bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol decreases local inflammatory markers and systemic endotoxin in patients with aggressive periodontitis
Authors: Zhang Qiang , Xu Shuhan , Xu Wenxiu , Zhou Yang , Luan Hairong , Wang Deli
Published: June 2022

Background:

Inflammation is hypothesized to contribute to the pathogenesis of periodontitis. Resveratrol (RV) is known for its anti-inflammatory properties. The purpose of this study was to investigate the inhibitory effect of RV on local inflammatory markers and systemic endotoxin in patients with periodontitis.

Methods:

A total of 160 patients with periodontitis were enrolled in this study. The selected patients were randomly divided into four groups and received placebo, high-dose (500 mg/d) of RV (HRV, n = 40), middle-dose (250 mg/d) of RV (middle dose RV (MRV), n = 40) and low-dose (125 mg/d) of RV (low dose RV (LRV), n = 40) with orally administration. All patients received an 8-week treatment. The periodontal status of patients with periodontitis was recorded by using clinical attachment level (CAL), bleeding index (BI), oral hygiene index-simplified (OHI-S), and probing pocket depth (PPD). The levels of inflammatory markers in serum and gingival crevicular fluid (GCF), and systemic levels of endotoxin were evaluated using high sensitivity enzyme-linked immuno sorbent assay.

Results:

Outcomes showed that symptoms of periodontitis determined by CAL, BI OHI-S and PPD were improved by RV compared to placebo. RV treatment decreased inflammatory markers in serum and GCF compared to placebo in patient with periodontitis. Systemic endotoxin declined more in the RV group than the placebo-treated group.

Conclusion:

In conclusion, data in the current study indicate that RV is an efficient drug for the treatment of patients with periodontitis. The findings of the present study find that RV inhibits systemic local inflammatory markers and systemic endotoxin and suggest that 500 mg/d RV is the ideal dose for patients with periodontitis.
Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing
Authors: Pham Anh-Hoa Nguyen , Thi Kim-Oanh Bui , Thi Mai-Huong Nguyen , Ngo Diem-Ngoc , Naritaka Nakayuki , Nittono Hiroshi , Hayashi Hisamitsu , Dao Trang Thi , Nguyen Kim-Huong Thi , Nguyen Hoai-Nghia , Giang Hoa , Tang Hung-Sang , Nguyen Tat-Thanh , Truong Dinh-Kiet , Tran Minh-Dien
Published: June 2022

Rationale:

Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death.

Patient concerns:

Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients.

Diagnoses:

The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr).

Interventions:

Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d.

Outcomes:

The patients’ symptoms, signs, and primary bile acids levels improved significantly.

Lessons:

Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes.
Transient Elastography Measures of Hepatic Steatosis and Fibrosis Are Associated With Body Composition Among US Adolescents
Authors: Unalp-Arida Aynur , Ruhl Constance E.
Published: June 2022

Objectives:

Obesity-related fatty liver disease impacts long-term adolescent liver health. We examined transient elastography assessed hepatic steatosis and fibrosis distributions and relationships with body composition and lifestyle factors in a United States national adolescent population sample.

Methods:

Liver stiffness and controlled attenuation parameter (CAP) were assessed on 1080 non-Hispanic white, non-Hispanic black, non-Hispanic Asian, and Hispanic boys and girls aged 12–19 years in the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Participants underwent anthropometry and dual-energy x-ray absorptiometry (DXA).

Results:

Compared with girls, boys had higher mean CAP (223.7 dB/m vs 215.3 dB/m) and liver stiffness (5.1 kPa vs 4.9 kPa). CAP and liver stiffness increased markedly with body mass index (BMI). In multivariable-adjusted analysis, CAP in the upper quartile was associated with Hispanic and non-Hispanic Asian ethnicity and increased BMI, waist-to-hip ratio, systolic blood pressure, and sedentary time, and decreased physical activity and Healthy Eating Index-2015 score. In multivariable-adjusted analysis, liver stiffness in the upper quartile was associated with male sex, non-Hispanic black ethnicity, and increased BMI, alanine aminotransferase, CAP, and serum cotinine. DXA total percent fat and trunk fat percent were positively related to CAP (P < 0.001 for each), but not to liver stiffness with multivariable adjustment. Results were similar with CAP and liver stiffness as continuous characteristics.

Conclusions:

In US adolescents, increased anthropometric and DXA body composition measures and lifestyle factors were associated with higher CAP and liver stiffness. Transient elastography and similar noninvasive markers may be utilized for early detection of liver disease in high-risk pediatric populations.
A concern for falling impacts quality of life for people with a lower limb amputation
Authors: Nugent Kristin , Payne Michael W , Viana Ricardo , Unger Janelle , Hunter Susan W
Published: June 2022

The purpose of this web-based survey study was to comprehensively evaluate subdomains of concern for falling and its association with quality of life (QoL) among people with lower-limb amputations (PLLA). Forty-eight adults (mean 61.8 ± 11.6 years) with a major (i.e. transtibial or transfemoral) amputation participated. Individuals were currently using a prosthesis for ambulation, completed a prosthetic rehabilitation program, had functional use of English and had access to an internet-connected device (e.g. laptop). Five standardized scales assessed a concern for falling: Modified Survey of Activities and Fear of Falling in the Elderly (mSAFFE), Activities-specific Balance Confidence (ABC) Scale, Prosthetic Limb Users Survey – Mobility (PLUS-M), Consequences of Falling Scale and Perceived Ability to Manage Falls Scale. QoL was evaluated using the WHO QoL-100 questionnaire. Spearman correlation analysis evaluated the relationship between the five concerns for falling scales. Five independent linear regression modeling evaluated the association of each concern for falling measure on QoL. Strong statistically significant correlations were found between mSAFFE and PLUS-M (rs = −0.87; P < 0.05). Three scales were significantly associated with QoL: mSAFFE [−1.16 (95% CI, −2.04 to −0.29)], ABC [0.36 (95% CI, 0.11–0.61)] and PLUS-M [0.50 (95% CI, 0.05–0.95)]. This is the first study to evaluate multiple concerns for falling subdomains among PLLA. Concern for falling should be addressed in prosthetic rehabilitation to improve community re-integration and QoL.
Guidelines for botulinum neurotoxin injection for facial contouring
Authors: Yi Kyu-Ho , Lee Hyung-Jin , Hur Hye-Won , Seo Kyle K , Kim Hee-Jin
Published: June 2022

The hypertrophied temporalis and masseter muscles give a muscular shaped and bulky contour to the face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, adverse effects have been reported owing to a lack of delicate anatomical information. The anatomical considerations when injecting botulinum neurotoxin into the temporalis and masseter muscles have been reviewed in the present study. Current knowledge on the localization of the botulinum neurotoxin injection point with more recent anatomical dissection and modified Sihler’s staining procedures was assessed. We found that for the muscles, the injection point can be more precisely demarcated. Optimal injection sites are presented for the temporalis and masseter muscles, and the injection technique has been suggested. We propose the optimal injection sites in relation to external anatomical landmarks for the frequently injected muscles of the face to facilitate the efficiency of botulinum neurotoxin injections. In addition, these guidelines would aid in more precise practice without the adverse effects of botulinum neurotoxin.
Voided Volume for Assessment of Bladder Emptying After Female Pelvic Floor Surgery: A Randomized Controlled Trial
Authors: Popiel Patrick , Getaneh Feven , Yeh Judy , Rickey Leslie , Bercik Richard , Harmanli Oz
Published: June 2022

Importance

To study alternative voiding trial (VT) methods after urogynecologic surgery that may potentially decrease catheterization.

Objective

The aim of the study is to compare voiding assessment based on a minimum spontaneous voided volume of 150 mL with the standard retrograde fill (RF) approach in women after urogynecologic procedures.

Study Design

Women undergoing urogynecologic surgery were randomized to RF or spontaneous void (SV) groups. Women in the RF group had their bladders backfilled with 300 mL of saline before catheter removal, those in the SV group did not. To pass the VT, patients in the RF group were required to void 150 mL at one time within 60 minutes, and patients in the SV group had to do the same within 6 hours. The primary outcome was the VT failure rate. We also compared the false pass rate, urinary tract infections, satisfaction, and preference of VT method.

Results

One hundred nine women were enrolled in the study, 54 had SV and 55 underwent RF. Baseline characteristics were not significantly different other than history of prior hysterectomy. There was no significant difference in procedures between the groups. There was no difference in VT failure rate between the groups—SV (7.4%) and RF (12.7%, P = 0.39). The false pass rate was 0 in each group. Urinary tract infection rates were similar between SV (14.8%) and RF (14.5%) groups (P = 0.34). Patient satisfaction for VT method was not significantly different.

Conclusions

Spontaneous VT was not superior to retrograde void trial. Therefore, we cannot recommend one method of VT after urogynecologic surgery.

Condensation

Voiding assessment based on minimum SV of 150 mL is comparable with VT with RF after surgeries for prolapse and urinary incontinence.
Multi-ancestry GWAS for venous thromboembolism identifies novel loci followed by experimental validation in zebrafish
Authors: Wolford Brooke N. , Zhao Yakun , Surakka Ida , Wu Kuan-Han H. , Yu Xinge , Richter Catherine E. , Bhatta Laxmi , Brumpton Ben , Desch Karl , Thibord Florian , Klarin Derek , Johnson Andrew D. , Trégouët David-Alexandre , Damrauer Scott M. , Smith Nicholas L. ,   INVENT,   MVP, Lo Faro Valeria , Tsuo Kristin ,   Global Biobank Meta-analysis Initiative (GBMI), Daly Mark , Neale Ben , Zhou Wei , Shavit Jordan A. , Willer Cristen. J.
Published: June 2022

Genome wide association study (GWAS) results for Venous Thromboembolism (VTE) across 9 international cohorts of the Global Biobank Meta-analysis Initiative (GBMI), with representation across six ancestry groups (cases=27,987, controls=1,035,290), were combined using inverse-variance weighted meta-analysis. This multi-ancestry GWAS resulted in 38 genome-wide significant loci, 9 of which are potentially novel. For each autosomal locus we performed gene prioritization using seven independent, yet converging, lines of evidence. Through prioritization we identified genes known for VTE (e.g., F5, F11, VWF), genes known to modify blood coagulation (e.g., STAB2), and genes without known coagulation mechanisms from functional studies (e.g., PLCG2, TC2N). We evaluated the function of six prioritized genes, including F7 as a positive control, using laser mediated endothelial injury to induce thrombosis in zebrafish. We used CRISPR/Cas9 to knock down these potentially causal genes and measured time to occlusion after laser injury. From this assay we have supportive evidence for a role of RASIP1 and TC2N in the modification of human VTE, and suggestive evidence for STAB2 and TSPAN15. This study expands the currently identified genomic architecture of VTE through biobank-based multi-ancestry GWAS, in silico candidate gene predictions, and in vivo functional follow-up of novel candidate genes.
Longitudinal pathway analysis using structural information with case studies in early type 1 diabetes
Authors: Jaakkola Maria K. , Kukkonen-Macchi Anu , Suomi Tomi , Elo Laura L.
Published: June 2022

We introduce a new method for Pathway Analysis of Longitudinal data (PAL), which is suitable for complex study designs, such as longitudinal data. The main advantages of PAL are the use of pathway structures and the suitability of the approach for study settings beyond currently available tools. We demonstrate the performance of PAL with three longitudinal datasets related to the early development of type 1 diabetes, involving different study designs and only subtle biological signals. Transcriptomic and proteomic data are represented among the test data. An R package implementing PAL is publicly available athttps://github.com/elolab/PAL.

Motivation

Pathway analysis is a frequent step in studies involving gene or protein expression data, but most of the available pathway methods are designed for simple case versus control studies of two sample groups without further complexity. The few available methods allowing the pathway analysis of more complex study designs cannot use pathway structures or handle the situation where the variable of interest is not defined for all samples. Such scenarios are common in longitudinal studies with so long follow up time that healthy controls are required to identify the effect of normal aging apart from the effect of disease development, which is not defined for controls. PAL is the first available pathway method to analyse such high-investment datasets.
Understanding the mechanism ofTrikatuin type 2 diabetes mellitus and lipid-related metabolic disorders: A network pharmacology approach
Authors: Chhabra Varun , Wadhawan Mohit , Katiyar Amit , Khuntia Bharat Krushna , Sharma Vandna , Rathore Shubhangi , kaur Punit , Sharma Gautam
Published: June 2022

Objective

Trikatu is an Indian polyherbal formulation comprising three herbs, i.e., Zingiber officinale, Piper longum, and Piper nigrum. It is traditionally used to treat metabolic disorders such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, its mechanism of action remains unknown. This study aims to explore the underlying therapeutic mechanism of Trikatu in T2DM and lipid metabolic disorders using network pharmacology (NP).

Methods

Trikatu phytochemicals were retrieved from various databases and screened on the basis of druglikeness and oral bioavailability (>30%) score. Putative targets of the bioactive phytochemicals were identified using TargetNet, Similarity Ensemble Approach, and Swiss Target Prediction databases. Protein-protein interaction (PPI) network of overlapping targets of phytochemicals and metabolic disorders was constructed using NetworkAnalyst 3.0. The Bioactive Phytochemical-Target-Pathway (BP-T-P) network was constructed using cytoscape v3.8.2, and the key targets of Trikatu were analyzed by Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.

Results

Twenty bioactive phytochemicals and 102 targets of Trikatu were identified. PPI network and enrichment analysis showed that 51 targets of Trikatu phytochemicals such as RXRA, STAT3 and ESR1, GSK3B, TNF, NOS2/3 regulate pathways like insulin resistance, steroid hormone biosynthesis, regulation of lipolysis in adipocytes, adipocytokine & cGMP-PKG signalling pathways, arachidonic acid metabolism and bile secretion. The results were validated by molecular docking which showed that RXRA, STAT3 and ESR1 strongly interact with their ligands alpha gurjunene, beta-sitosterol, piperlongumine, genistein and E-beta carotene, respectively.

Conclusion

Hence, the multiple target and multiple pathway approach of Trikatu can be further explored in pharmacokinetics / Pharmacodynamics studies.
Partial reuse of circadian clock genes along parallel clines of diapause in two moth species
Authors: Yu Yue , Huang Li-Li , Xue Fang-Sen , Dopman Erik B.
Published: June 2022

Understanding the molecular basis of repeated evolution is essential for improving our ability to predict evolution. Genes repeatedly used in independent cases of adaptation to similar environments are strong candidates for predicting adaptation across phylogeny. The Asian corn borer (Ostrinia furnacalis; ACB) and the European corn borer (Ostrinia nubilalis; ECB) are two closely related moths that display remarkable adaptability to a wide range of climate on two separate continents, largely manifesting as changes in the timing of diapause (dormancy), but the genetic basis of parallel clinal responses remains to be characterized. We extensively sampled the ACB cline in China in a genome-wide association study (GWAS) using pooled sequencing data (Pool-seq). We characterized the genetic basis of clinal diapause response in ACB and showed that genes involved in circadian rhythm were over-represented among the candidate genes under spatially varying selection. Comparing with previous results from ECB, we found that the circadian clock gene period (per), but not pigment-dispersing factor receptor (Pdfr), was repeatedly used, but the alleles were not shared between the species. The corn borers’ shared adaptability is likely based inperbut seemingly through independent mutational paths.
Tracing the origin of fish immunoglobulins
Authors: Mirete-Bachiller Serafin , Gambón-Deza Francisco
Published: June 2022

We have studied the origin of immunoglobulin genes in fish. There are two evolutionary lines of bony fish, Actinopterygii and Sarcopterygii. The former gave rise to most of the current fish and the latter to the animals that went to land. Non-teleost actinopterygians are significant evolutionary, sharing a common ancestor with sarcopterygians. There are three different immunoglobulin isotypes in ray-finned fish: IgM, IgD and IgT. We deduce that translocon formation in immunoglobulins genes occurred already in non-teleost Actinopterygii. We establish a relationship between no teleosts and teleostean fish at the domain level of different immunoglobulins. We found two evolutionary lines of immunoglobulin. A line that starts from Immunoglobulin M and another from an ancestral Immunoglobulin W. The M line is stable, and the W line gives rise to the IgD of the fish. Immunoglobulin T emerges by recombination between both lines.
The effect of breaking up sedentary time with calisthenics on neuromuscular function: a preliminary study
Authors: Mear Emily , Gladwell Valerie , Pethick Jamie
Published: June 2022

Prolonged sedentary behaviour has a detrimental effect on neuromuscular function and is associated with decreased muscle strength and force control, and a decreased ability to maintain balance. Breaking up sedentary time with regular bouts of physical activity has numerous health benefits, though the effects on neuromuscular function are unknown. This study aimed to investigate the effect of breaking up sedentary time with calisthenic exercise on neuromuscular function. To that end, 17 healthy adults, who spent ≥6 hours a day sitting, were randomly assigned to a four-week calisthenics intervention (n = 8) or a control group (n = 9). The calisthenics intervention involved performing up to eight sets of exercises during the working day (09:00-17:00); with one set consisting of eight repetitions of five different exercises (including squats and lunges). Before and immediately after the intervention, measures of knee extensor maximal voluntary contraction (MVC; right leg only) and submaximal force control (measures of the magnitude and complexity of force fluctuations; right leg only), and dynamic balance (Y balance test; both legs) were taken. The calisthenics intervention resulted in a significant increase in knee extensor MVC (P= 0.036), significant decreases in the standard deviation (P0.031) and coefficient of variation (P= 0.016) of knee extensor force fluctuations during contractions at 40% MVC, and a significant increase in Y balance test posterolateral reach with left leg stance (P= 0.046). These results suggest that breaking up sedentary time with calisthenics may be effective at increasing muscle strength, force steadiness and dynamic balance.

New findings

What is the central question of this study?

This study sought to determine whether breaking up sedentary time with a (4-week) calisthenics exercise intervention could improve neuromuscular function.

What is the main finding and its importance?

A 4-week calisthenic exercise intervention increased knee extensor maximal strength, knee extensor force steadiness during submaximal contractions, and aspects of dynamic balance. These results indicate the regularly breaking up sedentary time with calisthenics can mitigate against the negative effects of prolonged sedentary time.
On the adaptive meaning of chemically insignificant cues in multitrophic caterpillar-ant-plant symbioses
Authors: Lima Luan Dias , Assis Diego Santana , do Nascimento Fábio Santos , Kaminski Lucas Augusto
Published: June 2022

Ants use cuticular hydrocarbons (CHCs) as chemical cues for recognition, which are exploited by myrmecophiles to usufruct the benefits of the social habit. We aimed to identify the functional role of CHCs of two riodinid caterpillar species that obligately associate with different multitrophic ant-plant symbioses. Experiments of ant acceptance of caterpillars showed the concerted action of larval-ant-organs that produce liquid rewards (tentacle nectary organs, TNOs) and luring signals (anterior tentacle organs, ATOs) was key to ant appeasement and larval survival. Experiments changing the symbiosis were often lethal for the caterpillars, mainly after emptying the secretions of their TNOs and their ATOs were never activated. Chemical profiles of caterpillars were insignificant. Field bioassays with chemically insignificant palatable insect prey attracted fewer ants, indicating that insignificant cues may reduce the probability of ant attacks. Thus, caterpillars control the emission of signals of ant-organs during symbiosis, whereas the cues of CHCs are silenced. It is possible that a trade-off exists between signals under control and non-controlled cues. Chemical insignificance may allow for a crucial period for caterpillars to make tactical decisions to appease aggressive ants and could be extended to other communication channels according to the sensorial universe of the receiver.
MaD: Macromolecular Descriptors for Integrative Dynamic Modeling Supported by Cryo-EM Data
Authors: Träger Sylvain , Peraro Matteo Dal
Published: June 2022

The determination of atomic structures of large flexible systems remains a challenging task despite the recent advances in cryo-electron microscopy (cryo-EM) and de novo protein structure prediction. Few hybrid methods truly consider dynamics because deriving appropriate conformational ensembles and scoring functions robust to conformational differences is not trivial. We present here Macromolecular Descriptors (MaD) which, inspired by traditional computer vision concepts, remedies some of these limitations. MaD identifies feature points and encodes local structural information around them into resolution- and conformation-invariant descriptors. Efficient matching of descriptors from cryo-EM densities at low and medium resolution with those of high-resolution component structures yields a robust and accurate assembly prediction that does not require other experimental or computational input. Fast, scalable and easy to use, this method is able to incorporate native dynamic features as extracted from molecular simulations and identify the models that best match the target electron density. Therefore, MaD addresses some of the unanswered needs of the community in terms of the integrative modeling of large and flexible macromolecular complexes.
Scene-selective brain regions respond to embedded objects of a scene
Authors: Aminoff Elissa M. , Durham Tess
Published: June 2022

Objects are fundamental to scene understanding. Scenes are defined by embedded objects and how we interact with them. Paradoxically, scene processing in the brain is typically discussed in contrast to object processing. Using the BOLD5000 dataset (Chang et al., 2019), we examined whether objects within a scene predicted the neural representation of scenes, as measured by fMRI in humans. Stimuli included 1,179 unique scenes across 18 semantic categories. Object composition of scenes were compared across scene exemplars in different semantic categories, and separately, in exemplars of the same category. Neural representations in scene- and object-preferring brain regions were significantly related to which objects were in a scene, with the effect at times stronger in the scene-preferring regions. The object model accounted for more variance when comparing scenes within the same semantic category to scenes from different categories. Thus, the functional role of scene-preferring regions should include the processing of objects. This suggests visual processing regions may be better characterized with respect to which processes are engaged when interacting with the stimulus category, such as processing groups of objects in scenes, or processing a single object in our foreground, rather than the stimulus category itself.
Adaptation of a quantitative trait to a changing environment: new analytical insights on the asexual and infinitesimal sexual models
Authors: Garnier J. , Cotto O. , Bouin E. , Bourgeron T. , Lepoutre T. , Ronce O. , Calvez V.
Published: June 2022

Predicting the adaptation of populations to a changing environment is crucial to assess the impact of human activities on biodiversity. Many theoretical studies have tackled this issue by modeling the evolution of quantitative traits subject to stabilizing selection around an optimal phenotype, whose value is shifted continuously through time. In this context, the population fate results from the equilibrium distribution of the trait, relative to the moving optimum. Such a distribution may vary with the shape of selection, the system of reproduction, the number of loci, the mutation kernel or their interactions. Here, we develop a methodology that provides quantitative measures of population maladaptation and potential of survival directly from the entire profile of the phenotypic distribution, without any a priori on its shape. We investigate two different systems of reproduction (asexual and infinitesimal sexual models of inheritance), with various forms of selection. In particular, we recover that fitness functions such that selection weakens away from the optimum lead to evolutionary tipping points, with an abrupt collapse of the population when the speed of environmental change is too high. Our unified framework allows deciphering the mechanisms that lead to this phenomenon. More generally, it allows discussing similarities and discrepancies between the two systems of reproduction, which are ultimately explained by different constraints on the evolution of the phenotypic variance. We demonstrate that the mean fitness in the population crucially depends on the shape of the selection function in the infinitesimal sexual model, in contrast with the asexual model. In the asexual model, we also investigate the effect of the mutation kernel and we show that kernels with higher kurtosis tend to reduce maladaptation and improve fitness, especially in fast changing environments.

Highlights

Adaptation to a changing environment may generate non Normal phenotypic distribution.

The phenotypic variance at equilibrium truly depends on reproduction model;

Selection shapes mean fitness only in sexual infinitesimal model;

Weak selection away from the optimum leads to evolutionary tipping points with fast changes;

Frequent mutations with large effects reduce maladaptation and improve fitness.
Frequency-dependent viscosity of salmon ovarian fluid has biophysical implications for sperm-egg interactions
Authors: Graziano Marco , Palit Swomitra , Yethiraj Anand , Immler Simone , Gage Matthew JG , Purchase Craig
Published: June 2022

Gamete-level sexual selection of externally fertilising species is usually achieved by modifying sperm behaviour with mechanisms thought to alter the chemical environment in which gametes perform. In fish this can be accomplished through the ovarian fluid, a substance released with the eggs at spawning. While its biochemical effects in relation to sperm energetics have been investigated, the influence of the physical environment in which sperm compete remains poorly explored. Our objective was therefore to gain insights on the physical structure of this fluid and potential impacts on reproduction. Using soft-matter physics approaches of steady-state and oscillatory viscosity measurements, we subjected salmon ovarian fluids to variable shear stresses and frequencies resembling those exerted by sperm swimming through the fluid near eggs. We show that this fluid, which in its relaxed state is a gel-like substance, displays a non-Newtonian viscoelastic and shear-thinning profile, where the viscosity decreases with increasing shear rates. We concurrently find that this fluid obeys the Cox-Merz rule below 7.6 Hz and infringes it above, thus indicating a shear-thickening phase where viscosity increases provided it is probed gently enough. This suggests the presence of a unique frequency-dependant structural network with relevant implications on sperm energetics and fertilisation dynamics.
Tipping points in spatial ecosystems driven by correlated noise
Authors: Pal Krishnendu , Deb Smita , Dutta Partha Sharathi
Published: June 2022

Complex spatial systems can experience critical transitions or tippings on crossing a threshold value in their response to stochastic perturbations. Whilst previous studies have well-characterized the impact of white noise on tipping, the effect of correlated noise in spatial ecosystems remains largely unexplored. Here, we investigate the effect of both multiplicative and additive Ornstein-Uhlenbeck (OU) correlated noise on the occurrence of critical transitions in spatial ecosystems. We find that decreasing the noise correlation aggravates the chance of critical transitions - opposite to what is observed previously in temporal systems in the presence of OU-noise with fixed lag-1 correlation. Our results hold good and are supported by the analysis of three well-studied spatial ecological models of varying nonlinearity. We also compute spatial early warning indicators (e.g., spatial variance, spatial skewness, and spatial correlation) to determine their reliability in anticipating tipping points with variations in noise correlation. The indicators of critical transitions exhibit mixed success in forewarning the occurrence of a tipping point, as indicated by the distribution of Kendall’s rank correlation.
Meta-analysis of diurnal transcriptomics reveals strong patterns of concordance and discordance in mouse liver
Authors: Brooks Thomas G. , Manjrekar Aditi , Grant Gregory R.
Published: June 2022

The accumulation of public transcriptomic timeseries data enables robust meta-analyses that were not possible until recently. To assess the consistency of biological rhythms across studies, 43 public mouse liver tissue timeseries totaling 805 RNA-seq samples were obtained and analyzed. Only the control groups of each study were included, in order to create comparable data. Technical factors in RNA-seq library preparation were the largest contributors to transcriptome-level differences, beyond biological or experiment-specific factors such as lighting conditions. Core clock genes were remarkably consistent in phase across all studies, while phase distributions of other periodic genes were generally less consistent. Overlap of genes identified as rhythmic across studies was generally low, up to around 50% between some of the highest sample count studies. Distributions of phases of significant genes were remarkably inconsistent across studies, but genes consistently identified as rhythmic clustered near ZT0 and ZT12 in acrophase. Data was integrated across studies in a JIVE analysis, which showed that the top two components of joint within-study variation are determined by time of day. A shape-invariant model with random effects was fit to the genes to identify the underlying shape of the rhythms, consistent across all studies. This revealed the extent of asymmetric and multimodal genes.
Drosophila Cocaine Avoidance is Mediated by Peripheral Bitter Gustatory Neurons
Authors: Philyaw Travis J. , Titos Iris , Cummins Pearl N. , Rodan Aylin R. , Rothenfluh Adrian
Published: June 2022

Genetic variation contributes to heterogeneity in the prevalence of complex disorders such as addiction. The genetic risk for developing a substance use disorder can vary between drugs. The estimated heritability rate of cocaine addiction is 72%, higher than any other drug. Despite recognition of this significant genetic component, little is known about the specific genes and mechanisms that lead to the development of cocaine addiction. Drosophila is an effective model organism for identifying the genes that underlie complex behaviors, including addiction. While Drosophila exposed to cocaine display features of intoxication similar to those observed in mammals, there is currently no model of cocaine self-administration in flies. Because cocaine is a natural insecticide, we wondered if Drosophila might naively avoid it through bitter chemosensory detection. To answer this question, we performed cocaine consumption and preference assays comparing wild-type flies and bitter-taste mutants. Our results demonstrate that Drosophila detect and avoid cocaine through bitter sensing gustatory neurons, and that this process requires gustatory receptor 66a (Gr66a). Additionally, we identify a peripheral mechanism of avoidance through cocaine detection with Drosophila legs. Our findings reveal that preingestive mechanisms of toxin detection play a significant role in Drosophila cocaine avoidance and provide evidence that disrupting gustatory perception of cocaine is essential for self-administration and, therefore, developing a model of self-administration in Drosophila.
Fine-scale spatial genetic structure in a locally abundant native bunchgrass (Achnatherum thurberianum) including distinct lineages revealed within seed transfer zones
Authors: Osuna-Mascaró Carolina , Agneray Alison C. , Galland Lanie M. , Leger Elizabeth A. , Parchman Thomas L.
Published: June 2022

Analyses of the factors shaping spatial genetic structure in widespread plant species are important for understanding evolutionary history and local adaptation and have applied significance for guiding conservation and restoration decisions. Thurber’s needlegrass (Achnatherum thurberianum) is a widespread, locally abundant grass that inhabits heterogeneous arid environments of western North America and is of restoration significance. It is a common component of shrubland steppe communities in the Great Basin Desert, where drought, fire, and invasive grasses have degraded natural communities. Using a reduced representation sequencing approach, we generated SNP data at 5,677 loci across 246 individuals from 17A. thurberianumpopulations spanning five previously delineated seed zones from the western Great Basin. Analyses revealed pronounced population genetic structure, with individuals forming consistent geographical clusters across a variety of population genetic analyses and spatial scales. Low levels of genetic diversity within populations, as well as high population estimates of linkage disequilibrium and inbreeding, were consistent with self-fertilization as a contributor to population differentiation. Moreover, variance partitioning and partial RDA indicated local adaptation to the environment as an additional factor influencing the spatial distribution of genetic variation. The environmental variables driving these results were similar to those implicated in recent genecological work which inferred local adaptation in order to delineate seed zones. However, our analyses also reveal a complex evolutionary history ofA. thurberaniumin the Great Basin, where previously delineated seed zones contain distantly related populations. Overall, our results indicate that numerous factors shape genetic variation inA. thurberianumand that evolutionary history, along with differentiation across distinct geographic and environmental scales, should be considered for conservation and restoration plans.
An action-observation network in the common marmoset identified by ultra-high field fMRI
Authors: Zanini Alessandro , Dureux Audrey , Selvanayagam Janahan , Everling Stefan
Published: June 2022

The observation of others’ actions activates a network of temporal, parietal and premotor/prefrontal areas in macaque monkeys and humans. This action-observation network (AON) has been shown to play important roles in understanding the actions of others, learning by imitation, and social cognition in both species. It is unclear whether a similar network exists in New World primates, which separated from Old Word Primates ∼ 35 million years ago. Here we used ultra-high field fMRI at 9.4T in awake common marmosets (Callithrix jacchus) while they watched videos depicting the upper-limb of conspecifics performing goal-directed (grasping food) or non-goal-directed actions. We found that the observation of goal-directed actions, compared to non-goal directed ones, activated a temporo-parieto-frontal network, including areas 6 and 45 in premotor and prefrontal cortices, areas PGa-IPa, FST and the TE complex in occipito-temporal region and areas V6A, MIP, LIP and PG in the occipito-parietal cortex. These results show remarkable overlap with the AON observed in humans and macaques. These results demonstrate the existence of an evolutionarily conserved AON that likely predates the separation of Old and New World primates.
Scene-relative object motion biases depth percepts
Authors: French Ranran L. , DeAngelis Gregory C.
Published: June 2022

An important function of the visual system is to represent 3D scene structure from a sequence of 2D images projected onto the retinae. During observer translation, the relative image motion of stationary objects at different distances (motion parallax) provides potent depth information. However, if an object moves relative to the scene, this complicates the computation of depth from motion parallax since there will be an additional component of image motion related to scene-relative object motion. To correctly compute depth from motion parallax, only the component of image motion caused by self-motion should be used by the brain. Previous experimental and theoretical work on perception of depth from motion parallax has assumed that objects are stationary in the world. Thus, it is unknown whether perceived depth based on motion parallax is biased by object motion relative to the scene.

Naïve human subjects viewed a virtual 3D scene consisting of a ground plane and stationary background objects, while lateral self-motion was simulated by optic flow. A target object could be either stationary or moving laterally at different velocities, and subjects were asked to judge the depth of the object relative to the plane of fixation. Subjects showed a far bias when object and observer moved in the same direction, and a near bias when object and observer moved in opposite directions. This pattern of biases is expected if subjects confound image motion due to self-motion with that due to scene-relative object motion. These biases were large when the object was viewed monocularly, and were greatly reduced, but not eliminated, when binocular disparity cues were provided. Our findings establish that scene-relative object motion can confound perceptual judgements of depth during self-motion.
Weaver ants regulate the rate of prey delivery during collective vertical transport
Authors: Burchill Andrew T. , Pavlic Theodore P. , Pratt Stephen C. , Reid Chris R.
Published: June 2022

The collective transport of massive food items by ant teams is a striking example of biological cooperation, but it remains unclear how these decentralized teams coordinate to overcome the various challenges associated with transport. Previous research has focused on transport across horizontal surfaces and very shallow inclines, disregarding the complexity of natural foraging environments. In the ant Oecophylla smaragdina, prey are routinely carried up tree trunks to arboreal nests. Using this species, we induce collective transport over a variety of angled surfaces with varying prey masses to investigate how ants respond to inclines. We found that weight and incline pose qualitatively different challenges during transport. Prey were carried over vertical inclines faster than across horizontal surfaces even though inclines were associated with longer routes and a higher probability of dropping the load. This additional speed is associated with more transporters being allocated to vertical loads and not from the persistence of individual ants. Ant teams also regulated a stable “prey delivery rate” (rate of return per transporter) across all treatments. Our proposed constrained optimization model explains these results: prey intake rate at the colony level is maximized when the allocation of transporters yields a similar prey delivery rate across loads.
Breastfeeding outcomes in late preterm infants: a multi-centre prospective cohort study
Authors: Keir Amy , Rumbold Alice , Collins Carmel T , McPhee Andrew J , Varghese Jojy , Morris Scott , Sullivan Thomas R , Leemaqz Shalem , Middleton Philippa , Makrides Maria , Best Karen P
Published: June 2022

Objectives

To describe (1) infant feeding practices during initial hospitalisation and up to 6 months corrected age (CA) in infants born late preterm with mothers intending to breastfeed, (2) the impact of early feeding practices on hospital length of stay and (3) maternal and infant factors associated with duration of breastfeeding.

Methods

We conducted a prospective cohort study of infants born at 34+0 to 36+6 weeks gestational age during 2018-2020. Families were followed up until the infant reached 6 months of age (corrected for prematurity). Feeding practices during the birth hospitalisation, length of initial hospital stay, and the prevalence of exclusive or any breastfeeding at 6 weeks, 3 months, and 6 months CA were examined. Associations between maternal and infant characteristics and breastfeeding at 6 weeks, 3 months and 6 months CA were assessed using multivariable logistic regression models.

Results

270 infants were enrolled, of these, 30% were multiple births. Overall, 78% of infants received only breastmilk as their first feed, and 83% received formula during the hospitalisation. Seventy-four per cent of infants were exclusively breastfed at discharge, 41% at 6 weeks CA, 35% at 3 months CA, and 29% at 6 months CA. The corresponding combined exclusive and partial breastfeeding rates (any breastfeeding) were 72%, 64%, and 53% of babies at 6 weeks CA, 3 months CA, and 6 months CA, respectively. The mean duration of hospitalisation was 2.9 days longer (95% confidence interval (CI) 0.31, 5.43 days) in infants who received any formula compared with those receiving only breastmilk (adjusted for GA, maternal age, multiple birth, site, and neonatal intensive care unit admission). In multivariable models, receipt of formula as the first milk feed was associated with a reduction in exclusive breastfeeding at 6 weeks CA (odds ratio = 0.22; 95% CI 0.09 to 0.53) and intention to breastfeed >6 months with an increase (odds ratio = 4.98; 95% CI 2.39 to 10.40). Intention to breastfeed >6 months remained an important predictor of exclusive breastfeeding at 3 and 6 months CA.

Conclusions

Our study demonstrates that long-term exclusive breastfeeding rates were low in a cohort of women intending to provide breastmilk to their late preterm infants, with approximately half providing any breastmilk at 6 months CA. Formula as the first milk feed and intention to breastfeed >6 months were significant predictors of breastfeeding duration. Improving breastfeeding outcomes may require strategies to support early lactation and a better understanding of the ongoing support needs of this population.
SETH predicts nuances of residue disorder from protein embeddings
Authors: Ilzhoefer Dagmar , Heinzinger Michael , Rost Burkhard
Published: June 2022

Predictions for millions of protein three-dimensional structures are only a few clicks away since the release of AlphaFold2 results for UniProt. However, many proteins have so-called intrinsically disordered regions (IDRs) that do not adopt unique structures in isolation. These IDRs are associated with several diseases, including Alzheimer’s Disease. We showed that three recent disorder measures of AlphaFold2 predictions (pLDDT, “experimentally resolved” prediction and “relative solvent accessibility”) correlated to some extent with IDRs. However, expert methods predict IDRs more reliably by combining complex machine learning models with expert-crafted input features and evolutionary information from multiple sequence alignments (MSAs). MSAs are not always available, especially for IDRs, and are computationally expensive to generate, limiting the scalability of the associated tools. Here, we present the novel method SETH that predicts residue disorder from embeddings generated by the protein Language Model ProtT5, which explicitly only uses single sequences as input. Thereby, our method, relying on a relatively shallow convolutional neural network, outperformed much more complex solutions while being much faster, allowing to create predictions for the human proteome in about one hour on a consumer-grade PC with one NVIDIA GeForce RTX 3060. Trained on a continuous disorder scale (CheZOD scores), our method captured subtle variations in disorder, thereby providing important information beyond the binary classification of most methods. High performance paired with speed revealed that SETH’s nuanced disorder predictions for entire proteomes capture aspects of the evolution of organisms. Additionally, SETH could also be used to filter out regions or proteins with probable low-quality AlphaFold2 3D structures to prioritize running the compute-intensive predictions for large data sets. SETH is freely publicly available at: https://github.com/Rostlab/SETH.