A distinct sortase SrtB anchors and processes a streptococcal adhesin AbpA with a novel structural property.

Surface display of proteins by sortases in Gram-positive bacteria is crucial for bacterial fitness and virulence. We found a unique gene locus encoding an amylase-binding adhesin AbpA and a sortase B in oral streptococci. AbpA possesses a new distinct C-terminal cell wall sorting signal. We demonstrated that this C-terminal motif is required for anchoring AbpA to cell wall. In vitro and in vivo studies revealed that SrtB has dual functions, anchoring AbpA to the cell wall and processing AbpA into a ladder profile. Solution structure of AbpA determined by NMR reveals a novel structure comprising a small globular α/β domain and an extended coiled-coil heliacal domain. Structural and biochemical studies identified key residues that are crucial for amylase binding. Taken together, our studies document a unique sortase/adhesion substrate system in streptococci adapted to the oral environment rich in salivary amylase

Disturbed families or families disturbed: a reconsideration.

BACKGROUND: The relationship between anorexia nervosa (AN) and family disturbance has been a subject of debate since its first description. What began as a clear view of the pathologically disturbed family causing AN has become ever more complex over the decades. OBJECTIVE: The aim of this review is to explore the literature to examine the changes and evolution of clinical opinion around family dysfunction and AN over the last 20 years. METHODS: A narrative review of heterogeneous studies in peer-reviewed publications sourced from the major databases, including PubMed and ScienceDirect, to illuminate the topic of family distress and AN by highlighting the conflicting and complementary ways it has been studied. RESULTS: This review has highlighted the complexity of the relationship between anorectic sufferers and their families. It has explored the literature about parental burden, emotions and cognitive mechanisms together with parental attitudes about weight and shape. It is clear that there is no consistent psycho-social pathology in families which has been shown to be causative. However, over the last twenty years, research has highlighted the distress and family dysfunction caused by having to look after an anoretic child with poor mentalisation skills, insecure attachment and emotion dysregulation. CONCLUSION: The area has become clearer over the last 20 years; research suggests a bi-directional relationship between AN and family dysfunction, with difficult dynamics becoming entrenched within the family. This is best addressed, the consensus suggests, by specialist family therapy and carer skills interventions. Longitudinal research is needed to definitively answer the question with rigorous scientific certainty. EMB RATING: Level V. LEVEL OF EVIDENCE: Level I: Evidence obtained from: at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies. Level II: Evidence obtained from well-designed controlled trials without randomization. Level III: Evidence obtained from well-designed cohort or case-control analytic studies. Level IV: Evidence obtained from with multiple time series analysis such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence. Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees

Impact of a brief group intervention to enhance parenting and the home learning environment for children aged 6-36 months: A cluster randomised controlled trial

This is the final version of the article. Available from the publisher via the DOI in this record.This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. TRIAL REGISTRATION: 8 September 2011; ACTRN12611000965909 .This research was commissioned and funded by the Victorian Government Department of Education and Early Childhood Development (DEECD), and designed and conducted at the Parenting Research Centre. NH, EW, SB, AS, MT, MY and JN were employees of the Parenting Research Centre when this study was conducted. EW was part-funded by the Centre for Research Excellence in Child Language at Murdoch Childrens Research Institute (NHMRC grant 1023493). NH, EW, SB and JN are funded by the Australian Communities Foundation (Coronella sub-fund) at La Trobe University. OU is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. Views expressed are those of the authors and not necessarily those of DEECD, NIHR, NHS or the Department of Health

Polarizing Tweets on Climate Change

We introduce a framework to analyze the conversation between two competing groups of Twitter users, one who believe in the anthropogenic causes of climate change (Believers) and a second who are skeptical (Disbelievers). As a case study, we use Climate Change related tweets during the United Nation's (UN) Climate Change Conference - COP24 (2018), Katowice, Poland. We find that both Disbelievers and Believers talk within their group more than with the other group; this is more so the case for Disbelievers than for Believers. The Disbeliever messages focused more on attacking those personalities that believe in the anthropogenic causes of climate change. On the other hand, Believer messages focused on calls to combat climate change. We find that in both Disbelievers and Believers bot-like accounts were equally active and that unlike Believers, Disbelievers get their news from a concentrated number of news sources

Role Stress, Role Reward, and Mental Health in a Multiethnic Sample of Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN)

Abstract Background: Little is known about the independent associations of reward and stress within specific roles with multiple measures of mental health in an ethnically diverse community sample of midlife women. The objective of this study is to examine if (1) role reward (within each role and across roles) contributes directly to mental health and buffers the negative impact of role stress and (2) associations among role occupancy, role stress, and role reward and mental health vary by race/ethnicity. Methods: With separate logistic regression analysis, we investigated cross-sectional relationships between role stress and role reward with presence/absence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D≥16]), anxiety symptoms (feeling tense or nervous, irritable or grouchy, fearful for no reason, and heart pounding or racing total score≥4), or low social functioning (bottom 25th percentile of the Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in the third visit of the Study of Women's Health Across the Nation (SWAN), a longitudinal population-based study of menopause. Results: High reward across roles attenuated the negative impact of role stress on social functioning but not on anxiety or depression. High reward marriage buffered the impact of marital stress on depression, and high reward mothering buffered the effect of maternal stress on depression and social functioning. Compared to Caucasians, Hispanics and Chinese with high stress across roles had better social functioning, and African American mothers had lower odds of high depressive symptoms. Conclusions: Role reward buffers the negative impact of stress on social functioning and depression, but not on anxiety. Minorities may respond to role stress by seeking social support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98462/1/jwh%2E2011%2E3180.pd

Treatment of congenital extrahepatic portosystemic shunts in dogs : a systematic review and meta‐analysis

Background Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence-based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals Not used. Methods A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta-analysis was performed. Results Forty-eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P = .003). No other comparisons were statistically significant. Conclusions and Clinical Importance The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential

Cohort differences in disease and disability in the young-old: findings from the MRC Cognitive Function and Ageing Study (MRC-CFAS)

© 2007 Jagger et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

PTPRD and DCC Are Novel BACE1 Substrates Differentially Expressed in Alzheimer’s Disease: A Data Mining and Bioinformatics Study

The β-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is an extensively studied therapeutic target for Alzheimer’s disease (AD), owing to its role in the production of neurotoxic amyloid beta (Aβ) peptides. However, despite numerous BACE1 inhibitors entering clinical trials, none have successfully improved AD pathogenesis, despite effectively lowering Aβ concentrations. This can, in part, be attributed to an incomplete understanding of BACE1, including its physiological functions and substrate specificity. We propose that BACE1 has additional important physiological functions, mediated through substrates still to be identified. Thus, to address this, we computationally analysed a list of 533 BACE1 dependent proteins, identified from the literature, for potential BACE1 substrates, and compared them against proteins differentially expressed in AD. We identified 15 novel BACE1 substrates that were specifically altered in AD. To confirm our analysis, we validated Protein tyrosine phosphatase receptor type D (PTPRD) and Netrin receptor DCC (DCC) using Western blotting. These findings shed light on the BACE1 inhibitor failings and could enable the design of substrate-specific inhibitors to target alternative BACE1 substrates. Further-more, it gives us a greater understanding of the roles of BACE1 and its dysfunction in AD