Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression.

Retinoblastoma is an aggressive childhood cancer of the developing retina that initiates by biallelic RB1 gene inactivation. Tumor progression in retinoblastoma is driven by epigenetics, as retinoblastoma genomes are stable, but the mechanism(s) that drive these epigenetic changes remain unknown. Lymphoid-specific helicase (HELLS) protein is an epigenetic modifier directly regulated by the RB/E2F pathway. In this study, we used novel genetically engineered mouse models to investigate the role of HELLS during retinal development and tumorigenesis. Our results indicate that Hells-null retinal progenitor cells divide, undergo cell-fate specification, and give rise to fully laminated retinae with minor bipolar cells defects, but normal retinal function. Despite the apparent nonessential role of HELLS in retinal development, failure to transcriptionally repress Hells during retinal terminal differentiation due to retinoblastoma (RB) family loss significantly contributes to retinal tumorigenesis. Loss of HELLS drastically reduced ectopic division of differentiating cells in Rb1/p107-null retinae, significantly decreased the incidence of retinoblastoma, delayed tumor progression, and increased overall survival. Despite its role in heterochromatin formation, we found no evidence that Hells loss directly affected chromatin accessibility in the retina but functioned as transcriptional co-activator of E2F3, decreasing expression of cell cycle genes. We propose that HELLS is a critical downstream mediator of E2F-dependent ectopic proliferation in RB-null retinae. Together with the nontoxic effect of HELLS loss in the developing retina, our results suggest that HELLS and its downstream pathways could serve as potential therapeutic targets for retinoblastoma

A survey of the reformulation of Australian child-oriented food products

© 2013 Savio et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Childhood obesity is one of the most pressing public health challenges of the 21st century. Reformulating commonly eaten food products is a key emerging strategy to improve the food supply and help address rising rates of obesity and chronic disease. This study aimed to monitor reformulation of Australian child-oriented food products (products marketed specifically to children) from 2009–2011. Methods In 2009, all child-oriented food products in a large supermarket in metropolitan Adelaide were identified. These baseline products were followed up in 2011 to identify products still available for sale. Nutrient content data were collected from Nutrient Information Panels in 2009 and 2011. Absolute and percentage change in nutrient content were calculated for energy, total fat, saturated fat, sugars, sodium and fibre. Data were descriptively analysed to examine reformulation in individual products, in key nutrients, within product categories and across all products. Two methods were used to assess the extent of reformulation; the first involved assessing percentage change in single nutrients over time, while the second involved a set of nutrient criteria to assess changes in overall healthiness of products over time. Results Of 120 products, 40 remained unchanged in nutrient composition from 2009–2011 and 80 underwent change. The proportions of positively and negatively reformulated products were similar for most nutrients surveyed, with the exception of sodium. Eighteen products (15%) were simultaneously positively and negatively reformulated for different nutrients. Using percentage change in nutrient content to assess extent of reformulation, nearly half (n = 53) of all products were at least moderately reformulated and just over one third (n = 42) were substantially reformulated. The nutrient criteria method revealed 5 products (6%) that were positively reformulated and none that had undergone negative reformulation. Conclusion Positive and negative reformulation was observed to a similar extent within the sample indicating little overall improvement in healthiness of the child-oriented food supply from 2009–2011. In the absence of agreed reformulation standards, the extent of reformulation was assessed against criteria developed specifically for this project. While arbitrary in nature, these criteria were based on reasonable assessment of the meaningfulness of reformulation and change in nutrient composition. As well as highlighting nutrient composition changes in a number of food products directed to children, this study emphasises the need to develop comprehensive, targeted and standardised reformulation benchmarks to assess the extent of reformulation occurring in the food supply

Global landscape of mouse and human cytokine transcriptional regulation

Cytokines are cell-to-cell signaling proteins that play a central role in immune development, pathogen responses, and diseases. Cytokines are highly regulated at the transcriptional level by combinations of transcription factors (TFs) that recruit cofactors and the transcriptional machinery. Here, we mined through three decades of studies to generate a comprehensive database, CytReg, reporting 843 and 647 interactions between TFs and cytokine genes, in human and mouse respectively. By integrating CytReg with other functional datasets, we determined general principles governing the transcriptional regulation of cytokine genes. In particular, we show a correlation between TF connectivity and immune phenotype and disease, we discuss the balance between tissue-specific and pathogen-activated TFs regulating each cytokine gene, and cooperativity and plasticity in cytokine regulation. We also illustrate the use of our database as a blueprint to predict TF–disease associations and identify potential TF–cytokine regulatory axes in autoimmune diseases. Finally, we discuss research biases in cytokine regulation studies, and use CytReg to predict novel interactions based on co-expression and motif analyses which we further validated experimentally. Overall, this resource provides a framework for the rational design of future cytokine gene regulation studies.National Institutes of Health (NIH) [R00 GM114296 and R35 GM128625 to J.I.F.B., 5T32HL007501-34 to J.A.S.]; National Science Foundation [NSF-REU BIO-1659605 to M.M.]. Funding for open access charge: NIH [R35 GM128625]. (R00 GM114296 - National Institutes of Health (NIH); R35 GM128625 - National Institutes of Health (NIH); 5T32HL007501-34 - National Institutes of Health (NIH); NSF-REU BIO-1659605 - National Science Foundation; R35 GM128625 - NIH)Published versio

Effects of Combining Meditation Techniques on Short-Term Memory, Attention, and Affect in Healthy College Students.

Meditation refers to a family of self-regulation practices that focuses on training attention and awareness to foster psycho-emotional well-being and to develop specific capacities such as calmness, clarity, and concentration. We report a prospective convenience-controlled study in which we analyzed the effect of two components of Preksha Dhyāna – buzzing bee sound meditation (Mahapran dhvani) and color meditation (leśyā dhyāna) on healthy college students. Mahapran and leśya dhyāna are two Preksha Dhyāna practices that are based on sound and green color, respectively. The study population represents a suitable target as college students experience different stress factors during the school year. This study measures the individual and combined effects of two techniques (one focusing on sound and one focusing on color), on short-term memory, attention, and affect, in novice meditators. We used a battery of cognitive, performance, and compared results with baseline and control values. We found improved cognition, especially attention, short-term memory, and affect in terms of positivity and reduced negativity. Overall, the two techniques produced variable benefits and subjects showed improved scores over baseline for short-term memory, cognitive function, and overall wellbeing. Further studies are required to understand underlying mechanisms for the observed differences between the two techniques and to elucidate mechanisms underlying the more pronounced and global benefits observed with the combined techniques. These results underscore a need to examine individual components of meditation practices in order to individualize treatment approaches for attention disorders in young adults

AN ESSENTIAL TOOL TO BE OPTIMIZED: SYNDROMIC MANAGEMENT OF VAGINAL DISCHARGE IN HAITI

Background: Haiti, like many low-income countries in crisis, has limited resources for etiologic diagnosis of vaginal discharge. As such, we sought to characterize variability in diagnoses of women presenting with vaginal discharge syndrome, with the goal to improve standardization of syndromic management. Materials and Methods: Participants aged 18 years and older endorsing vaginitis, or dysuria were recruited at Jerusalem Clinic over two, one-week periods in April 2018 and July 2019. We calculated Spearman rank correlations among history, exam findings, and diagnoses based on clinical presentation, to understand presentation groupings and their management. Results: Among 98 women, median age was 33.5 years, and most frequent symptoms were: vaginal discharge (97%), vaginal itch (73%), and/or suprapubic pain (68%). Most common physical exam findings were vaginal discharge (86%), suprapubic/lower quadrant tenderness (29%), cervical motion tenderness (24%), and cervical erythema (20%). Most symptoms and physical exam findings were weakly correlated with each other. Nearly one-third (31%) were diagnosed with normal physiologic vaginal discharge or no diagnosis, followed by Bacterial vaginosis (31%), vulvovaginal candidiasis (15%), cervicitis/PID (13%), and STI (7%). No reported symptoms strongly differentiated diagnostic categories. Diagnoses varied considerably by exam findings. Conclusions: The weak correlations between symptoms, exam findings, and diagnoses could represent variability in assessment. In the absence of reliable and accessible laboratory testing, the importance of standardizing syndromic management becomes increasingly relevant. Results from our study support the utility of speculum examination and more standardized documentation of physical exam findings. Next steps include the development of local algorithms to promote standardization of treatment of vaginal discharge syndrome

Complete Genome Sequences of Mycobacterium smegmatis Phages NihilNomen and Carlyle, Isolated in Las Vegas, Nevada

We present the complete genomes of the Mycobacterium smegmatis phages Carlyle and NihilNomen, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by undergraduate students enrolled in the Phage Discovery course offered by the School of Life Sciences at the University of Nevada Las Vegas

Update: Antarctic Winterover as an Analog for Spaceflight Immune Dysregulation

Orbital spaceflight perturbs the human immune system significantly; Natural Killer (NK) and T-lymphocyte (T) cell functions are most susceptible to spaceflight-induced impairment. This loss of function may manifest in persistent latent virus reactivation (CMV, EBV, VZV), which does occur at a higher frequency in astronauts compared to earthlings

Combining Microarray Technology and Molecular Epidemiology to Identify Genes Associated with Invasive Group B Streptococcus

Many bacterial species function as both commensals and pathogens; we used this dual nature to develop a high-throughput molecular epidemiological approach to identifying bacterial virulence genes. We applied our approach to Group B Streptococcus (GBS). Three representative commensal and one invasive GBS isolates were selected as tester strains from a population-based collection. We used microarray-based comparative genomic hybridization to identify open reading frames (ORFs) present in two sequenced invasive strains, but absent or divergent in tester strains. We screened 23 variable ORFs against 949 GBS isolates using a GBS Library on a Slide (LOS) microarray platform. Four ORFs occurred more frequently in invasive than commensal isolates, and one appeared more frequently in commensal isolates. Comparative hybridization using an oligonucleotide microarray, combined with epidemiologic screening using the LOS microarray platform, enabled rapid identification of bacterial genes potentially associated with pathogenicity