Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility

Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients.

The Climate-system Historical Forecast Project: do stratosphere-resolving models make better seasonal climate predictions in boreal winter?

Using an international, multi-model suite of historical forecasts from the World Climate Research Programme (WCRP) Climate-system Historical Forecast Project (CHFP), we compare the seasonal prediction skill in boreal wintertime between models that resolve the stratosphere and its dynamics (“high-top”) and models that do not (“low-top”). We evaluate hindcasts that are initialized in November, and examine the model biases in the stratosphere and how they relate to boreal wintertime (Dec-Mar) seasonal forecast skill. We are unable to detect more skill in the high-top ensemble-mean than the low-top ensemble-mean in forecasting the wintertime North Atlantic Oscillation, but model performance varies widely. Increasing the ensemble size clearly increases the skill for a given model. We then examine two major processes involving stratosphere-troposphere interactions (the El Niño-Southern Oscillation/ENSO and the Quasi-biennial Oscillation/QBO) and how they relate to predictive skill on intra-seasonal to seasonal timescales, particularly over the North Atlantic and Eurasia regions. High-top models tend to have a more realistic stratospheric response to El Niño and the QBO compared to low-top models. Enhanced conditional wintertime skill over high-latitudes and the North Atlantic region during winters with El Niño conditions suggests a possible role for a stratospheric pathway.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Search for charge-asymmetric production of W ' bosons in t(t)over-bar + jet events from pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of the top-quark mass in t(t)over-bar events with dilepton final states in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for heavy Majorana neutrinos in mu(+/-)mu(+/-) + jets and e(+/-)e(+/-) + jets events in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for three-jet resonances in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for the standard model Higgs boson produced in association with W and Z bosons in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for pair produced fourth-generation up-type quarks in pp collisions at root s=7 TeV with a lepton in the final state

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inclusive and differential measurements of the t(t)over-bar charge asymmetry in proton-proton collisions root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for a Light Pseudoscalar Higgs Boson in the Dimuon Decay Channel in pp Collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Search for pair production of first- and second-generation scalar leptoquarks in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)