bluuebunny/crossref_metadata_2025_split huggingface dataset:
A trait-based understanding of the vulnerability of a paleotropical moth community to predation by a sympatric bat with flexible foraging strategies
Authors: Dey Pritha , Balakrishnan Rohini 
Published: August 2023

AbstractPrey profitability for a predator hunting diverse prey varies with species and seasons. Whereas prey selection by aerial-hawking or gleaning bats is well established, this is challenging to establish in species that adopt both these strategies flexibly. Measurable prey traits coupled with availability in the foraging grounds help characterize the vulnerability of prey species to predation.In the Western Ghats of India, a global biodiversity hotspot, we studied an anthropogenic landscape, where insectivorous bats are abundant and diverse, but their impact on moth communities is little understood. We investigated the morphological traits of a sympatric moth community that make them more vulnerable to predation byMegaderma spasma, a bat with flexible foraging strategies. We also established the seasonal composition of moth prey in the diet of the bat.We analyzed the discarded prey remains from several roosts, collected over three years, for seasonal patterns in the diet and selective hunting. Through light-trapping, we collected moth specimens in different seasons to assess the morphological traits of the moth community available in the foraging area of the bat.The traits likely to affect the profitability of prey moths were measured: forewing length, hindwing length, wingspan, and body length (a proxy for body size); forewing area, hindwing area, maneuverability, and wing loading (as a proxy for evasive flight capability), and forewing aspect ratio (as a proxy for wing shape).Our results showed that consumed moth prey diversity varies seasonally, with moths belonging to the Hepialidae family being preferred in the wet season. Moths belonging to the Sphingidae family were the most abundant in the diet, followed by Erebidae and Hepialidae. Sphingid moths have the lowest maneuverability, and highest forewing aspect ratio; the Hepialidae moths have the maximum body size followed by Sphingids thus confirming our hypothesis that larger moths with low evasive capabilities are more vulnerable to predation.Assessing vulnerability at the prey community level, we establish a framework for future research on moth-bat interactions from the diverse and less-explored paleotropical communities. Additionally, the study reiterates the usefulness of trait-based approaches to understanding prey-predator dynamics.
Universal pretreatment development for low-input proteomics using Lauryl Maltose Neopentyl Glycol
Authors: Konno Ryo , Ishikawa Masaki , Nakajima Daisuke , Endo Yusuke , Ohara Osamu , Kawashima Yusuke 
Published: August 2023

AbstractIn recent years, the demand for low-input proteomics, most notably single-cell proteomics (SCP), has increased. In this study, we developed a Lauryl Maltose Neopentyl Glycol (LMNG)-assisted sample preparation (LASP) method that suppresses the loss of proteins and peptides in samples by adding LMNG, a surfactant, to the digested solution and removing the LMNG simply via reversed phase solid-phase extraction. The advantage of removing LMNG during sample preparation for general proteomic analysis is that it prevents mass spectrometry (MS) contamination. When the LASP method was applied to the low-input SP3 method and on-bead digestion in immunoprecipitation-MS, the recovery of the digested peptides was greatly improved. Furthermore, we established a simple and operationally easy sample preparation method for SCP based on the LASP method (scpLASP) and identified a median of 1,175 proteins from a single HEK239F cell using liquid chromatography (LC)-MS/MS with a throughput of 80 samples per day.
Transthyretin has conformation-selective proteolytic activity against α-synuclein
Authors: Sárkány Zsuzsa , Gião Tiago , Liz Márcia Almeida , Planas Antoni , Macedo-Ribeiro Sandra , Cardoso Isabel , Arsequell Gemma , Martins Pedro M. 
Published: August 2023

AbstractTransthyretin (TTR) is a plasma protein known as a transporter of thyroxine and retinol but also can inhibit the formation of amyloid β-peptide (Aβ) fibrils and catalyze the proteolysis of apolipoprotein A-I and Aβ. Here, recombinant TTR is shown to have proteolytic activity against specific conformations of α-synuclein (aSyn), a protein that accumulates in intraneuronal inclusions characteristic of Parkinson’s disease (PD). Our discovery stemmed from the observation of a marked decrease in aSyn aggregation in the presence of submicromolar concentrations of TTR. Using integrated biophysical techniques, including advanced microscopy and mass spectrometry, we found that aSyn aggregation is prevented due to the proteolytic cleavage of free aSyn by TTR, in a reaction that is slower for S-glutathionylated TTR and faster for TTR preparations containing vestigial amounts of ∼70 kDa TTR oligomers (oTTR). Interestingly, this proteolysis-trigger effect is not unique to oTTR since it can also be induced by Teflon and glass surfaces independently of which TTR preparation is tested. Our results indicate that a change in aSyn conformation must precede the proteolysis step. The proteolysis of misfolded aSyn emerges as a possible TTR function with implications for the understanding of different neurodegenerative disorders.
Biophysical analysis reveals autophosphorylation as an important negative regulator of LRRK2 dimerization
Authors: Guaitoli Giambattista , Zhang Xiaojuan , Saitta Francesca , Miglionico Pasquale , Silbermann Laura M. , Ho Franz Y. , von Zweydorf Felix , Signorelli Marco , Tych Kasia , Fessas Dimitrios , Raimondi Francesco , Kortholt Arjan , Gloeckner Christian Johannes 
Published: August 2023

AbstractLeucine-rich repeat kinase 2 (LRRK2) is a large, multi-domain protein which is associated with Parkinson’s disease. Although high-resolution structures of LRRK2 are available, little is known about the complex dynamics behind the inter-domain regulation of LRRK2 and its perturbation by pathogenic variants. Previous studies have demonstrated that LRRK2 goes through an oligomerization cycle at the membrane, however it remains unclear in which form it exerts its kinase activity. Moreover, the LRRK2 monomer-dimer equilibrium and associated functional implications at a molecular level also need further investigation. In the present work, we used a multi-faceted approach to better understand LRRK2 oligomerization and suggest a functional model of how LRRK2 interacts with its substrates. To this end, we combined nano differential scanning calorimetry and mass photometry with molecular modelling. The thermal analysis resulted in a multistep denaturation profile, elucidating novel insights into the composite structural organization of the multi-domain protein LRRK2. Furthermore, LRRK2 shows a remarkable thermal stability, confirming its oligomeric nature. By using mass photometry, we could observe a monomer-dimer equilibrium which is altered by R1441G, a pathogenic variant within the Roc-COR interface. Most importantly, we could demonstrate that autophosphorylation induces LRRK2 monomerization, indicating a novel intramolecular feedback mechanism. Finally, we investigated the interaction of LRRK2 with its substrate, RAB10 by integrative computational modelling. The resulting models suggest that the monomeric form of LRRK2 is the favored protein conformation for the interaction with its substrate, leading to an increasing interest in the monomer-dimer equilibrium as a possible intervention point for the pathology.
Heterogeneity of radial spokes structural components and associated enzymes inTetrahymenacilia
Authors: Bicka Marta , Black Corbin , Ghanaeian Avrin , Joachimiak Ewa , Osinka Anna , Majhi Sumita , Konopka Anna , Bulska Ewa , Bui Khanh Huy , Wloga Dorota 
Published: August 2023

AbstractRadial spokes (RS), the T-shaped, multiprotein complexes of motile cilia, transmit regulatory signals from the central apparatus to the outer doublet complexes, including inner dynein arms. In the vast majority of ciliated species, RSs assemble as repeats of triplets (RS1-RS2-RS3), and each spoke is associated with a different subset of inner dynein arms. Studies inChlamydomonasand mice sperm flagella led to the identification of RS proteins (RSPs) and revealed that some structural components are either RS1- or RS2-specific. In contrast, the protein composition of RS3 remains largely unknown. We used the ciliateTetrahymena thermophilato investigate the protein composition of individual RSs, including the poorly characterized RS3. TheTetrahymenagenome encodes three RSP3 paralogs. Using engineeredRSP3knock-out mutants and previously studied RS mutants withCFAP61,CFAP91, orCFAP206deletion and complementary approaches, including bioinformatics, total ciliome comparisons, and cryo-electron tomography with subtomogram averaging, we identifiedTetrahymenaRSP orthologs and solved the composition of individual RSs, showing their subunit heterogeneity. We found that RSP3 proteins are components of RS1 and RS2 but not RS3. Based on the presence of the RSP3 paralog, we distinguished sub-types of RS1 (RSP3A- or RSP3B-containing) and RS2 spokes (RSP3B- or RSP3C-containing). We identified novel RS-associated proteins, including several enzymes that may locally regulate ADP/ATP levels, GMP-recycling-related enzymes, and enzymes regulating phosphorylation levels. These discoveries will help to better understand the molecular mechanism(s) that regulate cilia beating and overall cilia metabolism.Impact StatementIdentification of the subtypes of RS1 and RS2 spokes and RS1-3-specific RSPs. Discovery of the novel radial spoke structural components and RS-associated enzymes regulating ADP/ATP ratio and protein phosphorylation.
Decoding host-microbiome interactions through co-expression network analysis within the non-human primate intestine
Authors: Uehara Mika , Inoue Takashi , Hase Sumitaka , Sasaki Erika , Toyoda Atsushi , Sakakibara Yasubumi 
Published: August 2023

ABSTRACTThe gut microbiome affects the health status of the host through complex interactions with the host’s intestinal wall. These host-microbiome interactions may spatially vary along the physical and chemical environment of the intestine, but these changes remain unknown. This study investigated these intricate relationships through a gene co-expression network analysis based on dual transcriptome profiling of different intestinal sites—cecum, transverse colon, and rectum— of the primate common marmoset. We proposed a gene module extraction algorithm based on graph theory to find tightly interacting gene modules of the host and the microbiome from a vast co-expression network. The 27 gene modules identified by this method, which include both host and microbiome genes, not only produced results consistent with previous studies regarding the host-microbiome relationships, but also provided new insights into microbiome genes acting as potential mediators in host-microbiome interplays. Specifically, we discovered associations between the host geneFBP1, a cancer marker, and polysaccharide degradation-related genes (pfkAandfucI) coded byBacteroides vulgatus, as well as relationships between host B-cell specific genes (CD19,CD22,CD79B,PTPN6) and a tryptophan synthesis gene (trpB) coded byParabacteroides distasonis. Furthermore, our proposed module extraction algorithm surpassed existing approaches by successfully defining more functionally related gene modules, providing insights for understanding the complex relationship between the host and the microbiome.IMPORTANCEWe unveiled the intricate dynamics of the host-microbiome interactions along the colon by identifying closely interacting gene modules from a vast gene co-expression network, constructed based on simultaneous profiling of both host and microbiome transcriptomes. Our proposed gene module extraction algorithm, designed to interpret inter-species interactions, enabled the identification of functionally related gene modules encompassing both host and microbiome genes, which was challenging with conventional modularity maximization algorithms. Through these identified gene modules, we discerned previously unrecognized bacterial genes that potentially mediate in known relationships between host genes and specific bacterial species. Our findings underscore the spatial variations in host-microbiome interactions along the colon, rather than displaying a uniform pattern throughout the colon.
Molecular basis for short-chain thioester hydrolysis by acyl hydrolase domains intrans-acyltransferase polyketide synthases
Authors: Fage Christopher D. , Passmore Munro , Tatman Ben P. , Smith Helen G. , Jian Xinyun , Dissanayake Upeksha C. , Andrés Cisneros G. , Challis Gregory L. , Lewandowski Józef R. , Jenner Matthew 
Published: August 2023

ABSTRACTPolyketide synthases (PKSs) are multi-domain enzymatic assembly lines that biosynthesise a wide selection of bioactive natural products from simple building blocks. In contrast to theircis-acyltransferase (AT) counterparts,trans-AT PKSs rely on stand-alone AT domains to load extender units onto acyl carrier protein (ACP) domains embedded in the core PKS machinery.Trans-AT PKS gene clusters also encode acyl hydrolase (AH) domains, which are predicted to share the overall fold of AT domains, but hydrolyse aberrant acyl chains from ACP domains, thus ensuring efficient polyketide biosynthesis. How such domains specifically target short acyl chains, in particular acetyl groups, tethered as thioesters to the substrate-shuttling ACP domains, with hydrolytic rather than acyl transfer activity, has remained unclear. To answer these questions, we solved the first structure of an AH domain and performed structure-guided activity assays on active site variants. Our results offer key insights into chain length control and selection against coenzyme A-tethered substrates, and clarify how the interaction interface between AH and ACP domains contributes to recognition of cognate and non-cognate ACP domains. Combining our experimental findings with molecular dynamics simulations allowed for the production of a data-driven model of an AH:ACP domain complex. Our results advance the currently incomplete understanding of polyketide biosynthesis bytrans-AT PKSs, and provide foundations for future bioengineering efforts.
Microbial eukaryotic predation pressure and biomass at deep-sea hydrothermal vents: Implications for deep-sea carbon cycling
Authors: Hu Sarah K. , Anderson Rika E. , Pachiadaki Maria G. , Edgcomb Virginia P. , Serres Margrethe H. , Sylva Sean P. , German Christopher R. , Seewald Jeffrey S. , Lang Susan Q. , Huber Julie A. 
Published: August 2023

AbstractDeep-sea hydrothermal vent geochemistry shapes the foundation of the microbial food web by fueling chemolithoautotrophic microbial activity. Microbial eukaryotes (or protists) play a critical role in hydrothermal vent food webs as consumers, hosts of symbiotic bacteria, and as a nutritional source to higher trophic levels. We measured cell abundances and predation pressures of vent-associated microbial eukaryotes in low temperature diffuse hydrothermal fluids at the Von Damm and Piccard vent fields along the Mid-Cayman Rise in the Western Caribbean Sea. We present findings from experiments performed underin situpressure that show higher cell abundances and grazing rates compared to those done at 1 atmosphere (shipboard ambient pressure); this trend was attributed to the impact of depressurization on cell integrity. A relationship between protistan grazing rate, prey cell abundance, and temperature of end member hydrothermal vent fluid was observed at both vent fields, regardless of experimental approach. The quantification of protistan biomass and grazing pressure shows that hydrothermally-fueled microbial food webs play a significant role in the broader deep-sea carbon budget by contributing to local carbon export and supply of nutrient resources to the deep ocean.
An adult clock component links circadian rhythms to pancreatic β-cell maturation
Authors: Montalvo Ana P. , Gruskin Zoe L. , Leduc Andrew , Liu Mai , Gao Zihan , Ahn June H. , Straubhaar Juerg R. , Slavov Nikolai , Alvarez-Dominguez Juan R. 
Published: August 2023

AbstractHow ubiquitous circadian clocks orchestrate tissue-specific outputs is not well understood. Pancreatic β cell-autonomous clocks attune insulin secretion to daily energy cycles, and desynchrony from genetic or behavioral disruptions raises type 2 diabetes risk. We show that the transcription factor DEC1, a clock component induced in adult β cells, coordinates their glucose responsiveness by synchronizing energy metabolism and secretory gene oscillations.Dec1-ablated mice develop lifelong hypo-insulinemic diabetes, despite normal islet formation and intact circadianClockandBmal1activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, andDec1loss disrupts their transcription synchrony. Accordingly, β-cellDec1ablation causes hypo-insulinemia due to immature glucose responsiveness, dampening insulin rhythms. Thus, Dec1 links circadian clockwork to the β-cell maturation process, aligning metabolism to diurnal energy cycles.
Bifunctional Monosaccharides Preferentially Localize to Nuclear Subcompartments
Authors: Barahtjan Pavel , Iglesias-Artola Juan M. , Böhlig Kristin , Lohmann Annett , Nadler André 
Published: August 2023

AbstractRecent progress in glycan research has been driven by widespread implementations of metabolic oligosaccharide engineering. Complementing existing approaches, we here introduce bifunctional, UV-crosslinkable and clickable N-acetylglucosamine and N-acetylgalactosamine analogues, which enable direct visualization of the intracellular probe distribution as well as distinguishing monomeric and macromolecule-bound fractions. Using this feature, we find that monomeric N-acetylmonosaccharides partition into RNA-rich nuclear compartments such as nuclear speckles and nucleoli. This suggests the existence of spatially separated N-acetylmonosccharide pools within the nucleoplasm. Taken together, bifunctional N-acetylmonosaccharide probes are a powerful discovery tool for probing intracellular localization of monosaccharides and glycosylated macromolecules.
Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients’ neurons
Authors: Romanovsky Eva , Choudhary Ashwani , Peles David , Akel Ahmad Abu , Stern Shani 
Published: August 2023

ABSTRACTAutism spectrum disorders (ASDs) are highly heritable and result in abnormal repetitive behaviors and impairment in communication and cognitive skills. Previous studies have focused on the genetic correlation between ASDs and other neuropsychiatric disorders, but an in-depth understanding of the correlation to other disorders is required. We conducted an extensive meta-analysis of common variants identified in ASDs by genome-wide association studies (GWAS) and compared it to the consensus genes and single nucleotide polymorphisms (SNPs) of Schizophrenia (SCZ). We found approximately 75% of the SNPs that are associated with ASD are also associated with SCZ. We have also probed cellular phenotypes reported in ASD neurons compared to SCZ neurons from induced pluripotent stem cell (iPSC) models. Interestingly, Autism neurons start with an early maturation and schizophrenia neurons start with a late maturation, but both end up with deficits in synaptic activity when compared to control neurons as they mature.
Cryopreservation effect on DNA methylation profile in rainbow trout spermatozoa
Authors: El Kamouh Marina , Brionne Aurélien , Laurent Audrey , Labbé Catherine 
Published: August 2023

AbstractSpermatozoa are the cells the most commonly used for cryopreservation of valuable genetic resources in aquaculture. It is known that fish spermatozoa transmit to the embryo not only their genetic but also their epigenetic profile, particularly DNA methylation. Therefore, any alteration of the DNA methylation profile in spermatozoa induces the risk of transmitting epigenetic alterations to the offspring. The aim of this study was to assess the effect of cryopreservation on DNA methylation in rainbow trout spermatozoa. To trigger variable cellular response after freezing-thawing, spermatozoa from mature males were cryopreserved with dimethyl sulfoxide, methanol or glycerol as cryoprotectant. We observed that dimethyl sulfoxide was the best to preserve thawed spermatozoa functions. Methanol preserved only slightly all the cellular parameters, while glycerol failed to protect motility and fertilization ability. The consequences on DNA methylation were assessed using Reduced Representation Bisulfite Sequencing (RRBS). Sperm cryopreservation did not thoroughly impact DNA methylation, although 335 to 564 differentially methylated cytosines were characterized depending on the cryoprotectant. Very few of them were shared between cryoprotectants, and no correlation with the extent of cellular damage was found. Our study showed that DNA methylation was only slightly altered after sperm cryopreservation, and this may render further analysis of the risk for the progeny very challenging.
Hepatitis B virus x (HBx) protein increases cellular OCT3/4 and MYC and facilitates cellular reprogramming
Authors: Sanal Madhusudana Girija , Gupta Sarita , Saha Rahul , Vats Nisha , Sarin Shiv Kumar 
Published: August 2023

AbstractHBx is a multifunctional protein coded by the Hepatitis B virus which is involved in various cellular processes such as proliferation, cell survival/apoptosis, and histone methylation. HBx was reported to be associated with liver ‘cancer stem cells’. The stemness inducing properties of HBx could also facilitate the generation of pluripotent stem cells from somatic cells. It is well established that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSC) using a cocktail of transcription factors called Yamanaka’s factors (OCT4, SOX2, KLF4, and MYC). The reprogramming process proceeds step-by-step with reprogramming factor chromatin interactions, transcription and chromatin states changing during transitions. HBx is a ‘broad spectrum trans-activator’ and therefore could facilitate these transitions. We electroporated low passage and high passage (difficult to reprogram) fibroblasts using Yamanaka’s factors (YF) with and without HBx and evaluated the reprogramming efficiency. We also investigated the tri-lineage and terminal differentiation potential of iPSC derived using HBx. We found, addition of HBx to YF, improves iPSC derivation, and increases the efficiency of iPSC generation from ‘difficult or hard-to-reprogram samples’ such as high passage/senescent fibroblasts. Furthermore, we show that HBx can substitute the key transcription factor MYC in the YF cocktail to generate iPSC. Our results have practical value in improving the efficiency of pluripotent stem cell derivation from ‘difficult to reprogram’ somatic cells in addition to providing some insights into the mechanisms of liver carcinogenesis in chronic hepatitis B. To conclude, HBx improves the reprogramming efficiency of YFs. HBx increases the cellular levels of OCT3/4 and MYC.Lay summaryHBx is a protein made by hepatitis B virus. Yamanaka’s Factors (YF) are a mixture of ‘master-proteins’ which are used to convert adult cells to embryonic stem cells. We found that HBx protein can augment the efficiency of YF in generating these stem cells (concept summary figure).