Neural development features: Spatio-temporal development of the Caenorhabditis elegans neuronal network

The nematode Caenorhabditis elegans, with information on neural connectivity, three-dimensional position and cell linage provides a unique system for understanding the development of neural networks. Although C. elegans has been widely studied in the past, we present the first statistical study from a developmental perspective, with findings that raise interesting suggestions on the establishment of long-distance connections and network hubs. Here, we analyze the neuro-development for temporal and spatial features, using birth times of neurons and their three-dimensional positions. Comparisons of growth in C. elegans with random spatial network growth highlight two findings relevant to neural network development. First, most neurons which are linked by long-distance connections are born around the same time and early on, suggesting the possibility of early contact or interaction between connected neurons during development. Second, early-born neurons are more highly connected (tendency to form hubs) than later born neurons. This indicates that the longer time frame available to them might underlie high connectivity. Both outcomes are not observed for random connection formation. The study finds that around one-third of electrically coupled long-range connections are late forming, raising the question of what mechanisms are involved in ensuring their accuracy, particularly in light of the extremely invariant connectivity observed in C. elegans. In conclusion, the sequence of neural network development highlights the possibility of early contact or interaction in securing long-distance and high-degree connectivity

Variantes en dos genes candidatos para características de calidad de carne bovina en Argentina

521-532Meat quality is a term used to describe a range of attributes of meat. It is determined by genetic and environmental factors (slaughter age, feeding and pre and post-slaughter management). The current tendency is to study the candidate genes in order to develop molecular markers, which might be used for marker-assisted selection. The objective of this work was to evaluate the effect of polymorphisms (SNP, single nucleotide polymorphisms) in candidate genes for tenderness and fat content in steers fattened in grazing beef production systems of Argentina. Molecular methods were designed to analyze the SNP 4751 (C/T) in bovine capn1 gene (large subunit of u-calpain), associated with tenderness and two polymorphisms (exon 8:G/A and intron 9:C/T) in bovine ppargc1a gene (peroxisome proliferatoractivated receptor gamma coactivator 1-alpha) with effect on fat content in cow milk and fiber type in pigs. Information of Warner-Bratzler shear force and fat content from 60 Brangus and 21 Angus steers was used in association studies. Tenderness of cooked meat was evaluated at 1.7 and 14 days post-mortem. A large proportion of animals were heterozygotes (CT) at SNP 4751. No differences were found between genotypes of this SNP for WBSF. A low frequency of homozygote TT was found at SNP on intron 9 of the ppargc1a gene. This SNP showed no significant effect on WBSF and fat content. Two new SNPs (G/A and T/C) were identified within exon 8 of the ppargc1a gene, by multiple alignment of DNA sequences obtained from 24 bulls of different breeds (Angus, Brangus, Brahman and Braford). One of them (G/A) could be the cause of aminoacid substitution of serine by asparagine at position 364 of the protein. The A allele was not found in Angus. The SNP T/ C is a conservative substitution. It is important that Argentina generate information about factors affecting meat quality for optimizing the production and exportation of high quality beef

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

Normalization of a conversation tool to promote shared decision making about anticoagulation in patients with atrial fibrillation within a practical randomized trial of its effectiveness: a cross-sectional study.

BACKGROUND: Shared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual factors such as clinician burnout and organizational support, remain unclear. We explored these factors in the context of a practical multicenter randomized trial evaluating the effectiveness of an SDM conversation tool for patients with atrial fibrillation considering anticoagulation therapy. METHODS: In this cross-sectional study, we recruited clinicians who were regularly involved in conversations with patients regarding anticoagulation for atrial fibrillation. Clinicians reported their characteristics and burnout symptoms using the two-item Maslach Burnout Inventory. Clinicians were trained in using the SDM tool, and they recorded their perceptions of the tool's normalization potential using the Normalization MeAsure Development (NoMAD) survey instrument and verbally reflected on their answers to these survey questions. When possible, the training sessions and clinicians' verbal responses to the conversation tool were recorded. RESULTS: Our study comprised 183 clinicians recruited into the trial (168 with survey responses and 112 with recordings). Overall, clinicians gave high scores to the normalization potential of the intervention; they endorsed all domains of normalization to the same extent, regardless of site, clinician characteristics, or burnout ratings. In interviews, clinicians paid significant attention to making sense of the tool. Tool buy-in seemed to depend heavily on their ability to see the tool as accurate and "evidence-based" and their perceptions of having time in the consultation to use it. CONCLUSIONS: While time in the consultation remains a barrier, we did not find a significant association between burnout symptoms and normalization of an SDM conversation tool. Possible areas for improving the normalization of SDM conversation tools in clinical practice include enabling collaboration among clinicians to implement the tool and reporting how clinicians elsewhere use the tool. Direct measures of normalization (i.e., observing how often clinicians access the tool in practice outside of the clinical trial) may further elucidate the role that contextual factors, such as clinician burnout, play in the implementation of SDM. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02905032. Registered on 9 September 2016

Variantes en dos genes candidatos para características de calidad de carne bovina en Argentina

521-532Meat quality is a term used to describe a range of attributes of meat. It is determined by genetic and environmental factors (slaughter age, feeding and pre and post-slaughter management). The current tendency is to study the candidate genes in order to develop molecular markers, which might be used for marker-assisted selection. The objective of this work was to evaluate the effect of polymorphisms (SNP, single nucleotide polymorphisms) in candidate genes for tenderness and fat content in steers fattened in grazing beef production systems of Argentina. Molecular methods were designed to analyze the SNP 4751 (C/T) in bovine capn1 gene (large subunit of u-calpain), associated with tenderness and two polymorphisms (exon 8:G/A and intron 9:C/T) in bovine ppargc1a gene (peroxisome proliferatoractivated receptor gamma coactivator 1-alpha) with effect on fat content in cow milk and fiber type in pigs. Information of Warner-Bratzler shear force and fat content from 60 Brangus and 21 Angus steers was used in association studies. Tenderness of cooked meat was evaluated at 1.7 and 14 days post-mortem. A large proportion of animals were heterozygotes (CT) at SNP 4751. No differences were found between genotypes of this SNP for WBSF. A low frequency of homozygote TT was found at SNP on intron 9 of the ppargc1a gene. This SNP showed no significant effect on WBSF and fat content. Two new SNPs (G/A and T/C) were identified within exon 8 of the ppargc1a gene, by multiple alignment of DNA sequences obtained from 24 bulls of different breeds (Angus, Brangus, Brahman and Braford). One of them (G/A) could be the cause of aminoacid substitution of serine by asparagine at position 364 of the protein. The A allele was not found in Angus. The SNP T/ C is a conservative substitution. It is important that Argentina generate information about factors affecting meat quality for optimizing the production and exportation of high quality beef

Longitudinal direct medical costs associated with constipation in women: Constipation direct costs in women

Although direct medical costs for constipation related medical visits are thought to be high, to date there have been no studies examining longitudinal resource utilization in adults with constipation

Effectiveness of the Chest Pain Choice decision aid in emergency department patients with low-risk chest pain: study protocol for a multicenter randomized trial

BACKGROUND: Chest pain is the second most common reason patients visit emergency departments (EDs) and often results in very low-risk patients being admitted for prolonged observation and advanced cardiac testing. Shared decision-making, including educating patients regarding their 45-day risk for acute coronary syndrome (ACS) and management options, might safely decrease healthcare utilization. METHODS/DESIGN: This is a protocol for a multicenter practical patient-level randomized trial to compare an intervention group receiving a decision aid, Chest Pain Choice (CPC), to a control group receiving usual care. Adults presenting to five geographically and ethnically diverse EDs who are being considered for admission for observation and advanced cardiac testing will be eligible for enrollment. We will measure the effect of CPC on (1) patient knowledge regarding their 45-day risk for ACS and the available management options (primary outcome); (2) patient engagement in the decision-making process; (3) the degree of conflict patients experience related to feeling uninformed (decisional conflict); (4) patient and clinician satisfaction with the decision made; (5) the rate of major adverse cardiac events at 30 days; (6) the proportion of patients admitted for advanced cardiac testing; and (7) healthcare utilization. To assess these outcomes, we will administer patient and clinician surveys immediately after each clinical encounter, obtain video recordings of the patient-clinician discussion, administer a patient healthcare utilization diary, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. DISCUSSION: This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in low-risk chest pain patients from a variety of geographically and ethnically diverse EDs. TRIAL REGISTRATION: NCT01969240

A first look at the N- and O-glycosylation landscape in anuran skin secretions.

Amphibians secrete a complex array of molecules that shape their interactions with coinhabiting microorganisms and macroscopic predators. Glycans are a rapidly evolving and complex class of biomolecules implicated in intrinsic and extrinsic recognition events. Despite the numerous studies aiming at the biochemical characterization of anuran skin secretions, little is known about protein-linked oligosaccharides, their synthesis pathways, and their homing secreted glycoproteins. In the present report, LC-MS/MS was used to investigate the diversity of N- and O-linked oligosaccharides in the skin secretion of two South American frogs, Pithecopus azureus and Boana raniceps. Additionally, the enzymes responsible for glycan synthesis pathways were evaluated based on their skin tissue transcriptome. Our analyses allowed the annotation of various N- and O-glycan structures commonly found in vertebrate proteins. Paucimannosidic glycans were abundant in the skin secretion of both amphibians; however, hybrid and complex N-glycan structures were detected only in B. raniceps. A good correlation between the structures discovered in glycomic analyses and transcripts encoding enzymes necessary for their synthesis was obtained. Some transcripts such as those of MAN1A2, FUT8, and ST6GALNAC were found solely in B. raniceps. Finally, secreted N- and O- linked glycoproteins were predicted from the transcriptomic data, indicating that proteases and protease inhibitors are putative sources of the glycans described herein. Overall, our results show the presence of oligosaccharides in amphibians skin secretions and suggest that their diversity is species-specific, paving the way for novel perspectives involving amphibian evolution and ecology

Comparison of Continuous versus Categorical Tumor Measurement-Based Metrics to Predict Overall Survival in Cancer Treatment Trials

The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival

LIN-44/Wnt Directs Dendrite Outgrowth through LIN-17/Frizzled in C. elegans Neurons

Nervous system function requires proper development of two functional and morphological domains of neurons, axons and dendrites. Although both these domains are equally important for signal transmission, our understanding of dendrite development remains relatively poor. Here, we show that in C. elegans the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR dendrites fail to form, display stunted growth, or are misrouted. Manipulation of temporal and spatial expression of LIN-44, combined with cell-ablation experiments, indicates that this molecule is patterned during embryogenesis and acts as an attractive cue to define the site from which the dendrite emerges. Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is transmitted through the LIN-17 receptor, which acts cell autonomously in PQR. Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule, EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken together, our results reveal a crucial role for Wnt and Frizzled molecules in regulating dendrite development in vivo