bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture and related therapies for carpal tunnel syndrome
Authors: Bian Zhiyuan , Yu Jie , Tu Mingqi , Liao Binjun , Huang Jingmei , Jiang Yongliang , Fang Jianqiao
Published: December 2021

Background:

Carpal tunnel syndrome (CTS) is the most common peripheral nerve compression syndrome of the upper limb. Plenty of studies showed the effects of acupuncture therapy on relieving pain and improving functional status for CTS patients. Diverse types of acupuncture therapies have been used in the treatment for CTS, but their relative treatment effects are poorly understood. This study will evaluate the effects of different acupuncture and related therapies for CTS by conducting a systematic review and Bayesian network meta-analysis (NMA).

Methods:

We will search randomized controlled trials (RCTs) of acupuncture and related therapies for CTS in MEDLINE (via PubMed), EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Chinese Clinical Trial Register, and OpenGrey from inception to November 2021. Then, we will select eligible studies, extract data, and conduct risk of bias assessment using the Cochrane tool. Pairwise meta-analysis and Bayesian NMA will be performed in Stata 15.1 software and Aggregate Data Drug Information System 1.16.8 software. We will assess the quality of the evidence using the Confidence in Network Meta-Analysis application.

Results:

In this study, the treatment effects and safety of different acupuncture and related therapies for CTS will be evaluated.

Conclusion:

This study will provide evidence for choosing the optimal acupuncture and related therapies in the treatment for CTS.
Efficacy of acupuncture for melasma
Authors: Tang Liheng , Xian Jin , Zhang Ye , Zhang Changyun , Yu Huijuan , Tan Qiwen , Zhang Xin
Published: December 2021

Background:

Melasma is a common acquired hyperpigmentation of the skin. The clinical manifestations are light brown or dark brown patches symmetrically distributed on the cheeks, forehead, and mandibular with different shades and unclear borders. The treatment of melasma is extremely challenging due to its easy relapse and hard to cure. As a classical method of traditional Chinese medicine, acupuncture has been used to treat melasma in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on melasma. This study aims to assess the efficacy of acupuncture for melasma.

Methods:

We will perform a comprehensive retrieval in the following electronic databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, VIP database, Chinese Biomedical Literature Service System (SinoMed), Chinese Biomedicine (CBM) database, and TCM Literature Analysis from inception to July 1, 2021, to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, and exclude cohort studies and case reports. The meta-analyses will be conducted by using the Stata16. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. The X2andI2tests will be utilized to assess the statistical heterogeneity of evidence. We will conduct a meta-analysis if the studies can be combined. Otherwise, a narrative synthesis will be performed. Article screening and data extraction will be independently evaluated by 2 reviewers trained in methodology according to the established selection criteria. Any disagreements between the 2 reviewers will be resolved by reaching a consensus with the other authors (the third reviewer).

Results:

This study will systematically evaluate the clinical efficacy of acupuncture for melasma.

Conclusion:

The conclusion of this study will provide evidence to ensure the efficacy of acupuncture for melasma, so as to provide an objective and scientific basis for clinical practice.

Ethics and dissemination:

No ethical approval will be required because the data used are not linked to individual patient. The results of this review will be published in a peer-reviewed journal.

Registration number:

INPLASY2021110097.
The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis
Authors: Ayón-Pérez Miriam Fabiola , Topete-Córdoba Jonathan Joseph , Agraz-Cibrián Juan Manuel , Ortiz-Martínez Liliana , Durán-Avelar Ma. de Jesús , Vázquez-Reyes Alejandro , Vibanco-Pérez Norberto , Gutiérrez-Franco Jorge , Zambrano-Zaragoza José Francisco
Published: December 2021

Rheumatoid arthritis (RA) is an autoimmune disease characterized by an inflammatory process that affects mainly synovial tissue in joints, and by the production of cyclic citrullinated peptides (anti-CCP) antibodies. In the inflammatory process the regulation of the nuclear factor kappa B (NFkB) transcription factor activation is a key point in the production of inflammatory cytokines. On the other hand, polymorphisms in several genes could contribute to the promotion of the inflammatory process observed in RA, and the association of the rs28362491 polymorphism in the NFkB gene with RA has been studied in different population. Therefore, it could be one of the interest targets to analyze their association with RA in a Mexican population.

This is a case-control study to determine the influence of rs28362491 in the NFkB gene on RA and on clinical features of this disease, such as anti-CCP antibody levels, Disease Activity Score, and Health Assessment Questionnaire-Disability Index.

The genotype of rs28362491 in the NFkB gene was determined in 140 RA patients and 135 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method with the enzyme PflMI. The following clinical variables were also determined: anti-CCP levels, Disease Activity Score, and Spanish version of the Health Assessment Questionnaire Disability-Index.

Although no association of the polymorphism as a risk/protection factor with RA was found, the RA patients who carried the Ins/Ins genotype showed higher anti-CCP levels, while those with the Del/Del genotype showed higher Spanish version of the Health Assessment Questionnaire-Disability Index levels, compared to the other genotypes.

The NFkB -94 Ins/Del ATTG (rs28362491) polymorphism is, therefore, associated with higher levels of anti-CCP antibodies, though no significant association as a risk or protection factor in RA cases was identified.
Beneficial effects of Aloe ferox on lipid profile, blood pressure, and glycemic control in obese persons
Authors: Gherbon Adriana , Frandes Mirela , Timar Romulus , Nicula Marioara
Published: December 2021

Background:

Aloe ferox is one of the most widely used medicinal plants today, with the most intense detoxifying action of all aloe species, being used in the treatment of various diseases, including obesity. Our study aimed to assess the efficacy of Aloe ferox in obesity treatment.

Methods:

The study sample included 20 Romanian persons with obesity treated with diet and Aloe ferox based supplements, and 20 Romanian matched controls treated with diet and a placebo. The treatment included 2 capsules/day (Aloe ferox 460 mg) for 2 weeks, followed by a 2-week break, repeated 3 times. The blood pressure (systolic and diastolic) and anthropometric parameters, such as body mass index (BMI), total cholesterol, and abdominal circumference, as well as the biochemical parameters, fasting blood glucose (FBG), uric acid, and lipid profile was evaluated at baseline and after 3 months.

Results:

After 3 months of Aloe ferox administration, significant differences between the study group and the control group were observed regarding BMI (P = .03), total cholesterol (P = .032), low-density lipoprotein cholesterol (LDLc) (P = .01) and FBG (P = .018). Also, between the initial clinical, anthropometric, and biological parameters and those after the administration of Aloe ferox in the study group, we obtained significant differences regarding BMI (P = .002), LDLc (P = .039), fasting glycemia (P < .001) and diastolic blood pressure (P = .006).

Conclusions:

The administration of Aloe ferox to obese patients has been shown to achieve a significant reduction in body weight, BMI, LDLc, and FBG. These effects may be due to the laxative and detoxifying action of Aloe ferox components. As it can only be administered for limited periods due to side effects, further experimental and human studies of the efficacy of this plant in the treatment of obesity are needed.
Spectrum of mycobacterial pathogens responsible for head and neck tuberculosis-like presentation
Authors: Bala Kiran , Kumari Sanjana , Monga Rabia , Sagar Prem , Thakar Alok , Sharma S. C. , Singh Urvashi B.
Published: December 2021

Tuberculosis (TB) of the head and neck can be contained in the lymph nodes, larynx, oropharynx, salivary glands, nose and paranasal sinuses, ear, skin and skull. Head and neck TB presentations are varied in nature and thus difficult to diagnose. The clinical features, radiological findings, microbiological diagnostic modalities, surgical and medical management and outcomes of nine cases of head and neck TB are discussed in detail here, together with a thorough review of the literature. Patients presented with atypical symptoms such as discharging sinus, ear lobule swelling, otitis media, vision loss and facial weakness, long refractory otorrhoea and granulation tissue in the ear canal. We diagnosed tubercular skull base osteomyelitis (one case) and laryngeal tuberculosis (two cases), mastoid tuberculosis (one case) and non-tubercular mycobacterial infection involving the temporal bone (two cases), sino-nasal region (one case), maxilla (one cases) and ear lobule (one case) over a period of 8 months. All patients were managed successfully with a combination of surgery and a well-planned treatment regimen for non-tuberculous mycobacteria (NTM) or anti-tubercular drugs for TB. All had successful outcomes except one patient with tubercular skull base osteomyelitis who expired before the initiation of anti-tubercular therapy (ATT). High clinical suspicion followed by thorough diagnostic work-up for both TB and NTM would enable early diagnosis and complete treatment.
Genotypic and phenotypic portrait of Candida albicans clinical isolates colonizing the airways of patients with cystic fibrosis
Authors: Gnaien Mayssa , Kallel Aicha , Khalsi Fatma , Hamouda Samia , Smaoui Hanen , Khemiri Monia , Hadj Fredj Sondes , Messaoud Taieb , Boussetta Khadija , Kallel Kalthoum , d'Enfert Christophe , Bougnoux Marie-Elisabeth , Mardassi Helmi , Znaidi Sadri
Published: December 2021

Candida albicans colonizes the respiratory tract of patients with Cystic Fibrosis (CF). It competes with CF-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and contributes to disease severity. We serially recovered 160 C. albicans clinical isolates over a period of 30 months from the sputum of 23 pediatric and 2 adult antifungal-naive CF patients at Children’s Hospital Tunis and characterized the genotype and phenotype of a subset of strains using multilocus sequence typing (MLST) and growth assays on multiple stress-, filamentous growth- and biofilm-inducing media. Out of 16 patients regularly sampled for at least 9 months, 8 and 4 were chronically and transiently colonized with C. albicans, respectively. MLST analyses of 56 strains originating from 15 patients indicated that each patient was colonized with a single strain, while 8 patients (53%) carried isolates from clade 4 known to be enriched with strains from Middle East-Africa. A subset of these isolates with the same sequence type and colonizing 3 unrelated patients displayed altered susceptibility to cell wall-perturbing agents, suggesting changes in cell wall structure/function during growth in the CF lung. We also observed differential ability to filament and/or form biofilms in a set of identical isolates from clade 10 sampled over a period of 9 months in a pediatric CF patient, suggesting alterations in phenotypes associated with virulence. Our findings will rely on future whole-genome sequencing analyses to identify polymorphisms that could explain the emergence of new traits in C. albicans strains thriving in the CF host environment.
The impact of lemongrass, oregano, and thyme essential oils on Candida albicans’ virulence factors
Authors: Eddins Jennifer
Published: December 2021

Increased systemic infections and growing resistance of Candida species in immunosuppressed people have prompted research for additional treatment options. The purpose of this study was to investigate the potential of lemongrass, oregano, and thyme essential oils tested individually, combined, and combined with the antifungal agents fluconazole and caspofungin to kill Candida albicans isolates in a controlled laboratory setting. A quantitative design was used to analyze the experimental data collected and investigate risk factors related to age, gender, race, and co-morbidities. Kill rates of lemongrass, oregano, and thyme essential oils individually and combined, kill rates of fluconazole, caspofungin, and the kill rates when the antifungals were each combined with the three essential oils were compared using 117 isolates recovered from bloodstream infections between January 2009 through August 1, 2017. There were statistically significant increases in kill rates when the isolates were exposed to any of the combinations of essential oils tested. Data on the covariates age, gender, race, and co-morbidities were assessed for risk factors related to Candida albicans bloodstream infections. The age group 25-34, kidney failure, and solid organ tumor cancer, were all statistically significantly associated with an increased risk for Candida albicans bloodstream infections and multiple organ failure was negatively associated with the risk. Through the use of essential oils, the ability to reduce the number of patients becoming infected with life-threatening yeast infections could not only reduce mortality but also reduce the costs associated with serious infections.
Extending the proteomic characterization of Candida albicans exposed to stress and apoptotic inducers through data-independent acquisition mass espectrometry
Authors: Amador-García Ahinara , Malmström Johan , Monteoliva Lucia , Gil Concha
Published: December 2021

Candida albicans is a commensal fungus that causes systemic infections in immunosuppressed patients. In order to deal with the changing environment during commensalism or infection, C. albicans must reprogram its proteome. Characterizing the stress-induced changes in the proteome that C. albicans uses to survive should be very useful in the development of new antifungal drugs. We studied the C. albicans global proteome after exposure to hydrogen peroxide (H2O2) and acetic acid (AA), using a DIA-MS strategy. More than 2000 C. albicans proteins were quantified using an ion library previously constructed using DDA-MS. C. albicans responded to treatment with H2O2 with an increase in the abundance of many proteins involved in the oxidative stress response, protein folding and proteasome-dependent catabolism, which led to an increased proteasome activity. The data revealed a previously unknown key role for Prn1, a protein similar to pirins, in the oxidative stress response. Treatment with AA resulted in a general decrease in the abundance of proteins involved in amino acid biosynthesis, protein folding, and rRNA processing. Almost all proteasome proteins declined, as did proteasome activity. Apoptosis was observed after treatment with H2O2, but not AA. A targeted proteomic study of 32 proteins related to apoptosis in yeast supported the results found by DIA-MS and allowed the creation of an efficient method to quantify relevant proteins after treatment with stressors (H2O2, AA, and amphotericin B). This approach also uncovered a main role for Oye32, an oxidoreductase, suggesting this protein as a possible apoptotic marker common to many stressors.
Molecular epidemiology of Candida auris in Qatar using whole genome sequence data
Authors: Salah Husam , Sundararaju Sathyavathi , Dalil Lamya , Tang Patrick , Al-Wali Walid , Ben Abid Fatma , Tsui Kin-Ming (Clement)
Published: December 2021

Candida auris is an emerging, multidrug resistant fungal pathogen that has become a public health threat worldwide. Candida auris spreads easily among patients within and between hospitals, and the incidence of infections has increased substantially in the last decade. Multiple C. auris outbreaks have been reported worldwide including India, USA and United Kingdom. Infections and outbreaks caused by C. auris have also been reported in the Middle East region including Kuwait, Oman, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. This study uses whole genome sequencing (WGS) data to determine the epidemiology and the drug resistance mutations from C. auris in Qatar. Forty samples isolated from the patients and the hospital environment were sequenced by Illumina Nextseq. Core genome SNPs revealed that all isolates belonged to the Indian lineage, which could be originated from the expatriate labour from South Asia. The genetic variability among the isolates was low but comprised of more than one genetic cluster. The environmental isolates were identical to the clinical isolates, and the isolates from patients of different hospitals/outbreaks clustered together, suggesting the transmission of C. auris could be linked to infected/colonized patients and the hospital environment. Mutations associated with azole and echinocandin resistance were discussed.
Investigation of the zinc uptake system of the human fungal pathogen Candida parapsilosis
Authors: Takács Tamás , Mihály Németh Tibor , Szilovics Zóra , Vágvölgyi Csaba , Wilson Duncan , Gácser Attila
Published: December 2021

Candida parapsilosis is the second or third most commonly isolated Candida species from blood cultures and is frequently associated with infections in neonatal intensive care units. Candida species have several virulence factors enabling them to adapt to host environmental conditions and cause infections. These factors include adhesion, biofilm formation, and secretion of hydrolytic enzymes, such as acidic proteinases and lipases. Candida species also obtain heavy metal ions from their environment, such as zinc. Zinc is a cofactor of several proteins and a vital element in cellular mechanisms of the fungi. On the one hand, the host niche represents a zinc-limited environment, that indirectly inhibits microbial growth. In order to survive in such an environment, these pathogens have evolved a zinc transport system that allows them to access bound zinc ions during infection. On the other hand, high zinc ion concentration within the host can also be toxic to microbes e.g. in the phagosomes of Mycobacterium tuberculosis infected macrophages. In case of C. albicans, zinc acquisition processes are intensively studied, but we lack information of the zinc uptake, transfer and homeostasis mechanisms in C. parapsilosis. Here, predicted potential zinc transporters in C. parapsilosis using in silico analyses, generated homozygous knock out mutants and performed their phenotypical characterization by exposing them to various types of stressors and zinc limiting conditions. Furthermore, we analyzed their virulence traits by examining kinetics of fungal cell uptake by macrophages, their killing efficiency and also investigated zinc ion levels in the phagolysosome during in vitro infections
Conducting genetic interaction analysis with CRISPR-Cas9-based strategies in Candida albicans
Authors: Halder Viola , McDonnell Brianna , Shapiro Rebecca
Published: December 2021

Candida albicans is an opportunistic fungal pathogen found in the oral mucosa, the gut, the vaginal mucosa, and humans' skin. While C. albicans can cause superficial infections, severe invasive infections can occur in immunocompromised individuals. Understanding the survival mechanisms and pathogenesis of C. albicans is critical for novel antifungal drug discovery. Determining the relationships between different genes can create a genetic interaction map, which can identify complementary gene sets, central to C. albicans survival, as potential drug targets in combination therapy. A genetic approach using the CRISPR-Cas9-based genome editing platform will focus on genetic interaction analysis of C. albicans stress response genes. The ultimate goal is to create a stress response gene deletion library to study its pathogen survival role. This library of single and double stress response gene mutants will be screened under diverse growth conditions to assess their relative fitness. Genetic interaction analysis will help map out epistatic interactions between fungal genes involved in growth, survival, and pathogenesis and uncover putative targets for combination antifungal therapy based on negative or synthetic lethal genetic interactions.
Identifying Uncertainty States during Wayfinding in Indoor Environments: An EEG Classification Study
Authors: Zhu Bingzhao , Cruz-Garza Jesus G. , Shoaran Mahsa , Kalantari Saleh
Published: December 2021

The researchers used a machine-learning classification approach to better understand neurological features associated with periods of wayfinding uncertainty. The participants (n=30) were asked to complete wayfinding tasks of varying difficulty in a virtual reality (VR) hospital environment. Time segments when participants experienced navigational uncertainty were first identified using a combination of objective measurements (frequency of inputs into the VR controller) and behavioral annotations from two independent observers. Uncertainty time-segments during navigation were ranked on a scale from 1 (low) to 5 (high). The machine-learning model, a random forest classifier implemented using scikit-learn in Python, was used to evaluate common spatial patterns of EEG spectral power across the theta, alpha, and beta bands associated with the researcher-identified uncertainty states. The overall predictive power of the resulting model was 0.70 in terms of the area under the Receiver Operating Characteristics curve (ROC-AUC). These findings indicate that EEG data can potentially be used as a metric for identifying navigational uncertainty states, which may provide greater rigor and efficiency in studies of human responses to architectural design variables and wayfinding cues.
Establishing Normative Reference Values for the Utah Seated Medicine Ball Throw Protocol in Adolescents
Authors: Biggar Cory , Larson Abigail , DeBeliso Mark
Published: December 2021

The seated medicine ball throw (SMBT) is a field test intended to assess upper-body muscular power by measuring the maximal distance an individual can throw a medicine ball from an isolated, seated position (25). The SMBT has been used to assess upper-body power in various populations and to establish concurrent validity for other measures of upper-body power such as the bench press power test and the plyometric push-up. The SMBT is less costly and simpler to incorporate into a field test battery than other upper body power assessments. While the SMBT is a valid, reliable field test for upper-body power, normative reference standards for most populations, including adolescent (12-15 years old) physical education students, do not exist.

Purpose

This study reports distances thrown in the SMBT to establish normative reference values in male and female physical education students, ages 12-15 years old.

Methods

One hundred thirteen untrained male and female physical education students aged 12-15 years performed the SMBT field test three times on a single testing day. Participants threw a 2kg medicine ball with a 19.5 cm diameter while seated at a 90° after recording height, body mass, and BMI.

Results

Participant data was separated by age gender for analysis. Mean and standard deviation for the SMBT for males was 4.3±0.7m and 5.2±0.8 m for ages 12-13 and 14-15, respectively, and for females was 3.4±0.5m and 3.7±0.5m for ages 12-13 and 14-15, respectively. Pearson correlation coefficients for between-trials comparisons for males and females ranged from r=0.85-0.97. Pearson correlation coefficients for average SMBT and age of participants was r=0.93. Normative reference values as percentile ranks for the SMBT scores for age groups 12-13 and 14-15 among males and females, respectively, were also established.

Conclusion

The data presented provides an initial set of normative reference standards for coaches and students to determine upper-body muscular power using the SMBT.
Flv3A facilitates O2 photoreduction and affects H2 photoproduction independently of Flv1A in diazotrophic Anabaena filaments
Authors: Santana-Sánchez A. , Nikkanen L. , Toth G. , Ermakova M. , Kosourov S. , Walter J. , He M. , Aro E-M. , Allahverdiyeva Y.
Published: December 2021

The model heterocyst-forming filamentous cyanobacterium, Anabaena sp. PCC 7120 (Anabaena) represents multicellular organisms capable of simultaneously performing oxygenic photosynthesis in vegetative cells and the O2-sensitive N2-fixation inside the heterocysts. The flavodiiron proteins (FDPs) have been shown to participate in photoprotection of photosynthesis by driving excess electrons to O2 (Mehler-like reaction). Here, we addressed the physiological relevance of the vegetative cell-specific Flv1A and Flv3A on the bioenergetic processes occurring in diazotrophic Anabaena under variable CO2. We demonstrate that both Flv1A and Flv3A are required for proper induction of the Mehler-like reaction upon a sudden increase in light intensity, which is likely important for the activation of carbon-concentrating mechanisms (CCM) and CO2 fixation. Under ambient CO2 diazotrophic conditions, Flv3A is capable of mediating moderate O2 photoreduction, independently of Flv1A, but in coordination with Flv2 and Flv4. Strikingly, the lack of Flv3A resulted in strong downregulation of the heterocyst-specific uptake hydrogenase, which led to enhanced H2 photoproduction under both oxic and micro-oxic conditions. These results reveal a novel regulatory network between the Mehler-like reaction and the diazotrophic metabolism, which is of great interest for future biotechnological applications.
Genomic signatures of desert adaptation at gene-rich regions in zebu cattle from the African drylands
Authors: Tijjani Abdulfatai , Salim Bashir , da Silva Marcos Vinicius Barbosa , Eltahir Hamza A. , Musa Taha H. , Marshall Karen , Hanotte Olivier , Musa Hassan H.
Published: December 2021

Sudan, the largest country in Africa, acts as a corridor between North and sub-Saharan Africa along the river Niles. It comprises warm arid and semi-arid grazing lands, and it is home to the second-largest African population of indigenous livestock. Indigenous Sudanese cattle are mainly indicine/zebu (humped) type. They thrive in the harshest dryland environments characterised by high temperatures, long seasonal dry periods, nutritional shortages, and vector diseases challenges. We investigated genome diversity in six indigenous African zebu breeds sampled in Sudan (Aryashai, Baggara, Butana, Fulani, Gash, and Kenana). We adopted three genomic scan approaches to identify candidate selective sweeps regions (ZHp, FST, XP-EHH). We identified a set of gene-rich selective sweep regions shared across African and Asian zebu or unique to Sudanese zebu. In particular, African and Asian zebu candidate gene-rich regions are detected on chromosomes 2, 5 and 7. They include genes involved in immune response, body size and conformation, and stress response to heat. In addition, a 250 kb selective sweep on chromosome 16 was detected exclusively in five Sudanese zebu populations. This region spans seven genes, including PLCH2, PEX10, PRKCZ and SKI, which are involved in alternative adaptive metabolic strategies of insulin signalling, glucose homeostasis, and fat metabolism. Together, these genes may contribute to the zebu cattle resilience to heat, nutritional and water shortages. Our results highlight the putative importance of selection at gene-rich genome regions, which might be under a common regulatory genetic control, as an evolutionary mechanism for rapid adaptation to the complexity of environmental challenges.
Precise quantification of behavioral individuality from 80 million decisions across 183,000 flies
Authors: de Bivort Benjamin , Buchanan Sean , Skutt-Kakaria Kyobi , Gajda Erika , O’Leary Chelsea , Reimers Pablo , Akhund-Zade Jamilla , Senft Rebecca , Maloney Ryan , Ho Sandra , Werkhoven Zach , Smith Matthew A-Y
Published: December 2021

Individual animals behave differently from each other. This variability is a component of personality and arises even when genetics and environment are held constant. Discovering the biological mechanisms underlying behavioral variability depends on efficiently measuring individual behavioral bias, a requirement that is facilitated by automated, high-throughput experiments. We compiled a large data set of individual locomotor behavior measures, acquired from over 183,000 fruit flies walking in Y-shaped mazes. With this data set we first conducted a “computational ethology natural history” study to quantify the distribution of individual behavioral biases with unprecedented precision and examine correlations between behavioral measures with high power. We discovered a slight, but highly significant, left-bias in spontaneous locomotor decision-making. We then used the data to evaluate standing hypotheses about biological mechanisms affecting behavioral variability, specifically: the neuromodulator serotonin and its precursor transporter, heterogametic sex, and temperature. We found a variety of significant effects associated with each of these mechanisms that were behavior-dependent. This indicates that the relationship between biological mechanisms and behavioral variability may be highly context dependent. Going forward, automation of behavioral experiments will likely be essential in teasing out the complex causality of individuality.
Integration of allocentric and egocentric visual information in a convolutional / multilayer perceptron network model of goal-directed gaze shifts
Authors: Khoozani Parisa Abedi , Bharmauria Vishal , Schütz Adrian , Wildes Richard P. , Crawford J. Douglas
Published: December 2021

Allocentric (landmark-centered) and egocentric (eye-centered) visual codes are fundamental for spatial cognition, navigation, and goal-directed movement. Neuroimaging and neurophysiology suggest these codes are segregated initially, but then reintegrated in frontal cortex for movement control. We created and validated a theoretical framework for this process using physiologically constrained inputs and outputs. To implement a general framework, we integrated a Convolutional Neural Network (CNN) of the visual system with a Multilayer Perceptron (MLP) model of the sensorimotor transformation. The network was trained on a task where a landmark shifted relative to the saccade target. These visual parameters were input to the CNN, the CNN output and initial gaze position to the MLP, and a decoder transformed MLP output into saccade vectors. Decoded saccade output replicated idealized training sets with various allocentric weightings, and actual monkey data where the landmark shift had a partial influence (R2= 0.8). Furthermore, MLP output units accurately simulated prefrontal response field shifts recorded from monkeys during the same paradigm. In summary, our model replicated both the general properties of the visuomotor transformations for gaze and specific experimental results obtained during allocentric-egocentric integration, suggesting it can provide a general framework for understanding these and other complex visuomotor behaviors.
Poor prognosis of stage I lung adenocarcinoma patients determined by elevated expression over pre/minimally invasive status of COL11A1 and THBS2 in the focal adhesion pathway
Authors: Shang Jun , Zhao Yue , Jiang He , Yang Jingcheng , Zhang Naixin , Ren Luyao , Chen Qingwang , Yu Ying , Shi Leming , Chen Haiquan , Zheng Yuanting
Published: December 2021

Around 20% of stage I lung adenocarcinoma (LUAD) patients die within five years after surgery, and efforts for developing gene-expression based models for risk-tailored post-surgery treatment are largely unsatisfactory due to overfitting-related lack of validation and extrapolation. Because patients with adenocarcinomas in situ (AIS) and minimally invasive (MIA) LUAD are completely curable by surgical resection, we hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. We first found focal adhesion (FA) as the only pathway significantly perturbed at both genomic and transcriptomic levels by comparing 98 AIS/MIA and 99 invasive LUAD patients. Then, we identified two FA pathway genes (COL11A1 and THBS2) strongly upregulated from AIS/MIA to stage I while expressed steadily from normal to AIS/MIA. Furthermore, unsupervised clustering separated stage I patients into two molecularly and prognostically distinct subtypes (S1 and S2) based solely on the expression levels of COL11A1 and THBS2 (FA2). Subtype S1 looked like AIS/MIA, whereas S2 exhibited more somatic alterations, elevated expression of COL11A1 and THBS2, and more activated cancer-associated fibroblast (CAF). The prognostic performance of the knowledge-driven and overfitting-resistant FA2 model was validated with 12 external data sets and may help reliably identify high-risk stage I patients for more intensive post-surgery treatment.
The impact of shielding during the COVID-19 pandemic on mental health: Evidence from the English Longitudinal Study of Ageing
Authors: Di Gessa Giorgio , Price Debora
Published: December 2021

Background

During the COVID-19 pandemic, older and clinically vulnerable people were instructed to shield or stay at home to save lives. Policies restricting social contact and human interaction pose a risk to mental health, but we know very little about the impact of shielding and stay at home orders on the mental health of older people.

Aims

Understand the extent to which shielding contributes to poorer mental health.

Method

Exploiting longitudinal data from Wave 9 (2018/19) and two COVID-19 sub-studies (June/July 2020; November/December 2020) of the English Longitudinal Study of Ageing we use logistic and linear regression models to investigate associations between patterns of shielding during the pandemic and mental health, controlling for socio-demographic characteristics, pre-pandemic physical and mental health, and social isolation measures.

Results

By December 2020, 70% of older people were still shielding or staying at home, with 5% shielding throughout the first 9 months of the pandemic. Respondents who shielded experienced worse mental health. Although prior characteristics and lack of social interactions explain some of this association, even controlling for all covariates, those shielding throughout had higher odds of reporting elevated depressive symptoms (OR=1.87, 95%CI=1.22;2.87) and reported lower quality of life (B=-1.28, 95%CI=-2.04;-0.52) than those who neither shielded nor stayed at home. Shielding was also associated with increased anxiety.

Conclusions

Shielding itself seems associated with worse mental health among older people, highlighting the need for policymakers to address the mental health needs of those who shielded, both in emerging from the current pandemic and for the future.
Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo
Authors: Zalghout Sara , Vo Sophie , Arocas Véronique , Jadoui Soumaya , Hamade Eva , Badran Bassam , Oudar Olivier , Charnaux Nathalie , Boulaftali Yacine , Bouton Marie-Christine , Richard Benjamin
Published: December 2021

Glycosaminoglycans (GAGs) pooling has been considered since long as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, few information is provided about GAGs composition or potential implication in TAA pathology. Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype and various aspects of inflammation in the vascular wall. In the current work, the regulation of Sdc-1 protein was examined in human TAA by ELISA and immunohistochemistry. In addition, the role of Sdc-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that Sdc-1 protein is over expressed in human TAA aortas compared to healthy counterparts and that SMCs are the major cell type expressing Sdc-1. Similarly, in the mouse model used, Sdc-1 expression was increased in TAA aortas compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that Sdc-1 was dispensable for TAA prevalence or rupture. In addition, Sdc-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that Sdc-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to Sdc-1 expression alteration in TAA.
The effects of locomotion on sensory-evoked haemodynamic responses in the cortex of awake mice
Authors: Eyre Beth , Shaw Kira , Sharp Paul , Boorman Luke , Lee Llywelyn , Shabir Osman , Berwick Jason , Howarth Clare
Published: December 2021

Investigating neurovascular coupling in awake rodents is becoming ever more popular due, in part, to our increasing knowledge of the profound impacts that anaesthesia can have upon brain physiology. Although awake imaging brings with it many advantages, we still do not fully understand how voluntary locomotion during imaging affects sensory-evoked haemodynamic responses. In this study we investigated how evoked haemodynamic responses can be affected by the amount and timing of locomotion. Using an awake imaging set up, we used 2D-Optical Imaging Spectroscopy (2D-OIS) to measure changes in cerebral haemodynamics within the sensory cortex of the brain during either 2s whisker stimulation or spontaneous (no whisker stimulation) experiments, whilst animals could walk on a spherical treadmill. We show that locomotion alters haemodynamic responses. The amount and timing of locomotion relative to whisker stimulation is important, and can significantly impact sensory-evoked haemodynamic responses. If locomotion occurred before or during whisker stimulation, the amplitude of the stimulus-evoked haemodynamic response was significantly altered. Therefore, monitoring of locomotion during awake imaging is necessary to ensure that conclusions based on comparisons of evoked haemodynamic responses (e.g., between control and disease groups) are not confounded by the effects of locomotion.
Different armpits under my new nose: olfactory sex but not gender affects implicit measures of embodiment
Authors: Roel Lesur Marte , Stussi Yoann , Bertrand Philippe , Delplanque Sylvain , Lenggenhager Bigna
Published: December 2021

Research has shown that conflicting multisensory signals may alter embodiment to the point of self-identifying with a foreign body, but the role of olfaction in this process has been overlooked. Here, we study in healthy participants how sex (male and female sweat odors) and gender (male and female cosmetic scents) olfactory stimuli contribute to embodiment. Participants saw from the perspective of a sex mismatching person in virtual reality and received synchronous visuo-tactile stimulation to elicit illusory embodiment of the seen body while smelling either sex- or gender-congruent stimuli. We assessed implicit (skin conductance responses to visual threats) and explicit (questionnaire) measures of embodiment. Stronger responses to threat were found when participants smelled the sex-congruent compared to the sex-incongruent odor, while no such differences were found for the cosmetic scents. According to the questionnaire, embodiment did not differ between conditions. Post-experimental assessment of the presented cues, suggest that while both sweat odors were considered generally male, cosmetic scents were not. The presented scents were generally not associated to the embodied body. Our results suggest that sex-related body odors influence implicit but not explicit aspects of embodiment and are in line with unique characteristics of olfaction in other aspects of cognition.
Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior
Authors: Kelly Kevin P. , Alassaf Mroj , Sullivan Camille E. , Brent Ava E. , Goldberg Zachary H. , Poling Michelle E. , Dubrulle Julien , Rajan Akhila
Published: December 2021

Diet-induced obesity (DIO) leads to dysfunctional feeding behavior. However, the precise molecular nodes underlying diet-induced dysregulation of satiety sensing and feeding motivation are poorly understood. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation to mammalian nutrient sensing and energy balance. Using a longitudinal high sugar regime in Drosophila, we sought to address how lipid alteration in fat cells alters feeding behavior. We find that prolonged exposure to HSD degrades the hunger-driven feeding (HDF) response. Lipidomics analysis reveals that longitudinal exposure to HSD significantly alters whole body phospholipid profiles. By performing a systematic screen for phospholipid enzymes, we identify Pect as a critical regulator of hunger-driven feeding. Pect is a rate-limiting enzyme in the phosphatidylethanolamine (PE) biosynthesis pathway and the fly ortholog of human PCYT2. We show that disrupting Pect only in the fat body causes insulin-resistant phenotypes and a loss of hunger-driven feeding. Excitingly, we find that overexpression of Pect restores HSD-induced loss of hunger-driven feeding response. Strikingly human studies have noted a correlation between PCYT2/Pect levels and clinical obesity. Now, our unbiased studies in Drosophila provide specific genetic evidence for Pect in maintaining nutrient sensing during DIO. Our study provides novel insights into the role of phospholipids in interorgan communication of nutrient status.
Replication origins drive genetic and phenotypic variation in humans
Authors: Murat Pierre , Guilbaud Guillaume , Sale Julian E.
Published: December 2021

DNA replication starts with the activation of the replicative helicases, polymerases and associated factors at thousands of origins per S-phase 1. Due to local torsional constraints generated during licensing 2 and the switch between polymerases of distinct fidelity and proofreading ability following firing 3,4, origin activation has the potential to induce DNA damage and mutagenesis. However, whether sites of replication initiation exhibit a specific mutational footprint has not yet been established. Here we demonstrate that mutagenesis is increased at early and highly efficient origins. The elevated mutation rate observed at these sites is caused by two distinct mutational processes consistent with formation of DNA breaks at the origin itself and local error-prone DNA synthesis in the immediate vicinity of the origin. We demonstrate that these replication-dependent mutational processes create the skew in base composition observed at human replication origins. Further, we show that mutagenesis associated with replication initiation exerts an influence on phenotypic diversity in human populations disproportionate to the origins’ genomic footprint: by increasing mutational loads at gene promoters and splice junctions the presence of an origin influences both gene expression and mRNA isoform usage. These findings have important implications for our understanding of the mutational processes that sculpt the human genome.
Human TLR4 and noncanonical inflammasome differ in their ability to respond to distinct lipid A variants
Authors: Alexander-Floyd Jasmine , Bass Antonia R. , Harberts Erin M. , Grubaugh Daniel , Buxbaum Joseph D. , Brodsky Igor E. , Ernst Robert K. , Shin Sunny
Published: December 2021

Detection of Gram-negative bacterial lipid A by the extracellular sensor, MD-2/TLR4 or the intracellular inflammasome sensors, CASP4 and CASP5, induces robust inflammatory responses. The chemical structure of lipid A, specifically the phosphorylation and acylation state, varies across and within bacterial species, potentially allowing pathogens to evade or suppress host immunity. Currently, it is not clear how distinct alterations in the phosphorylation or acylation state of lipid A affect both human TLR4 and CASP4/5 activation. Using a panel of engineered lipooligosaccharides (LOS) derived fromYersinia pestiswith defined lipid A structures that vary in their acylation or phosphorylation state, we identified that differences in phosphorylation state did not affect TLR4 or CASP4/5 activation. However, the acylation state differentially impacted TLR4 and CASP4/5 activation. Specifically, all of the examined tetra-, penta-, and hexa-acylated LOS variants activated CASP4/5-dependent responses, whereas TLR4 responded to penta- and hexa-acylated LOS but did not respond to tetra-acylated LOS or pentaacylated LOS lacking the secondary acyl chain at the 3’ position. As expected, lipid A alone was sufficient for TLR4 activation; however, human macrophages required both lipid A and the core oligosaccharide to mount a robust CASP4/5 inflammasome response. Our findings show that human TLR4 and CASP4/5 detect both shared and non-overlapping LOS/lipid A structures, which enables the innate immune system to recognize a wider range of bacterial LOS/lipid A, thereby constraining the ability of pathogens to evade innate immune detection.
The costs and benefits of dispersal in small populations
Authors: Polechová Jitka
Published: December 2021

Abstract

Dispersal has three major effects on adaptation. First, gene flow mixes alleles adapted to different environments, potentially hindering (swamping) adaptation. Second, it brings in other variants and inflates genetic variance: this aids adaptation to spatially (and temporally) varying environments but if selection is hard, it lowers the mean fitness of the population. Third, neighbourhood size, which determines how weak genetic drift is, increases with dispersal – when genetic drift is strong, increase of the neighbourhood size with dispersal aids adaptation. In this note I focus on the role of dispersal in environments which change gradually across space, and when local populations are quite small such that genetic drift has a significant effect. Using individual-based simulations, I show that in small populations, even leptokurtic dispersal benefits adaptation, by reducing the power of genetic drift. This has implications for management of fragmented or marginal populations: the beneficial effect of increased dispersal into small populations is stronger than swamping of adaption under a broad range of conditions, including a mixture of local and long-distance dispersal. However, when environmental gradient is steep, heavily fat-tailed dispersal will swamp continuous adaptation so that only patches of locally adapted subpopulations remain.