Childhood socioeconomic status and childhood maltreatment: Distinct associations with brain structure

The present study examined the relationship between childhood socioeconomic status (SES), childhood maltreatment, and the volumes of the hippocampus and amygdala between the ages of 25 and 36 years. Previous work has linked both low SES and maltreatment with reduced hippocampal volume in childhood, an effect attributed to childhood stress. In 46 adult subjects, only childhood maltreatment, and not childhood SES, predicted hippocampal volume in regression analyses, with greater maltreatment associated with lower volume. Neither factor was related to amygdala volume. When current SES and recent interpersonal stressful events were also considered, recent interpersonal stressful events predicted smaller hippocampal volumes over and above childhood maltreatment. Finally, exploratory analyses revealed a significant sex by childhood SES interaction, with women’s childhood SES showing a significantly more positive relation (less negative) with hippocampus volume than men’s. The overall effect of childhood maltreatment but not SES, and the sex-specific effect of childhood SES, indicate that different forms of stressful childhood adversity affect brain development differently

Lessons from Elwha Ecosystem Restoration: Integrating science, policy, and management

After decades of debate, planning, and environmental impact studies, the largest planned dam removal project in history was conducted on the Elwha River in Washington State, USA, from 2011 to 2014. Because this was such a unique and unprecedented project, the planning, implementation, and monitoring has occurred over 30 years and required diverse expertise across multiple stakeholders. This knowledge portfolio required that individuals and organizations with different missions collaborate effectively to ensure a successful project. The story of this river, with rugged headwaters, protected wilderness, legendary and culturally important salmon runs, and two hydroelectric dams whose placement marshaled wholesale socioeconomic and ecological changes, has become an iconic saga of change, perseverance and renewal. The two dams blocked fish migrations and disrupted sediment transport for a century, disrupting the ecological structure and function of the Elwha River. Removal of the 64-m and 32-m tall dams and the release of a large portion of the 21 million cubic meters of stored reservoir sediment, has provided a living laboratory to study the patterns, processes and outcomes of dam removal across freshwater, estuarine, and marine ecosystem boundaries from multiple scientific perspectives. This collaborative multidisciplinary approach has allowed us to improve our understanding of ecosystem responses and linkages while making the Elwha River one of the best studied dam removal projects

Conceptualizing Ecological Responses to Dam Removal: If You Remove It, What’s to Come?

One of the desired outcomes of dam decommissioning and removal is the recovery of aquatic and riparian ecosystems. To investigate this common objective, we synthesized information from empirical studies and ecological theory into conceptual models that depict key physical and biological links driving ecological responses to removing dams. We define models for three distinct spatial domains: upstream of the former reservoir, within the reservoir, and downstream of the removed dam. Emerging from these models are response trajectories that clarify potential pathways of ecological transitions in each domain. We illustrate that the responses are controlled by multiple causal pathways and feedback loops among physical and biological components of the ecosystem, creating recovery trajectories that are dynamic and nonlinear. In most cases, short-term effects are typically followed by longer-term responses that bring ecosystems to new and frequently predictable ecological condition, which may or may not be similar to what existed prior to impoundment

Effects of Sorafenib on Intra-Tumoral Interstitial Fluid Pressure and Circulating Biomarkers in Patients with Refractory Sarcomas (NCI Protocol 6948)

Purpose: Jain Sorafenib is a multi-targeted tyrosine kinase inhibitor with therapeutic efficacy in several malignancies. Sorafenib may exert its anti-neoplastic effect in part by altering vascular permeability and reducing intra-tumoral interstitial hypertension. As correlative science with a phase II study in patients with advanced soft-tissue sarcomas (STS), we evaluated the impact of this agent on intra-tumor interstitial fluid pressure (IFP), serum circulating biomarkers, and vascular density. Patients and Methods: Patients with advanced STS with measurable disease and at least one superficial lesion amenable to biopsy received sorafenib 400 mg twice daily. Intratumoral IFP and plasma and circulating cell biomarkers were measured before and after 1–2 months of sorafenib administration. Results were analyzed in the context of the primary clinical endpoint of time-to-progression (TTP). Results: In 15 patients accrued, the median TTP was 45 days (range 14–228). Intra-tumoral IFP measurements obtained in 6 patients at baseline showed a direct correlation with tumor size. Two patients with stable disease at two months had post-sorafenib IFP evaluations and demonstrated a decline in IFP and vascular density. Sorafenib significantly increased plasma VEGF, PlGF, and SDF1$\alpha$ and decreased sVEGFR-2 levels. Increased plasma SDF1$\alpha$ and decreased sVEGFR-2 levels on day 28 correlated with disease progression. Conclusions: Pretreatment intra-tumoral IFP correlated with tumor size and decreased in two evaluable patients with SD on sorafenib. Sorafenib also induced changes in circulating biomarkers consistent with expected VEGF pathway blockade, despite the lack of more striking clinical activity in this small series

Prediction of protein structural classes for low-homology sequences based on predicted secondary structure

<p>Abstract</p> <p>Background</p> <p>Prediction of protein structural classes (<it>α</it>, <it>β</it>, <it>α </it>+ <it>β </it>and <it>α</it>/<it>β</it>) from amino acid sequences is of great importance, as it is beneficial to study protein function, regulation and interactions. Many methods have been developed for high-homology protein sequences, and the prediction accuracies can achieve up to 90%. However, for low-homology sequences whose average pairwise sequence identity lies between 20% and 40%, they perform relatively poorly, yielding the prediction accuracy often below 60%.</p> <p>Results</p> <p>We propose a new method to predict protein structural classes on the basis of features extracted from the predicted secondary structures of proteins rather than directly from their amino acid sequences. It first uses PSIPRED to predict the secondary structure for each protein sequence. Then, the <it>chaos game representation </it>is employed to represent the predicted secondary structure as two time series, from which we generate a comprehensive set of 24 features using <it>recurrence quantification analysis</it>, <it>K-string based information entropy </it>and <it>segment-based analysis</it>. The resulting feature vectors are finally fed into a simple yet powerful Fisher's discriminant algorithm for the prediction of protein structural classes. We tested the proposed method on three benchmark datasets in low homology and achieved the overall prediction accuracies of 82.9%, 83.1% and 81.3%, respectively. Comparisons with ten existing methods showed that our method consistently performs better for all the tested datasets and the overall accuracy improvements range from 2.3% to 27.5%. A web server that implements the proposed method is freely available at <url>http://www1.spms.ntu.edu.sg/~chenxin/RKS_PPSC/</url>.</p> <p>Conclusion</p> <p>The high prediction accuracy achieved by our proposed method is attributed to the design of a comprehensive feature set on the predicted secondary structure sequences, which is capable of characterizing the sequence order information, local interactions of the secondary structural elements, and spacial arrangements of <it>α </it>helices and <it>β </it>strands. Thus, it is a valuable method to predict protein structural classes particularly for low-homology amino acid sequences.</p

Contribution of CXCL12 secretion to invasion of breast cancer cells

INTRODUCTION: Neu (HER2/ErbB2) is overexpressed in 25% to 30% of human breast cancer, correlating with a poor prognosis. Researchers in previous studies who used the mouse mammary tumor virus Neu-transgenic mouse model (MMTV-Neu) demonstrated that the Neu-YB line had increased production of CXCL12 and increased metastasis, whereas the Neu-YD line had decreased metastasis. In this study, we examined the role of increased production of CXCL12 in tumor cell invasion and malignancy. METHODS: We studied invasion in the tumor microenvironment using multiphoton intravital imaging, in vivo invasion and intravasation assays. CXCL12 signaling was altered by using the CXCR4 inhibitor AMD3100 or by increasing CXCL12 expression. The role of macrophage signaling in vivo was determined using a colony-stimulating factor 1 receptor (CSF-1R) blocking antibody. RESULTS: The Neu-YD strain was reduced in invasion, intravasation and metastasis compared to the Neu-YB and Neu deletion mutant (activated receptor) strains. Remarkably, in the Neu-YB strain, in vivo invasion to epidermal growth factor was dependent on both CXCL12-CXCR4 and CSF1-CSF-1R signaling. Neu-YB tumors had increased macrophage and microvessel density. Overexpression of CXCL12 in rat mammary adenocarcinoma cells increased in vivo invasion as well as microvessel and macrophage density. CONCLUSIONS: Expression of CXCL12 by tumor cells results in increased macrophage and microvessel density and in vivo invasiveness

New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements