bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of nasogastric tube on oral microbiome among long-term care patients
Authors: Wang Ding-Han , Tsai Fa-Tzu , Tu Hsi-Feng , Yang Cheng-Chieh , Hsu Ming-Lun , Huang Lin-Jack , Lin Chiu-Tzu , Hsu Wun-Eng , Lin Yu-Cheng
Published: September 2022

Dysbiosis of oral microbiome causes chronic diseases including dental caries and periodontitis, which frequently affects elderly, frail patients receiving long-term care. Severely disabled patients may require nutritional supply via nasogastric (NG) tube, which impacts patients’ oral condition and possibly microbial composition. However, little is known about the effect of NG tube on oral microbes and its potential ramification. Here, by using 16S rRNA next-generation sequencing, we characterized the tongue microbiome of 27 patients fed with NG tubes and 26 others fed orally. The microbial compositions of NG-tube and oral-feeding patients were substantially different, with more Gram-negative aerobes enriched in the presence of NG tube. Specifically, NG-tube patients presented more opportunistic pathogens like Corynebacterium and Pseudomonas associated with pneumonia, and lower levels of commensal Streptococcus and Veillonella. Together, we present a systematic, high-throughput profiling of oral microbiome with regards to NG tube indwelling, providing empirical evidence for better clinical practice.

Importance

Long-term use of NG tubes on elderly patients often leads to poor oral hygiene and chronic infectious diseases, e.g. periodontitis and tooth decay. More importantly, because patients fed with NG tubes usually have swallowing dysfunctions, they are more likely to suffer from aspiration pneumonia, a life-threatening lung infection caused by inhalation of oral bacteria. Together, clinical implications of chronic NG-tube indwelling are significantly related to oral microbes. Understanding the effects of NG tubes on oral microbiome would generally inform how clinical care should be given, particularly antimicrobial therapy.
A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer
Authors: Inglebert Marine , Dettwiler Martina , Hahn Kerstin , Letko Anna , Drögemüller Cord , Doench John , Brown Adam , Memari Yasin , Davies Helen , Degasperi Andrea , Nik-Zainal Serena , Rottenberg Sven
Published: September 2022

Mammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts. We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (CMT), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors. We established the long-term culture of 24 organoid lines from 16 patients, including organoids derived from normal mammary epithelium or benign lesions. CMT organoids recapitulated key morphological and immunohistological features of the primary tissue from which they were derived, including hormone receptor status. Furthermore, genetic characteristics (driver gene mutations, DNA copy number variations, and single-nucleotide variants) were conserved within tumororganoid pairs. We show how CMT organoids are a suitable model for in vitro drug assays and can be used to investigate whether specific mutations predict therapy outcomes. In addition, we could genetically modify the CMT organoids and use them to perform pooled CRISPR/Cas9 screening, where library representation was accurately maintained. In summary, we present a robust 3D in vitro preclinical model that can be used in translational research, where organoids from normal, benign as well as malignant mammary tissues can be propagated from the same patient to study tumorigenesis.
Developmental Basis of SHH Medulloblastoma Heterogeneity
Authors: Gold Maxwell P. , Ong Winnie , Masteller Andrew M. , Galindo Julie Anne , Park Noel R. , Saurez Raul A. , Vladoiu Maria C. , Donovan Laura K. , Walker Adam D. , Benetatos Joseph , Garzia Livia , Wechsler-Reya Robert J. , Mesirov Jill P. , Korshunov Andrey , Pomeroy Scott L. , Davidson Shawn M. , Cotter Jennifer A. , Taylor Michael D. , Fraenkel Ernest
Published: September 2022

Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. The sonic hedgehog (SHH) subtype accounts for 30% of MB cases and likely arises from mutations in granule cell precursors (GCPs), neuronal progenitors of the cerebellar cortex that differentiate into granule neurons. SHH MB is extremely heterogeneous, but it is unknown whether this heterogeneity relates to the tumors’ developmental origins. To investigate this question, we performed single-nucleus RNA-Sequencing on seven highly differentiated SHH MB with extensively nodular histology and observed malignant cells resembling each stage of granule neuron development. Using novel computational approaches, we connected these results to published datasets and found that established molecular subtypes of SHH MB are enriched for specific developmental cell types. Additionally, some genomic copy number variations are associated with certain developmental stages, and we observed distinct metabolic and histological profiles for tumors containing cells resembling late-stage granule neurons. This work details computational and experimental approaches that can be repurposed for analysis of tumor cell differentiation in other cancers.
Modelling perception as a hierarchical competition differentiates imagined, veridical, and hallucinated percepts
Authors: Sulfaro Alexander A , Robinson Amanda K , Carlson Thomas A
Published: September 2022

Mental imagery is a process by which thoughts become experienced with sensory characteristics. Yet, it is not clear why mental images appear diminished compared to veridical images, nor how mental images are phenomenologically distinct from hallucinations, another type of non-veridical sensory experience. Current evidence suggests that imagination and veridical perception share neural resources. If so, we argue that considering how neural representations of externally-generated stimuli (i.e. sensory input) and internally-generated stimuli (i.e. thoughts) might interfere with one another can sufficiently differentiate veridical, imaginary, and hallucinatory perception. We here use a simple computational model of a serially-connected, hierarchical network with bidirectional information flow to emulate the primate visual system. We show that modelling even first-approximations of neural competition can more coherently explain imagery phenomenology than non-competitive models. Our simulations predict that, without competing sensory input, imagined stimuli should ubiquitously dominate hierarchical representations. However, with competition, imagination should dominate high-level representations but largely fail to outcompete sensory inputs at lower processing levels. To interpret our findings, we assume low-level stimulus information (e.g. in early visual cortex) contributes most to the sensory aspects of perceptual experience, while high-level stimulus information (e.g. towards temporal regions) contributes most to its abstract aspects. Our findings therefore suggest that ongoing bottom-up inputs during waking life may prevent imagination from overriding veridical sensory experience. In contrast, internally-generated stimuli may be hallucinated when sensory input is dampened or eradicated. Our approach can explain individual differences in imagery, along with aspects of daydreaming, hallucinations, and non-visual mental imagery.
LncDLSM: Identification of Long Non-coding RNAs with Deep Learning-based Sequence Model
Authors: Wang Ying , Zhao Pengfei , Du Hongkai , Cao Yingxin , Peng Qinke , Fu Laiyi
Published: September 2022

Long non-coding RNAs (LncRNAs) serve a vital role in regulating gene expressions and other biological processes. Differentiation of lncRNAs from protein-coding transcripts helps researchers dig into the mechanism of lncRNA formation and its downstream regulations related to various diseases. Previous works have been proposed to identify lncRNAs, including traditional bio-sequencing and machine learning approaches. Considering the tedious work of biological characteristic-based feature extraction procedures and inevitable artifacts during bio-sequencing processes, those lncRNA detection methods are not always satisfactory. Hence, in this work, we presented lncDLSM, a deep learning-based framework differentiating lncRNA from other protein-coding transcripts without dependencies on prior biological knowledge. lncDLSM is a helpful tool for identifying lncRNAs compared with other biological feature-based machine learning methods and can be applied to other species by transfer learning achieving satisfactory results. Further experiments showed that different species display distinct boundaries among distributions corresponding to the homology and the specificity among species, respectively. An online web server is provided to the community for easy use and efficient identification of lncRNA, available athttp://39.106.16.168/lncDLSM.
Identifying the potential for sustainable human–wildlife coexistence by integrating willingness to coexist with habitat suitability models
Authors: Vogel Susanne Marieke , Vasudev Divya , Ogutu Joseph O. , Taek Purity , Berti Emilio , Goswami Varun R. , Kaelo Michael , Buitenwerf Robert , Munk Michael , Li Wang , Wall Jake , Gelete Desalegn Chala , Amoke Irene , Odingo Alice , Svenning Jens-Christian
Published: September 2022

Persistence of large mammals in the Anthropocene depends on human willingness to coexist with them, but this is rarely incorporated into habitat suitability or conservation priority assessments. We propose a framework that integrates human willingness-to-coexist with habitat suitability assessments to identify areas of high potential for sustainable coexistence. We demonstrate its applicability for elephants and rhinos in the socio-ecological system of Maasai Mara, Kenya, by integrating spatial distributions of people’s willingness-to-coexist based on Bayesian hierarchical models using 556 household interviews, with socio-ecological habitat suitability mapping validated with long-term elephant observations from aerial surveys. Willingness-to-coexist was higher if people had little personal experience with a species, and strongly reduced by experiencing a species as a threat to humans. The sustainable coexistence potential framework highlights areas of low socio-ecological suitability, and areas that require more effort to increase positive stakeholder engagement to achieve long-term persistence of large herbivores in human-dominated landscapes.
Regulation of neuropathic pain by microglial Orai1 channels
Authors: Tsujikawa Shogo , DeMeulenaere Kaitlyn E , Centeno Marivi V , Ghazisaeidi Shahrzad , Martin Megan E. , Tapies Martinna R. , Maneshi Mohammad M , Yamashita Megumi , Stauderman Kenneth A , Apkarian Apkar V , Salter Michael W , Prakriya Murali
Published: September 2022

Microglia are important mediators of neuroinflammation that underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity are not well-understood. We investigated the role of Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion of Orai1 in microglia attenuates Ca2+ signaling and the production of inflammatory cytokines by proalgesic agonists. Conditional deletion of Orai1 attenuated microglia proliferation in the dorsal horn, spinal cytokines levels, and potentiation of excitatory neurotransmission following peripheral nerve injury. These cellular effects were accompanied by mitigation of pain hyperalgesia in Orai1 knockout mice. A small-molecule Orai1 inhibitor, CM4620, similarly mitigated allodynia in male mice. Surprisingly, these protective effects were not seen in female mice, revealing striking sexual dimorphism in Orai1 regulation of microglial reactivity and hyperalgesia. These findings indicate that Orai1 channels are key regulators of the sexually dimorphic role of microglia for the neuroinflammation that underlies neuropathic pain.
Molecular Dynamics Simulations Show How Antibodies May Rescue HIV-1 Mutants Incapable of Infecting Host Cells
Authors: Rajendra Dharanish , Maroli Nikhil , Dixit Narendra M , Maiti Prabal K
Published: September 2022

High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells was found to be rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue is important to develop and improve antibody-based therapies. To unravel the underlying mechanisms, we performed fully atomistic molecular dynamics simulations of the HIV-1 gp41 trimer responsible for viral entry into host cells, its entry-deficient variant, and its complex with the rescuing antibody. We find that the Q563R mutation, which the entry-deficient variant carries, prevents the native conformation of the gp41 6-helix bundle required for entry and stabilizes an alternative conformation instead. This is the consequence of substantial changes in the secondary structure and interactions between the domains of gp41. Binding of the antibody F240 to gp41 reverses these changes and re-establishes the native conformation, resulting in rescue. To test the generality of this mechanism, we performed simulations with the entry-deficient L565A variant and antibody 3D6. We find that 3D6 binding was able to reverse structural and interaction changes introduced by the mutation and restore the native gp41 conformation. Viral variants may not only escape antibodies but be aided by them in their survival, potentially compromising antibody-based therapies, including vaccination and passive immunization. Our simulation framework could serve as a tool to assess the likelihood of such resistance against specific antibodies.
Gas modulating microcapsules for spatiotemporal control of hypoxia
Authors: Molley Thomas G. , Jiang Shouyuan , Kopecky Chantal , Ranaweera Chavinya D. , Jalandhra Gagan K. , Rnjak-Kovacina Jelena , Kilian Kristopher A.
Published: September 2022

Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 8% with deviations having major biological consequences. In this work, we developed an approach to encapsulate enzymes and nanozymes, at an unprecedented loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, and cancer spheroids. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourage neovascularization, providing scope for topical treatments or hydrogel wound dressings. We further demonstrate versatility by loading capsules with ceria nanorods as “nanozymes” to modulate active oxygen species with potential as a cytoprotective treatment. The approach can be used in multiple formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform’s simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials where controlling hypoxia may be clinically advantageous.
Structural basis of the transcription termination factor Rho engagement with transcribing RNA polymerase
Authors: Murayama Yuko , Ehara Haruhiko , Aoki Mari , Goto Mie , Yokoyama Takeshi , Sekine Shun-ichi
Published: September 2022

Transcription termination is an essential step in transcription by RNA polymerase (RNAP) and crucial for gene regulation. For many bacterial genes, transcription termination is mediated by the ATP-dependent RNA translocase/helicase Rho, which causes the dissociation of RNA/DNA from RNAP elongation complex (EC). However, structural basis of the interplay between Rho and RNAP remains obscure. Here we report the cryo-electron microscopy structure of the Rho-engaged EC. The Rho hexamer binds RNAP through the C-terminal domains, which surround the RNA-exit site of RNAP, directing the nascent RNA seamlessly from the RNA exit to the Rho central channel. The β-flap tip at the RNA exit is critical to the Rho-dependent RNA release, and its deletion causes an alternative Rho-RNAP binding mode, which is irrelevant to termination. The Rho-binding site overlaps with the binding sites of other macromolecules, such as ribosomes, providing a general basis of gene regulation.

Teaser

Cryo-EM captures the structure of an RNA polymerase elongation complex engaged with the termination factor Rho.
Contrasting genomic evolution between domesticated and wild Kluyveromyces lactis yeast populations
Authors: Friedrich Anne , Gounot Jean-Sébastien , Tsouris Andreas , Bleykasten Claudine , Freel Kelle , Caradec Claudia , Schacherer Joseph
Published: September 2022

The process of domestication has variable consequences on genome evolution leading to different phenotypic signatures. Access to the complete genome sequences of a large number of individuals makes it possible to explore the different facets of this domestication process. Here, we sought to explore the genome evolution of the Kluyveromyces lactis yeast species, a well-known species for its involvement in dairy processes but also present in natural environments. Using a combination of short and long-read sequencing strategies, we investigated the genomic variability of 41 Kluyveromyces lactis isolates and found that the overall genetic diversity of this species is very high (π = 2.9 x 10-2) compared to other species such as Saccharomyces cerevisiae (π = 3 x 10-3). However, the domesticated dairy population shows a reduced level of diversity (π = 7 x 10-4), probably due to a domestication bottleneck. In addition, this entire population is characterized by the introgression of the LAC4 and LAC12 genes, responsible for lactose fermentation and coming from the closely related species, Kluyveromyces marxianus, as previously described. Our results also highlighted that the LAC4/LAC12 gene cluster was acquired through multiple and independent introgression events. Finally, we also identified several genes that could play a role in adaptation to dairy environments through copy number variation. These genes are involved in sugar consumption, flocculation and drug resistance, and may play a role in dairy processes. Overall, our study illustrates contrasting genomic evolution and sheds new light on the impact of domestication processes on it.
Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients
Authors: Xiao Jun , Zhang Fan , Liu Wenju , Zang Weidong
Published: September 2022

Aim

To identify the potential post-healing EMT related miRNAs associated with lymph node metastatic gastric cancer (LNMGC).

Methods

Both RNA expression and clinical medical data were obtained from the TCGA dataset. We performed differential expression and normalization analysis of miRNAs. Cox linear regression model confirmed the differentially expressed miRNAs (DEmiRNAs) and clinical medical parameters related to overall survival (OS). The role of target genes of DEmiRNAs was determined according to the role enrichment analysis.

Results

We obtained a total of 7531 DEmRNAs and 267 DEmRNAs, of which 185 DEmRNAs were down-regulated and 82 DEmRNAs were up-regulated. We randomly divided the LMNGC cases (n=291) into a training group (n=207) and a test group (n=84). The results showed that a total of 103, 11, 13 and 83 overlapping genes were associated with hsa-mir-141-3p, hsa-mir-4664-3p, hsa-mir-125b-5p and hsa-mir-7-5p, respectively. Kaplan-Meier determined that these four miRNAs can effectively distinguish high-risk and low-risk groups, and have a good indicator role (all p<0.05). Multivariate cox regression analysis also showed that EMT-related miRNA predictive model and lymph node metastasis were both prognostic risk factors (all p<0.05). The ROC curve showed that this feature had high accuracy (AUC>0.7, p<0.05). In addition, KEGG analysis showed that EMT-related pathways were mainly enriched in HIF-1 signaling pathway and focal adhesion.

Conclusions

Our study demonstrated that EMT-related miRNAs could serve as independent prognostic markers in pN1-3 GC patients.
Hydrostatic pressure and lateral actomyosin tension control stretch and tension of the basement membrane in epithelia
Authors: Guerra Santillán Karla Y. , Dahmann Christian , Fischer-Friedrich Elisabeth
Published: September 2022

The shaping of epithelial tissues into functional organs often depend on asymmetries in mechanical tension present at the apical and basal sides of cells. Contraction of an actomyosin meshwork underlying the apical side of cells is known to generate apical tension. The basal side of cells is also associated with an actomyosin meshwork, but it is, in addition, connected to a specialized extracellular matrix, the basement membrane. However, how basal tension is generated, and the role of the basement membrane in this process, are not well understood. Here, using atomic force microscopy, we measure mechanical tension in the basal surface of the wing disc epithelium of Drosophila. We find that basal tension depends on both the actomyosin cytoskeleton and the basement membrane, and that it is proportional to lateral surface tension and hydrostatic pressure. Collagen IV turnover and mobility are slow indicating that the basement membrane can store elastic stresses. Our data suggest that elastic stresses in the basement membrane induced by basement membrane stretch are a key factor in the adjustment of basal tension. Hydrostatic pressure and lateral actomyosin contractility are two driving forces by which epithelial cells can maintain this basement membrane stretch.
WDFY4 deficiency in NOD mice abrogates autoimmune diabetes and insulitis
Authors: Ferris Stephen T. , Chen Jing , Ohara Ray A. , Ou Feiya , Wu Renee , Kim Sunkyung , Liu Tiantian , Murphy Theresa L. , Murphy Kenneth M.
Published: September 2022

The events that initiate autoimmune diabetes in NOD mice remain poorly understood. CD4 and CD8 T cells are both required but whether either cell initiates disease is unclear. To test whether CD4 T cell infiltration into islet required damage to β cells induced by autoreactive CD8 T cells, we selectively inactivated Wdfy4 in NOD mice (NOD.Wdfy4-/-) using CRISPR/Cas9 targeting. Similar to C57BL/6 Wdfy4-/- mice NOD.Wdfy4-/- mice develop type 1 conventional dendritic cells (cDC1) that are unable to cross-present cell-associated antigens required to activate CD8 T cells. By contrast, cDC1 from heterozygous Wdfy4+/- mice can cross-present normally. Heterozygous NOD.Wdfy4+/- mice develop diabetes similar to NOD mice, but NOD.Wdfy4-/- mice neither develop diabetes nor prime autoreactive CD8 T cells in vivo. By contrast, NOD.Wdfy4-/- mice can process and present MHC-II-restricted autoantigens and can activate β cell specific CD4 T cells in lymph nodes, and yet do not develop CD4 T cell infiltration in islets. These results indicate that the priming of autoreactive CD8 T cells in NOD mice requires cross-presentation by cDC1. Further, autoreactive CD8 T cells are required not only to develop diabetes, but to recruit autoreactive CD4 T cells into islets of NOD mice, perhaps in response to progressive β cell damage.
Elevated levels of lamin A promote HR and NHEJ-mediated repair mechanisms in etoposide-treated ovarian cancer cells
Authors: Sengupta Duhita , Sengupta Kaushik
Published: September 2022

Lamins are emerging as major regulators in the maintenance of nuclear architecture and genome organization. Extensive research for the last two decades has enormously contributed to understanding the roles of lamins in various signaling mechanisms which are drastically modified in neoplasia. It is interesting to record that alteration in lamin A/C expression and distribution drives tumorigenesis of almost all tissues of human bodies. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls several genomic events that transform the cells to be sensitive to chemotherapeutic agents. This genomic and chromosomal instability is the most common feature found in cases of high-grade ovarian serous carcinoma. Here, we report elevated levels of lamins in OVCAR3 cells (High grade ovarian serous carcinoma cell line) in comparison to IOSE (Immortalised ovarian surface epithelial cells) and consequently altered damage repair machinery in OVCAR3. We have analyzed the changes in global gene expression as a sequel to DNA damage induced by etoposide in ovarian carcinoma where lamin A is particularly elevated in expression and reported some differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We highlight new avenues unraveling the role of upregulated lamin A in confronting chemically induced genomic instability in the context of high grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.
Enhancing Robustness, Precision and Speed of Traction Force Microscopy with Machine Learning
Authors: Kratz Felix Sebastian , Moellerherm Lars , Kierfeld Jan
Published: September 2022

Traction patterns of adherent cells provide important information on their interaction with the environment, cell migration or tissue patterns and morphogenesis. Traction force microscopy is a method aimed at revealing these traction patterns for adherent cells on engineered substrates with known constitutive elastic properties from deformation information obtained from substrate images. Conventionally, the substrate deformation information is processed by numerical algorithms of varying complexity to give the corresponding traction field via solution of an ill-posed inverse elastic problem. We explore the capabilities of a deep convolutional neural network as a computationally more efficient and robust approach to solve this inversion problem. We develop a general purpose training process based on collections of circular force patches as synthetic training data, which can be subjected to different noise levels for additional robustness. The performance and the robustness of our approach against noise is systematically characterized for synthetic data, artificial cell models and real cell images, which are subjected to different noise levels. A comparison to state-of-the-art Bayesian Fourier transform traction cytometry reveals the precision, robustness, and speed improvements achieved by our approach, leading to an acceleration of traction force microscopy methods in practical applications.
Length-limitation of astral microtubules orients cell divisions in intestinal crypts
Authors: Jad Saleh , Marc-Antoine Fardin , Olivia Frenoy , Matis Soleilhac , Cécile Gaston , Hongyue Cui , Tien Dang , Gaudin Noémie , Audrey Vincent , Nicolas Minc , Delphine Delacour
Published: September 2022

Planar spindle orientation is critical for epithelial tissue organization, and generally instructed from the long cell shape axis or cortical polarity domains. We introduced mouse intestinal organoid crypts to study spindle orientation in a monolayered mammalian epithelium. Although spindles were planar in this tissue, mitotic cells remained elongated along the apico-basal axis and polarity complexes were segregated to basal poles, so that spindles oriented in an unconventional manner, orthogonal to both polarity and geometric cues. Using high-resolution 3D imaging, simulations, cell shape and cytoskeleton manipulations, we show that planar divisions resulted from a length-limitation in mitotic-phase astral microtubules which precludes them from interacting with basal polarity, and oriented spindles from the local geometry of apical domains. Accordingly, lengthening microtubules affected spindle planarity, cell positioning and crypt arrangement. We conclude that microtubule length regulation may serve as a key mechanism for spindles to sense local cell shapes and tissue forces to preserve mammalian epithelial architecture.
Altered litter and cellulose decomposition across an anthropogenic habitat modification gradient in Sulawesi, Indonesia
Authors: Holle Mukhlish J. M. , Lewis Owen T.
Published: September 2022

Many tropical regions in Southeast Asia have experienced extensive habitat modification, creating a mosaic of forested and agricultural land. The capacity of these human-modified tropical landscapes to support biodiversity and ecosystem functions and services is of considerable practical interest.

Decomposition of plant material is a key process maintaining the nutrient cycle in both natural and agro-ecosystems, but few studies have documented the relative contributions of different guilds of decomposers, acting on different plant substrates, across different tropical land-uses.

We measured decomposition of leaf litter and cellulose across a gradient of anthropogenic habitat modification (forest, shrubland, and corn farmland) within Panua Nature Reserve, Sulawesi, Indonesia. The influence of fungi and the litter invertebrate community were investigated experimentally.

Decomposition of both substrates was significantly lower in corn plantations than in forest sites. Partial exclusion of litter invertebrates, but not fungi, significantly reduced decomposition, but the feeding guild composition of the litter invertebrate community did not differ significantly across habitat types.

Our results confirm that even small-scale agricultural areas adjacent to forest fragments can experience impaired ecosystem functions. These changes can be linked to reduced invertebrate activity, apparently independent of the functional structure of the litter invertebrate community. Effective management of human-modified landscapes will be needed to maintain nutrient cycling, even in areas where agroecosystems and tropical forests occur in close proximity.

Highlights

Habitat modification alters litter and cellulose decomposition

Small-scale agriculture near forest fragments can impair ecosystem functions.

Exclusion of litter invertebrates, but not fungi, significantly reduced decomposition.

Maintaining nutrient cycling requires effective management of human-altered landscapes.
Var|Decrypt: a novel and user-friendly tool to explore and prioritize variants in whole-exome sequencing data
Authors: Salma Mohammad , Alaterre Elina , Moreaux Jérôme , Soler Eric
Published: September 2022

Motivation

High throughput sequencing (HTS) offers unprecedented opportunities for the discovery of causative gene variants in multiple human disorders including cancers, and has revolutionized clinical diagnostics. However, despite more than a decade of use of HTS-based assays, extracting relevant functional information from whole exome sequencing (WES) data remains challenging, especially for non-specialists lacking in-depth bioinformatic skills.

Results

To address this limitation, we developed Var|Decrypt, a web-based tool designed to greatly facilitate WES data browsing and analysis. Var|Decrypt offers a wide range of gene and variant filtering possibilities, clustering and enrichment tools, providing an efficient way to derive patient-specific functional information and to prioritize gene variants for functional analyses. We applied Var|Decrypt on WES datasets of 10 acute erythroid leukemia patients, a rare and aggressive form of leukemia, and recovered known disease oncogenes in addition to novel putative drivers. We additionally benchmarked Var|Decrypt on an independent dataset of ~90 multiple myeloma WES, recapitulating the identified deregulated genes and pathways, showing the general applicability and versatility of Var|Decrypt for WES analysis.
Impaired baroreceptor reflex sensitivity in pelvic suspension rats is associated with sympathovagal imbalance but not with carotid artery structural change
Authors: Bhatnaagar A , Deepak KK , Roy A , Anil AK , Sharma B , Singh A , Netam RK
Published: September 2022

Introduction

In space, cephalad shift of body fluid equalizes the blood pressure throughout the body leading to various cardiovascular disturbances in space and upon return on earth. Effects of microgravity on humans can be simulated on earth by hindlimb unloading (HU) rat models l. This study was planned to examine the Effect of 15 days hindlimb unloading on baroreflex sensitivity, Herat rate variability (HRV) and carotid artery structure in rats.

Material and methods

18 male Wistar rats weighing 250-300 gm were randomly divided into control and hindlimb unloading groups and housed in separate cages for 15 days. Body weight, food and water intake was measured every day. The pelvic suspension method was used to simulate effects of microgravity. To record HRV, ECG was recorded in lead II configuration on the 15th day. Then blood pressure was recorded directly from the carotid artery. Linear regression of arterial pressure and RR interval used to derive the Baroreflex sensitivity. Vessel wall thickness, intimal thickness, smooth muscle cell layer thickness & luminal diameter were compared after H&E staining. Ultrathin sectioning and counter-staining was done for electron microscopy and Changes in endothelial thickness, elastic lamina, and deeper artery structures were observed. Statistical analysis was done using Graphpad Prism (version 9.0). Unpaired t-test, Mann Whitney and 2 way ANOVA were used according to groups and distribution of parameters.

Results

We found significant differences in Food intake (p □0.001), Body weight (p □0.001), Heart rate (p=0.031), BRS (p= 0.026), R-R interval (p=0.0246), heart rate variability parameters {SDSD (p=0.0001), RMSD (p= 0.0001), VLF(p=0.001),HF (p=0.0054), LF/HF Ratio (p= 0.0001)}. We did not found significant changes in Water intake, MAP, SBP, DBP, Vessel wall thickness, Luminal Diameter, Intimal thickness, Smooth muscle thickness, in H&E staining and in electron microscopy.

Conclusion

Chronic microgravity simulation using pelvic suspension showed a decrease in BRS after 15 days of HU; however 15 days of HU was not insufficient to produce any structural changes in the carotid artery. BRS changes were accompanied by change in vascular vasoconstriction and vasodilation properties which were due to alteration in the sympathetic and parasympathetic outflow.
Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2
Authors: Haji Shojiro , Ito Taiki , Guenther Carla , Nakano Miyako , Shimizu Takashi , Mori Daiki , Chiba Yasunori , Tanaka Masato , Mishra Sushil K , Willment Janet A. , Brown Gordon D. , Nagae Masamichi , Yamasaki Sho
Published: September 2022

C-type lectin receptors (CLRs) elicit immune responses upon recognition of glycoconjugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing β-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on platelets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O-glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podoplanin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.
Single-cell analysis of bovine muscle-derived cell types for cultured meat production
Authors: Messmer Tobias , Dohmen Richard GJ , Schaeken Lieke , Melzener Lea , Hueber Rui , Godec Mary , Post Mark J , Flack Joshua E
Published: September 2022

‘Cultured’ meat technologies leverage the proliferation and differentiation of animal-derived stem cells ex vivo to produce edible tissues for human consumption in a sustainable fashion. However, skeletal muscle is a dynamic and highly complex tissue, involving the interplay of numerous mono- and multinucleated cells, including muscle fibres, satellite cells (SCs) and fibro-adipogenic progenitors (FAPs), and recreation of the tissue in vitro thus requires the characterisation and manipulation of a broad range of cell types. Here, we use a single-cell RNA sequencing approach to characterise cellular heterogeneity within bovine muscle and muscle-derived cell cultures over time. Using this data, we identify numerous distinct cell type, and develop robust protocols for the easy purification and proliferation of several of these populations. We note overgrowth of undesirable cell types within heterogeneous proliferative cultures as a barrier to efficient cultured meat production, and use transcriptomics to identify conditions that favour the growth of SCs in the context of serum-free medium. Combining RNA velocities computed in silico with time-resolved flow cytometric analysis, we characterise dynamic subpopulations and transitions between active, quiescent, and committed states of SCs, and demonstrate methods for modulation of these states during long-term proliferative cultures. This work provides an important reference for advancing our knowledge of bovine skeletal muscle biology, and its application in the development of cultured meat technologies.
Arc ubiquitination regulates endoplasmic reticulum-mediated Ca2+release and CaMKII signaling
Authors: Ghane Mohammad A. , Allen Zachary D. , Miller Cassandra L. , Dong Bin , Yang Jenny J. , Fang Ning , Mabb Angela M.
Published: September 2022

Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the mechanism by which this occurs and its consequences on other mGluR-mediated signaling events is unknown. Here we show that disrupting Arc ubiquitination on key amino acid residues leads to derangements in Ca2+release from the endoplasmic reticulum (ER) during pharmacological activation of Group I mGluRs. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination increased Arc self-association and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII. Notably, these interactions were also excluded at secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+signaling that is needed for mGluR-LTD, which in turn, may regulate CaMKII and its interactions with Arc.
Divergent microbial traits influence the transformation of living versus dead root inputs to soil carbon
Authors: Sokol Noah W. , Foley Megan M. , Blazewicz Steven J. , Battacharyya Amrita , Estera-Molina Katerina , Firestone Mary , Greenlon Alex , Hungate Bruce A. , Kimbrel Jeffrey , Liquet Jose , Lafler Marissa , Marple Maxwell , Nico Peter , Slessarev Eric , Pett-Ridge Jennifer
Published: September 2022

Soil microorganisms influence the global carbon cycle by transforming plant inputs into soil organic carbon (SOC), but the microbial traits that facilitate this process are unresolved. While current theory and biogeochemical models suggest microbial carbon-use efficiency and growth rate are positive predictors of SOC, recent observations demonstrate these relationships can be positive, negative, or neutral. To parse these contradictory effects, we used a13C-labeling experiment to test whether different microbial traits influenced the transformation of plant C into SOC within the microbial habitats surrounding living root inputs (rhizosphere) versus decaying root litter (detritusphere), under both normal soil moisture and droughted conditions. In the rhizosphere, bacterial-dominated communities with fast growth, high carbon-use efficiency, and high production of extracellular polymeric substances formed microbial-derived SOC under normal moisture conditions. However, in the detritusphere – and the rhizosphere under drought – more fungal-dominated communities with slower growth but higher exoenzyme activity formed plant-derived SOC. These findings emphasize that microbial traits linked with SOC accrual are not universal, but contingent on how microorganisms allocate carbon under different resource conditions and environmental stressors.
An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes
Authors: Smrt Sean T. , Escobar Cristian A. , Dey Souvik , Cross Timothy A. , Zhou Huan-Xiang
Published: September 2022

Mycobacteria tuberculosis (Mtb)inflicts a quarter of the worldwide population. Most drugs for treating tuberculosis target cell growth and division. With rising drug resistance, it becomes ever more urgent to better understandMtbcell division. This process begins with the formation of the Z-ring via polymerization of FtsZ and anchoring of the Z-ring to the inner membrane. Here, by combining solution and solid-state NMR spectroscopy with molecular dynamics simulations and other techniques, we show that the transmembrane protein FtsQ is a membrane anchor of theMtbZ-ring. In the otherwise disordered N-terminal cytoplasmic region of FtsQ (residues 1-99), a 29-residue, Arg/Ala-rich α-helix is formed that interacts with upstream acidic residues in solution and with acidic lipids at the membrane surface. The same helix also binds to the GTPase domain of FtsZ, with enormous implications for drug binding and Z-ring formation including its curvature.
Neighbourhood effect of weeds on wheat root endospheric mycobiota
Authors: Hu Jie , Ricono Claire , Fournier Paola , Mondy Samuel , Vandenkoornhuyse Philippe , Mony Cendrine
Published: September 2022

Microorganisms associated with plants provide essential functions to their hosts, and therefore affect ecosystem productivity. Agricultural intensification has modified microbial diversity in the soil reservoir and may affect plant microbial recruitment. Weeds develop spontaneously in crop fields, and could influence microorganisms associated with crop plants through a neighbourhood effect. We explore the effect of weed species on crop plant microbiota as potentially auxiliary plants that affect agricultural productivity.

We combined field and controlled laboratory studies to analyse the neighbourhood effect of weeds on wheat root endospheric mycobiota and growth. First, we analysed the effect of weed species diversity and identity recorded in the neighbourhood of individual wheat plants on soil and wheat root mycobiota in the field. Second, we used a plant-matrix design in laboratory conditions to test the effect of weed identity (9 weed treatments) and their ability to transmit root mycobiota to wheat roots, and the resulting impact on wheat growth.

In contrast to soil mycobiota, we demonstrated that wheat root endospheric mycobiota was influenced by the diversity and identity of weeds developing in their 1 m2 neighbourhood. Wheat root endospheric microbiota strongly differs in terms of richness and composition depending on the neighbouring weed plant species. Weed species transmitted from 13% to 74% of their root microbiota to wheat roots depending on weed identity in controlled conditions.

Synthesis. Weed neighbours modified wheat plant performance, possibly as a result of competitive interactions and changes in microbiota. Our findings suggest that crop root mycobiota was variable and was modulated by their weed neighbourhood. Synergistic effects between mycobiota of crops and weeds could therefore contribute to soil biodiversity and sustainable agriculture.
Transcriptome and chromatin accessibility landscapes across 25 distinct human brain regions expand the susceptibility gene set for neuropsychiatric disorders
Authors: Dong Pengfei , Bendl Jaroslav , Misir Ruth , Shao Zhiping , Edelstien Jonathan , Davis David A , Haroutunian Vahram , Scott William K. , Acker Susanne , Lawless Nathan , Hoffman Gabriel E. , Fullard John F. , Roussos Panos
Published: September 2022

Brain region- and cell-specific transcriptomic and epigenomic molecular features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions are strongly enriched for neuropsychiatric disease risk variants. Using an integrative approach, we characterized the function of the brain region-specific chromatin co-accessibility and gene-coexpression modules that are robustly associated with genetic risk for neuropsychiatric disorders. In addition, we identified a novel set of genes that is enriched for disease risk variants but is independent of cell-type specific gene expression and known susceptibility pathways. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and suggest a unique contribution of epigenetic modifications from subcortical areas to neuropsychiatric disorders.
Characterization of b-value dependent T2 relaxation rates for probing neurite microstructure
Authors: Ning Lipeng , Westin Carl-Fredrik , Rathi Yogesh
Published: September 2022

Brain tissue microstructure is characterized by heterogeneous diffusivity and transversal relaxation rates. Standard diffusion MRI (dMRI) is acquired using a single echo time (TE) and only provides information about heterogeneous diffusivity in the underlying tissue. Combined relaxation diffusion MRI (rdMR) integrates dMRI with multiple TEs to probe the coupling between relaxation rate and diffusivity. This work introduces a method to model rdMRI data signals by characterizing the apparent relaxation rate related to dMRI with different b-values. The proposed approach can extrapolate dMRI signals to ultra-long or ultra-short TEs to increase or reduce signals from intra-neurite water to improve the characterization of neurite microstructure without solving multi-compartment models. The performance of the proposed method was examined using an in vivo dataset acquired from a clinical scanner to estimate neurite sizes.