The different facets of organelle interplay - an overview of organelle interactions

ReviewThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.Membrane-bound organelles such as mitochondria, peroxisomes, or the endoplasmic reticulum (ER) create distinct environments to promote specific cellular tasks such as ATP production, lipid breakdown, or protein export. During recent years, it has become evident that organelles are integrated into cellular networks regulating metabolism, intracellular signaling, cellular maintenance, cell fate decision, and pathogen defence. In order to facilitate such signaling events, specialized membrane regions between apposing organelles bear distinct sets of proteins to enable tethering and exchange of metabolites and signaling molecules. Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level. However, historical and recent observations imply that other organelles like peroxisomes, lysosomes, and lipid droplets might also be involved in the formation of such apposing membrane contact sites. Alternatively, reports on so-called mitochondria derived-vesicles (MDV) suggest alternative mechanisms of organelle interaction. Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy—a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling. This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.BBSRCFP-7-PEOPLE-2012-Marie Curie-ITN 316723 PERFUMEPortuguese Foundation for Science and Technology (FCT

Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota

Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies

A Systematic Evaluation of Websites Offering Information on Chronic Kidney Disease

In this study, we described the content and characteristics of 40 non-proprietary websites offering information about chronic kidney disease (CKD) and evaluated their information quality using the DISCERN scale and readability using Flesch Reading Ease and Flesch-Kincaid grade level. The areas in which the websites scored the lowest on the DISCERN scale were whether the website discussed knowledge gaps, presented balanced information, and was clear about the information source. Websites that rated higher quality on the DISCERN scale were more difficult to read. The quality and readability of many websites about CKD to be used as meaningful educational resources for patients who desire to learn more about CKD and treatment options remain inadequate

Consumption-based emission accounting for Chinese cities

Most of China’s CO2 emissions are related to energy consumption in its cities. Thus, cities are critical for implementing China’s carbon emissions mitigation policies. In this study, we employ an input-output model to calculate consumption-based CO2 emissions for thirteen Chinese cities and find substantial differences between production- and consumption-based accounting in terms of both overall and per capita carbon emissions. Urban consumption not only leads to carbon emissions within a city’s own boundaries but also induces emissions in other regions via interregional trade. In megacities such as Shanghai, Beijing and Tianjin, approximately 70% of consumption-based emissions are imported from other regions. Annual per capita consumption-based emissions in the three megacities are 14, 12 and 10 tonnes of CO2 per person, respectively. Some medium-sized cities, such as Shenyang, Dalian and Ningbo, exhibit per capita emissions that resemble those in Tianjin. From the perspective of final use, capital formation is the largest contributor to consumption-based emissions at 32–65%. All thirteen cities are categorized by their trading patterns: five are production-based cities in which production-based emissions exceed consumption-based emissions, whereas eight are consumption-based cities, with the opposite emissions pattern. Moreover, production-based cities tend to become consumption-based as they undergo socioeconomic development

Primary histologic diagnosis using automated whole slide imaging: a validation study

BACKGROUND: Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution. METHODS: Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive. RESULTS: In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication. CONCLUSION: The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology

Collision activity during training increases total energy expenditure measured via doubly labelled water

Purpose: Collision sports are characterised by frequent high intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. Methods: Using a randomised crossover design, six professional young male rugby league players completed two different five-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly seven days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. Results: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ±0.07; p=0.0021) total energy expenditure across the five-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ±0.74; p=0.007) session rating of perceived exertion and a very likely greater (-14.6 ± 3.3%; ES = -1.60 ±0.51; p=0.002) decrease in wellbeing 24h later. Conclusions: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused” alongside the kinematic “work required”. Key words: Nutrition, Recovery, Contact, Rugb

Convergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis

Stephen Baylin and colleagues show that a combined genetic and epigenetic analysis of breast and colon cancers identifies a number of clinically significant genes targeted by multiple modes of inactivation

Recent developments in multiple sclerosis therapeutics

Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought

Adverse childhood experiences and mental health in young adults: a longitudinal survey

BACKGROUND: Adverse childhood experiences (ACEs) have been consistently linked to psychiatric difficulties in children and adults. However, the long-term effects of ACEs on mental health during the early adult years have been understudied. In addition, many studies are methodologically limited by use of non-representative samples, and few studies have investigated gender and racial differences. The current study relates self-reported lifetime exposure to a range of ACEs in a community sample of high school seniors to three mental health outcomes–depressive symptoms, drug abuse, and antisocial behavior–two years later during the transition to adulthood. METHODS: The study has a two-wave, prospective design. A systematic probability sample of high school seniors (N = 1093) was taken from communities of diverse socioeconomic status. They were interviewed in person in 1998 and over the telephone two years later. Gender and racial differences in ACE prevalence were tested with chi-square tests. Each mental health outcome was regressed on one ACE, controlling for gender, race/ethnicity, and SES to obtain partially standardized regression coefficients. RESULTS: Most ACEs were strongly associated with all three outcomes. The cumulative effect of ACEs was significant and of similar magnitude for all three outcomes. Except for sex abuse/assault, significant gender differences in the effects of single ACEs on depression and drug use were not observed. However, boys who experienced ACEs were more likely to engage in antisocial behavior early in young adulthood than girls who experienced similar ACEs. Where racial/ethnic differences existed, the adverse mental health impact of ACEs on Whites was consistently greater than on Blacks and Hispanics. CONCLUSION: Our sample of young adults from urban, socio-economically disadvantaged communities reported high rates of adverse childhood experiences. The public health impact of childhood adversity is evident in the very strong association between childhood adversity and depressive symptoms, antisocial behavior, and drug use during the early transition to adulthood. These findings, coupled with evidence that the impact of major childhood adversities persists well into adulthood, indicate the critical need for prevention and intervention strategies targeting early adverse experiences and their mental health consequences

Attentional control theory in childhood: enhanced attentional capture by non-emotional and emotional distractors in anxiety and depression

Attentional control theory (ACT) proposes that anxiety is associated with executive functioning deficits. The theory has been widely investigated in adults. The current study tested whether symptoms of childhood anxiety and depression were associated with experimentally measured attentional control in the context of non-emotional and emotional stimuli. Sixty-one children (mean age = 9.23 years, range = 8.39 - 10.41) reported their trait anxiety and depression symptoms and completed three visual search tasks. The tasks used a variant of an irrelevant singleton paradigm and measured attentional capture by task-irrelevant non-emotional (color) and emotional (facial expressions) distractors. Significant attentional capture by both non-emotional and emotional distractors was observed, and was significantly correlated with trait anxiety and symptoms of depression. The strength of relationship between attentional capture and the symptoms did not differ significantly for non-emotional and emotional distractors. The results suggest that symptoms of childhood anxiety and depression are associated with poorer attentional control both in the presence of emotional and non-emotional stimuli, supporting ACT in younger populations. This attentional deficit in the context of non-emotional information might be as central to childhood internalizing symptoms as attentional biases often observed on tasks investigating processing of emotional stimuli