylogenetic signals detected during a single species pool calculation may not accurately reflect the phylogenetic conservatism of the trait in a plant community. We suggest testing for robustness of phylogenetic signals using random sub-sampling tests.
Visualization of Retroplacental Clear Space Disruption in a Mouse Model of Placental Accreta
Authors: Badachhape Andrew A. , Bhandari Prajwal , Devkota Laxman , Srivastava Mayank , Tanifum Eric A. , George Verghese , Fox Karin A. , Yallampalli Chandrasekhar , Annapragada Ananth V. , Ghaghada Ketan B.
Published: July 2022

Introduction

Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work we characterized RPCS disruption in a mouse model of placenta accreta spectrum (PAS) using these agents.

Methods

Contrast-enhanced MRI (CE-MRI) and computed tomography (CE-CT) using liposomal nanoparticles bearing gadolinium (liposomal-Gd) and iodine were performed in pregnant Gab3-/- and wild type (WT) mice at day 16 of gestation. CE-MRI was performed on a 1T scanner using a 2D T1-weighted sequence (100×100×600 µm3 voxels) and CE-CT was performed at a higher resolution (70×70×70 µm3 voxels). Animals were euthanized post-imaging and feto-placental units (FPUs) were harvested for histological examination. RPCS conspicuity was scored through blinded assessment of images.

Results

Pregnant Gab3-/- mice show elevated rates of complicated pregnancy. Contrast-enhanced imaging demonstrated frank infiltration of the RPCS of Gab3-/- FPUs. RPCS in Gab3-/- FPUs was smaller in volume, demonstrated a heterogeneous signal profile, and received lower conspicuity scores than WT FPUs. Histology confirmed in vivo findings and demonstrated staining consistent with a thinner RPCS in Gab3-/- FPUs.

Discussion

Imaging of the Gab3-/- mouse model at late gestation with liposomal contrast agents enabled in vivo characterization of morphological differences in the RPCS that could cause the observed pregnancy complications. An MRI-based method for visualizing the RPCS would be valuable for early detection of invasive placentation.
ModelArray: a memory-efficient R package for statistical analysis of fixel data
Authors: Zhao Chenying , Tapera Tinashe M. , Bagautdinova Joëlle , Bourque Josiane , Covitz Sydney , Gur Raquel E. , Gur Ruben C. , Larsen Bart , Mehta Kahini , Meisler Steven L. , Murtha Kristin , Muschelli John , Roalf David R. , Sydnor Valerie J. , Valcarcel Alessandra M. , Shinohara Russell T. , Cieslak Matthew , Satterthwaite Theodore D.
Published: July 2022

Diffusion MRI is the dominant non-invasive imaging method used to characterize white matter organization in health and disease. Increasingly, fiber-specific properties within a voxel are analyzed using fixels. While tools for conducting statistical analyses of fixel data exist, currently available tools are memory intensive, difficult to scale to large datasets, and support only a limited number of statistical models. Here we introduce ModelArray, a memory-efficient R package for mass-univariate statistical analysis of fixel data. With only several lines of code, even large fixel datasets can be analyzed using a standard personal computer. At present, ModelArray supports linear models as well as generalized additive models (GAMs), which are particularly useful for studying nonlinear effects in lifespan data. Detailed memory profiling revealed that ModelArray required only limited memory even for large datasets. As an example, we applied ModelArray to fixel data derived from diffusion images acquired as part of the Philadelphia Neurodevelopmental Cohort (n=938). ModelArray required far less memory than existing tools and revealed anticipated nonlinear developmental effects in white matter. Moving forward, ModelArray is supported by an open-source software development model that can incorporate additional statistical models and other imaging data types. Taken together, ModelArray provides an efficient and flexible platform for statistical analysis of fixel data.

HIGHLIGHTS

ModelArray is an R package for mass-univariate statistical analysis of fixel data

ModelArray is memory-efficient even for large-scale datasets

ModelArray supports linear and nonlinear modeling and is extensible to more models

ModelArray facilitates easy statistical analysis of large-scale fixel data

Graphical abstract
Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments
Authors: Goel Viraat Y. , Huseyin Miles K. , Hansen Anders S.
Published: July 2022

Although enhancers are central to the regulation of mammalian gene expression, the mechanisms underlying Enhancer-Promoter (E-P) interactions remain unclear. Chromosome conformation capture (3C) methods effectively capture large-scale 3D genome structure but struggle to achieve the depth necessary to resolve fine-scale E-P interactions. Here, we develop Region Capture Micro-C (RCMC) by combining MNase-based 3C with a tiling region-capture approach and generate the deepest 3D genome maps reported thus far with only modest sequencing. By applying RCMC in mouse embryonic stem cells and reaching the genome-wide equivalent of ∼200 billion unique contacts, RCMC reveals previously unresolvable patterns of highly nested and focal 3D interactions, which we term microcompartments. Microcompartments frequently connect enhancers and promoters and are largely robust to loss of loop extrusion and inhibition of transcription. We therefore propose that many E-P interactions form through a compartmentalization mechanism, which may explain why acute cohesin depletion only modestly affects global gene expression.
Dual-stream cortical feedbacks mediate sensory prediction
Authors: Chu Qian , Ma Ou , Hang Yuqi , Tian Xing
Published: July 2022

Predictions are constantly generated from diverse sources to optimize cognitive functions in the ever-changing environment. However, the neural origin and generation process of top-down induced prediction remain elusive. We hypothesized that motor-based and memory-based predictions are mediated by distinct feedback networks from motor and memory systems to the sensory cortices. Using fMRI and a dual imagery paradigm, we showed that motor and memory upstream systems excited the auditory cortex in a content-specific manner. Moreover, the inferior and posterior parts of the parietal lobe differentially relayed predictive signals in motor-to-sensory and memory-to-sensory networks. Our results reveal the functionally distinct neural networks that mediate top-down sensory prediction and ground the neurocomputational basis of predictive processing.
Genome assembly of the polyclad flatworm Prostheceraeus crozieri
Authors: Leite Daniel J. , Piovani Laura , Telford Maximilian J.
Published: July 2022

Polyclad flatworms are widely thought to be one of the least derived of the flatworm classes and, as such, are well placed to investigate evolutionary and developmental features such as spiral cleavage and larval diversification lost in other platyhelminths. Prostheceraeus crozieri, formerly Maritigrella crozieri, is an emerging model polyclad flatworm that already has some useful transcriptome data but, to date, no sequenced genome. We have used high molecular weight DNA extraction and long read PacBio sequencing to assemble the highly repetitive (67.9%) P. crozieri genome (2.07 Gb). We have annotated 43,325 genes, with 89.7% BUSCO completeness. Perhaps reflecting its large genome, introns were considerably larger than other free-living flatworms, but evidence of abundant transposable elements suggests genome expansion has been principally via transposable elements activity. This genome resource will be of great use for future developmental and phylogenomic research.
Qualitative and quantitative analysis of the constitutive bark of Q. ilex x Q. suber hybrids
Authors: de Burgos Gonzalo , Díez-Morales Eduardo , López de Heredia Unai , Soto Álvaro
Published: July 2022

Hybridization and introgression between cork oak (Quercus suber) and holm oak (Q. ilex) have traditionally been reckoned as undesirable processes, since hybrid individuals lack the profitable bark characteristics of cork oak. Nevertheless, a systematic and quantitative description of the bark of these hybrids at the microscopic level based on a significant number of individuals was not available to date.

In this work we provide such a qualitative and quantitative description, identifying the most relevant variables for their classification. Hybrids show certain features intermediate between those of the parent species, as well as other unique features, as the general suberization of inactive phloem, reported here for the first time. These results suggest a relevant hybridization-induced modification of the genetic expression patterns. Therefore, hybrid individuals provide a valuable material to disentangle the molecular mechanisms underpinning bark development in angiosperms.
Noise correlations in the owl optic tectum are differentially impacted by unimodal vs crossmodal competitors
Authors: Totten Douglas J , DeBello William M
Published: July 2022

Multisensory integration in mammalian superior colliculus and its avian homolog, the optic tectum, is essential for rapid orienting towards salient stimuli. The benefits of combining across modalities is expected to depend in part on interneuronal noise correlations (NCs) and trial-to-trial response variance (Fano factor; FF), yet there is scant data on these topics. Here we used multielectrode arrays (MEAs) to record simultaneously from cohorts of single units in the deep layers of the owl optic tectum (OTd). Stimuli were presented individually or simultaneously as spatially aligned or non-aligned competitors. NC values varied from -0.35 to 0.94, an unexpectedly large range, and decreased only modestly as receptive fields diverged. Spatially aligned bimodal stimuli summed in a largely additive fashion over a wide range of response magnitudes. Most of the observed variance in bimodal NCs and FFs could be accounted for by an additive rule without accounting for internal noise. For non-aligned stimuli, crossmodal competitors decreased FFs, whereas unimodal competitors did not. Most striking, visual competitors decreased NCs for auditory drivers but increased NCs for visual drivers, indicating that the OTd network is differentially wired to process bimodal competitors. In total, these data provide novel descriptive information regarding the correlational structure of OTd neurons underlying multisensory processing.

SIGNIFICANCE STATEMENT

In the owl auditory midbrain and its mammalian homologs, little is known regarding the ensemble response properties during multisensory integration. Using microelectrode arrays we found that noise correlations between pairs of neurons evoked by auditory, visual and bimodal stimuli were large and variable. When two non-aligned (competitor) stimuli were presented simultaneously, response reliability and noise correlations were driven down for crossmodal but not unimodal competitors, which suggests distinct processing strategies. This novel finding predicts that visual competitors drive an increase in localization accuracy for auditory targets.
Rewiring Dynamics of Functional Connectome in Motor Cortex during Motor Skill Learning
Authors: Meamardoost Saber , Hwang EunJung , Bhattacharya Mahasweta , Ren Chi , Wang Linbing , Mewes Claudia , Zhang Ying , Komiyama Takaki , Gunawan Rudiyanto
Published: July 2022

The brain’s connectome continually rewires throughout the life of an organism. In this study, we sought to elucidate the operational principles of such rewiring by analyzing the functional connectomes in mouse primary motor cortex (M1) during a 14-session (day) lever-press task learning in response to an auditory cue. Specifically, we employed Calcium imaging recordings of L2/3 and L5 of M1 in awake mice to reconstruct and analyze functional connectomes across learning sessions. Our results show that functional connectomes in L2/3 and L5 follow a similar learning-induced rewiring trajectory. More specifically, the connectomes rewire in a biphasic manner, where functional connectivity increases over the first few learning sessions, and then, it is gradually pruned to return to a homeostatic level of network density. We demonstrated that the increase of network connectivity in L2/3 connectomes, but not in L5, generates neuronal co-firing activity that correlates with higher motor performance (shorter cue-to-reward time), while motor performance remains relatively stable throughout the pruning phase. The results show a biphasic rewiring principle that involves the maximization of reward / performance and maintenance of network density. Finally, we demonstrated that the connectome rewiring in L2/3 is clustered around a core set of movement-associated neurons that form a highly interconnected hub in the connectomes, and that the activity of these core neurons stably encodes movement throughout learning.

Significance Statement

Connectomes in the motor cortex rewire during motor skill learning, but the operational principle behind this rewiring is yet to be determined. Here, we characterized the rewiring dynamics of functional connectomes in L2/3 and L5 of M1 in mice engaging in a lever-press learning, using two-photon fluorescence microscopy data. We identified a universal biphasic rewiring trajectory across animals and layers in the motor cortex that reflects two objectives: an exploratory phase that increases functional connectivity and optimizes motor performance, and a pruning phase that brings connectivity back to a homeostatic level while maintaining motor performance. We found further that connectome rewiring during motor skill learning concentrates around a core set of highly interconnected neurons in L2/3 that reliably encode movements.
Innexin-mediated adhesion between glia is required for axon ensheathment in the peripheral nervous system
Authors: Das Mriga , Cheng Duo , Matzat Till , Auld Vanessa J.
Published: July 2022

Glia are essential to protecting and enabling nervous system function and a key glial function is the formation of the glial sheath around peripheral axons. Each peripheral nerve in the Drosophila larva is ensheathed by three glial layers, which structurally support and insulate the peripheral axons. How peripheral glia communicate with each other and between layers is not well established and we investigated the role of Innexins in mediating glial function in the Drosophila periphery. Of the eight Drosophila Innexins, we found two (Inx1 and Inx2) are important for peripheral glia development. In particular loss of Inx1 and Inx2 resulted in defects in the wrapping glia leading to disruption of the glia wrap. Of interest loss of Inx2 in the subperineurial glia also resulted in defects in the neighbouring wrapping glia. Inx plaques were observed between the subperineurial glia and the wrapping glia suggesting that gap junctions link these two glial cell types. We found Inx2 is key to Ca+2 pulses in the peripheral subperineurial glia but not in the wrapping glia, and we found no evidence of gap junction communication between subperineurial and wrapping glia. Rather we have clear evidence that Inx2 plays an adhesive and channel-independent role between the subperineurial and wrapping glia to ensure the integrity of the glial wrap.
Involuntary breathing movement pattern recognition and classification via force based sensors
Authors: Singh Rajat Emanuel , Fleury Jordan M. , Gupta Sonu , Bachman Nate P. , Alumbaugh Brent , White Gannon
Published: July 2022

The study presents a novel scheme that recognizes and classifies different sub-phases within the involuntary breathing movement (IBM) phase during breath-holding (BH). We collected force data from eight recreational divers until the conventional breakpoint (CB). They were in a supine position on force plates. We segmented their data into the no-movement (NM) phase aka easy phase and IBM phase (comprising several events or sub-phases of IBM). The acceleration and jerk were estimated from the data to quantify the IBMs, and phase portraits were developed to select and extract specific features. The K means clustering was performed on these features to recognize different sub-phases within the IBM phase. We found five-six optimal clusters separating different sub-phases within the IBM phase. These clusters separating different sub-phases have physiological relevance to internal struggle and were labeled as classes for classification using support vector machine (SVM), naive bayes (NB), decision tree (DT), and K-nearest neighbor (K-NN). In comparison with no feature selection and extraction, we found that our phase portrait method of feature selection and extraction had a low computational cost and high robustness of 96–99% accuracy.
GBZ File Format for Pangenome Graphs
Authors: Sirén Jouni , Paten Benedict
Published: July 2022

Motivation

Pangenome graphs representing aligned genome assemblies are being shared in the text-based Graphical Fragment Assembly format. As the number of assemblies grows, there is a need for a file format that can store the highly repetitive data space-efficiently.

Results

We propose the GBZ file format based on data structures used in the Giraffe short read aligner. The format provides good compression, and the files can be efficiently loaded into in-memory data structures. We provide compression and decompression tools and libraries for using GBZ graphs, and we show that they can be efficiently used on a variety of systems.

Availability

C++ and Rust implementations are available athttps://github.com/jltsiren/gbwtgraphandhttps://github.com/jltsiren/gbwt-rs, respectively.

Contact

jouni.siren@iki.fi

Supplementary information

Supplementary data are available online.
Graph-Based Pharmacokinetic-Pharmadynamic Modeling for Large Scale Systems: Nanoparticles Case
Authors: Lazebnik Teddy , Weitman Hanna , Kaminka Gal A.
Published: July 2022

Pharmaceutical nanoparticles (NPs) carrying molecular payloads are used for medical purposes such as diagnosis and medical treatment. They are designed to modify the pharmacokinetics-pharmacodynamics (PKPD) of their associated payloads, to obtain better clinical results. Currently, the research process of discovering the PKPD properties of new candidates for efficient clinical treatment is complicated and time-consuming.In silicoexperiments are known to be powerful tools for studying biological and clinical processes and therefore can significantly improve the process of developing new and optimizing current NPs-based drugs. However, the current PKPD models are limited by the number of parameters they can take into consideration and the ability to solve large-scalein vivosettings, thus providing relatively large errors in predicting treatment outcomes. In this study, we present a novel mathematical graph-based model for PKPD of NPs-based drugs. The proposed model is based on a population of NPs performing a directed walk on a graph describing the blood vessels and organs, taking into consideration the interactions between the NPs and their environment. In addition, we define a mechanism to perform different prediction queries on the proposed model to analyze twoin vivoexperiments with eight different NPs, done on mice, obtaining a fitting of 0.84 ± 0.01 and 0.66 ± 0.01 (mean ± standard deviation), respectively, comparing thein vivovalues and thein silicoresults.
In search of a brain microbiome: A machine learning search pipeline for electron microscopy images of brain tissue
Authors: Matelsky Jordan K. , Shih Celina , Hijazi Khalil , Johnson Erik C.
Published: July 2022

The healthy human brain has long been considered a sterile environment, with the blood brain barrier preventing the formation of a bacterial brain microbiome. Recent electron microscopy (EM) imaging of brain tissue has, however, provided the first preliminary evidence of bacteria in otherwise healthy brain slices. Whether due to contamination, disease, or a previously unknown relationship of bacteria to healthy brain tissue, novel tools are needed to detect and search for bacteria in nanoscale, volumetric EM images. While computer vision tools are widely used in cell segmentation and object detection problems in EM imaging, no bacteria detection tool or dataset exists. Overcoming the rarity of training data, this work presents the first pipeline for training a bacteria detection network for EM images, leveraging existing deep networks for object detection. A deployment and proofreading pipeline is presented, along with characterization of deployment to public EM image datasets. While bacteria in healthy brain tissue were not discovered in this work, this tool presents an opportunity for large scale bacteria search in EM imaging for both scientific discovery and experimental quality control, and serves more generally as a framework for sparse object detection in large imagery datasets.
Variation in whole-body regeneration between Botrylloides morphs and species
Authors: Temiz Berivan , Wilson Megan J.
Published: July 2022

Regeneration is a characteristic of the animal kingdom, and regenerative capacity is limited to higher taxonomical levels. In contrast, some basal animals like urochordates maintain a unique regeneration capacity, such as undergoing whole-body regeneration (WBR), an ability not observed in other chordates. Botryllids are colonial urochordates that can recreate new bodies through WBR from solely vascular tissue within ~2 weeks. To date, some species from the botryllid family were reported to orchestrate WBR, including B. diegensis. This study provided two novel records of WBR of B. jacksonianum and B. aff. anceps along with the two distinct morphs of B. diegensis. Interestingly, B. aff. anceps executed twin-body regeneration while this was limited to one-body for B. jacksonianum and B. diegensis. Histological sections validate the formation of multiple niches during WBR. Furthermore, the process of regeneration is phenotypically more similar between B. aff. anceps and B. diegensis. In contrast, the type of WBR in B. jacksonianum is similar to vascular budding as the niches were built from the vascular epithelium without undergoing significant tissue remodelling.
Three consecutive glycolysis enzymes are involved in autophagic flux regulation through monitoring nutrient availability
Authors: Lee Du-Hwa , Choi Ilyeong , Park Seung Jun , Kim Sumin , Choi Min-Soo , Lee Ho-Seok , Pai Hyun-Sook
Published: July 2022

Autophagy serves as an important recycling route for growth and survival of eukaryotic organisms in nutrient-deficient conditions. When confronted with starvation, metabolic flux is coordinated by individual metabolic enzymes. Given that the metabolic diversity of carbon in eukaryotes is related to their lifestyle, autophagy may be modulated by metabolic enzymes by monitoring carbon flux. Here, we attempted to identify carbon metabolic genes that modulate autophagy using VIGS screening of 45 glycolysis- and the Calvin-Benson cycle-related genes. We report here that three consecutive triose-phosphate-processing enzymes involved in the cytosolic glycolysis, TPI (triose-phosphate-isomerase), GAPC (glyceraldehyde-3-phosphate dehydrogenase), and PGK (phosphoglycerate kinase), designated TGP, negatively regulate autophagy. Depletion of TGP enzymes result in spontaneous autophagy induction and increases ATG1 kinase activity. TGP enzymes interact with ATG101, a regulatory component of the ATG1 kinase complex. Spontaneous autophagy induction and abnormal growth under insufficient sugar in the TGP mutants is suppressed by crossing with the atg101 mutant. Considering that triose-phosphates are photosynthates transported to the cytosol from active chloroplasts, the TGP enzymes may be strategically positioned to monitor the flow of photosynthetic sugars and modulate autophagy accordingly. Collectively, these results suggest that TGP enzymes negatively control autophagy acting upstream of the ATG1 complex, which is critical for seedling development.
Genetic screens identified dual roles of MAST kinase and CREB within a single thermosensory neuron in the regulation of C. elegans thermotaxis behavior
Authors: Nakano Shunji , Nakayama Airi , Kuroyanagi Hiroo , Yamashiro Riku , Tsukada Yuki , Mori Ikue
Published: July 2022

Animals integrate sensory stimuli presented at the past and present, assess the changes in their surroundings and navigate themselves toward preferred environment. Identifying the molecular and circuit mechanisms of such sensory integration is pivotal to understand how the nervous system generates perception and behavior. Previous studies on thermotaxis behavior of Caenorhabditis elegans suggested that a single thermosensory neuron AFD plays an essential role in integrating the past and present temperature information and is essential for the neural computation that drives the animal toward the preferred temperature region. However, the molecular mechanisms by which AFD executes this neural function remained elusive. Here we report multiple forward genetic screens to identify genes required for thermotaxis. We reveal that kin-4, which encodes the C. elegans homolog of MAST kinase, plays dual roles in thermotaxis and can promote both cryophilic and thermophilic drives. We also uncover that a thermophilic defect of mutants for mec-2, which encodes a C. elegans homolog of stomatin, can be suppressed by a loss-of-function mutation in the gene crh-1, encoding a C. elegans homolog CREB transcription factor. Calcium imaging analysis from freely-moving animals suggest that mec-2 and crh-1 function in AFD and regulate the neuronal activity of its post-synaptic interneuron AIY. Our results suggest that a stomatin family protein can control the dynamics of neural circuitry through the transcriptional regulation within a sensory neuron.
Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals
Authors: Winnett Alexander Viloria , Akana Reid , Shelby Natasha , Davich Hannah , Caldera Saharai , Yamada Taikun , Reyna John Raymond B. , Romano Anna E. , Carter Alyssa M. , Kim Mi Kyung , Thomson Matt , Tognazzini Colten , Feaster Matthew , Goh Ying-Ying , Chew Yap Ching , Ismagilov Rustem F.
Published: July 2022

Background

In a recent household-transmission study of SARS-CoV-2, we found extreme differences in SARS-CoV-2 viral loads among paired saliva, anterior-nares swab (ANS) and oropharyngeal swab specimens collected from the same timepoint. We hypothesized these differences may hinder low-analytical-sensitivity assays (including antigen rapid diagnostic tests, Ag-RDTs) using a single specimen type (e.g., ANS) from reliably detecting infected and infectious individuals.

Methods

We evaluated a daily at-home ANS Ag-RDT (Quidel QuickVue) in a cross-sectional analysis of 228 individuals and in a longitudinal analysis (throughout infection) of 17 individuals enrolled early in the course of infection. Ag-RDT results were compared to RT-qPCR results and high, presumably infectious viral loads (in each, or any, specimen type).

Results

The ANS Ag-RDT correctly detected only 44% of timepoints from infected individuals on cross-sectional analysis, and in this population had an inferred limit of detection of 7.6×106copies/mL. From the longitudinal cohort, daily Ag-RDT clinical sensitivity was very low (<3%) during the early, pre-infectious period of the infection. Further, the Ag-RDT detected ≤63% of presumably infectious timepoints. The poor observed clinical sensitivity of the Ag-RDT was similar to what was predicted based on quantitative ANS viral loads and the inferred limit of detection of the ANS Ag-RDT being evaluated, indicating high-quality self-sampling.

Conclusion

Nasal Ag-RDTs, even when used daily, can miss individuals infected with the Omicron variant and even those presumably infectious. Evaluations of Ag-RDT detection of infected or infectious individuals should be compared with a composite (multi-specimen) infection status to correctly assess performance.

Key points

Nasal-swab rapid antigen tests have low analytical sensitivity and the sampling of only the nasal cavity hinders their ability to detect infected individuals, including those with high and presumably infectious viral loads in throat or saliva specimens.
Long COVID in Cancer patients: Preponderance of Symptoms in Majority of Patients over Long Time Period
Authors: Dagher Hiba , Chaftari Anne-Marie , Subbiah Ishwaria M. , Malek Alexandre E. , Jiang Ying , Lamie Peter , Granwehr Bruno , John Teny , Yepez Eduardo , Borjan Jovan , Reyes Cielito , Flores Mary , Khawaja Fareed , Pande Mala , Ali Noman , Rojo Raniv , Karp Daniel D. , Hachem Ray , Raad Issam
Published: July 2022

Background

An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery.

Methods

We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020 and Sept 1, 2020 and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients’ electronic medical records to capture the the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months.

Results

We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%) and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%) and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were readmitted for COVID-related reasons.

Conclusions

More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even one year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia and gastro-intestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8,5% requiring a COVID-19 related re-admission.
Procalcitonin for Antimicrobial Stewardship Among Cancer Patients Admitted with COVID-19
Authors: Dagher Hiba , Chaftari Anne-Marie , Mulanovich Patricia , Jiang Ying , Hachem Ray , Malek Alexandre E. , Borjan Jovan , Viola George M. , Raad Issam
Published: July 2022

Background

Procalcitonin (PCT) has been used to guide antibiotic therapy in bacterial infections. We aimed to determine the role of PCT in decreasing the duration of empiric antibiotic therapy among cancer patients admitted with COVID-19.

Methods

This retrospective study included cancer patients admitted to our institution for COVID-19 between March 1, 2020, and June 28, 2021, with a PCT test done within 72 hours after admission. Patients were divided into 2 groups: PCT <0.25 ng/ml and PCT ≥0.25 ng/ml. We assessed pertinent cultures, antibacterial use, and duration of empiric antibacterial therapy.

Results

The study included 530 patients (median age, 62 years [range, 13-91]). All the patients had ≥1 culture test within 7 days following admission. Patients with PCT <0.25 ng/ml were less likely to have a positive culture than were those with PCT ≥0.25 ng/ml (6% [20/358] vs 17% [30/172]; p<0.0001). PCT <0.25 ng/ml had a high negative predictive value for bacteremia and 30-day mortality. Patients with PCT <0.25 ng/ml were less likely to receive intravenous (IV) antibiotics for >72 hours than were patients with PCT ≥0.25 ng/ml (45% [162/358] vs 69% [119/172]; p<0.0001). Among patients with PCT <0.25 ng/ml and negative cultures, 30-day mortality was similar between those who received IV antibiotics for ≥72 hours and those who received IV antibiotics for shorter durations (2% [2/111] vs 3% [5/176], p=0.71).

Conclusions

Among cancer patients with COVID-19, PCT level <0.25 ng/ml is associated with lower likelihood of bacterial co-infection and greater likelihood of a shorter antibiotic course. In patients with PCT level <0.25 ng/ml and negative cultures, an antibiotic course of > 72 hours is unnecessary. PCT could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19.
Effect of psilocybin on marble-burying in ICR mice: Role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder
Authors: Singh Sandeep , Botvinnik Alexander , Shahar Orr , Wolf Gilly , Yakobi Corel , Saban Michal , Salama Adham , Lotan Amit , Lerer Bernard , Lifschytz Tzuri
Published: July 2022

Background

Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble-burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder.

Aims

To explore 1) the role of 5-HT2A and 5-HT1A receptors in the effect of psilocybin on marble-burying; 2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; 3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head-twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects.

Methods

Male ICR mice were administered psilocybin 4.4 mg/kg, escitalopram 5 mg/kg, 8-OH-DPAT 2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the MBT. HTR was examined in a magnetometer-based assay.

Results

1) Psilocybin and escitalopram significantly reduced marble-burying. The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907. The 5-HT1A agonist, 8-OH-DPAT reduced marble-burying as did the 5-HT1A partial agonist, buspirone. The effect of 8-OH-DPAT was additive to that of psilocybin but that of buspirone was not. The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin. 2) Psilocybin injections over 3.5 hours had no effect on marble-burying and the effect of bolus injection was not persistent. 3) Co-administration of buspirone with psilocybin blocked its effect on HTR

Conclusions

Neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble-burying. Co-administration with buspirone may block the psychedelic effects of psilocybin without impeding its anti-obsessional effects.
The genome of the oomycete Peronosclerospora sorghi, a cosmopolitan pathogen of maize and sorghum, is inflated with dispersed pseudogenes
Authors: Fletcher Kyle , Martin Frank , Isakeit Thomas , Cavanaugh Keri , Magill Clint , Michelmore Richard
Published: July 2022

Several species in the oomycete genus Peronosclerospora cause downy mildew on maize and can result in significant yield losses in Asia. Biosurveillance of these pathogens is a high priority to prevent epidemics on maize in the US and consequent damage to the US economy. The unresolved taxonomy and dearth of molecular resources for Peronosclerospora spp. hinder these efforts. P. sorghi is a pathogen of sorghum and maize with a global distribution, for which limited diversity has been detected in the southern USA. We characterized the genome, transcriptome, and mitogenome of an isolate, representing the US pathotype 6. The highly homozygous genome was assembled using 10x Genomics linked reads and scaffolded using Hi-C into 13 chromosomes. The total assembled length was 319.6 Mb—larger than any other oomycete previously assembled. The mitogenome was 38 kb, similar in size to other oomycetes, although it had a unique gene order. Nearly 20,000 genes were annotated in the nuclear genome, more than described for other downy mildew causing oomycetes. The 13 chromosomes of P. sorghi were highly syntenic with the 17 chromosomes of Peronospora effusa with conserved centromeric regions and distinct chromosomal fusions. The increased assembly size and gene count of P. sorghi is due to extensive retrotransposition, resulting in putative pseudogenization. Ancestral genes had higher transcript abundance and were enriched for differential expression. This study provides foundational resources for analysis of Peronosclerospora and comparisons to other oomycete genera. Further genomic studies of global Peronosclerospora spp. will determine the suitability of the mitogenome, ancestral genes, and putative pseudogenes for marker development and taxonomic relationships.
M1 and M2 macrophages differentially regulate colonic crypt renewal
Authors: Raveenthiraraj Sathuwarman , Awanis Griselda , Chieppa Marcello , Sobolewski Anastasia
Published: July 2022

The colonic epithelium is the most rapidly renewing tissue in the body and is organized into a single cell layer of invaginations called crypts. Crypt renewal occurs through Lgr5+ gut stem cells situated at the crypt base, which divide, produce daughter cells that proliferate, migrate, differentiate into all the cells required for normal gut function (eg. Goblet cells, enterocytes), and are finally shed into the crypt lumen. In health this rapid renewal helps maintain barrier function next to the hostile gut luminal environment that contains microbes and food. In parallel, the peri-cryptal lamina propria hosts the largest monocyte-derived macrophage population in the human body. Different macrophage phenotypes have been associated with intestinal health/intact barrier function, namely M2 compared to M1 macrophages that indicate inflammation/compromised barrier function. However, the direct effect of different macrophage subtypes have on colonic crypt renewal is not well understood. In this study we have utilized a reductionist 3D in vitro co-culture model to determine the regulatory capacity of M1 and M2 macrophages on colonic crypt renewal. We show that colonic crypt proliferation is increased in the presence of M1 or M2 macrophages, while we further demonstrate that a decrease in goblet and tuft cell expression as well as an increase in Lgr5+ stem cell numbers is only achieved through M1-crypt crosstalk in a contact dependent manner.
Generic Purpose Pharmacokinetics-Pharmacodynamics Mathematical Model For Nanomedicine Targeted Drug Delivery: Mouse Model
Authors: Lazebnik Teddy , Weitman Hanna , Kaminka Gal A.
Published: July 2022

Pharmaceutical nanoparticles (NPs) carrying molecular payloads are used for medical purposes such as diagnosis and medical treatment. Currently, the research process of discovering a new applicative candidate for efficient clinical treatment is a time- and resource-consuming process due to the uncertainty of how NP behaves which requires a large number of experiments to study the properties of NPs-based drugs for clinical usage. In silico experiments are known to be powerful tools for studying biological and clinical systems and evaluating a drug’s efficiency, which can significantly reduce the number of in vivo experiments required. To this extent, in this study, we present a novel spatio-temporal pharmacokinetics-pharmacodynamics (PKPD) model of NPs based drugs. The proposed model takes into consideration the blood flow in the cardiovascular system as well as PKPD dynamics taking place during the drug’s flow and in the target sites. We show that the proposed model has a better fidelity compared to previous models on five in vivo experiments with 13 different NPs, done on mice.
Placement of new comb cells built by honeybees is guided by sub-cell scale features to align with the existing layout
Authors: Gallo Vincent , Bridges Alice , Woodgate Joseph , Chittka Lars
Published: July 2022

The comb of honeybees has long been the subject of curiosity and admiration. Its noteworthy features include the even hexagonal layout and the sharing of walls, both side walls and bases, that provide a maximum storage volume while using a minimum of wax for its construction. The efficiency of its structure relies on a regular layout where cells are positioned correctly relative to each other. Each new cell should be placed exactly between two previously constructed cells, a task made more difficult by the incomplete nature of cells at the edge of comb where the new ones are to be built. By offering bees shaped wax stimuli we have identified sub-cell scale shapes that trigger certain patterns of behaviour by honeycomb construction workers. These behaviours, we found, cause the creation of a new cell to be aligned to small concavities and for cell walls to be built mid-way between two such stimuli. We show that by responding to the form of partially constructed comb, the bees build the next iteration of cells and walls at the locations necessary for the repeated pattern of cells to continue.