bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation of the Ileal Anal Pouch: Do Biologics Really Change the Trajectory?
Authors: Lightner Amy L
Published: October 2019

Inflammatory conditions of the ileal pouch are relatively common after ileal pouch anal anastomoses. Although biologics can induce mucosal healing and may have decreased rates of colectomy for medically refractory ulcerative colitis in recent years, they have not decreased rates of pouch failure due to inflammatory conditions of the pouch.
Minimal DNA Electron Transfer Catalysts Switched by a Chaotropic Ion
Authors: Hoog Tanner G. , Pawlak Matthew R. , Aufdembrink Lauren M. , Bachan Benjamin R. , Galles Matthew B. , Bense Nicholas B. , Adamala Katarzyna P. , Engelhart Aaron E.
Published: October 2019

Here we demonstrate that a DNA nanodevice can perform switchable electron transfer. The nanodevice is comprised of two strands, one of which can be selectively switched between a G-quadruplex and duplex or single-stranded conformations. In the G-quadruplex state, it binds the cofactor hemin, enabling peroxidase activity. This switching ability arises from our discovery that perchlorate, a chaotropic Hofmeister ion, selectively destabilizes duplex over G-quadruplex DNA. By varying perchlorate concentration, we show that the device can be switched between states that do and do not catalyze electron transfer catalysis. State switching can be achieved in three ways: thermally, by dilution, or by concentration. In each case, when operated in the presence of the cofactor hemin, the device catalyzes electron transfer in only the G-quadruplex state.
MTHFR gene A1298C polymorphism and Alzheimer’s disease susceptibility
Authors: Rai Vandana
Published: October 2019

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme involved in homocysteine/methionone metabolism. It catalyzes the conversion of 5,10methlenetetrahydrofolate in to 5methyltetrahydrofolate. A number of studies have examined the association of MTHFR A1298C polymorphism as risk factor for Alzheimer’s disease (AD), but the results were contradictory. To clarify the influence of MTHFR A1298C polymorphism on Alzheimer’s disease (AD), a meta-analysis of ten case-control studies was carried out. Four electronic databases were searched up to August, 2019 for suitable articles. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. All statistical analyses were performed by MetaAnalyst program.

The results of meta-analysis suggested that except allele contrast model, A1298C polymorphism is not risk for Alzheimer’s disease using overall comparisons in three genetic models (C vs. A: OR= 1.26, 95%CI= 0.912-1.76, p= 0.04; CC+AC vs. AA: OR= 1.43; 95%CI= 0.85-2.44; p=0.05; CC vs. AA: OR= 1.16, 95%CI= .88-1.55, p= 0.51; AC vs. AA: 1.55; 95%CI= 0.81-2.93,p=0.07). Publication bias was absent in all five genetic models. In conclusion, results of present meta-analysis showed no significant association between MTHFR A1298C polymorphism and AD risk.
Mechanisms of tissue-specific genetic regulation revealed by latent factors across eQTLs
Authors: He Yuan , Chhetri Surya B. , Arvanitis Marios , Srinivasan Kaushik , Aguet François , Ardlie Kristin G. , Barbeira Alvaro N. , Bonazzola Rodrigo , Im Hae Kyung ,   GTEx Consortium, Brown Christopher D. , Battle Alexis
Published: October 2019

Background

Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), varies across tissues in complex patterns ranging from highly tissue-specific effects to effects shared across many or all tissues. Improved characterization of these patterns may allow us to better understand the biological mechanisms that underlie tissue-specific gene regulation and disease etiology.

Results

We develop a constrained matrix factorization model to learn patterns of tissue sharing and tissue specificity of eQTLs across 49 human tissues from the Genotype-Tissue Expression (GTEx) project. The learned factors include patterns reflecting tissues with known biological similarity or shared cell types, in addition to a dense factor representing a universal genetic effect across all tissues. To explore the regulatory mechanisms that generate tissue-specific patterns of expression, we evaluate chromatin state enrichment and identify specific transcription factors with binding sites enriched for eQTLs from each factor.

Conclusions

Our results demonstrate that matrix factorization can be applied to learn the tissue specificity pattern of eQTLs and that it exhibits better biological interpretability than heuristic methods. We present a framework to characterize the tissue specificity of eQTLs, and we identify examples of tissue-specific eQTLs that may be driven by tissue-specific transcription factor (TF) binding, with relevance to interpretation of disease association.
Longitudinal study of persistence in professional development outcomes of early career biology faculty
Authors: Emery Nathan C , Maher Jessica Middlemis , Ebert-May Diane
Published: October 2019

The diversity of teaching professional development (PD) programs that occurred over the last few decades merits our collective attention to assess the impact of these programs over time. In general, the goal of PD programs is that participants continue to practice what they learn in the long term. However, we do not know the degree to which the outcomes of these programs were achieved and ultimately persist. We tracked postdoc participants from the Faculty Institutes for Reformed Science Teaching (FIRST) IV program into their current position as early-career faculty at institutions across the United States. We assessed their teaching approaches, practices, and student perceptions of the learning environment over 6-10 years. Additionally, the FIRST IV faculty were paired with colleagues of similar status in the same departments. We found that professional development outcomes from the FIRST IV program persisted over time and across a significant career transition, from postdoc to faculty. These participants not only maintained their student-centered practices, but were significantly more student-focused than their peers. Lastly, we found that faculty approaches to teaching were correlated with observed teaching practices in the classroom for both groups of faculty. These results provide compelling evidence for the success of the FIRST IV program and the long-term persistence of professional development outcomes.
Pitfalls in estimating the global carbon removal via forest expansion – a comment on Bastin et al. (2019)
Authors: Krause Andreas , Arneth Almut , Bayer Anita , Buras Allan , Knoke Thomas , Zang Christian , Rammig Anja
Published: October 2019

We believe the carbon removal potential of 205 Gt C reported by Bastin et al. (2019) to be overestimated. The authors did not consider the carbon already stored on the land with identified tree restoration potential. For instance, grasslands and degraded forests have similar soil carbon stocks as old-growth forests. Accounting for these inconsistencies in the calculation, we estimate a carbon removal potential of 81 Gt C, i.e. only 39% of the Bastin et al. estimate. In addition, some of the assumptions about potential restoration area seem questionable and an essential question remains unanswered: why do areas identified as suitable for tree growth currently lack tree cover?
Hormonal and modality specific effects on males’ emotion recognition ability
Authors: Lausen Adi , Broering Christina , Penke Lars , Schacht Annekathrin
Published: October 2019

Successful emotion recognition is a key component of our socio-emotional communication skills. However, little is known about the factors impacting males’ accuracy in emotion recognition tasks. This pre-registered study examined potential candidates, focusing on the modality of stimulus presentation, emotion category, and individual hormone levels. We obtained accuracy and reaction time scores from 312 males who categorized voice, face and voice-face stimuli for nonverbal emotional content. Results showed that recognition accuracy was significantly higher in the audio-visual than in the auditory or visual modality. While no significant association was found for testosterone and cortisol alone, the effect of the interaction with recognition accuracy and reaction time was significant, but small. Our results establish that audio-visual congruent stimuli enhance recognition accuracy and provide novel empirical support by showing that the interaction of testosterone and cortisol modulate to some extent males’ accuracy and response times in emotion recognition tasks.
Nonsense suppression position effect implicates poly(A)-binding protein in the regulation of translation termination
Authors: Wu Chan , Roy Bijoyita , He Feng , Jacobson Allan
Published: October 2019

Readthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series ofLUCnonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3’-end, decreasing progressively across theLUCORF but increasing with 3’-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboringpab1mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.
Isolation and comparative genomic analysis of reuterin-producingLactobacillus reuterifrom poultry gastrointestinal tract
Authors: Greppi Anna , Asare Paul Tetteh , Schwab Clarissa , Zemp Niklaus , Stephan Roger , Lacroix Christophe
Published: October 2019

Lactobacillus reuteriis a natural inhabitant of selected animal and human gastrointestinal tract (GIT). Certain strains have the capacity to transform glycerol to 3-hydroxypropionaldehyde (3-HPA), further excreted to form reuterin, a potent antimicrobial system. Reuterin-producing strains may be applied as a natural antimicrobial in feed to prevent pathogen colonization of animals, such as in poultry, and replace added antimicrobials. To date, only sevenL. reuteristrains isolated from poultry have been characterized which limits phylogenetic studies and host-microbes interactions characterization. This study aimed to isolateL. reuteristrains from poultry GIT and to characterize their reuterin production and antimicrobial resistance (AMR) profiles using phenotypic and genetic methods. Seventy reuterin-producing strains were isolated from poultry crop, faeces and caeca and twenty-five selected for further characterization. Draft genomes were generated for the new 25 isolates and integrated in a phylogenetic tree of 40 strains from different hosts. Phylogenetic analysis based on gene content as well as on core genomes showed grouping of the selected 25L. reuteripoultry isolates within the poultry/human lineage VI. Strains harbouringpdu-cob-cbi-hemgenes (23/25) produced between 156 mM ± 11 and 330 mM ± 14 3-HPA, from 600 mM of glycerol, in the conditions of the test. All 25 poultry strains were sensitive to cefotaxime (MIC between 0.016 and 1 μg/mL) and penicillin (MIC between 0.02 and 4 μg/mL). Akin to the reference strains DSM20016 and SD2112, the novel isolates were resistant to penicillin, possibly associated with identified point mutations inponA,pbpX,pbpFandpbpB. All strains resistant to erythromycin (4/27) carried the ermB gene, and it was only present in poultry strains. All strains resistant to tetracycline (5/27) harbored tetW gene. This study confirms the evolutionary history of poultry/human lineage VI and identifiespdu-cob-cbi-hemas a frequent trait but not always present in this lineage.L. reuteripoultry strains producing high 3-HPA yield may have potential to prevent enteropathogen colonization of poultry.
Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings
Authors: Silote Gabriela P. , de Oliveira Sabrina F.S. , Ribeiro Deidiane E. , Machado Mayara S. , Andreatini Roberto , Joca Sâmia R. L. , Beijamini Vanessa
Published: October 2019

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.

Highlights

Ketamine induces mixed effects in animal anxiety tests

Few studies investigated the individual effects of S-ketamine in anxiety/fear tests

None study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors

Systemic ketamine does not affect panic-like behaviors in the elevated T-maze
Spontaneous variability in gamma dynamics described by a linear harmonic oscillator driven by noise
Authors: Spyropoulos Georgios , Dowdall Jarrod Robert , Schölvinck Marieke Louise , Bosman Conrado Arturo , Lima Bruss , Peter Alina , Onorato Irene , Klon-Lipok Johanna , Roese Rasmus , Neuenschwander Sergio , Singer Wolf , Vinck Martin , Fries Pascal
Published: October 2019

Circuits of excitatory and inhibitory neurons can generate rhythmic activity in the gamma frequency-range (30-80Hz). Individual gamma-cycles show spontaneous variability in amplitude and duration. The mechanisms underlying this variability are not fully understood. We recorded local-field-potentials (LFPs) and spikes from awake macaque V1, and developed a noise-robust method to detect gamma-cycle amplitudes and durations. Amplitudes and durations showed a weak but positive correlation. This correlation, and the joint amplitude-duration distribution, is well reproduced by a dampened harmonic oscillator driven by stochastic noise. We show that this model accurately fits LFP power spectra and is equivalent to a linear PING (Pyramidal Interneuron Network Gamma) circuit. The model recapitulates two additional features of V1 gamma: (1) Amplitude-duration correlations decrease with oscillation strength; (2) Amplitudes and durations exhibit strong and weak autocorrelations, respectively, depending on oscillation strength. Finally, longer gamma-cycles are associated with stronger spike-synchrony, but lower spike-rates in both (putative) excitatory and inhibitory neurons. In sum, V1 gamma-dynamics are well described by the simplest possible model of gamma: A linear harmonic oscillator driven by noise.
SKIPHOS: non-kinase specific phosphorylation site prediction with random forests and amino acid skip-gram embeddings
Authors: Dang Thanh Hai , Trac Quang Thinh , Phan Huy Kinh , Nguyen Manh Cuong , Pham Thi Quynh Trang
Published: October 2019

Motivation

Phosphorylation, which is catalyzed by kinase proteins, is in the top two most common and widely studied types of known essential post-translation protein modification (PTM). Phosphorylation is known to regulate most cellular processes such as protein synthesis, cell division, signal transduction, cell growth, development and aging. Various phosphorylation site prediction models have been developed, which can be broadly categorized as being kinase-specific or non-kinase specific (general). Unlike the latter, the former requires a large enough number of experimentally known phosphorylation sites annotated with a given kinase for training the model, which is not the case in reality: less than 3% of the phosphorylation sites known to date have been annotated with a responsible kinase. To date, there are a few non-kinase specific phosphorylation site prediction models proposed.

Results

This paper proposes SKIPHOS, a non-kinase specific phosphorylation site prediction model based on random forests on top of a continuous distributed representation of amino acids. Experimental results on the benchmark dataset and the independent test set demonstrate that SKIPHOS compares favorably to recent state-of-the-art related methods for three phosphorylation residues. Although being trained on phosphorylation sites in mamals, SKIPHOS can yield predictions for Y residues better than PHOSFER, a recently proposed plants-specific phosphorylation prediction model.

Availability and Implementation

SKIPHOS Web Server is freely available for non-commercial use athttp://fit.uet.vnu.edu.vn/SKIPHOSorhttp://112.137.130.46:5000.

Contact

hai.dang@vnu.edu.vn

Supplementary information

Supplementary data are available atBioinformaticsonline.
Control of brain state transitions with light
Authors: Barbero-Castillo Almudena , Riefolo Fabio , Matera Carlo , Caldas-Martínez Sara , Mateos-Aparicio Pedro , Weinert Julia F. , Claro Enrique , Sánchez-Vives Maria Victoria , Gorostiza Pau
Published: October 2019

Behavior is driven by specific neuronal activity and can be directly associated with characteristic brain states. The oscillatory activity of neurons contains information about the mental state of an individual, and the transition between physiological brain states is largely controlled by neuromodulators. Manipulating neural activity, brain rhythms or synchronization is of significant therapeutic interest in several neurological disorders and can be achieved by different means such as transcranial current and magnetic stimulation techniques, and by light through optogenetics, although the clinical translation of the latter is hampered by the need of gene therapy. Here, we directly modulate brain rhythms with light using a novel photoswitchable muscarinic agonist. Synchronous slow wave activity is transformed into a higher frequency pattern in the cerebral cortex both in slices in vitro and in anesthetized mice. These results open the way to the study of the neuromodulation and control of spatiotemporal patterns of activity and pharmacology of brain states, their transitions, and their links to cognition and behavior, in different organisms without requiring any genetic manipulation.
B-cell enforced expression of the mouse ortholog of MYD88L265P is responsible for Waldenström-like B-cell lymphoma
Authors: Ouk Catherine , Roland Lilian , Saintamand Alexis , Gachard Nathalie , Thomas Morgane , Devéza Mélanie , Faumont Nathalie , Feuillard Jean , Vincent-Fabert Christelle
Published: October 2019

Here, we created a conditional transgenic mouse model with insertion of a sequence coding for both MYD88L252P and the Yellow Fluorescent Protein (YFP) into the rosa26-locus. B-cell specific induction of the transgene constantly led to spleen enlargement with expansion of YFP positive B-cells in 8-12 month-old mice, with a moderate B-cell proliferation increase. Being clonal or oligoclonal, these B-cells exhibited a marked morphological and immunophenotypic lymphoplasmocytic aspect with a plasma cell transcriptomic signature and a serum immunoglobulin M peak. Therefore, continuous activation of MYD88 in mice can lead on its own to a lymphoma close to Waldenström Macroglobulinemia.

Key point

B-cell specific enforced expression of MYD88L252P leads to a clonal indolent lymphoplasmocytic B-cell lymphoma with a serum IgM peak.
Structural effects and functional implications of phalloidin and jasplakinolide binding to actin filaments
Authors: Pospich Sabrina , Merino Felipe , Raunser Stefan
Published: October 2019

Actin undergoes structural transitions during polymerization, ATP hydrolysis and subsequent release of inorganic phosphate. Several actin binding proteins sense specific states during this transition and can thus target different regions of the actin filament. Here we show in atomic detail that phalloidin, a mushroom toxin that is routinely used to stabilize and label actin filaments, suspends the structural changes in actin, likely influencing its interaction with actin binding proteins. Furthermore, high-resolution cryo-EM structures reveal structural rearrangements in F-actin upon inorganic phosphate release in phalloidin-stabilized filaments. We find that the effect of the sponge toxin jasplakinolide differs from the one of phalloidin, despite their overlapping binding site and similar interactions with the actin filament. Analysis of structural conformations of F-actin suggests that stabilizing agents trap states within the natural conformational space of actin.

Abstract Figure

Highlights

Five high-resolution cryo-EM structures of stabilized filamentous actin

Phalloidin traps different structural states depending on when it is added

The effect of phalloidin and jasplakinolide on filamentous actin is not identical

Both toxins likely interfere with the binding of proteins sensing F-actin’s nucleotide state
A Novel Droplet Digital PCR Human mtDNA Assay for Global Fecal Source Tracking
Authors: Zhu Kevin , Suttner Brittany , Konstantinidis Konstantinos T. , Brown Joe
Published: October 2019

Human mitochondrial DNA (mtDNA) provides a promising target for microbial source tracking because it is unique to humans and universal across human individuals. We developed a droplet digital PCR (ddPCR) assay, hCYTB484, targeting the cytochrome b gene of the human mtDNA and compared the performance of the hCYTB484 assay with a widely used assay targeting human-associated Bacteroides, the HF183/BacR287 assay. We also defined and validated the analytical limit of detection and analytical lower limit of quantification; these analytical limits determine the concentration levels above which samples are declared to be positive and quantifiable for the target, respectively. We found both assays to be highly specific (95%) against cow and pig feces; however, the hCYTB484 was more sensitive when tested against individual human feces from US, Bangladesh, and Mozambique (100% versus a mean of 51% across the 3 countries). To further compare the performance of the two assays, we utilized a receiver operating characteristic curve, showing that the hCYTB484 marker was widely distributed across human feces from the 3 different geographical regions tested and in higher quantities than the HF183/BacR287 marker. The higher performance of the hCYTB484 marker in individual feces is a desirable characteristic in the detection of fecal pollution from sources to which fewer individuals contribute, such as non-sewered types of sanitation that serve most of Earth’s population and carry the highest risk of exposure to fecal-oral pathogens.

Importance

The usefulness of an ideal human-specific, culture- and library-independent marker to the microbial source tracking field is reflected by the numerous efforts to develop such markers; however, thus far, microbial-based markers of this type have exhibited variable source-specificity across geographies and variable sensitivity across scales of fecal waste. Most of the world’s population is served by non-sewered forms of sanitation that also carry the highest risk of exposure to fecal-oral pathogens. This reality underscores the need for markers of human fecal contamination that have high sensitivity in fecal pollution sources to which fewer individuals contribute to, such as fecal sludges found in pit latrines. We show that human mtDNA-based methods can be highly source-specific and highly sensitive in smaller scales of fecal pollution, providing a useful addition to the microbial source tracking toolbox by complementing the variable performance of microbial-based markers.
A general quantitative relation linking bacterial cell growth and the cell cycle
Authors: Zheng Hai , Bai Yang , Jiang Meiling , Tokuyasu Taku A. , Huang Xiongliang , Zhong Fajun , Fu Xiongfei , Kleckner Nancy , Hwa Terence , Liu Chenli
Published: October 2019

The foundation of bacterial cell cycle studies has long resided in two interconnected dogmas between biomass growth, DNA replication, and cell division during exponential growth: the SMK growth law that relates cell mass (a measure of cell size) to growth rate1, and Donachie’s hypothesis of a growth-rate-independent initiation mass2. These dogmas have spurred many efforts to understand their molecular bases and physiological consequences3–12. Most of these studies focused on fast-growing cells, with doubling times shorter than 60 min. Here, we systematically studied the cell cycle ofE. colifor a broad range of doubling times (24 min to over 10 hr), with particular attention on steady-state growth. Surprisingly, we observed that neither dogma held across the range of growth rates examined. In their stead, a new linear relation unifying the slow- and fast-growth regimes was revealed between the cell mass and the number of cell divisions it takes to replicate and segregate a newly initiated pair of replication origins. This and other findings in this study suggest a single-cell division model, which not only reproduces the bulk relations observed but also recapitulates the adder phenomenon established recently for stochastically dividing cells13–15. These results allowed us to develop quantitative insight into the bacterial cell cycle, providing a firm new foundation for the study of bacterial growth physiology.
Real‐world experiences of apremilast in clinics for Japanese patients with psoriasis
Authors: Saruwatari Hiroshi
Published: October 2019

Psoriasis, though not an immediately life‐threatening disorder, still lowers quality of life and disrupts daily functions. While many treatments for psoriasis exist, few are convenient and safe long term; even if sufficiently effective, treatments themselves often decrease quality of life and make long‐term treatment adherence difficult. Approved in Japan in December 2016, apremilast was expected to function as a simple, long‐term, systemic therapeutic agent for psoriasis. We report on the clinical outcomes of administrating apremilast for 2 years as observed in 46 psoriatic patients at the Saruwatari Dermatology Clinic between March 2017 and February 2019. We believe the ease of clinic consultation (as compared with large general hospital consultation) draws patients who are busy or have mild symptoms, and consequently poor adherence to regular visits and treatment, reflecting realistic conditions. Major adverse events with apremilast treatment were diarrhea (37.0%) and nausea (15.3%), with most cases of diarrhea being mild. Drug survival analysis by the Kaplan–Meier method revealed a 1‐year continuation rate of 46.8% and a 2‐year continuation rate of 37.4%. Dermatology Life Quality Index (DLQI) scores during the observation period declined from 9.3 to 2.8 (P < 0.0001) on average, with the DLQI‐0/1 achievement rate being 28.6%. Based on our findings, we conclude that apremilast is suitable as a long‐lasting basic treatment that is easy to prescribe in small clinics and easy to use in everyday life.
Sex, senescence, sources and sinks
Authors: Galipaud Matthias , Kokko Hanna
Published: October 2019

Why do most organisms age, and why do most of them reproduce sexually? Does sex rejuvenate? We review progress that has been made linking theories of senescence with those of sexual reproduction.

We show that there is a dearth of theory against the numerous questions waiting to be answered theoretically or empirically: observed senescence patterns are a result of past selection acting on individuals of different age categories and abundances, modes of reproduction (asexual, sexual, facultatively sexual, via buds or zygotes). Modular organisms present their own challenges. Assigning offspring an unambiguous age of zero at birth is often too simplistic.

We also comment on germline mutations as a form of ageing over generations (Lansing effect) and ask whether there is value in reinvigorating an old metaphor (1988, Sex and death in the protozoa. New York, NY, USA: Cambridge University Press) of chairs and their chairmakers who both are subject to deterioration over time, since endogenous repair is never foolproof.

Future theory could usefully revisit a known mathematical analogy between selection on senescence across age classes and source–sink theory. Some modes of reproduction (particularly asexuality) may yield offspring that are, in a sense, already aged, with the problem increasing over generations (ultimately leading to a demographic sink). Insofar as sexuality ‘rejuvenates’, it does so through a gamble that, with some frequency, produces ‘exogenously repaired’ individuals that act as a source of genes to future generations. This gamble has been argued to be managed best when life cycles include a unicellular stage (zygote), an argument that could be usefully complemented with an analysis of the relevant economic trade‐offs between offspring size and number.

A free Plain Language Summary can be found within the Supporting Information of this article.
Navigating through therpackages for movement
Authors: Joo Rocío , Boone Matthew E. , Clay Thomas A. , Patrick Samantha C. , Clusella‐Trullas Susana , Basille Mathieu
Published: October 2019

The advent of miniaturized biologging devices has provided ecologists with unprecedented opportunities to record animal movement across scales, and led to the collection of ever‐increasing quantities of tracking data. In parallel, sophisticated tools have been developed to process, visualize and analyse tracking data; however, many of these tools have proliferated in isolation, making it challenging for users to select the most appropriate method for the question in hand. Indeed, within thersoftware alone, we listed 58 packages created to deal with tracking data or ‘tracking packages’.

Here, we reviewed and described each tracking package based on a workflow centred around tracking data (i.e. spatio‐temporal locations (x,y,t)), broken down into three stages: pre‐processing, post‐processing and analysis, the latter consisting of data visualization, track description, path reconstruction, behavioural pattern identification, space use characterization, trajectory simulation and others.

Supporting documentation is key to render a package accessible for users. Based on a user survey, we reviewed the quality of packages' documentation and identified 11 packages with good or excellent documentation.

Links between packages were assessed through a network graph analysis. Although a large group of packages showed some degree of connectivity (either depending on functions or suggesting the use of another tracking package), one third of the packages worked in isolation, reflecting a fragmentation in thermovement‐ecology programming community.

Finally, we provide recommendations for users when choosing packages, and for developers to maximize the usefulness of their contribution and strengthen the links within the programming community.
Re‐assessing microbiomes in the low‐biomass reproductive niche
Authors: O’Callaghan JL , Turner R , Dekker Nitert M , Barrett HL , Clifton V , Pelzer ES
Published: October 2019

The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation‐independent studies suggests that the female upper genital tract is not sterile; however, the significance of this for reproductive health and disease remains to be elucidated fully. Further, diagnosis and treatment of infectious reproductive tract pathologies using cultivation‐independent technologies represents a largely unchartered area of modern medical science. The challenge now is to design well‐controlled experiments to account for the ease of contamination known to confound molecular‐based studies of low‐biomass niches, including the uterus and placenta. This will support robust assessment of the potential function of microorganisms, microbial metabolites, and cell‐free bacterial DNA on reproductive function in health and disease.

Tweetable abstract

Molecular microbial studies of low‐biomass niches require stringent experimental controls to reveal causal relations in reproductive health and disease.
G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy
Authors: Lai Shuiqing , Fu Xiaoying , Yang Shufen , Zhang Shuting , Lin Qiuxiong , Zhang Mengzhen , Chen Hongmei
Published: October 2019

Background

G protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).

Methods

C57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ < 1 were regarded as LVDD.

Results

Compared to 8‐week‐old diabetic mice and 12‐week‐old control mice, GRK2‐mRNA level and expression in myocardial tissues of 12‐week‐old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen‐3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12‐week‐old diabetic mice elevated as well. The GRK2‐mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.

Conclusions

GRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.
Magnetocardiography for identification of coronary ischemia in patients with chest pain and normal resting 12‐lead electrocardiogram
Authors: Ramesh Raja , Senthilnathan Sengottuvel , Satheesh Santhosh , Swain Pragyna Parimita , Patel Rajesh , Ananthakrishna Pillai Ajith , Katholil Gireesan , Selvaraj Raja J.
Published: October 2019

Background

Identification of coronary ischemia in patients presenting with chronic chest pain is difficult as resting ECG can be normal. Diagnosis of coronary ischemia requires evaluation during exercise or pharmacological stress. A noninvasive test to identify coronary ischemia at rest without the need for exercise is desirable. We studied the diagnostic accuracy of magnetocardiography (MCG) at rest to detect coronary ischemia in these patients.

Methods

Patients with chronic chest pain and suspected coronary ischemia with a normal ECG were included. Patients underwent treadmill test (TMT) and were divided into TMT positive and TMT negative groups. MCG was recorded in a magnetically shielded room. Iso‐field contour maps generated at the T‐wave peak were compared between the groups. From the magnetic field map (MFM), the magnetic field angle at T‐wave peak was calculated and was also compared across the two groups.

Results

There were a total of 29 patients, 12 with positive TMT and 17 with negative TMT. An abnormal magnetic field angle was more common in the TMT positive group (72% vs. 6%). Abnormal contour maps in the form of nondipole patterns or abnormal orientation were seen in 81.8% (9/11) patients in TMT positive group and 6.8% (1/17) patients in the TMT negative group (p < .001).

Conclusion

Abnormal magnetic field angle and abnormal magnetic field maps in MCG recorded at rest are able to identify the presence of coronary ischemia in patients with chronic chest pain and a normal resting ECG.
Cervico‐vaginal placental α‐macroglobulin‐1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor
Authors: Radan Anda‐Petronela , Aleksandra Polowy Justyna , Heverhagen Anneke , Simillion Cedric , Baumann Marc , Raio Luigi , Schleussner Ekkehard , Mueller Martin , Surbek Daniel
Published: October 2019

Introduction

Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α‐macroglobulin‐1 as a new diagnostic marker in the prediction of preterm birth.

Material and methods

We performed a prospective observational trial in women with intact membranes between 24+0 and 36+6 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α‐macroglobulin‐1 measurements in cervicovaginal fluid regarding three different presentation‐to‐delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α‐macroglobulin‐1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements.

Results

We included 126 women in the study. We detected high specificity (97%‐98%) and negative predictive value (89%‐97%) for placental α‐macroglobulin‐1 at all time intervals. We assessed placental α‐macroglobulin‐1 in combination with cervical length measurements (≤15 mm) in the sub‐group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7‐ and 14‐day presentation‐to‐delivery intervals.

Conclusions

Our study provides evidence that placental α‐macroglobulin‐1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations.
Students’ Need Satisfaction Profiles: Similarity and Change over the Course of a University Semester
Authors: Gillet Nicolas , Morin Alexandre J.S. , Huyghebaert‐Zouagh Tiphaine , Alibran Emilie , Barrault Servane , Vanhove‐Meriaux Charlotte
Published: October 2019

Self‐determination theory positions the satisfaction of students’ needs for autonomy, competence, and relatedness as important determinants of various educational outcomes. In this study, we identify subpopulations of students characterized by distinct configurations of need satisfaction in the educational context, and assess the extent to which the nature of these configurations, and students’ individual profiles, remain stable over the course of a university semester. We also examine the role of perfectionism in the prediction of profile membership, and how these profiles relate to a variety of educational outcomes. A total of 521 first‐year undergraduate university students completed our measures at the beginning and end of a university semester. We identified five need satisfaction profiles, which remained unchanged over the course of the study. Students characterized by higher levels of self‐oriented perfectionism were more likely to be a member of a profile characterized by high levels of relatedness and global needs satisfaction associated with average levels of competence need satisfaction (“Globally Satisfied and Highly Connected” profile) relative to the other ones, and into the “Globally Satisfied” profile relative to the “Globally Dissatisfied, Highly Connected, and Competence Deficient” profile. Finally, the “Globally Dissatisfied, Highly Connected, and Competence Deficient” profile was associated with the least desirable outcomes (the lowest levels of students’ interest toward their studies, satisfaction, and attendance, and the highest levels of dropout intentions).
High‐throughput sequencing of T‐cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies
Authors: Komkov Alexander , Miroshnichenkova Anna , Nugmanov Gaiaz , Popov Alexander , Pogorelyy Mikhail , Zapletalova Eva , Jelinkova Hana , Pospisilova Sarka , Lebedev Yuri , Chudakov Dmitriy , Olshanskaya Yulia , Plevova Karla , Maschan Michael , Mamedov Ilgar
Published: October 2019

Rearrangements of T‐ and B‐cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been used so far due to the lack of a method for its rearrangement detection in genomic DNA. Here we propose the first high‐throughput sequencing based method for the identification of clonal TRA gene rearrangements at the DNA level. The method is based on target amplification of the rearranged TRA locus using an advanced multiplex polymerase chain reaction system and high‐throughput sequencing, and has been tested on DNA samples from peripheral blood of healthy donors. Combinations of all functional V‐ and J‐segments were detected, indicating the high sensitivity of the method. Additionally, we identified clonal TRA rearrangements in 57 out of 112 tested DNA samples of patients with various T‐lineage lymphoproliferative disorders. The method fills the existing gap in utilizing the TRA gene for a wide range of studies, including clonality assessment, MRD monitoring and clonal evolution analysis in different lymphoid malignancies.
Mycobacterium tuberculosis does not show evidence of molecular DNA in human cadaveric ocular tissues in an endemic setting
Authors: Chauhan Harish , Bansal Reema , Kumar Aman , Sharma Surya P. , Gude Geethanjali , Nahar Uma , Singh Ramandeep , Jain Arun K. , Gupta Vishali
Published: October 2019

Background

Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra‐pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known.

Methods

We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel‐based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real‐time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non‐tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology.

Results

The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl‐Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology.

Conclusions

MTB could not be detected in human ocular tissues in latent state in India, a TB‐endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.
Japan Esophageal Society classification for predicting the invasion depth of superficial esophageal squamous cell carcinoma: Should it be modified now?
Authors: Goda Kenichi , Irisawa Atsushi
Published: October 2019

This Editorial refers to the article by Tanaka et al., p 49–55 and Kimura et al., p 56–64 of this issue.
Combined soil and foliar ZnSO4 application improves wheat grain Zn concentration and Zn fractions in a calcareous soil
Authors: Zhao Aiqing , Wang Bini , Tian Xiaohong , Yang Xingbin
Published: October 2019

Dietary zinc (Zn) deficiency is a common micronutrient deficiency in humans. Zinc fertilization has been proved to be an effective approach to improve grain Zn concentration in wheat and alleviate Zn deficiency in humans. To maximize the potential of Zn fertilization, it is necessary to select appropriate Zn fertilizer forms and application methods. Here, combined soil and foliar application of ZnSO4, rather than Zn‐EDTA, effectively increased grain Zn concentration in winter wheat (Triticum aestivum L. cv. “Xiaoyan 22”) grown in a calcareous soil. However, neither ZnSO4 nor Zn‐EDTA, when applied to the soil or the foliage alone, had any significant effect on grain Zn concentration. The fractions of Zn loosely bound to organic matter, carbonate‐bound Zn and manganese oxide‐bound Zn in the rhizosphere soil changed dynamically over the course of the wheat growth period, with the highest levels found at the jointing stage. The residual ZnSO4 fertilizer had a positive effect on grain Zn concentration in the subsequent wheat crop due to increased storage of phytic acid in wheat grains and high concentrations of Zn loosely bound to organic matter and carbonate‐bound Zn in the soil. In comparison, Zn‐EDTA applied to the soil only increased the exchangeable‐Zn fraction, and had little residual effect on any other Zn fraction. Repeated soil applications of Zn‐EDTA would be effective to improve grain Zn concentration in wheat plants in subsequent years.

Highlights

Effects of Zn fertilization in a calcareous soil were tested by a 3‐year field experiment.

Combined soil and foliar application of ZnSO4 improved grain Zn concentration in wheat.

Foliar ZnSO4 or Zn‐EDTA application alone had no significant effects on grain Zn concentration.

Soil ZnSO4 application had a long‐term positive effect on grain Zn concentration in the subsequent wheat crop.