bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Platelet Agonists and Priming on the Formation of Platelet Populations
Authors: Veninga Alicia , Baaten Constance C. F. M. J. , De Simone Ilaria , Tullemans Bibian M. E. , Kuijpers Marijke J. E. , Heemskerk Johan W. M. , van der Meijden Paola E. J.
Published: October 2021

Platelets from healthy donors display heterogeneity in responsiveness to agonists. The response thresholds of platelets are controlled by multiple bioactive molecules, acting as negatively or positively priming substances. Higher circulating levels of priming substances adenosine and succinate, as well as the occurrence of hypercoagulability, have been described for patients with ischaemic heart disease. Here, we present an improved methodology of flow cytometric analyses of platelet activation and the characterisation of platelet populations following activation and priming by automated clustering analysis.

Platelets were treated with adenosine, succinate, or coagulated plasma before stimulation with CRP-XL, 2-MeSADP, or TRAP6 and labelled for activated integrin αIIbβ3 (PAC1), CD62P, TLT1, CD63, and GPIX. The Super-Enhanced Dmax subtraction algorithm and 2% marker (quadrant) setting were applied to identify populations, which were further defined by state-of-the-art clustering techniques (tSNE, FlowSOM).

Following activation, five platelet populations were identified: resting, aggregating (PAC1 + ), secreting (α- and dense-granules; CD62P + , TLT1 + , CD63 + ), aggregating plus α-granule secreting (PAC1 + , CD62P + , TLT1 + ), and fully active platelet populations. The type of agonist determined the distribution of platelet populations. Adenosine in a dose-dependent way suppressed the fraction of fully activated platelets (TRAP6 > 2-MeSADP > CRP-XL), whereas succinate and coagulated plasma increased this fraction (CRP-XL > TRAP6 > 2-MeSADP). Interestingly, a subset of platelets showed a constant response (aggregating, secreting, or aggregating plus α-granule secreting), which was hardly affected by the stimulus strength or priming substances.
Occurrence and Morphology of MB2 Canals in Maxillary First Molars in an Indian Subpopulation: A Cone Beam Computed Tomography Study
Authors: Shetty Aditya , Bhat Raksha , Babu Bessy , Hegde Mithra N. , Shetty Chitharanjan , Shetty Preethesh , Latha Senthilkumar Priyanka
Published: October 2021

Introduction Molars have been known to display varied morphologies. Maxillary first molar is the tooth with the largest volume and most complex root and root canal anatomy; also, possibly the most treated and least understood posterior tooth. The present study aimed to investigate the occurrence and morphology of MB2 canals in maxillary first molars in an Indian subpopulation (Dakshina kannada) using cone beam CT (CBCT) imaging.

Materials and Methods A total of 330 maxillary molars were placed on “U-” shaped modelling wax template, mimicking the natural arch and digitally scanned, of which 196 scans met the inclusion criteria and were analyzed for unusual root canal anatomy by CBCT. To analyze the occurrence and morphology of the canals, the acquired data was examined by two endodontists and discussed till an agreement was reached.

Results The results were subjected to descriptive analysis. The majority of patients 103 (52.6%) teeth showed the presence of MB2 canals. As much as 83.5% of teeth depicted Vertucci's type II morphology, and 16.5% teeth presented with Vertucci's type IV morphology.

Conclusion CBCT overcomes the limitations of conventional radiography. However, the decision to use CBCT in the management of endodontic problems must be based on a case-by-case basis and only when sufficient diagnostic information is not obtained from diagnostic tests.
Effect of Radiofrequency Waves of Mobile Phones on Distortion Product Otoacoustic Emissions
Authors: Nayak Swetapadma , Aroor Rajeshwary , Shastri Usha , Goutham M. K. , Sinha Devika
Published: October 2021

Objective The prolonged exposure to electromagnetic fields of mobile phones can damage the cochlear hair cells, which can be detected by otoacoustic emission (OAE). To know the effect of mobile phones on hearing, the young volunteers were subjected to prolonged mobile phone usage and changes in OAE were recorded.

Materials and Methods Twenty-eight volunteers with normal hearing were made to talk one full hour continuously on the mobile phone. Distortion product otoacoustic emission (DPOAE) was measured prior to the usage of mobile phones and immediately after the use (post-exposure 1) and 24 hours after the use (post-exposure 2). The values were compared.

Results Out of the 28 volunteers, 20 were females and 8 were males. Twenty-one volunteers preferred the right ear while using mobile phones, 7 preferred the left ear. There was no statistically significant difference between the baseline DPOAE values and values of post-exposure 1 and 2 when only the preferred ear was taken into consideration. When the preferred ear was compared with nonpreferred ear, a statistically significant difference was found only in the low frequencies between the pre-exposure and post-exposure 1 values.

Conclusion This study shows there was no significant correlation between OAE and prolonged mobile phone exposure when the preferred ear was not considered.
Health care professionals and care staff challenges and experiences of managing sexual expression among older adults ≥60 years in long-term care facilities: a qualitative review and meta-synthesis
Authors: Ho Pei Juan , Goh Yong Shian
Published: October 2021

Long-term care (LTC) facilities, in which older adults are institutionalised, have the responsibility to address their residents’ rights, privacy and comfort in expressing themselves sexually in an acceptable manner. However, many older adults have reported barriers in their sexual expression, which is often a result of the care staff’s attitudes in the facilities. This review synthesis evidence from qualitative studies on the challenges faced by care staff when supporting sexual expression of older residents in LTC facilities. The systematic review and meta-synthesis is reported according to the Enhanced Transparency in Reporting the Synthesis of Qualitative Research Statement. A systematic literature search for peer-reviewed studies was conducted on PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, PsycINFO, CINAHL and ProQuest Theses and Dissertations from inception until December 2020. Sandelowski and Barroso’s two-step approach was used to synthesise the evidence. Seventeen qualitative studies published between 2004 and 2020 were included. This review encapsulated the experiences and challenges of 4,387 care staff whose age ranged from 18 to 69 years. Through the meta-synthesis, four themes were identified: varying manifestations of sexual expression and situations encountered, a spectrum of care staff’s attitudes, setting boundaries in dementia care and workplace support. Managing sexual expression can be challenging for the care staff, given the complex interplay between personal beliefs, social contexts, moral dilemmas, practical barriers and the lack of clear policies. This review highlighted the need to equip them with knowledge, skills and confidence in managing sexuality in LTC facilities.
Prevalence of Discordant Procalcitonin Use at an Academic Medical Center
Authors: Seymann Gregory B , Bevins Nicholas , Wu Christina , Fitzgerald Robert
Published: October 2021

Objectives

Despite multiple trials demonstrating that procalcitonin (PCT) is an effective tool for antibiotic stewardship, inconsistent application in real-world settings continues to fuel controversy regarding its clinical utility. We sought to determine rates of concordance between PCT results and antibiotic prescribing in hospitalized patients.

Methods

We performed a retrospective review of all inpatient encounters at an academic tertiary care health system with a PCT result between February 2017 and October 2019. Concordant prescribing was defined as starting or continuing antibiotics following an elevated PCT (>0.5 ng/mL) finding and withholding or stopping antibiotics following a low PCT (< 0.1 ng/mL) finding.

Results

Antibiotic prescribing decisions were discordant from the PCT level in 32.5% of our sample. Among patients not receiving antibiotics at the time of testing, 25.9% (430 of 1,662) were prescribed antibiotics despite a low PCT result. Among patients already receiving antibiotics, treatment was continued despite a low PCT level in 80.4% (728 of 906) of cases. Enhanced decision support tools introduced during the study period had no impact on PCT use for antibiotic decisions.

Conclusions

Overall concordance between PCT results and antibiotic use is relatively low in a real-world setting. The potential value of PCT for antibiotic stewardship may not be fully realized.
The eyes reflect an internal cognitive state hidden in the population activity of cortical neurons
Authors: Johnston Richard , Snyder Adam C , Khanna Sanjeev B , Issar Deepa , Smith Matthew A
Published: October 2021

Decades of research have shown that global brain states such as arousal can be indexed by measuring the properties of the eyes. The spiking responses of neurons throughout the brain have been associated with the pupil, small fixational saccades, and vigor in eye movements, but it has been difficult to isolate how internal states affect the eyes, and vice versa. While recording from populations of neurons in the visual and prefrontal cortex (PFC), we recently identified a latent dimension of neural activity called “slow drift,” which appears to reflect a shift in a global brain state. Here, we asked if slow drift is correlated with the action of the eyes in distinct behavioral tasks. We recorded from visual cortex (V4) while monkeys performed a change detection task, and PFC, while they performed a memory-guided saccade task. In both tasks, slow drift was associated with the size of the pupil and the microsaccade rate, two external indicators of the internal state of the animal. These results show that metrics related to the action of the eyes are associated with a dominant and task-independent mode of neural activity that can be accessed in the population activity of neurons across the cortex.
JAMIR-eQTL: Japanese genome-wide identification of microRNA expression quantitative trait loci across dementia types
Authors: Akiyama Shintaro , Higaki Sayuri , Ochiya Takahiro , Ozaki Kouichi , Niida Shumpei , Shigemizu Daichi
Published: October 2021

MicroRNAs (miRNAs) are small non-coding RNAs shown to regulate gene expression by binding to complementary transcripts. Genetic variants, including single-nucleotide polymorphisms and short insertions/deletions, contribute to traits and diseases by influencing miRNA expression. However, the association between genetic variation and miRNA expression remains to be elucidated. Here, by using genotype data and miRNA expression data from 3448 Japanese serum samples, we developed a computational pipeline to systematically identify genome-wide miRNA expression quantitative trait loci (miR-eQTLs). Not only did we identify a total of 2487 cis-miR-eQTLs and 3 155 773 trans-miR-eQTLs at a false discovery rate of <0.05 in six dementia types (Alzheimer’s disease, dementia with Lewy bodies, vascular dementia, frontotemporal lobar degeneration, normal-pressure hydrocephalus and mild cognitive impairment) and all samples, including those from patients with other types of dementia, but also we examined the commonality and specificity of miR-eQTLs among dementia types. To enable data searching and downloading of these cis- and trans-eQTLs, we developed a user-friendly database named JAMIR-eQTL, publicly available at https://www.jamir-eqtl.org/. This is the first miR-eQTL database designed for dementia types. Our integrative and comprehensive resource will contribute to understanding the genetic basis of miRNA expression as well as to the discovery of deleterious mutations, particularly in dementia studies.

Database URL: https://www.jamir-eqtl.org/
Sex difference in the risk factor distributions and outcomes after coronary artery bypass graft surgery in the young population
Authors: Hosseini Kaveh , Yavari Negin , Pashang Mina , Jalali Arash , Nalini Mahdi , Majdi Nassab Farzaneh , Sadeghian Saeed , Salehi Omran Abbas , Bagheri Jamshid , Poorhosseini Hamidreza , Salarifar Mojtaba , Ahmadi Tafti Seyed Hossein , Tajdini Masih
Published: October 2021

OBJECTIVES

Coronary artery disease is becoming a major health concern in the young population. Male and female patients may experience different journeys after coronary artery disease events. We aimed to evaluate risk factors and compare outcomes between young male and female patients undergoing coronary artery bypass graft surgery (CABG).

METHODS

In this registry-based large sample size study, patients undergoing isolated CABG at a young age (premature isolated CABG) between 2007 and 2016 were included and followed up until 2020. Premature was defined as women and men younger than 55 years old. The main end points of the study were 7-year all-cause mortality and 7-year major adverse cardiovascular and cerebrovascular events (MACCEs).

RESULTS

Of a total of 24 428 patients who underwent CABG, 7217 patients (men-to-women ratio ≈4:1) with premature isolated CABG were included. The median follow-up duration was 78.5 months (75.2–81.6 months). The prevalence rates of diabetes mellitus, hypertension, dyslipidaemia and obesity were significantly higher in women than in men (58.3% vs 28.6%, 64.2% vs 38.5%, 69.7% vs 55.3% and 44.7 vs 23.9, respectively; all Ps < 0.05). The risk factor burden (mean of the risk factor count per year) was also higher among the female population. Diabetes mellitus was the common mortality predictor between men and women. In the subgroup analysis (interaction analysis in the adjusted model), hypertensive females had a higher rate of MACCE and a higher rate of mortality than hypertensive males; however, this difference was not significant in the non-hypertensive population. Opium addiction was a strong predictor of MACCE and all-cause mortality among men. Female patients had a higher rate of 7-year MACCE (hazard ratio, 1.33; 95% confidence interval, 1.16–1.51) and a higher rate of 7-year all-cause mortality (hazard ratio, 1.23; 95% confidence interval, 0.98–1.53).

CONCLUSIONS

The risk factor profile and predictors of outcomes were different between our female and male patients. Women carried a higher risk of events and mortality after CABG at a young age.
E-health literacy levels of high school students in Turkey: results of a cross-sectional study
Authors: Tümer Adile , Sümen Adem
Published: October 2021

Digital health literacy is defined as the ability to search, find, and understand health information available on electronic resources and to use the information obtained from these resources to address a health problem. This study aimed to identify the digital health literacy levels of high school students and the factors that contribute to its development. This cross-sectional study was conducted with 1250 high school students from 10 high schools. The data were collected using the descriptive characteristics form and e-Health Literacy Scale (eHEALS) for adolescents. The mean age of the students was 15.92 ± 0.95 years and 50.8% of them were girls. The mean score on the eHEALS was 27.52 ± 6.76, which was in the high digital health literacy range (eHEALS ≥ 26). The results indicated the mean digital health literacy scores were high in students who lived in a nuclear family, who understood the importance of good health, who had easy access to the Internet and who had highly educated parents with high income levels. Encouraging the development of digital health literacy through school curricula could offer opportunities for all young people to develop digital health literacy, regardless of socio-economic status or family situation.
Microscopic and Transcriptomic Analyses of Dalbergoid Legume Peanut Reveal a Divergent Evolution Leading to Nod-Factor-Dependent Epidermal Crack-Entry and Terminal Bacteroid Differentiation
Authors: Raul Bikash , Bhattacharjee Oindrila , Ghosh Amit , Upadhyay Priya , Tembhare Kunal , Singh Ajeet , Shaheen Tarannum , Ghosh Asim Kumar , Torres-Jerez Ivone , Krom Nick , Clevenger Josh , Udvardi Michael , Scheffler Brian E. , Ozias-Akins Peggy , Sharma Ravi Datta , Bandyopadhyay Kaustav , Gaur Vineet , Kumar Shailesh , Sinharoy Senjuti
Published: October 2021

Root nodule symbiosis (RNS) is the pillar behind sustainable agriculture and plays a pivotal role in the environmental nitrogen cycle. Most of the genetic, molecular, and cell-biological knowledge on RNS comes from model legumes that exhibit a root-hair mode of bacterial infection, in contrast to the Dalbergoid legumes exhibiting crack-entry of rhizobia. As a step toward understanding this important group of legumes, we have combined microscopic analysis and temporal transcriptome to obtain a dynamic view of plant gene expression during Arachis hypogaea (peanut) nodule development. We generated comprehensive transcriptome data by mapping the reads to A. hypogaea, and two diploid progenitor genomes. Additionally, we performed BLAST searches to identify nodule-induced yet-to-be annotated peanut genes. Comparison between peanut, Medicago truncatula, Lotus japonicus, and Glycine max showed upregulation of 61 peanut orthologs among 111 tested known RNS-related genes, indicating conservation in mechanisms of nodule development among members of the Papilionoid family. Unlike model legumes, recruitment of class 1 phytoglobin-derived symbiotic hemoglobin (SymH) in peanut indicates diversification of oxygen-scavenging mechanisms in the Papilionoid family. Finally, the absence of cysteine-rich motif-1-containing nodule-specific cysteine-rich peptide (NCR) genes but the recruitment of defensin-like NCRs suggest a diverse molecular mechanism of terminal bacteroid differentiation. In summary, our work describes genetic conservation and diversification in legume–rhizobia symbiosis in the Papilionoid family, as well as among members of the Dalbergoid legumes.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Impact of Management Strategies on the Development and Status of Potato Cyst Nematode Populations in Switzerland: An Overview from 1958 to Present
Authors: Ruthes Andrea Caroline , Dahlin Paul
Published: October 2021

Globodera rostochiensis and G. pallida are some of the most successful and highly specialized plant parasitic nematodes and among the most regulated quarantine pests globally. In Switzerland, they have been monitored by annual surveys since their first detection in Swiss soil in 1958. The dataset created was reviewed to produce an overview of the development and actual status of potato cyst nematodes (PCNs) in Switzerland. Positive fields represent 0.2% of all the samples analyzed, and their distribution is limited to central-west and western Switzerland, suggesting that new introduction of PCNs and the spread of the initial introduced PCN populations did not occur. In this way, the integrated management used in Switzerland appears to be effective. However, the increasing availability of potato varieties with resistance to G. rostochiensis and the limited availability of varieties with resistance to G. pallida, together with other biotic and abiotic factors, have promoted changes in the dominance of either species. Consequently, an extended monitoring program is of interest to Swiss farmers, to avoid favoring virulent traits that could be present in Swiss Globodera populations.
Protein Phosphatase CgPpz1 Regulates Potassium Uptake, Stress Responses, and Plant Infection in Colletotrichum gloeosporioides
Authors: Zhang Yun-Zhao , Li Bing , Pan Yu-Ting , Fang Yu-Lan , Li De-Wei , Huang Lin
Published: October 2021

Protein phosphatases play important roles in the regulation of various cellular processes in eukaryotes. The ascomycete Colletotrichum gloeosporioides is a causal agent of anthracnose disease on some important crops and trees. In this study, CgPPZ1, a protein phosphate gene and a homolog of yeast PPZ1, was identified in C. gloeosporioides. Targeted gene deletion showed that CgPpz1 was important for vegetative growth and asexual development, conidial germination, and plant infection. Cytological examinations revealed that CgPpz1 was localized to the cytoplasm. The ΔCgppz1 mutant was hypersensitive to osmotic stresses, cell wall stressors, and oxidative stressors. Taken together, our results indicated that CgPpz1 plays an important role in the fungal development and virulence of C. gloeosporioides and the multiple stress responses generated.
Using self-controlled case series to understand the relationship between conflict and cholera in Nigeria and the Democratic Republic of Congo
Authors: Charnley Gina E C , Jean Kévin , Kelman Ilan , Gaythorpe Katy A M , Murray Kris A
Published: October 2021

Cholera outbreaks significantly contribute to disease mortality and morbidity in low- and middle-income countries. Cholera outbreaks have several social and environmental risk factors and extreme conditions can act as catalysts. A social extreme with known links to infectious disease outbreaks is conflict, causing disruption to services, loss of income and displacement. Here, we used the self-controlled case series method in a novel application and found that conflict increased the risk of cholera in Nigeria by 3.6 times and 19.7% of cholera outbreaks were attributable to conflict. In the Democratic Republic of Congo (DRC), conflict increased the risk of cholera by 2.6 times and 12.3% of cholera outbreaks were attributable to conflict. Our results highlight the importance of rapid and sufficient assistance during conflict-related cholera outbreaks, while also working towards conflict resolution and addressing pre-existing vulnerabilities such as poverty and access to healthcare.

Article Summary Line

Conflict significantly increased the risk of cholera outbreaks in Nigeria and the Democratic Republic of Congo and pre-existing vulnerabilities and conflict resolution should be a top priority to protect health.
Social mobility and biological aging among older adults in the United States
Authors: Graf GH , Zhang Y , Domingue BW , Harris KM , Kothari M , Kwon D , Muennig P , Belsky DW
Published: October 2021

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We analyzed blood-chemistry and DNA methylation (DNAm) data from n=9286 participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study to test associations of life-course social mobility with biological aging. We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation “clocks” and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ~0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility revealed differential effects by racial identity, suggesting that mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging.

Significance Statement

Upward social mobility may disrupt effects of early-life disadvantage on aging-related health decline. However, the stresses of crossing social boundaries can have biological costs. To investigate the balance of these forces, we analyzed social mobility from reports of childhood circumstances, education, and later-life wealth in 9,286 older adults in the US Health and Retirement Study. We quantified life-course health impacts of social mobility from blood-chemistry and DNA-methylation analysis of biological aging. We found that educational mobility alone benefited Black Americans less than White Americans, whereas mobility that produced accumulation of wealth into later-life was associated with delayed biological aging across social categories. Black-White disparities in healthy-aging outcomes of educational mobility may reflect inequalities in social gains realized from education.
Objective measures of reward sensitivity and motivation in people with high vs low anhedonia
Authors: Slaney Chloe , Perkins Adam M. , Davis Robert , Penton-Voak Ian , Munafò Marcus R , Houghton Conor J. , Robinson Emma S.J.
Published: October 2021

Background

Anhedonia – a diminished interest or pleasure in activities – is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience, and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development.

Methods

Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith-Hamilton Pleasure Scale).

Results

Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis.

Conclusions

Our findings suggest that anhedonia is a heterogenous symptom associated with impairments in reward sensitivity and effort-based decision-making.
Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand
Authors: Liu Zoe Shih-Jung , Sattabongkot Jetsumon , White Michael , Chotirat Sadudee , Kumpitak Chalermpon , Takashima Eizo , Harbers Matthias , Tham Wai-Hong , Healer Julie , Chitnis Chetan E , Tsuboi Takafumi , Mueller Ivo , Longley Rhea J
Published: October 2021

Plasmodium vivax is the dominant Plasmodium spp. causing the disease malaria in low-transmission regions outside of Africa. These regions often feature high proportions of asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address the presence and maintenance of such antibody responses to P. vivax particularly in low-transmission regions. We followed 34 patients in western Thailand after symptomatic P. vivax infections to monitor antibody kinetics over 9 months, during which no recurrent infections occurred. We assessed total IgG, IgG subclass and IgM levels to up to 52 P. vivax proteins every 2-4 weeks using a multiplexed Luminex® assay, and identified protein-specific variation in antibody longevity. Generally, an increase in antibody level was observed within 1-week post symptomatic infection, followed by an exponential decay of different rates. We observed mostly IgG1 dominance and IgG3 sub-dominance in this population. IgM responses followed similar kinetic patterns to IgG, with some proteins unexpectedly inducing long-lived IgM responses. We also monitored antibody responses against 27 IgG-immunogenic antigens in 30 asymptomatic individuals from a similar region. Our results demonstrate that most antigens induced robust and long-lived total IgG responses following asymptomatic infections in the absence of (detected) boosting infections. Our work provides new insights into the development and maintenance of naturally acquired immunity to P. vivax and will guide the potential use of serology to indicate immune status and/or identify populations at risk.
Crustacean cardiac ganglion model reveals constraints on morphology and conductances
Authors: Dopp Dan , Samarth Pranit , Wang Jing , Kick Daniel , Schulz David J. , Nair Satish S.
Published: October 2021

The crustacean cardiac ganglion (CG) network coordinates the rhythmic contractions of the heart muscle to control the circulation of blood. The network consists of 9 cells, 5 large motor cells (LC1-5) and 4 small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical model of an LC that is morphologically realistic and includes provision for inputs from the SCs via a gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, maximal conductances in three compartments of an LC are determined by random sampling from a biologically-characterized 9D-parameter space, followed by a three-stage rejection protocol that checks for conformity with electrophysiological features from single cell traces. LC models that pass the single cell rejection protocol are then incorporated into a network model which is then used in a final rejection protocol stage. Using disparate experimental data, the study provides hitherto unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology including the role of its SIZ, and the differential roles of active conductances in the three compartments. Further, we extend analyses of emergent conductance relationships and correlations in model neurons relative to their biological counterparts, allowing us to make inferences both with respect to the biological system as well as the implications of the ability to detect such relationships in populations of model neurons going forward.
Convergent energy state-dependent antagonistic signalling by CART and NPY modulates the plasticity of forebrain neurons to regulate feeding in zebrafish
Authors: Bodas Devika S. , Maduskar Aditi , Kaniganti Tarun , Wakhloo Debia , Balasubramanian Akilandeswari , Subhedar Nishikant , Ghose Aurnab
Published: October 2021

Dynamic re-configuration of circuit function subserves the flexibility of innate behaviours tuned to physiological states. Internal energy stores adaptively regulate feeding-associated behaviours by integrating opposing hunger and satiety signals at the level of neural circuits. Across vertebrate lineages, the neuropeptides CART and NPY have potent anorexic and orexic functions, respectively, and show energy state-dependent expression in interoceptive neurons. However, how the antagonistic activities of these peptides modulate circuit plasticity remains unclear.

Using behavioural, neuroanatomical and activity analysis in adult zebrafish, along with pharmacological interventions, we show that CART and NPY activities converge on a population of neurons in the dorsomedial telencephalon (Dm). While CART facilitates glutamatergic neurotransmission at the Dm, NPY dampens the response to glutamate. In energy-rich states, CART enhances NMDA receptor (NMDAR) function by PKA/PKC mediated phosphorylation of the NR1 subunit of the NMDAR complex. Conversely, starvation triggers NPY-mediated reduction in phosphorylated NR1 via calcineurin activation and inhibition of cAMP production leading to reduced responsiveness to glutamate.

Our data identify convergent integration of CART and NPY inputs by the Dm neurons to generate nutritional state-dependent circuit plasticity that is correlated with the behavioural switch induced by the opposing actions of satiety and hunger signals.
Impacts of dams on freshwater turtles: a global review to identify conservation solutions
Authors: Bárcenas-García Andrea , Michalski Fernanda , Morgan William H. , Smith Rebecca K. , Sutherland William J. , Gibbs James P. , Norris Darren
Published: October 2021

Background and Research Aims

Dams impact freshwater ecosystems and biodiversity. Freshwater turtles are at direct and indirect risk due to changes caused by damming including the loss of terrestrial and aquatic nesting habitats, changes to food availability and blocking movement. Effective management of these impacts requires robust evidence in order to gain an understanding of conservation solutions that work.

Methods

We reviewed the global scientific literature that evaluated the impact of dams on freshwater turtles, and carried out additional searches of literature published in seventeen languages for studies evaluating actions to mitigate dam impacts.

Results

The search produced 47 published articles documenting dam impacts on 30 freshwater turtle species from seven families (Chelidae, Chelydridae, Emydidae, Geoemydidae, Kinosternidae, Podocnemididae and Trionychidae) in 13 countries. Few studies were found from Europe and Asia and none from Africa. Most studies were from temperate latitudes, where studies focused more on adults and less threatened species compared with tropical latitudes. More than half of the studies (57%, n = 27) suggested actions to help mitigate dam impacts. Yet, only five studies (three temperate and two tropical) documented the effect of interventions (dam removal, flow management, artificial pond maintenance and community-based action).

Conclusion

These findings demonstrate a serious lack of documented evidence evaluating mitigation actions for dam impacts on freshwater turtles. Implications for Conservation: This lack of evidence reinforces the importance of strengthening and maintaining robust long-term studies needed to develop effective and adaptive conservation actions for this group of threatened vertebrates particularly in tropical regions.
Developing a More Accurate Biomedical Literature Retrieval Method using Deep Learning and Citations in PubMed Central Full-text Articles
Authors: Lo Chun-chao , Tian Shubo , Tao Yuchuan , Hao Jie , Zhang Jinfeng
Published: October 2021

Most queries submitted to a literature search engine can be more precisely written as sentences to give the search engine more specific information. Sentence queries should be more effective, in principle, than short queries with small numbers of keywords. Querying with full sentences is also a key step in question-answering and citation recommendation systems. Despite the considerable progress in natural language processing (NLP) in recent years, using sentence queries on current search engines does not yield satisfactory results. In this study, we developed a deep learning-based method for sentence queries, called DeepSenSe, using citation data available in full-text articles obtained from PubMed Central (PMC). A large amount of labeled data was generated from millions of matched citing sentences and cited articles, making it possible to train quality predictive models using modern deep learning techniques. A two-stage approach was designed: in the first stage we used a modified BM25 algorithm to obtain the top 1000 relevant articles; the second stage involved re-ranking the relevant articles using DeepSenSe. We tested our method using a large number of sentences extracted from real scientific articles in PMC. Our method performed substantially better than PubMed and Google Scholar for sentence queries.
NAToRA, a relatedness-pruning method to minimize the loss of dataset size in genetic and omics analyses
Authors: Leal Thiago Peixoto , Furlan Vinicius C , Gouveia Mateus Henrique , Saraiva Duarte Julia Maria , Fonseca Pablo AS , Tou Rafael , de Oliveira Scliar Marilia , de Araujo Gilderlanio Santana , Zolini Camila , Diniz Peixoto Maria Gabriela Campolina , Santos Carvalho Maria Raquel , Lima-Costa Maria Fernanda , Gilman Robert H , Tarazona-Santos Eduardo , Rodrigues Maíra Ribeiro
Published: October 2021

Genetic and omics analyses frequently require independent observations, which is not guaranteed in real datasets. When relatedness cannot be accounted for, solutions involve removing related individuals (or observations) and, consequently, a reduction of available data. We developed a network-based relatedness-pruning method that minimizes dataset reduction while removing unwanted relationships in a dataset. It uses node degree centrality metric to identify highly connected nodes (or individuals) and implements heuristics that approximate the minimal reduction of a dataset to allow its application to large datasets. NAToRA outperformed two popular methodologies (implemented in software PLINK and KING) by showing the best combination of effective relatedness-pruning, removing all relatives while keeping the largest possible number of individuals in all datasets tested and also, with similar or lesser reduction in genetic diversity. NAToRA is freely available, both as a standalone tool that can be easily incorporated as part of a pipeline, and as a graphical web tool that allows visualization of the relatedness networks. NAToRA also accepts a variety of relationship metrics as input, which facilitates its use. We also present a genealogies simulator software used for different tests performed in the manuscript.
Structure in motion: visual motion perception as online hierarchical inference
Authors: Bill Johannes , Gershman Samuel J. , Drugowitsch Jan
Published: October 2021

Identifying the structure of motion relations in the environment is critical for navigation, tracking, prediction, and pursuit. Yet, little is known about the mental and neural computations that allow the visual system to infer this structure online from a volatile stream of visual information. We propose online hierarchical Bayesian inference as a principled solution for how the brain might solve this complex perceptual task. We derive an online Expectation-Maximization algorithm that explains human percepts qualitatively and quantitatively for a diverse set of stimuli, covering classical psychophysics experiments, ambiguous motion scenes, and illusory motion displays. We thereby identify normative explanations for the origin of human motion structure perception and make testable predictions for new psychophysics experiments. The proposed online hierarchical inference model furthermore affords a neural network implementation which shares properties with motion-sensitive cortical areas and motivates a novel class of experiments to reveal the neural representations of latent structure.
Rapid Assessment of the Temporal Function and Phenotypic Reversibility of Neurodevelopmental Disorder Risk Genes inC. elegans
Authors: Kepler Lexis D. , McDiarmid Troy A. , Rankin Catharine H.
Published: October 2021

Hundreds of genes have been implicated in neurodevelopmental disorders. Previous studies have indicated that some phenotypes caused by decreased developmental function of select risk genes can be reversed by restoring gene function in adulthood. However, very few risk genes have been assessed for adult reversibility. We developed a strategy to rapidly assess the temporal requirements and phenotypic reversibility of neurodevelopmental disorder risk gene orthologs using a conditional protein degradation system and machine vision phenotypic profiling inCaenorhabditis elegans. Using this approach, we measured the effects of degrading and re- expressing orthologs of 3 neurodevelopmental risk genesEBF3, BRN3A, andDYNC1H1across 30 morphological, locomotor, sensory, and learning phenotypes at multiple timepoints throughout development. We found some degree of phenotypic reversibility was possible for each gene studied. However, the temporal requirements of gene function and degree of phenotypic reversibility varied by gene and phenotype. The data reflects the dynamic nature of gene function and the importance of using multiple time windows of degradation and re-expression to understand the many roles a gene can play over developmental time. This work also demonstrates a strategy of using a high-throughput model system to investigate temporal requirements of gene function across a large number of phenotypes to rapidly prioritize neurodevelopmental disorder genes for re-expression studies in other organisms.

SUMMARY STATEMENT

We developed a strategy that combines a conditional and reversible protein degradation system with our high-throughput machine vision tracking system to assess the temporal windows of gene function and reversibility of phenotypic disruptions associated with neurodevelopmental disorder risk gene orthologs usingC. elegans. Using this approach, we assessed 3 genes (unc- 3,unc-86, anddhc-1)and found that post-embryonic rescue was possible for each gene and each phenotypic feature class assessed. Re-activation of certain genes was able to reverse multiple phenotypic disruptions late into development without inducing novel phenotypes, prioritizing them for further study.
Single Pulse Heating of Nanoparticle Array for Biological Applications
Authors: Xie Chen , Kang Peiyuan , Cazals Johan , Castelán Omar Morales , Randrianalisoa Jaona , Qin Zhenpeng
Published: October 2021

With the ability to convert external excitation into heat, nanomaterials play an essential role in many biomedical applications. Two modes of nanoparticle (NP) array heating, nanoscale-confined heating (NCH) and macroscale-collective heating (MCH), have been found and extensively studied. Despite this, the resulting biological response at protein level remains elusive. In this study, we developed a computational model to systematically investigate the single-pulsed heating of NP array and corresponding protein denaturation/activation. We found that NCH may lead to targeted protein denaturation, however, nanoparticle heating does not lead to nanoscale selective TRPV1 channel activation. The excitation duration and NP concentration are primary factors that determine a window for targeted protein denaturation, and together with heating power, we defined quantified boundaries for targeted protein denaturation. Our results boost our understandings in the NCH and MCH under realistic physical constraints and provide a robust guidance to customize biomedical platforms with desired NP heating.
Neural knowledge assembly in humans and deep networks
Authors: Nelli Stephanie , Braun Lukas , Dumbalska Tsvetomira , Saxe Andrew , Summerfield Christopher
Published: October 2021

Human understanding of the world can change rapidly when new information comes to light, such as when a plot twist occurs in a work of fiction. This flexible “knowledge assembly” requires few-shot reorganisation of neural codes for relations among objects and events. However, existing computational theories are largely silent about how this could occur. Here, participants learned a transitive ordering among novel objects within two distinct contexts, before exposure to new knowledge that revealed how they were linked. BOLD signals in dorsal frontoparietal cortical areas revealed that objects were rapidly and dramatically rearranged on the neural manifold after minimal exposure to linking information. We then adapt stochastic online gradient descent to permit similar rapid knowledge assembly in a neural network model.
Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate slows aging in mice
Authors: Jiang Zhou , Wang Juan , Imai Denise , Snider Tim , Mangalindan Ruby , Morton John , Zhu Lida , Salmon Adam B. , Wezeman Jackson , Klug Jenna , Hu Jiayi , Menon Vinal , Marka Nicholas , Neidernhofer Laura , Ladiges Warren
Published: October 2021

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs each targeting different but overlapping processes. In order to determine if combining drugs previously shown to improve lifespan would have greater impact than any individuyal drug, a diet containing rapamycin at 14 ppm, acarbose at 1000 ppm, and phenylbutyrate at 1000 ppm was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice fed the cocktail diet showed a strain and gender-dependent phenotype consistent with healthy aging including decreased body fat and blood glucose, improved cognition, and increased grip strength and walking ability compared to mice fed individual drug or control diets. A cocktail diet containing ½ dosing of each compound was overall less effective than the full dose. The composite age-related lesion score of heart, lungs, liver and kidney was decreased in mice fed the cocktail diet compared to mice fed individual drug or control diets suggesting an interactive advantage of the three drugs. Senescence and inflammatory cytokine levels in kidneys from mice fed the cocktail diet were lower than in kidneys from mice fed control diet, and consistent with low expression levels in kidneys from young untreated mice, suggesting the cocktail diet delayed aging partly by senolytic and anti-inflammatory effects.
Multi-species mechanistic model of functional response provides new insights into predator-mediated interactions in a vertebrate community
Authors: Beardsell Andréanne , Gravel Dominique , Clermont Jeanne , Berteaux Dominique , Gauthier Gilles , Bêty Joël
Published: October 2021

1.

Abstract

Prey handling processes are considered a key driver of short-term positive indirect effects between prey sharing the same predator. However, a growing body of research indicates that predators are rarely limited by such processes in the wild. Density-dependent changes in predator foraging be-havior can also generate positive indirect effects but they are rarely included as explicit functions of prey densities in functional response models. With the aim of untangling proximate drivers of species interactions in natural communities and improve our ability to quantify interaction strength, we extended the Holling multi-species model by including density-dependent changes in predator foraging behavior. Our model, based on species traits and behavior, was inspired by the verte-brate community of the arctic tundra, where the main predator (the arctic fox) is an active forager feeding primarily on cyclic small rodent (lemming) populations and eggs of various tundra-nesting bird species. Short-term positive indirect effects of lemmings on birds have been documented over the circumpolar Arctic but the underlying proximate mechanisms remain poorly known. We used a unique data set, containing high-frequency GPS tracking, accelerometer, behavioral, and experimental data to parameterize the multi-species model, and a 15-year time series of prey densities and bird nesting success to evaluate inter-action strength between species. Our results showed that: (i) prey handling processes play a minor role in our system and (ii) density-dependent changes in predator foraging behavior can be the proximate drivers of a predominant predator-mediated interaction observed in the arctic tundra. Mechanisms outlined in our study have been little studied and may play a significant role in natural systems. We hope that our study will provide a useful starting point to build mechanistic models of predation, and we think that our approach could conceivably be applied to a broad range of food webs.