bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-economic determinants of anthropometric measures of abdominal adiposity among older people in England
Authors: Iparraguirre Jose , SzeLam Sam
Published: July 2019

Objective:

to look into the socio-economic determinants of levels of three anthropometric measures of abdominal adiposity among older people in England -body mass index, waist circumference (WC), and waist-hip ratio (WHR)- and of changes along two health risk classifications: the World Health Organisation classification based on BMI levels and the WHO combined classification based on BMI and waist circumference measurements.

Design:

quantile regression and multinomial analysis using data from the English Longitudinal Study of Ageing (ELSA), wave 2 (2004-05) and wave 4 (2008-09)

Results:

The quantile analysis on levels led to disparate results depending on the wave, which would question results previously published based on only one wave. However, we found that age tends to present an inverse U-shaped relationship with BMI and WC, smoking is negatively associated with BMI and positively with WC and WHR, alcohol consumption is negatively associated with BMI and WC levels, net total wealth is negatively related with the three anthropometric measures, educational attainment is negatively associated with each measure, and depression is positively associated with each measure. The multinomial analysis found that living in a larger household size increases the likelihood of becoming or remaining unhealthy irrespective of which classification we used. Furthermore, using the BMI-based categorisation, the initial category is highly relevant as a predictor of the category four years later and alcohol consumption would be positively associated with being or becoming obese. From the combined BMI-WC categorisation, we found that net total wealth would be negatively associated with becoming or remaining unhealthy whereas depression is a significant predictor of becoming or remaining unhealthy.
Segmenting DNA sequence into words based on statistical language model
Authors: Liang Wang
Published: July 2019

This paper presents a novel method to segment/decode DNA sequences based on n-gram statistical language model. Firstly, we find the length of most DNA “words” is 12 to 15 bps by analyzing the genomes of 12 model species. The bound of language entropy of DNA sequence is about 1.5674 bits. After building an n-gram biology languages model, we design an unsupervised ‘probability approach to word segmentation’ method to segment the DNA sequences. The benchmark of segmenting method is also proposed. In cross segmenting test, we find different genomes may use the similar language, but belong to different branches, just like the English and French/Latin. We present some possible applications of this method at last.
The persistent impact of incidental experience
Authors: Wilder Matthew , Jones Matt , Ahmed Alaa , Curran Tim , Mozer Michael
Published: July 2019

As we perform daily activities-- driving to work, unlocking the office door, grabbing a coffee cup-- our actions seem automatic and preprogrammed. Nonetheless, routine, well-practiced behavior is continually modulated by incidental experience: in repetitive experimental tasks, recent (~4) trials reliably influence performance and action choice. Psychological theories downplay the significance of sequential effects, explaining them as rapidly decaying perturbations of behavior with no long-term consequences. We challenge this traditional perspective in two studies designed to probe the impact of more distant experience, finding evidence for effects spanning up to a thousand intermediate events. We present a normative theory in which these persistent effects reflect optimal adaptation to a dynamic environment exhibiting varying rates of change. The theory predicts a heavy-tailed decaying influence of past experience, consistent with our data, and suggests that individual incidental experiences are catalogued in a temporally extended memory utilized to optimize subsequent behavior.
Diet transition to a high-fat diet for 3 weeks reduces brain omega-3-fatty acid levels, alters BDNF signaling and induces anxiety & depression-like behavior in adult rats
Authors: Sharma Sandeep , Zhuang Yumei , Gomez-Pinilla Fernando
Published: July 2019

Background:

The consumption of diets high in calories and low in nutrient value is becoming increasingly common in modern society, which can lead to metabolic disorders like diabetes and obesity, and potentially to psychiatric disorders. We have performed studies to assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, and anxiety and depression-like behavior. Methods: Pregnant rats were fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. Anxiety and depression-like behaviors were assessed by using open field (OF) and elevated plus maze (EPM). Molecular assessments were performed in the frontal cortex and hippocampus as dysfunctions in these brain regions are main contributors towards depression, anxiety-like behavior and stress.

Results:

We found that the HFD increased vulnerability for anxiety and depression-like behavior, and that these modifications harmonized with changes in the anxiety-related neuropeptide Y (NPY)-1 receptor. The HFD reduced levels of brain-derived neurotrophic factor (BDNF), and the BDNF signaling receptor pTrkB, as well as the cyclic AMP response element binding protein (CREB), in these brain regions. Brain DHA contents were significantly associated with the levels of anxiety and depression-like behavior in these rats.

Conclusions:

These results suggest that the change in dietary lifestyle leading to alteration of dietary n3/n-6 fatty acids levels imposes a risk factor for anxiety-like behaviors. Dietary DHA might help for building cognitive reserve that can resist psychiatric disorders.
A Quantitative Model for Human Olfactory Receptors
Authors: Hassan Sk. Sarif , Pal Choudhury Pabitra , Bose Aritra
Published: July 2019

A wide variety of chemicals having distinct odors are smelled by humans. Odor perception initiates in the nose, where it is detected by a large family of olfactory receptors (ORs). Based on divergence of evolutionary model a sequence of human ORs database has been proposed by D. Lancet et al (2000, 2006). It is quite impossible to infer whether a given sequence of nucleotides is a human OR or not, without any biological experimental validation. In our perspective, a proper quantitative understanding of these ORs is required to justify or nullify whether a given sequence is a human OR or not. In this paper, all human OR sequences have been quantified, and a set of clusters have been made using the quantitative results based on two different metrics. Using this proposed quantitative model, one can easily make probable justification or deterministic nullification whether a given sequence of nucleotides is a probable human OR homologue or not, without seeking any biological experiment. Of course a further biological experiment is essential to validate the probable human OR homologue.
Lost in translation: Toward a formal model of multilevel, multiscale medicine
Authors: Wallace Rodrick
Published: July 2019

For a broad spectrum of low level cognitive regulatory and other biological phenomena, isolation from signal crosstalk between them requires more metabolic free energy than permitting correlation. This allows an evolutionary exaptation leading to dynamic global broadcasts of interacting physiological processes at multiple scales. The argument is similar to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological subsystems. Not only is the living state characterized by cognition at every scale and level of organization, but by multiple, shifting, tunable, cooperative larger scale broadcasts that link selected subsets of functional modules to address problems. This multilevel dynamical viewpoint has implications for initiatives in translational medicine that have followed the implosive collapse of pharmaceutical industry 'magic bullet' research. In short, failure to respond to the inherently multilevel, multiscale nature of human pathophysiology will doom translational medicine to a similar implosion.
Inferring decoding strategy from choice probabilities in the presence of noise correlations
Authors: Haefner Ralf , Gerwinn Sebastian , Macke Jakob , Bethge Matthias
Published: July 2019

The activity of cortical neurons in sensory areas covaries with perceptual decisions, a relationship often quantified by choice probabilities. While choice probabilities have been measured extensively, their interpretation has remained fraught with difficulty. Here, we derive the mathematical relationship between choice probabilities, read-out weights and noise correlations within the standard neural decision making model. Our solution allows us to prove and generalize earlier observations based on numerical simulations, and to derive novel predictions. Importantly, we show how the read-out weight profile, or decoding strategy, can be inferred from experimentally measurable quantities. Furthermore, we present a test to decide whether the decoding weights of individual neurons are optimal, even without knowing the underlying noise correlations. We confirm the practical feasibility of our approach using simulated data from a realistic population model. Our work thus provides the theoretical foundation for a growing body of experimental results on choice probabilities and correlations.
A novel predicted calcium-regulated kinase family implicated in neurological disorders
Authors: Dudkiewicz Małgorzata , Lenart Anna , Pawłowski Krzysztof
Published: July 2019

Protein kinases are essential effectors of cellular signaling. Surprisingly, using bioinformatics tools, we predicted protein kinase structure and function for proteins of unknown function (FAM69 family) coded by five related human genes and their Metazoan homologues. Analysis of three-dimensional structure models and conservation of the classic catalytic motifs of protein kinases in four of human FAM69 proteins suggests they might have retained catalytic phosphotransferase activity. The FAM69 genes, FAM69A, FAM69B, FAM69C, C3ORF58 and CXORF36, are by large uncharacterized molecularly, yet linked to several neurological disorders in genetics studies. An EF-hand Ca2+-binding domain in FAM69A and FAM69B proteins, inserted within the structure of the kinase domain, suggests they function as Ca2+-dependent kinases.
Structural Analysis of Outer Membrane Beta-stranded Porins using Temperature Factor
Authors: Kumar Abhishek
Published: July 2019

Computational and statistical analysis has formed a large component of the biophysical efforts put forth to understand protein structure and function, due to the diversity and complexity of their structure. Outer membrane proteins form a diverse and complex set of proteins. Of these, porins which allow passage of molecules across the membrane interface have been analyzed here from a biophysical and structural perspective. The objective of this study is to analyze the structural organization of porins using atomic temperature factor as a parameter. Generally atomic temperature factors of molecules from crystal structures indicate the degree of mobility or disorder seen in the crystal structure. As good crystal structures have fewer possibilities of errors so there is less chance that errors are playing roles in temperature factors. Structures of six porins (four 16 stranded beta barrel porins and two 8 stranded beta barrel porins) were taken from the PDB for the analysis based on resolution and R-factor. Programs and scripts were written for extracting the temperature factors for the beta strands, loops and turns so that the analysis could be done for different atom-types and residue-types. The residue distribution and mobility distribution was found to be characteristic of each of the porins. The mobility and residue distribution amongst the secondary structural elements were found to follow the level of homology at the sequence and structural level. The loops that had defined functional roles in structural terms were found to have lower temperature factors than the other loops. The turn regions that are thought to face the periplasmic region in the cell, showed higher temperature factors. For both the 16 stranded and the 8 stranded barrels it was found one part of the barrel (the lower wall or ‘inner’ wall comprising the trimer interface in the case of the 16 stranded barrels) was more rigid and the other half of the barrel (the higher or ‘outer’ wall) showed more mobility as seen from the temperature factors. This seems to be an intrinsic structural component of the beta barrels.
Can bacteria adapt to starvation-free environment?
Authors: Kitahara Kei
Published: July 2019

Bacteria will experience starvation-free environment if infinite nutrition is supplied continuously for a long period. In this study, an evolutionary experiment was performed for 118 days where bacteria adapted to starvation-free environment and reduced their doubling time. It is anticipated that this finding will help to select bacterial strains that can grow more rapidly in rich media.
Category of Metabolic-Replication Systems in Biology and Medicine
Authors: Baianu I.
Published: July 2019

Metabolic-repair models, or (M,R)-systems were introduced in Relational Biology by Robert Rosen. Subsequently, Rosen represented such (M,R)-systems (or simply MRs)in terms of categories of sets, deliberately selected without any structure other than the discrete topology of sets. Theoreticians of life's origins postulated that Life on Earth has begun with the simplest possible organism, called the primordial. Mathematicians interested in biology attempted to answer this important question of the minimal living organism by defining the functional relations that would have made life possible in such a minimal system- a grandad and grandma of all living organisms on Earth.
Cancer Clinical Trials Optimization and Pharmacogenomics
Authors: Baianu I.
Published: July 2019

A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several recent clinical studies have shown that gene expression data for cancer cells can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general,'personalized medicine' that will have to be validated through optimally designed clinical trials in cancer. A Human Cancer Genomes and Epigenetics Project is proposed that can provide the essential data required for the optimal design of clinical trials with the goal of achieving significant improvements of the survival rates of cancer patients participating in clinical trials for advanced cancer stages. The results of such a six-year Human Cancer Genomes and Epigenetics Project should also greatly aid with the accelerated, rational development of effective anti-cancer medicines and the chemoprevention of cancers.
Mind over chatter: plastic up-regulation of the fMRI alertness network by EEG neurofeedback
Authors: Lanius Ruth , Ros Tomas , Theberge Jean , Frewen Paul , Kluetsch Rosemarie , Densmore Maria , Calhoun Vince
Published: July 2019

EEG neurofeedback (NFB) is a brain-computer interface (BCI) approach used to shape brain oscillations by means of real-time feedback from the electroencephalogram (EEG), which is known to reflect neural activity across cortical networks. Although NFB is being evaluated as a novel tool for treating brain disorders, evidence is scarce on the mechanism of its impact on brain function. In this study with 34 healthy participants, we examined whether, during the performance of an attentional auditory oddball task, the functional connectivity strength of distinct fMRI networks would be plastically altered after a 30-min NFB session of alpha-band reduction (n=17) versus a sham-feedback condition (n=17). Our results reveal that compared to sham, NFB induced a specific increase of functional connectivity within the alertness/salience network (dorsal anterior and mid cingulate), which was detectable 30 minutes after termination of training. Crucially, these effects were significantly correlated with reduced mind-wandering 'on-task' and were coupled to NFB-mediated resting state reductions in the alpha-band (8-12 Hz). No such relationships were evident for the sham condition. Although group default-mode network (DMN) connectivity was not significantly altered following NFB, we observed a positive association between modulations of resting alpha amplitude and precuneal connectivity, both correlating positively with frequency of mind-wandering. Our findings demonstrate a temporally direct, plastic impact of NFB on large-scale brain functional networks, and provide promising neurobehavioral evidence supporting its use as a noninvasive tool to modulate brain function in health and disease.
Comments on “Assessing future risk: quantifying the effects of sea level rise on storm surge risk for the southern shores of Long Island, New York”
Authors: Burton David
Published: July 2019

Tide gauge and satellite data indicate that the rate of sea level rise has not increased significantly in response to the last 3/4 century of CO2 emissions, so there is no reason to expect that it will do so in response to the next 3/4 century of CO2 emissions. The best prediction for sea level in the future is simply a linear projection of the history of sea level at the same location in the past. For Long Island, that is about 7-8 inches by 2080.
Music can reduce cognitive dissonance
Authors: Masataka Nobuo , Perlovsky Leonid
Published: July 2019

The fundamental cognitive functions of music in the brain have not been known and evolutionary reasons for musical abilities seem mysterious. A recent hypothesis suggested that a fundamental function of music has been to help mitigating cognitive dissonances. A cognitive dissonance is "a discomfort caused by holding conflicting cognitions" simultaneously; it usually leads to devaluation of conflicting knowledge. Since every concept implies some degree of contradictions to other knowledge, unmitigated cognitive dissonances could prevent evolution of cognition. Thus music might be fundamental for the evolution of cognition. Here we provide experimental confirmation of this hypothesis using a classical paradigm known to induce a cognitive dissonance and devaluation of a dissonant object; in presence of music devaluation has not occurred.
Quantum Genetics and Quantum Automata Models of Quantum-Molecular Evolution Involved in the Evolution of Organisms and Species
Authors: Baianu I.
Published: July 2019

Previous theoretical or general approaches to the problems of Quantum Genetics and Molecular Evolution are considered in this article from the point of view of Quantum Automata Theory first published by the author in 1971 and further developed in several recent articles. The representation of genomes and Interactome networks in categories of many-valued logic LMn –algebras that are naturally transformed during biological evolution, or evolve through interactions with the environment provide a new insight into the mechanisms of molecular evolution, as well as organismal evolution, in terms of sequences of quantum automata. Phenotypic changes are expressed only when certain environmentally-induced quantum-molecular changes are coupled with an internal re-structuring of major submodules of the genome and Interactome networks related to cell cycling and cell growth. Contrary to the commonly held view of 'standard’ Darwinist models of evolution, the evolution of organisms and species occurs through coupled multi-molecular transformations induced not only by the environment but actually realized through internal re-organizations of genome and interactome networks. The biological, evolutionary processes involve certain epigenetic transformations that are responsible for phenotypic expression of the genome and Interactome transformations initiated at the quantum-molecular level. It can thus be said that only quantum genetics can provide correct explanations of evolutionary processes that are initiated at the quantum--multi-molecular levels and propagate to the higher levels of organismal and species evolution.Biological evolution should be therefore regarded as a multi-scale process which is initiated by underlying quantum (coupled) multi-molecular transformations of the genomic and interactomic networks, followed by specific phenotypic transformations at the level of organism and the variable biogroupoids associated with the evolution of species which are essential to the survival of the species. The theoretical framework introduced in this article also paves the way to a Quantitative Biology approach to biological evolution at the quantum-molecular, as well as at the organismal and species levels. This is quite a substantial modification of the 'established’ modern Darwinist, and also of several so-called `molecular evolution’ theories.
Double burden of malnutrition among urban Bengalee adolescent boys in Midnapore, West Bengal, India
Authors: Bisai S , Khongsdier R , Bose K , Mahalanabis D
Published: July 2019

Malnutrition is an important public health problem worldwide. Therefore a study was undertaken to assess the prevalence of adolescent thinness, overweight and obesity in Midnapore town, West Bengal, India. A total of 974 adolescent boys aged 10-18 years were selected following multistage cluster sampling method from three higher secondary schools. Data was collected using pretested questionnaire following standard technique. Presence of thinness was evaluated using the cut-off values of international survey as suggested by Cole et al (2007). While overweight and obesity was determine by using international cut-off values develop by Cole et al (2000) based on international surveys as recommended by IOTF. Overall the prevalence of thinness, overweight and obesity were 20.8%, 14.9% and 3.8%, respectively. This study developed age specific smooth BMI percentile values using LMS method. Moreover, the study also developed BMI cut-off values to define thinness, overweight and obesity. In conclusion, the present analyses indicated that the prevalence of adolescent undernutrition is still a major problem. In addition, there was also an emerging trend for overweight/obesity, thereby indicating a double burden of malnutrition as observed in other developing countries.
Strong and weak competitors can coexist in the same niche
Authors: Kalmykov Lev , Kalmykov Vyacheslav
Published: July 2019

The competitive exclusion principle postulates that two trophically identical but fitness different species can not stably coexist in the same niche. However, this principle contradicts the observed nature's species richness. This fact is known as the biodiversity paradox. Here, using a simple cellular automaton model, we mechanistically show how two trophically identical, but fitness different species may stably coexist in the same niche. As environment is stable and any trade-offs are absent in this model, it strongly violates the competitive exclusion principle.
Visual Molecular Dynamics Investigations of the Impact of Hydrophobic Nanoparticles on Prognosis of Alzheimer’s Disease and Cancers
Authors: Baianu I. , Charles M , Prisecaru V.
Published: July 2019

The possible impact of hydrophobic lectin nanoparticles on the prognosis and progression of Alzheimer's disease (AD) and cancers was investigated by Visual Molecular Dynamics (VMD) computer modeling programs available from the Beckmann Advanced Research Institute at the University of Illinois at Urbana. Our results indicate the possibility of impeding pathological aggregation of certain proteins such as modified tau- or beta-amyloid that are currently being considered as possible causes of Alzheimer's disease. VMD programs serve as useful tools for investigation hydrophobic protein aggregation that may play a role in aging of human populations.
Angiogenesis in Chronic Obstructive Pulmonary Disease
Authors: Matarese Alessandro , Santulli Gaetano
Published: July 2019

Angiogenesis is a crucial component of lung pathophysiology, not only in cancer but also in other disorders, such as chronic obstructive pulmonary disease (COPD). In COPD angiogenesis is definitely able to control and orchestrate the progression of airway remodeling. Herein, we provide several remarkable translational aspects of angiogenesis in COPD, exploring both basic and clinical research in this field. Indeed, we present a number of pro- and anti-angiogenic factors, which can be also used as potential biomarkers to monitor disease progression.This pre-print has subsequently been published at http://www.unisa.it/uploads/7100/06.pdf
Synchronized Mammalian Cells in Culture: A Comparison of Normal and KB Cancer Cell Growth
Authors: Baianu I.
Published: July 2019

Experimentation and tests with cells in culture and cell synchronization or synchrony are important in order to be able to make both reliable and high-sensitivity measurements. This is also very important for mechanistic studies of cell division control, oncogenesis and tumor growth. A comparison is made in this article between the initially synchronized cell growth of rabbit and KB cells in synchronized cultures.
Micron-gap spacers with ultrahigh thermal resistance and mechanical robustness for direct energy conversion
Authors: Nicaise Samuel M. , Lin Chen , Azadi Mohsen , Bozorg-Grayeli Tara , Adebayo-Ige Promise , Lilley Drew E. , Pfitzer Yann , Cha Wujoon , Van Houten Kyana , Melosh Nicholas A. , Howe Roger T. , Schwede Jared W. , Bargatin Igor
Published: July 2019

In thermionic energy converters, the absolute efficiency can be increased up to 40% if space-charge losses are eliminated by using a sub-10-µm gap between the electrodes. One practical way to achieve such small gaps over large device areas is to use a stiff and thermally insulating spacer between the two electrodes. We report on the design, fabrication and characterization of thin-film alumina-based spacers that provided robust 3–8 μm gaps between planar substrates and had effective thermal conductivities less than those of aerogels. The spacers were fabricated on silicon molds and, after release, could be manually transferred onto any substrate. In large-scale compression testing, they sustained compressive stresses of 0.4–4 MPa without fracture. Experimentally, the thermal conductance was 10–30 mWcm−2K−1and, surprisingly, independent of film thickness (100–800 nm) and spacer height. To explain this independence, we developed a model that includes the pressure-dependent conductance of locally distributed asperities and sparse contact points throughout the spacer structure, indicating that only 0.1–0.5% of the spacer-electrode interface was conducting heat. Our spacers show remarkable functionality over multiple length scales, providing insulating micrometer gaps over centimeter areas using nanoscale films. These innovations can be applied to other technologies requiring high thermal resistance in small spaces, such as thermophotovoltaic converters, insulation for spacecraft and cryogenic devices.
Toward point-of-care assessment of patient response: a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning
Authors: Ahuja Karan , Rather Gulam M. , Lin Zhongtian , Sui Jianye , Xie Pengfei , Le Tuan , Bertino Joseph R. , Javanmard Mehdi
Published: July 2019

We present a novel method to rapidly assess drug efficacy in targeted cancer therapy, where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells. We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy. Currently commercially available devices for the automated analysis of cell viability are based on staining, which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis. Our approach requires as little as 20 μL of volume and avoids staining allowing for further downstream molecular analysis. To the best of our knowledge, this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning, particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier, to assess viability of cells without staining or labelling.
Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”
Authors: Masters Elysia A. , Trombetta Ryan P. , de Mesy Bentley Karen L. , Boyce Brendan F , Gill Ann Lindley , Gill Steven R. , Nishitani Kohei , Ishikawa Masahiro , Morita Yugo , Ito Hiromu , Bello-Irizarry Sheila N. , Ninomiya Mark , Brodell James D. , Lee Charles C. , Hao Stephanie P. , Oh Irvin , Xie Chao , Awad Hani A. , Daiss John L. , Owen John R. , Kates Stephen L. , Schwarz Edward M. , Muthukrishnan Gowrishankar
Published: July 2019

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high.Staphylococcus aureusis responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including:Staphylococcalabscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast,S. aureusintracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome againstS. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.
Musa balbisiana genome reveals subgenome evolution and functional divergence
Authors: Wang Zhuo , Miao Hongxia , Liu Juhua , Xu Biyu , Yao Xiaoming , Xu Chunyan , Zhao Shancen , Fang Xiaodong , Jia Caihong , Wang Jingyi , Zhang Jianbin , Li Jingyang , Xu Yi , Wang Jiashui , Ma Weihong , Wu Zhangyan , Yu Lili , Yang Yulan , Liu Chun , Guo Yu , Sun Silong , Baurens Franc-Christophe , Martin Guillaume , Salmon Frederic , Garsmeur Olivier , Yahiaoui Nabila , Hervouet Catherine , Rouard Mathieu , Laboureau Nathalie , Habas Remy , Ricci Sebastien , Peng Ming , Guo Anping , Xie Jianghui , Li Yin , Ding Zehong , Yan Yan , Tie Weiwei , D’Hont Angélique , Hu Wei , Jin Zhiqiang
Published: July 2019

Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
Incidence of type II diabetes in chronic obstructive pulmonary disease: a nested case–control study
Authors: Gayle Alicia , Dickinson Scott , Poole Chris , Pang Marie , Fauconnot Ornella , Quint Jennifer K.
Published: July 2019

We investigated the incidence of type II diabetes mellitus (T2DM) among people with COPD and whether exposure to inhaled corticosteroid (ICS) and exacerbation status was associated with T2DM. This descriptive cohort study used primary care data from the Clinical Practice Research Datalink (CPRD). The patient cohort included people with a diagnosis of COPD and previous smoking history registered at a CPRD practice between January 2010 and December 2016. We determined incidence rates by age, gender and deprivation. Using a nested case–control design—where cases and controls are drawn from the cohort population—we matched 1:5 with patients by age, gender and GP practice and estimated odds of T2DM using logistic regression (adjusting for smoking status, deprivation, BMI, hypertension, coronary heart disease and heart failure). We identified 220,971 COPD patients; mean age at COPD diagnosis was 66 years (SD 12) and 54% were male. The incidence rate of T2DM in COPD patients was 1.26 per 100 patient years (95% CI: 1.24–1.28) and was higher among men (1.32 vs 1.18 among women). The adjusted odds ratio for T2DM was 1.47 (95% CI: 1.36–1.60) among frequent exacerbators (≥2 treated exacerbations per year) compared to infrequent exacerbators and the odds ratio for patients receiving high-dose ICS (>800 mcg budesonide equivalent dose) was 1.73 (95% CI 1.65–1.82) compared to patients receiving no ICS therapy. Incidence of T2DM among COPD patients is high and exposure to ICS and frequent exacerbations are associated with a higher risk of T2DM among patients with COPD.
Towards Quality by Design and process analytical technology for enhanced nutrient recovery from wastewaters
Authors: Vaneeckhaute Céline
Published: July 2019

Recovering nutrients from wastewater as sustainable bio-based products provides a key solution to major environmental problems. Classical technology development approaches for resource recovery largely ignore the real-world variability in raw waste materials, which currently hinders the successful implementation of recovery strategies. A major challenge is to create a consistent and environmentally friendly supply of high-quality end-products that can compete with fossil-derived products currently on the market. This paper suggests the use of a Quality by Design approach as adapted from the pharmaceutical industry to ensure a high standard of quality consistency. Key elements of this approach involve mathematical models and integrated design-control strategies that support the production of high-quality marketable end-products from variable input waste and wastewater streams. Further research in terms of cost evaluation and optimisation of such approach for resource recovery applications is needed. A regulatory framework for Process Analytical Technology implementation in the field is also suggested.
Syndecan-4 regulates extravillous trophoblast migration by coordinating protein kinase C activation
Authors: Jeyarajah Mariyan J. , Jaju Bhattad Gargi , Kops Brianna F. , Renaud Stephen J.
Published: July 2019

Extravillous trophoblast (EVT) invasion is an essential component of human placentation. Poor EVT invasion is associated with obstetrical complications including preeclampsia. Integration of cues from the extracellular environment is required for directional EVT invasion, but how EVTs coordinate responses to these cues is not well understood. Syndecan-4 (SDC4) is a transmembrane heparan sulfate proteoglycan that binds to, and modulates the activity of, many extracellular proteins implicated in placental development. Therefore, we determined the functional importance of SDC4 for EVT invasion. We found that SDC4 is expressed by a first trimester EVT line (HTR8), and in EVTs in placenta throughout pregnancy, with higher expression during early pregnancy than at term. Higher expression was also observed in placentas from preeclampsia compared to normotensive pregnancies. SDC4-deficient HTR8 EVTs exhibited reduced migration and Matrigel-based invasion, both under basal conditions and following exposure to basic fibroblast growth factor and heparin-binding epidermal growth factor. SDC4-deficient HTR8 EVTs also showed reduced protein kinase C-alpha (PKCα) and AKT phosphorylation. SDC4 directly bound to activated PKCα in EVTs, and inhibition of PKCα decreased EVT invasion and migration. Our findings reveal an essential role of SDC4 as a regulator of EVT motility, in part through coordination of PKCα activation.
Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study
Authors: Manzoor Saika , Ganie Mohd Ashraf , Amin Shajrul , Shah Zaffar A , Bhat Imtiyaz A , Yousuf S. Douhath , Jeelani Humira , Kawa Iram A , Fatima Qudsia , Rashid Fouzia
Published: July 2019

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1β, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.
Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues
Authors: Yoshida Yukihiro , Fujigaki Hidetsugu , Kato Koichi , Yamazaki Kyoka , Fujigaki Suwako , Kunisawa Kazuo , Yamamoto Yasuko , Mouri Akihiro , Oda Akifumi , Nabeshima Toshitaka , Saito Kuniaki
Published: July 2019

The enzyme kynurenine aminotransferase (KAT) catalyses the conversion of kynurenine (KYN) to kynurenic acid (KYNA). Although the isozymes KAT1–4 have been identified, KYNA is mainly produced by KAT2 in brain tissues. KNYA is an antagonist of N-methyl-D-aspartate and α-7-nicotinic acetylcholine receptors, and accumulation of KYNA in the brain has been associated with the pathology of schizophrenia. Therefore, KAT2 could be exploited as a therapeutic target for the management of schizophrenia. Although currently available KAT2 inhibitors irreversibly bind to pyridoxal 5′-phosphate (PLP), inhibition via this mechanism may cause adverse side effects because of the presence of other PLP-dependent enzymes. Therefore, we identified novel selective KAT2 inhibitors by screening approximately 13,000 molecules. Among these, glycyrrhizic acid (GL) and its analogues, glycyrrhetinic acid (GA) and carbenoxolone (CBX), were identified as KAT2 inhibitors. These compounds were highly selective for KAT2 and competed with its substrate KYN, but had no effects on the other 3 KAT isozymes. Furthermore, we demonstrated that in complex structures that were predicted in docking calculations, GL, GA and CBX were located on the same surface as the aromatic ring of KYN. These results indicate that GL and its analogues are highly selective and competitive inhibitors of KAT2.
Atomistic mechanisms underlying the activation of the G protein-coupled sweet receptor heterodimer by sugar alcohol recognition
Authors: Mahalapbutr Panupong , Darai Nitchakan , Panman Wanwisa , Opasmahakul Aunchan , Kungwan Nawee , Hannongbua Supot , Rungrotmongkol Thanyada
Published: July 2019

The human T1R2-T1R3 sweet taste receptor (STR) plays an important role in recognizing various low-molecular-weight sweet-tasting sugars and proteins, resulting in the release of intracellular heterotrimeric G protein that in turn leads to the sweet taste perception. Xylitol and sorbitol, which are naturally occurring sugar alcohols (polyols) found in many fruits and vegetables, exhibit the potential caries-reducing effect and are widely used for diabetic patients as low-calorie sweeteners. In the present study, computational tools were applied to investigate the structural details of binary complexes formed between these two polyols and the T1R2-T1R3 heterodimeric STR. Principal component analysis revealed that the Venus flytrap domain (VFD) of T1R2 monomer was adapted by the induced-fit mechanism to accommodate the focused polyols, in which residues 233–268 moved significantly closer to stabilize ligands. This finding likely suggested that these structural transformations might be the important mechanisms underlying polyols-STR recognitions. The calculated free energies also supported the VFD of T1R2 monomer as the preferential binding site for such polyols, rather than T1R3 region, in accord with the lower number of accessible water molecules in the T1R2 pocket. The E302 amino acid residue in T1R2 was found to be the important recognition residue for polyols binding through a strongly formed hydrogen bond. Additionally, the binding affinity of xylitol toward the T1R2 monomer was significantly higher than that of sorbitol, making it a sweeter tasting molecule.
Therapeutic effect of gold nanoparticles on DSS-induced ulcerative colitis in mice with reference to interleukin-17 expression
Authors: Abdelmegid Amira M. , Abdo Fadia K. , Ahmed Fayza E. , Kattaia Asmaa A. A.
Published: July 2019

Ulcerative colitis (UC) is among the most challenging human diseases. Nanotechnology has incontestable promising outcomes in inflammatory bowel diseases. This study aimed to investigate the therapeutic effect of naked gold nanoparticles (AuNPs) on dextran sodium sulphate (DSS) induced ulcerative colitis in mice. We also examined the expression of interleukin-17 (IL-17) following AuNPs treatment. Mice were randomly divided into control, DSS and DSS+ AuNPs groups. Severity of colitis was assessed by disease activity index (DAI) measurement. At the end of the experiment, the final body weights were recorded. The colon was dissected and processed for histopathological examinations by light and electron microscopes. Colon homogenates were prepared for assay of tissue malondialdehyde (MDA) and real-time PCR analysis of IL-17A. Immunohistochemical localization of IL-17A was carried out. Scanning electron microscopy (SEM) and Energy Dispersive X-ray (EDX) detector were used to detect the presence of AuNPs in the colonic tissue of DSS+ AuNPs groups. Our results showed that AuNPs effectively targeted the colonic tissue, and reduced changes induced by DSS. The underlying mechanisms could be related to anti-oxidant effect (as evident by decreasing tissue MDA) and anti-inflammatory potential of AuNPs. Our study draws attention to as a novel therapeutic strategy for treating UC.
Enhanced activity of highly conformal and layered tin sulfide (SnSx) prepared by atomic layer deposition (ALD) on 3D metal scaffold towards high performance supercapacitor electrode
Authors: Ansari Mohd Zahid , Parveen Nazish , Nandi Dip K. , Ramesh Rahul , Ansari Sajid Ali , Cheon Taehoon , Kim Soo-Hyun
Published: July 2019

Layered Sn-based chalcogenides and heterostructures are widely used in batteries and photocatalysis, but its utilizations in a supercapacitor is limited by its structural instability and low conductivity. Here, SnSx thin films are directly and conformally deposited on a three-dimensional (3D) Ni-foam (NF) substrate by atomic layer deposition (ALD), using tetrakis(dimethylamino)tin [TDMASn, ((CH3)2N)4Sn] and H2S that serves as an electrode for supercapacitor without any additional treatment. Two kinds of ALD-SnSx films grown at 160 °C and 180 °C are investigated systematically by X-ray diffractometry, Raman spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). All of the characterization results indicate that the films deposited at 160 °C and 180 °C predominantly consist of hexagonal structured-SnS2 and orthorhombic-SnS phases, respectively. Moreover, the high-resolution TEM analyses (HRTEM) reveals the (001) oriented polycrystalline hexagonal-SnS2 layered structure for the films grown at 160 °C. The double layer capacitance with the composite electrode of SnSx@NF grown at 160 °C is higher than that of SnSx@NF at 180 °C, while pseudocapacitive Faradaic reactions are evident for both SnSx@NF electrodes. The superior performance as an electrode is directly linked to the layered structure of SnS2. Further, the optimal thickness of ALD-SnSx thin film is found to be 60 nm for the composite electrode of SnSx@NF grown at 160 °C by controlling the number of ALD cycles. The optimized SnSx@NF electrode delivers an areal capacitance of 805.5 mF/cm2 at a current density of 0.5 mA/cm2 and excellent cyclic stability over 5000 charge/discharge cycles.