bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Energy Expenditure During Walking and Step Length in Patients With Heart Failure
Authors: Yoshimura Kae , Urabe Yukio , Maeda Noriaki , Yoshida Toshinobu
Published: April 2019

Objective:

Step length (SL) is an important indicator of physical function in older individuals and patients with heart failure (HF). The aim of this study was to investigate correlations between energy expenditure during walking and SL in patients with HF in different age groups.

Subjects and Methods:

A total of 44 patients participated in this study. The patients were divided into 2 groups with age younger than 65 years (the nonelderly group) and 65 years or older (the elderly group). Oxygen uptake (

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2) during walking was measured for 6 minutes at a self-selected speed using the FitMate Pro (COSMED, Rome, Italy). The highest values of

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2 (h

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2) and O2 cost during walking were determined. Step length (m), SL/height ratio (%), walking speed, and handgrip strength (HS) were also measured. All patients underwent a symptom-limited, graded exercise test on a cycle ergometer to derive peak

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2.

Results and Conclusions:

Height was significantly correlated with SL in the nonelderly group (r = 0.56, P = .010) but not in the elderly group. h

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2 was not correlated with SL or SL/height ratio. In the elderly group, O2 cost was negatively correlated with SL (r =−0.61, P = .027) but not with SL/height ratio. There was a significant correlation between HS and SL only in the elderly group (r = 0.58, P = .001). These results suggest that SL might be a useful index that reflects energy expenditure during walking in elderly patients with HF.
Effect of Diaphragm Postisometric Relaxation in Older Adults
Authors: Fronczek-Wojciechowska Magdalena , Mysłek Karolina , Sajek Aleksandra , Padula Gianluca , Kopacz Karolina
Published: April 2019

Objective:

To analyze the diaphragm postisometric relaxation (PIR) effect in older people.

Subjects and Methods:

The study group comprised 23 people with a mean age of 65 (5) years. Examinations consisted of spirometry, pulse oximetry, chest circumference test, and palpation of diaphragm. Examination was done twice, before and after the program of exercises related to diaphragm PIR.

Results and Conclusions:

Slow vital capacity, maximal voluntary ventilation, chest mobility, and oxygen saturation were significantly higher after diaphragm PIR. Diaphragm tension improved in 30% of participants. PIR of diaphragm can improve respiratory parameters, chest mobility, and diaphragm tension without influence on the heart rate.
Influence of the Nordic Walking Intervention Program on the Improvement of Functional Parameters in Older Women
Authors: Panou Helen , Giovanis Vasilios , Tsougos Elias , Angelidis George
Published: April 2019

Background:

Nordic Walking is a total body type of exercise that can be performed by nonathletes as a health-promoting physical activity.

Aims:

In the present study, we aimed to evaluate the impact of a Nordic Walking interventional program in older adults, with regard to the potential improvements in functional parameters.

Methods:

Thirty-five women (mean age: 67.86 years, SD: 4.44 years) participated in a 25-week Nordic Walking program, while 25 women (control group, mean age: 76.97 years, SD: 8.14 years) did not engage to any type of exercise during the same period. Functional parameters were assessed using the Senior Fitness Test and the Bosco Counter-Movement Jump Test at baseline and after the completion of the program.

Results:

In the experimental group, improvements were observed in all functional parameters assessed by the Senior Fitness Test, including strength, flexibility, movement coordination, dynamic balance, and aerobic capacity. No such correlations were found in the control group. Similarly, with regard to the parameters recorded using the Counter-Movement Jump Test, there was an improvement in strength from baseline to the final measurements.

Conclusions:

Our findings confirmed previous evidence regarding the beneficial effects of Nordic Walking on functional parameters in older adults.
Dynapenic Abdominal Obesity as a Risk Factor for Falls in Older Women
Authors: Pereira Juscelia Cristina , de Moraes Elias Julia , Neri Silvia G. R. , Gadelha André Bonadias , Lemos Rafael Raposo , Lima Ricardo M.
Published: April 2019

Background:

The combination of dynapenia and central obesity has been introduced as dynapenic abdominal obesity (D/AO), but its relationship with falls-related phenotypes is unclear.

Objectives:

To investigate the association between D/AO, risk of falls, dynamic balance, and fear of falling in older women.

Design:

Cross-sectional study.

Methods:

A total of 217 women (68.03 ± 6.21 years) underwent waist circumference and handgrip measurements. Risk of falls (QuickScreen), the Timed Up and Go test, and fear of falling were also evaluated. Dynapenia was classified using the lower tertile of handgrip strength as cutoff value (20.67 kgf), while obesity was considered a waist circumference of greater than 88 cm; D/AO was the combination of both criteria.

Results:

Dynapenic abdominal obesity was associated with increased probability of falls (χ2 = 32.392; P < .001), reflecting decreased sit-to-stand performance (P = .001), reaction time (P < .001), peripheral sensation (P = .05), and postural balance (P = .05). Time to complete the Timed Up and Go test was significantly higher in D/AO group (P < .001). Finally, D/AO (30.08 ± 7.81) and abdominal obesity (27.77 ± 7.40) women presented increased fear of falling than normal (23.22 ± 5.50) and dynapenic (26.61 ± 8.33) groups (P < .05).

Conclusion:

Dynapenic abdominal obesity is associated with increased risk and fear of falls and reduced dynamic balance in older women. These relationships are stronger than those observed for obesity or dynapenia alone.
Utilization of Point-of-Care Ultrasonography (POCUS) for Small Bowel Obstruction
Authors: Elliott Kyle R. , Dunn Matthew J. , Krueger Timothy D. , Steele David A.
Published: April 2019

Small bowel obstruction is a frequently encountered condition throughout emergency departments and accounts for a large number of surgical hospital admissions. Point-of-care ultrasonography (POCUS) by emergency providers can serve as a valuable tool to assist in prompt and accurate diagnosis, which could potentially reduce the quantity of undesirable effects such as radiation and cost seen with other advanced imaging modalities (e.g., computed tomography).
The Use of Ketamine as an Adjunct to Treating Opioid Refractory Cancer-Related Pain in the Emergency Department
Authors: Brockett-Walker Camille
Published: April 2019

The Research to Practice column is designed to provide advanced practice registered nurses (APRNs) with an analysis of a current research topic with implications for practice change within the emergency care settings. This review examines a recent study conducted by K. J. Bowers, K. B. McAllister, M. Ray, and C. Heitz (2017) entitled “Ketamine as an adjunct to opioids for acute pain in the emergency department: A randomized controlled trial.” The authors conducted a randomized, double-blinded, placebo-controlled trial at a single academic emergency department (ED) to compare standard opioid pain control in the ED population to the use of ketamine in conjunction with opioids in the same population. Participants were randomized into either the ketamine group, receiving 0.1 mg/kg of ketamine in conjunction with an intravenous opioid, or to the control group, receiving an equivalent volume of normal saline in addition to an intravenous opioid. Participants were evaluated for adequacy of pain control, side effects, and level of sedation every 30 min up to the 120-min time point. Data revealed that patients receiving ketamine had a statistically significant lower mean pain score, 0.6512 (p = 0.0083), compared with patients in the control group. The data also showed that patient satisfaction with pain control was similar for the ketamine group and the control group. These and other associated findings have implications for APRN practice, including managing acute pain in the ED setting and preventing hospital admission of acute-on-chronic pain exacerbations in the ED.
Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease
Authors: Cai Mengjie , Guo Zhiwei , Xing Guoqiang , Peng Haitao , Zhou Liang , Chen Huaping , McClure Morgan A. , He Lin , Xiong Liangwen , He Bin , Du Fei , Mu Qiwen
Published: April 2019

Objective:

The purpose of this meta-analysis was to evaluate the therapeutic effect of transcranial direct current stimulation (tDCS) on mild to moderate Alzheimer disease (AD) patients.

Materials and Methods:

PubMed, Embase, Web of Science, and Cochrane Library were searched until April 2018. The primary cognitive outcomes were extracted from included articles. A crude standardized mean difference with 95% CI was calculated by using fixed or random effect models.

Results:

Seven studies with 146 patients were included in this meta-analysis. The pooled result showed that tDCS significantly improved cognitive function of AD patients (standardized mean difference=0.37; 95% CI, 0.09-0.65; P=0.01). Subgroup analyses showed that: a single session of tDCS was significantly effective (P<0.05) whereas repeated sessions of tDCS was not lower current density (0.06 mA/cm2) (P>0.05) but not higher current density (0.08 mA/cm2) significantly improved cognitive performance; stimulating the temporal cortex (P<0.05) but not the left dorsal lateral prefrontal cortex significantly improved cognitive function of AD patients; and improved cognitive function occurred in the group with higher education (P<0.05) but not in the group with lower education.

Conclusions:

Current evidence suggests that tDCS has a beneficial effect in mild to moderate AD patients. We must be cautious about the results of subgroup analysis given small sample sizes, and further well-designed studies with larger sample size are required to verify these results.
GenMap: Fast and Exact Computation of Genome Mappability
Authors: Pockrandt Christopher , Alzamel Mai , Iliopoulos Costas S. , Reinert Knut
Published: April 2019

We present a fast and exact algorithm to compute the (k, e)-mappability. Its inverse, the (k, e)-frequency counts the number of occurrences of each k-mer with up to e errors in a sequence. The algorithm we present is a magnitude faster than the algorithm in the widely used GEM suite while not relying on heuristics, and can even compute the mappability for short k-mers on highly repetitive plant genomes. We also show that mappability can be computed on multiple sequences to identify marker genes illustrated by the example of E. coli strains. GenMap allows exporting the mappability information into different formats such as raw output, wig and bed files. The application and its C++ source code is available on https://github.com/cpockrandt/genmap.
Thede novoreference genome and transcriptome assemblies of the wild tomato speciesSolanum chilense
Authors: Stam Remco , Nosenko Tetyana , Hörger Anja C. , Stephan Wolfgang , Seidel Michael , Kuhn José M.M. , Haberer Georg , Tellier Aurelien
Published: April 2019

Background

Wild tomato species, likeSolanum chilense, are important germplasm resources for enhanced biotic and abiotic stress resistance in tomato breeding. In addition,S. chilenseserves as a model system to study adaptation of plants to drought and to investigate the evolution of seed banks. However to date, the absence of a well annotated reference genome in this compulsory outcrossing, very diverse species limits in-depth studies on the genes involved.

Findings

We generated ∼134 Gb of DNA and 157 Gb of RNA sequence data ofS chilense, which yielded a draft genome with an estimated length of 914 Mb in total encoding 25,885 high-confidence (hc) predicted gene models, which show homology to known protein-coding genes of other tomato species. Approximately 71% (18,290) of the hc gene models are additionally supported by RNA-seq data derived from leaf tissue samples. A benchmarking with Universal Single-Copy Orthologs (BUSCO) analysis of predicted gene models retrieved 93.3% BUSCO genes, which is in the current range of high-quality genomes for non-inbred plants. To further verify the genome annotation completeness and accuracy, we manually inspected the NLR resistance gene family and assessed its assembly quality. We revealed the existence of unique gene families of NLRs toS. chilense. Comparative genomics analyses ofS. chilense, cultivated tomatoS. lycopersicumand its wild relativeS. pennelliirevealed similar levels of highly syntenic gene clusters between the three species.

Conclusions

We generated the first genome and transcriptome sequence assembly for the wild tomato speciesSolanum chilenseand demonstrated its value in comparative genomics analyses. We make these genomes available for the scientific community as an important resource for studies on adaptation to biotic and abiotic stress inSolanaceae, on evolution of self-incompatibility, and for tomato breeding.
Estimating the Relative Probability of Direct Transmission between Infectious Disease Patients
Authors: Leavitt Sarah V , Lee Robyn S , Sebastiani Paola , Horsburgh Charles R. , Jenkins Helen E , White Laura F
Published: April 2019

Background

Estimating infectious disease parameters such as the serial interval (time between symptom onset in primary and secondary cases) and reproductive number (average number of secondary cases produced by a primary case) are important to understand infectious disease dynamics. Many estimation methods require linking cases by direct transmission, a difficult task for most diseases.

Methods

Using a subset of cases with detailed genetic or contact investigation data to develop a training set of probable transmission events, we build a model to estimate the relative transmission probability for all case-pairs from demographic, spatial and clinical data. Our method is based on naive Bayes, a machine learning classification algorithm which uses the observed frequencies in the training dataset to estimate the probability that a pair is linked given a set of covariates.

Results

In simulations we find that the probabilities estimated using genetic distance between cases to define training transmission events are able to distinguish between truly linked and unlinked pairs with high accuracy (area under the receiver operating curve value of 95%). Additionally only a subset of the cases, 10-50% depending on sample size, need to have detailed genetic data for our method to perform well. We show how these probabilities can be used to estimate the average effective reproductive number and apply our method to a tuberculosis outbreak in Hamburg, Germany.

Conclusions

Our method is a novel way to infer transmission dynamics in any dataset when only a subset of cases has rich contact investigation and/or genetic data.

KEY MESSAGES

This method provides a way to calculate the relative probability that two infectious disease patients are connected by direct transmission using clinical, demographic, geographic, and genetic characteristics.

We use a naïve Bayes, a machine learning technique to estimate these probabilities using a training set of probable links defined by contact investigation or pathogen WGS data on a subset of cases.

These probabilities can be used to explore possible transmission chains, rule out transmission events, and estimate the reproductive number.
Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures
Authors: Brahmachari Sumitabha , Marko John F.
Published: April 2019

Eukaryote cell division features a chromosome compaction-decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compaction-segregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops - a polymer “brush” - where active extrusion of loops controls the brush structure. Given topoisomerase (TopoII)-catalyzed topology fluctuations, we find that inter-chromosome entanglements are minimized for a certain “optimal” loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction, and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle, and highlights a mechanism of directing Topo-II mediated strand passage via loop extrusion driven lengthwise compaction.
Unraveling the relation between EEG-correlates of attentional orienting and sound localization performance: a diffusion model approach
Authors: Klatt Laura-Isabelle , Schneider Daniel , Schubert Anna-Lena , Hanenberg Christina , Lewald Jörg , Wascher Edmund , Getzmann Stephan
Published: April 2019

Understanding the contribution of cognitive processes and their underlying neurophysiological signals to behavioral phenomena has been a key objective in recent neuroscience research. Using a diffusion-model framework, we investigated to what extent well-established correlates of spatial attention in the electro-encephalogram contribute to behavioral performance in an auditory free-field sound-localization task. Younger and older participants were instructed to indicate the horizontal position of a pre-defined target among three simultaneously presented distractors. The central question of interest was whether posterior alpha lateralization and amplitudes of the anterior contralateral N2 subcomponent (N2ac) predict sound localization performance (accuracy, mean reaction time) and/or diffusion model parameters (drift rate, boundary separation, non-decision time). Two age groups were compared to explore whether in older adults, who struggle with multi-speaker environments, the brain-behavior relationship would differ from younger adults. Regression analyses revealed that N2ac amplitudes predicted drift rate and accuracy, whereas alpha lateralization was not related to behavioral or diffusion modeling parameters. This was true irrespective of age. The results indicate that a more efficient attentional filtering and selection of information within an auditory scene, reflected by increased N2ac amplitudes, was associated with a higher speed of information uptake (drift rate) and better localization performance (accuracy), while the underlying response criteria (threshold separation), mean reaction times, and non-decisional processes remained unaffected. The lack of a behavioral correlate of post-stimulus alpha power lateralization constrast the well-established notion that pre-stimulus alpha power reflects a functionally relevant attentional mechanism. This highlights the importance of distinguishing anticipatory from post-stimulus alpha power modulations.
Epidemic Growth Rates and Host Movement Patterns Shape Management Performance for Pathogen Spillover at The Wildlife-livestock Interface
Authors: Manlove Kezia R. , Sampson Laura M. , Borremans Benny , Cassirer E. Frances , Miller Ryan S. , Pepin Kim M. , Besser Thomas E. , Cross Paul C.
Published: April 2019

ABSTRACT

Managing pathogen spillover at the wildlife-livestock interface is a key step toward improving global animal health, food security, and wildlife conservation. However, predicting the effectiveness of management actions across host-pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific. We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objective was used to evaluate management performance. This framework may be a useful step in advancing how we classify and prioritise responses to novel pathogen spillover threats, and evaluate current management actions for pathogens emerging at the wildlife-livestock interface.
Relationship between gut microbiota and circulating metabolites in population-based cohorts
Authors: Vojinovic Dina , Radjabzadeh Djawad , Kurilshikov Alexander , Amin Najaf , Wijmenga Cisca , Franke Lude , Ikram M. Arfan , Uitterlinden Andre G. , Zhernakova Alexandra , Fu Jingyaun , Kraaij Robert , van Duijn Cornelia M.
Published: April 2019

Gut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. As recent development in metabolomics allows classifying the lipoprotein particles into more details, we aimed to examine the impact of gut microbiota on circulating metabolites measured by Nuclear Magnetic Resonance (1H-NMR) technology in 2,309 individuals from the Rotterdam Study and the LifeLines-DEEP cohort in whom gut microbiota was profiled using 16S rRNA gene sequencing. The relationship between gut microbiota and metabolites was assessed by linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, and multiple testing. Our analysis revealed association of 32 microbial families and genera with very-low-density and high-density subfractions, serum lipid measures, glycolysis-related metabolites, amino acids, and acute phase reaction markers. These observations provide novel insights into the role of microbiota in host metabolism and support the potential of gut microbiota as a target for therapeutic and preventive interventions.
Workplace Harassment and Risk of Depression Among Adults in the United States
Authors: Aduse-Poku Livingstone , Jahanfar Shayester
Published: April 2019

Purpose

The purpose of the study is to perform an analysis of the relationship between workplace harassment and risk depression among adults in the United States.

Methods

Across-sectional study of 33772 adults was done using the National Health Interview Survey (NHIS) sample adult data in the USA. The variables collected included depression, harassment, age, race, sex, and marital status. Data was analyzed using IBM Statistical Package for the Social Sciences (SPSS) for windows, version 25.0.

Results

Results showed a possible relationship between workplace harassment and depression among adults. Adults who were harassed were 0.39 times more likely to be depressed than those who were not harassed (95%CI: 0.45-0.81), after adjusting for sex, age, race, marital status, pay, and number of years on the job, the odd was almost the same [AOR (95%CI):0.55(0.40-0.77)].

Conclusion

The findings of the study show that there is a positive association between workplace harassment and depression.
Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program
Authors: Chivet M , Marchioretti C , Pirazzini M , Piol D , Scaramuzzino C , Polanco JM , Nath S , Zuccaro E , Nogara L , Canato M , Marcucci L , Parodi S , Romanello V , Armani A , D’Antonio M , Sambataro F , Dassi E , Pegoraro E , Sorarù G , Rinaldi C , Lieberman AP , Blaauw B , Sandri M , Basso M , Pennuto M
Published: April 2019

Spinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. Although clinical and experimental evidence highlight a primary role for skeletal muscle in the onset, progression, and outcome of disease, the pathophysiological and molecular processes underlying SBMA muscle atrophy are poorly understood. Here we show that polyQ-expanded AR alters intrinsic muscle force generation before denervation. Reduced muscle force was associated with a switch in fiber-type composition, disrupted muscle striation, altered calcium (Ca++) dynamics in response to muscle contraction, and aberrant expression of excitation-contraction coupling (ECC) machinery genes in transgenic, knock-in and inducible SBMA mice and patients. Importantly, treatment to suppress polyQ-expanded AR toxicity restored ECC gene expression back to normal. Suppression of AR activation by surgical castration elicited similar ECC gene expression changes in normal mice, suggesting that AR regulates the expression of these genes in physiological conditions. Bioinformatic analysis revealed the presence of androgen-responsive elements on several genes involved in muscle function and homeostasis, and experimental evidence showed AR-dependent regulation of expression and promoter occupancy of the most up-regulated gene from transcriptomic analysis in SBMA muscle, i.e. sarcolipin, a key ECC gene. These observations reveal an unpredicted role for AR in the regulation of expression of genes involved in muscle contraction and Ca++ dynamics, a level of muscle function regulation that is disrupted in SBMA muscle, yet restored by pharmacologic treatment.
Retromer repletion with AAV9-VPS35 restores endosomal function in the mouse hippocampus
Authors: Qureshi Yasir H. , Berman Diego E. , Klein Ronald L. , Patel Vivek M. , Simoes Sabrina , Kannan Suvarnambiga , Cox Rebecca , Waksal Samuel D , Stevens Beth , Petsko Gregory A. , Small Scott A.
Published: April 2019

Retromer has emerged as a master conductor of endosomal trafficking, and VPS35 and other retromer-related proteins are found to be deficient in late-onset Alzheimer’s disease (AD). Depleting VPS35 in neurons impairs retromer function, affecting for example the trafficking of the amyloid-precursor protein (APP) and the glutamate receptor GluA1. Whether VPS35 repletion, after chronic in vivo depletion, can rescue these impairments remains unknown. Here we set out to address this question by using a viral vector approach for VPS35 repletion. First, we completed a series of studies using neuronal cultures in order to optimize AAV9-VPS35 delivery, and to understand how exogenous VPS35 expression affects its endogenous levels as well as its binding to other retromer proteins. Next, we completed a series of studies in wildtype mice to determine the optimum protocol for in vivo delivery of AAV9-VPS35 to the hippocampus. We relied on this information to deliver AAV9-VPS35 to the hippocampus of mice genetically engineered to have chronic, neuronal-selective, VPS35 depletion. VPS35 repletion in the hippocampus was found to normalize APP cleavage and to restore glutamate receptor levels. Unexpectedly, chronic VPS35 depletion in neurons caused glial activation, similar to the pattern observed in AD, which was also partially normalized by VPS35 repletion. Taken together, these studies strengthen the mechanistic link between retromer and AD, and have therapeutic implications.
Serotonergic modulation of visual neurons inDrosophila melanogaster
Authors: Sampson Maureen M , Myers Gschweng Katherine M , Hardcastle Ben J , Bonanno Shivan L , Sizemore Tyler R , Arnold Rebecca C , Gao Fuying , Dacks Andrew M , Frye Mark A , Krantz David E
Published: April 2019

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing in the face of a highly variable stimulus space. Serotonergic neurons broadly innervate the optic ganglia ofDrosophila melanogaster, a widely used model for studying vision. The role for serotonergic signaling in theDrosophilaoptic lobe and the mechanisms by which serotonin regulates visual neurons remain unclear. Here we map the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina, and show that serotonin can modulate visual responses. Serotonin receptors are expressed in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for the initial steps of visual processing, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicates that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla is the primary site of serotonergic regulation for these neurons. Serotonin increases intracellular calcium in L2 terminals in layer M2 and alters the kinetics of visually induced calcium transients in L2 neurons following dark flashes. These effects were not observed in flies without a functional 5-HT2B, which displayed severe differences in the amplitude and kinetics of their calcium response to both dark and light flashes. While we did not detect serotonin receptor expression in L1 neurons, they also undergo serotonin-induced calcium changes, presumably via cell non-autonomous signaling pathways. We provide the first functional data showing a role for serotonergic neuromodulation of neurons required for initiating visual processing inDrosophilaand establish a new platform for investigating the serotonergic neuromodulation of sensory networks.

Author Summary

Serotonergic neurons innervate theDrosophila melanogastereye, but the function of serotonergic signaling is not known. We found that serotonin receptors are expressed in all neuropils of the optic lobe and identify specific neurons involved in visual information processing that express serotonin receptors. We then demonstrate that activation of these receptors can alter how visual information is processed. These are the first data suggesting a functional role for serotonergic signaling inDrosophilavision. This study contributes to the understanding of serotonin biology and modulation of sensory circuits.
Altered directed functional connectivity of the right amygdala in depression: high-density EEG study
Authors: Damborská Alena , Honzírková Eliška , Barteček Richard , Hořínková Jana , Fedorová Sylvie , Ondruš Šimon , Michel Christoph M. , Rubega Maria
Published: April 2019

The cortico-striatal-pallidal-thalamic and limbic circuits are suggested to play a crucial role in the pathophysiology of depression. Stimulation of deep brain targets might improve symptoms in treatment-resistant depression. However, a better understanding of connectivity properties of deep brain structures potentially implicated in deep brain stimulation (DBS) treatment is needed. Using high-density EEG, we explored the directed functional connectivity at rest in 25 healthy subjects and 26 patients with moderate to severe depression within the bipolar affective disorder, depressive episode, and recurrent depressive disorder. We computed the Partial Directed Coherence on the source EEG signals focusing on the amygdala, anterior cingulate, putamen, pallidum, caudate, and thalamus. The global efficiency for the whole brain and the local efficiency, clustering coefficient, outflow, and strength for the selected structures were calculated. In the right amygdala, all the network metrics were significantly higher (p<0.001) in patients than in controls. The global efficiency was significantly higher (p<0.05) in patients than in controls, showed no correlation with status of depression, but decreased with increasing medication intake (R2 = 0.59 and p = 1.52e − 05). The amygdala seems to play an important role in neurobiology of depression. Practical treatment studies would be necessary to assess the amygdala as a potential future DBS target for treating depression.
Effect of mannose modified chitosan on uptake of nanoparticles by macrophages
Authors: Lowsberg David , Smith John
Published: April 2019

This report provided a new method to prepare and evaluate mannose-modified chitosan-coated lactic acid-glycolic acid copolymer (PLGA) nanoparticles, and to investigate their effects on macrophage toxicity and macrophage uptake. The PLGA nanoparticles loaded with ovalbumin (OVA) were prepared by double emulsion method. The size and zeta potential of the nanoparticles were determined by laser granulometry after mannose-modified chitosan coating. The nanoparticles were observed by transmission electron microscopy. The appearance of the form, the BCA method to determine the OVA content, calculate the drug loading and release. The OVA nanoparticles labeled with fluorescein isothiocyanate (FITC) were co-incubated with macrophages (RAW 264. 7), cell viability was determined by MTT assay, and uptake was examined by fluorescence microscopy. Results The size and ζ potential of OVA-PLGA nanoparticles increased with the increase of chitosan coating concentration (P < 0.05), and OVA drug loading range was 7. 2% to 8. 4%. Chitosan and mannose modified chitosan coating FITC-OVAPLGA nanoparticles and RAW 264. 7 After incubation, there was little effect on cell viability (P > 0.05), but it significantly promoted macrophage uptake by FITC-OVA-PLGA nanoparticles (P < 0.05).
Signaling via GABAB receptors regulates early development and neurogenesis in the basal metazoan Nematostella vectensis
Authors: Levy Shani , Brekhman Vera , Bakhman Anna , Sebé-Pedrós Arnau , Kosloff Mickey , Lotan Tamar
Published: April 2019

The metabotropic gamma-amino-butyric acid B receptor (GABABR) is a G protein–coupled receptor that mediates neuronal inhibition by the neurotransmitter GABA. Here, we identified putative GABAB receptors and signaling modulators in the basal sea anemone Nematostella vectensis. Activation of GABABR signaling reversibly arrests planula-to-polyp transformation during early development and affects the neurogenic program. We identified four Nematostella GABABR homologs that have the conserved 3D extracellular domains and residues needed for binding of GABA and the GABABR agonist baclofen. Transcriptomic analysis, combined with spatial analysis of baclofen-treated planulae, revealed that baclofen down-regulated pro-neural factors such as NvSoxB(2), NvNeuroD1 and NvElav1. Baclofen also inhibited neuron development and extended neurites, resulting in an under-developed and less organized nervous system. Our results shed light on cnidarian development and suggest an evolutionarily conserved function for GABABR in regulation of neurogenesis, highlighting Nematostella as a new model system to study GABABR signaling.
The bumble bee microbiome increases survival of bees exposed to selenate toxicity
Authors: Rothman Jason A. , Leger Laura , Graystock Peter , Russell Kaleigh , McFrederick Quinn S.
Published: April 2019

Bumble bees are important and widespread insect pollinators who face many environmental challenges. For example, bees are exposed to the metalloid selenate when foraging on pollen and nectar from plants growing in contaminated soils. As it has been shown that the microbiome of animals reduces metalloid toxicity, we assayed the ability of the bee microbiome to increase survivorship against selenate challenge. We exposed uninoculated or microbiota‐inoculated Bombus impatiens workers to a field‐realistic dose of 0.75 mg l−1 selenate and found that microbiota‐inoculated bees survive slightly but significantly longer than uninoculated bees. Using 16S rRNA gene sequencing, we found that selenate exposure altered gut microbial community composition and relative abundance of specific core bacteria. We also grew two core bumble bee microbes – Snodgrassella alvi and Lactobacillus bombicola – in selenate‐spiked media and found that these bacteria grew in the tested concentrations of 0.001–10 mg l−1 selenate. Furthermore, the genomes of these microbes harbour genes involved in selenate detoxification. The bumble bee microbiome slightly increases survivorship when the host is exposed to selenate, but the specific mechanisms and colony‐level benefits under natural settings require further study.
Separating noise from signal:
Authors: WILF EITAN
Published: April 2019

Because ethnomethodology was founded in cybernetics, it institutionalized the idea that interactants strive to maintain interactional order and compensate for disorder through negative feedback mechanisms such as “repair work.” This idea informed a key strand in the study of human‐machine interaction in the United States, especially the idea that humans are inclined to repair the gaps in machines’ behavior and thus sustain the feeling that they are interacting with intentional entities. In some situations, however, humans prefer to expose and even exacerbate machines’ interactional incompetence. Such a preference manifests the aesthetic category of the uncanny, here theorized as the sudden awareness of the material foundations of one's immediate world, an awareness that emerges when those foundations become “noisy” and begin to reflexively point to themselves.
Reply to: Qigong as a Promising Mind‐Body Exercise for Cognitive Functioning
Authors: Wu Chunxiao , Tang Chunzhi
Published: April 2019

This letter comments on the letter by Ibanez et al.
Burnout: Can we help?
Authors: Menahem Samuel
Published: April 2019

The recent editorial highlighting factors that may lead to burnout among the paediatric fraternity drew attention to those at most risk. They included ‘intelligent, committed, single young women’ more so then men and those who were ‘high achievers with empathy who take the patients' problems to heart’. Yet little appears to be available to ameliorate the stresses experienced by clinicians while building their resilience and improving their understanding of the interactions between themselves and the patient/parents. Drawing on past experience, a psychologically orientated approach to clinical care is emphasised. This approach required greater knowledge of one's self together with the need to commune with like‐minded colleagues. That led to a Balint‐type weekly group led by a child psychiatrist where experiences were exchanged, new knowledge acquired and mutual support provided. That in turn led to further study and the acquisition of new skills, including ongoing supervision to achieve a therapeutic interview. The latter was facilitated by carefully listening to the patient/parent, recognising the hidden agenda, struggling with non‐compliant parents and appreciating concepts such as transference and counter‐transference as it related to the patient–doctor interaction. Such insights may help paediatricians improve their therapeutic effectiveness and increase their personal satisfaction, thus adding a bonus to the essential requirement of a knowledge‐based diagnosis and management plan. Yet, only a few avenues are available to acquire such experiences, which need to be made available not only to those who recognise their importance but to all. How best to achieve these goals remains unresolved.
Credibility in Policy Expertise: The Function of Boundaries Between Research and Policy
Authors: Williams Kate
Published: April 2019

As science becomes an increasingly crucial resource for addressing complex challenges in society, extensive demands are placed upon the researchers who produce it. Creating valuable expert knowledge that intervenes in policy or practice requires knowledge brokers to facilitate interactions at the boundary between research and policy. Yet, existing research lacks a compelling account of the ways in which brokerage is performed to gain credibility. Drawing on mixed‐method analysis of 12 policy research settings, I outline a novel set of strategies for attaining symbolic power, whereby policy experts position themselves and others via conceptual distances drawn between the “world of ideas” and the “world of policy and practice.” Disciplinary distance works to situate research as either disciplinary or undisciplinary, epistemic distance creates a boundary between complex specialist research and direct digestible outputs, temporal distance represents the separation of slow rigorous research and agile responsive analysis, and economic distance situates research as either pure and intrinsic or marketable and fundable. I develop a theoretical account that unpacks the boundaries between research communities and shows how these boundaries permit policy research actors to achieve various strategic aims.
Detection of HLA‐C*14:51 in a Vietnamese cord blood specimen
Authors: Yang Kuo‐Liang , Phu Chi‐dung , Lin Py‐Yu
Published: April 2019

A nucleotide substitution in codon 140 of HLA‐C*14:02:01:01 results in a novel allele, HLA‐C*14:51.
UBC‐Nepal expedition: phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude
Authors: Hoiland Ryan L. , Howe Connor A. , Carter Howard H. , Tremblay Joshua C. , Willie Chris K. , Donnelly Joseph , MacLeod David B. , Gasho Chris , Stembridge Mike , Boulet Lindsey M. , Niroula Shailesh , Ainslie Philip N.
Published: April 2019

Key points

Sherpa have lived in the Nepal Himalaya for 25–40 thousand years and display positive physiological adaptations to hypoxia.

Sherpa have previously been demonstrated to suffer less negative cerebral side effects of ascent to extreme altitude, yet little is known as to whether or not they display differential regulation of oxygen delivery to the brain compared to lowland natives.

We demonstrate that Sherpa have lower brain blood flow during ascent to and acclimatization at high altitude compared to lowlanders and that this difference in flow is not attributable to factors such as mean arterial pressure, blood viscosity and pH.

The observed lower cerebral oxygen delivery in Sherpa likely represents a positive adaptation that may indicate a cerebral hypometabolic conservation of energy at altitude and/or decreased risk of other cerebral consequences such as vasogenic oedema.

Debilitating side effects of hypoxia manifest within the central nervous system; however, high‐altitude natives of the Tibetan plateau, the Sherpa, experience negligible cerebral effects compared to lowland natives at extreme altitude. Phenotypical optimization of the oxygen cascade has been demonstrated in the systemic circulation of Tibetans and Sherpa, likely underscoring their adapted capacity to thrive at altitude. Yet, little is known as to how the cerebral circulation of Sherpa may be adapted. To examine potential differences in cerebral oxygen delivery in Sherpa compared to lowlanders we measured arterial blood gases and global cerebral blood flow (duplex ultrasound) during a 9 day ascent to 5050 m. Although cerebral oxygen delivery was maintained during ascent in lowlanders, it was significantly reduced in the Sherpa at 3400 m (−30.3 ± 21.6%; P < 0.01) and 4371 m (−14.2 ± 10.7%; P = 0.03). Furthermore, linear mixed effects modelling indicated that independent of differences in mean arterial pressure, pH and blood viscosity, race accounts for an approximately 100 mL min−1 (∼17–34%) lower cerebral blood flow in Sherpa compared to lowlanders across ascent to altitude (P = 0.046). To ascertain the role of chronic hypoxia independent of the ascent, Sherpa who had not recently descended were also examined at 5050 m. In these Sherpa, cerebral oxygen delivery was also lower compared to lowlanders (∼22% lower; P < 0.01). We highlight new information about the influence of race and genetic adaptation in the regulation of cerebral oxygen delivery. The lower cerebral oxygen delivery in the Sherpa potentially represents a positive adaptation considering Sherpa endure less deleterious cerebral consequences than lowlanders at altitude.
A blood-based prognostic biomarker in IBD
Authors: Biasci Daniele , Lee James C , Noor Nurulamin M , Pombal Diana R , Hou Monica , Lewis Nina , Ahmad Tariq , Hart Ailsa , Parkes Miles , McKinney Eoin F , Lyons Paul A , Smith Kenneth G C
Published: April 2019

Objective

We have previously described a prognostic transcriptional signature in CD8 T cells that separates patients with IBD into two phenotypically distinct subgroups, termed IBD1 and IBD2. Here we sought to develop a blood-based test that could identify these subgroups without cell separation, and thus be suitable for clinical use in Crohn’s disease (CD) and ulcerative colitis (UC).

Design

Patients with active IBD were recruited before treatment. Transcriptomic analyses were performed on purified CD8 T cells and/or whole blood. Phenotype data were collected prospectively. IBD1/IBD2 patient subgroups were identified by consensus clustering of CD8 T cell transcriptomes. In a training cohort, machine learning was used to identify groups of genes (‘classifiers’) whose differential expression in whole blood recreated the IBD1/IBD2 subgroups. Genes from the best classifiers were quantitative (q)PCR optimised, and further machine learning was used to identify the optimal qPCR classifier, which was locked down for further testing. Independent validation was sought in separate cohorts of patients with CD (n=66) and UC (n=57).

Results

In both validation cohorts, a 17-gene qPCR-based classifier stratified patients into two distinct subgroups. Irrespective of the underlying diagnosis, IBDhi patients (analogous to the poor prognosis IBD1 subgroup) experienced significantly more aggressive disease than IBDlo patients (analogous to IBD2), with earlier need for treatment escalation (hazard ratio=2.65 (CD), 3.12 (UC)) and more escalations over time (for multiple escalations within 18 months: sensitivity=72.7% (CD), 100% (UC); negative predictive value=90.9% (CD), 100% (UC)).

Conclusion

This is the first validated prognostic biomarker that can predict prognosis in newly diagnosed patients with IBD and represents a step towards personalised therapy.
Endothelial Cell Inflammation and Barriers Are Regulated by the Rab26-Mediated Balance between β2-AR and TLR4 in Pulmonary Microvessel Endothelial Cells
Authors: Chen Huaping , Yuan Ming , Huang Chunji , Xu Zhi , Li Mingchun , Zhang Chun , Gao Zhan , Zhang Mingzhou , Xu Jiancheng , Qian Hang , You Jiegen , He Binfeng , Wang Guansong , Hu Mingdong
Published: April 2019

Rab26 GTPase modulates the trafficking of cell surface receptors, such as G protein-coupled receptors including α2-adrenergic receptors in some cell types. However, the effect of Rab26 on β2-adrenergic receptor (β2-AR) trafficking or/and Toll-like receptor 4 (TLR4) expression in human pulmonary microvascular endothelial cells (HPMECs) is still unclear. Here, we investigated the role of Rab26 in regulating the expression of β2-ARs and TLR4 in HPMECs and the effect of these receptors’ imbalance on endothelial cell barrier function. The results showed that there was unbalance expression in these receptors, where β2-AR expression was remarkably reduced, and TLR4 was increased on the cell membrane after lipopolysaccharide (LPS) treatment. Furthermore, we found that Rab26 overexpression not only upregulated β2-ARs but also downregulated TLR4 expression on the cell membrane. Subsequently, the TLR4-related inflammatory response was greatly attenuated, and the hyperpermeability of HPMECs also was partially relived. Taken together, these data suggest that basal Rab26 maintains the balance between β2-ARs and TLR4 on the cell surface, and it might be a potential therapeutic target for diseases involving endothelial barrier dysfunction.