Cell Cycle-Dependent Binding of Yeast Heat Shock Factor to Nucleosomes

In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of histones. We have investigated the mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82-ΔHSE1). We find that activated HSF cannot bind a stable, sequence-positioned nucleosome in G1-arrested cells. It can do so readily, however, following release from G1 arrest or after the imposition of either an early S- or late G2-phase arrest. Surprisingly, despite the S-phase requirement, HSF nucleosomal binding activity is restored in the absence of hsp82 replication. These results contrast with the prevailing paradigm for activator-nucleosome interactions and implicate a nonreplicative, S-phase-specific event as a prerequisite for HSF binding to nucleosomal sites in vivo

Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models

Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB), caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum). The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR) and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF) in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors) collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early assessment of the risk of SNB, facilitating sound disease management decisions prior to planting of wheat

Group-Based Training on Trial-Based Functional Analysis

A functional behavior assessment (FBA) of challenging behavior has been identified as a High-Leverage Practice in the social/emotional/behavior area (HLPs; McLeskey et al., 2017). Despite the importance of FBAs to classroom practices, many FBAs are conducted outside of classroom settings. Evidence suggests that FBAs may be more effective when conducted in a child’s typical classroom setting. A trial-based functional assessment (TBFA) is a variant of an FBA that is conducted by practitioners in a child’s classroom environment. The purpose of this paper is to outline the important components that should be included in a TBFA group training designed for practitioners in the field

Automated 4D analysis of dendritic spine morphology: applications to stimulus-induced spine remodeling and pharmacological rescue in a disease model

Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease

microRNAs Sculpt Neuronal Communication in a Tight Balance That Is Lost in Neurological Disease

Since the discovery of the first microRNA 25 years ago, microRNAs (miRNAs) have emerged as critical regulators of gene expression within the mammalian brain. miRNAs are small non-coding RNAs that direct the RNA induced silencing complex to complementary sites on mRNA targets, leading to translational repression and/or mRNA degradation. Within the brain, intra- and extracellular signaling events tune the levels and activities of miRNAs to suit the needs of individual neurons under changing cellular contexts. Conversely, miRNAs shape neuronal communication by regulating the synthesis of proteins that mediate synaptic transmission and other forms of neuronal signaling. Several miRNAs have been shown to be critical for brain function regulating, for example, enduring forms of synaptic plasticity and dendritic morphology. Deficits in miRNA biogenesis have been linked to neurological deficits in humans, and widespread changes in miRNA levels occur in epilepsy, traumatic brain injury, and in response to less dramatic brain insults in rodent models. Manipulation of certain miRNAs can also alter the representation and progression of some of these disorders in rodent models. Recently, microdeletions encompassing MIR137HG, the host gene which encodes the miRNA miR-137, have been linked to autism and intellectual disability, and genome wide association studies have linked this locus to schizophrenia. Recent studies have demonstrated that miR-137 regulates several forms of synaptic plasticity as well as signaling cascades thought to be aberrant in schizophrenia. Together, these studies suggest a mechanism by which miRNA dysregulation might contribute to psychiatric disease and highlight the power of miRNAs to influence the human brain by sculpting communication between neurons

Common garden versus common practice – Phenotypic changes in Trifolium pratense L. in response to repeated mowing

Plants react to various biotic and abiotic factors by adjusting their growth pattern. This process, called phenotypic plasticity, can also be observed in the agronomical important fodder plant Trifolium pratense L. (red clover) which is grown worldwide for its high pro-tein content and soil improving ability. After cutting it changes its growth pattern due to phenotypic plasticity and initiates a second growth phase. Here, we analyze the regrowth dynamics of red clover in response to grazing or mowing by recording the plant’s architecture, leaf morphology, and growth performance in different cutting experiments. As previous studies were limited in the number of individuals and carried out via common garden experiments, we analyzed the regrowth reaction of T. pratense under standard agricul-tural field conditions. T. pratense forms smaller and rounder leaflets after repeated cutting, compensated by the production of more bio-mass. Nitrogen contents were subjected to seasonal changes, rather than by changes through cutting. As middle to late cut plants had higher regrowth capacities and regrew more biomass than early cut plants, an optimal time point for biomass harvest can be suggested to maximize the total yield of red clover biomass

Sugary Drink FACTS 2014: Some Progress but Much Room for Improvement in Marketing to Youth

This report updates a 2011 report on the same topic. Using the same methods as the last report, researchers examined changes in the nutritional content of sugar-sweetened drinks including sodas, fruit drinks, flavored waters, sports drinks, iced teas, as well as zero-calorie energy drinks and shots. They also analyzed marketing tactics for 23 companies that advertised these products, including amount spent to advertise in all media; child and teen exposure to advertising and brand appearances on TV and visits to beverage company websites, including differences for black and Hispanic youth; advertising on websites popular with children and teens; and marketing in newer media like mobile apps and social media. Researchers also examined changes in advertising of diet beverages, 100% juice, and water

Trauernormen: historische und gegenwärtige Perspektiven

"Ziel des Beitrags ist es, eine historische Perspektive auf die Trauer im westlichen Kulturraum zu entwickeln und die darin wirkenden Trauernormen zu verdeutlichen. Den theoretischen Rahmen bildet das Konzept der Gefühlsnormen von Arlie Hochschild. Mit einer Verlagerung von Trauer aus der Gemeinschaft und Öffentlichkeit in die Privatheit - weitgehend losgelöst von festgelegten Ritualen und Praktiken - lässt sich ein historischer Wandel von Verhaltensnormen hin zu Gefühlsnormen im Rahmen einer Emotionalisierung der Trauer feststellen. Empirische Befunde einer Online-Befragung in der Schweiz und Deutschland verdeutlichen die gegenwärtigen Trauernormen und individuellen Erfahrungen im Erleben der Trauer. Die Ergebnisse geben u. a. Hinweise auf die Kontrolle von Trauergefühlen, die Schwierigkeiten, mit anderen über die Trauer zu sprechen und eine Unsicherheit im sozialen Umgang mit Trauernden." (Autorenreferat)"The article adopts a historical perspective on grieving in Western culture and traces contemporary grieving norms. Arlie Hochschild's concept of feeling rules provides the theoretical framework. As grieving has shifted from the community and the public sphere to private sphere - where it is no longer embedded in set rituals and practices -, we can also observe a historical shift from behavioral norms to feeling norms in the course of an emotionalization of grieving. Empirical findings from an online survey in Switzerland and Germany elucidate contemporary grieving norms and illustrate individual experiences of grieving. The results indicate, among other things, how the emotions involved in grieving are controlled and what difficulties exist in verbalizing grief to others. They also point to insecurity in social interaction with those grieving." (author's abstract

Trauernormen: historische und gegenwärtige Perspektiven

"Ziel des Beitrags ist es, eine historische Perspektive auf die Trauer im westlichen Kulturraum zu entwickeln und die darin wirkenden Trauernormen zu verdeutlichen. Den theoretischen Rahmen bildet das Konzept der Gefühlsnormen von Arlie Hochschild. Mit einer Verlagerung von Trauer aus der Gemeinschaft und Öffentlichkeit in die Privatheit - weitgehend losgelöst von festgelegten Ritualen und Praktiken - lässt sich ein historischer Wandel von Verhaltensnormen hin zu Gefühlsnormen im Rahmen einer Emotionalisierung der Trauer feststellen. Empirische Befunde einer Online-Befragung in der Schweiz und Deutschland verdeutlichen die gegenwärtigen Trauernormen und individuellen Erfahrungen im Erleben der Trauer. Die Ergebnisse geben u. a. Hinweise auf die Kontrolle von Trauergefühlen, die Schwierigkeiten, mit anderen über die Trauer zu sprechen und eine Unsicherheit im sozialen Umgang mit Trauernden." (Autorenreferat)"The article adopts a historical perspective on grieving in Western culture and traces contemporary grieving norms. Arlie Hochschild's concept of feeling rules provides the theoretical framework. As grieving has shifted from the community and the public sphere to private sphere - where it is no longer embedded in set rituals and practices -, we can also observe a historical shift from behavioral norms to feeling norms in the course of an emotionalization of grieving. Empirical findings from an online survey in Switzerland and Germany elucidate contemporary grieving norms and illustrate individual experiences of grieving. The results indicate, among other things, how the emotions involved in grieving are controlled and what difficulties exist in verbalizing grief to others. They also point to insecurity in social interaction with those grieving." (author's abstract

Assessing estrogen-induced proliferative response in an endometrial cancer cell line using a universally applicable methodological guide

Objective: Translational endometrial cancer (EC) research benefits from an in vitro experimental approach using EC cell lines. We demonstrated the steps that are required to examine estrogen induced proliferative response, a simple yet important research question pertinent to EC and devised a pragmatic methodological workflow for utilising EC cell lines in experimental models. Methods/materials: Comprehensive review of all commercially available EC cell lines was carried out, and Ishikawa cell line was selected to study the oestrogen responsiveness with HEC1A, RL95-2 and MFE280 cell lines as comparators where appropriate, examining relevant differential molecular (steroid receptors) and functional (phenotype, anchorage-independent growth, hormone responsiveness, migration, invasion and chemosensitivity) characteristics in 2D and 3D cultures in vitro using immunocytochemistry, immunofluorescence, qPCR and western blotting. In vivo tumour, formation and chemosensitivity were also assessed in a chick chorioallantoic membrane (CAM) model. Results: Short Tandem Repeat (STR) analysis authenticated the purchased cell lines while gifted cells deviated significantly from the published profile. We demonstrate the importance of prior assessment of the suitability of each cell line for the chosen in vitro experimental technique. Prior establishment of baseline, non-enriched conditions was required to induce a proliferative response to estrogen. The CAM model was a suitable in vivo multi-cellular animal model for EC, for producing rapid and reproducible data. Conclusions: We have developed a methodological guide for EC researchers when using endometrial cell lines to answer important translational research questions (exemplified by estrogen responsive cell proliferation), to facilitate robust data, while saving time and resources