bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Anatomy for Fibular Free Flap Focusing on the Inferior Tibiofibular Syndesmotic System: A Cadaveric Study and Case Series of 3-Dimensional Prefabricate Cutting Guided Fibular Free Flap
Authors: Ongsiriporn Mathee , Chaikangwan Irin , Piyaman Parkpoom , Khongchu Nachasa , Akaranuchat Nutthawut , Yodrabum Nutcha
Published: October 2021

Even though there are many options for mandibular reconstruction, a free fibula osteocutaneous flap is regarded as the most frequently used flap. Despite having some previous anatomical studies pertaining to syndesmotic ligaments, there is no study pointing out that surgical landmarks can be used while free fibula osteocutaneous flaps are performed and used for surgical landmarks in order to avoid syndesmotic ligament injuries. Therefore, this study investigates the characteristics and relationship between inferior syndesmotic ligaments and fibula in cadavers. A total of 140 legs were obtained from 83 embalmed cadavers as well as other soft ones, which were donated for the inferior tibiofibular syndes- motic system's study. Detailed dissection and measurement of each ligament's distance to the end of the fibula and lateral malleolus were performed. Distances from the distal end of the fibula to anterior inferior tibiofibular ligament, posterior inferior tibiofibular, and inferior transverse ligament, and the lower border of the interosseous membrane are 3.5 ± 0.4 cm, 3.4 ± 0.5 cm, 1.9 ± 0.4 cm, and 5 ± 1 cm (mean ± SD), respectively. Distance from the most distal part of the fibula to lateral malleolus is 1.6 ± 0.4 cm (mean ± SD). Thus, the remaining distance of the fibular should be left at least 4 cm without disrupting the syndesmotic ligament complex. It is argued that the lateral malleolus can be applied as a surgical landmark while harvesting fibula.
Analysis of Orbital Blowout Fracture Location and Hess Area Ratio
Authors: Osaki Takeo , Tamura Ryosuke , Sakakibara Shunsuke , Nomura Tadashi , Hashikawa Kazunobu , Terashi Hiroto
Published: October 2021

This study aimed to analyze the Hess area ratio (HAR%) in cases of blowout fracture treated in our department and clarify the outline of eye movement disorders in blowout fractures. Patients who underwent surgery for orbital blowout fractures in our department were included. Fracture locations were classified into 5 types (A, outside floor; B, C, anterior and posterior floor; and D, E, anterior and posterior medial wall). The HAR% was compared before and after surgery in eligible cases. The relationship between the fracture location and preoperative HAR% was investigated using multiple regression analysis. The study involved 85 patients. Hess area ratio was higher postoperatively than preoperatively (70.75 ± 18.26 versus 90.06 ± 13.99, P 
< 0.01). The postoperative HAR% tended to be higher when the iliac bones were compared to other materials; however, this difference was not significant (90.73 ± 12.91 versus 80.30 ± 17.81, P = 0.178). Fracture locations C and E significantly contributed to the prediction of HAR% as negative regression coefficients (P = 0.024 and 0.013, respectively). The posterior fracture area on both the orbital floor and medial wall contributed to the decrease in preoperative HAR%. This observation indicates that the reconstruction of the posterior region is extremely crucial.
Hemodynamic Effect of Resuscitative Endovascular Balloon Occlusion of the Aorta in Hemodynamic Instability Secondary to Acute Cardiac Tamponade in a Porcine Model
Authors: McGreevy David T. , Björklund Janina , Nilsson Kristofer F. , Hörer Tal M.
Published: October 2021

Background:

The pre-hospital use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is increasing, although it remains controversial, in part because of suggested contraindications such as acute cardiac tamponade (ACT). As both the pre-hospital and in-hospital use of REBOA might potentially occur with concurrent ACT, knowledge of the hemodynamic effect of REBOA in this setting is crucial. This study, therefore, aimed at investigating the physiological effects of REBOA in hemodynamic instability secondary to ACT in a porcine model. We hypothesize that REBOA can temporarily increase systemic blood pressure and carotid blood flow, and prolong survival, in hemodynamic shock caused by ACT.

Methods:

Fourteen pigs (24–38 kg) underwent ACT, through true cardiac injury and hemorrhage into the pericardial space, and were allowed to hemodynamically deteriorate. At a systolic blood pressure (SBP) of 50 mm Hg (SBP50) they were randomized to total occlusion REBOA in zone 1 or to a control group. Survival, hemodynamic parameters, carotid blood flow (CBF), femoral blood flow (FBF), cardiac output (CO), end-tidal CO2, and arterial blood gas parameters were analyzed.

Results:

REBOA intervention was associated with a significant increase in SBP (50 mm Hg to 74 mm Hg, P = 0.016) and CBF (110 mL/min to 195 mL/min, P = 0.031), with no change in CO, compared to the control group. At 20 min after SBP50, the survival rate in the intervention group was 86% and in the control group 14%, with time to death being significantly longer in the intervention group.

Conclusions:

This randomized animal study demonstrates that REBOA can help provide hemodynamic stabilization and prolong survival in hemodynamic shock provoked by ACT. It is important to stress that our study does not change the fact that urgent pericardiocentesis or cardiac surgery is, and should remain, the standard optimal treatment for ACT.

Level of evidence: Prospective, randomized, experimental animal study. Basic science study, therapeutic.
Comparison of gut viral communities in diarrhoea and healthy dairy calves
Authors: Lu Xiang , Hua Xiuguo , Wang Yan , Zhang Dong , Jiang Shengyao , Yang Shixing , Wang Xiaochun , Shen Quan , Zhou Tianji , Lin Zhibing , Zhang Wen , Cui Li
Published: October 2021

Calf diarrhoea has been a major cause of economic losses in the global dairy industry. Many factors, including multiple pathogen infections, can directly or indirectly cause calf diarrhoea. This study compared the faecal virome between 15 healthy calves and 15 calves with diarrhoea. Significantly lower diversity of viruses was found in samples from animals with diarrhoea than those in the healthy ones, and this feature may also be related to the age of the calves. Viruses belonging to the families Astroviridae and Caliciviridae that may cause diarrhoea in dairy calves have been characterized, which revealed that reads of caliciviruses and astroviruses in diarrhoea calves were much higher than those in healthy calves. Five complete genomic sequences closely related to Smacoviridae have been identified, which may participate in the regulation of the gut virus community ecology of healthy hosts together with bacteriophages. This research provides a theoretical basis for further understanding of known or potential enteric pathogens related to calf diarrhoea.
The open pan-genome architecture and virulence landscape of Mycobacterium bovis
Authors: Reis Ana C. , Cunha Mónica V.
Published: October 2021

Animal tuberculosis (TB) is an emergent disease caused by

Mycobacterium bovis

, one of the animal-adapted ecotypes of the

Mycobacterium tuberculosis

complex (MTC). In this work, whole-genome comparative analyses of 70

M

.

bovis

were performed to gain insights into the pan-genome architecture. The comparison across

M. bovis

predicted genome composition enabled clustering into the core- and accessory-genome components, with 2736 CDS for the former, while the accessory moiety included 3897 CDS, of which 2656 are restricted to one/two genomes only. These analyses predicted an open pan-genome architecture, with an average of 32 CDS added by each genome and show the diversification of discrete

M. bovis

subpopulations supported by both core- and accessory-genome components. The functional annotation of the pan-genome classified each CDS into one or several COG (Clusters of Orthologous Groups) categories, revealing ‘transcription’ (total average CDSs, n=258), ‘lipid metabolism and transport’ (n=242), ‘energy production and conversion’ (n=214) and ‘unknown function’ (n=876) as the most represented. The closer analysis of polymorphisms in virulence-related genes in a restrict group of

M. bovis

from a multi-host system enabled the identification of clade-monomorphic non-synonymous SNPs, illustrating clade-specific virulence landscapes and correlating with disease severity. This first comparative pan-genome study of a diverse collection of

M. bovis

encompassing all clonal complexes indicates a high percentage of accessory genes and denotes an open, dynamic non-conservative pan-genome structure, with high evolutionary potential, defying the canons of MTC biology. Furthermore, it shows that

M. bovis

can shape its virulence repertoire, either by acquisition and loss of genes or by SNP-based diversification, likely towards host immune evasion, adaptation and persistence.
A systematic review of enteric pathogens and antibiotic resistance genes in outdoor urban aerosols
Authors: Ginn Olivia , Lowry Sarah , Brown Joe
Published: October 2021

Aerosol transport of enteric microbiota including fecal pathogens and antimicrobial resistance genes (ARGs) has been documented in a range of settings but remains poorly understood outside indoor environments. We conducted a systematic review of the peer-reviewed literature to summarize evidence on specific enteric microbiota including enteric pathogens and ARGs that have been measured in aerosol samples in urban settings where the risks of outdoor exposure and antibiotic resistance (AR) spread may be highest. Following PRISMA guidelines, we conducted a key word search for articles published within the years 1990-2020 using relevant data sources. Two authors independently conducted the keyword searches of databases and conducted primary and secondary screenings before merging results. To be included, studies contained extractable data on enteric microbes and AR in outdoor aerosols regardless of source confirmation and reported on qualitative, quantitative, or viability data on enteric microbes or AR. Qualitative analyses and metric summaries revealed that enteric microbes and AR have been consistently reported in outdoor aerosols, generally via relative abundance measures, though gaps remain preventing full understanding of the role of the aeromicrobiological pathway in the fate and transport of enteric associated outdoor aerosols. We identified remaining gaps in the evidence base including a need for broad characterization of enteric pathogens in bioaerosols beyond bacterial genera, a need for greater sampling in locations of high enteric disease risk, and a need for quantitative estimation of microbial and nucleic acid densities that may be applied to fate and transport models and in quantitative microbial risk assessment.

FUNDING

This study was funded by the National Science Foundation under grant number 1653226. This funding source had no role in the design of this study and had no role during its execution, analyses, interpretation of the data, or decision to submit results.
The Persistence of Neutralising Antibodies up to 11 months after SARS-CoV-2 Infection in the Southern Region of New Zealand
Authors: McGregor Reuben , Craigie Alyson , Jack Susan , Upton Arlo , Moreland Nicole J. , Ussher James
Published: October 2021

During the first wave of SARS-CoV-2 infection in New Zealand a cohort of 78 PCR-confirmed COVID-19 cases was recruited in the Southern District Health Board region. Here we report on this unique cohort nearly 1-year after infection. There was no known community transmission in the region over the study period due to New Zealand’s elimination status at the time, nor had any participants received a COVID-19 vaccine. In the absence of re-exposure, antibody reactivity to the viral spike protein, as well as neutralising antibodies to both the ancestral strain and the delta variant remained relatively stable between 8 and 11 months post-infection. This suggests long-lived antibody responses can be generated from a single natural infection event. However, given the risks of serious disease associated with SARS-CoV-2 infection, vaccination is still strongly recommended.
Combining Navigator and Optical Prospective Motion Correction for High-Quality 500 μm Resolution Quantitative Multi-Parameter Mapping at 7T
Authors: Vaculčiaková Lenka , Podranski Kornelius , Edwards Luke J. , Ocal Dilek , Veale Thomas , Fox Nick C. , Haak Rainer , Ehses Philipp , Callaghan Martina F. , Pine Kerrin J. , Weiskopf Nikolaus
Published: October 2021

PURPOSE

High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients.

METHODS

Camera-based optical prospective motion correction (PMC) and free-induction decay (FID) navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics.

RESULTS

NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections.

CONCLUSION

Navigator correction and PMC significantly improved the quality of PD, R1 and R2* maps, particularly in less compliant elderly volunteers and dementia patients.
Deep autoencoder for interpretable tissue-adaptive deconvolution and cell-type-specific gene analysis
Authors: Chen Yanshuo , Wang Yixuan , Chen Yuelong , Cheng Yuqi , Wei Yumeng , Li Yunxiang , Wang Jiuming , Wei Yingying , Chan Ting-Fung , Li Yu
Published: October 2021

Single-cell RNA-sequencing has become a powerful tool to study biologically significant characteristics at explicitly high resolution. However, its application on emerging data is currently limited by its intrinsic techniques. Here, we introduce Tissue-AdaPtive autoEncoder (TAPE), a deep learning method connecting bulk RNA-seq and single-cell RNA-seq to achieve precise deconvolution in a short time. By constructing an interpretable decoder and training under a unique scheme, TAPE can predict cell-type fractions and cell-type-specific gene expression tissue-adaptively. Compared with popular methods on several datasets, TAPE has a better overall performance and comparable accuracy at cell type level. Additionally, it is more robust among different cell types, faster, and sensitive to provide biologically meaningful predictions. Moreover, through the analysis of clinical data, TAPE shows its ability to predict cell-type-specific gene expression profiles with biological significance. We believe that TAPE will enable and accelerate the precise analysis of high-throughput clinical data in a wide range.
Transcriptomic profiling of sex-specific olfactory neurons reveals subset-specific receptor expression inCaenorhabditis elegans
Authors: Reilly Douglas K. , Schwarz Erich M. , Muirhead Caroline S. , Robidoux Annalise N. , Narayan Anusha , Doma Meenakshi K. , Sternberg Paul W. , Srinivasan Jagan
Published: October 2021

The nematodeCaenorhabditis elegansutilizes chemosensation to navigate an ever-changing environment for its survival. A class of secreted small-molecule pheromones, termed ascarosides, play an important role in olfactory perception by affecting biological functions ranging from development to behavior. The ascaroside ascr#8 mediates sex-specific behaviors, driving avoidance in hermaphrodites and attraction in males. Males sense ascr#8 via the ciliated male-specific cephalic sensory (CEM) neurons, which exhibit radial symmetry along dorsal-ventral and left-right axes. Calcium imaging studies suggest a complex neural coding mechanism that translates stochastic physiological responses in these neurons to reliable behavioral outputs. To test the hypothesis that neurophysiological complexity arises from differential expression of genes, we performed cell-specific transcriptomic profiling; this revealed between 18 and 62 genes with at least two-fold higher expression in a specific CEM neuron type versus both other CEM neurons and adult males. These included two G protein coupled receptor (GPCR) genes,srw-97anddmsr-12, that were specifically expressed in non-overlapping subsets of CEM neurons and whose expression was confirmed by GFP reporter analysis. Single CRISPR-Cas9 knockouts of eithersrw-97ordmsr-12resulted in partial defects, while a double knockout of bothsrw-97anddmsr-12completely abolished the attractive response to ascr#8. Together, our results suggest that the evolutionarily distinct GPCRs SRW-97 and DMSR-12 act non-redundantly in discrete olfactory neurons to facilitate male-specific sensation of ascr#8.
Techniques to Produce and Evaluate Realistic Multivariate Synthetic Data
Authors: Heine John , Fowler Erin E.E. , Berglund Anders , Schell Michael J. , Eschrich Steven
Published: October 2021

Background

Data modeling in biomedical-healthcare research requires a sufficient sample size for exploration and reproducibility purposes. A small sample size can inhibit model performance evaluations (i.e., the small sample problem).

Objective

A synthetic data generation technique addressing the small sample size problem is evaluated. We show: (1) from the space of arbitrarily distributed samples, a subgroup (class) has a latent multivariatenormal characteristic; (2) synthetic populations (SPs) ofunlimitedsize can be generated from this class with univariate kernel density estimation (uKDE) followed by standard normal random variable generation techniques; and (3) samples drawn from these SPs are statistically like their respective samples.

Methods

Three samples (n = 667), selectedpseudo-randomly,were investigated each with 10 input variables (i.e., X). uKDE (optimized with differential evolution) was used to augment the sample size in X (i.e., the input variables). The enhanced sample size was used to construct maps that produced univariate normally distributed variables in Y (mapped input variables). Principal component analysis in Y produced uncorrelated variables in T, where the univariate probability density functions (pdfs) were approximated as normal with specific variances; a given SP in T was generated with normally distributed independent random variables with these specified variances. Reversing each step produced the respective SPs in Y and X. Synthetic samples of the same size were drawn from these SPs for comparisons with their respective samples. Multiple tests were deployed: to assess univariate and multivariate normality; to compare univariate and multivariate pdfs; and to compare covariance matrices.

Results

One sample was approximately multivariate normal in X and all samples were approximately multivariate normal in Y, permitting the generation ofunlimitedsized SPs. Uni/multivariate pdf and covariance comparisons (in X, Y and T) showed similarity between samples and synthetic samples.

Conclusions

The work shows that a class of multivariate samples has a latentnormal characteristic; for such samples, our technique is a simplifying mechanism that offers an approximate solution to the small sample problem by generating similar synthetic data. Further studies are required to understand this latent normal class, as two samples exhibited this characteristic in the study.
Integration of GWAS and TWAS to elucidate the genetic architecture of natural variation for leaf cuticular conductance in maize
Authors: Lin Meng , Qiao Pengfei , Matschi Susanne , Vasquez Miguel , Ramstein Guillaume P. , Bourgault Richard , Mohammadi Marc , Scanlon Michael J. , Molina Isabel , Smith Laurie G. , Gore Michael A.
Published: October 2021

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association study (GWAS/TWAS) to identify candidate genes putatively regulating variation in leafgc. Of the 22 plausible candidate genes identified, five were predicted to be involved in cuticle precursor biosynthesis and export, two in cell wall modification, nine in intracellular membrane trafficking, and seven in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor theISTL1genomic region from eight donor parents were evaluated forgc, confirming the association betweengcandISTL1in a haplotype-based association analysis. The findings of this study provide novel insights into the role of regulatory variants in the development of the maize leaf cuticle, and will ultimately assist breeders to develop drought-tolerant maize for target environments.

Sentence summary

We performed an integrated GWAS/TWAS and identified 22 candidate genes putatively regulating variation in maize leafgc. The association betweengcand the strongest candidate causal gene,ISTL1, was validated with maize nested near-isogenic lines.
RCX – an R package adapting the Cytoscape Exchange format for biological networks
Authors: Auer Florian , Kramer Frank
Published: October 2021

Motivation

The Cytoscape Exchange (CX) format is a JSON-based data structure designed for the transmission of biological networks using standard web technologies. It was developed by the network data exchange (NDEx), which itself serves as online commons to share and collaborate on biological networks. Furthermore, the Cytoscape software for the analysis and visualization of biological networks contributes structure elements to capture the visual layout within the CX format. However, there is a fundamental difference between data handling in web standards and R. A manual conversion requires detailed knowledge of the CX format to reproduce and work with the networks.

Results

Here we present a software package to create, handle, validate, visualize and convert networks in CX format to standard data types and objects within R. Networks in this format can serve as a source for biological knowledge, and also capture the results of the analysis of those while preserving the visual layout across all platforms. The RCX package connects the R environment for statistical computing with outside platforms for storage and collaboration, as well as further analysis and visualization of biological networks.

Availability

RCX is a free and open-source R package, available on Bioconductor from release 3.15 (https://bioconductor.org/packages/RCX) and via GitHub (https://github.com/frankkramer-lab/RCX).

Contact

florian.auer@informatik.uni-augsburg.de

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Camel nanobodies broadly neutralize SARS-CoV-2 variants
Authors: Hong Jessica , Kwon Hyung Joon , Cachau Raul , Chen Catherine Z. , Butay Kevin John , Duan Zhijian , Li Dan , Ren Hua , Liang Tianyuzhou , Zhu Jianghai , Dandey Venkata P. , Martin Negin , Esposito Dominic , Ortega-Rodriguez Uriel , Xu Miao , Borgnia Mario J. , Xie Hang , Ho Mitchell
Published: October 2021

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two VHH nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of ≥5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants.

One-Sentence Summary

Dromedary camel (Camelus dromedarius) VHH phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.
Major sex differences in allele frequencies for X chromosome variants in the 1000 Genomes Project data
Authors: Wang Zhong , Sun Lei , Paterson Andrew D.
Published: October 2021

An unexpectedly high proportion of SNPs on the X chromosome in the 1000 Genomes Project phase 3 data were identified with significant sex differences in minor allele frequencies (sdMAF). sdMAF persisted for many of these SNPs in the recently released high coverage whole genome sequence, and it was consistent between the five super-populations. Among the 245,825 common biallelic SNPs in phase 3 data presumed to be high quality, 2,039 have genome-wide significant sdMAF (p-value <5e-8). sdMAF varied by location: (NPR)=0.83%, pseudo-autosomal region (PAR1)=0.29%, PAR2=13.1%, and PAR3=0.85% of SNPs had sdMAF, and they were clustered at the NPR-PAR boundaries, among others. sdMAF at the NPR-PAR boundaries are biologically expected due to sex-linkage, but have generally been ignored in association studies. For comparison, similar analyses found only 6, 1 and 0 SNPs with significant sdMAF on chromosomes 1, 7 and 22, respectively. Future X chromosome analyses need to take sdMAF into account.
Of Biofilms and Beehives: An Analogy-Based Instructional Tool to Introduce Biofilms to High-School and Undergraduate Students
Authors: Kadam Snehal , Chattopadhyay Ankita , Kaushik Karishma S
Published: October 2021

The concept of biofilms and biofilm-based research is largely absent or minimally described in high school and undergraduate life science curriculum. While it is well-established that microbes, such as bacteria and fungi most often exist in multicellular biofilm communities, descriptions in standard biology textbooks continue to focus on the single-celled form of microbial life. We have developed an analogy-based instructional tool to introduce and explain biofilms to high school and undergraduate students. The module employs an analogy with beehives, given that biofilms and beehives are both ‘superorganism’ states, to explain key biofilm features such as development and structure, chemical communication, division of labor and emergent properties. We delivered this analogy based learning tool to a cohort of 49 high school and undergraduate students, and based on participant feedback and learnings, present a formal evaluation of the instructional tool. Further, we outline prerequisites and learning approaches that can enable the delivery of this module in classroom and virtual learning settings, including suggestions for pre-lesson reading, student-centred interactive activities, and specific learning objectives. Taken together, this instructional analogy holds potential to serve as an educational tool to introduce biofilms in high school and undergraduate curricula in a relatable and comprehensible manner.
Patient-derived endometrial organoids from MRKH patients: Insight in disease causing pathways
Authors: Brucker Sara Y. , Hentrich Thomas , Schulze-Hentrich Julia M. , Pietzsch Martin , Wajngarten Noel , Singh Anjali Ralhan , Rall Katharina , Koch André
Published: October 2021

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focusses on DNA-sequencing efforts and, so far, failed to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point at potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.
Climate-driven variation in biotic interactions provides a narrow and variable window of opportunity for an insect herbivore at its ecological margin
Authors: Stewart James E. , Maclean Ilya M.D. , Trujillo Gara , Bridle Jon , Wilson Robert J.
Published: October 2021

Climate-driven geographic range shifts have been associated with transitions between dietary specialism and generalism at range margins. The mechanisms underpinning these often transient niche breadth modifications are poorly known, but utilisation of novel resources likely depends on phenological synchrony between the consumer and resource. We use a climate-driven range and host shift by the butterflyAricia agestisto test how climate-driven changes in host phenology and condition affect phenological synchrony, and consider implications for host use.

Our data suggest that the perennial plant which was the primary host before range expansion is a more reliable resource than the annual Geraniaceae upon which the butterfly has become specialised in newly colonised parts of its range. In particular, climate-driven phenological variation in the novel hostGeranium dissectumgenerates a narrow and variable ‘window of opportunity’ for larval productivity in summer. Therefore, although climatic change may allow species to shift hosts and colonise novel environments, specialisation on phenologically-limited hosts may not persist at ecological margins as climate change continues. We highlight the potential role for phenological (a)synchrony in determining lability of consumer-resource associations at range margins, and the importance of considering causes of synchrony in biotic interactions when predicting range shifts.
Sex differences in migraine: A twin study
Authors: Morgan Fitzgerald , Saelzler Ursula G. , Panizzon Matthew S.
Published: October 2021

Migraine is a neurological disorder with a prominent sex difference such that two thirds of sufferers are female. The mechanisms behind the preponderance of migraine in women have yet to be elucidated. With data on 51,872 participants from the Swedish Twin Registry, we report results from two distinct analyses intended to clarify the degree to which genetic and environmental factors contribute to sex differences in migraine. First, we fit a sex-limitation model to determine if quantitative genetic differences (i.e., is migraine equally heritable across men and women) and/or qualitative genetic differences (i.e., are different genes involved in migraine across men and women) were present. Next, we used a multilevel logistic regression model to compare the prevalence of migraine in individuals from opposite-sex and same-sex twin pairs to determine whether differences in the prenatal hormone environment contribute to migraine risk. In the final analytic sample, women were found to have a significantly higher rate of migraine without aura relative to men (17.6% vs 5.5%). The results from an ADE sex-limitation model indicate that migraine is equally heritable in men and women, with a broad sense heritability of .45, (95% CI = .40 - .50), while results from a reduced AE sex-limitation model provide subtle evidence for differences in the genes underlying migraine across men and women. The logistic regression analysis revealed a significant increase in migraine risk for females with a male co-twin relative to females with a female co-twin (OR = 1.51, 95% CI = 1.26 – 1.81). These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females. This effect points to a potential prenatal neuroendocrine factor in the development of migraine.
Visuomotor adaptation modulates the clustering of sleep spindles into trains
Authors: Solano Agustín , Riquelme Luis A. , Perez-Chada Daniel , Della-Maggiore Valeria
Published: October 2021

Sleep spindles are thought to promote memory consolidation. Recently, we have shown that visuomotor adaptation (VMA) learning increases the density of spindles and promotes the coupling between spindles and slow oscillations, locally, with the level of spindle-SO synchrony predicting overnight memory retention. Yet, growing evidence suggests that the rhythmicity in spindle occurrence may also influence the stabilization of declarative and procedural memories. Here, we examined if VMA learning promotes the temporal organization of sleep spindles into trains. We found that VMA increased the proportion of spindles and spindle-SO couplings in trains. In agreement with our previous work, this modulation was observed over the contralateral hemisphere to the trained hand, and predicted overnight memory retention. Interestingly, spindles grouped in a cluster showed greater amplitude and duration than isolated spindles. The fact that these features increased as a function of train length, provides evidence supporting a biological advantage of this temporal arrangement. Our work opens the possibility that the periodicity of NREM oscillations may be relevant in the stabilization of procedural memories.

CONTRIBUTION STATEMENT

Ever since the discovery of memory systems, the study of the mechanisms supporting the consolidation of declarative and procedural memories has progressed somewhat in parallel. We now know, however, that structures originally thought of as purely declarative such as the hippocampus, participate in the consolidation of procedural tasks. Recently, we showed that sleep predicts long-term motor memory through the local synchrony between fast sleep spindles and slow oscillations, a mechanism initially described for the consolidation of declarative memories. Novel evidence has linked the rhythmicity in the occurrence of spindles to memory stabilization. This framework proposes that temporally clustered spindles into trains of two or more separated by 3-6 seconds, may favor the reinstatement and subsequent reprocessing of previously acquired memories. This temporal arrangement may facilitate mnemonic replay and neocortical integration. In the present study, we show that motor learning promotes the organization of spindles into trains, locally, over the contralateral hemisphere, and that this modulation predicts overnight memory retention. Spindle grouping also augmented the proportion of spindle-SO couplings in trains. Importantly, spindles in a cluster increased their duration and amplitude as a function of train length, pointing to a physiological benefit of this temporal organization.
Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells from HIV+ Controllers and Non-Controllers
Authors: George Ashley F. , Luo Xiaoyu , Neidleman Jason , Hoh Rebecca , Vohra Poonam , Thomas Reuben , Shin Min-Gyoung , Lee Madeline J. , Blish Catherine A. , Deeks Steven G. , Greene Warner C. , Lee Sulggi A. , Roan Nadia R.
Published: October 2021

T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. In this study, we used 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers, and antiretroviral therapy (ART)-suppressed individuals who had started therapy during chronic vs. acute infection, the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5-counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.
In vitro characterisation and clinical evaluation of the diagnostic accuracy of a new antigen test for SARS-CoV-2 detection
Authors: Montoya J.J. , Rubio J.M. , Ouahid Y. , Lopez A. , Madejon A. , Gil-Garcia A.I. , Hannam R.J. , Butler H.R.E. , Castan P.
Published: October 2021

Background and aims

Quick, user-friendly and sensitive diagnostic tools are the key to controlling the spread of the SARS-CoV-2 pandemic in the new epidemiologic landscape. The aim of this work is to characterise a new Covid-19 antigen test that uses an innovative chromatographic Affimer®-based technology designed for the qualitative detection of SARS-CoV-2 antigen. As rapid technology to detect Covid-19, the test was extensively characterised in vitro. Once the analytical parameters of performance were set, the test system was challenged in a test field study. The aim of this study was to evaluate its diagnostic accuracy, as compared by the gold standard RT-PCR and other existing lateral flow tests.
A Novel Indicator for COVID-19 Pandemic Assessment and Comparison
Authors: Mukherjee Kanchan
Published: October 2021

Introduction

In an increasingly globalized world, no country can remain immune to the effect of the COVID-19 pandemic. The pandemic has exposed the need for effective public health surveillance in the interest of global health security. However, current indicators are limited in doing a comparative intercountry assessment and comparison because of variation in testing rates and reporting standards. Hence, this study attempts at addressing this gap.

Methods

The study proposes incremental change in cases per testing rate (ICTR) as an indicator for doing cross country comparison of the pandemic progress. The equation for calculating this indicator is explained in this study. This is followed by measuring its strength of association and predictive power for determining change in SARS-CoV-2 cases in five countries (USA, UK, India, Pakistan and Bangladesh).

Results and discussion

ICTR was found to have a significantly higher strength of association and predictive power (than the existing indicator-test positivity rate) for determining change in cases over different time periods. Using ICTR, cross country comparison was done for the five countries for15 months to draw deeper insights into the progress of the pandemic.

Conclusions

The study finds ICTR to be a suitable indicator for intercountry comparison and intracountry monitoring of the pandemic, which would be useful for global COVID-19 surveillance.
A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure
Authors: Liu Hongbo , Gao Xiang , Wang Guoyong , Zhang Jianjun , Zhou Jiajie , Wei Tingting , Zhang Yu , Liu Yujiao , Piao Jinhua , Zhang Qiulei , Wang Yayuan , Ma Xin , Zhu Xiaoting , Rao Yikun , Xia Wenjuan , Xie Heng , Zhang Wei
Published: October 2021

The COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.
Comparative transcriptome analysis of Cryptomeria japonica between solid and liquid culture
Authors: Konishi Shogo
Published: October 2021

This manuscript has been withdrawn by the authors as it was submitted and made public without the appropriate authorizations. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection
Authors: Rousseau Matthieu , Mariano Livia Lacerda , Canton Tracy , Ingersoll Molly A
Published: October 2021

Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper cell polarization, comprised of Th1, Th2, and Th17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered T helper cell polarization leading to poor memory. Surprisingly, however, T helper cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue resident memory (TRM) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that TRMcells are necessary for immune memory, transfer of lymph node or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that TRMcells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared to unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for TRMcells in the memory response to bacterial infection in this mucosa, providing a target for non-antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.

One Sentence Summary

TRMare necessary and sufficient for memory to recurrent UTI
Mandrake: visualising microbial population structure by embedding millions of genomes into a low-dimensional representation
Authors: Lees John A. , Tonkin-Hill Gerry , Yang Zhirong , Corander Jukka
Published: October 2021

In less than a decade, population genomics of microbes has progressed from the effort of sequencing dozens of strains to thousands, or even tens of thousands of strains in a single study. There are now hundreds of thousands of genomes available even for a single bacterial species and the number of genomes is expected to continue to increase at an accelerated pace given the advances in sequencing technology and widespread genomic surveillance initiatives. This explosion of data calls for innovative methods to enable rapid exploration of the structure of a population based on different data modalities, such as multiple sequence alignments, assemblies and estimates of gene content across different genomes. Here we present Mandrake, an efficient implementation of a dimensional reduction method tailored for the needs of large-scale population genomics. Mandrake is capable of visualising population structure from millions of whole genomes and we illustrate its usefulness with several data sets representing major pathogens. Our method is freely available both as an analysis pipeline (https://github.com/johnlees/mandrake) and as a browser-based interactive application (https://gtonkinhill.github.io/mandrake-web/).
DNA methylation patterns differ between free-living Rhizobium leguminosarum RCAM1026 and bacteroids formed in symbiosis with pea (Pisum sativum L.)
Authors: Afonin Alexey , Emma Gribchenko , Zorin Evgeny , Sulima Anton , Zhukov Vladimir
Published: October 2021

Rhizobium leguminosarum (Rl) is a common name for several genospecies of rhizobia able to form nitrogen-fixing nodules on the roots of pea (Pisum sativum L.) and undergo terminal differentiation into a symbiotic form called bacteroids. In this work, we compared the genomes of the free-living and differentiated forms of the Rl strain RCAM1026 using Oxford Nanopore long reads. No significant genome rearrangements were observed, but the relative abundances of replicons were different between the cell states. GANTC, GGCGCC and GATC methylated motifs have been found in the genome, along with genes for methyltransferases with matching predicted targets. Methylation patterns for the GANTC and GATC motives differed significantly depending on the cell state, which indicates their possible connection to the regulation of symbiotic differentiation. The GGCGCC motif was completely methylated in both bacteria states, and, apparently, is a target for the modification-restriction system. Currently, the methylation patterns in symbiotic bacteria are not extensively studied, so a further investigation of the topic coupled with gene expression data is needed to elucidate the function of differential methylation in terminal differentiation of R. leguminosarum and other rhizobia.