Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH): study protocol

Background: Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other) cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. Methods/design: The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Discussion: Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward

Immersive bilingualism reshapes the core of the brain

Bilingualism has been shown to affect the structure of the brain, including cortical regions related to language. Less is known about subcortical structures, such as the basal ganglia, which underlie speech monitoring and language selection, processes that are crucial for bilinguals, as well as other linguistic functions, such as grammatical and phonological acquisition and processing. Simultaneous bilinguals have demonstrated significant reshaping of the basal ganglia and the thalamus compared to monolinguals. However, it is not clear whether these effects are due to learning of the second language (L2) at a very young age or simply due to continuous usage of two languages. Here, we show that bilingualism-induced subcortical effects are directly related to the amount of continuous L2 usage, or L2 immersion. We found significant subcortical reshaping in non-simultaneous (or sequential) bilinguals with extensive immersion in a bilingual environment, closely mirroring the recent findings in simultaneous bilinguals. Importantly, some of these effects were positively correlated to the amount of L2 immersion. Conversely, sequential bilinguals with comparable proficiency and age of acquisition (AoA) but limited immersion did not show similar effects. Our results provide structural evidence to suggestions that L2 acquisition continuously occurs in an immersive environment, and is expressed as dynamic reshaping of the core of the brain. These findings propose that second language learning in the brain is a dynamic procedure which depends on active and continuous L2 usage

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Coffee resistance to the main diseases : leaf rust and coffee berry disease

Sucesso considerável tem sido obtido no uso do melhoramento clássico para o controle de doenças de plantas economicamente importantes, tais como a ferrugem alaranjada das folhas e a antracnose dos frutos do cafeeiro (CBD). Há um grande consenso de que o uso de plantas geneticamente resistentes é o meio mais apropriado e eficaz em termos de custos do controle das doenças das plantas, sendo também um dos elementos chave do melhoramento da produção agrícola. Tem sido também reconhecido que um melhor conhecimento do agente patogênico e dos mecanismos de defesa das plantas permitirá o desenvolvimento de novas abordagens no sentido de aumentar a durabilidade da resistência. Após uma breve descrição de conceitos na área da resistência das plantas às doenças, nesta revisão tentou-se dar uma idéia do progresso na investigação da ferrugem alaranjada do cafeeiro e do CBD relativamente ao processo de infecção e variabilidade dos agentes patogênicos, melhoramento do cafeeiro para a resistência e mecanismos de resistência do cafeeiro

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

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

The impact on sleep of a multidisciplinary cognitive behavioural pain management programme: a pilot study

Background: Reduced sleep quality is a common complaint among patients with chronic pain, with 50-80% of patients reporting sleep disturbance. Improvements in pain and quality of life measures have been achieved using a multidisciplinary cognitive behavioural therapy pain management programme (CBT-PMP) that aims to recondition attitudes to pain, and improve patients' self-management of their condition. Despite its high prevalence in patients with chronic pain, there is very limited objective evidence for the effect of this intervention on sleep quality. The primary research objective is to investigate the short-term effect of a multidisciplinary CBTPMP on subjective (measured by Pittsburg Sleep Quality Index) and objective sleep quality (measured by Actigraphy) in patients with chronic pain by comparison with a control group. The secondary objectives will investigate changes in function and mood, and then explore the relationship between objective and subjective sleep quality and physical and psychological outcome measures. Methods/Design: Patients who fulfil the inclusion criteria for attendance on the multidisciplinary CBT-PMP in the Adelaide and Meath Hospital, Tallaght, Dublin and are currently listed on the PMP waiting list will be invited to participate in this pilot study. Potential patients will be screened for sleep disturbance [determined by the Pittsburgh Sleep Quality Index (PSQI)]. Those patients with a sleep disturbance (PSQI >5) will be assigned to either the intervention group (immediate treatment), or control group (deferred treatment, i.e. the PMP they are listed for is more than six months away) based on where they appear on the waiting list. Baseline measures of sleep, function, and mood will be obtained using a combination of self-report questionnaires (the Hospital Anxiety and Depression Scale, the Short Form 36 health survey, the Pittsburgh Sleep Quality Index, the Tampa Scale for Kinesiophobia), and functional outcome measures. Sleep will be measured for seven days using actigraphy (Actiwatch 7). These measures will be repeated after the four week multidisciplinary cognitive behavioural therapy pain management programme, and at a two month follow-up. The waiting list control group will be assessed at baseline, and two months later. Analysis for the primary outcome will include between group differences of subjective and objective sleep parameters from baseline to follow-up using Independent T-tests or Mann-Whitney U tests. The secondary outcomes establishing relationships between the sleep variables and physical and psychological outcome measures will be established using multiple linear regression models. Discussion: This pilot study will evaluate the impact of a multidisciplinary CBT-PMP on both subjective and objective measures of sleep in patients with chronic pain and provide guidance for a larger clinical trial. Trial Registration: Current controlled trial ISRCTN: ISRCTN7491359