According to previous research, natural polyamines exert a role in regulating cell committment and differentiation from stemness during skeletal development. In order to assess whether distinct polyamine patterns are associated with different skeletal cell types, primary cultures of stem cells, chondrocytes or osteoblasts were dedicated for HPLC analysis of intracellular polyamines. Spermine (SPM) and Spermidine (SPD) levels were higher in adipose derived stem cells (ASC) compared to mature skeletal cells, i.e. chondrocytes and osteoblasts, confirming the connection of polyamine content with stemness. To establish whether polyamines can protect ASC against oxidative DNA damage in a 3-D differentiation model, the level of γH2AX was measured by western blot, and found to correlate with age and BMI of patients. Addition of either polyamine to ASC was able to hinder DNA damage in the low micromolecular range, with marked reduction of γH2AX level at 10 µM SPM and 5 µM SPD. Molecular analysis of the mechanisms that might underlie the protective effect of polyamine supplementation evidences a possible involvement of autophagy. Altogether, these results support the idea that polyamines are able to manage both stem cell differentiation and cell oxidative damage, and therefore represent appealing tools for regenerative and cell based applications.

In the last decade, avian gene preservation research has focused on the use of the early precursors of the reproductive cells, the primordial germ cells (PGCs). This is because avian PGCs have a unique migration route through the vascular system which offers easy accessibility. Furthermore, culturing of the cells in vitro, freezing/thawing, reintegration into a recipient embryo and the development of the germ cells can be carried out in well-defined laboratory circumstances. The efficient recovery of the donor genotype and the frequency of germline transmission from the surrogate host animals are still areas which need further development. Thus, the aim of the present study was to investigate an infertile interspecific hybrid (recipient) as an appropriate host for primordial germ cells from native poultry breeds. Guinea fowl × chicken hybrids were produced, the crossing was repeated inversely. The phenotype, the hatching time, the hatching rate, the sex ratio, the presence of own germ cells, the fertility and the phenotype of viable hybrids and the incidence of chromosomal abnormalities of dead hybrid embryos were described. 6.65% viable offspring was obtained with crossing of Guinea fowl females with domestic fowl males. Crossing of domestic fowl hens with Guinea fowl male resulted in lower fertility, 0.14% viable offspring. Based on the investigations, the observed offspring from the successful crossing were sterile male hybrids, thus an extreme form of Haldane's rule was manifested. The sterile hybrid male embryos were tested by injecting fluorescently labeled chicken PGCs. The integration rate of labeled PGCs was measured in 7.5-day, 14.5-day and 18.5-day old embryonic gonads. 50%, 5.3% and 2.4% of the injected hybrid embryos survived and 40%, 5.3% and 2.4% of the examined gonads contained fluorescent labeled donor PGCs. Therefore, these sterile hybrid males may be suitable recipients for male PGCs and possibly for female PGCs although with lower efficiency. This research work shows that the sterility of hybrids can be used in gene conservation to be a universal host for PGCs of different avian species.

Research suggests that sleep duration and obesity are related, but the direction of this association remains uncertain. We applied autoregressive cross-lag models to evaluate the directionality of the relationship between sleep duration and BMI from adolescence through emerging and young adulthood, life stages where the risk for developing obesity are particularly high. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined sex-stratified associations between sleep duration and BMI in this cohort from adolescence (ages 12-18, year 1996), to emerging adulthood (ages 18-24, 2001-2002), to young adulthood (ages 24-32, 2008), controlling for key confounders. For both males and females, higher BMI during an earlier developmental stage was associated with shorter sleep duration in the subsequent stage (both Bs = -0.02, ps < 0.01). However, sleep duration at an earlier developmental stage was not associated with BMI at the subsequent stage. Findings suggest that researchers should be cautious when interpreting cross-sectional relationships between sleep and BMI, as higher BMI may precede shorter sleep during adolescence to young adulthood. Researchers may also wish to account for potential bi-directional associations when modeling sleep and BMI using longitudinal data.

The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation.

The ClpXP machinery is a two-component protease complex that performs targeted protein degradation in bacteria and mitochondria. The complex consists of the AAA+ chaperone ClpX and the peptidase ClpP. The hexameric ClpX utilizes the energy of ATP binding and hydrolysis to engage, unfold and translocate substrates into the catalytic chamber of tetradecameric ClpP, where they are degraded. Formation of the complex involves a symmetry mismatch, because hexameric AAA+ rings bind axially to the opposing stacked heptameric rings of the tetradecameric ClpP. Here we present the cryo-EM structure of ClpXP from Listeria monocytogenes. We unravel the heptamer-hexamer binding interface and provide novel insight into the ClpX-ClpP cross-talk and activation mechanism. Comparison with available crystal structures of ClpP and ClpX in different states allows us to understand important aspects of the complex mode of action of ClpXP and provides a structural framework for future pharmacological applications.

Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes. Here, we show that the role of cohesin in chromosome organization requires the histone chaperone FACT ('facilitates chromatin transcription') in Saccharomyces cerevisiae. We find that FACT interacts directly with cohesin, and is dynamically required for its localization on chromatin. Depletion of FACT in metaphase cells prevents cohesin accumulation at pericentric regions and causes reduced binding on chromosome arms. Using the Hi-C technique, we show that cohesin-dependent TAD (topological associated domain)-like structures in G1 and metaphase chromosomes are reduced in the absence of FACT. Sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our data show that FACT contributes to the formation of cohesin-dependent TADs, thus uncovering a new role for this complex in nuclear organization during interphase and mitotic chromosome folding.

Distribution patterns of biodiversity and the factors influencing them are important in conservation and management strategies of natural resources. With impending threats from increased human population and global climatic changes, there is an urgent need for a comprehensive understanding of these patterns, more so in species-rich tropical montane ecosystems where little is known about plant diversity and distribution. Vascular species richness along elevation and climatic gradients of Aberdare ranges forest were explored. A total of 1337 species in 137 families, 606 genera, 82 subspecies and 80 varieties were recorded. Correlations, simple linear regression and Partial least square regression analysis were used to assess richness and diversity patterns of total plants, herbs, shrubs, climbers, arboreal and endemic species from 2000-4000 m above sea level. Total plant species richness showed a monotonic declining relationship with elevation with richness maxima at 2000-2100 m a.s.l., while endemic species richness had a positive unimodal increase along elevation with peaks at 3600-3700 m a.s.l. Herbs, shrubs, climbers and arboreal had significant negative relationships with altitude, excluding endemism which showed positive relations. In contrast, both air and soil temperatures had positive relationships with taxa richness groups and negative relations with endemic species. Elevation was found to have higher relative influence on plant richness and distribution in Aberdare ranges forest. For effective conservation and management of biodiversity in Aberdare, localized dynamic conservation interventions are recommended in contrast to broad and static strategies. Establishment of conservation zones and migration corridors are necessary to safeguard biodiversity in line with envisaged global climatic vicissitudes.

Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated.

Exosomal nucleic acid (exoNA) is a feasible target to improve the sensitivity of EGFR mutation testing in non-small cell lung cancer patients with limited cell-free DNA (cfDNA) mutant copies. However, the type and size of target exoNA related to the sensitivity of EGFR mutation testing has not been explored extensively.

We assess the tobacco advertisement, promotion and sponsorship (TAPS) ban enforcement in sales points in Panama in 2017.

Being the second most populous African country, Ethiopia represents a huge opportunity for the tobacco industry to recruit new smokers. Ethiopia signed the convention to ratify WHO Framework Convention on Tobacco Control (FCTC) in 2004 and ratified in 2014. We reviewed Ethiopia's tobacco control legislative history pre- and post-ratification of the WHO FCTC and evaluated the level of compliance of the National Tobacco Control Directive (NTCD) with the WHO FCTC.

Accumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone remodeling, which ultimately leads to osteoporosis. Therefore, reducing the ROS generation during osteogenesis of BMSCs may be an effective way to reverse the impairment of osteogenesis. Melatonin (MLT) has been reported to act as an antioxidant during cell proliferation and differentiation, but its antioxidant effect and mechanism of action during osteogenesis of MSCs in the inflammatory microenvironment, especially in the presence of TNF-α, remain unknown and need further study. In our study, we demonstrate that melatonin can counteract the generation of ROS and the inhibitory osteogenesis of BMSCs induced by TNF-α, by upregulating the expression of antioxidases and downregulating the expression of oxidases. Meanwhile, MLT can inhibit the phosphorylation of p65 protein and block the degradation of IκBα protein, thus decreasing the activity of the NF-κB pathway. This study confirmed that melatonin can inhibit the generation of ROS during osteogenic differentiation of BMSCs and reverse the inhibition of osteogenic differentiation of BMSCs in vitro, suggesting that melatonin can antagonize TNF-α-induced ROS generation and promote the great effect of osteogenic differentiation of BMSCs. Accordingly, these findings provide more evidence that melatonin can be used as a candidate drug for the treatment of osteoporosis.

Migration evolved as a behavior to enhance fitness through exploiting spatially and temporally variable resources and avoiding predation or other threats. Globally, landscape alterations have resulted in declines to migratory populations across taxa. Given the long time periods over which migrations evolved in native systems, it is unlikely that restored populations embody the same migratory complexity that existed before population reductions or regional extirpation.We used GPS location data collected from 209 female bighorn sheep (Ovis canadensis) to characterize population and individual migration patterns along elevation and geographic continuums for 18 populations of bighorn sheep with different management histories (i.e., restored, augmented, and native) across the western United States.Individuals with resident behaviors were present in all management histories. Elevational migrations were the most common population-level migratory behavior. There were notable differences in the degree of individual variation within a population across the three management histories. Relative to native populations, restored and augmented populations had less variation among individuals with respect to elevation and geographic migration distances. Differences in migratory behavior were most pronounced for geographic distances, where the majority of native populations had a range of variation that was 2-4 times greater than restored or augmented populations. Synthesis and applications. Migrations within native populations include a variety of patterns that translocation efforts have not been able to fully recreate within restored and augmented populations. Theoretical and empirical research has highlighted the benefits of migratory diversity in promoting resilience and population stability. Limited migratory diversity may serve as an additional factor limiting demographic performance and range expansion. We suggest preserving native systems with intact migratory portfolios and a more nuanced approach to restoration and augmentation in which source populations are identified based on a suite of criteria that includes matching migratory patterns of source populations with local landscape attributes.

Steroid sulfatase (STS) cleaves sulfate groups from steroid hormones; its expression/activity increases in late pregnancy and into the postpartum period. STS-deficient human and mouse mothers display elevated psychopathology and abnormal behaviour respectively; in mice, these effects can be partially normalised by antipsychotic (ziprasidone) administration.

Persons with schizophrenia are particularity susceptible to poor oral health. Symptoms of schizophrenia often affect oral health behaviors and lifestyle. The aim was to explore coping strategies used by people with schizophrenia in oral health in order to understand and to best involve them in the management of their own oral health in daily life.

Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignant cancers with no effective targets and treatments. However, the molecular pathogenesis of HCC remains largely uncertain. The aims of our study were to find crucial genes involved in HCC through multidimensional methods and revealed potential molecular mechanisms. Here, we reported the gene expression profile GSE121248 findings from 70 HCC and 37 adjacent normal tissues, all of which had chronic hepatitis B virus (HBV) infection, we were seeking to identify the dysregulated pathways, crucial genes and therapeutic targets implicated in HBV-associated HCC. We found 164 differentially expressed genes (DEGs) (92 downregulated genes and 72 upregulated genes). Gene ontology (GO) analysis of DEGs revealed significant functional enrichment of mitotic nuclear division, cell division, and the epoxygenase P450 pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly enriched in metabolism, cell cycle regulation and the p53 signaling pathway. The Mcode plugin was calculated to construct a module complex of DEGs, and the module was mainly enriched in cell cycle checkpoints, RHO GTPase effectors and cytochrome P450. Considering a weak contribution of each gene, gene set enrichment analysis (GSEA) was performed, revealing results consistent with those described above. Six crucial proteins were selected based on the degree of centrality, including NDC80, ESR1, ZWINT, NCAPG, ENO3 and CENPF. Real-time quantitative PCR analysis validated the six crucial genes had the same expression trend as predicted. Furthermore, the methylation data of The Cancer Genome Atlas (TCGA) with HCC showed that mRNA expression of crucial genes was negatively correlated with methylation levels of their promoter region. The overall survival reflected that high expression of NDC80, CENPF, ZWINT, and NCAPG significantly predicted poor prognosis, whereas ESR1 high expression exhibited a favorable prognosis. The identification of the crucial genes and pathways would contribute to the development of novel molecular targets and biomarker-driven treatments for HCC.

The aim of this study was to compare health-related quality of life (HRQoL) and disability and fear of movement in patients with non-specific chronic neck pain (NSCNP) associated with dizziness with respect to patients with isolated NSCNP in primary care settings.

Licorice (Glycyrrhiza spp. L.) is used as a natural sweetener and medicinal herb in European and Asian countries. Molecular studies have been conducted to find differences between wild and cultivated species because most wild species are highly resistant to abiotic and biotic stresses compared with their cultivated species. However, few molecular markers have been developed for studying the genetic diversity and population structure of licorice species and to identify differences between cultivars. Thus, the present study aimed to develop a set of genomic simple sequence repeat (SSR) markers for molecular studies of these species.

Introduction Wearable cardioverter defibrillators (WCD) are recommended for patients with a high risk of sudden cardiac death (SCD) secondary to arrhythmia that have not qualified for placement of an implantable cardiac defibrillator (ICD). This study provides insights into a single-center experience with WCD in terms of its usage and safety. Materials and methods We studied all patients that were prescribed a WCD in the Fairview Hospital in Cleveland Clinic Health System, from January 2014 to June 2016. Institutional Review Board of the Cleveland Clinic approved the study. A retrospective chart review was performed to collect data regarding demographics and baseline comorbidities including age, gender, history of hypertension, diabetes, coronary artery disease, and chronic kidney disease. The patients that were lost to follow up in our electronic medical record (EMR) were excluded. Ejection fraction (EF) at the time of diagnosis and follow-up was recorded. The primary outcome was ICD placement at follow up focusing on appropriate use while the secondary outcome was delivery of shock (appropriate or inappropriate) focusing on efficacy and safety of the device. Patients were stratified based on ICD placement. Statistical Package for the Social Sciences (SPSS), version 23 (IBM Corp., NY, USA) was used for the statistical analysis. Results We identified 73 patients with WCD placement. After the exclusion of 23/73 (31.5%) patients due to loss of follow-up, 50 patients were included in the study (n=50). Clinical characteristics showed 66% patients were males, 76% had hypertension, 40% had diabetes, 34% had chronic kidney disease, 56% patient had a New York Heart Association functional status of >II and 34% were on anti-arrhythmic medication. Indication for WCD use was ischemic cardiomyopathy in 23/50 (46%) patients and non-ischemic cardiomyopathy in 27/50 (54%) patients. No ICD was placed in 39/50 (78%) patients and ICD was placed in 11/50 (22%) patients at end time of follow up. Mean age was 59.9 years (95% confidence interval (CI), 55.9 - 63.9 years) in the group with no ICD placement and 63.5 years (95% CI, 56.5 - 70.6 years) in the group with ICD placement. Mean EF in the group with no ICD placement at the time of diagnosis was 25.8% (95% CI, 23.8% - 27.9%) which improved by 18.8% to a mean EF of 44.6% (41.1% - 48.1%) at the follow-up. Mean EF in the group with ICD placement was 32.7% (95% CI, 27.6% - 37.9%) which reduced by 4.1% to mean EF of 28.6% (95% CI, 12.2% - 44.9%) which was statistically significant (p<0.0001). Patients who had no ICD placement were followed for an average of 162 days and with ICD placement for 78 days. There was no difference between ischemic or nonischemic groups in getting the ICD. There were no shocks delivered whether appropriate or inappropriate in our population. Conclusion Almost a quarter of the patients that were prescribed WCD in our center ended up with an implanted device which demonstrates appropriate use. Equally important was the observed safety of WCDs as a treatment modality with no inappropriate shocks recorded in the followed cohort.

Problematic opioid use, constituted by a myriad of conditions ranging from misuse to use disorders, has continued to receive an increasing amount of attention in recent years resulting from the high use of opioids in the United States coinciding with morbidity and mortality. Deaths from drug overdoses increased by over 11% between 2014 and 2015, which supports the need for identification of problematic opioid use in additional health care settings. One of these settings is community pharmacy. The community pharmacy is a unique health service setting to identify and potentially intervene with patients at risk of or exhibit problematic opioid use. Problematic opioid use can be identified using one of the various screening tools in conjunction with evaluating prescription drug monitoring systems. A total of 12 tools were identified that could be employed in community pharmacy settings for identifying problematic opioid use. This review highlights these tools and strategies for use that can be utilized in the community pharmacy, which should be adapted to individual pharmacy settings and local needs. Future research should assess pharmacy personnel's knowledge and perceptions of problematic opioid use and associated screening tools and interventions, which tools can be most effectively used in a community pharmacy, workflow needs to implement problematic opioid use screenings, and the impact of pharmacist engagement in problematic opioid use screening on patient clinical outcomes.