bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and Phenotypic Comparison of Polyhydroxyalkanoates Producing Strains of genusCaldimonas/Schlegelella
Authors: Musilova Jana , Kourilova Xenie , Hermankova Kristyna , Bezdicek Matej , Ieremenko Anastasiia , Dvorak Pavel , Obruca Stanislav , Sedlar Karel 
Published: September 2023

AbstractPolyhydroxyalkanoates (PHAs) have emerged as an ecologically friendly alternative to conventional polyesters. In this study, we present a comprehensive analysis of the genomic and phenotypic characteristics of three non-model thermophilic bacteria known for their ability to produce PHAs:Schlegelella aquaticaLMG 23380T,Caldimonas thermodepolymeransDSM 15264, andC. thermodepolymeransLMG 21645 accompanied by a comparison with the type strainC. thermodepolymeransDSM 15344T. We have assembled the first complete genomes of these three bacteria and performed the structural and functional annotation. This analysis has provided valuable insights into the biosynthesis of PHAs and has allowed us to propose a comprehensive scheme for the carbohydrate metabolism in the studied bacteria. Through phylogenomic analysis, we have confirmed the synonymity betweenCaldimonasandSchlegelellagenera, and further demonstrated thatS. aquaticaandS. koreensis, currently classified as orphan species, belong to theCaldimonasgenus.SummaryThe genomic and phenotypic analysis ofSchlegelella aquaticaLMG 23380TandCaldimonas thermodepolymeransDSM 15264 and LMG 21645 sheds light on the production of sustainable polyesters known as polyhydroxyalkanoates (PHAs). The genome assembly and functional annotation highlight key genes related to PHA production and other important traits. Notably,C. thermodepolymeransstands out with its uniquexyloperon, making it a highly promising candidate for biotechnological PHA production from xylose-rich lignocellulosic resources. The study emphasizes the importance of a polyphasic approach combining genotypic and phenotypic analyses in prokaryotic taxonomy, emphasizing the need for exploration in the genomic era. By uncovering the key traits of these bacteria, this research opens new horizons towards sustainable production of environmentally friendly polyesters.
Primate Saccade Rhythmicity
Authors: Näher Tim , Zhang Yufeng , Pandinelli Martina , Fries Pascal 
Published: September 2023

AbstractActive sensing behaviors in rodents display theta (4-8 Hz) rhythmicity. Whether similar rhythmicity exists in primate saccadic eye movements has remained a matter of debate. We studied saccade dynamics in 22 human participants and two macaque monkeys, examining the influence of different visual stimuli and tasks. Inter-saccadic intervals (ISIs) reliably revealed a characteristic duration and under certain conditions clear theta rhythmicity. Rhythmicity was strongest for saccades with short ISIs. Surprisingly, the degree of rhythmicity was not due to spatial regularity of the visual scene, but it was shaped by task demands. Macro- and micro-saccade ISIs shared similar characteristic durations. Naturally occurring micro-saccades provided evidence that ISIs can become more regular without becoming faster. During free-viewing, subsequent ISIs show long-range correlation structure and the visual system switched between states of low and high rhythmicity. Humans and macaques showed similar saccade dynamics, suggesting a potential common evolutionary trait in primate active visual sensing.
Kinetochore and ionomic adaptation to whole genome duplication
Authors: Bray Sian M. , Hämälä Tuomas , Zhou Min , Busoms Silvia , Fischer Sina , Desjardins Stuart D. , Mandáková Terezie , Moore Chris , Mathers Thomas C. , Cowan Laura , Monnahan Patrick , Koch Jordan , Wolf Eva M. , Lysak Martin A. , Kolar Filip , Higgins James D. , Koch Marcus A. , Yant Levi 
Published: September 2023

AbstractTransforming genomic and cellular landscapes in a single generation, whole genome duplication (WGD) brings fundamental challenges, but is also associated with diversification. How is WGD tolerated, and what processes commonly evolve to stabilize the resulting polyploid? Here we study this inCochleariaspp., which have experienced multiple WGDs in the last 300,000 years. We first generate a chromosome-scale genome and sequence 113 individuals from 33 diploid, tetraploid, hexaploid, and outgroup populations. We detect the clearest post-WGD selection signatures in functionally interacting kinetochore components and ion transporters. We structurally model these derived selected alleles, identifying striking WGD-relevant functional variation, and then compare these results to independent recent post-WGD selection inArabidopsis arenosaandCardamine amara. Most prominent in these results is genetic evidence of at least four functionally interacting kinetochore complex subunits in adaptation to WGD at the centromere among our very top selective sweep outliers. In addition, some of the same biological processes evolve in all three WGDs, but specific genes recruited are flexible. This points to a polygenic basis for modifying systems that control the kinetochore, meiotic crossover number, DNA repair, ion homeostasis, and cell cycle. Given that DNA management (especially repair) is the most salient category with the strongest selection signal, we speculate that the generation rate of structural genomic variants may be altered by WGD in young polyploids, contributing to their occasionally spectacular adaptability observed across kingdoms.Significance StatementWhole-genome duplication (WGD) occurs in all kingdoms and is linked to adaptation, speciation, domestication, and even cancer outcome. But WGD is a shock to the system, and commonly disrupts cell division due to increased DNA management burden and transformed cell physiology. Nevertheless, the hopeful monster that survives WGD is special, occasionally experiencing runaway success. Why do some thrive but others die? Here we introduce a powerful new model, Cochlearia, which has benefitted from multiple WGDs, and we provide the first genetic evidence of rapid adaptation of functionally interacting components of the cell division machinery, the kinetochore. We also compare which processes and genes evolve to stabilize the new polyploid in three independent cases and highlight common mechanisms.
Molecular and network disruptions in neurodevelopment uncovered by single cell transcriptomics analysis ofCHD8heterozygous cerebral organoids
Authors: Astorkia Maider , Liu Yang , Pedrosa Erika M. , Lachman Herbert M. , Zheng Deyou 
Published: September 2023

AbstractAbout 100 genes have been associated with significantly increased risks of autism spectrum disorders (ASD) with an estimate of ∼1000 genes that may be involved. The new challenge now is to investigate the molecular and cellular functions of these genes during neural and brain development, and then even more challenging, to link the altered molecular and cellular phenotypes to the ASD clinical manifestations. In this study, we use single cell RNA-seq analysis to study one of the top risk gene,CHD8, in cerebral organoids, which models early neural development. We identify 21 cell clusters in the organoid samples, representing non-neuronal cells, neural progenitors, and early differentiating neurons at the start of neural cell fate commitment. Comparisons of the cells with one copy of theCHD8knockout and their isogenic controls uncover thousands of differentially expressed genes, which are enriched with function related to neural and brain development, with genes and pathways previously implicated in ASD, but surprisingly not for Schizophrenia and intellectual disability risk genes. The comparisons also find cell composition changes, indicating potential altered neural differential trajectories uponCHD8reduction. Moreover, we find that cell-cell communications are affected in theCHD8knockout organoids, including the interactions between neural and glial cells. Taken together, our results provide new data for understanding CHD8 functions in the early stages of neural lineage development and interaction.
SeqVerify: An accessible analysis tool for cell line genomic integrity, contamination, and gene editing outcomes
Authors: Pierson Smela Merrick , Pepe Valerio , Church George M. 
Published: September 2023

1.SummaryOver the last decade, advances in genome editing and pluripotent stem cell (PSC) culture have let researchers generate edited PSC lines to study a wide variety of biological questions. However, abnormalities in cell lines such as aneuploidy, on-target and off-target editing errors, and microbial contamination can arise during PSC culture or due to undesired editing outcomes. Any of these abnormalities can invalidate experiments, so detecting them is crucial. The ongoing decline of next-generation sequencing prices has made whole genome sequencing (WGS) an effective quality control option, since WGS can detect any abnormality involving changes to DNA sequences or presence of unwanted sequences. However, this approach has suffered from a lack of easily usable data analysis software. Here, we present SeqVerify, a computational pipeline designed to take raw WGS data and a list of intended edits, and verify that the edits are present and that there are no abnormalities. We anticipate that SeqVerify will be a useful tool for researchers generating edited PSCs, and more broadly, for cell line quality control in general.
Diurnal cycles drive rhythmic physiology and promote survival in facultative phototrophic bacteria
Authors: Tinguely Camille , Paulméry Mélanie , Terrettaz Céline , Gonzalez Diego 
Published: September 2023

SummaryBacteria have evolved many strategies to spare energy when nutrients become scarce. One widespread such strategy is facultative phototrophy, which helps heterotrophs supplement their energy supply using light. Our knowledge on the impact that such behaviors have on bacterial fitness and physiology is, however, still limited. Here, we study how a representative of the genusPorphyrobacter,in which aerobic anoxygenic phototrophy is ancestral, responds to different light regimes under nutrient limitation. We show that bacterial survival in stationary phase relies on functional reaction centers and varies depending on the light regime. Under dark-light alternance, our bacterial model presents a diphasic life history dependent on phototrophy: during dark phases, the cells inhibit DNA replication and part of the population lyses and releases nutrients, while subsequent light phases allow for the recovery and renewed growth of the surviving cells. We correlate these cyclic variations with a pervasive pattern of rhythmic transcription which reflects global changes in diurnal metabolic activity. Finally, we demonstrate that, compared to either a phototrophy null mutant or a bacteriochlorophyllaoverproducer, the wild type strain is better adapted to natural environments, where regular dark-light cycles are interspersed with additional accidental dark episodes. Overall, our results highlight the importance of light-induced biological rhythms in a new model of aerobic anoxygenic phototroph representative of an ecologically important group of environmental bacteria.
An altered cell-specific subcellular distribution of translesion synthesis DNA polymerase kappa (POLK) in aging neurons
Authors: Abdelmageed Mofida , Palanisamy Premkumar , Vernail Victoria , Silberman Yuval , Paul Shilpi , Paul Anirban 
Published: September 2023

AbstractGenomic stability is critical for cellular function, however, in the central nervous system highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. Interneurons associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which will help design strategies for longevity, healthspan, and prevention of neurodegeneration.
Flight power muscles have a coordinated, causal role in hawkmoth pitch turns
Authors: Wood Leo , Putney Joy , Sponberg Simon 
Published: September 2023

ABSTRACTFlying insects solve a daunting control problem of generating a patterned and precise motor program to stay airborne and generate agile maneuvers. In this motor program consisting of every action potential controlling wing musculature, each muscle encodes significant information about movement in precise spike timing down to the millisecond scale. While individual muscles share information about movement, we do not yet know if they have separable effects on an animal’s motion, or if muscles functionally interact such that the effects of any muscle’s timing depends heavily on the state of the entire musculature. To answer these questions, we performed spike-resolution electromyography and precise stimulation of individual spikes in the hawkmothManduca sextaduring tethered flapping. We specifically explored how the flight power muscles themselves may contribute to pitch control which is necessary to stabilize flight. Combining correlational study of visually-induced turns with causal manipulation of spike timing, we discovered likely coordination patterns for pitch turns, investigated if these correlational patterns can individually drive pitch control, and studied whether the precise spike timing of indirect power muscles can lead to pitch maneuvers. We observed significant timing change of the main downstroke muscles, the dorsolongitudinal muscles (DLMs), associated with whether a moth was pitching up or down. Causally inducing this timing change in the DLMs with electrical stimulation produced a consistent, mechanically relevant feature in pitch torque, establishing that indirect power muscles inManducahave a control role in pitch. Because changes were evoked in unconstrained flapping in only the DLMs, however, these pitch torque features left large unexplained variation. We find this unexplained variation indicates significant functional overlap in pitch control such that precise timing of one power muscle does not produce a precise turn, demonstrating the importance of coordination across the entire motor program for flight.Summary StatementWe investigate how individual muscles contribute to flight by manipulating muscle timing in behaving hawkmoths. We find precise timing of single muscles does not produce precise turns, highlighting the importance of coordination across the entire motor program.
Syngap1Promotes Cognitive Function through Regulation of Cortical Sensorimotor Dynamics
Authors: Vaissiere Thomas , Michaelson Sheldon D. , Creson Thomas , Goins Jessie , Fürth Daniel , Balazsfi Diana , Rojas Camilo , Golovin Randall , Meletis Konstantinos , Miller Courtney A. , O’Connor Daniel , Fontolan Lorenzo , Rumbaugh Gavin 
Published: September 2023

SummaryPerception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene,Syngap1, in cortical excitatory neurons is required for formation of somatomotor networks that promote SMI-mediated perception. CorticalSyngap1expression was necessary and sufficient for setting tactile sensitivity, sustaining tactile object exploration, and promoting tactile learning. Mice with deficientSyngap1expression exhibited impaired neural dynamics induced by exploratory touches within a cortical-thalamic network known to promote attention and perception. Disrupted neuronal dynamics were associated with circuit-specific long-range synaptic connectivity abnormalities. Our data support a model where autonomousSyngap1expression in cortical excitatory neurons promotes cognitive abilities through assembly of circuits that integrate temporally-overlapping sensory and motor signals, a process that promotes perception and attention. These data provide systems-level insights into the robust association betweenSyngap1expression and cognitive ability.
Identification of Host Restriction Factors Critical for Recombinant AAV Transduction of Polarized Human Airway Epithelium
Authors: Hao Siyuan , Zhang Xiujuan , Ning Kang , Feng Zehua , Park Soo Yeun , Kuz Cagla Aksu , McFarlin Shane , Richart Donovan , Cheng Fang , Zhang Elizabeth Yan , Zhang-Chen Aaron , Yan Ziying , Qiu Jianming 
Published: September 2023

AbstractRecombinant (r)AAV2.5T was selected from the directed evolution of an AAV capsid library in human airway epithelium (HAE). The capsid gene of rAAV2.5T is a chimera of the N-terminal unique coding sequence of AAV2 VP1 unique (VP1u) and the VP2- and VP3-coding sequence of AAV5 with a single amino acid mutation of A581T. We conducted two rounds of genome wide CRISPR gRNA library screening for host factors limiting rAAV2.5T transduction in HeLa S3 cells. The screen identified several genes that are critical for rAAV2.5T transduction in HeLa S3 cells, including previously reported genesKIAA0319L,TM9SF2,VPS51, andVPS54, as well as a novel geneWDR63. We verified the role of KIAA0319L and WDR63 in rAAV2.5T transduction of polarized HAE by utilizing CRISPR gene knockouts. Although KIAA0319L, a proteinaceous receptor for multiple AAV serotypes, played an essential role in rAAV2.5T transduction of polarized HAE either from apical or basolateral side, our findings demonstrated that the internalization of rAAV2.5T was independent of KIAA0319L. Importantly, we confirmed WDR63 is an important player in rAAV2.5T transduction of HAE, while not being involved in vector internalization and nuclear entry. Furthermore, we identified that the basal stem cells of HAE can be significantly transduced by rAAV2.5T.SignificanceThe essential steps of a successful gene delivery by rAAV include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel geneWDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.
Lipid constituents fromCissus trifoliatastems
Authors: Méndez-López Luis Fernando , González Llerena José Luis , Espinosa-Rodríguez Bryan Alejandro , Balderas-Rentería Isaías , Camacho-Corona María Del Rayo 
Published: September 2023

AbstractObjectiveThe stems from plants of the genusCissusare used in traditional medicine worldwide. In MexicoCissus trifoliatais employed for the management of several diseases, however little is known about the active compounds. The present investigation focuses on the extraction, isolation, and characterization of the lipid contents from the stems ofC. trifoliataby chromatographic, spectroscopic, and spectrometric techniques.MethodsThe hexane extract was fractionated sequentially with hexane and ethanol and visualized by TLC. The compounds were isolated by column chromatography and structurally elucidated using NMR. In addition, the complete extract and solids obtained by fractionations were analyzed by GC-MS.ResultsAccording to NMR signals, solids present in the hexane extract correspond to hentriacontane, octatetracontane, octacosanoic acid, tricosyl tetracosanoate and sitosterol. Furthermore, the analysis by GC-MS found 33 compounds, and the most abundant were hentriacontane, squalene, palmitic acid, oleic acid, β-sitosterol, and nonacosane.ConclusionThis report describes the major constituents in the hexane extract fromCissus trifoliatastems. Our analysis suggests an abundant composition of higher alkanes, fatty acids, and sterols, which are the major lipid components of cuticular waxes and plant cell membranes.
Broad intraspecies killing activity inPseudomonas syringaedue to the combinatorial action of LPS-interacting bacteriocins
Authors: Weaver Savannah L. , Casamassima Emma , Nguyen Anh Evy , Baltrus David A. 
Published: September 2023

ABSTRACTBacteriocins are a diverse group of highly specific antimicrobials produced by bacteria, thought to mainly target and kill strains that are closely related to and which therefore potentially compete in the same niche space as producer cells. Single strains can produce more than one type of bacteriocin, with each usually having differing modes of action and receptors for binding, and with strain specificity for each independent bacteriocin due to the requirement for these molecules to bind to receptors in target cells prior to carrying out antibacterial functions. Here we show thatPseudomonas syringaepv. aptata DSM50252 (Ptt) displays broad intraspecific killing activity due to combinatorial and non-overlapping activities of phage derived bacteriocins (referred to as tailocins) as well as a prophage encoded lectin-like bacteriocin (aptatacin L1). These results highlight how single strains can maintain broad killing activity against a variety of potential competitors by targeting multiple conformations of a shared receptor, and provide additional evidence that tailocins and aptatacin L1 both utilize rhamnose moieties in the LPS as potential receptors for binding.