Intestinal Regulatory Systems of Invertebrates and Their Probable Evolution in Multicellular Animals

A wide distribution of regulatory (endocrine, nerve) cells in the digestive tract epithelium has been shown in representatives of taxons at different levels of the evolutionary tree, and their brief comparative characteristics are presented. The hypothesis is put forward that the intestinal regulatory systems, on having initially appeared based on predominantly nerve elements, were subsequently complicated due to the appearance of various endocrine cells originating from the epithelial ones. In the course of evolution, the spatial separation occurred of this heterogeneous system into the intraepithelial endocrine and subepithelial nerve components, this process running in parallel in the rows of protostomian and deuterostomian animals.     

被捕食动物对捕食者的识别研究及在放归中的应用

对捕食者的认知能力是当前生态学研究的一个热点。一些物种具有对捕食者先天的识别能力,而一些物种必须通过后天学习才能获得对捕食者的认知能力,还有许多动物通过社会学习和文化传播获得对捕食者的识别能力。本文就国外被捕食动物对捕食者的识别的研究进展进行综述,并讨论了该项研究对野外放归工作提供的重要理论意义和应用价值。     

Hospital-Based Program to Increase Child Safety Restraint Use among Birthing Mothers in China

Objective

To evaluate a hospital-based educational program to increase child safety restraint knowledge and use among birthing mothers.

Methods

A prospective experimental and control study was performed in the Obstetrics department of hospitals. A total of 216 new birthing mothers from two hospitals (114 from intervention hospital and 102 from comparison hospital) were recruited and enrolled in the study. Intervention mothers received a height chart, an 8-minute video and a folded pamphlet regarding child safety restraint use during their hospital stay after giving birth. Evaluation data on the child safety seat (CSS) awareness, attitudes, and use were collected among both groups before and after the intervention. An additional phone interview was conducted among the intervention mothers two months after discharge.

Results

No significant differences existed between groups when comparing demographics. Over 90% of the intervention mothers found the educational intervention to be helpful to some extent. A significantly higher percentage of mothers in the intervention than the comparison group reported that CSS are necessary and are the safest seating practice. Nearly 20% of the intervention mothers actually purchased CSS for their babies after the intervention. While in both the intervention and comparison group, over 80% of mothers identified the ages of two through five as needing CSS, fewer than 50% of both groups identified infants as needing CSS, even after the intervention.

Conclusion

The results indicated that child safety restraint education implemented in hospitals helps increase birthing mothers'' overall knowledge and use of CSS. Further efforts are needed to address specific age-related needs to promote car seats use among infants.     

Food Preference,Keeper Ratings,and Reinforcer Effectiveness in Exotic Animals: The Value of Systematic Testing

Food preference describes the behavior of selecting between items for consumption; reinforcer effectiveness is the functional effect of that item in controlling behavior. Food preference and reinforcer effectiveness were examined in giant pandas (Ailuropoda melanoleuca) and African elephants (Loxodonta africana). A pairwise comparison between food items was used to assess food preference. High-, moderate-, and low-preference items were selected and tested for reinforcer effectiveness. High-preference items controlled behavior more effectively than less-preferred items. Caregiver ratings of food preferences were also collected for each subject, but these reports did not necessarily coincide with actual subject preferences. Caregiver ratings correlated with the food preferences of only 1 individual of each species; thus, preferences of 1 nonhuman animal may be falsely generalized to all animals of that species. Results suggest that food choice and reinforcer effectiveness should be investigated empirically and not rely on anecdotal reports.     

A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.     

Cystic Fibrosis, A Disease of Animals As Well As Man

Cystic fibrosis, a genetically inherited disease of the exocrine glands in man, has no known counterpart in animals. The symptoms in man produced by mucous obstructing the lungs, pancreas and liver have been described. The signs, symptoms and course of an analogous disease in animals have been predicted. If an analogous disease in animals can be discovered, it is anticipated that it will make possible significant advances in the study of the normal and pathological physiology of the abnormal exocrine glands and will lead to a means of controlling the human disease.     

Dissection of Regulatory Networks that Are Altered in Disease via Differential Co-expression

Comparing the gene-expression profiles of sick and healthy individuals can help in understanding disease. Such differential expression analysis is a well-established way to find gene sets whose expression is altered in the disease. Recent approaches to gene-expression analysis go a step further and seek differential co-expression patterns, wherein the level of co-expression of a set of genes differs markedly between disease and control samples. Such patterns can arise from a disease-related change in the regulatory mechanism governing that set of genes, and pinpoint dysfunctional regulatory networks.Here we present DICER, a new method for detecting differentially co-expressed gene sets using a novel probabilistic score for differential correlation. DICER goes beyond standard differential co-expression and detects pairs of modules showing differential co-expression. The expression profiles of genes within each module of the pair are correlated across all samples. The correlation between the two modules, however, differs markedly between the disease and normal samples.We show that DICER outperforms the state of the art in terms of significance and interpretability of the detected gene sets. Moreover, the gene sets discovered by DICER manifest regulation by disease-specific microRNA families. In a case study on Alzheimer''s disease, DICER dissected biological processes and protein complexes into functional subunits that are differentially co-expressed, thereby revealing inner structures in disease regulatory networks.     

Activation of Salmonella Typhi-Specific Regulatory T Cells in Typhoid Disease in a Wild-Type S. Typhi Challenge Model

Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (T_reg) by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating T_reg between volunteers diagnosed with typhoid (TD) and those who were not (No TD). TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with T_reg homing to the gut. Additionally, S. Typhi-specific T_reg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1). We further demonstrate that depletion of T_reg results in increased S. Typhi-specific cytokine production by CD8+ T_EM in vitro. These results suggest that the tissue distribution of activated T_reg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.     

Association of Parkinson Disease with Structural and Regulatory Variants in the HLA Region

Historically, association of disease with the major histocompatibility complex (HLA) genes has been tested with HLA alleles that encode antigen-binding affinity. The association with Parkinson disease (PD), however, was discovered with noncoding SNPs in a genome-wide association study (GWAS). We show here that several HLA-region SNPs that have since been associated with PD form two blocks tagged by rs3129882 (p = 9 × 10⁻¹¹) and by rs9268515 and/or rs2395163 (p = 3 × 10⁻¹¹). We investigated whether these SNP-associations were driven by HLA-alleles at adjacent loci. We imputed class I and class II HLA-alleles for 2000 PD cases and 1986 controls from the NeuroGenetics Research Consortium GWAS and sequenced a subset of 194 cases and 204 controls. We were therefore able to assess accuracy of two imputation algorithms against next-generation-sequencing while taking advantage of the larger imputed data sets for disease study. Additionally, we imputed HLA alleles for 843 cases and 856 controls from another GWAS for replication. PD risk was positively associated with the B^∗07:02_C^∗07:02_DRB5^∗01_DRB1^∗15:01_DQA1^∗01:02_DQB1^∗06:02 haplotype and negatively associated with the C^∗03:04, DRB1^∗04:04 and DQA1^∗03:01 alleles. The risk haplotype and DQA1^∗03:01 lost significance when conditioned on the SNPs, but C^∗03:04 (OR = 0.72, p = 8 × 10⁻⁶) and DRB1^∗04:04 (OR = 0.65, p = 4 × 10⁻⁵) remained significant. Similarly, rs3129882 and the closely linked rs9268515 and rs2395163 remained significant irrespective of HLA alleles. rs3129882 and rs2395163 are expression quantitative trait loci (eQTLs) for HLA-DR and HLA-DQ (9 × 10⁻⁵ ≥ P_eQTL ≥ 2 × 10⁻⁷⁹), suggesting that HLA gene expression might influence PD. Our data suggest that PD is associated with both structural and regulatory elements in HLA. Furthermore, our study demonstrates that noncoding SNPs in the HLA region can be associated with disease irrespective of HLA alleles, and that observed associations with HLA alleles can sometimes be secondary to a noncoding variant.