bluuebunny/crossref_metadata_2025 huggingface dataset:
The Significance of Bell's Palsy That Presents as Monocranial Versus Polycranial Neuropathy: A Case Series and Systematic Literature Review
Authors: Ziv Oren , Hazout Chen , Goldberg Nitzan , Tavdi Alex , Zholkovsky Ariel , Kordeluk Sofia , El-Saied Sabri , Dinur Anat Bahat , Ben-Zion Joshua , Muhanna Nidal , Ungar Omer J.
Published: October 2023

Purpose

To investigate the effect of Bell's palsy (BP) presenting as polycranial neuropathy (PCN) compared with BP caused by isolated facial nerve (CNVII).

Methods

We carried out a retrospective cohort study of the medical records of all consecutive patients who were diagnosed with BP at a single tertiary referral center between 2010 and 2017. Included were patients 18 years or older who were clinically diagnosed with BP and completed 7 days of systemic steroidal treatment and at least 6 months of follow-up. The patients were divided into two groups according to whether the BP derived from a monocranial neuropathy or a PCN. Demographics and BP severity and outcome were compared between these groups. A systematic literature review using Medline via “PubMed,” “Embase,” and “Web of Science” was conducted.

Results

In total, 321 patients with BP were enrolled. The median (interquartile range) age at presentation was 44 (33–60) years. Sex distribution showed male predominance of 57.6% (n = 185) versus 42.4% (n = 136), and 21.2% (n = 68) had PCN. The most concomitantly affected cranial nerve (CN) was the trigeminal (CNV; n = 32, 47%), followed by the glossopharyngeal nerve (CNIX; n = 14, 21%) and the audiovestibular nerve (CNVIII; n = 10, 15%). Age, House-Brackmann score on presentation, and diabetes mellitus (DM) were independent predictors for PCN etiology (p = 0.001, p = 0.034, and p < 0.001, respectively). Each increase in 1 year of age was associated with additional odds ratio (95% confidence interval) of 0.97 (0.95–0.99) for PCN. The odds ratio (95% confidence interval) associated with DM was 8.19 (4.02–16.70). Our systematic literature review identified 1,440 patients with the PCN type of BP. The most commonly affected CN was the trigeminus (25–48%), followed by the glossopharyngeal and audiovestibular nerves (2–19% and 0–43%, respectively).

Conclusion

The severity of facial weakness on initial presentation among PCN patients was significantly higher compared with the monocranial neuropathy–type BP patients. The authors believe that the significant association and prevalence rate ratio between DM and PCN warrant that a patient presenting with PCN undergo screening for DM.
Evaluation of Stroke Risk Following COVID-19 mRNA Bivalent Vaccines Among U.S. Adults Aged ≥65 Years
Authors: Lu Yun , Matuska Kathryn , Nadimpalli Gita , Ma Yuxin , Duma Nathan , Zhang Henry , Chiang Yiyun , Lyu Hai , Chillarige Yoganand , Kelman Jeffrey , Forshee Richard , Anderson Steven A.
Published: October 2023

In January 2023, the United States Food and Drug Administration and the Centers for Disease Control and Prevention noted a safety concern for ischemic stroke in adults ≥65 years receiving the BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. This self-controlled case series analysis evaluated stroke risk among Medicare fee-for-service beneficiaries aged ≥65 years receiving: 1) a Pfizer-BioNTech (BNT162b2; WT/OMI BA.4/BA.5) or Moderna (mRNA-1273.222) COVID-19 bivalent vaccine, 2) high-dose/adjuvanted influenza vaccines, and 3) concomitant COVID-19 bivalent vaccines and influenza vaccines, from August 31 to November 6, 2022.

The primary analysis did not find elevated stroke risk following COVID-19 bivalent vaccines. In the age subgroup analyses, only the ≥85 year age group had a risk of NHS (Incident Rate Ratio (IRR)=1.36, 95% CI 1.09 – 1.69 [1-21 days]) and NHS/TIA (IRR=1.28, 95% CI 1.08 – 1.52 [1-21 days]) with BNT162b2 Bivalent WT/OMI BA.4/BA.5. Among beneficiaries receiving a concomitant COVID-19 bivalent vaccine and a high-dose/adjuvanted influenza vaccine, an increased risk was observed for NHS (IRR=1.20, 95% CI 1.01 – 1.42 [22-42 days]) with BNT162b2 Bivalent WT/OMI BA.4/BA.5 and for TIA (IRR=1.35, 95% CI 1.06 – 1.74 [1-21 days]) with mRNA-1273.222.

Results of the secondary analyses showed a small increased risk of NHS following high-dose or adjuvanted influenza vaccines (IRR=1.09, 95% CI 1.02 – 1.17 [22-42 days]).
Migration routes and wintering sites of the Aquatic WarblersAcrocephalus paludicolabreeding in Lithuania and North Belarus
Authors: Flade Martin , Lisovski Simeon , Eigirdas Vytauras , Giessing Benedikt , Jiguet Fréderic , Keišs Oskars , Nemtchinov Maxim
Published: October 2023

For the effective protection of the globally threatened Aquatic Warbler in its entire range, knowledge of the migration and wintering areas as well as their current conservation status is of great importance. The question on where the different breeding population overwinter where (connectivity) equally important. This is also essential when new breeding populations are re-established in restored breeding sites through translocation from other, distant areas, as recently performed in Lithuania. From previous geolocator studies in central Ukraine and south-western Belarus, as well as from ringing data, it was known that these populations overwinter in Mali (Inner Niger Delta IND) and southern Mauritania. In addition, at least some birds of the NE-Polish breeding population overwinter in the Senegal delta (ring recovery). In 2018 and 2019, the migratory routes, stopover and wintering sites of two breeding populations at the north-western distribution range border in N-Belarus (29 males) and Lithuania (31 males) were investigated using light-level geolocators. All 19 recovered data loggers recorded almost complete annual cycles from mid-July to at least early April. Migration and overwintering sites of both populations did not differ significantly. Most (16 out of 19) birds also spent the winter in the Inner Niger Delta and surrounding wetlands within and around Mali. Only one bird from Belarus hiberbated in the Senegal Delta. One of the Lithuanian birds overwintered in northern Burkina Faso, another northern Nigeria. In addition, important details about the course of migration routes, timing and resting areas could be obtained. For example, the outstanding importance of Morocco and northern Algeria as resting areas on spring migration became obvious. The investigations applying geolocators resulted in a very complex and differentiated picture of the migration and stopover pattern of adult male Aquatic Warblers.
Maternal high-fat diet affects the contents of eggs and causes abnormal development in the medaka fish
Authors: Inoue Yusuke , Fukushima Manatsu , Hirasawa Go , Furukawa Fumiya , Takeda Hiroyuki , Umatani Chie
Published: October 2023

Maternal nutritional status can affect development and metabolic phenotypes of their progeny in animals. The effects of maternal diet are thought to be mediated mainly by changes inside oocytes such as organelles, maternal RNAs, and metabolites. However, to what extent each factor contributes to offspring phenotypes remains uncertain, especially in viviparous mammalian systems, where factors other than oocytes, such as placenta and milk, need to be considered. Here, using the medaka fish as an oviparous vertebrate model, we examined whether maternal high-fat diet (mHFD) feeding affects offspring development, and what kind of changes occur in the contents of mature eggs. We found that mHFD caused the high frequency of embryonic deformities of offspring, accompanied by downregulation of transcription- and translation-related genes and zygotic transcripts at the blastula stage. Transcriptomic and metabolomic analyses of mature eggs suggested decreased catabolism of amino acids and glycogen, moderate upregulation of endoplasmic reticulum stress-related genes, and elevated lipid levels in mHFD eggs. Furthermore, HFD females showed upregulation of follicle-stimulating hormone, a higher incidence of oocyte atresia and downregulation of egg protein genes in the liver. These data suggested that attenuated amino acid catabolism triggered by decreased yolk protein load/processing, as well as elevated lipid levels inside eggs, are the prime candidates that account for the higher incidence of embryonic deformities in mHFD offspring. Our study presents a comprehensive data on the changes inside eggs in mHFD model of non-mammalian vertebrates, and provides insights into the mechanisms of parental nutritional effects on their offspring.
Aβ-affine bifunctional copper chelators capable of Aβ-induced oxidative stress reduction and amyloid disaggregation
Authors: Krasnovskaya Olga , Abramchuk Daniil , Vaneev Alexander , Gorelkin Peter , Abakumov Maxim , Timoshenko Roman , Chmelyuk Nelly , Vadekhina Veronika , Kuanaeva Regina , Dubrovin Evgeniy V. , Kolmogorov Vasilii , Beloglazkina Elena , Erofeev Alexander
Published: October 2023

Alz-5 acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity. Single-cell ROS measurements provided by Pt-nanoelectrode technique revealed a significant antioxidant properties of Alz-5 in Aβ42- affected SH-SY5Y cell. AFM data obtained on Aβ42fibrils clearly indicate an anti-aggregating property of Alz-5. Young’s modulus mapping on living SH-SY5Y cells revealed an ability of Alz-5 to decrease cell rigidity in Aβ42- affected SH-SY5Y cells.
Relative Homoplasy Index: A New Cross-comparable Metric for Quantifying Homoplasy in Discrete Character Datasets
Authors: Steell Elizabeth M. , Hsiang Allison Y. , Field Daniel J.
Published: October 2023

Homoplasy is among the main hinderances to phylogenetic inference. However, investigating patterns of homoplasy can also improve our understanding of macroevolution, for instance by revealing evolutionary constraints on morphology, or highlighting convergent form-function relationships. Several methods have been proposed to quantify the extent of homoplasy in discrete character matrices, but the consistency index (CI) and retention index (RI) have remained the most widely used for decades, with little recent scrutiny of their function. Here, we test the performance of CI and RI using simulated and empirical datasets and investigate patterns of homoplasy with different matrix scenarios. In addition, we describe and test a new scaled metric, the relative homoplasy index (RHI), implemented in the R statistical environment. The results suggest that, unlike the RI, the CI does not constitute a direct measure of homoplasy. However, the RI consistently underestimates the extent of homoplasy in phylogenetic character-taxon matrices, particularly in datasets characterised by high levels of homoplasy. By contrast, RHI—the newly proposed metric—outperforms both methods in sensitivity to homoplasy levels, and is scaled between zero and one for comparison of values between different datasets. Using both simulated and empirical phylogenetic datasets, we show that relative levels of homoplasy remain constant with the addition of novel characters, and, in contrast to earlier work, decrease with the addition of taxa. Our results help illuminate the inherent properties of homoplasy in cladistic matrices, opening new potential avenues of research for investigating patterns of homoplasy in macroevolutionary studies.
Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR
Authors: Mikelov Artem , Nefediev George , Tashkeev Alexander , Rodriguez Oscar L. , Ortmans Diego A. , Skatova Valeriia , Izraelson Mark , Davydov Alexey , Poslavsky Stanislav , Rahmouni Souad , Watson Corey T. , Chudakov Dmitriy , Boyd Scott D. , Bolotin Dmitry
Published: October 2023

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), has been shown to be of critical importance for immune responses to pathogens and vaccines. In recent years, B cell and T cell receptor repertoire sequencing (Rep-Seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci in different populations. Here we present a novel algorithm for extra-sensitive and specific variable (V) and joining (J) gene allele inference and genotyping allowing reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput genotyping and novel allele discovery from a wide variety of existing datasets. The developed algorithm is a part of the MiXCR software (https://mixcr.com) and can be incorporated into any pipeline utilizing upstream processing with MiXCR.

We demonstrate the accuracy of this approach using Rep-Seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) Rep-Seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA; TRB) Rep-Seq dataset, representing 134 individuals. This allowed us to assess the genetic diversity of genes within the IGH, TRA and TRB loci in different populations and demonstrate the connection between antibody repertoire gene usage and the number of allelic variants present in the population. Finally we established a database of allelic variants of V and J genes inferred from Rep-Seq data and their population frequencies with free public access athttps://vdj.online.
Alkaline and loess grasslands with contrasting richness and biomass patterns are not separated on the CSR strategy spectrum
Authors: McIntosh-Buday Andrea , Sonkoly Judit , Molnár Attila , Szél-Tóth Katalin , Törő-Szijgyártó Viktória , Madar Szilvia , Károlyi Evelin , Díaz Cando Patricia Elizabeth , Kovacsics-Vári Gergely , Tóthmérész Béla , Török Péter
Published: October 2023

Studying the relationship between biodiversity patterns and processes in vegetation has been at the centre of interest in vegetation ecology for several decades. By studying the biomass of loess and alkaline grasslands along a water and salinity gradient, we aimed to analyse species diversity and CSR functional type patterns. We aimed to test the following hypotheses: i) The biomass and species richness scores and the species composition are significantly different between the sampled grassland community types. ii) The sampled communities are well separated based on the CSR strategy spectrum. iii) The amount of green biomass and litter are positively correlated with competitiveness and negatively with stress tolerance. The biomass and species richness scores and the species composition of the sampled communities along the sampled gradients were significantly different; the highest species richness, evenness and Shannon diversity values were found in loess grasslands. The highest level of litter accumulation was found in alkaline meadows. The communities were well separated in the ordinations but surprisingly, calculation of coordinates for CSR strategy types have not shown clear separation of the grassland community types. Based on the results we can conclude that the current CSR classification is too robust to delineate grassland communities in alkaline landscapes which are markedly different in composition. We point out that the CSR classification is based on the magnitude of stress, and it is not able to differentiate between the various forms of stress which might be responsible for the marked compositional differences. Therefore, developing an index focusing specifically on the functional characterisation of stressed communities and able to differentiate between different forms of stress (e.g., water and/or salinity stress) would be highly beneficial for future studies.
Scale dependency of taxonomic and functional diversity in old-growth and secondary loess steppic grasslands
Authors: Török Péter , Teleki Balázs , Erdős László , McIntosh-Buday Andrea , Ruprecht Eszter , Tóthmérész Béla
Published: October 2023

Widespread campaigns on forest restoration and various tree planting actions lower the awareness of the importance of grasslands for carbon sequestration or biodiversity conservation. Even lower attention is given to the conservation of biodiversity and ecosystem functioning in remnants of ancient, so called old-growth grasslands. Old-growth grasslands in general harbour high biodiversity and even small patches of these can act as important refuges for many plant and animal species in urbanised or agriculture driven landscapes. Spontaneous succession of grassland is frequently viewed as a cost-effective tool for grassland restoration, but its applicability is strongly dependent on many local to landscape-scale factors and the recovery often slow. Thus, for the assessment of the effectiveness of spontaneous succession as a restoration tool, it is essential to compare the species diversity and functional attributes of old-growth and secondary grasslands. We studied the taxonomic and functional diversity in thirteen loess steppic grasslands (8 old-growth and 5 secondary) using differently sized plots ranging from 0.01 to 100m2. Our results indicated that there are remarkable differences in taxonomic and functional diversity between old-growth grasslands and secondary ones. We also point out that during secondary succession there is a likely functional saturation of the species assembly in the first few decades of recovery, and while patterns and structure of secondary grasslands became quite similar to those of old-growth grasslands, the species richness and diversity remains still much lower. Old-growth grasslands support considerable plant diversity, and species composition is slow to recover if destroyed for agricultural land use. This underlines the priority of protecting existing old-growth grassland remnants over restoration actions and the recovery of secondary grasslands.
Mapping the topography of spatial gene expression with interpretable deep learning
Authors: Chitra Uthsav , Arnold Brian J. , Sarkar Hirak , Ma Cong , Lopez-Darwin Sereno , Sanno Kohei , Raphael Benjamin J.
Published: October 2023

Spatially resolved transcriptomics technologies provide high-throughput measurements of gene expression in a tissue slice, but the sparsity of this data complicates the analysis of spatial gene expression patterns such as gene expression gradients. We address these issues by deriving atopographic mapof a tissue slice—analogous to a map of elevation in a landscape—using a novel quantity called theisodepth. Contours of constant isodepth enclose spatial domains with distinct cell type composition, while gradients of the isodepth indicate spatial directions of maximum change in gene expression. We develop GASTON, an unsupervised and interpretable deep learning algorithm that simultaneously learns the isodepth, spatial gene expression gradients, and piecewise linear functions of the isodepth that model both continuous gradients and discontinuous spatial variation in the expression of individual genes. We validate GASTON by showing that it accurately identifies spatial domains and marker genes across several biological systems. In SRT data from the brain, GASTON reveals gradients of neuronal differentiation and firing, and in SRT data from a tumor sample, GASTON infers gradients of metabolic activity and epithelial-mesenchymal transition (EMT)-related gene expression in the tumor microenvironment.
Cardiac-sympathetic contractility and neural alpha-band power: cross-modal collaboration during approach-avoidance conflict
Authors: Dundon Neil M. , Stuber Alexander , Bullock Tom , Garcia Javier O. , Babenko Viktoriya , Rizor Elizabeth , Yang Dengxian , Giesbrecht Barry , Grafton Scott T.
Published: October 2023

As evidence mounts that the cardiac-sympathetic system reacts to challenging cognitive settings, we ask if these responses are passive companions or if they are instead fundamentally intertwined with cognitive function. Healthy human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous neural and cardiac signals. Participants were reward-sensitive, but also experienced approach-avoidance “conflict” when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters revealed that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics suggested that widening decision boundaries served to combat reward-sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac “contractility” (an index of sympathetically-mediated positive inotropy). We also saw evidence of conflict-specific collaboration between the neural and cardiac-sympathetic signals. Specific to states of conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal’s singular influence. Cross-trial coherence analyses provided additional support for a direct role of cardiac-sympathetics in nurturing fair assessment of information streams during conflict by disrupting the prepotent reward signals. We conclude that cardiac-sympathetic activity is not a mere companion, rather it is a critical component collaborating with cognitive processes to combat reward-sensitivity during the approach-avoidance conflict.
A likelihood-based framework for demographic inference from genealogical trees
Authors: Fan Caoqi , Cahoon Jordan L. , Dinh Bryan L. , Ortega-Del Vecchyo Diego , Huber Christian , Edge Michael D. , Mancuso Nicholas , Chiang Charleston W.K.
Published: October 2023

The demographic history of a population drives the pattern of genetic variation and is encoded in the gene-genealogical trees of the sampled alleles. However, existing methods to infer demographic history from genetic data tend to use relatively low-dimensional summaries of the genealogy, such as allele frequency spectra. As a step toward capturing more of the information encoded in the genome-wide sequence of genealogical trees, here we propose a novel framework called the genealogical likelihood (gLike), which derives the full likelihood of a genealogical tree under any hypothesized demographic history. Employing a graph-based structure, gLike summarizes across independent trees the relationships among all lineages in a tree with all possible trajectories of population memberships through time and efficiently computes the exact marginal probability under a parameterized demographic model. Through extensive simulations and empirical applications on populations that have experienced multiple admixtures, we showed that gLike can accurately estimate dozens of demographic parameters when the true genealogy is known, including ancestral population sizes, admixture timing, and admixture proportions. Moreover, when using genealogical trees inferred from genetic data, we showed that gLike outperformed conventional demographic inference methods that leverage only the allele-frequency spectrum and yielded parameter estimates that align with established historical knowledge of the past demographic histories for populations like Latino Americans and Native Hawaiians. Furthermore, our framework can trace ancestral histories by analyzing a sample from the admixed population without proxies for its source populations, removing the need to sample ancestral populations that may no longer exist. Taken together, our proposed gLike framework harnesses underutilized genealogical information to offer exceptional sensitivity and accuracy in inferring complex demographies for humans and other species, particularly as estimation of genome-wide genealogies improves.
ECOD domain classification of 48 whole proteomes from AlphaFold Structure Database using DPAM
Authors: Schaeffer R. Dustin , Zhang Jing , Medvedev Kirill E. , Cong Qian , Grishin Nick V.
Published: October 2023

Protein structure prediction has now been deployed widely across several different large protein sets. Large-scale domain annotation of these predictions can aid in the development of biological insights. Using our Evolutionary Classification of Protein Domains (ECOD) from experimental structures as a basis for classification, we describe the detection and cataloging of domains from 48 whole proteomes deposited in the AlphaFold Database. On average, we can provide positive classification (either of domains or other identifiable non-domain regions) for 90% of residues in all proteomes. We classified 746,349 domains from 536,808 proteins comprised of over 226,424,000 amino acid residues. We examine the varying populations of homologous groups in both eukaryotes and bacteria. In addition to containing a higher fraction of disordered regions and unassigned domains, eukaryotes show a higher proportion of repeated proteins, both globular and small repeats. We enumerate those highly populated domains that are shared in both eukaryotes and bacteria, such as the Rossmann domains, TIM barrels, and P-loop domains. Additionally, we compare the sampling of homologous groups from this whole proteome set against our stable ECOD reference and discuss groups that have been enriched by structure predictions. Finally, we discuss the implication of these results for protein target selection for future classification strategies for very large protein sets.

Author Summary

Proteins can contain one or more domains, regions that are evolutionary independent and convey fiction and function. Here we present our classification of proteins within 48 proteomes provided by the AlphaFold Structural Database. These proteomes span multiple model organisms used in research as a common ground for studying biological principles as well as organisms involved in prevalent human infectious diseases. We classify these domains by our AlphaFold-specific Domain Parser for AlphaFold Models (DPAM), which was previously tested on the human proteome. We find that eukaryotic and bacterial proteomes can be classified to different degrees, with significantly more disordered and low-confident regions in eukaryotic proteins.
Effects of hippocampal noninvasive theta-burst stimulation on consolidation of associative memory in healthy older adults
Authors: Popa Traian , Beanato Elena , Wessel Maximilian J. , Menoud Pauline , Windel Fabienne , Vassiliadis Pierre , Violante Ines R. , Alania Ketevan , Dzialecka Patrycja , Grossman Nir , Neufeld Esra , Hummel Friedhelm C.
Published: October 2023

Stimulation of deep brain areas can offer benefits against cognitive impairments associated with aging. So far, this was only possible via invasive methods accompanied by risks. Grossmanet al.proposed a new noninvasive stimulation technique, transcranial temporal interference electric stimulation (tTIS), which can be steered to target and modulate activity of deep brain structures. Memory capacity depends on subcortical structures such as the hippocampus, hence, modulation of hippocampal activity could benefit declining cognitive functions. The current study investigates whether theta-burst patterned tTIS targeting the hippocampus influences performance of associative memory in older adults. We found that theta-burst patterned tTIS, but not the control stimulation, improved recollection time in a follow-up 24h after the stimulation, suggesting that theta-burst patterned tTIS can influence the efficiency of longer-term encoding. This outcome indicates that tTIS may provide a new noninvasive deep brain stimulation method to modulate senescent memory processes.
Panera: A novel framework for surmounting uncertainty in microbial community modelling using Pan-genera metabolic models
Authors: Palanikumar Indumathi , Sinha Himanshu , Raman Karthik
Published: October 2023

Over the last decade, microbiome research has witnessed exponential growth, largely driven by the widespread availability of metagenomic data. Despite this influx of data, 16S ‘targeted amplicon’ sequencing, which offers relatively lower resolution, still dominates the landscape over whole-genome shotgun sequencing. Existing algorithms for constructing metabolic models of microbial communities primarily rely on whole-genome sequences and do not fully harness the potential of 16S datasets.

In this study, we report ‘Panera’, a novel framework designed to model microbial communities under uncertainty and yet perform inferences by building pan-genus metabolic models. We tested the performance of the models from our approach by analysing their ability to capture the functionality of the entire genus and individual species within a genus. We further exercise the model to explore the comprehensive metabolic abilities of a genus, shedding light on metabolic commonalities between microbial groups. Furthermore, we showcase its application in characterising microbial community models using 16S data. Our hybrid community models, which combine both GSMM and pan-genus metabolic models, exhibit a 10% reduction in prediction error, with error rates diminishing as community size increases.

Overall, the Panera framework represents a potent and effective approach for metabolic modelling, enabling robust predictions of the metabolic phenotypes of microbial communities, even when working with limited 16S data. This advancement has the potential to greatly impact the field of microbiome research, offering new insights into the metabolic dynamics of diverse microbial ecosystems.
Exploring the genetic architecture of ecophysiological traits in microbial ecology using statistical analysis of the properties of protein sequences: application to the glycogen accumulating organism (GAO) phenotype
Authors: Williams Rohan B. H. , Bessarab Irina , Wise Michael J. , Arumugam Krithika
Published: October 2023

Nearly 50 years ago, King and Wilson introduced a key distinction between two types of genetic variation–named structural and regulatory variation–for exploring the molecular basis for phenotypic traits. Structural variation is genetic variation that will influence gene product structure via changes in coding sequence, whereas regulatory variation will influence the control of gene product expression. Here we repurpose these concepts to study the molecular basis of eco-physiological traits observed in microbial ecology, focusing on a specialized glycogen accumulating phenotype, known to be exhibited by a phylogenetically diverse group of microbes. We analyse the statistical properties of the protein sequence of the 1,4–α–glucan branching enzyme (glgB), a key enzyme responsible for formation of glycogen from linear glucans. We show that theglgBproteins in a subgroup of these organisms show unusual statistical properties of protein sequence length, sequence similarity and patterning of functional domains, compared to organisms that do not exhibit this phenotype. These findings suggest a role for structural genetic variation in determining this phenotype in some species. Our analysis holds implications for dissecting the genetic/genomic architecture of complex traits exhibited by microbial communities and also provides a complementary framework to presence–absence level analyses that are ubiquitous in microbial ecology.
Exclusive D-lactate-isomer production during a reactor-microbiome conversion of lactose-rich waste by controlling pH and temperature
Authors: Schütterle Dorothea M. , Hegner Richard , Temovska Monika , Ortiz-Ardila Andrés E. , Angenent Largus T.
Published: October 2023

Lactate is among the top-ten-biobased products. It occurs naturally as D– or L-isomer and as a racemic mixture (DL-lactate). Generally, lactate with a high optical purity is more valuable. In searching for suitable renewable feedstocks for lactate production, unutilized organic waste streams are increasingly coming into focus. Here, we investigated acid whey, which is a lactose-rich byproduct of yogurt production, that represents a considerable environmental footprint for the dairy industry. We investigated the steering of the lactate-isomer composition in a continuous and open culture system (HRT = 0.6 d) at different pH values (pH 5.0vs.pH 6.5) and process temperatures (38°C to 50°C). The process startup was achieved by autoinoculation. At a pH of 5.0 and a temperature of 47°C-50°C, exclusive D-lactate production occurred because of the dominance ofLactobacillusspp. (> 95% of relative abundance). The highest volumetric D-lactate production rate of 722 ± 94.6 mmol C L-1d-1(0.90 ± 0.12 g L-1h-1), yielding 0.93 ± 0.15 mmol C mmol C-1, was achieved at a pH of 5.0 and a temperature of 44°C (n= 18). At a pH of 6.5 and a temperature of 44°C, we found a mixture of DL-lactate (average D-to-L-lactate production rate ratio of 1.69 ± 0.90), which correlated with a high abundance ofStreptococcusspp. andEnterococcusspp. However, exclusive L-lactate production could not be achieved. Our results show that for the continuous conversion of lactose-rich dairy waste streams, the pH was a critical process parameter to control the yield of lactate isomers by influencing the composition of the microbiota. In contrast, temperature adjustments allowed the improvement of bioprocess kinetics.
Decrypting corals: Does regulatory evolution underlie environmental specialization of coral cryptic lineages?
Authors: Gallery Dominique N , Rippe John P , Matz Mikhail V
Published: October 2023

A recent study has shown that two common Caribbean corals,Montastrea cavernosaandSiderastrea siderea, in the Florida Keys each consist of four genetically distinct lineages. These lineages are strongly specialized to a certain depth and, to a lesser extent, to nearshore or offshore habitat. We hypothesized that the lineages’ environmental specialization is at least in part due to regulatory evolution, which would be manifested as the emergence of groups of coregulated genes (“modules”) demonstrating lineage-specific responses to different reef environments. Our hypothesis also predicted that genes belonging to such modules would show greater genetic divergence between lineages than other genes. Contrary to these expectations, responses of cryptic lineages to natural environmental variation were essentially the same at the genome-wide gene coexpression network level. Moreover, none of the identified coregulated gene modules exhibit elevated between-lineage divergence. The environmental specialization of cryptic lineages must, therefore, come from relatively subtle adjustments to gene function or regulation that are not detectable at the gene network level and/or involve other constituents of the coral holobiont rather than the coral host.
Investigating the Impact of Microplastics on Fish Muscle Cell Proliferation and Differentiation: Enhancing Food Safety in Cultivated Meat Production
Authors: Sun Taozhu , Timoneda Alfonso , Banavar Amiti , Ovissipour Reza
Published: October 2023

Cultivated meat, a sustainable alternative to traditional livestock farming, has gained attention for its potential environmental and health benefits. However, concerns about microplastic contamination pose challenges, especially when sourcing cells from marine organisms prone to microplastic bioaccumulation. Additionally, the pervasive presence of microplastics in laboratory settings, ingredients, and during the production, increases the risk of unintentional contamination. This study focused on Atlantic mackerel (Scomber scombrus) skeletal muscle cell lines to examine the effects of microplastic exposure, represented by fluorescent polyethylene microspheres (10-45 µm) on cell performance including cell proliferation, cell viability, gene expression, and differentiation processes critical for cultivated meat production. The results revealed significant impacts on cell attachment and proliferation at microplastic concentrations of 1 µg/mL, 10 µg/mL, and 50 µg/mL. Notably, the 10 µg/mL concentration exerted the most pronounced effects on cell viability during both attachment and proliferation phases. While the results indicated that both microplastic concentration and size influence cell viability, cell differentiation remained unaffected, and additional contributing factors require further investigation. These findings underscore the necessity of thoroughly exploring microplastic-cell interactions to ensure food safety and safeguard health within the burgeoning cultivated meat industry.
Non-contact respiratory measurements of outdoor-housed rhesus macaques (Macaca mulatta) using millimeter-wave radar systems
Authors: Minami Toshiki , Sanematsu Daisuke , Iwata Itsuki , Sakamoto Takuya , Myowa Masako
Published: October 2023

Respiration is an invaluable signal that facilitates the real-time observation of physiological dynamics. In recent years, the advancement of non-contact measurement technology has gained momentum in capturing physiological dynamics in natural settings. This technology is anticipated to find utility in healthcare, not only in humans but also in captive animals, to enhance animal welfare. Currently, the predominant non-contact approach for captive animals involves measuring vital signs through subtle variations in skin color. However, this approach is limited when dealing with body regions covered with hair or outdoor environments under fluctuating sunlight. In contrast, millimeter-wave radar systems, which employ millimeter waves that can penetrate animal fur, exhibit minimal susceptibility to sunlight interference. Thus, this method holds promise for non-contact vital measurements in natural and outdoor settings. In this study, we validated a millimeter-wave radar methodology for capturing respiration in outdoor-housed rhesus macaques (Macaca mulatta). The radar was positioned beyond the captive enclosure and maintained at a distance of > 5 m from the target. Millimeter waves were transmitted to the target, and the reflected waves were used to estimate skin surface displacement associated with respiration. The results revealed periodic skin surface displacement, and the estimated respiratory rate was within the reported range of respiratory rates for rhesus macaques. This result suggests the potential applicability of millimeter-wave radar for non-contact respiration monitoring in outdoor-housed macaques. The continued advancement of non-contact vital measurement technology will contribute to the mental and physical monitoring of captive animals to establish comfortable captive environments.

Research Highlights

Millimeter-wave radar systems succeeded in the non-contact measurement of respiration in outdoor-housed rhesus macaques from > 5 m. Our results demonstrate the feasibility of radar-based remote monitoring to assess the welfare of zoo-housed animals.
Human Motor Endplate Survival after Chronic Peripheral Nerve Injury
Authors: Gupta Ranjan , Johnston Tyler R. , Chen Vivian Y. , Gonzales Luigi P. , Steward Oswald
Published: October 2023

Objective

Degeneration of motor endplates (MEPs) in denervated muscle is thought to be a key factor limiting functional regeneration after peripheral nerve injury (PNI) in humans. However, there is currently no paradigm to determine MEP status in denervated human muscle to estimate likelihood of reinnervation success. Here, we present a quantitative analysis of MEP status in biopsies of denervated muscles taken during nerve repair surgery and ensuing functional recovery.

Methods

This is a retrospective single-surgeon cohort study of patients (n=22) with upper extremity PNI confirmed with electromyography (EMG), treated with nerve transfers. Muscle biopsies were obtained intra-operatively from 10 patients for MEP morphometric analysis. Age at time of surgery ranged from 22-77 years and time from injury to surgery ranged from 2.5 -163 months. Shoulder range of motion (ROM) and Medical Research Council (MRC) scores were recorded pre-op and at final follow-up.

Results

Surviving MEPs were observed in biopsies of denervated muscles from all patients, even those greater than six months from injury. Average postoperative ROM improvement (assessed between 6-9 months post-surgery) was: forward flexion 84.3 ± 51.8°, abduction 62.5 ± 47.9°, and external rotation 25.3 ± 28.0°.

Interpretation

While it is believed that MEP degeneration 6 months post-injury prevents reinnervation, this data details MEP persistence beyond this timepoint along with significant functional recovery after nerve surgery. Accordingly, persistence of MEPs in denervated muscles may predict the extent of functional recovery from nerve repair surgery.
Nurse-led point-of-care ultrasonography with telemedicine review to improve the impact of antenatal care: a formative qualitative study in Kenya
Authors: Kumar Meghan Bruce , Mulongo Caleb Mike , Pincerato Lucia , DeVita MariaVittoria , Saidi Salima , Gakii Yvonne , Morino GianFranco , Kumar Pratap
Published: October 2023

The informal settlements of Nairobi have higher neonatal and infant mortality rates than the average for Nairobi. Universal access to important diagnostics like ultrasonography is poor and inequitable due to the high cost of devices and limited availability of skilled sonographers. Recent advances of mobile ultrasound probes connected to smartphones, with or without artificial intelligence support, have improved access to devices; but skills to perform and interpret scans continue to be limited. The SonoMobile intervention involved training nurse-midwives to conduct point-of-care obstetric ultrasound scans in antenatal care clinics in urban informal settlements. Scan data and images were shared, using telemedicine technology, with remote sonographers, who reviewed scan images and data, and provided reports. This qualitative study of 61 respondents from diverse stakeholder groups describes the acceptability, utility and potential sustainability of nurse-led, point-of-care obstetric ultrasonography with telemedicine review. Perceived value of nurse-led obstetric ultrasonography include improving access and affordability of obstetric ultrasonography services, timely identification and referral of high-risk pregnancies, and improving awareness of appropriate antenatal care among underserved populations. The relative affordability of SonoMobile was described as a critical enabler for a business model targeting low- and middle-income segments of the population, and for increasing quality and equity of antenatal care coverage. Areas highlighted for improvement include strengthening supervision of nurse trainees, broadening the scope of nurse training, and development of clear regulatory guidelines for nurse-led obstetric ultrasonography. The study highlights the complex task shifting required to provide universal access to a life-saving technology in an LMIC health system.
An annual gene expression profile of markers for programmed cell death and polyphenols biosynthesis across heartwood forming stems inRobinia pseudoacacia
Authors: Lau Sylas , Lange Henrik , Magel Elisabeth
Published: October 2023

Heartwood formation is a developmental defense strategy in trees that transforms the inner stem core through the deposition of natural antimicrobial preservatives. The defining cellular events in this process are the accumulation of specialized metabolites conjoined with the death of living cells in the transition zone. While previous studies have characterized heartwood compounds and deposition, the cell death aspects are often neglected. Thus, the correlation of these defining cellular events remained unclear, while the exact timing of occurrence and regional involvement within the stem became topics for debate. In this study, members of metacaspases and vacuolar processing enzymes were isolated as programmed cell death (PCD) markers to explore their correlation with those of polyphenol biosynthesis. We collected heartwood-forming stems fromR. pseudoacaciamonthly for a year and monitored their expression through real-time PCR. Our results revealed novel markers of PCD in xylem parenchyma cells and demonstrated their corresponding fluctuation in expression with markers of polyphenols across the stem regions. The annual expression profile demonstrated regional stem development along with weather data on a monthly scale. This work provides a framework to compare the xylem-specific PCD in stages of stem development and a preliminary overview of how they correspond to external conditions over an annual cycle.
Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO
Authors: Lucas Cormac J. , Sheridan Ryan M. , Reynoso Glennys V. , Davenport Bennett J. , McCarthy Mary K , Martin Aspen , Hesselberth Jay R. , Hickman Heather D. , Tamburini Beth A. J. , Morrison Thomas E.
Published: October 2023

Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we find that during the first 24 h of infection, CHIKV RNA accumulates in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response, including recruitment of myeloid cells to the LN, was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary LECs diminished in number, suggesting further functional impairment of the LN by infection. Consistent with this idea, we find that antigen acquisition by LECs, a key function of LN LECs during infection and immunization, was reduced during pathogenic CHIKV infection.
Diversity of visual inputs to Kenyon cells of theDrosophilamushroom body
Authors: Ganguly Ishani , Heckman Emily L. , Litwin-Kumar Ashok , Josephine Clowney E. , Behnia Rudy
Published: October 2023

The arthropod mushroom body is well-studied as an expansion layer that represents olfactory stimuli and links them to contingent events. However, 8% of mushroom body Kenyon cells inDrosophila melanogasterreceive predominantly visual input, and their tuning and function are poorly understood. Here, we use the FlyWire adult whole-brain connectome to identify inputs to visual Kenyon cells. The types of visual neurons we identify are similar across hemispheres and connectomes with certain inputs highly overrepresented. Many visual projection neurons presynaptic to Kenyon cells receive input from large swathes of visual space, while local visual interneurons, providing smaller fractions of input, receive more spatially restricted signals that may be tuned to specific features of the visual scene. Like olfactory Kenyon cells, visual Kenyon cells receive sparse inputs from different combinations of visual channels, including inputs from multiple optic lobe neuropils. The sets of inputs to individual visual Kenyon cells are consistent with random sampling of available inputs. These connectivity patterns suggest that visual coding in the mushroom body, like olfactory coding, is sparse, distributed, and combinatorial. However, the expansion coding properties appear different, with a specific repertoire of visual inputs projecting onto a relatively small number of visual Kenyon cells.