bluuebunny/crossref_metadata_2025 huggingface dataset:
Falsirhodobacter algicola sp. nov., a member of the Rhodobacteraceae isolated from the marine red algae Grateloupia sp.
Authors: Cho Eun-Seo , An Chang Woo , Bae Seung Seob , Chung Dawoon , Yu Woon-Jong , Kim Jaoon Young Hwan , Choi Grace , Kwon Yong Min
Published: September 2023

A Gram-negative, pale yellow-pigmented, non-flagellated, motile, rod-shaped and aerobic bacterium, designated strain PG104T, was isolated from red algae Grateloupia sp. collected from the coastal area of Pohang, Republic of Korea. Growth of strain PG104T was observed at 15–35 °C (optimum, 30 °C), pH 6.0–10.0 (optimum, pH 7.5–8.0) and in the presence of 0–8.0 % (w/v) NaCl (optimum, 5.0 %). The predominant fatty acids included C17 : 0, C18 : 0, 11-methyl C18 : 1
 ω7c and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c) and the major respiratory quinone was Q-10. Polar lipids included phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid and one unidentified aminolipid. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain PG104T formed a phylogenetic lineage with members of the genus

Falsirhodobacter

and exhibited 16S rRNA gene sequence similarities of 97.1 and 96.6 % to

Falsirhodobacter deserti

W402T and

Falsirhodobacter halotolerans

JA744T, respectively. The complete genome of strain PG104T consisted of a single circular chromosome of approximately 2.8 Mbp with five plasmids. Based on polyphasic taxonomic data, strain PG104T represents a novel species in the genus

Falsirhodobacter

, for which the name Falsirhodobacter algicola sp. nov. is proposed. The type strain of Falsirhodobacter algicola is PG104T (=KCTC 82230T=JCM 34380T).
Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh
Authors: Lempens Pauline , Van Deun Armand , Aung Kya J. M. , Hossain Mohammad A. , Behruznia Mahboobeh , Decroo Tom , Rigouts Leen , de Jong Bouke C. , Meehan Conor J.
Published: September 2023

The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44 % of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8 %) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.
The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies
Authors: Kikawa Caroline , Cartwright-Acar Catiana H. , Stuart Jackson B. , Contreras Maya , Levoir Lisa M. , Evans Matthew J. , Bloom Jesse D. , Goo Leslie
Published: September 2023

Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.

Importance

The wide endemic range of mosquito-vectored flaviviruses – such as Zika virus and dengue virus serotypes 1-4 – places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue towards development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.
A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system
Authors: Costacurta Francesco , Dodaro Andrea , Bante David , Schöppe Helge , Sprenger Bernhard , Moghadasi Seyed Arad , Fleischmann Jakob , Pavan Matteo , Bassani Davide , Menin Silvia , Rauch Stefanie , Krismer Laura , Sauerwein Anna , Heberle Anne , Rabensteiner Toni , Ho Joses , Harris Reuben S. , Stefan Eduard , Schneider Rainer , Kaserer Teresa , Moro Stefano , von Laer Dorothee , Heilmann Emmanuel
Published: September 2023

Nirmatrelvir was the first protease inhibitor (PI) specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mproresistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mprovariants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available PIs (nirmatrelvir and ensitrelvir) with cell-based and biochemical assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mproinhibitors, will help to understand SARS-CoV-2 protease-inhibitor-resistance mechanisms and show the relevance of specific mutations in the clinic, thereby informing treatment decisions.

Teaser

Understanding how SARS-CoV-2 could counter the antiviral drug nirmatrelvir and what it means for the future of COVID-19 treatment.
Resuscitating Sleeping Beauties: reviving a six-hundred-year-old amoeba and endosymbiont
Authors: Issam Hasni , Tall Mamadou Lamine , Bailly Matthieu Le , Colson Philippe , Levasseur Anthony , Raoult Didier , Scola Bernard La , Drancourt Michel
Published: September 2023

Coprolites are sources of ancient human gut microbiota and parasites. Paleomicrobiological investigation of a 14th-century coprolite revealed amoeba cysts that when cultured were identified asAcanthamoeba castellaniistrain Namur. Genomic DNA sequencing indicated a 69-Mb, 57.9% GC content genome encoding 40,545 proteins, including 266 amoeba sequences sharing the best hit with amoeba-resisting microorganisms, including 170 with giant viruses. An endosymbiont we namedCoprolita marseillensiswas revealed by electron microscopy that harbored a 1-Mb genome of Rickettsiales ancestry encoding 1,738 predicted genes. Most of the amoeba genomic complement was related to biological functions giving the amoeba the capacity to survive in various ecological niches, including genes associated with anaerobic respiration and dormancy that were detected in bacteria resuscitated from permafrost, but not in controls that had not been resurrected. Investigating these 600-year-old “sleeping beauties” indicated the centuries-long survival of unicellular organisms and the mixed capability of anaerobic respiration coupled with dormancy.
Sediment source and dose influence the larval performance of the threatened coralOrbicella faveolata
Authors: Serrano Xaymara M. , Rosales Stephanie M. , Miller Margaret W. , Palacio-Castro Ana M. , Williamson Olivia M. , Gomez Andrea , Baker Andrew C.
Published: September 2023

The effects of turbidity and sedimentation stress on early life stages of corals are poorly understood, particularly in Atlantic species. Dredging operations, beach nourishment, and other coastal construction activities can increase sedimentation and turbidity in nearby coral reef habitats and have the potential to negatively affect coral larval development and metamorphosis, reducing sexual reproduction success. In this study, we investigated the performance of larvae of the threatened Caribbean coral speciesOrbicella faveolataexposed to sediments collected from a reef site in southeast Florida recently impacted by dredging (Port Miami), and compared it to the performance of larvae exposed to sediments collected from the offshore, natal reef of the parent colonies. In a laboratory experiment, we tested whether low and high doses of each of these sediment types affected the survival, settlement, and respiration of coral larvae compared to a no-sediment control treatment. In addition, we analyzed the sediments used in the experiments with 16S rRNA gene amplicon sequencing to assess differences in the microbial communities present in the Port versus Reef sediments, and their potential impact on coral performance. Overall,O. faveolatalarvae exposed to high doses of either sediment type (Port or Reef) exhibited reduced survival and settlement rates, but only the Port sediments resulted in adverse effects in the low-dose treatment. Sediments collected near the Port also contained different microbiomes than Reef sediments, and higher relative abundances of the bacteria Desulfobacterales, which has been associated with coral disease. We hypothesize that differences in microbiomes between the two sediments may be a contributing factor in explaining the observed differences in larval performance. Together, these results suggest that the settlement success and survival ofO. faveolatalarvae are more readily compromised by encountering port inlet sediments compared to reef sediments, with potentially important consequences for the recruitment success of this species in affected areas.
AAO2 impairment improves aldehyde detoxification by AAO3 in Arabidopsis leaves exposed to UVC or Rose Bengal
Authors: Nurbekova Zhadyrassyn , Srivastava Sudhakar , Du Nja Zai , Turečková Veronica , Strand Miroslav , Omarov Rustem , Sagi Moshe
Published: September 2023

Among the three active aldehyde oxidases inArabidopsis thalianaleaves (AAO1-3), AAO3, which catalyzes the oxidation of abscisic-aldehyde to abscisic-acid, was shown recently to function as a reactive aldehyde detoxifier. Notably,aao2KOmutants exhibited less senescence symptoms and lower aldehyde accumulation, such as acrolein, benzaldehyde, and HNE than in wild-type leaves exposed to UV-C or Rose-Bengal. The effect of the absence of AAO2 expression on aldehyde detoxification by AAO3 and/or AAO1 was studied by comparing the response of wild-type plants to the response ofaao1Singlemutant,aao2KOmutants and single mutants ofaao3Ss. Notably,aao3Ssexhibited similar aldehyde accumulation and chlorophyll content toaao2KOtreated with UV-C or Rose-Bengal. In contrast, wild-type andaao1Sexhibited higher aldehyde accumulation that resulted in lower remaining chlorophyll than in aao2KOleaves, indicating that the absence of active AAO2 enhanced AAO3 detoxification activity inaao2KOmutants. In support of this notion, employing abscisic-aldehyde as a specific substrate marker for AAO3 activity revealed enhanced AAO3 activity inaao2KOandaao3Ssleaves compared to wild-type treated with UV-C or Rose Bengal. The similar abscisic acid level accumulated in leaves of unstressed or stressed genotypes indicates that aldehyde detoxification by AAO3 is the cause for better stress resistance inaao2KOmutants. Employing the sulfuration process (known to activate aldehyde oxidases) in wild-type,aao2KO, andmolybdenum-cofactor sulfurase(aba3-1) mutant plants revealed that the active AAO2 in WT employs sulfuration processes essential for AAO3 activity level, resulting in the lower AAO3 activity in WT than AAO3 activity inaao2KO.
Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test
Authors: Beitelshees Amber L. , Streeten Elizabeth A. , Yazdi Zhinous Shahidzadeh , Whitlatch Hilary B. , Mitchell Braxton D. , Shuldiner Alan R. , Montasser May E. , Taylor Simeon I.
Published: September 2023

Aim

DPP4 inhibitors are widely prescribed as treatments for type 2 diabetes. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses.

Methods

Sitagliptin (100 mg) was administered to 47 healthy volunteers. Several endpoints were measured to assess clinically relevant responses – including the effect of sitagliptin on glucose and insulin levels during an oral glucose tolerance test (OGTT).

Results

This pilot study confirmed that sitagliptin (100 mg) decreased the area under the curve for glucose during an OGTT (p=0.0003). Furthermore, sitagliptin promoted insulin secretion during the early portion of the OGTT as reflected by an increase in the ratio of plasma insulin at 30 min divided by plasma insulin at 60 min (T30:T60) from 0.87+/-0.05 to 1.62+/-0.36 mU/L (p=0.04). The magnitude of sitagliptin’s effect on insulin secretion (as judged by the increase in the T30:T60 ratio for insulin) was correlated with the magnitude of sitagliptin-induced increase in the area under the curve for intact plasma GLP1 levels during the first hour of the OGTT. This study confirmed previously reported sex differences in glucose and insulin levels during an OGTT. Specifically, females exhibited higher levels of glucose and insulin at the 90-180 min time points. However, we did not detect significant sex-associated differences in the magnitude of sitagliptin-induced changes in T30:T60 ratios for either glucose or insulin.

Conclusions

T30:T60 ratios for insulin and glucose during an OGTT provide useful indices to assess pharmacodynamic responses to DPP4 inhibitors.
Inferring vaccine efficacy and mode of action from human challenge studies
Authors: Miura Fuminari , Klinkenberg Don , Ainslie Kylie E.C. , Backer Jantien A. , Leung Ka Yin , McDonald Scott A. , de Boer Pieter , Wallinga Jacco
Published: September 2023

To assess the long-term effect of a vaccination programme, understanding both the efficacy and the mode of action of the vaccine is crucial. The actual mode of action is difficult to infer from field trials, because of the heterogeneity of exposure to infection. Here we show an approach to determine both vaccine efficacy and the mode of action of vaccines from human challenge studies. Our approach reveals how vaccines alter an individual’s susceptibility, and identifies a mixture of different modes of action as a function of the challenged dose. By applying the proposed method to influenza challenge data, we illustrate that potentially the lowest vaccine efficacy may occur at intermediate doses, suggesting a hypothesis that moderate transmission intensities might be optimal for establishing infections in vaccinated individuals.

One sentence summary

Human challenge studies reveal the protection mechanism of vaccines by measuring variation in susceptibility to infection.
Augmenting complex and dynamic performance through mindfulness-based cognitive training: an evaluation of training adherence, trait mindfulness, personality and resting-state EEG
Authors: Dziego Chloe A. , Bornkessel-Schlesewsky Ina , Schlesewsky Matthias , Sinha Ruchi , Immink Maarten A. , Cross Zachariah R.
Published: September 2023

Human performance applications of mindfulness-based training have demonstrated its utility in enhancing cognitive functioning. Previous studies have illustrated how these interventions can improve performance on traditional cognitive tests, however, little investigation has explored the extent to which mindfulness-based training can optimise performance in more dynamic and complex contexts. Further, from a neuroscientific perspective, the underlying mechanisms responsible for performance enhancements remain largely undescribed. With this in mind, the following study aimed to investigate how a short-term mindfulness intervention (one week) augments performance on a dynamic and complex task (target motion analyst task; TMA) in young, healthy adults (n= 40, agerange= 18 - 38). Linear mixed effect modelling revealed that increased adherence to the mindfulness-based training regime (ranging from 0-21 sessions) was associated with improved performance in the second testing session of the TMA task, controlling for baseline performance. Further analyses of resting-state electroencephalographic (EEG) metrics and additional individual factors demonstrated enhancements associated with training adherence remained relatively consistent across varying levels of participants’ resting-state EEG metrics, personality measures (i.e., trait mindfulness, neuroticism, conscientiousness), self-reported enjoyment and timing of intervention adherence. Our results thus indicate that mindfulness-based cognitive training leads to performance enhancements in distantly related tasks, irrespective of several individual differences. We also revealed nuances in the magnitude of cognitive enhancements contingent on the timing of adherence, regardless of total volume of training. Overall, our findings suggest that mindfulness-based training could be used in a myriad of settings to elicit transferable performance enhancements.
NeurOne: High-performance Motor Unit-Computer Interface for the Paralyzed
Authors: Braun Dominik I. , Souza de Oliveira Daniela , Bayer Patricia , Ponfick Matthias , Kinfe Thomas Mehari , Vecchio Alessandro Del
Published: September 2023

We have recently demonstrated that humans with motor-and-sensory complete cervical spinal cord injury (SCI) can modulate the activity of spared motor neurons that control the movements of paralyzed muscles. These motor neurons still receive highly functional cortical inputs that proportionally control flexion and extension movements of the paralyzed hand digits. In this study, we report a series of longitudinal experiments in which subjects with motor complete SCI received motor unit feedback from NeurOne. NeurOne is a software that realizes super-fast digitalization of motor neuron spiking activity (32 frames/s) and control of these neural ensembles through a physiological motor unit twitch model that enables intuitive brain-computer interactions closely matching the voluntary force modulation of healthy hand digits. We asked the subjects (n=3, 3-4 laboratory visits) to match a target displayed on a monitor through a cursor that was controlled by the modulation of the recruitment and rate coding of the spared motor units using a motor unit twitch model. The attempted movements of the paralyzed hands involved grasping and hand digit extension/flexion. The target cursor was scaled in a way that the subjects could increase or decrease feedback by either recruiting or derecruiting motor units, or by modulating the instantaneous discharge rate. The subjects learned to control the motor unit output with high levels of accuracy across different target intensities up to the maximal achievable discharge rate. Indeed, the high-performance motor output was surprisingly stable in a similar way as healthy subjects modulated the muscle force output recorded by a dynamometer. Therefore, NeurOne enables tetraplegic individuals an intuitive control of the paralyzed muscles through a digital neuromuscular system.

Significance Statement

Our study demonstrates the remarkable ability of individuals with complete cervical spinal cord injuries to modulate spared motor neurons and control paralyzed muscles. Utilizing NeurOne, a software, we enabled intuitive brain-computer interactions by digitalizing motor neuron spiking activity and employing a motor unit twitch model. Through this interface, tetraplegic individuals achieved high levels of accuracy and proportional control which closely resembled motor function in intact humans. NeurOne provides a promising digital neuromuscular interface, empowering individuals to control assistive devices super-fast and intuitive. This study signifies an important advancement in enhancing motor function and improving the quality of life for those with spinal cord injuries.
Household income does not affect the pleiotropy of schizophrenia genetic liability with mental and physical health outcomes
Authors: Kouakou Manuela R. , Cabrera-Mendoza Brenda , Pathak Gita A. , Cannon Tyrone D. , Polimanti Renato
Published: September 2023

Background and Hypothesis

Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ.

Study Design

We investigated genome-wide datasets related to SCZ (52,017 cases and 75,889 controls) from the Psychiatric Genomics Consortium, household income (HI; N=361,687) from UK Biobank, and 2,202 medical endpoints assessed in up to 342,499 FinnGen participants. A phenome-wide genetic correlation analysis of SCZ and HI was performed, also assessing whether SCZ genetic correlations were influenced by HI effect on SCZ. Additionally, SCZ and HI direct effects on medical endpoints were estimated using multivariable Mendelian randomization (MR).

Study Results

SCZ and HI showed overlapping genetic correlations with 70 traits (p<2.89×10−5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, and musculoskeletal phenotypes. SCZ genetic correlations with these traits were not affected by HI effect on SCZ. Considering Bonferroni multiple testing correction (p<7.14×10−4), MR analysis indicated that SCZ and HI may affect medical abortion (SCZ odds ratio, OR=1.07; HI OR=0.78), panic disorder (SCZ OR=1.20; HI OR=0.60), personality disorders (SCZ OR=1.31; HI OR=0.67), substance use (SCZ OR=1.2; HI OR=0.68), and adjustment disorders (SCZ OR=1.18; HI OR=0.78). Multivariable MR analysis confirmed that SCZ effects on these outcomes were independent of HI.

Conclusions

The effect of SCZ genetic liability on mental and physical health may not be strongly affected by socioeconomic differences. This suggests that SCZ-specific strategies are needed to reduce negative health outcomes affecting patients and high-risk individuals.
Analysis of a Pilot Study Delivering Cancer Survivorship Education to Community Healthcare Professionals Utilizing the Project ECHO model
Authors: Pariser Ashley , Johns Kevin , Champion Dena , Roberts Andrea , Fugett Susan , Holley Erin , Schreiber Candice , Presley Carolyn J. , Todd Jalyn , Honeychuck Andrew , Hunt Katherine , Lu Yurong , Ramaswamy Bhuvaneswari , Bose Brill Seuli
Published: September 2023

Purpose

This pilot study evaluated a 12-week Cancer Survivorship curriculum delivered utilizing the Project Echo® model on provider self-efficacy (SE), knowledge (KN), and professional improvement (PI).

Methods

Providers affiliated with the Mercy Health System were enrolled in two cohorts. Six one-hour sessions were developed from a needs assessment and delivered over 12 weeks. Participants completed pre and post session surveys evaluating 3 domains: SE, KN and PI. The average score for survey items overall and within each domain was compared pre- and postsurvey results.

Results

Twenty-six participants completed the baseline survey and 22 completed the poststudy survey. For cohort 1, the overall score (0.94 (0.45,1.42) (P=0.0023), SE (1.1 (0.5,1.7) p = 0.003), and KN domain (1.03 (0.45,1.62) p= 0.0036) scores significantly increased. For cohort 2, the overall score (0.617 (0.042,1.193) p=0.0378), the SE (0.728(0.048,1.407), p = 0.0379), and KN domains (0.665 (0.041,1.289), p= 0.0387) increased significantly. The PI did not change for either cohort.

Conclusions

This Cancer Survivorship ECHO pilot resulted in a statistically significant increase in provider self-efficacy and knowledge. All 22 participants rated the Cancer Survivorship ECHO pilot experience as a positive (greater than neutral) on their training.

Implications for Cancer Survivors

The Cancer Survivorship ECHO model may serve as a scalable strategy for building cancer survivorship care capacity in community-based oncology practices through equipping multidisciplinary teams to meet the needs of cancer survivors within their community. Further research is needed to assess implementation of this model into novel settings and evaluate its impact on patient outcomes.
Dietary Assessment and Prevention of Hypertension in Nigeria: Protocol for a Retrospective Cross-sectional Study for the Development and Validation of a Food Frequency Questionnaire for Clinical Use
Authors: Batubo Nimisoere P. , Moore J. Bernadette , Zulyniak Michael A.
Published: September 2023

Introduction

Contrary to North America and Europe, the prevalence of hypertension is rising in West Africa. With a transition from whole foods to processed foods in Nigeria, diet plays a key driver of hypertension. To combat this, the national nutritional guidelines in Nigeria were implemented, but their translation into actionable tools for clinicians remains a challenge. Currently, there are no simple dietary assessment tools that are concise and suitable to be incorporated into clinical care without requiring extensive data analysis while still providing personalised dietary support to their patients. This study aims to deliver a clinically tested and validated short dietary assessment tool for clinicians, patients, and researchers across Nigeria to provide personalised dietary advice for patients with hypertension.

Methods

The study will be conducted in two phases: Phase 1 (n=75) will investigate the feasibility of the short FFQ and its agreement with 24-hour dietary recalls (3x) in a clinical setting in Nigeria. During the analysis of Phase 1 data, a scoring system will be developed based on the associations between individual food items in the FFQ and measures of hypertension. Phase 2 (n=50) will assess the acceptability of the FFQ and validate the association between the FFQ score and hypertension.

Expected outcomes

The development of a clinically tested and validated short food frequency questionnaire that will be ready to use by clinicians, patients, and researchers across Nigeria to support the prevention and management of hypertension.

Conclusion

This study will contribute to knowledge on dietary assessment and hypertension prevention by developing a validated and acceptable FFQ, which will be valuable for clinicians and researchers for personalised dietary recommendations to combat hypertension in Nigeria.Keywords:West Africa, diet, food, LMIC, blood pressure.
Strong early impact of letrozole on ovulation induction outperforms clomiphene citrate in polycystic ovary syndrome: a systematic review with meta-analysis
Authors: Vajna Rita Zsuzsanna , Géczi András Mihály , Meznerics Fanni Adél , Ács Nándor , Hegyi Péter , Feig Emma Zoé , Fehérvári Péter , Kiss-Dala Szilvia , Várbíró Szabolcs , Hetthessy Judit Réka , Sára Levente
Published: September 2023

Background

Polycystic ovary syndrome is one of the most frequent endocrinological problems causing infertility in women worldwide. The main problem in these women is hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. In this systematic review and meta-analysis, we aimed to investigate the efficacy of a relatively new drug for ovulation induction, letrozole, by comparing it to the first line of treatment for ovulation induction, clomiphene citrate.

Methods

A literary search was conducted in three databases and included randomized clinical trials comparing letrozole and clomiphene citrate for ovulation induction for women with polycystic ovary syndrome. The diagnosis of polycystic ovary syndrome was determined according to the Rotterdam criteria. We pooled data using a random-effects model.

Results

Our search provided a total of 1,994 articles, of which we included 25 studies. In the letrozole group, endometrial thickness was significantly higher (Mean Difference=1.70, Confidence Interval: 0.55-2.86; Heterogeinity: I2=97%, p-value=0.008); odds for ovulation (Odds Ratio=1.8, Confidence Interval: 1.21-2.69; Heterogeinity: I2=51%, p-value=0.010) and pregnancy (Odds Ratio=1.96, Confidence Interval: 1.37-2.81; Heterogeinity: I2=32%, p- value=0.002) were significantly higher; the resistance index of subendometrial arteries was significantly lower (Mean Difference=-0.15, Confidence Interval: -0.27- -0.04; Heterogeneity: I2=92%, p-value=0.030).

Conclusion

Women with polycystic ovary syndrome treated with letrozole for ovulation induction had higher ovulation and pregnancy rates, their endometrium became thicker, the resistance index of subendometrial arteries was lower. The lower resistance index of the subendometrial arteries can improve intrauterine circulation, which may provide better circumstances for embryo implantation and development.
Deep learning to extract the meteorological by-catch of wildlife cameras
Authors: Alison Jamie , Payne Stephanie , Alexander Jake M. , Bjorkman Anne D. , Clark Vincent Ralph , Gwate Onalenna , Huntsaar Maria , Iseli Evelin , Lenoir Jonathan , Mann Hjalte Mads Rosenstand , Steenhuisen Sandy-Lynn , Høye Toke Thomas
Published: September 2023

Microclimate – proximal climatic variation at scales of meters and minutes – can exacerbate or mitigate the impacts of climate change on biodiversity. However, most microclimate studies are temperature-centric, and do not consider meteorological factors such as sunshine, hail and snow. Meanwhile, remote cameras have become a primary tool to monitor wild plants and animals, even at micro-scales, with deep learning tools to rapidly convert images into ecological data. However, deep learning applications for wildlife imagery have focused exclusively on living subjects. Here, we identify an overlooked opportunity to extract latent, yet ecologically relevant, meteorological information.

We produce an annotated image dataset of micrometeorological conditions across 49 wildlife cameras in South Africa’s Maloti-Drakensberg and the Swiss Alps. We train ensemble deep learning models to classify conditions as overcast, sunshine, hail or snow. Our best model achieves 91.7% accuracy on test cameras not seen during training. Furthermore, we show how effective accuracy is raised to 96% by disregarding 14.1% of classifications where ensemble member models did not reach a consensus. Unlike previous studies we test model performance in remote and novel locations, distinguishing overcast and sunny conditions in Svalbard, Norway with 79.3% accuracy (93.9% consensus accuracy).

Our model rapidly classifies sunshine, snow and hail in almost 2 million unlabeled images. Resulting micrometeorological data illustrated common seasonal patterns of summer hailstorms and autumn snowfalls across mountains in the northern and southern hemispheres. However, daily patterns of sunshine and shade diverged between sites, impacting daily temperature cycles. Crucially, we leverage micrometeorological data to demonstrate that (1) experimental warming using open-top chambers shortens early snow events in autumn, and (2) image-derived sunshine marginally outperforms sensor-derived temperature when predicting bumblebee foraging. These methods generate novel micrometeorological variables in synchrony with biological recordings, enabling new insights from an increasingly global network of wildlife cameras.
PanEffect: A pan-genome visualization tool for variant effects in maize
Authors: Andorf Carson M , Haley Olivia C , Hayford Rita K , Portwood John L , Sen Shatabdi , Cannon Ethalinda K , Gardiner Jack M , Woodhouse Margaret R
Published: September 2023

Understanding the effects of genetic variants is crucial for accurately predicting traits and phenotypic outcomes. Recent advances have utilized protein language models to score all possible missense variant effects at the proteome level for a single genome, but a reliable tool is needed to explore these effects at the pan-genome level. To address this gap, we introduce a new tool called PanEffect. We implemented PanEffect at MaizeGDB to enable a comprehensive examination of the potential effects of coding variants across 51 maize genomes. The tool allows users to visualize over 550 million possible amino acid substitutions in the B73 maize reference genome and also to observe the effects of the 2.3 million natural variations in the maize pan-genome. Each variant effect score, calculated from the Evolutionary Scale Modeling (ESM) protein language model, shows the log-likelihood ratio difference between B73 and all variants in the pan-genome. These scores are shown using heatmaps spanning benign outcomes to strong phenotypic consequences. Additionally, PanEffect displays secondary structures and functional domains along with the variant effects, offering additional functional and structural context. Using PanEffect, researchers now have a platform to explore protein variants and identify genetic targets for crop enhancement.

Availability and implementation: The PanEffect code is freely available on GitHub (https://github.com/Maize-Genetics-and-Genomics-Database/PanEffect). A maize implementation of PanEffect and underlying datasets are available at MaizeGDB (https://www.maizegdb.org/effect/maize/).
Generative Diffusion Models for Antibody Design, Docking, and Optimization
Authors: Peng Zhangzhi , Han Chenchen , Wang Xiaohan , Li Dapeng , Yuan Fajie
Published: September 2023

In recent years, optimizing antibody binding affinity for biomedical applications has become increasingly important. However, traditional wet-experiment-based approaches are time-consuming and inefficient. To address this issue, we propose a diffusion model-based antibody optimization pipeline to improve binding affinity. Our approach involves two key models: AbDesign for designing antibody sequences and structures, and AbDock, a paratope-epitope docking model, used for screening designed CDRs. On an independent test set, our AbDesign demonstrates the exceptional performance of an RMSD of 2.56Å in structure design and an amino acid recovery of 36.47% in sequence design. In a paratope-epitope docking test set, our AbDock achieves a state-of-the-art performance of DockQ 0.44, irms 2.71Å, fnat 0.40, and Lrms 6.29Å. The effectiveness of the optimization pipeline is further experimentally validated by optimizing a flaviviruse antibody 1G5.3, resulting in a broad-spectrum antibody that demonstrates improved binding to 6 out of the nine tested flaviviruses. This research offers a general-purpose methodology to enhance antibody functionality without training on data from specific antigens.
TheMUC19gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection
Authors: Villanea Fernando A. , Peede David , Kaufman Eli J. , Añorve-Garibay Valeria , Chevy Elizabeth T. , Villa-Islas Viridiana , Witt Kelsey E. , Zeloni Roberta , Marnetto Davide , Moorjani Priya , Jay Flora , Valdmanis Paul N. , Ávila-Arcos María C. , Huerta-Sánchez Emilia
Published: September 2023

We study the gene MUC19, for which modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global populations, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations and are under positive selection. This study provides the first example of positive selection acting on archaic alleles at coding sites and VNTRs. Finally, we find that some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression.

One-Sentence Summary

Modern humans and Neanderthals carry a Denisovan variant of theMUC19gene, which is under positive selection in populations of Indigenous American ancestry.
Maresin-1 promotes neuroprotection and prevents disease progression in experimental models of multiple sclerosis through metabolic reprogramming and shaping innate and adaptive disease-associated cell types
Authors: Zahoor Insha , Nematullah Mohammad , Ahmed Mohammad Ejaz , Fatma Mena , Mir Sajad , Ayasolla Kamesh , Cerghet Mirela , Palaniyandi Suresh , Ceci Veronica , Carrera Giulia , Buttari Fabio , Centonze Diego , Mao-Draayer Yang , Rattan Ramandeep , Chiurchiù Valerio , Giri Shailendra
Published: September 2023

Multiple sclerosis (MS) is one of the most common inflammatory neurodegenerative diseases in young adults and causes neurological abnormalities and disability. We studied the effect of maresin 1 (MaR1) on the progression of disease in a relapsing-remitting form of experimental allergic encephalomyelitis (RR-EAE). Treatment with MaR1 in RR-EAE accelerated inflammation resolution, protected against neurological deficits, and delayed disease progression by decreasing immune cell infiltration (CD4+IL17+ and CD4+IFNγ+) into the CNS. Furthermore, the administration of MaR1 increased the production of IL-10, predominantly in macrophages and CD4+ cells. However, neutralizing IL-10 with an anti-IL-10 antibody abolished the protective effect of MaR1 on RR-EAE, suggesting that IL-10 plays a role in mediating the protective effect of MaR1 on EAE. Metabolism is rapidly becoming recognized as an important factor influencing the effector function of many immune cells. Using cutting-edge metabolic assays, our study revealed that compared with vehicle treatment, MaR1 treatment effectively restored the metabolic dysregulation observed in CD4+ cells, macrophages, and microglia in the treated group. Furthermore, MaR1 treatment reversed defective efferocytosis in EAE mice, which was potentially facilitated by the induction of metabolic alterations in macrophages and microglia. MaR1 treatment also protected myelin in the EAE group and regulated the metabolism of O4+ oligodendrocytes by restoring metabolic dysregulation through improved mitochondrial function and decreased glycolysis. Overall, in a preclinical MS animal model, MaR1 treatment produced anti-inflammatory and neuroprotective effects. It also triggered metabolic reprogramming in disease-associated cell types, accelerated efferocytosis, and preserved myelination. These data support that MaR1 has potential as a novel treatment agent for MS and other autoimmune diseases.

Abstract Figure

Highlights

MaR1 expedited inflammation resolution and prevented neurological impairments in RR-EAE.

IL-10 plays a role in mediating the protective effect of MaR1 on EAE.

MaR1 repaired CD4, macrophage, and microglia metabolic abnormalities.

MaR1 therapy restored efferocytosis in EAE.

MaR1 preserved myelin and improved O4+ oligodendrocyte metabolism.
Host-pathogen-vector continuum in a changing landscape: Drivers ofBartonellaprevalence and evidence of historic spillover in a multi-host community
Authors: Ansil B.R. , Viswanathan Ashwin , Ramachandran Vivek , Yeshwanth H.M. , Sanyal Avirup , Ramakrishnan Uma
Published: September 2023

Small mammals and their ectoparasites present a unique system to investigate the eco-epidemiology of multi-host vector-borne pathogens and identify specific bacterial spillover determinants. We applied ecological and evolutionary analyses in a rainforest-human-use mosaic to investigateBartonella spp.across small mammal and ectoparasite communities. We observed substantial overlap among small mammal communities in different habitat types, predominantly driven by habitat generalists. Most ectoparasites were generalists, infecting multiple hosts. We observed highBartonellaprevalence at both study sites –a forest-plantation mosaic (47.4%) and a protected area (28.8%). Seven of the ten ectoparasite species sampled were also positive forBartonella, following prevalence trends in their hosts. A generalised linear model revealed an independent association between aggregated ectoparasite load in hosts andBartonellaprevalence, implicating ectoparasites in transmission.Bartonellalineages from small mammals were host-specific, while ectoparasites carriedBartonellaassociated with other small mammal hosts, indicating the potential for cross-species transmission. Phylogenetic ancestral trait reconstruction ofBartonellahaplotypes suggest historic spillover events in the small mammal community, validating the potential for contemporary spillover events. These results highlight the necessity to disentangle the complex relationship between hosts, ectoparasites, and pathogens to understand the zoonotic implications of undetected spillover events in such multi-host communities.
Oxytocin, but not vasopressin, decreases willingness to harm others by promoting moral emotions of guilt and shame
Authors: Zheng Xiaoxiao , Wang Jiayuan , Yang Xi , Xu Lei , Becker Benjamin , Sahakian Barbara J. , Robbins Trevor W. , Kendrick Keith M.
Published: September 2023

Prosocial and moral behaviors have overlapping neural systems but whether they involve similar neurochemical systems is unclear. In the current pre-registered randomized placebo controlled trial on 180 adult male and female subjects we investigated effects of intranasal administration of two prosocial neuropeptides, oxytocin or vasopressin, on moral emotion ratings for situations involving accidental or intentional harm to others and in judgments of moral dilemmas where harm is inflicted for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame only for intentional harm and reduced endorsement of choices where direct intentional harm to others could achieve a greater good. Effects of oxytocin on guilt and shame were partially mediated by trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes unwillingness to deliberately harm others irrespective of the consequences. This may reflect stronger associations between oxytocin and empathy and vasopressin with aggression.
A gut meta-interactome map reveals modulation of human immunity by microbiome effectors
Authors: Young Veronika , Dohai Bushra , Hitch Thomas C. A. , Hyden Patrick , Weller Benjamin , van Heusden Niels S. , Saha Deeya , Macgregor Jaime Fernandez , Maseko Sibusiso B. , Lin Chung-Wen , Boujeant Mégane , Choteau Sébastien A. , Ober Franziska , Schwehn Patrick , Rothballer Simin , Altmann Melina , Altmann Stefan , Strobel Alexandra , Rothballer Michael , Tofaute Marie , Heinig Matthias , Clavel Thomas , Twizere Jean-Claude , Vincentelli Renaud , Boes Marianne , Krappmann Daniel , Falter Claudia , Rattei Thomas , Brun Christine , Zanzoni Andreas , Falter-Braun Pascal
Published: September 2023

The molecular mechanisms by which the gut microbiome influences human health remain largely unknown. Pseudomonadota is the third most abundant phylum in normal gut microbiomes. Several pathogens in this phylum can inject so-called virulence effector proteins into host cells. We report the identification of intact type 3 secretion systems (T3SS) in 5 - 20% of commensal Pseudomonadota in normal human gut microbiomes. To understand their functions, we experimentally generated a high-quality protein-protein meta-interactome map consisting of 1,263 interactions between 289 bacterial effectors and 430 human proteins. Effector targets are enriched for metabolic and immune functions and for genetic variation of microbiome-influenced traits including autoimmune diseases. We demonstrate that effectors modulate NF-κB signaling, cytokine secretion, and adhesion molecule expression. Finally, effectors are enriched in metagenomes of Crohn’s disease, but not ulcerative colitis patients pointing toward complex contributions to the etiology of inflammatory bowel diseases. Our results suggest that effector-host protein interactions are an important regulatory layer by which the microbiome impacts human health.
Uncertainty-aware single-cell annotation with a hierarchical reject option
Authors: Theunissen Lauren , Mortier Thomas , Saeys Yvan , Waegeman Willem
Published: September 2023

Abstract

Automatic cell type annotation methods assign cell type labels to new datasets by extracting relationships from a reference RNA-seq dataset. However, due to the limited resolution of gene expression features, there is always uncertainty present in the label assignment. To enhance the reliability and robustness of annotation, most machine learning methods address this uncertainty by providing a full reject option, i.e. when the predicted confidence score of a cell type label falls below a user-defined threshold, no label is assigned and no prediction is made. As a better alternative, some methods deploy hierarchical models and consider a so-called partial rejection by returning internal nodes of the hierarchy as label assignment. However, because a detailed experimental analysis of various rejection approaches is missing in the literature, there is no consensus on best practices, superiority of certain methods, and potential drawbacks associated with rejection. We evaluate three annotation approaches (1) full rejection (2) partial rejection and (3) no rejection for both flat and hierarchical probabilistic classifiers. Our findings indicate that hierarchical classifiers are superior when rejection is applied, with partial rejection being the preferred rejection approach, as it preserves a significant amount of label information. For optimal rejection implementation, the rejection threshold should be determined through careful examination of a method’s rejection behavior. Without rejection, flat and hierarchical annotation perform equally well, as long as the cell type hierarchy accurately captures transcriptomic relationships.