bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared evolutionary path in social microbiomes
Authors: Frazão Nelson , Gordo Isabel
Published: February 2023

Social networks can influence the ecology of gut bacteria, shaping the species composition of the gut microbiome in humans and other animals. Gut commensals evolve and can adapt at a rapid pace when colonizing healthy hosts. Here, we aimed at assessing the impact of host-to-host bacterial transmission onEscherichia colievolution in the mammalian gut. Using anin vivoexperimental evolution approach in mice, we found a transmission rate of 7% (±3% 2SE) ofE. colicells per day between hosts inhabiting the same household. Consistent with the predictions of a simple population genetics model of mutation-selection-migration, the level of shared events resulting from within host evolution is greatly enhanced in co-housed mice, showing that hosts undergoing the same diet and habit are not only expected to have similar microbiome species compositions but also similar microbiome evolutionary dynamics. Furthermore, we estimated the rate of mutation accumulation ofE. colito be 2.9×10−3(±5×10−42SE) mutations/genome/generation, irrespective of the social context of the regime. Our results reveal the impact of bacterial migration across hosts in shaping the adaptive evolution of new strains colonizing gut microbiomes.
POLCAM: Instant molecular orientation microscopy for the life sciences
Authors: Bruggeman Ezra , Zhang Oumeng , Needham Lisa-Maria , Körbel Markus , Daly Sam , Cheetham Matthew , Peters Ruby , Wu Tingting , Klymchenko Andrey S. , Davis Simon J. , Paluch Ewa K. , Klenerman David , Lew Matthew D. , O’Holleran Kevin , Lee Steven F.
Published: February 2023

Current methods for single-molecule orientation localization microscopy (SMOLM) require optical setups and algorithms that can be prohibitively slow and complex, limiting the widespread adoption for biological applications. We present POLCAM, a simplified SMOLM method based on polarized detection using a polarization camera, that can be easily implemented on any wide-field fluorescence microscope. To make polarization cameras compatible with single-molecule detection, we developed theory to minimize field of view errors, used simulations to optimize experimental design, and developed a fast algorithm based on Stokes parameter estimation which can operate over 1000 fold faster than the state of the art, enabling near instant determination of molecular anisotropy. To aid in the adoption of POLCAM, we developed open-source image analysis software, and a website detailing hardware installation and software use. To illustrate the potential of POLCAM in the life sciences, we applied our method to study alpha-synuclein fibrils, the actin cytoskeleton of mammalian cells, fibroblast-like cells and the plasma membrane of live human T cells.
How do different functional groups of crop perform in temperate silvoarable agroforestry systems? A case study
Authors: Vaccaro Christina , Six Johan , Schöb Christian
Published: February 2023

Agroforestry systems provide a number of ecosystem services and are frequently considered as a promising diversification strategy for more sustainable and climate resilient primary production. Still, less than 1% of the agricultural land in the European Union is silvoarable agroforestry. Most agroforestry field trials compare one crop type with a control in open field with no additional environmental treatments such as nutrient and water availability, thereby limiting our understanding of the ecological processes underlying the potential benefits of agroforestry for food production. The present experimental study addresses three factors (shade, fertilisation, irrigation) on three functionally different crop species (field bean, summer barley, summer rapeseed) and a C4-grass (Echinochloa crus-galli) in a Swiss agroforestry system. The objective of this study was to assess if and how crop performance (physiological traits, yield) between functional groups varies and if and how shade-induced crop yield reductions diverge between treatment combinations, aiming to provide general functional crop species and management recommendations as a guideline for a successful agroforestry practice in temperate Europe. Summer barley (−44%) and field bean (−38%) showed significant yield declines, similar to summer rapeseed with a significant biomass decline (−35%). Shade significantly increased the occurrence of lodging in barley. Rapeseed in particular performed better when fertilised (+40% biomass). Our results enable to estimate the range of potential yield losses in the competitive zone near mature trees for functionally different crop types and serve as a decision-support for species selection in temperate European agroforestry systems.
Characterization of human XPD helicase activity with Single Molecule Magnetic Tweezers
Authors: Mao Chunfeng , Mills Maria
Published: February 2023

XPD helicase is a DNA unwinding enzyme involved in multiple cellular processes. As part of TFIIH, XPD opens a repair bubble in DNA for access by proteins in the nucleotide excision repair pathway. XPD uses the energy from ATP hydrolysis to translocate in the 5’ to 3’ direction on one strand of duplex DNA, displacing the opposite strand in the process. We used magnetic tweezers assays to measure the double-stranded DNA (dsDNA) unwinding and single-stranded DNA (ssDNA) translocation activities of human XPD by itself. In our experimental setup, hXPD exhibits low unwinding processivity of ~14 bp and slow overall unwinding rate of ~0.3 bp/s. Individual unwinding and translocation events were composed of fast and slow runs and pauses. Analysis of these events gave similar mean run sizes and rates for unwinding and translocation, suggesting that unwinding is a reflection of translocation. The analysis also revealed that hXPD spent similar time stalling and unwinding. hXPD translocated on ssDNA at a similar overall rate as that of unwinding, pointing to an active helicase. However, we observed modest effects of DNA sequence on stalling and unwinding initiation position. Considering the slow unwinding rate, high probability of base pair separation at the ssDNA/dsDNA fork, and the observed DNA sequence dependences, we propose that hXPD is most likely a partially active helicase. Our results provide detailed information on the basal activity of hXPD which enhances our mechanistic understanding of hXPD activity.

SIGNIFICANCE

Human XPD helicase is a major component of the general transcription factor TFIIH. TFIIH is essential in both transcription and nucleotide excision repair. Mutations in hXPD are associated with cancers and autosomal recessive disorders. Here we directly measured the dsDNA unwinding and ssDNA translocation of human XPD helicase by itself. Our measurements provide detailed information on the basal activity of human XPD, which enhance our mechanistic understanding of the activity of XPD in the cell, provide a basis for better understanding of the clinical phenotypes, and aid in drug design targeting hXPD related diseases.
Differential regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) receptor tetramerization by auxiliary subunits
Authors: Certain Noele , Gan Quan , Bennett Joseph , Hsieh Helen , Wollmuth Lonnie P.
Published: February 2023

AMPA receptor (AMPAR) auxiliary subunits are specialized, non-transient binding partners of AMPARs that modulate their ion channel gating properties and pharmacology, as well as their biogenesis and trafficking. The most well characterized families of auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs) and the more recently discovered GSG1-L. These auxiliary subunits can promote or reduce surface expression of AMPARs in neurons, thereby impacting their functional role in membrane signaling. Here, we show that CNIH-2 enhances the tetramerization of wild type and mutant AMPARs, possibly by increasing the overall stability of the tetrameric complex, an effect that is mainly mediated by interactions with the transmembrane domain of the receptor. We also find CNIH-2 and CNIH-3 show receptor subunit-specific actions in this regard with CNIH-2 enhancing both GluA1 and GluA2 tetramerization whereas CNIH-3 only weakly enhances GluA1 tetramerization. These results are consistent with the proposed role of CNIHs as endoplasmic reticulum cargo transporters for AMPARs. In contrast, TARP γ-2, TARP γ-8, and GSG1-L have no or negligible effect on AMPAR tetramerization. On the other hand, TARP γ-2 can enhance receptor tetramerization but only when directly fused with the receptor at a maximal stoichiometry. Notably, surface expression of functional AMPARs was enhanced by CNIH-2 to a greater extent than TARP γ-2 suggesting that this distinction aids in maturation and membrane expression. These experiments define a functional distinction between CNIHs and other auxiliary subunits in the regulation of AMPAR biogenesis.
Systematic comparison of risky choices in humans and monkeys
Authors: Seak Leo Chi U , Ferrari-Toniolo Simone , Jain Ritesh , Nielsen Kirby , Schultz Wolfram
Published: February 2023

The past decades have seen tremendous progress in fundamental studies on economic choice in humans. However, elucidation of the underlying neuronal processes requires invasive neurophysiological studies that are met with difficulties in humans. Monkeys as evolutionary closest relatives offer a solution. The animals display sophisticated and well-controllable behavior that allows to implement key constructs of proven economic choice theories. However, the similarity of economic choice between the two species has never been systematically investigated. We investigated compliance with the independence axiom (IA) of expected utility theory as one of the most demanding choice tests and compared IA violations between humans and monkeys. Using generalized linear modeling and cumulative prospect theory (CPT), we found that humans and monkeys made comparable risky choices, although their subjective values (utilities) differed. These results suggest similar fundamental choice mechanism across these primate species and encourage to study their underlying neurophysiological mechanisms.
Planarian LDB and SSDP proteins scaffold transcriptional complexes for regeneration and patterning
Authors: Medlock-Lanier Taylor , Clay Kendall B. , Roberts-Galbraith Rachel H.
Published: February 2023

Sequence-specific transcription factors often function as components of large regulatory complexes. LIM-domain binding protein (LDB) and single-stranded DNA-binding protein (SSDP) function as core scaffolds of transcriptional complexes in animals and plants. Little is known about potential partners and functions for LDB/SSDP complexes in the context of tissue regeneration. In this work, we find that planarian LDB1 and SSDP2 promote tissue regeneration, with a particular function in mediolateral polarity reestablishment. We find that LDB1 and SSDP2 interact with one another and with characterized planarian LIM-HD proteins Arrowhead, Islet1, and Lhx1/5-1.SSDP2andLDB1also function withislet1in polarity reestablishment and withlhx1/5-1in serotonergic neuron maturation. Finally, we show new roles for LDB1 and SSDP2 in regulating gene expression in the planarian intestine and parenchyma; these functions may be LIM-HD-independent. Together, our work provides insight into LDB/SSDP complexes in a highly regenerative organism. Further, our work provides a strong starting point for identifying and characterizing potential binding partners of LDB1 and SSDP2 and for exploring roles for these proteins in diverse aspects of planarian physiology.
Performance of a winter wheat composite cross population in two temperate agroforestry systems – a case study
Authors: Vaccaro Christina , Mascher Fabio , Six Johan , Schöb Christian
Published: February 2023

In agroforestry systems (AFS), where environmental conditions are highly variable at small spatial scales, the use of uniform genetic material of a single cultivar commonly grown in monoculture cropping might not be optimal. However, the use of composite cross populations (CCPs) that contain an inherent genetic variability might be a promising approach to match the environmental variability created by trees in AFS. In this experimental trial, the performance of a CCP (‘CC-2k’) of winter wheat was compared to a commercial variety (‘Wiwa’) in a split-plot design in two AFS (Feusisberg, Wollerau) in Central Switzerland. The factor variety (p < 0.05) and the interactions of site and distance to tree (p < 0.05) and site and variety (p < 0.05) significantly affected wheat yield at the plot level. CC-2k and Wiwa yield (across all distances) amounted to 1.9 ± 0.7 Mg ha−1and 2.0 ± 0.8 Mg ha−1, respectively, in Feusisberg and to 1.9 ± 0.9 Mg ha−1and 0.7 ± 0.4 Mg ha−1, respectively, in Wollerau. Wiwa had a higher protein, Fe and Ca content than CC-2k. Therefore, while the CC-2k outperformed the commercial organic variety Wiwa in terms of yield in one of the two AFS, Wiwa outperformed CC-2k in terms of quality. The composite cross population might be better adapted to the heterogenous environment of agroforestry systems but fails to reach the high-quality product of modern elite cultivars. Further improvements in terms of quality might make CCPs highly interesting for diversified agricultural systems with larger environmental heterogeneity than common monoculture cropping systems.
Three-dimensional fruit growth analysis clarifies developmental mechanisms underlying complex shape diversity in persimmon fruit
Authors: Kusumi Akane , Nishiyama Soichiro , Tao Ryutaro
Published: February 2023

How fruit size and shape are determined is of research interest in agriculture and developmental biology. Fruit typically exhibits three-dimensional structures with genotype-dependent geometric features. Although minor developmental variations have been recognized, little research has fully visualized and measured these variations throughout fruit growth. In this study, a high-resolution 3D scanner was used to investigate the fruit development of 51 persimmon (Diospyros kaki) cultivars with various complex shapes. We obtained 2,380 3D fruit models that fully represented fruit appearance, and enabled precise and automated measurements of unique geometric features throughout fruit development. The 3D fruit model analysis identified key stages that determined the shape attributes at maturity. Typically, genetic diversity in vertical groove development was found, and such grooves can be filled by tissue expansion in the carpal fusion zone during fruit development. Furthermore, transcriptome analysis of fruit tissues from groove/non-groove tissues revealed gene co-expression networks that were highly associated with groove depth variation. The presence ofYABBYhomologs was most closely associated with groove depth and indicated the possibility that this pathway is a key molecular contributor to vertical groove depth variation. These results demonstrate the validity of fruit 3D growth analysis, which is a powerful tool for identifying the developmental mechanisms of fruit shape variation and the molecular basis of this diversity.
Transmissibility of clinically relevant atovaquone-resistantPlasmodium falciparumby anopheline mosquitoes
Authors: Balta Victoria A. , Stiffler Deborah , Sayeed Abeer , Tripathi Abhai K. , Elahi Rubayet , Mlambo Godfree , Bakshi Rahul P. , Dziedzic Amanda G. , Jedlicka Anne E. , Nenortas Elizabeth , Romero-Rodriguez Keyla , Canonizado Matthew A. , Mann Alexis , Owen Andrew , Sullivan David J. , Prigge Sean T. , Sinnis Photini , Shapiro Theresa A.
Published: February 2023

Rising numbers of malaria cases and deaths underscore the need for new interventions. Long-acting injectable medications, such as those now in use for HIV prophylaxis, offer the prospect of a malaria “chemical vaccine”, combining the efficacy of a drug (like atovaquone) with the durability of a biological vaccine. Of concern, however, is the possible selection and transmission of drug-resistant parasites. We addressed this question by generating clinically relevant, highly atovaquone-resistant,Plasmodium falciparummutants competent to infect mosquitoes. Isogenic paired strains, that differ only by a single Y268S mutation in cytochrome b, were evaluated in parallel in southeast Asian (Anopheles stephensi) or African (Anopheles gambiae) mosquitoes, and thence in humanized mice. Fitness costs of the mutation were evident along the lifecycle, in asexual parasite growth in vitro and in a progressive loss of parasites in the mosquito. In numerous independent experiments, microscopic exam of salivary glands from hundreds of mosquitoes failed to detect even one Y268S sporozoite, a defect not rescued by coinfection with wild type parasites. Furthermore, despite uniformly successful transmission of wild type parasites fromAn. stephensito FRG NOD huHep mice bearing human hepatocytes and erythrocytes, multiple attempts with Y268S-fed mosquitoes failed: there was no evidence of parasites in mouse tissues by microscopy, in vitro culture, or PCR. These studies confirm a severe-to-lethal fitness cost of clinically relevant atovaquone-resistantP. falciparumin the mosquito, and they significantly lessen the likelihood of their transmission in the field.

Significance

New tools are needed to protect individuals from malaria and to control malaria in the field. Atovaquone plus proguanil is a commonly used and well-tolerated medicine to prevent malaria. No drug resistance has been reported from its prophylactic use, but tablets must be taken daily. Giving atovaquone as a single injection may provide much longer-lasting protection, against both falciparum and vivax malaria, but there is concern this may create drug resistance. In this study we showed that clinically relevant atovaquone-resistant malaria parasites survive poorly, if at all, in mosquitoes, and that mosquitoes do not transmit drug-resistant parasites to humanized mice. These findings lessen the likelihood that an atovaquone “chemical vaccine” would lead to the spread of atovaquone resistance.
Anthelmintic efficacy ofHolarrhena pubescensagainstRaillietinaspp. of domestic fowl through ultrastructural, histochemical, biochemical and GLCM analysis
Authors: Saha Rachita , Gupta Manjil , Majumdar Rima , Saha Subrata , Kar Pradip Kumar
Published: February 2023

Holarrhena pubescensis a well-known medicinal plant used in ethno-traditional medicine and tribal folklore medicine in West Bengal, India. This article focuses on depicting the anthelmintic efficacy of ethanolic extract and Ethyl acetate fraction of the stem bark ofHolarrhena pubescensagainst the cestodeRaillietinaspp. through efficacy testing, ultra-structural observations, histochemical and biochemical studies on some tegumental enzymes i.e., Acid Phosphatase (AcPase), Alkaline Phosphatase (AlkPase), Adenosine Triphosphatase (ATPase) and 5’-Nucleotidase (5’-Nu) along with Gray Level Co-occurrence Matrix (GLCM) analysis of histochemistry images. Praziquantel was used as the reference drug. Investigations revealed 10mg/ml of crude extract was determined as the most efficacious dose and the Ethyl acetate fraction showed the most anthelmintic property. Ultrastructural studies through Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) clearly showed the damage in head, sucker, proglottids, proximal and distal cytoplasm (DC), microtriches (MT), basal lamina (BL), nuclear membrane (NM), and, nucleolus (NL) in the treated worms. Histochemical studies revealed decrease in staining intensity for all the tegumental enzymes in the treated worms compared to control. The GLCM analysis strongly supported the result of histochemical studies. Biochemical studies revealed marked reduction in enzyme activity in the treated worms with maximum reduction in the activity of 5’-Nu (77.8%) followed by ATPase (63.17%).
Benchmarking of novel green fluorescent proteins for the quantification of protein oligomerization in living cells
Authors: Petrich Annett , Aji Amit Koikkarah , Dunsing Valentin , Chiantia Salvatore
Published: February 2023

Protein-protein-interactions play an important role in several cellular functions. Quantitative non-invasive techniques are applied in living cells to evaluate such interactions, thereby providing a broader understanding of complex biological processes. Fluorescence fluctuation spectroscopy describes a group of quantitative microscopy approaches for the characterization of molecular interactions at single cell resolution. Through the obtained molecular brightness, it is possible to determine the oligomeric state of proteins. This is usually achieved by fusing fluorescent proteins (FPs) to the protein of interest. Recently, the number of novel green FPs has increased, with consequent improvements to the quality of fluctuation-based measurements. The photophysical behavior of FPs is influenced by multiple factors (including photobleaching, protonation-induced “blinking” and long-lived dark states). Assessing these factors is critical for selecting the appropriate fluorescent tag for live cell imaging applications. In this work, we focus on novel green FPs that are extensively used in live cell imaging. A systematic performance comparison of several green FPs in living cells under different pH conditions using Number & Brightness (N&B) analysis and scanning fluorescence correlation spectroscopy was performed. Our results show that the new FP Gamillus exhibits higher brightness at the cost of lower photostability and fluorescence probability (pf), especially at lower pH. mGreenLantern, on the other hand, thanks to a very highpf, is best suited for multimerization quantification at neutral pH. At lower pH, mEGFP remains apparently the best choice for multimerization investigation. These guidelines provide the information needed to plan quantitative fluorescence microscopy involving these FPs, both for general imaging or for Protein-protein-interactions quantification via fluorescence fluctuation-based methods.
Dynamic mapping of proteome trafficking within and between living cells by TransitID
Authors: Xu Wei Qin , Cheah Joleen S. , Xu Charles , Messing James , Freibaum Brian D. , Boeynaems Steven , Taylor J. Paul , Udeshi Namrata D. , Carr Steven A. , Ting Alice Y.
Published: February 2023

The ability to map trafficking for thousands of endogenous proteins at once in living cells would reveal biology currently invisible to both microscopy and mass spectrometry. Here we report TransitID, a method for unbiased mapping of endogenous proteome trafficking with nanometer spatial resolution in living cells. Two proximity labeling (PL) enzymes, TurboID and APEX, are targeted to source and destination compartments, and PL with each enzyme is performed in tandem via sequential addition of their small-molecule substrates. Mass spectrometry identifies the proteins tagged by both enzymes. Using TransitID, we mapped proteome trafficking between cytosol and mitochondria, cytosol and nucleus, and nucleolus and stress granules, uncovering a role for stress granules in protecting the transcription factor JUN from oxidative stress. TransitID also identifies proteins that signal intercellularly between macrophages and cancer cells. TransitID introduces a powerful approach for distinguishing protein populations based on compartment or cell type of origin.
A Phase 2, Randomized, Double-blind, Placebo-controlled Study of oral RP7214, a DHODH inhibitor, in Patients with Symptomatic Mild SARS-CoV-2 Infection
Authors: Nair Ajit , Barde Prajak , Routhu Kasi V , Vakkalanka Swaroop ,   RP7214-2101 Study Group
Published: February 2023

Introduction

COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of immense global public health concern. RP7214, a novel, potent, oral, inhibitor of DHODH, has shown preclinical evidence in inhibiting viral replication and lung inflammation.

Methods

This was a randomized, double-blind, placebo-controlled phase 2 study in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., hypertension, diabetes mellitus) for developing severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a placebo for 14 days in a blinded fashion and were followed up to 30 days. Patients also received supportive therapy (e.g., antipyretics and antitussives for symptomatic relief) at the discretion of the investigator. The endpoints were Covid 19 related hospitalization rate by Day 15, SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms improvement by Day 15, safety, and the immuno-modulatory effect of RP7214.

Results

A total of 163 patients were treated in the study; 82 received RP7214 and 81 received placebo. Of the total patients, 44.2% had received Covid-19 vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of the patients in the study required hospitalization. There was no difference in the mean change of viral load between RP7214 and placebo. In the subgroup analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Days 3 and 7, respectively. Similarly, in non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Day 3. Overall, there was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. For all other endpoints, there was no difference between RP7214 and placebo. Majority of the reported AEs were mild and not related either to study treatment.

Conclusions

RP7214 at 400 mg BID dose level showed a statistically significant reduction in viral load at an early stage of the disease and in non-vaccinated patients. There was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. RP7214 showed a favorable safety profile. Further development of RP7214 in Covid 19 in a mild symptomatic population with co-morbidities and treated at an early stage of disease may show benefit.
Cerebral Topographies of Perceived and Felt Emotions
Authors: Saarimäki H , Nummenmaa L , Volynets S , Santavirta S , Aksiuto A , Sams M , Jääskeläinen IP , Lahnakoski JM
Published: February 2023

Emotions modulate behavioral priorities based on exteroceptive and interoceptive inputs, and the related central and peripheral changes may often be experienced subjectively. Yet, it remains unresolved whether the perceptual and subjectively felt components of the emotion processes rely on shared brain mechanisms. We applied functional magnetic resonance imaging, a rich set of emotional movies, and high-dimensional, continuous ratings of perceived and felt emotions depicted in the same movies to investigate their cerebral organization. Eight main dimensions of emotions evoked during natural movie scene perception were represented in the brain across numerous spatial scales and patterns. Perceived and felt emotions generalized both between individuals and between different samples of stimuli depicting the same emotions. The neural affective space demonstrated an anatomical gradient from responses independent of specific emotions in polysensory areas and default mode regions to more localized and emotion-specific discrete processing in subcortical regions. Differences in neural activations during felt and perceived emotions suggest that temporoparietal areas and precuneus have a key role in computing the affective value of the sensory input. This affective value is then transformed into the subjective emotional experience in the anterior prefrontal cortices, cerebellum, and thalamus. Altogether these data reveal the similarities and differences of domain-general and emotion-specific affect networks in the brain during a wide range of perceived and felt emotions.
Geography and environmental pressure are predictive of class-specific radioresistance in black fungi
Authors: Aureli Lorenzo , Coleine Claudia , Delgado-Baquerizo Manuel , Ahren Dag , Cemmi Alessia , Sarcina Ilaria Di , Onofri Silvano , Selbmann Laura
Published: February 2023

Black fungi are among the most resistant organisms to ionizing radiation on Earth. However, our current knowledge is based on studies on a few isolates, while the overall radioresistance limits across this microbial group and the relationship with local environmental conditions remains largely undetermined. To address this knowledge gap, we assessed the survival of 101 strains of black fungi isolated across a worldwide spatial distribution to gamma radiation doses up to 100 kGy. We found that intra and inter-specific taxonomy, UV radiation and precipitation levels primarily influence the radioresistance in black fungi. Altogether, this study provides insights into the adaptive mechanisms of black fungi to extreme environments and highlights the role of local adaptation in shaping the survival capabilities of these extreme-tolerant organisms.

Originality statement

Although previous studies showed the extraordinary ability of a few strains of black fungi to survive ionizing radiation, the overall radioresistance of this group of organisms has not been defined yet. Moreover, how and why radioresistance shifts across environmental gradients remain virtually unknown. Here, we collected black fungi from locations across the globe and found that biogeography shapes the responses of black fungi to environmental stress with UV light being significantly correlated with radiotolerance. Our study provides a clear picture of the boundaries of life for black fungi under ionizing radiation; further, we demonstrate, for the first time, that this ability in such microorganisms, not only is related to taxonomy, but also may be a consequence of their adaptation to various factors encountered in the environment where they live.
Sex-specific declines in cholinergic-targeting tRNA fragments in the nucleus accumbens in Alzheimer’s disease
Authors: Shulman Dana , Dubnov Serafima , Zorbaz Tamara , Madrer Nimrod , Paldor Iddo , Bennett David A. , Seshadri Sudha , Mufson Elliott J. , Greenberg David S. , Loewenstein Yonatan , Soreq Hermona
Published: February 2023

Introduction

Females with Alzheimer’s disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in tRNA fragments (tRFs) targeting cholinergic transcripts (CholinotRFs).

Methods

We analyzed small RNA-sequencing data from thenucleus accumbens(NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation.

Results

NAc CholinotRFs of mitochondrial genome origin showed reduced levels that correlated with elevations in their predicted cholinergic-associated mRNA targets. Single cell RNA seq from AD temporal cortices showed altered sex-specific levels of cholinergic transcripts in diverse cell types; inversely, human-originated neuroblastoma cells under cholinergic differentiation presented sex-specific CholinotRF elevations.

Discussion

Our findings support CholinotRFs contributions to cholinergic regulation, predicting their involvement in AD sex-specific cholinergic loss and dementia.
Enhancer-promoter interactions are reconfigured through the formation of long-range multiway chromatin hubs as mouse ES cells exit pluripotency
Authors: Lando D. , Ma X. , Cao Y. , Jartseva A. , Stevens T. J. , Boucher W. , Reynolds N. , Montibus B. , Hall D. , Lackner A , Ragheb R. , Leeb M , Hendrich B. D. , Laue E. D.
Published: February 2023

Enhancers are genomic DNA sequences that bind transcription factors, chromatin regulators and non-coding transcripts to modulate the expression of target genes. They have been found to act from different locations relative to a gene and to modulate the activity of promoters up to ∼1 Mb away. Here we report the first 3D genome structures of single mouse ES cells as they are induced to exit pluripotency, transition through a formative stage and undergo neuroectodermal differentiation. In order to directly study how interactions between enhancers and promoters are reconfigured genome wide we have determined 3D structures of haploid cells using single cell Hi-C, where we can unambiguously map the contacts to particular chromosomes. We find that there is a remarkable reorganisation of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. Genes important for pluripotency exit establish contacts with emerging enhancers within multiway chromatin hubs as cells enter the formative state, consistent with these structural changes playing an important role in establishing new cell identities. Furthermore, we find that different multiway chromatin hubs, and thus different enhancer-promoter interactions, are formed in different individual cells. Our results suggest that studying genome structure in single cells will be important to identify key changes in enhancer-promoter interactions that occur as cells undergo developmental transitions.
Genetic investigation of honeybee populations in Kazakhstan
Authors: Gritsenko D. , Temirbayeva K. , Taskuzhina A. , Kostuykova V. , Pozharskiy A. , Khusnitdinova M. , Krupskiy O. , Mayer A. , Nuralieva U.
Published: February 2023

Beekeeping as a staple of agriculture in Kazakhstan is believed to have emerged when external bee specimens were introduced into the country. The Central Russian bee (Apis mellifera mellifera) has been present throughout Kazakhstanian apiaries for a long time since its import into Eastern Kazakhstan at the end of the 18thcentury. To date, six subspecies have been distributed across the country (A.m. sossimai,A.m. carpatica,A.m. mellifera,A.m. ligustica, А.m. caucasica, andA.m. carnica). According to mitochondrial haplotype analysis based on DraI mtDNA COI-COII (DmCC) test, local samples were represented by C2 (316), C1 (99), and M4 (7) haplotypes. The results of simple sequence repeats (SSR) genotyping revealed a large polymorphism at nine microsatellite loci, with the number of alleles amounting to 35 (AP55), 32 (AP43), 25 (A124), 18 (A113), 13 (A88), 12 (A43), 11 (A007), 7 (A28), and 5 (A24). Relative to the expected heterozygosity (He), the observed heterozygosity (Ho) was slightly higher for most markers considering both the overall samples and individual populations. The inbreeding coefficient confirmed the excess outbreeding for the geographical populations of car-Shym-T (−0,105), car-zham-A (−0,114), Zhet-Alakol (−0,008), and Zhet-Ushbulak (−0,028). The admixture of honeybee local populations was confirmed by the research presented here.The differentiation of populations was only possible by geographical location according to clustering analysis. A considerable degree of genetic admixtures among subspecies was identified in every population. The subspecies were not separated from each other. None of the groups formed by the neighbor-joining tree based on Nei’s genetic distance included a precise subspecies or population. All groups represented an admixture of subspecies from different populations.

Unregulated cross-breeding for the past 50 years has laid the foundation for the promiscuous genetic nature of honeybee populations in Kazakhstan. It could be concluded that some samples were the result of cross-breeding with endemic beeApis mellifera pomonellasince most apiaries were located in areas of endemic bee distribution.
Transcription activator WCC recruits deacetylase HDA3 to control transcription dynamics and bursting in Neurospora
Authors: Oehler Michael , Diernfellner Axel C.R. , Brunner Michael
Published: February 2023

RNA polymerase II initiates transcription either randomly or in bursts. We examined the light-dependent transcriptional activator White Collar Complex (WCC) ofNeurosporato characterize the transcriptional dynamics of the strongvivid(vvd) promoter and the weakerfrequency(frq) promoter. We show that WCC is not only an activator but also represses transcription by recruiting histone deacetylase 3 (HDA3). Our data suggest that bursts offrqtranscription are governed by a long-lived refractory state established and maintained by WCC and HDA3 at the core promoter, whereas transcription ofvvdis determined by WCC binding dynamics at an upstream activating sequence. Thus, in addition to stochastic binding of transcription factors, transcription factor-mediated repression may also influence transcriptional bursting.

TEASER

Balanced interaction of transcription factor with coactivator and corepressors determines transcription dynamics and bursting.
A simple mechanism for integration of quorum sensing and cAMP signalling inV. cholerae
Authors: Walker Lucas M. , Haycocks James R.J. , van Kessel Julia C. , Dalia Triana N. , Dalia Ankur B. , Grainger David C.
Published: February 2023

Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived “autoinducer” signalling molecules, that accumulate in the local environment. Individual cells sense autoinducer abundance, to infer population density, and alter their behaviour accordingly. InVibrio cholerae, quorum sensing signals are transduced by phosphorelay to the transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene expression patterns. In this work, we have mapped the genome-wide distribution of LuxO and HapR inV. cholerae. Whilst LuxO has a small regulon, HapR targets 32 loci. Many HapR targets coincide with sites for the cAMP receptor protein (CRP) that regulates the transcriptional response to carbon starvation. This overlap, also evident in otherVibriospecies, results from similarities in the DNA sequence bound by each factor. At shared sites, HapR and CRP simultaneously contact the double helix and binding is stabilised by direct interaction of the two factors. Importantly, this involves a CRP surface that usually contacts RNA polymerase to stimulate transcription. As a result, HapR can block transcription activation by CRP. Thus, by interacting at shared sites, HapR and CRP integrate information from quorum sensing and cAMP signalling to control gene expression. This likely allowsV. choleraeto regulate subsets of genes during the transition between aquatic environments and the human host.
Surf4 deficiency reduces intestinal lipid absorption and secretion and decreases metabolism in mice
Authors: Tao Geru , Wang Hao , Shen Yishi , Zhai Lei , Liu Boyan , Wang Bingxiang , Chen Wei , Xing Sijie , Chen Yuan , Gu Hong-mei , Qin Shucun , Zhang Da-wei
Published: February 2023

Background

Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surfeit4 (Surf4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown.

Methods

We developed inducible intestinal-specificSurf4knockdown mice (Surf4IKO) usingVil1Cre-ERT2andSurf4floxmice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum.

Results

Surf4IKOmice, especially maleSurf4IKOmice, displayed significant body weight loss, increased mortality, and reduced metabolism.Surf4IKOmice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes ofSurf4IKOmice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered inSurf4IKOmice. In addition,Surf4IKOmice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels.

Conclusion

Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

Highlights

Intestinal Surf4 deficiency reduces chylomicron secretion.

Lack of intestinal Surf4 reduces absorption of dietary lipids.

Silencing intestinal Surf4 reduces serum lipid levels.

Intestinal Surf4 deficiency leads to lipid accumulation in intestinal villi.

Intestinal Surf4 is essential for dietary lipid absorption and secretion.
Gender quota in the civil service and female participation: Evidence from Nepal
Authors: Upadhaya Hari Prasad , Kwon Illoong
Published: February 2023

Female quotas for high‐ranking positions in corporations and governments should (i) increase the hiring of women and (ii) inspire more women to apply for these positions. The goal will be that eventually, (iii) even without the quota, more women will apply to and succeed in high‐ranked positions. This paper exploits the variations of female quotas in Nepalese civil service exams across years, services, ranks and exams within the same service to investigate these three effects. Empirical results show that female quotas in a given exam increase applications and the hiring of women. Even in exams without a quota, the female quotas of other exams within the same service increase the number of female applicants.
Surface layer proteins in species of the family Lactobacillaceae
Authors: Palomino M. Mercedes , Allievi Mariana C. , Gordillo Tania B. , Bockor Sabrina S. , Fina Martin Joaquina , Ruzal Sandra M.
Published: February 2023

The S‐layer or surface layer protein (SLP) is the most ancient biological envelope, highly conserved in several Bacteria and Archaea. In lactic acid bacteria (LAB), SLP is only found in species belonging to the Lactobacillaceae family, many of them considered probiotic microorganisms. New reclassification of members within the Lactobacillaceae family (International Journal of Systematic and Evolutionary Microbiology, 2020, 70, 2782) and newly sequenced genomes demands an updated revision on SLP genes and domain organization. There is growing information concerning SLP occurrence, molecular biology, biophysical properties, and applications. Here, we focus on the prediction of slp genes within the Lactobacillaceae family, and specifically, on the neat interconnection between the two different modular SLP domain organizations and the new reclassified genera. We summarize the results in a concise tabulated manner to review the present knowledge on SLPs and discuss the most relevant and updated concepts regarding SLP sequence clustering. Our assessment is based on sequence alignments considering the new genera classification and protein domain definition with post‐translational modifications. We analyse the difficulties encountered to resolve the SLPs 3D structure, describing the need for structure prediction approaches and the relation between protein structure and its anchorage mechanism to the cell wall. Finally, we enumerate new SLP applications regarding heterologous display, pathogen exclusion, immunostimulation, and metal binding.
Indigenous sustainable finance as a research field: A systematic literature review on indigenising ESG, sustainability and indigenous community practices
Authors: Poyser Andre , Daugaard Dan
Published: February 2023

Sustainable finance research has come into its own as an established area in the finance literature. The increased awareness of sustainability and global concerns around environmental, social and governance (ESG) issues, particularly among institutional investors, has catalysed a shift towards greater research and publications in this area. Accompanying this is the emerging body of work being produced on indigenous investments and indigenous community practices. These nascent strands of literature tell a story of the shift that is taking place within the finance field. To chart this shift and create a harmonised view of these bodies of work, this paper conducts a systematic literature review of the significant nexus between sustainable investments and indigenous approaches to sustainability. We present a framework for conceptualising and characterising the various stands of literature and, in so doing, make the case for Indigenous Sustainable Finance (ISF) as a distinct disciplinary field. This paper argues that ISF is distinct from mainstream sustainable finance and other social and management sciences and constitutes a legitimate, well‐defined sub‐field of research in its own right.
The TH22‐mediated IL‐22 deficiency associated with premature ovarian insufficiency
Authors: Zhang Wenzhe , Xu Shiru , Zhang Rongrong , Li Zhuqing , Li Nianyu , Zhang Xiruo , Lu Yueshuang , Bian Yuehong , Yang Ping , Fang Fang , Qin Yingying , Jiao Xue
Published: February 2023

Research question

Is deficiency of IL‐22 associated with premature ovarian insufficiency (POI)?

Design

Levels of IL‐22 and IL‐22BP, IL‐22‐producing T cells, and IL22RA1/IL10R2 expression were measured and compared among 29 patients with POI, 42 with precursor stage of POI (pre‐POI) and 46 control women. Correlation of serum IL‐22 and IL‐22+CD4+T subsets with ovarian reserve markers were further analyzed.

Results

IL‐22 levels in serum significantly differed among control women and patients with pre‐POI and POI, with the lowest concentrations in POI group (p = .019). Significant reduction of peripheral CD4+IL‐22+T cells was observed in patients with POI (p = .010), which mainly contributed by decrease of CD4+IL‐22+IL‐17− TH22 cells (p = .012) but not TH17 cells (p = .125). Levels of serum IL‐22 and IL‐22‐producing CD4+T subsets were significantly correlated with ovarian reserve markers, including AMH, bilateral AFC, follicle‐stimulating hormone (FSH), and E2 (p < .05). The specific receptor IL22RA1 expression was marginally reduced in granulosa cells from patients with pre‐POI (p = .051). No difference of IL‐22BP was observed either in serum (p = .216) or follicular fluid (p = .856) among groups.

Conclusions

Our study first demonstrated the significant association between TH22‐mediated IL‐22 deficiency and ovarian insufficiency, which provide new insights into the autoimmune disturbance and opens new avenues for exogenous IL‐22 administration as potential intervention of POI.