Genome-wide analysis reveals a cell cycle–dependent mechanism controlling centromere propagation

Centromeres are the structural and functional foundation for kinetochore formation, spindle attachment, and chromosome segregation. In this study, we isolated factors required for centromere propagation using genome-wide RNA interference screening for defects in centromere protein A (CENP-A; centromere identifier [CID]) localization in Drosophila melanogaster. We identified the proteins CAL1 and CENP-C as essential factors for CID assembly at the centromere. CID, CAL1, and CENP-C coimmunoprecipitate and are mutually dependent for centromere localization and function. We also identified the mitotic cyclin A (CYCA) and the anaphase-promoting complex (APC) inhibitor RCA1/Emi1 as regulators of centromere propagation. We show that CYCA is centromere localized and that CYCA and RCA1/Emi1 couple centromere assembly to the cell cycle through regulation of the fizzy-related/CDH1 subunit of the APC. Our findings identify essential components of the epigenetic machinery that ensures proper specification and propagation of the centromere and suggest a mechanism for coordinating centromere inheritance with cell division

Substituting carbohydrate at lunch for added protein increases fat oxidation during subsequent exercise in healthy males

Context How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear. Objective Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake. Methods Twelve healthy males completed three trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 h (∼16:15) and post-exercise ad-libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and acylated ghrelin (AG) were measured for 5 h post-lunch. Results Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (p < 0.001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; p < 0.05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all p < 0.01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all p < 0.01). AG was lower during HI-CARB and LO-CARB versus FAST (p < 0.01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; p < 0.001) and HI-CARB (-313 ± 284 kcal; p < 0.001). Conclusion Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake

Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently

Neoliberalism and University Education in Sub-Saharan Africa

This article reviews the history of university development in Sub-Saharan Africa (SSA) and discusses the impact of neoliberal policies. This will be followed by an examination of the problems facing universities in the region. The following questions will be explored: (a) Are the existing universities in SSA serving the development needs of the region? (b) Are these universities up to the task of moving SSA out of the predicaments it faces such as famine, HIV/AIDS, poverty, diseases, debt, and human rights abuses? Finally, the article argues that for universities to play a role in the development of the region, a new paradigm that makes university education a public good should be established

Forcing single-column models using high-resolution model simulations

To use single column models (SCMs) as a research tool for parametrisation development and process studies, the SCM must be supplied with realistic initial profiles, forcing fields and boundary conditions. We propose a new technique for deriving these required profiles, motivated by the increase in number and scale of high-resolution convection-permitting simulations. We suggest that these high-resolution simulations be coarse-grained to the required resolution of an SCM, and thereby be used as a proxy for the ‘true’ atmosphere. This paper describes the implementation of such a technique. We test the proposed methodology using high-resolution data from the UK Met Office’s Unified Model (MetUM), with a resolution of 4 km, covering a large tropical domain. This data is coarse grained and used to drive the European Centre for Medium-Range Weather Forecast’s (ECMWF) Integrated Forecasting 26 System (IFS) SCM. The proposed method is evaluated by deriving IFS SCM forcing profiles from a consistent T639 IFS simulation. The SCM simulations track the global model, indicating a consistency between the estimated forcing fields and the ‘true’ dynamical forcing in the global model. We demonstrate the benefits of selecting SCM forcing profiles from across a large-domain, namely robust statistics, and the ability to test the SCM over a range of boundary conditions. We also compare driving the SCM with the coarse-grained datase to driving it using the ECMWF operational analysis. We conclude by highlighting the importance of understanding biases in the high-resolution dataset, and suggest that our approach be used in combination with observationally derived forcing datasets

Exercise-induced ‘browning’ of adipose tissues

Global rates of obesity continue to rise and are necessarily the consequence of a long-term imbalance between energy intake and energy expenditure. This is the result of an expansion of adipose tissue due to both the hypertrophy of existing adipocytes and hyperplasia of adipocyte precursors. Exercise elicits numerous physiological benefits on adipose tissue, which are likely to contribute to the associated cardiometabolic benefits. More recently it has been demonstrated that exercise, through a range of mechanisms, induces a phenotypic switch in adipose tissue from energy storing white adipocytes to thermogenic beige adipocytes. This has generated the hypothesis that the process of adipocyte ‘browning’ may partially underlie the improved cardiometabolic health in physically active populations. Interestingly, ‘browning’ also occurs in response to various stressors and could represent an adaptive response. In the context of exercise, it is not clear whether the appearance of beige adipocytes is metabolically beneficial or whether they occur as a transient adaptive process to exercise-induced stresses. The present review discusses the various mechanisms (e.g. fatty acid oxidation during exercise, decreased thermal insulation, stressors and angiogenesis) by which the exercise-induced ‘browning’ process may occur

Ageing vision and falls: a review

Background: Falls are the leading cause of accidental injury and death among older adults. One of three adults over the age of 65 years falls annually. As the size of elderly population increases, falls become a major concern for public health and there is a pressing need to understand the causes of falls thoroughly. Main body of the abstract: While it is well documented that visual functions such as visual acuity, contrast sensitivity, and stereo acuity are correlated with fall risks, little attention has been paid to the relationship between falls and the ability of the visual system to perceive motion in the environment. The omission of visual motion perception in the literature is a critical gap because it is an essential function in maintaining balance. In the present article, we first review existing studies regarding visual risk factors for falls and the effect of ageing vision on falls. We then present a group of phenomena such as vection and sensory reweighting that provide information on how visual motion signals are used to maintain balance. Conclusion: We suggest that the current list of visual risk factors for falls should be elaborated by taking into account the relationship between visual motion perception and balance control

Nurse prescribing of medicines in Western European and Anglo-Saxon countries: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>A growing number of countries are introducing some form of nurse prescribing. However, international reviews concerning nurse prescribing are scarce and lack a systematic and theoretical approach. The aim of this review was twofold: firstly, to gain insight into the scientific and professional literature describing the extent to and the ways in which nurse prescribing has been realised or is being introduced in Western European and Anglo-Saxon countries; secondly, to identify possible mechanisms underlying the introduction and organisation of nurse prescribing on the basis of Abbott's theory on the division of professional labor.</p> <p>Methods</p> <p>A comprehensive search of six literature databases and seven websites was performed without any limitation as to date of publication, language or country. Additionally, experts in the field of nurse prescribing were consulted. A three stage inclusion process, consisting of initial sifting, more detailed selection and checking full-text publications, was performed independently by pairs of reviewers. Data were synthesized using narrative and tabular methods.</p> <p>Results</p> <p>One hundred and twenty-four publications met the inclusion criteria. So far, seven Western European and Anglo-Saxon countries have implemented nurse prescribing of medicines, viz., Australia, Canada, Ireland, New Zealand, Sweden, the UK and the USA. The Netherlands and Spain are in the process of introducing nurse prescribing. A diversity of external and internal forces has led to the introduction of nurse prescribing internationally. The legal, educational and organizational conditions under which nurses prescribe medicines vary considerably between countries; from situations where nurses prescribe independently to situations in which prescribing by nurses is only allowed under strict conditions and supervision of physicians.</p> <p>Conclusions</p> <p>Differences between countries are reflected in the jurisdictional settlements between the nursing and medical professions concerning prescribing. In some countries, nurses share (full) jurisdiction with the medical profession, whereas in other countries nurses prescribe in a subordinate position. In most countries the jurisdiction over prescribing remains predominantly with the medical profession. There seems to be a mechanism linking the jurisdictional settlements between professions with the forces that led to the introduction of nurse prescribing. Forces focussing on efficiency appear to lead to more extensive prescribing rights.</p

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability