bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel assay for endangered Hong Kong grouper (Epinephelus akaara) to assess eDNA shedding, decay, and population status
Authors: Chung Arthur , Kam Y.C. , Schunter Celia
Published: March 2024

Overexploitation is a major threat to marine ecosystems, causing collapse of numerous fisheries since the 19thcentury. The Hong Kong Grouper (Epinephelus akaara) is a commercial fish species that suffered at least 50-80% population declines in the past 40 years throughout its distribution range. Yet there has been minimal research or specific management, resulting in insufficient data on abundance, reproduction and habitat utilization. Here we aim to develop a novel species-specific quantitative PCR (qPCR) assay to detect potential occurrence ofE. akaarathrough non-invasive environmental water samples. We developed a qPCR assay amplifying 71 bps of the mitochondrial ND2 gene which offers high sensitivity and specificity. To quantify theE. akaarapopulation with the emerging environmental DNA (eDNA) tool, however, species-specific shedding and decay rates are crucial. The decay rate ofE. akaarawas similar to that of reported values of other marine fish species. However, the shedding rate ofE. akaarawas found to be few orders of magnitude lower which may be related to the relatively low activity and energy use from solitary and sedentary behavior of groupers. This highlights the importance of empirically determining species or taxon-specific shedding and decay rates to inform accurate abundance estimates with modelling tools for eDNA concentrations. Only 6 out of 88 water samples (6.81%) collected across 4 sampling seasons and 11 sites around Hong Kong showed positive signals at a concentration below limit of detection of the assay, implying its rarity in Hong Kong nowadays. Overall, we demonstrate that eDNA with our qPCR assay is efficient and sensitive in detecting the target species and is a promising tool in documenting endangered species for species management and conservation.
Influenza sequence validation and annotation using VADR
Authors: Calhoun Vincent C , Hatcher Eneida L , Yankie Linda , Nawrocki Eric P
Published: March 2024

Tens of thousands of influenza sequences are deposited into the GenBank database each year. The software tool FLAN has been used by GenBank since 2007 to validate and annotate incoming influenza sequence submissions, and has been publicly available as a webserver but not as a standalone tool. VADR is a general sequence validation and annotation software package used by GenBank for Norovirus, Dengue virus and SARS-CoV-2 virus sequence processing that is available as a standalone tool. We have created VADR influenza models based on the FLAN reference sequences and adapted VADR to accurately annotate influenza sequences. VADR and FLAN show consistent results on the vast majority of influenza sequences, and when they disagree VADR is usually correct. VADR can also accurately process influenza D sequences as well as influenza A H17, H18, H19, N10 and N11 subtype sequences, which FLAN cannot. VADR 1.6.3 and the associated influenza models are now freely available for users to download and use.
ComprehensiveInvitroandInsilicoAnalysis of Secondary Metabolites fromDatura metel: Promising Anti-Alzheimer’s Therapeutics
Authors: Sharma Meenakshi , Jain Mukul , Patil Nil , Barnwal Abhishek , Tayade Sumeet , Delta Anil Kumar , Kole Chittaranjan , Kaushik Prashant
Published: March 2024

This research investigates secondary metabolites fromDatura metelas potential anti-Alzheimer’s therapies. In vitro techniques isolated extracts for AD pathology targeting, with in silico analysis identifying gene targets for prevention. Apigenin, Luteolin, and Withanolide A were studied, each with 300 potential gene targets and core gene counts of 54, 52, and 58 respectively. Lipinski’s Rule assessed their pharmacological properties, showing good absorption but limited blood-brain barrier penetration. Protein interaction mapping revealed shared targets among the compounds. GO enrichment and KEGG pathway analysis highlighted their impact on biological processes and pathways, suggesting their anti-Alzheimer’s potential. Luteolin notably reduced Aβ1–42 levels by up to 35.2% (*p<0.05) in SH-SY5Y cells, positioning it and Withanolide A as promising multi-functional Alzheimer’s medications. These findings underscore the significance of Datura phytochemicals in AD prevention and treatment.
Characterization of Genome-wide Phylogenetic Conflict Uncovers Evolutionary Modes of Carnivorous Fungi
Authors: Zhang Weiwei , Fan Yani , Deng Wei , Chen Yue , Wang Shunxian , Kang Seogchan , Steenwyk Jacob Lucas , Xiang Meichun , Liu Xingzhong
Published: March 2024

Mass extinction has often paved the way for rapid evolutionary radiation, resulting in the emergence of diverse taxa within specific lineages. While the emergence and diversification of carnivorous nematode-trapping fungi (NTF) in Ascomycota has been linked to the Permian-Triassic (PT) extinction, the processes underlying NTF radiation remain unclear. Here, we conducted phylogenomic analyses using 23 genomes spanning three NTF lineages, each employing distinct nematode traps — mechanical traps (Drechslerellaspp.), three-dimensional (3-D) adhesive traps (Arthrobotrysspp.), and two-dimensional (2-D) adhesive traps (Dactylellinaspp.), and one non-NTF species as the outgroup. This analysis revealed how diverse mechanisms contributed to the tempo of NTF evolution and rapid radiation. The genome-scale species tree of NTFs suggested thatDrechslerellaemerged earlier thanArthrobotrysandDactylellina. Extensive genome-wide phylogenetic discordance was observed, mainly due to incomplete lineage sorting (ILS) between lineages (∼81.3%). Modes of non-vertical evolution (i.e., introgression and horizontal gene transfer) also contributed to phylogenetic discordance. The ILS genes that are associated with hyphal growth and trap morphogenesis (e.g., those associated with the cell membrane system and cellular polarity division) exhibited signs of positive selection.
Circadian control in the timing of critical periods duringDrosophilalarval neuronal development
Authors: Doran Sarah , Bradlaugh Adam A. , Corke Jack , Baines Richard A.
Published: March 2024

Critical periods (CPs) of development are temporal windows of heightened neural plasticity. Activity perturbation during CPs can produce significant, and permanent, alterations to the development of neural circuits. In this study we report a circadian mechanism underlying the timing of CPs inDrosophilaembryonic and larval development. These CPs occur at ∼24 hr intervals and are open to manipulation through blue light (BL)-activation of the circadian regulator Cryptochrome (CRY). This manipulation is sufficient to destabilize the larval CNS, evidenced by an induced seizure phenotype when tested at third instar (L3). In addition to CRY nulls, genetic ablation of theperiodgene also mitigates the BL exposure seizure phenotype and, moreover, alleles ofperiodthat affect circadian timing alter the timing of the CPs. Our analysis shows a clear role for the main clock neuropeptide, pigment dispersing factor (PDF), to transduce the output of these CPs. Targeted PDF receptor knockdown, in either GABAergic or CRY-positive neurons, is sufficient to prevent the CRY-mediated seizure phenotype. This study is a first demonstration of a circadian mechanism inDrosophilalarvae, and whilst this alone is of major significance, our results highlight the potential of usingDrosophilalarvae as a model to investigate the impact of circadian rhythms on early neuronal development in higher organisms, which remains experimentally challenging.

Significance Statement

Whilst the role of the biological clock is well understood in adult organisms, the same is not true for embryonic development. How the maternal clock impacts the mammalian fetus remains poorly understood. Given that many expectant mothers experience altered circadian rhythms, largely due to nightshift working, it is important to address these concerns. Here we identify clock-mediated periods in neural development of the embryonic Drosophila which can be manipulated by light. These findings provide an experimental opportunity to better understand the role of the circadian clock in early development.
Deep learning to decode sites of RNA translation in normal and cancerous tissues
Authors: Clauwaert Jim , McVey Zahra , Gupta Ramneek , Yannuzzi Ian , Menschaert Gerben , Prensner John R.
Published: March 2024

The biological process of RNA translation is fundamental to cellular life and has wide-ranging implications for human disease. Yet, accurately delineating the variation in RNA translation represents a significant challenge. Here, we develop RiboTIE, a transformer model-based approach to map global RNA translation. We find that RiboTIE offers unparalleled precision and sensitivity for ribosome profiling data. Application of RiboTIE to normal brain and medulloblastoma cancer samples enables high-resolution insights into disease regulation of RNA translation.
GeneSqueeze: A Novel Lossless, Reference-Free Compression Algorithm for FASTQ/A Files
Authors: Nazari Foad , Patel Sneh , LaRocca Melissa , Czarny Ryan , Schena Giana , Murray Emma K.
Published: March 2024

As sequencing becomes more accessible, there is an acute need for novel compression methods to efficiently store this data. Omics technologies can enhance biomedical research and individualize patient care, but they demand immense storage capabilities, especially when applied to longitudinal studies. Addressing the storage challenges posed by these technologies is crucial for omics technologies to achieve their full potential. We present a novel lossless, reference-free compression algorithm, GeneSqueeze, that leverages the patterns inherent in the underlying components of FASTQ files (i.e., nucleotide sequences, quality scores and read identifiers). GeneSqueeze provides several benefits, including an auto-tuning compression protocol based on each sample’s distribution, lossless preservation of IUPAC nucleotides and read identifiers, and unrestricted FASTQ/A file attributes (i.e., read length, read depth, or read identifier format). We compared GeneSqueeze to the general-purpose compressor, gzip, and to the domain-specific compressor, SPRING. GeneSqueeze achieved up to three times higher compression ratios as compared to gzip, regardless of read length, read depth, or file size. GeneSqueeze achieved 100% lossless compression, with the original and decompressed files perfectly matching for all tested samples, preserving read identifiers, quality scores, and IUPAC nucleotides, in contrast to SPRING. Overall, GeneSqueeze represents a competitive and specialized compression method optimized for FASTQ/A files containing nucleotide sequences that has the potential to significantly reduce the storage and transmission costs associated with large omics datasets without sacrificing data integrity.
2P-NucTag: on-demand phototagging for molecular analysis of functionally identified cortical neurons
Authors: Shi Jingcheng , Nutkovich Boaz , Kushinsky Dahlia , Rao Bovey Y , Herrlinger Stephanie A , Tsivourakis Emmanouil , Mihaila Tiberiu S , Malina Katayun Cohen-Kashi , OToole Cliodhna K , Conde Paredes Margaret E , Yong Hyun C , Sanner Brynn M , Xie Angel , Varol Erdem , Losonczy Attila , Spiegel Ivo
Published: March 2024

Neural circuits are characterized by genetically and functionally diverse cell types. A mechanistic understanding of circuit function is predicated on linking the genetic and physiological properties of individual neurons. However, it remains highly challenging to map the transcriptional properties to functionally heterogeneous neuronal subtypes in mammalian cortical circuits in vivo. Here, we introduce a high-throughput two-photon nuclear phototagging (2P-NucTag) approach optimized for on-demand and indelible labeling of single neurons via a photoactivatable red fluorescent protein following in vivo functional characterization in behaving mice. We demonstrate the utility of this function-forward pipeline by selectively labeling and transcriptionally profiling previously inaccessible place and silent cells in the mouse hippocampus. Our results reveal unexpected differences in gene expression between these hippocampal pyramidal neurons with distinct spatial coding properties. Thus, 2P-NucTag opens a new way to uncover the molecular principles that govern the functional organization of neural circuits.
Analysis of the limitedM. tuberculosisaccessory genome reveals potential pitfalls of pan-genome analysis approaches
Authors: Marin Maximillian G. , Wippel Christoph , Quinones-Olvera Natalia , Behruznia Mahboobeh , Jeffrey Brendan M. , Harris Michael , Mann Brendon C. , Rosenthal Alex , Jacobson Karen R. , Warren Robin M. , Li Heng , Meehan Conor J. , Farhat Maha R.
Published: March 2024

Pan-genome analysis is a fundamental tool for studying bacterial genome evolution; however, the variety of methods used to define and measure the pan-genome poses challenges to the interpretation and reliability of results. To quantify sources of bias and error related to common pan-genome analysis approaches, we evaluated different approaches applied to curated collection of 151Mycobacterium tuberculosis(Mtb) isolates.Mtbis characterized by its clonal evolution, absence of horizontal gene transfer, and limited accessory genome, making it an ideal test case for this study. Using a state-of-the-art graph-genome approach, we found that a majority of the structural variation observed inMtboriginates from rearrangement, deletion, and duplication of redundant nucleotide sequences. In contrast, we found that pan-genome analyses that focus on comparison of coding sequences (at the amino acid level) can yield surprisingly variable results, driven by differences in assembly quality and the softwares used. Upon closer inspection, we found that coding sequence annotation discrepancies were a major contributor to inflatedMtbaccessory genome estimates. To address this, we developed panqc, a software that detects annotation discrepancies and collapses nucleotide redundancy in pan-genome estimates. When applied toMtbandE. colipan-genomes, panqc exposed distinct biases influenced by the genomic diversity of the population studied. Our findings underscore the need for careful methodological selection and quality control to accurately map the evolutionary dynamics of a bacterial species.
A chromosome-level genome assembly of the Hispid cotton rat (Sigmodon hispidus), a model for human pathogenic virus infections
Authors: Lilue Jingtao , Corvelo André , Gómez-Garrido Jèssica , Yang Fengtang , Akagi Keiko , Green Gia , Ng Bee Ling , Fu Beiyuan , Chorostecki Uciel Pablo , Warner Sarah , Marcet-Houben Marina , Keane Thomas , Mullikin James C. , Alioto Tyler , Gabaldón Toni , Hubert Benjamin , Symer David E. , Niewiesk Stefan
Published: March 2024

Background

The cotton rat (Sigmodon hispidus), a rodent species native to the Americas, has emerged as a valuable laboratory model of infections by numerous human pathogens including poliovirus and respiratory syncytial virus (RSV).

Results

Here we report the first reference assembly of the cotton rat genome organized at a chromosomal level, providing annotation of 24,878 protein-coding genes. Data from PCR-free whole genome sequencing, linked-read sequencing and RNA sequencing from pooled cotton rat tissues were analyzed to assemble and annotate this novel genome sequence. Spectral karyotyping data using fluorescent probes derived from mouse chromosomes facilitated the assignment of cotton rat orthologs to syntenic chromosomes, comprising 25 autosomes and a sex chromosome in the haploid genome. Comparative phylome analysis revealed both gains and losses of numerous genes including immune defense genes against pathogens. We identified thousands of recently retrotransposed L1 and SINE B2 elements, revealing widespread genetic innovations unique to this species.

Conclusions

We anticipate that annotation and characterization of the first chromosome-level cotton rat genome assembly as described here will enable and accelerate ongoing investigations into its host defenses against viral and other pathogens, genome biology and mammalian evolution.
Transcriptional landscape of the dorsal raphe serotonin neurons rendering stress resiliency
Authors: Andoh Chihiro , Otani Suzuka , Noguchi Takuma , Hagiwara Masako , Nishitani Naoya , Kawai Hiroyuki , Fukui Yuto , Koda Masashi , Morishita Hinako , Nomura Kento , Oki Moeka , Hori Harune , Shirakawa Hisashi , Kaneko Shuji , Nagayasu Kazuki
Published: March 2024

Major depressive disorder (MDD) is a serious and large social problem, yet the pathophysiology of MDD and the action mechanism of antidepressants are still poorly understood. A number of studies have reported that activation and inactivation of serotonin neurons in the dorsal raphe nucleus (DRN) cause antidepressant-like effects and depressive-like behaviors, respectively. Also, their physiological neural activities are increased when mice were chronically administered an SSRI and decreased in mice exposed to chronic social defeat stress (CSDS), a mouse model of depression. However, the molecular mechanism underlying these neural activity changes in DRN serotonin neurons remains unclear. In this study, we performed a DRN serotonin neuron-specific comprehensive gene expression analysis by using Translating Ribosome Affinity Purification (TRAP) technology in both chronic SSRI-treated mice as a model of antidepressant treatment and CSDS mice as a model of depression. It revealed that many gene expression changes were the opposite between SSRI-treated mice and CSDS-susceptible mice. Among these, we identified S100a10 as a prodepressive gene in DRN serotonin neurons, and we found that Interleukin-4 (IL-4) – Signal Transducer and Activator of Transcription 6 (STAT6) pathway and 5-HT1Breceptor were the upstream and downstream molecules of S100a10, respectively. Our findings provide insights into molecular mechanisms underlying the action of antidepressants and stress resiliency.
Long-read genome sequencing and variant reanalysis increase diagnostic yield in neurodevelopmental disorders
Authors: Hiatt Susan M , Lawlor James MJ , Handley Lori H , Latner Donald R , Bonnstetter Zachary T , Finnila Candice R , Thompson Michelle L , Boston Lori Beth , Williams Melissa , Rodriguez Nunez Ivan , Jenkins Jerry , Kelley Whitley V , Bebin E Martina , Lopez Michael A , Hurst Anna CE , Korf Bruce R , Schmutz Jeremy , Grimwood Jane , Cooper Gregory M
Published: March 2024

Variant detection from long-read genome sequencing (lrGS) has proven to be considerably more accurate and comprehensive than variant detection from short-read genome sequencing (srGS). However, the rate at which lrGS can increase molecular diagnostic yield for rare disease is not yet precisely characterized. We performed lrGS using Pacific Biosciences "HiFi" technology on 96 short-read-negative probands with rare disease that were suspected to be genetic. We generated hg38-aligned variants and de novo phased genome assemblies, and subsequently annotated, filtered, and curated variants using clinical standards. New disease-relevant or potentially relevant genetic findings were identified in 16/96 (16.7%) probands, eight of which (8/96, 8.33%) harbored pathogenic or likely pathogenic variants. Newly identified variants were visible in both srGS and lrGS in nine probands (~9.4%) and resulted from changes to interpretation mostly from recent gene-disease association discoveries. Seven cases included variants that were only interpretable in lrGS, including copy-number variants, an inversion, a mobile element insertion, two low-complexity repeat expansions, and a 1 bp deletion. While evidence for each of these variants is, in retrospect, visible in srGS, they were either: not called within srGS data, were represented by calls with incorrect sizes or structures, or failed quality-control and filtration. Thus, while reanalysis of older data clearly increases diagnostic yield, we find that lrGS allows for substantial additional yield (7/96, 7.3%) beyond srGS. We anticipate that as lrGS analysis improves, and as lrGS datasets grow allowing for better variant frequency annotation, the additional lrGS-only rare disease yield will grow over time.
Association between Paediatric Mild Traumatic Brain Injury and Two-Year Psychiatric Outcomes Largely Explained by Pre-Existing Mental Health Problems
Authors: Revill Grace , Poole Norman , Carlisi Christina , David Anthony S. , Bell Vaughan
Published: March 2024

Background

Evidence that mild traumatic brain injury (mTBI) causes psychiatric problems in children has been mixed. Investigating this issue has been difficult due to the lack of representative longitudinal data on child mTBI that includes adequate measures of subsequent mental health symptoms and service use in young people.

Methods

We used data from the ABCD longitudinal cohort study to examine the association between mTBI and psychiatric diagnoses, symptoms, and psychiatric service use in over 11,000 children aged 9-10 at i) baseline, and ii) with new cases of mTBI since baseline and psychiatric outcomes and service use at two-year follow-up. We also compared mTBI cases to a comparison group of participants with orthopaedic injury but without mTBI. Mixed-effects models were used and adjusted for demographic and social covariates, with missing data imputed using random forest multiple imputation. To account for baseline mental health outcomes, we used propensity-score matching to identify a comparison sample matched on potential confounding variables and baseline outcome measures.

Results

When examined without adjustment for baseline mental health, both lifetime mTBI at baseline, and new occurrence of mTBI at two-year follow-up, were reliably associated with an increased risk of DSM-5 anxiety and behavioural disorders, mental health symptom scores measured psychometrically, and increased psychiatric service use. These associations were not present, or occasionally only minimally present, in the orthopaedic injury comparison group. However, controlling for baseline mental health using propensity-score matching resulted in no association between new incidence mTBI and psychiatric symptoms, diagnoses and service use, with the exception of parent-reported anxiety and conduct symptom scores in supplementary analyses.

Conclusion

The association between childhood mTBI and subsequent psychiatric problems and service use may be largely explained by pre-existing mental health problems.
CITE-seq analysis reveals human cytomegalovirus and diabetes-associated adaptive NK cell alterations in cardiovascular disease
Authors: Armstrong Sujit Silas , Chen Daniel G. , Kumar Sunil , Heath James R. , Feinstein Matthew J. , Greenland John R. , Calabrese Daniel R. , Lanier Lewis L. , Ley Klaus , Shemesh Avishai
Published: March 2024

Coronary artery disease (CAD) is a leading cause of mortality worldwide with Diabetes and human cyto-megalovirus (HCMV) infection as risk factors. CAD’s influence on human NK cells is not well characterized. CITE-seq analysis of a CAD cohort of 61 patients revealed distinctly higher NK cellSPON2expression and lowerIFNGexpression in severe CAD patients. Interestingly, HCMV+patients displayed lowerSPON2ex-pression while diabetes status reversed the HCMV effect. Diabetes led to diminished adaptive FcεRIγ−/lowNK cell frequencies and was associated with a higher PBMCIL15/TGFBtranscript ratio, while TGFB in-creased in severe CAD.SPON2expression corresponded to changes in conventional vs. adaptive NK cell frequencies, andSPON2/IFNGratio decreased in inflamed plaque tissue with an increased adaptive NK cell gene signature and was increased in severe CAD patients. Our results indicate that theSPON2/IFNGra-tio and adaptive NK cell gene signature associated with stenosis severity or inflammation in CAD.
Microvascular structure variability explains variance in fMRI functional connectivity
Authors: Gaudreault François , Desjardins Michèle
Published: March 2024

The influence of regional brain vasculature on resting-state fMRI BOLD signals is well documented. However, the role of brain vasculature is often overlooked in functional connectivity research. In the present report, utilizing publicly available whole-brain vasculature data in the mouse, we investigate the relationship between functional connectivity and brain vasculature. This is done by assessing interregional variations in vasculature through a novel metric termed vascular similarity. First, we identify features to describe the regional vasculature. Then, we employ multiple linear regression models to predict functional connectivity, incorporating vascular similarity alongside metrics from structural connectivity and spatial topology. Our findings reveal a significant correlation between functional connectivity strength and regional vasculature similarity, especially in anesthetized mice. We also show that multiple linear regression models of functional connectivity using standard predictors are improved by including vascular similarity. We perform this analysis at the cerebrum and whole-brain levels using data from both male and female mice. Our findings regarding the relation between functional connectivity and the underlying vascular anatomy may enhance our understanding of functional connectivity based on fMRI and provide insights into its disruption in neurological disorders.
Universal Cold RNA Phase Transitions
Authors: Rissone P. , Severino A. , Pastor I. , Ritort F.
Published: March 2024

RNA’s diversity of structures and functions impacts all life forms sinceprimordia. We use calorimetric force spectroscopy to investigate RNA folding landscapes in previously unexplored low-temperature conditions. We find that Watson-Crick RNA hairpins, the most basic secondary structure elements, undergo a glass-like transition below TG∼ 20°C where the heat capacity abruptly changes and the RNA folds into a diversity of misfolded structures. We hypothesize that an altered RNA biochemistry, determined by sequence-independent ribose-water interactions, outweighs sequence-dependent base pairing. The ubiquitous ribose-water interactions lead to universal RNA phase transitions below TG, such as maximum stability at TS∼ 5°C where water density is maximum, and cold denaturation at TC∼ −50°C. RNA cold biochemistry may have a profound impact on RNA function and evolution.
High-resolution scRNA-seq reveals genomic determinants of antigen expression hierarchy in African Trypanosomes
Authors: McWilliam Kirsty R. , Keneskhanova Zhibek , Cosentino Raúl O. , Dobrynin Atai , Smith Jaclyn E. , Subota Ines , Mugnier Monica R. , Colomé-Tatché Maria , Siegel T. Nicolai
Published: March 2024

Antigenic variation is an immune evasion strategy used by many different pathogens. It involves the periodic, non-random switch in the expression of different antigens throughout an infection. How the observed hierarchy in antigen expression is achieved has remained a mystery. A key challenge in uncovering this process has been the inability to track transcriptome changes and potential genomic rearrangements in individual cells during a switch event. Here, we report the establishment of a highly sensitive single-cell RNA-seq (scRNA-seq) approach for the model protozoan parasiteTrypanosoma brucei. This approach has revealed genomic rearrangements that occur in individual cells during a switch event. Our data show that following a double-strand break (DSB) in the transcribed antigen-coding gene – an important trigger for antigen switching – the type of repair mechanism and the resultant antigen expression depend on the availability of a homologous repair template in the genome. When such a template was available, repair proceeded through segmental gene conversion, creating new, mosaic antigen-coding genes. Conversely, in the absence of a suitable template, a telomere-adjacent antigen-coding gene from a different part of the genome was activated by break-induced replication. Our results reveal the critical role of available repair sequence in the antigen selection mechanism. Additionally, our study demonstrates the power of highly sensitive scRNA-seq methods in detecting genomic rearrangements that drive transcriptional changes at the single-cell level.
No evidence that shrinking and shapeshifting meaningfully affect how birds respond to warming and cooling
Authors: Tabh Joshua K.R. , Persson Elin , Correia Maria , Cuív Ciarán Ó , Thoral Elisa , Nord Andreas
Published: March 2024

Across the globe, birds and mammals are becoming smaller and longer-limbed. Although the cause of these changes is unclear, many argue that each provide thermoregulatory benefits in a warmer world by easing heat dissipation. Here, we show that neither body size nor limb length in a model species (the Japanese quail) influenced metabolic costs of warming during a cold challenge. In the heat, larger body sizes increased metabolic costs of thermoregulation, however, this effect was moderate and almost always negated by cooling from the limbs (>97% of cases). Rearing in the warmth (30°C) relative to the cold (10°C) reduced body sizes and increased limb lengths at adulthood but thermoregulatory benefits of these changes in later heat exposures were absent. Our findings demonstrate that shrinking and shape-shifting are unlikely to ease thermoregulation in contemporary birds or reflect selection for such. Alternative contributors, including neutral or non-adaptive plasticity, should be further investigated.

Teaser

Using experimental data, we show for the first time that shrinking and shape-shifting – which has been described as the third general response to climate change in animals – does not inherently provide thermoregulatory benefits to birds in a warming world. Further research evaluating the drivers of shape-shifts (including neutral plasticity and temporal reductions in resource abundance) is needed before we can determine why animals shrink under climate change.
SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis
Authors: Breunig Kira , Lei Xiufen , Montalbano Mauro , Guardia Gabriela D. A. , Ostadrahimi Shiva , Alers Victoria , Kosti Adam , Chiou Jennifer , Klein Nicole , Vinarov Corina , Wang Lily , Li Mujia , Song Weidan , Kraus W. Lee , Libich David S. , Tiziani Stefano , Weintraub Susan T. , Galante Pedro A. F. , Penalva Luiz O. F.
Published: March 2024

RNA binding proteins (RBPs) containing intrinsically disordered regions (IDRs) are present in diverse molecular complexes where they function as dynamic regulators. Their characteristics promote liquid-liquid phase separation (LLPS) and the formation of membraneless organelles such as stress granules and nucleoli. IDR-RBPs are particularly relevant in the nervous system and their dysfunction is associated with neurodegenerative diseases and brain tumor development. Serpine1 mRNA-binding protein 1 (SERBP1) is a unique member of this group, being mostly disordered and lacking canonical RNA-binding domains. We defined SERBP1’s interactome, uncovered novel roles in splicing, cell division and ribosomal biogenesis, and showed its participation in pathological stress granules and Tau aggregates in Alzheimer’s brains. SERBP1 preferentially interacts with other G-quadruplex (G4) binders, implicated in different stages of gene expression, suggesting that G4 binding is a critical component of SERBP1 function in different settings. Similarly, we identified important associations between SERBP1 and PARP1/polyADP-ribosylation (PARylation). SERBP1 interacts with PARP1 and its associated factors and influences PARylation. Moreover, protein complexes in which SERBP1 participates contain mostly PARylated proteins and PAR binders. Based on these results, we propose a feedback regulatory model in which SERBP1 influences PARP1 function and PARylation, while PARylation modulates SERBP1 functions and participation in regulatory complexes.
Genetic designs for stochastic and probabilistic biocomputing
Authors: Grozinger Lewis , Miró-Bueno Jesús , Goñi-Moreño Ángel
Published: March 2024

The programming of computations in living cells can be done by manipulating information flows within genetic networks. Typically, a single bit of information is encoded by a single gene’s steady state expression. Expression is discretized into high and low levels that correspond to 0 and 1 logic values, analogous to the high and low voltages in electronic logic circuits. However, the processes of molecular signaling and computation in living systems challenge this computational paradigm with their dynamic, stochastic and continuous operation. Although there is a good understanding of these phenomena in genetic networks, and there are already stochastic and probabilistic models of computation which can take on these challenges, there is currently a lack of work which puts both together to implement computations tailored to these features of living matter. Here, we design genetic networks for stochastic and probabilistic computing paradigms and develop the theory behind their operation. Moving beyond the digital abstraction, we explore the concepts of bit-streams (sequences of pulses acting as time-based signals) and probabilistic-bits or p-bits (values that can be either 1 or 0 with an assigned probability), as more suitable candidates for the encoding and processing of information in genetic networks. Specifically, the conceptualization of signals as stochastic bit-streams allows for encoding information in the frequency of random expression pulses, offering advantages such as robustness to noise. Additionally, the notion of p-bit enables the design of genetic circuits with capabilities surpassing those of current genetic logic gates, including invertibility. We design several circuits to illustrate these advantages and provide mathematical models and computational simulations that demonstrate their functionality. Our approach to stochastic and probabilistic computing in living cells not only enhances and reflects understanding of information processing in biological systems but also presents promising avenues for designing genetic circuits with advanced functionalities.
HIV and Hepatitis B virus co-infection in Mozambique: policy review and health professionals’ knowledge and practices
Authors: dos Muchangos Vanda , Chambal Lúcia , Nilsson Charlotta , Sevene Esperança
Published: March 2024

Background

Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) co-infection is a public health problem affecting 2.7 million worldwide. In Mozambique, the prevalence of this co-infection is 9.1%, calling for specific policies on prevention, diagnosis and adequate management in health facilities caring for HIV patients. This study aimed to review the existing policies and to assess the knowledge and practices of health professionals about HIV/HBV co-infection.

Methods

A document and literature review to describe the existing policies and guidelines on HIV/HBV co-infection in Mozambique was performed. Key informants were contacted to clarify or add information. Health Professionals who care for HIV-positive patients in four health centers in Maputo City, the capital of Mozambique, responded to a questionnaire on knowledge and practices about this co-infection. Qualitative analysis was done to identify main themes using content analysis. Descriptive statistics of socio-demographic, knowledge and practice variables was presented using the SPSS Program version 20 and bivariate analysis was applied to describe the association between variables.

Results

Twenty-one policy documents were found, and five key informants were interviewed. Fifty-two participants answered the questionnaire. Only one policy document explicitly referred to HIV/HBV co-infection treatment. Most Health Professionals (96%) were aware of HIV/HBV co-infection. Although the only existing policy is on the treatment, few (33%) referenced antiretroviral formulations containing Tenofovir and Lamivudine. Only 29% of Health Professionals reported screening HIV patients for HBV and 21% practiced HIV/HBV co-infection counselling. No statistically significant differences were found when relating the socio-demographic variables with knowledge and practices.

Conclusion

Policy documents relating to prevention, diagnosis and clinical management of HIV/HBV co-infection were rare or absent. Health Professionals had little knowledge about HIV/HBV co-infection. Defining adequate policies and training of Health Professionals may help increase awareness, increase counselling of patients for disease prevention, diagnosis and proper management of HIV/HBV co-infected patients.
A CRISPR mediated point-of-care assay for the detection of mucosal calprotectin in an animal model of ulcerative colitis
Authors: Chia Selena , Guo Tianruo , Goldys Ewa M. , Payne Sophie C. , Lovell Nigel H. , Shivdasani Mohit N. , Deng Fei
Published: March 2024

Inflammatory bowel disease (IBD) is a chronic disorder associated with inflammation in the gastrointestinal tract, leading to a range of debilitating symptoms. Fecal calprotectin is an established biomarker for ulcerative colitis (UC), one of the main IBD diseases, which provides indications of the presence and severity of inflammation in the digestive tract. Enzyme-Linked Immunosorbent Assay (ELISA) as a gold standard approach for fecal calprotectin detection is time-consuming and impractical in point-of-care settings. Moreover, obtaining fecal samples from patients is challenging and inhibits longitudinal monitoring. To overcome these limitations, we designed a new approach for detecting calprotectin which leverages clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology. We successfully developed a portable tube-based CRISPR/Cas assay for point-of-care testing of calprotectin. This assay showed a detection range from 1-10000 ng/mL (over 4 log units), using both fluorescent and colorimetric analytical techniques. The established assay was further validated through measurements in mucosal samples obtained in an anesthetised preclinical rodent model of UC, with 2-3 times higher calprotectin concentration detected in UC rat samples compared to that of healthy control animals. This point-of-care test may provide a rapid, precise, and user-friendly approach for the diagnosis and monitoring of IBD through mucosal sample testing.
PEPerMINT: Peptide Abundance Imputation in Mass Spectrometry-based Proteomics using Graph Neural Networks
Authors: Pietz Tobias , Gupta Sukrit , Schlaffner Christoph N. , Ahmed Saima , Steen Hanno , Renard Bernhard Y. , Baum Katharina
Published: March 2024

Motivation: Accurate quantitative information about the protein abundance is crucial for understanding a biological system and its dynamics. Protein abundance is commonly estimated using label-free, bottom-up mass spectrometry protocols. Here, proteins are digested into peptides before quantification via mass spectrometry. However, missing peptide abundance values, which can make up more than 50% of all abundance values, are a common issue. They result in missing protein abundance values, which then hinder accurate and reliable downstream analyses. Results: To impute missing abundance values, we propose PEPerMINT, a graph neural network model working directly on the peptide level that flexibly takes both peptide-to-protein relationships in a graph format as well as amino acid sequence information into account. We benchmark our method against eleven common imputation methods on six diverse datasets, including cell lines, tissue, and plasma samples. We observe that PEPerMINT consistently outperforms other imputation methods. Its prediction performance remains high for varying degrees of missingness, different evaluation approaches and differential expression prediction. As an additional novel feature, PEPerMINT provides meaningful uncertainty estimates and allows for tailoring imputation to the user's needs based on the reliability of imputed values. Availability and implementation: The code is available at https://github.com/DILiS-lab/pepermint.
Discovery and heterologous expression of functional 4-O-dimethylallyl-L-tyrosine synthases from lichen-forming fungi
Authors: Iacovelli Riccardo , He Siqi , Sokolova Nika , Lokhorst Iris , Borg Maikel , Fodran Peter , Haslinger Kristina
Published: March 2024

Fungal DMATS-type aromatic prenyltransferases are a family of biosynthetic enzymes that catalyze the prenylation of a range of aromatic substrates during the biosynthesis of bioactive indole alkaloids, diketopiperazines, and meroterpenoids. Together with their broad substrate scope and soluble nature, this makes DMATS-type prenyltransferases particularly adept for applications in biocatalysis, for example to derivatize aromatic drug leads and improve their bioactivity. Here, we investigated four putative DMATS-type prenyltransferases from lichen-forming fungi, an underexplored group of organisms that produce more than 1,000 unique metabolites. We were able to successfully express two functional lichen prenyltransferases in the heterologous hostA. oryzae, which allowed us to identify them as 4-O-dimethylallyltyrosine synthases. Our extensive bioinformatic analysis shows that related lichen prenyltransferases are likely not active on indoles but rather on aromatic polyketides and phenylpropanoids, common metabolites in these organisms. Overall, our work not only provides new insights into fungal DMATS-type prenyltransferases at the family level, but it also enables future efforts aimed at identifying new candidates for biocatalytic transformations of aromatic compounds.
Selective Posterior Cerebral Artery Wada Better Predicts Good Memory and Naming Outcomes Following Selective Stereotactic Thermal Ablation for Medial Temporal Lobe Epilepsy Than Internal Carotid Artery Wada
Authors: Drane Daniel L. , Acerbo Emma , Rogers Anna , Pedersen Nigel P. , Williamson Adam , Stern Matthew A. , Dickey Adam S. , Howard Brian M. , Bearden Donald J. , Okada Noah , Staikova Ekaterina , Gutekunst Claire Anne , Alwaki Abdulrahman , Gershon Timothy , Jirsa Viktor , Gross Robert E. , Loring David W. , Kheder Ammar , Willie Jon T.
Published: March 2024

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH). We included all patients being considered for SLAH who underwent both ICA-Wada and PCA-Wada at a single institution. Memory and confrontation naming assessments were conducted using standardized neuropsychological tests to assess pre- to post-surgical changes in cognitive performance. Of 13 patients who initially failed the ICA-Wada, only one patient subsequently failed the PCA-Wada (p=0.003, two-sided binomial test withp0=0.5) demonstrating that these tests assess different brain regions or networks. PCA-Wada had a high negative predictive value for the safety of SLAH, compared to ICA-Wada, as none of the patients who underwent SLAH after passing the PCA-Wada experienced catastrophic memory decline (0 of 9 subjects,p<.004, two-sided binomial test withp0=0.5), and all experienced a good cognitive outcome. In contrast, the single patient who received a left anterior temporal lobectomy after failed ICA- and passed PCA-Wada experienced a persistent, near catastrophic memory decline. On confrontation naming, few patients exhibited disturbance during the PCA-Wada. Following surgery, SLAH patients showed no naming decline, while open resection patients, whose surgeries all included ipsilateral temporal lobe neocortex, experienced significant naming difficulties (Fisher’s exact test,p<.05). These findings demonstrate that (1) failing the ICA-Wada falsely predicts memory decline following SLAH, (2) PCA-Wada better predicts good memory outcomes of SLAH for MTLE, and (3) the MTL brain structures affected by both PCA-Wada and SLAH are not directly involved in language processing.
Can motion capture improve task-based fMRI studies of motor function post-stroke? A systematic review
Authors: Belkacemi Zakaria , van Dokkum Liesjet E.H. , Tchechmedjiev Andon , Lepetit-Coiffe Matthieu , Mottet Denis , Le Bars Emmanuelle
Published: March 2024

Background

Variability in motor recovery after stroke represents a major challenge in its understanding and management. While functional MRI has traditionally been used to address post-stroke motor function in relation to clinical outcome, it lacks details about movement characteristics linked to observed brain activations. Combining fMRI with detailed information of motor function by using motion capture (mocap) might provide clinicians with additional information about mechanisms of motor impairment after stroke.

Objectives

We aimed to identify fMRI and mocap coupling approaches and to evaluate their potential contribution to the understanding of motor function post-stroke.

Method

A systematic literature review was performed according to PRISMA guidelines, on studies using fMRI and mocap in post-stroke individuals. We assessed the internal, external, statistical, and technological validity of each study. Data extraction included study design and analysis procedures used to couple brain activity with movement characteristics.

Results

Of the 404 studies found, 23 were included in the final review. The overall study quality was moderate (0.6/1). The majority of studies focused on the upper limb, using a wide variety of motor tasks. Half of the studies performed a statistical analysis between movement and brain activity by either using kinematics as variables during group or individual level regression or correlation. This permitted establishing a link between motor characteristics and brain activations. Mocap was also integrated without statistical confrontation, to compare results between fMRI and kinematics, or to incorporate real-time movement information to supply external devices, like motor feedback.

Conclusion

Our review suggests that the simultaneous use of fMRI and Mocap provides new insights compared with conventional fMRI analysis. It allows a better understanding of post-stroke motor function, although being still subject to practical and technological limitations. Further research is needed to optimize and standardize both data measurement and processing procedures.