bluuebunny/crossref_metadata_2025 huggingface dataset:
In Search of Gender in Historical Political Economy
Authors: Teele Dawn L. , Grosjean Pauline A.
Published: December 2022

This chapter summarizes the quantitative literature on the origins and manifestations of women’s political and economic progress over the last two hundred years. It discusses key critical junctures that durably changed women’s economic roles, such as the Industrial Revolution, the introduction of the contraceptive pill, and large-scale conflict, as well as some of the institutionally imposed constraints on women’s social, economic, and political roles, and how these were overcome. To conclude, the chapter calls for more empirical evidence from underresearched areas and for a new and coherent theoretical paradigm that would not only account for the stubborn persistence of gender inequality but also incorporate the progress made by related disciplines on the understanding and definition of gender, masculinity, and intersectionality.
Increased sensitivity to chemically induced colitis in mice harboring a DNA-binding deficient aryl hydrocarbon receptor
Authors: Alvik Karoline , Shao Peng , Hutin David , Baglole Carolyn , Grant Denis M , Matthews Jason
Published: December 2022

The aryl hydrocarbon receptor (AHR), a transcription factor best known for mediating toxic responses of environmental pollutants, also integrates metabolic signals to promote anti-inflammatory responses, intestinal homeostasis, and maintain barrier integrity. AHR regulates its target genes through direct DNA-binding to aryl hydrocarbon response elements (AHREs) but also through tethering to other transcription factors in a DNA-binding independent manner. However, it is not known if AHR’s anti-inflammatory role in the gut requires its ability to bind to AHREs. To test this, we determined the sensitivity of Ahrdbd/dbd mice, a genetically modified mouse line that express an AHR protein incapable of binding to AHREs, to dextran sulfate sodium (DSS)-induced colitis. Ahrdbd/dbd mice exhibited more severe symptoms of intestinal inflammation than Ahr+/+ mice. None of the Ahrdbd/dbd mice survived after the 5-day DSS followed by 7-day washout period. By day 6, the Ahrdbd/dbd mice had severe body weight loss, shortening of the colon, higher disease index scores, enlarged spleens, and increased expression of several inflammation genes, including interleukin 1b (Il-1b), Il-6, Il-17, C-x-c motif chemokine ligand 1 (Cxcl1), Cxcl2, Prostaglandin-endoperoxide synthase (Ptgs2), and lipocalin-2. Our findings show that AHR’s DNA-binding domain and ability to bind to AHREs are required to reduce inflammation, maintain a healthy intestinal environment, and protect against DSS-induced colitis.
Recall of delirium and related distress in elderly hospitalized patients: A prospective study
Authors: Moura Maria Leonor , Martins Sónia , Correia Raquel , Pinho Elika , Paulo Cristiana , Silva Maria João , Teixeira Ana , Fontes Liliana , Lopes Luís , Paiva José Artur , Azevedo Luís Filipe , Fernandes Lia
Published: December 2022

Background: Delirium is a very common neuropsychiatric disorder in the elderly, with a significant physical and psychological burden. Much is still unknown about its psychological effects. This study aims to identify the proportion of patients who recall delirium and to analyze the distress caused by it. In addition, this study aims to analyze the association between delirium recall and related distress and global psychological distress regarding hospitalization.

Methods: This is a prospective study with elderly hospitalized patients in level-2 units of intensive care medicine department of a university hospital. Exclusion criteria were a Glasgow Coma Scale total ≤11, brain injury, blindness, deafness, or inability to communicate. Delirium was daily assessed with the Confusion Assessment Method. Delirium recall and related distress in patients were measured using the Delirium Experience Questionnaire. Global psychological distress was assessed with the Kessler Psychological Distress Scale.

Results: From 105 patients, 38 (36.2%) developed delirium. Most patients did not remember the delirium episode (64.7%). Among those who remembered (35.3%), most described delirium as a distressing experience (75%). Delirium recall was associated with high global psychological distress (P = .029).

Conclusions: Distress related to delirium is high, namely in patients who recall the episode. Global psychological distress during hospitalization is associated with delirium recall. This study highlights the need to assess the experience of delirium in these patients, as well as the importance of providing support and psychological interventions to minimize the associated distress.
Misconceptions in the Use of Body Mass Index
Authors: Solorzano Amberly Ashly , Stevens Sarah Marie , Doak Colleen Marie
Published: December 2022

Organizations such as the World Health Organization, Centers for Disease Control and Prevention, and American Medical Association all recognize the limitations of using body mass index (BMI) to define obesity (BMI ≥ 30 kg/m2). However, BMI is commonly used for screening and is also used in clinical practice as a standalone measure to define “overweight” (BMI, 25-29.9 kg/m2) and “obesity” (BMI ≥ 30 kg/m2). This review describes the genesis of the use of BMI and its value in research and description of populations, while showing that when it is used for diagnosis at the individual level, it falls down at certain age, sex, and race/ethnic groups. A brief history of the BMI, from its inception to its current use in identifying “obesogenic” environments, is provided. Although BMI is currently used in screening, for clinical assessment and management, many other indices are more accurate and useful. This report summarizes the benefits of BMI, in monitoring the ongoing global obesity epidemic, and its limitations as a screening or diagnostic tool in clinical settings.
A 20-Year Review of Recumbent Pedestrian Fatalities (2001–2020)
Authors: Tiemensma Marianne , Byard Roger W.
Published: December 2022

A retrospective study was performed in the Northern Territory of Australia of all cases of pedestrian fatalities where the decedents had been sitting, crouching, sleeping, or lying on or next to a road, over a 20-year period (January 1, 2001 to December 31, 2020). Of the 865 road traffic fatalities, 161 (19%) were pedestrians, and 42 of these were recumbent at the time of the incident (26% of all pedestrians). The most common age range was 30 to 39 years with a male to female ratio of 25:17. No individuals younger than 15 years were involved. Acute alcohol intoxication played a role in death in all of the cases with medium to high range blood alcohol concentrations. In addition, cannabis or its metabolites were detected in 6 cases, and methylamphetamine in 1 case. A history of chronic alcohol use or dependence was known in 6 (14%) of cases. In no case was an underlying medical condition contributory to death. The majority of incidents occurred at night. This study has shown a very high incidence of recumbent pedestrian deaths in an Australian subpopulation related to acute alcohol intoxication, decreased visibility, and vulnerability because of their position on or proximate to a road.
Mutations in atpG2 may confer resistance to gentamicin in Listeria monocytogenes
Authors: Ng Jamie May Ling , Ngeow Yun Fong , Saw Seow Hoon , Ng Hien Fuh , Zin Thaw
Published: December 2022

Introduction Listeriosis, a foodborne infection caused by

Listeria monocytogenes

, could lead to febrile listerial gastroenteritis and a more invasive form which is often associated with a high mortality and hospitalisation rate. Gentamicin, used as an adjunct therapy with ampicillin, remains the treatment of choice for this life-threatening and invasive infection.

Gap statement Nevertheless, there is little data on gentamicin resistance determinants in

L. monocytogenes

.

Aim In this study, we selected and characterised B2b, a gentamicin-resistant mutant derived from

L. monocytogenes

ATCC 19115 to determine the target(s) of resistance in

L. monocytogenes

after exposure to gentamicin.

Methodology Whole-genome sequencing was carried out to identify the mutation site(s) and possible mechanism(s) of resistance. The mutant was characterised using antimicrobial susceptibility testing and PCR. For biological verifications, complementation and allelic exchange mutagenesis were carried out.

Results We found that the gentamicin resistance in B2b was caused by a 10 bp deletion in atpG2 which encodes a gamma subunit of the ATP synthase in

L. monocytogenes

. Using atpG2 PCR, various other mutations were identified in other gentamicin resistant mutants derived from ATCC 19115. In addition, the mutation from B2b, when introduced into

L. ivanovii

, also caused gentamicin resistance in this

Listeria

species.

Conclusion Hence, atpG2 mutations appear to be important determinants of gentamicin resistance not only in

L. monocytogenes

but possibly also in other

Listeria

species.
Genome-wide Associations, Polygenic Risk, and Mendelian Randomization Reveal Limited Interactions between John Henryism and Cynicism
Authors: Chapleau Richard R.
Published: December 2022

Chronic occupational stress and an individual’s reaction to that stress often lead to burnout syndrome. We sought to use genetics to evaluate what, if any, interactions exist between John Henryism (JH) and cynicism in hopes of clarifying holistic risk factors of burnout syndrome. We performed genome-wide association studies in a discover phase with 1,852 samples and validated associations in a replication phase of 465 samples, both from the CARDIA study, and used supervised machine learning to developing genetic risk algorithms. We identified 933 genetic associations and developed a classification algorithm for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7. We found significant genetic components to these traits but no evidence of an interaction between JH and cynicism, so while there may be a genetic risk component, JH does not appear to contribute to burnout risk.
Switching the left and the right hearts: A novel bi-ventricle mechanical support strategy with spared native single-ventricle
Authors: Şişli Emrah , Yıldırım Canberk , Başar Aka İbrahim , Tuncer Osman Nuri , Atay Yüksel , Özbaran Mustafa , Pekkan Kerem
Published: December 2022

Mechanical circulatory support (MCS) is used as a bridge-to-heart transplantation for end-stage failing Fontan patients with single-ventricle (SV) circulation. Donor shortage and complexity of the single-ventricle circulation physiology demands novel circulatory support systems and alternative solutions. An out-of-the-box circulation concept in which the left and right ventricles are switched with each other inspired a novel bi-ventricle MCS configuration for the “failing” Fontan patients. In the proposed configuration, the systemic circulation is maintained by a conventional mechanical ventricle assist device while the venous circulation is delegated to the native SV. This approach spares the SV and puts it to a new use at the right-side providing the most needed venous flow pulsatility. To analyze its feasibility and performance, 8 realistic Fontan circulation scenarios have been studied via a multi-compartmental lumped parameter cardiovascular model (LPM). Model is developed specifically for simulating the SV circulation and validated against pulsatile mock-up flow loop measurements for the ideal (Fontan), failed (VD) and assisted Fontan (PVR-cmcs) scenarios. The proposed surgical configuration maintained the cardiac index (3-3.5 l/min/m2) providing a normal mean systemic arterial pressure. For a failed SV with low ejection fraction (EF=26%), representing a typical systemic failure, proposed configuration introduced a venous/pulmonary pulsatility of ∼28 mmHg and a drop of 2 mmHg in central venous pressure (CVP) with acceptable pulmonary artery pressures (17.5 mmHg). In the pulmonary vascular resistance (PVR) failure model, it provided approximately 5 mmHg drop in CVP with venous/pulmonary pulsatility reaching ∼22 mmHg. For high PVR failure case with a healthy SV (EF = 44%) pulmonary hypertension is likely to occur, indicating a need for precise functional assessment of the failed-ventricle before it is considered for the proposed arrangement. Comprehensivein vitroandin silicoresults encourage this concept as an economical alternative to the conventional bi-ventricle MCS pending animal experiments.
Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells
Authors: Yamaya Kei , Wang Bin , Memar Nadin , Odiba Arome Solomon , Woglar Alexander , Gartner Anton , Villeneuve Anne M.
Published: December 2022

RAD54 family DNA translocases partner with RAD51 recombinases to ensure stable genome inheritance, exhibiting biochemical activities both in promoting recombinase removal and in stabilizing recombinase association with DNA. Understanding how such disparate activities of RAD54 paralogs align with their biological roles is an ongoing challenge. Here we investigate thein vivofunctions ofC. elegansRAD54 paralogs RAD-54.L and RAD-54.B during meiotic prophase, revealing distinct contributions to the dynamics of RAD-51 association with DNA and to the progression of meiotic double-strand break repair (DSBR). While RAD-54.L is essential for RAD-51 removal from meiotic DSBR sites to enable recombination progression, RAD-54.B is largely dispensable for meiotic DSBR. However, RAD-54.B is required to prevent hyperaccumulation of RAD-51 on unbroken DNA during a key meiotic sub-stage when protein kinase CHK-2 is active. Moreover, DSB-independent hyperaccumulation of RAD-51 foci in the absence of RAD-54.B is RAD-54.L-dependent, revealing a hidden activity of RAD-54.L in promoting promiscuous RAD-51 association that is antagonized by RAD-54.B. We propose a model wherein a division of labor among RAD-54 paralogs allows germ cells to ramp up their capacity for efficient homologous recombination that is crucial to successful meiosis while counteracting potentially deleterious effects of unproductive RAD-51 association with unbroken DNA.
Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins
Authors: Benton Richard , Himmel Nathaniel J.
Published: December 2022

Insect Odorant receptors and Gustatory receptors define a superfamily of seven-transmembrane domain ligand-gated ion channels (termed here 7TMICs), with homologs identified across Animalia except Chordata. Previously, we used sequence-based screening methods to reveal conservation of this family in unicellular eukaryotes and plants (DUF3537 proteins) (Bentonet al., 2020). Here we combine three-dimensional structure-based screening,ab initioprotein folding predictions, phylogenetics and expression analyses to characterize additional candidate homologs with tertiary but little or no primary structural similarity to known 7TMICs, including proteins in disease-causing Trypanosoma. Unexpectedly, we identify structural similarity between 7TMICs and PHTF proteins, a deeply-conserved family of unknown function, whose human orthologs display enriched expression in testis, cerebellum and muscle. We also discover divergent groups of 7TMICs in insects, which we term the Gustatory receptor-like (Grl) proteins. SeveralDrosophila melanogaster Grls display selective expression in subsets of taste neurons, suggesting that they are previously-unrecognized insect chemoreceptors. Although we cannot exclude the possibility of remarkable structural convergence, our findings support the origin of 7TMICs in a eukaryotic common ancestor, counter previous assumptions of complete loss of 7TMICs in Chordata, and highlight the extreme evolvability of this protein fold, which likely underlies its functional diversification in different cellular contexts.
Maternal control of spontaneous dormancy termination inDaphnia pulex
Authors: Porter Robert J. , Gutierrez Grace M. , Barnard-Kubow Karen B. , Bergland Alan O.
Published: December 2022

This study examined maternal influence and life-history consequences of diapause termination timing inDaphnia pulex. We raised clonal isolates ofD. pulexin mesocosms and observed hatching rates prior to and after exposing embryos to a cold shock. A substantial proportion of individuals hatched early, prior to the cold shock. We found that siblings from the same ephippium were more likely than expected by chance to emerge at the same time, even after dissection and separation, suggesting the presence of a maternal effect that influences diapause duration. We also found that for individuals who emerged early, the time to first reproduction was significantly delayed, and individuals produced fewer resting embryos in subsequent generations. We suggest that early diapause termination may be driven by maternal effects to generate offspring that emerge from dormancy at different times.
Multiparametric sensing of outer membrane vesicle-derived supported lipid bilayers demonstrates the specificity of bacteriophage interactions
Authors: Bali Karan , Lu Zixuan , McCoy Reece , Treiber Jeremy , Savva Achilleas , Kaminski Clemens F. , Salmond George , Salleo Alberto , Mela Ioanna , Monson Rita , Owens Róisín M.
Published: December 2022

The use of bacteriophage, viruses that specifically infect bacteria, as antibiotics has become an area of great interest in recent years as the effectiveness of conventional antibiotics recedes. The detection of phage interactions with specific bacteria in a rapid and quantitative way is key for identifying phage of interest for novel antimicrobials. Outer membrane vesicles (OMVs) derived from gram-negative bacteria can be used to make supported lipid bilayers (SLBs) and thereforein vitromembrane models that contain naturally occurring components of the bacterial outer membrane. In this study, we usedEscherichia coliOMV derived SLBs and use both fluorescent imaging and surface sensitive techniques to show their interactions with T4 phage. We also integrate these bilayers with microelectrode arrays (MEAs) functionalised with the conducting polymer PEDOT:PSS and show that the pore forming interactions of the phage with the SLBs can be monitored using electrical impedance spectroscopy. To highlight our ability to detect specific phage interactions, we also generate SLBs using OMVs derived fromCitrobacter rodentium, which is resistant to T4 phage infection, and identify their lack of interaction with phage. The work presented here shows how interactions occurring between phage and these complex SLB systems can be monitored using a range of experimental techniques. We believe this approach can be used to identify phage against bacterial strains of interest, as well as more generally to monitor any pore forming structure (such as defensins) interacting with bacterial outer membranes, and thus aid in the development of next generation antimicrobials.
Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife populations
Authors: Schreiner Courtney L. , Basinski Andrew J. , Remien Christopher H. , Nuismer Scott L.
Published: December 2022

1

Zoonotic pathogens spread by wildlife continue to spill into human populations and threaten human lives. A potential way to reduce this threat is by vaccinating wildlife species that harbor pathogens that are infectious to humans. Unfortunately, even in cases where vaccines can be distributed en masse as edible baits, achieving levels of vaccine coverage sufficient for pathogen elimination is rare. Developing vaccines that self-disseminate may help solve this problem by magnifying the impact of limited direct vaccination. Although models exist that quantify how well these self-disseminating vaccines will work when introduced into temporally stable wildlife populations, how well they will perform when introduced into populations with pronounced seasonal population dynamics remains unknown. Here we develop and analyze mathematical models of fluctuating wildlife populations that allow us to study how reservoir ecology, vaccine design, and vaccine delivery interact to influence vaccine coverage and opportunities for pathogen elimination. Our results demonstrate that the timing of vaccine delivery can make or break the success of vaccination programs. As a general rule, the effectiveness of self-disseminating vaccines is optimized by introducing after the peak of seasonal reproduction when the number of susceptible animals is near its maximum.
NanopoReaTA: a user-friendly tool for nanopore-seq real-time transcriptional analysis
Authors: Wierczeiko Anna , Pastore Stefan , Mündnich Stefan , Busch Anne M. , Dietrich Vincent , Helm Mark , Butto Tamer , Gerber Susanne
Published: December 2022

Oxford Nanopore Technologies’ (ONT) sequencing platform offers an excellent opportunity to perform real-time analysis during sequencing. This feature allows for early insights into experimental data and accelerates a potential decision-making process for further analysis, which can be particularly relevant in the clinical context. Although some tools for the real-time analysis of DNA-sequencing data already exist, there is currently no application available for differential transcriptome data analysis designed for scientists or physicians with limited bioinformatics knowledge. Here we introduce NanopoReaTA, a user-friendly real-time analysis toolbox for RNA sequencing data from ONT. Sequencing results from a running or finished experiment are processed through an R Shiny-based graphical user interface (GUI) with an integratedNextflowpipeline for whole transcriptome or gene-specific analyses. NanopoReaTA provides visual snapshots of a sequencing run in progress, thus enabling interactive sequencing and rapid decision-making that could also be applied to clinical cases.

Availability

https://github.com/AnWiercze/NanopoReaTA

Contact

buttamer@uni-mainz.deandsugerber@uni-mainz.de
A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle
Authors: Marrella Mackenzie A. , Biase Fernando H.
Published: December 2022

Background

Infertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production.

Results

Using a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7×10-7; and rs109366560, chr11:37666527, P = 2.6×10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm= 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm= 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category.

Conclusions

Our multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.
Exact Probability Distribution for the ROC Area Under Curve
Authors: Ekström Joakim , Ögren Jim , Sjöblom Tobias
Published: December 2022

The Receiver Operating Characteristic (ROC) is ade factostandard for determining the accuracy ofin vitrodiagnostic (IVD) medical devices, and thus exactness in its probability distribution is crucial toward accurate statistical inference. We show the exact probability distribution of the ROC AUC-value, hence exact critical values and p-values are readily obtained. Because the exact calculations are computationally intense, we demonstrate a method of geometric interpolation which is exact in a special case but generally an approximation, vastly increasing computational speeds. The method is illustrated through open access data, demonstrating superiority of 26 composite biomarkers relative to a predicate device. Especially under correction for testing of multiple hypotheses, traditional asymptotic approximations are encumbered by considerable imprecision, adversely affecting IVD device development. The ability to obtain exact p-values will allow more efficient IVD device development.
Alignment-based protein mutational landscape prediction: doing more with less
Authors: Abakarova Marina , Marquet Ćeline , Rera Michael , Rost Burkhard , Laine Elodie
Published: December 2022

The wealth of genomic data has boosted the development of computational methods predicting the phenotypic outcomes of missense variants. The most accurate ones exploit multiple sequence alignments, which can be costly to generate. Recent efforts for democratizing protein structure prediction have overcome this bottleneck by leveraging the fast homology search of MMseqs2. Here, we show the usefulness of this strategy for mutational outcome prediction through a large-scale assessment of 1.5M missense variants across 72 protein families. Our study demonstrates the feasibility of producing alignment-based mutational landscape predictions that are both high-quality and compute-efficient for entire proteomes. We provide the community with the whole human proteome mutational landscape and simplified access to our predictive pipeline.

Significant statement

Understanding the implications of DNA alterations, particularly missense variants, on our health is paramount. This study introduces a faster and more efficient approach to predict these effects, harnessing vast genomic data resources. The speed-up is possible by establishing that resource-saving multiple sequence alignments suffice even as input to a method fitting few parameters given the alignment. Our results opens the door to discovering how tiny changes in our genes can impact our health. They provide valuable insights into the genotype-phenotype relationship that could lead to new treatments for genetic diseases.
Shifts in competitive structures can drive variation in species’ phenology
Authors: Dumandan Patricia Kaye T. , Yenni Glenda M. , Ernest S. K. Morgan
Published: December 2022

For many species, a well-documented response to anthropogenic climate change is a shift in various aspects of its life-history, including its timing or phenology. Often, these phenological shifts are associated with changes in abiotic factors used as proxies for resource availability or other suitable conditions. Resource availability, however, can also be impacted by competition, but the impact of competition on phenology is less studied than abiotic drivers. We fit generalized additive models (GAMs) to a long-term experimental dataset on small mammals monitored in the southwestern United States and show that altered competitive landscapes can drive shifts in breeding timing and prevalence, and that, relative to a dominant competitor, other species exhibit less specific responses to environmental factors. These results suggest that plasticity of phenological responses, that is often described in the context of annual variation in abiotic factors, can occur in response to biotic context as well. Variation in phenological responses under different biotic conditions shown here further demonstrates that a more nuanced understanding of shifting biotic interactions is useful to better understand and predict biodiversity patterns in a changing world.
Game of full siblings in Mendelian populations
Authors: Garay József , Szilágyi András , Varga Tamás , Csiszár Villő , Móri Tamás F.
Published: December 2022

We adapt the concept of evolutionary stability to familial selection when a game theoretic conflicts between siblings determines the survival rate of each sibling in monogamous, exogamous families in a diploid, panmictic population. Similarly to the classical evolutionary game theory, the static condition of evolutionary stability of mixed Nash equilibrium implies the local stability of the genotype dynamics, in spite of that the mating table based genotype dynamics is not a replicator dynamics.

We apply our general result to the case where a matrix game determines the survival rate of siblings. In our numerical studies we consider the prisoner’s dilemma between siblings, when the cooperator and defector behaviour are unequally determined by a recessive-dominant allele pair at an autosomal locus. When the prisoner’s dilemma game is strict (cf. iterated one) and the cooperator phenotype is recessive resp. dominant, then the cooperator and defector phenotypes are the unique stable phenotypes, respectively. When the prisoner’s dilemma game is not strict, both phenotypes coexist, independently of the genotype-phenotype mapping. However, the frequencies of the phenotypes are different according to which phenotype is dominant.
GeneSegNet: a deep learning framework for cell segmentation by integrating gene expression and imaging
Authors: Wang Yuxing , Wang Wenguan , Liu Dongfang , Hou Wenpin , Zhou Tianfei , Ji Zhicheng
Published: December 2022

When analyzing data from in situ RNA detection technologies, cell segmentation is an essential step in identifying cell boundaries, assigning RNA reads to cells, and studying the gene expression and morphological features of cells. We developed a deep-learning-based method, GeneSegNet, that integrates both gene expression and imaging information to perform cell segmentation. GeneSegNet also employs a recursive training strategy to deal with noisy training labels. We show that GeneSegNet significantly improves cell segmentation performances over existing methods that either ignore gene expression information or underutilize imaging information.
Genomic evaluation of a case ofLacticaseibacillus rhamnosusendocarditis: comparison with commercial yogurt isolates and examination of global population structure
Authors: Santoiemma Phillip P. , Cohn Susan E. , Gatesy Samuel W. M. , Hauser Alan R. , Agrawal Saaket , Theodorou Maria , Bachta Kelly E.R. , Ozer Egon A.
Published: December 2022

Probiotics, including yogurt commonly containing bacteria of theLactobacillusgroup, are widely used to promote microbiome health and to prevent gastrointestinal or other infections, especially in the setting of antibiotic use. Rarely, however,Lactobacillusbacteria have caused invasive or severe infections in patients. In this report, we present a patient with fatalLacticaseibacillusbacteremia and endocarditis who frequently consumed yogurt. Whole genome sequencing identified the patient’s bloodstream isolate asLacticaseibacillus(formerlyLactobacillus)rhamnosus, and sequencing ofLactobacillusisolates from selected commercial yogurt preparations revealed one isolate nearly identical to the patient’s isolate, differing by only one nucleotide (adenine to guanine substitution leading to a M1A amino acid change in the start codon of thenrdRgene). To place these sequences into broader context ofL. rhamnosusstrains, we compared them to 602L. rhamnosusgenome sequences publicly available through the National Center for Biotechnology Information repository. Both isolates belonged to a clade, identified in this report as clade YC, composed of mostly gastrointestinal isolates from healthy individuals, some of which also differed by only a single nucleotide from the patient’s isolate. Members of clade YC had only rarely been previously identified in invasive infections. In summary, theLacticaseibacillusstrain causing this patient’s infection may have originated from a commercial dairy product or from the commensal flora of his gastrointestinal tract. This study demonstrates that whole genome sequencing may be insufficient to reliably determine the source of invasive infections caused byL. rhamnosus.

IMPORTANCE

Active culture and probiotic foods and supplements are often used to promote gut health. Though largely considered safe for human consumption, there are rare reports of severe infections linked to bacterial species used in these products. Using whole genome sequencing, we examined a case of fatal infection withLacticaseibacillus rhamnosusin the patient’s blood. By comparing the bacterial genome sequence from the patient to strains cultured from 4 commercial yogurt samples and 602 publicly available sequences ofL. rhamnosusfrom around the world, we found that it was nearly identical to one of the yogurt strains and equally similar to other strains from both probiotics and healthy individuals’ gastrointestinal tracts. These findings show that even with whole genome sequencing it can be difficult to determine the source of an invasiveL. rhamnosusinfection, whether from recent consumption of a probiotic or dairy product versus from the gastrointestinal microbiome.
The Creation of a Multidomain Neighborhood Environmental Vulnerability Index Across an Urban Center
Authors: Uong Stephen P. , Zhou Jiayi , Lovinsky-Desir Stephanie , Albrecht Sandra S. , Azan Alexander , Chambers Earle C. , Sheffield Perry E. , Thompson Azure , Wilson Joseph , Baidal Jennifer Woo , Stingone Jeanette A.
Published: December 2022

Compared to previous studies that have typically used a single summary score, we aimed to construct a multidomain neighborhood environmental vulnerability index (NEVI) to characterize the magnitude and variability of area-level factors with the potential to modify the health effects of environmental pollutants. Using the Toxicological Prioritization Index framework and data from the 2015-2019 U.S. Census American Community Survey and the 2020 CDC PLACES Project, we quantified census tract-level vulnerability overall and in 4 primary domains (demographic, economic, residential, and health status), 24 subdomains, and 54 distinct area-level features for New York City (NYC). Overall and domain-specific indices were calculated by summing standardized feature values within the subdomains and then aggregating and weighting subdomains within equally-weighted primary domains. In citywide comparisons, NEVI was correlated with both the Neighborhood Deprivation Index (r = 0.91) and the Social Vulnerability Index (r = 0.87) but provided additional information on features contributing to vulnerability. Vulnerability varied spatially across NYC, and hierarchical cluster analysis using subdomain scores revealed six patterns of vulnerability across domains: 1) low in all, 2) primarily low except residential, 3) medium in all, 4) high demographic, economic, and residential 5) high economic, residential, and health status, and 6) high demographic, economic and health status. Created using a tool that offers flexibility for theory-based construction, NEVI provided detailed metrics of vulnerability across domains that can inform targeted research and public health interventions aimed at reducing the health impacts from environmental exposures across an urban center.
Long-term safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells isolated at the point of care: 41 months follow-up of a prospective, randomized, controlled, first-in-human clinical trial
Authors: Lundeen Mark , Hurd Jason L. , Hayes Matthew , Hayes Meredith , Facile Tiffany R. , Furia John P. , Maffulli Nicola , Alt Christopher , Alt Eckhard U. , Schmitz Christoph , Pearce David A.
Published: December 2022

Background

Symptomatic, partial-thickness rotator cuff tears (sPTRCT) are problematic. Management of sPTRCT with fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and leads to improved shoulder function without adverse effects. This study tested the hypothesis that management of sPTRCT with injection of UA-ADRCs is safe and more effective than injection of corticosteroid even in the long run.

Methods

Subjects who had completed a former randomized controlled trial were enrolled in the present study. At baseline these subjects had not responded to physical therapy treatments for at least six weeks, and were randomly assigned to receive either a single injection of an average 11.4 × 106 UA-ADRCs (n = 11) or a single injection of 80 mg of methylprednisolone (n = 5). Safety was assessed by rigorously documenting and evaluating treatment emergent adverse events. As per protocol efficacy was assessed using the ASES Total score, RAND Short Form-36 Health Survey (SF-36) Total score and VAS pain score at 24 weeks (W24) and W52 post-treatment as well as at 33.2 ± 1.0 (mean ± standard deviation) months (M33) and 40.6 ± 1.9 months (M41) post-treatment. Magnetic resonance imaging (MRI) of the index shoulder was performed at baseline, W24, W52, M33 and M41 post-treatment.

Results

There were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. Injection of UA-ADRCs resulted in significantly higher mean ASES Total scores at W24, W52 and M41, a significantly higher mean SF-36 Total score at W24, and significantly higher mean VAS Pain scores at W24 and W52 post-treatment than injection of corticosteroid (p<0.05). Treatment outcome could not be assessed using measurements of tear volume on MRI scans. On the other hand, MRI scans at W24 post-treatment allowed to “watch the UA-ADRCs at work”. There was no relationship between treatment outcome and baseline data, including those data characterizing UA-ADRCs that can be collected with a clinical test.

Conclusions

The present study further supports management of sPTRCT with injection of UA-ADRCs.

Trial registration

Clinicaltrials.govNCT04077190(September 4, 2019).
Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
Authors: Khan Archie A. , Langston Harry C. , Walsh Louis , Roscoe Rebecca , Jayawardhana Shiromani , Francisco Amanda F. , Taylor Martin C. , McCann Conor J. , Kelly John M. , Lewis Michael D.
Published: December 2022

Digestive Chagas disease (DCD) is an enteric neuropathy caused byTrypanosoma cruziinfection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology, and the impact of treatment with the front-line drug benznidazole. Curative treatment at 6 weeks post-infection resulted in sustained recovery of GI transit function, whereas sub-curative treatment led to infection relapse and gradual return of DCD symptoms. Neuro-immune gene expression profiles shifted from chronic inflammation to a tissue repair signature after cure, accompanied by increased glial cell activity and regenerative neurogenesis in the myenteric neuronal plexus. Delaying treatment until 24 weeks post-infection led to a partial reversal of the DCD phenotype, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronicT. cruziinfection and is not an inevitable consequence of acute stage denervation. The risk that irreversible enteric neuromuscular tissue damage and dysfunction will develop highlights the importance of prompt diagnosis and treatment. Finally, these findings support the concept of treating asymptomaticT. cruziinfected individuals with benznidazole to prevent DCD development.
Studies on the co-metabolism of glucose and glycerol in the fungusUmbelopsis isabellina
Authors: Dritsas Panagiotis , Aggelis George
Published: December 2022

Over the past few years it is observed an increased interest for oleaginous microorganisms in the perspective to produce microbial oils of great commercial interest through the consumption of low/zero cost substrates. In this paper, the physiology of the fungusUmbelopsis isabellinagrowing on blends of glycerol and glucose was investigated. In all experiments the fungus completely consumed glucose and produced satisfactory quantities of biomass containing reserve lipids in high percentages. However, glycerol concentration in the growth medium was negatively correlated to glucose assimilation rate, mainly during the balanced-growth phase. Nevertheless, at high initial concentrations, glycerol was partially consumed and seemed to contribute positively to the suppression of lipid degradation. Following the discovery of this complex regulatory mechanism regarding glucose and glycerol co-assimilation, the activity of three key-enzymes namely aldolase, glycerol kinase and glycerol dehydrogenase, which are implicated in glycerol and glucose assimilation, was investigated. The experiments revealed a clear preference of the fungus for glucose over glycerol. On the other hand, storage polysaccharides are degraded instead of storage lipid at the late oleaginous phase for maintenance purpose. These new biochemical features will enable the design of appropriate growth media for the co-fermentation of these two substrates byU. isabellinawith the aim to maximize lipid accumulation.
Repetition accelerates neural markers of memory consolidation
Authors: Yu Wangjing , Zadbood Asieh , Chanales Avi J. H. , Davachi Lila
Published: December 2022

No sooner is an experience over than its neural memory representation begins to be strengthened and transformed through the process of memory replay. Using fMRI, we examined how memory strength manipulated through repetition during encoding modulates post-encoding replay in humans. Results revealed that repetition did not increase replay frequency in the hippocampus. However, replay in cortical regions and hippocampal-cortical coordinated replay were significantly enhanced for repeated events, suggesting that repetition accelerates the consolidation process. Interestingly, we found that replay frequency in both hippocampus and cortex modulated behavioral success on an immediate associative recognition test for the weakly encoded information, indicating a significant role for post-encoding replay in rescuing once-presented events. Together, our findings highlight the relationships of replay to stabilizing weak memories and accelerating cortical consolidation for strong memories.
Combinatorial circuit dynamics orchestrate flexible motor patterns inDrosophila
Authors: Shiozaki Hiroshi M. , Wang Kaiyu , Lillvis Joshua L. , Xu Min , Dickson Barry J. , Stern David L.
Published: December 2022

Motor systems flexibly implement diverse motor programs to pattern behavioral sequences, yet their neural underpinnings remain unclear. Here, we investigated the neural circuit mechanisms of flexible courtship behavior inDrosophila. Courting males alternately produce two types of courtship song. By recording calcium signals in the ventral nerve cord (VNC) in behaving flies, we found that different songs are produced by activating overlapping neural populations with distinct motor functions in a combinatorial manner. Recordings from the brain suggest that song is driven by two descending pathways – one defines when to sing and the other specifies what song to sing. Connectomic analysis reveals that these “when” and “what” descending pathways provide structured input to VNC neurons with different motor functions. These results suggest that dynamic changes in the activation patterns of descending pathways drive different combinations of motor modules, thereby flexibly switching between different motor actions.
Mathematical modelling of brain mTOR activity identifies selective vulnerability of cell types and signalling pathways
Authors: Pokhilko Alexandra , Sleven Hannah , Cader M. Zameel
Published: December 2022

The mTOR pathway is a global regulator of protein biosynthesis and cellular homeostasis. Understanding the differences in mTOR pathway activity between cell types is important for elucidating the role of mTOR in physiological and pathophysiological processes. The non-linear structure of the pathway, with multiple feedback loops and inputs complicates the interpretation of experimental data and requires mathematical modelling. We modelled mTOR activation under healthy and disease conditions using recently published single nuclei gene expression data from the human brain. The model predicts substantial variations in mTOR pathway activity between cell types, with neurons and astrocytes being highly sensitive to insulin and neuregulins, while vascular smooth muscle cells and pericytes are highly sensitive to PDGF. Two principal negative regulators of mTOR - TSC and PTEN have prominent roles in PDGF-mediated mTOR activation in endothelial cells and oligodendrocytes. In Alzheimer’s Disease brain we find that insulin-mediated activitation of mTOR pathway is selectively upregulated in microglia and oligodendrocytes and downregulated in other cells. Our mathematical modelling characterises ligand sensitivity of cerebrovascular cell types and provides insights into the brain mTOR dynamics in health and disease.