bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis
Authors: Mitchell Caroline M. , Srinivasan Sujatha , Zhan Xiang , Wu Michael C. , Reed Susan D. , Guthrie Katherine A. , LaCroix Andrea Z. , Fiedler Tina , Munch Matthew , Liu Congzhou , Hoffman Noah G. , Blair Ian A. , Newton Katherine , Freeman Ellen W. , Joffe Hadine , Cohen Lee , Fredricks David N.
Published: June 2017

Objective:

To examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.

Methods:

For this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.

Results:

Of the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.

Conclusions:

Presence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.
Missing documentation in breast cancer survivors: genitourinary syndrome of menopause
Authors: Cook Elise D. , Iglehart Elena I. , Baum George , Schover Leslie L. , Newman Lonzetta L.
Published: June 2017

Objective:

Breast cancer survivors often take hormonal treatments to prevent the recurrence of breast cancer, particularly aromatase inhibitors that can worsen the symptoms of genitourinary syndrome of menopause (GSM) such as dyspareunia, dysuria, and urinary incontinence, all of which may adversely affect survivors’ quality of life. Few breast cancer survivors experiencing GSM receive adequate assessment or treatment.

Methods:

In this descriptive study, we reviewed medical records for documented GSM and any treatments administered or referrals for treatment in 800 female patients who visited the Breast Cancer Survivorship Clinic at a comprehensive cancer center between July 1, 2010 and June 30, 2011, either at least 5 years after completion of treatment for invasive breast cancer or at least 6 months after completion of treatment for ductal carcinoma in situ.

Results:

Of the 279 patients with documented symptoms of vaginal atrophy, only 111 (39.8%) had documentation of having received any form of treatment or referral. Of the 71 patients with documented symptoms of urinary tract atrophy, only 33.8% had documentation of having received treatment or referral for treatment.

Conclusion:

Breast cancer survivors often experience GSM due to lack of estrogen. The worrisome lack of documentation of assessment or treatment for GSM in a large breast cancer survivorship practice reveals missed opportunities to improve quality of life. Dissemination of recent progress in the development of GSM assessment tools, patient handouts, and new treatments to providers who care for breast cancer survivors is needed to improve this process.
CHANGES IN CHOROIDAL THICKNESS IN CLINICALLY SIGNIFICANT PSEUDOPHAKIC CYSTOID MACULAR EDEMA
Authors: Fleissig Efrat , Cohen Shai , Iglicki Matias , Goldstein Michaella , Zur Dinah
Published: June 2017

Purpose:

To investigate choroidal thickness in eyes with clinically significant pseudophakic cystoid macular edema (PCME) during the acute phase and following resolution of the edema, using enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT).

Methods:

This is a retrospective, observational clinical study. Patients' records were reviewed for cases of clinically significant PCME after uneventful phacoemulsification surgery. Choroidal thickness was measured at time of PCME diagnosis in both eyes and after CME resolution in the affected eye using enhanced depth imaging spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering). Measurements were taken subfoveal and 1.5 mm nasal, temporal, inferior, and superior from the center of the fovea. Statistical analysis was performed using paired t-test and Pearson correlation.

Results:

Mean subfoveal choroidal thickness in 34 eyes with PCME measured 258 ± 83 μm at baseline and decreased to 215 ± 79 μm after CME resolution (P < 0.001). Mean subfoveal choroidal thickness measured at baseline in fellow eyes was significantly lower (194 ± 77 μm) compared to acute PCME (P < 0.001) and after CME resolution (P = 0.011).

Conclusion:

Choroidal thickness is increased in eyes with PCME and decreases following edema resolution. These findings may strengthen the hypothesis of an inflammatory pathogenesis in PCME.
Objectively Measured Daily Physical Activity and Postural Changes as Related to Positive and Negative Affect Using Ambulatory Monitoring Assessments
Authors: Aggio Daniel , Wallace Karen , Boreham Nicola , Shankar Aparna , Steptoe Andrew , Hamer Mark
Published: June 2017

Objective

The aim of the study was to determine whether objectively measured daily physical activity and posture of sitting, standing, and sit-to-stand transitions are associated with daily assessments of affect.

Methods

Participants (N = 51, 49% female) wore ActivPal accelerometers for 24 h/d for seven consecutive days. Time spent sitting, standing, and being physically active and sit-to-stand transitions were derived for each day. Participants also completed a mood inventory each evening. Multilevel models examined within- and between-person associations of daily physical activity with positive and negative affect, adjusting for age, sex, body mass index, education, and sleep duration.

Results

Within-person associations showed that a 1-hour increase in daily physical activity was associated with a decrease in negative affect over the same day (B = −0.11, 95% confidence interval [CI], −0.21 to −0.01). Between-person associations indicated a borderline significant association between higher average daily physical activity levels and higher positive affect (B = 1.85, 95% CI = −0.25 to 3.94). There were no between- or within-person associations between sitting, standing, and sit-to-stand transitions with affect.

Conclusions

Promoting physical activity may be a potential intervention strategy to acutely suppress negative affective states.
Palliative oxygen for chronic breathlessness: what new evidence?
Authors: Ahmadi Zainab , Currow David C. , Ekström Magnus
Published: June 2017

Purpose of review

Supplemental oxygen improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia, but the effect of oxygen therapy in mild or moderate hypoxaemia to reduce symptomatic chronic breathlessness remains unclear. This review provides an overview of recent evidence about the role of oxygen therapy for the relief of chronic breathlessness in advanced illness.

Recent findings

In COPD, a recent Cochrane review strengthens earlier findings regarding the positive effect of supplemental oxygen compared with air during exercise test in the training setting. The novel analysis of effect of oxygen therapy on quality of life (QoL) showed no clear effect. Short-burst oxygen therapy given before exercise had no effect and should not be used.

Supplemental oxygen during exercise has been shown to reduce breathlessness in patients with COPD who have no or mild hypoxaemia, but it is not clear whether the reduction in breathlessness shown in the laboratory setting translates into a clinically important benefit. Further studies are needed to establish this.
Physiological thermal limits predict differential responses of bees to urban heat-island effects
Authors: Hamblin April L. , Youngsteadt Elsa , López-Uribe Margarita M. , Frank Steven D.
Published: June 2017

Changes in community composition are an important, but hard to predict, effect of climate change. Here, we use a wild-bee study system to test the ability of critical thermal maxima (CT
max
, a measure of heat tolerance) to predict community responses to urban heat-island effects in Raleigh, NC, USA. Among 15 focal species, CT
max
ranged from 44.6 to 51.3°C, and was strongly predictive of population responses to urban warming across 18 study sites (
r
2
= 0.44). Species with low CT
max
declined the most. After phylogenetic correction, solitary species and cavity-nesting species (bumblebees) had the lowest CT
max
, suggesting that these groups may be most sensitive to climate change. Community responses to urban and global warming will likely retain strong physiological signal, even after decades of warming during which time lags and interspecific interactions could modulate direct effects of temperature.
Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment
Authors: Tsai Hsieh-Fu , Trubelja Alen , Shen Amy Q. , Bao Gang
Published: June 2017

Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensionalin vitrohuman tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.
Model-based analysis of an outbreak of bubonic plague in Cairo in 1801
Authors: Didelot Xavier , Whittles Lilith K. , Hall Ian
Published: June 2017

Bubonic plague has caused three deadly pandemics in human history: from the mid-sixth to mid-eighth century, from the mid-fourteenth to the mid-eighteenth century and from the end of the nineteenth until the mid-twentieth century. Between the second and the third pandemics, plague was causing sporadic outbreaks in only a few countries in the Middle East, including Egypt. Little is known about this historical phase of plague, even though it represents the temporal, geographical and phylogenetic transition between the second and third pandemics. Here we analysed in detail an outbreak of plague that took place in Cairo in 1801, and for which epidemiological data are uniquely available thanks to the presence of medical officers accompanying the Napoleonic expedition into Egypt at that time. We propose a new stochastic model describing how bubonic plague outbreaks unfold in both rat and human populations, and perform Bayesian inference under this model using a particle Markov chain Monte Carlo. Rat carcasses were estimated to be infectious for approximately 4 days after death, which is in good agreement with local observations on the survival of infectious rat fleas. The estimated transmission rate between rats implies a basic reproduction numberR0of approximately 3, causing the collapse of the rat population in approximately 100 days. Simultaneously, the force of infection exerted by each infected rat carcass onto the human population increases progressively by more than an order of magnitude. We also considered human-to-human transmission via pneumonic plague or human specific vectors, but found this route to account for only a small fraction of cases and to be significantly below the threshold required to sustain an outbreak.
Direct enzymatic bioelectrocatalysis: differentiating between myth and reality
Authors: Milton Ross D. , Minteer Shelley D.
Published: June 2017

Enzymatic bioelectrocatalysis is being increasingly exploited to better understand oxidoreductase enzymes, to develop minimalistic yet specific biosensor platforms, and to develop alternative energy conversion devices and bioelectrosynthetic devices for the production of energy and/or important chemical commodities. In some cases, these enzymes are able to electronically communicate with an appropriately designed electrode surface without the requirement of an electron mediator to shuttle electrons between the enzyme and electrode. This phenomenon has been termed direct electron transfer or direct bioelectrocatalysis. While many thorough studies have extensively investigated this fascinating feat, it is sometimes difficult to differentiate desirable enzymatic bioelectrocatalysis from electrocatalysis deriving from inactivated enzyme that may have also released its catalytic cofactor. This article will review direct bioelectrocatalysis of several oxidoreductases, with an emphasis on experiments that provide support for direct bioelectrocatalysis versus denatured enzyme or dissociated cofactor. Finally, this review will conclude with a series of proposed control experiments that could be adopted to discern successful direct electronic communication of an enzyme from its denatured counterpart.
Cultural sexual selection in monogamous human populations
Authors: Nakahashi Wataru
Published: June 2017

In humans, both sexes sometimes show peculiar mating preferences that do not appear to increase their fitness either directly or indirectly. As humans may transmit their preferences and target culturally, and these may be artificially modifiable, I develop theoretical models where a preference and/or a trait are culturally transmitted with a restriction of the trait modification. I assume a monogamous population where some individuals fail to find a mate, and this affects the preference and the trait in the next time step. I show that a strong aversion to, or high tolerance of, failed individuals are necessary for the evolution of irrational preferences that neither seek good genes nor any direct benefit. This evolution is more likely to occur when the preference and/or the trait are cultural rather than genetic. These results may partly explain why humans sometimes show mating preferences for exaggerated physical and cultural traits.
Memory for stimulus sequences: a divide between humans and other animals?
Authors: Ghirlanda Stefano , Lind Johan , Enquist Magnus
Published: June 2017

Humans stand out among animals for their unique capacities in domains such as language, culture and imitation, yet it has been difficult to identify cognitive elements that are specifically human. Most research has focused on how information is processed after it is acquired, e.g. in problem solving or ‘insight’ tasks, but we may also look for species differences in the initial acquisition and coding of information. Here, we show that non-human species have only a limited capacity to discriminate ordered sequences of stimuli. Collating data from 108 experiments on stimulus sequence discrimination (1540 data points from 14 bird and mammal species), we demonstrate pervasive and systematic errors, such as confusing a red–green sequence of lights with green–red and green–green sequences. These errors can persist after thousands of learning trials in tasks that humans learn to near perfection within tens of trials. To elucidate the causes of such poor performance, we formulate and test a mathematical model of non-human sequence discrimination, assuming that animals represent sequences as unstructured collections of memory traces. This representation carries only approximate information about stimulus duration, recency, order and frequency, yet our model predicts non-human performance with a 5.9% mean absolute error across 68 datasets. Because human-level cognition requires more accurate encoding of sequential information than afforded by memory traces, we conclude that improved coding of sequential information is a key cognitive element that may set humans apart from other animals.
Epidemic and endemic pathogen dynamics correspond to distinct host population microbiomes at a landscape scale
Authors: Jani Andrea J. , Knapp Roland A. , Briggs Cheryl J.
Published: June 2017

Infectious diseases have serious impacts on human and wildlife populations, but the effects of a disease can vary, even among individuals or populations of the same host species. Identifying the reasons for this variation is key to understanding disease dynamics and mitigating infectious disease impacts, but disentangling cause and correlation during natural outbreaks is extremely challenging. This study aims to understand associations between symbiotic bacterial communities and an infectious disease, and examines multiple host populations before or after pathogen invasion to infer likely causal links. The results show that symbiotic bacteria are linked to fundamentally different outcomes of pathogen infection: host–pathogen coexistence (endemic infection) or host population extirpation (epidemic infection). Diversity and composition of skin-associated bacteria differed between populations of the frog,
Rana sierrae
, that coexist with or were extirpated by the fungal pathogen,
Batrachochytrium dendrobatidis
(Bd). Data from multiple populations sampled before or after pathogen invasion were used to infer cause and effect in the relationship between the fungal pathogen and symbiotic bacteria. Among host populations, variation in the composition of the skin microbiome was most strongly predicted by pathogen infection severity, even in analyses where the outcome of infection did not vary. This result suggests that pathogen infection shapes variation in the skin microbiome across host populations that coexist with or are driven to extirpation by the pathogen. By contrast, microbiome richness was largely unaffected by pathogen infection intensity, but was strongly predicted by geographical region of the host population, indicating the importance of environmental or host genetic factors in shaping microbiome richness. Thus, while both richness and composition of the microbiome differed between endemic and epidemic host populations, the underlying causes are most likely different: pathogen infection appears to shape microbiome composition, while microbiome richness was less sensitive to pathogen-induced disturbance. Because higher richness was correlated with host persistence in the presence of Bd, and richness appeared relatively stable to Bd infection, microbiome richness may contribute to disease resistance, although the latter remains to be directly tested.
Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) Neisseria meningitidis clone in the African meningitis belt
Authors: Lamelas Araceli , Hauser Julia , Dangy Jean-Pierre , Hamid Abdul-Wahab M. , Röltgen Katharina , Abdul Sater Mohamad R. , Hodgson Abraham , Sie Ali , Junghanss Thomas , Harris Simon R. , Parkhill Julian , Bentley Stephen D. , Pluschke Gerd
Published: June 2017

Countries of the African ‘meningitis belt’ are susceptible to meningococcal meningitis outbreaks. While in the past major epidemics have been primarily caused by serogroup A meningococci, W strains are currently responsible for most of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the first time in 2002, with the first meningitis cases caused by these bacteria reported in 2003. Here we describe results of a comparative whole-genome analysis of 74 W:ST-2881 strains isolated within the framework of two longitudinal colonization and disease studies conducted in Ghana and Burkina Faso. Genomic data indicate that the W:ST-2881 clone has emerged from Y:ST-175(CC175) bacteria by capsule switching. The circulating W:ST-2881 populations were composed of a variety of closely related but distinct genomic variants with no systematic differences between colonization and disease isolates. Two distinct and geographically clustered phylogenetic clonal variants were identified in Burkina Faso and a third in Ghana. On the basis of the presence or absence of 17 recombination fragments, the Ghanaian variant could be differentiated into five clusters. All 25 Ghanaian disease isolates clustered together with 23 out of 40 Ghanaian isolates associated with carriage within one cluster, indicating that W:ST-2881 clusters differ in virulence. More than half of the genes affected by horizontal gene transfer encoded proteins of the ‘cell envelope’ and the ‘transport/binding protein’ categories, which indicates that exchange of non-capsular antigens plays an important role in immune evasion.
Increased ParB level affects expression of stress response, adaptation and virulence operons and potentiates repression of promoters adjacent to the high affinity binding sitesparS3andparS4inPseudomonas aeruginosa
Authors: Kawałek Adam , Głąbski Krzysztof , Bartosik Aneta Agnieszka , Fogtman Anna , Jagura-Burdzy Grażyna
Published: June 2017

Similarly to its homologs in other bacteria,Pseudomonas aeruginosapartitioning protein ParB facilitates segregation of newly replicated chromosomes. Lack of ParB is not lethal but results in increased frequency of anucleate cells production, longer division time, cell elongation, altered colony morphology and defective swarming and swimming motility. Unlike in other bacteria, inactivation ofparBleads to major changes of the transcriptome, suggesting that, directly or indirectly, ParB plays a role in regulation of gene expression in this organism.

ParB overproduction affects growth rate, cell division and motility in a similar way as ParB deficiency. To identify primary ParB targets, here we analysed the impact of a slight increase in ParB level onP. aeruginosatranscriptome. ParB excess, which does not cause changes in growth rate and chromosome segregation, significantly alters the expression of 176 loci. Most notably, the mRNA level of genes adjacent to high affinity ParB binding sitesparS1-4close tooriCis reduced. Conversely, in cells lacking eitherparBor functionalparSsequences the orfs adjacent toparS3andparS4are upregulated, indicating that direct ParB-parS3/parS4interactions repress the transcription in this region. In addition, increased ParB level brings about repression or activation of numerous genes including several transcriptional regulators involved in SOS response, virulence and adaptation. Overall, our data support the role of partitioning protein ParB as a transcriptional regulator inPseudomonas aeruginosa.
Comparative analyses of toxin-associated gene homologs from an Old World viper,Daboia russelii
Authors: Krishnan Neeraja M. , Panda Binay
Published: June 2017

Availability of snake genome sequences has opened up exciting areas of research on comparative genomics and gene diversity. One of the challenges in studying snake genomes is the acquisition of biological material from live animals, especially from the venomous ones. Additionally, in certain countries, Government permission is required to handle live snakes, making the process cumbersome and time-consuming. Here, we report comparative sequence analyses of toxin gene homologs from Russells viper (Daboia russelii) using whole-genome sequencing data obtained from the shed skin. When compared with the major venom proteins in Russells viper studied previously, we found 45-100% sequence similarity between the venom proteins and their skin homologs. Additionally, comparative analyses of 20 toxin gene family homologs provided evidence of unique sequence motifs in nerve growth factor (NGF), platelet derived growth factor (PDGF), Kunitz/Bovine pancreatic trypsin inhibitor (Kunitz BPTI), cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) and cysteine-rich secretory protein (CRISP). We identified V11 and T35 in the NGF domain; F23 and A29 in the PDGF domain; N69, K2 and A5 in the CAP domain; and Q17 in the CRISP domain to be responsible for differences in the largest pockets across the protein domain structures in crotalines, viperines and elapids from the in silico structure-based analysis. Similarly, residues F10, Y11 and E20 appear to play an important role in the protein structures across the kunitz protein domain of viperids and elapids. Our study sheds light on the usefulness of studying venom protein homologs from skin, their unique features and evolution in vipers. Data deposition: Russells viper sequence data is deposited in the NCBI SRA database under the accession number SRR5506741 and sequences for the individual venom-associated gene homologs to GenBank (accession numbers in Table S1).
Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño
Authors: Aguilar-Rangel M. Rocío , Chávez Montes Ricardo A. , Gonzalez-Segovia Eric , Ross-Ibarra Jeffrey , Simpson June K. , Sawers Ruairidh J. H.
Published: June 2017

Background

Gene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions.

Methods

Allele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments.

Results

A total of 2386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles that mirrored the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a constitutive stress response. Constitutive stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates.

Discussion

Constitutive activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between PT and B73 alleles indicate the presence ofcis-acting regulatory variation linked to stress-related genes in PT. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation.
Genetic and Environmental Influences on Pubertal Hormones in Human Hair across Development
Authors: Grotzinger Andrew D. , Briley Daniel A. , Engelhardt Laura E. , Mann Frank D. , Patterson Megan W. , Tackett Jennifer L. , Tucker-Drob Elliot M. , Harden K. Paige
Published: June 2017

Background:Puberty is a complex biopsychosocial process that is linked to an array of psychiatric and medical disorders that emerge in adolescence and persist across the lifespan. Although the pubertal process is driven by neuroendocrine changes, few quantitative genetic studies have directly measured puberty-relevant hormones. Hair samples can now be assayed for accumulation of hormones over several months. In contrast to more conventional salivary measures, hair measures are not confounded by diurnal variation or hormonal reactivity.

Methods:In an ethnically and socioeconomically diverse sample of 1,286 child and adolescent twins and multiples from 672 unique families, we estimated genetic and environmental influences on concentrations of testosterone, DHEA, and progesterone in hair across the period of 8 to 18 years of age.

Results:We identified sex-specific developmental windows of maximal heritability in each hormone. Peak heritability for DHEA occurred at age 9.8 years for males and 10.0 years for females. Peak heritability for testosterone occurred at age 12.5 and 15.2 years for males and females, respectively. Peak heritability for male progesterone occurred at 11.2 years, while the heritability of female progesterone remained uniformly low.

Conclusion:This is the first study of genetic influences on pubertal hormone concentrations in human hair and is the largest of the heritability of pubertal hormones in any form. The identification of specific developmental windows when genetic signals for hormones are maximized has critical implications for well-informed models of hormone-behavior associations in childhood and adolescence.
A Longitudinal Model for Functional Connectivity Networks Using Resting-State fMRI
Authors: Hart Brian , Cribben Ivor , Fiecas Mark ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2017

Many neuroimaging studies collect functional magnetic resonance imaging (fMRI) data in a longitudinal manner. However, the current network modeling literature lacks a general framework for analyzing functional connectivity (FC) networks in fMRI data obtained from a longitudinal study. In this work, we build a novel longitudinal FC network model using a variance components approach. First, for all subjects’ visits, we account for the autocorrelation inherent in the fMRI time series data using a non-parametric technique. Second, we use a generalized least squares approach to estimate 1) the within-subject variance component shared across the population, 2) the FC network, and 3) the FC network’s longitudinal trend. Our novel method for longitudinal FC networks seeks to account for the within-subject dependence across multiple visits, the variability due to the subjects being sampled from a population, and the autocorrelation present in fMRI data, while restricting the number of parameters in order to make the method computationally feasible and stable. We develop a permutation testing procedure to draw valid inference on group differences in baseline FC and change in FC over time between a set of patients and a comparable set of controls. To examine performance, we run a series of simulations and apply the model to longitudinal fMRI data collected from the Alzheimer’s Disease Neuroimaging Initiative database.
Project MinE: study design and pilot analyses of a large-scale whole genome sequencing study in amyotrophic lateral sclerosis
Authors:   Project MinE ALS Sequencing Consortium, Rheenen Wouter Van , Pulit Sara L. , Dekker Annelot M. , Khleifat Ahmad Al , Brands William J. , Iacoangeli Alfredo , Kenna Kevin P. , Kooyman Maarten , McLaughlin Russell L. , Middelkoop Bas , Moisse Matthieu , Schellevis Raymond D. , Shatunov Aleksey , Sproviero William , Tazelaar Gijs H.P. , Van der Spek Rick A.A. , Van Doormaal Perry T.C. , Van Eijk Kristel R. , van Vugt Joke J.F.A. , Basak A. Nazli , Glass Jonathan D. , Hardiman Orla , Hide Winston , Landers John E , Mora Jesus S. , Morrison Karen E. , Robberecht Wim , Newhouse Stephen , Shaw Christopher E. , Shaw Pamela J. , Van Damme Philip , Van Es Michael A. , Al-Chalabi Ammar , Van den Berg Leonard H. , Veldink Jan H.
Published: June 2017

The most recent genome-wide association study in amyotrophic lateral sclerosis (ALS) demonstrates a disproportionate contribution from low-frequency variants to genetic susceptibility of disease. We have therefore begun Project MinE, an international collaboration that seeks to analyse whole-genome sequence data of at least 15,000 ALS patients and 7,500 controls. Here, we report on the design of Project MinE and pilot analyses of newly whole-genome sequenced 1,264 ALS patients and 611 controls drawn from the Netherlands. As has become characteristic of sequencing studies, we find an abundance of rare genetic variation (minor allele frequency < 0.1 %), the vast majority of which is absent in public data sets. Principal component analysis reveals local geographical clustering of these variants within The Netherlands. We use the whole-genome sequence data to explore the implications of poor geographical matching of cases and controls in a sequence-based disease study and to investigate how ancestry-matched, externally sequenced controls can induce false positive associations. Also, we have publicly released genome-wide minor allele counts in cases and controls, as well as results from genic burden tests.
Molecular insights into conformational dynamics associated with the open-closed-phosphorylated states of PITPα
Authors: Kotyada Chaithanya
Published: June 2017

Phosphatidylinositol transfer proteins (PITPα) are lipid carrier proteins that are involved in replenishing the phosphatidylinositol lipid molecules on the plasma membranes. Transitions between the open and closed state conformations are necessary steps in the mechanism of lipid transfer by PITPα. The apo (open state) conformation is assumed to occur at the membrane surface during the lipid exchange while the lipid bound (closed state) conformation is required for transfer activity. The transfer of phosphatidylinositol by PITPα is controlled by the phosphorylation of S166 in its regulatory region. We wanted to decipher the molecular basis for structure-function relationship between the open-closed-phosphorylated states of PITPα. We used all-atom Molecular Dynamics Simulations to study the conformational dynamics in each of these states. Our study shows that the open state is highly dynamic and its transition to closed state would stabilize PITPα. We observed restricted conformational sampling of the phosphorylated state which provide basis for its decreased lipid transfer activity. Further, using analysis of residue-residue contact maps and hydrogen bond interactions we discuss the impact of phosphorylation on the global conformation of PITPα. Overall, our work provides insights into the structural dynamics in each state and their functional significance.
Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
Authors: Stamouli Sofia , Anderlid Britt-Marie , Willfors Charlotte , Thiruvahindrapuram Bhooma , Wei John , Berggren Steve , Nordgren Ann , Scherer Stephen W , Lichtenstein Paul , Tammimies Kristiina , Bölte Sven
Published: June 2017

Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. Here, we sought to investigate the contribution of CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on MZ pairs discordant for autism spectrum disorder (ASD) using the PsychChip array. In our collection, no postzygoticde novoCNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. When analyzing the burden of rare CNVs among pairs concordant and discordant for ASD/NDD in comparison with typically developed (TD) pairs, no differences were found. However, we did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p=0.02). Our results are in concordance with earlier findings that postzygoticde novoCNV events are typically rare in genomic DNA derived from saliva or blood and, in the majority of MZ twins, do not explain the discordance of NDDs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.
The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow
Authors: Pfeifer Susanne P. , Laurent Stefan , Sousa Vitor C. , Linnen Catherine R. , Foll Matthieu , Excoffier Laurent , Hoekstra Hopi E. , Jensen Jeffrey D.
Published: June 2017

The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island-specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at theAgoutilocus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 660,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of theAgoutipigmentation locus. Furthermore, mutations at this locus are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration.
Reference Quality Assembly of the 3.5 Gb genome ofCapsicum annuumfrom a Single Linked-Read Library
Authors: Hulse-Kemp Amanda M. , Maheshwari Shamoni , Stoffel Kevin , Hill Theresa A. , Jaffe David , Williams Stephen , Weisenfeld Neil , Ramakrishnan Srividya , Kumar Vijay , Shah Preyas , Schatz Michael C. , Church Deanna M. , Deynze Allen Van
Published: June 2017

Background

Linked-Read sequencing technology has recently been employed successfully forde novoassembly of multiple human genomes, however the utility of this technology for complex plant genomes is unproven. We evaluated the technology for this purpose by sequencing the 3.5 gigabase (Gb) diploid pepper(Capsicum annuum)genome with a single Linked-Read library. Plant genomes, including pepper, are characterized by long, highly similar repetitive sequences. Accordingly, significant effort is used to ensure the sequenced plant is highly homozygous and the resulting assembly is a haploid consensus. With a phased assembly approach, we targeted a heterozygous F1derived from a wide cross to assess the ability to derive both haplotypes for a pungency gene characterized by a large insertion/deletion.

Results

The Supernova software generated a highly ordered, more contiguous sequence assembly than all currently availableC. annuumreference genomes. Eighty-four percent of the final assembly was anchored and oriented using fourde novolinkage maps. A comparison of the annotation of conserved eukaryotic genes indicated the completeness of assembly. The validity of the phased assembly is further demonstrated with the complete recovery of both 2.5 kb insertion/deletion haplotypes of thePUN1locus in the F1sample that represents pungent and non-pungent peppers.

Conclusions

The most contiguous pepper genome assembly to date has been generated through this work which demonstrates that Linked-Read library technology provides a rapid tool to assemblede novocomplex highly repetitive heterozygous plant genomes. This technology can provide an opportunity to cost-effectively develop high-quality reference genome assemblies for other complex plants and compare structural and gene differences through accurate haplotype reconstruction.
Sex-biased transcriptomic response of the reproductive axis to stress
Authors: Calisi Rebecca , Austin Suzanne H. , Lang Andrew S. , MacManes Matthew D.
Published: June 2017

Stress is a well-known cause of reproductive dysfunction in many species, including birds, rodents, and humans. However, little is known of the genomic basis for this dysfunction and how it may differ between the sexes. Using the classic reproductive model of the rock dove (Columba livia), we conducted the most in-depth investigation to date of how stress affects all gene transcription of a biological system essential for facilitating reproduction - the hypothalamic-pituitary-gonadal (HPG) axis. The HPG transcriptome responded to stress in both sexes, but females exhibited more differential expression than males, and these stress responsive genes were mostly unique to females. This result may be due to 1) fluctuations in the female endocrine environment to facilitate ovulation and follicle maturation, and 2) their evolutionary history. We offer a vital genomic foundation on which sex-specific reproductive dysfunction can be studied, as well as novel gene targets for genetic intervention and therapy investigations.
Unravelling the participation of stakeholders in the governance models of social enterprises in Greece
Authors: Argyrou Aikaterini , Blomme Robert J. , Lambooy Tineke , Kievit Henk
Published: June 2017

Purpose

This paper aims to examine the concept of participatory governance through membership in the context of the tailor-made legal form for social enterprises in Greece, i.e. the social cooperative enterprise (Koinsep). As such, the paper aims to contribute to the theoretical discussion regarding the participation of stakeholders in the governance of social enterprises not only as a theoretical construct prescribed by law but also by examining its implementation in practice.

Design/methodology/approach

The development of two in-depth case studies demonstrate whether and how the application and implementation of legal requirements regarding governance and membership permit and encourage stakeholders to participate in the decision-making processes of social enterprises. The study accordingly showcases the influence exerted by the legal regime over the social enterprise.

Findings

The case studies demonstrate how participatory governance is not realised in a formal manner in the organisational set-up of two social enterprises. It thereby shows how stakeholders and employees participate informally in the decision-making processes of Greek social enterprises, although legislation is conducive to formal means of participation.

Research limitations/implications

This study is part of a larger project involving a comparative research of tailor-made legal forms of social enterprises and corresponding organisations in three jurisdictions, i.e. Greece, Belgium, and the UK. In this study, the research was limited to the legal form of Koinsep.

Practical implications

This paper also contributes to the development of a better understanding of the Koinsep as a new tailor-made legal form for social enterprises in Greece. It therefore, sheds light in its function and its participatory governance structure.

Originality/value

The study is an original attempt to theoretically and practically examine the subject of participatory governance in the Greek social enterprises context.
Fast multipole cell-based domain integration method for treatment of volume potentials in 3D elasticity problems
Authors: Wang Qiao , Zhou Wei , Cheng Yonggang , Ma Gang , Chang Xiaolin
Published: June 2017

Purpose

Domain integrals, known as volume potentials in 3D elasticity problems, exist in many boundary-type methods, such as the boundary element method (BEM) for inhomogeneous partial differential equations. The purpose of this paper is to develop an accurate and reliable technique to effectively evaluate the volume potentials in 3D elasticity problems.

Design/methodology/approach

An adaptive background cell-based domain integration method is proposed for treatment of volume potentials in 3D elasticity problems. The background cells are constructed from the information of the boundary elements based on an oct-tree structure, and the domain integrals are evaluated over the cells rather than volume elements. The cells that contain the boundary elements can be subdivided into smaller sub-cells adaptively according to the sizes and levels of the boundary elements. The fast multipole method (FMM) is further applied in the proposed method to reduce the time complexity of large-scale computation.

Findings

The method is a boundary-only discretization method, and it can be applied in the BEM easily. Much computational time is saved by coupling with the FMM. Numerical examples demonstrate the accuracy and efficiency of the proposed method..

Originality/value

Boundary elements are used to create adaptive background cells, and domain integrals are evaluated over the cells rather than volume elements. Large-scale computation is made possible by coupling with the FMM.
An appraisal of the barriers to client involvement in health and safety in Nigeria’s construction industry
Authors: Umeokafor Nnedinma
Published: June 2017

Purpose

The purpose of this paper is to present the findings of a study that identified and assessed the barriers to client involvement in health and safety (H&S) in the Nigerian construction industry.

Design/methodology/approach

On the basis of literature review and a pilot study, structured questionnaires were designed and administered to clients and their representatives in ongoing construction projects in Nigeria. Descriptive and inferential statistics were then adopted while analysing the data.

Findings

The research reveals that the major barriers to client involvement in H&S in Nigeria’s construction industry focus on the gaps created by lack of H&S legislation in specifying client roles and responsibilities in H&S, trust and confidence in the supply chain, low levels of awareness at various levels, procurement issues, the attitudes of the various members of the project team and resource-related issues. In total, 20 barriers to client involvement in H&S were identified and assessed.

Practical implications

Policy makers will find the study beneficial as it provides a good understanding of the issues to address while making policies that seek to involve the client in H&S in Nigeria.

Originality/value

While the findings offer insight on the barriers to client involvement in H&S in Nigeria’s construction industry, the study also contributes to the discourse in developing countries. The paper recommends transparent steps in procurement, H&S legislation that factors in economic incentives and community and financial institutions contributions to involving clients in H&S. The study is the first attempt to investigate the barriers to client involvement in construction H&S in Nigeria, contributing to the dearth of H&S literature in Nigeria.