High PITX1 expression in lung adenocarcinoma patients is associated with DNA methylation and poor prognosis

Background

Pituitary homeobox 1 (PITX1) is a member of the PITX gene family which is vital to proper development of early embryo. However, the relationship of PITX1 expression and overall survival (OS) in non-small cell lung cancer (NSCLC) is not clear.

The effects of enriched environment on the behavioral and corticosterone response to methamphetamine in adolescent and adult mice

Methamphetamine alters behavior and the stress response system. Relatively little research has examined the effects of methamphetamine in adolescents and compared these effects to those in adults. Housing in enriched environments has been explored as one way to protect against the effects of methamphetamine, but the findings are conflicting and no study has examined how enriched environment may alter the behavioral and corticosterone responses to methamphetamine in adolescent and adult rodents. We examined the long‐term effects of methamphetamine exposure on anxiety, social behavior, behavioral despair, and corticosterone levels in adolescent and adult mice housed in enriched or isolated environments. Enriched environment did not alter the behavioral or corticosterone response to methamphetamine. Methamphetamine exposure decreased anxiety and increased behavioral despair in adult mice, but methamphetamine did not alter behavior in adolescent mice. There was no effect of methamphetamine on social behavior or corticosterone levels. Our findings demonstrate that the specific environmental enrichment paradigm used in this study was not sufficient to mitigate the behavioral effects of methamphetamine and that adolescent mice are relatively resistant to the effects of methamphetamine compared to adult mice.     

An innovative medical school curriculum to enhance exposure to genetics and genomics: Updates and outcomes

PurposeIn 2011, we introduced an innovative parallel curriculum at Baylor College of Medicine, formerly called the Genetics Track Curriculum and now called the Genetics and Genomics Pathway, aimed at providing an opportunity for an enriched educational experience throughout medical school. In this report, we describe our 10-year experience with the program and highlight growth in enrollment as well as academic achievements of graduating students.MethodsWe reviewed the data of students enrolled in this pathway, including retention, satisfaction, student-driven curriculum changes, scholarly outcomes, and career outcomes.ResultsFrom September 2011 to June 2021, 121 students were enrolled in the Genetics and Genomics Pathway program. In total, 64 students (64/121 = 53%) left the program before graduating (the majority, after their first year). Of the 57 remaining students, 29 graduated (29/57, approximately 51%), and 4 of the 29 students (4/29 = 14%) matched into a genetics training program.ConclusionThis novel program serves as a mechanism for garnering increased interest and competence in medical genetics. The longitudinal nature of the program fosters enthusiasm for genetics and provides ample opportunity to develop valuable research skills. Given the ongoing shortage of providers in this field, such programs are vital to increase the size of the workforce and broaden the knowledge of providers in diverse fields.     

Evaluation of a novel kit (TF-Test) for the diagnosis of intestinal parasitic infections

Intestinal parasitic infections are currently a source of concern for Public Health agencies in developing and developed countries. Since three ovum‐and‐parasite stool examinations have been demonstrated to provide sensitive results, we designed a practical and economical kit (TF‐Test) that is now commercially available (Immunoassay Com. Ind. Ltda., São Paulo, Brazil). This kit allows the separate collection of three fecal specimens into a preservative solution. The specimens are then pooled, double‐filtered, and concentrated by a single rapid centrifugation process. The TF‐Test was evaluated in four different laboratories in a study using 1,102 outpatients and individuals living in an endemic area for enteroparasitosis. The overall sensitivity found using the TF‐Test (86.2–97.8%) was significantly higher (P<0.01) than the sensitivity of conventional techniques such as the Coprotest (NL Comércio Exterior Ltda, São Paulo, Brazil) and the combination of Lutz/Hoffman, Faust, and Rugai techniques (De Carli, Diagnóstico Laboratorial das Parasitoses Humanas. Métodos e Técnicas, 1994), which ranged from 48.3% to 75.9%. When the above combined three specimen technique was repeated with three specimens collected on different days, its sensitivity became similar (P>0.01) to that of the TF‐Test. The kappa index values of agreement for the TF‐Test were consistent (P<0.01), being higher and ranking in a better position than conventional techniques. The high sensitivity, cost/benefit ratio, and practical aspects demonstrate that the TF‐Test is suitable for individual diagnosis, epidemiological inquiries, or evaluation of chemotherapy in treated communities. J. Clin. Lab. Anal. 18:132–138, 2004. © 2004 Wiley‐Liss, Inc.     

基于改进TF-IDF算法的基因通路富集方法

提出一种综合考虑通路局部和全局信息的基因通路富集分析（GIGSEA）方法。首先利用基因相互作用数据,通过基因在通路的局部重要性和在通路数据库的全局特异性计算基因的影响力;然后将基因影响力和表型相关性值融合在一起,计算通路的富集分数;最后通过置换基因富集出统计学显著的通路。将GIGSEA方法运用于肝细胞癌和结肠直肠癌数据集进行风险通路富集,与基因集富集分析方法相比,GIGSEA方法能富集出一些新的相关通路,并排除无关的通路,提高疾病相关通路的富集效果。     

Combination of Cobe AutoPBSC and Gambro Elutra as a platform for monocyte enrichment in dendritic cell (DC) therapy: clinical study

Monocytes are a common source for generating dendritic cells (DCs). The aim of the present study was to evaluate the efficiency of a platform for monocyte collection and enrichment in a clinical setting. The platform was based on the combination of two semiautomated devices; the Cobe Spectra Auto PBSC for mononuclear cells (MNC) collection followed by counterflow elutriation for monocyte enrichment (Gambro BCT Elutra). Twenty-four patients with various types of epithelial cancer participated in the study. MNC collections were first performed as large volume leukapheresis (LVL). Subsequently, MNC products were processed with an elutriation system for monocyte isolation. LVL resulted in the collection of MNC at a median of 8.1 x 10(9) cells, containing of 31.4% monocytes. A similar efficacy was also shown in patients with lower peripheral blood counts. Elutriation of the MNC product with the Cobe Elutra device resulted in the enrichment of monocytes at a median of 2.7 x 10(9) cells, with a recovery of 80.2% and a purity of 90.7%. These monocytes were then successfully developed into DCs for clinical therapy after in vitro manipulation. These data suggest that the combination of the Cobe Spectra Auto PBSC and the Gambro BCT Elutra is an effective platform for monocyte enrichment in clinical practice according to GCP standards and GMP guidelines, and can be easily implemented in the clinical routine under current DC protocols.     

吗啡急性处理小鼠的微阵列数据分析和生物标记识别

目的通过生物信息学方法,识别吗啡急性处理小鼠的差异表达基因及其富集的通路。方法从高通量基因表达数据库(Gene Expression Omnibus)下载吗啡急性处理小鼠的微阵列数据,并调用R语言3.1.0软件的质量控制包Affy QCReport 1.42.0对数据样本进行质量控制分析,运用R语言的微阵列数据线性模型识别吗啡处理前后的差异表达基因,采用表达分析系统检测算法进行差异表达基因的通路富集分析。结果吗啡急性处理小鼠的微阵列基因表达数据具有良好的均一性和阵列强度相似性,识别得到Gm11627、Zfand4、Zbtb16、Pkp2和Plin4等481个差异表达基因和癌症、黑素原生成和丝裂原活化蛋白激酶信号等8条代谢通路。结论所识别的差异表达基因和代谢通路成为吗啡急性处理小鼠潜在的生物标记。     

13C-Enrichment of Urinary Uric Acid after l-[Ring-2-13C]Histidine Dose in Adult Humans

We determined whether ring-2 carbon of histidine is folate-dependently transferred to carbons 8 (C₈) and/or 2 (C₂) in urinary uric acid in humans. Two adults collected each urine void for four days. Aliquots of urine for the first day were used for baseline values; then the subjects ingested 0.7 g (3.3 mmol) of l-[ring-2-¹³C]histidine and collected urine for three experimental days. Aliquots were analyzed for percentage ¹³C-content at C₂ and C₈ by a liquid-chromatography-mass spectrometry method. Percentage enrichment was determined by subtracting time-of-day paired baseline percentage ¹³C-content from experimental percentage ¹³C-content for each void. C₂ was predominantly ¹³C-enriched in the majority of voids. The percentage enrichments at C₂ for two subjects were 0.14 (±0.028 [SEM], n = 26) and 0.18 (±0.049, n = 21), whereas at C₈, they were 0.008 (±0.006) and −0.005 (±0.008), respectively. The mean C₂-enrichments were significantly greater than zero (p < 0.01), whereas those of C₈ were not (p > 0.2). The enrichment had a diurnal rhythm peaking in the morning. Our results may be useful in the estimation of the timing for the administration of drugs that interfere with purine nucleotide biosynthesis in the treatment of cancer and autoimmune disease.     

BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment

Sensory, motor, and cognitive stimuli, resulting from interactions with the environment, play a key role in optimizing and modifying the neuronal circuitry required for normal brain function. An experimental animal model for this phenomenon comprises environmental enrichment (EE) in rodents. EE causes profound changes in neuronal and signaling levels of excitation and plasticity throughout the entire central nervous system and the hippocampus is particularly affected. The mechanisms underlying these changes are not yet fully understood. As brain‐derived neurotrophic factor (BDNF) supports hippocampal long‐term potentiation (LTP), we explored whether it participates in the facilitation of synaptic plasticity and hippocampus‐dependent learning that occurs following EE. In the absence of EE, LTP elicited by high‐frequency stimulation was equivalent in wildtype mice and heterozygous BDNF^+/? siblings. LTP elicited by theta‐burst stimulation in BDNF^+/? mice was less than in wildtypes. Long‐term depression (LTD) was also impaired. EE for three weeks, beginning after weaning, improved hippocampal LTP in both wildtype and transgenic animals, with LTP in transgenics achieving levels seen in wildtypes in the absence of EE. Object recognition memory was evident in wildtypes 24 h and 7 days after initial object exposure. EE improved memory performance in wildtypes 24 h but not 7 days after initial exposure. BDNF^+/? mice in the absence of EE showed impaired memory 7 days after initial object exposure that was restored by EE. Western blotting revealed increased levels of BDNF, but not proBDNF, among both EE cohorts. These data support that BDNF plays an intrinsic role in improvements of synaptic plasticity and cognition that occur in EE. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Environmental factors as modulators of neurodegeneration: Insights from gene–environment interactions in Huntington's disease

Unlike many other neurodegenerative diseases with established gene–environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity.