The vertebrate tail bud: three germ layers from one tissue

Summary The tail bud of amniote embryos comprises a mass of apparently undifferentiated mesenchymal cells located at the caudal limit of the embryo, representing the remains of Hensen's node and the primitive streak. These cells have the potential to give rise to a variety of different tissues including the posterior or secondary neural tube, the tail gut, and somites and their derivatives. This seemingly homogeneous accumulation of cells therefore has the capacity to differentiate into tissues which in more cranial regions of the embryo are derived from cells of different germ layers. In this review, the tissue contributions of the tail bud in various vertebrate classes are discussed, with particular attention to the mesenchymal-to-epithelial transformation that characterizes the process of secondary neurulation, and which distinguishes it from the epithelial folding that occurs during primary neurulation in more cranial regions. Recent studies suggest that the transformation is accompanied by extensive changes in the cell surface oligosaccharide complement of the differentiating cells, and that the sialyted form of N-CAM is expressed both temporally and spatially in a manner that suggests a role for it in the process. The pluripotential nature of the tail bud mesenchyme may be revealed experimentally by grafting the tissue ectopically, or by culturing it on different substrata. In the latter case, the mesenchyme can be demonstrated to give rise to myocytes, chondrocytes, neuroepithelium and neural crest derivatives such as melanocytes, depending on the nature of the culture substratum. It is concluded that the tail bud mesenchyme represents a developing system which is readily amenable to experimentation and should provide insights into the general mechanisms of cell differentiation and transformation.     

Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement

The murine IgG2a monoclonal antibody 6-19 binds to a wide variety of nonhematopoietic cells including human marrow-derived stromal cells but does not bind to marrow or peripheral blood cells. We studied the effects of this antibody and rabbit complement on marrow cells. Fibroblast colonies were eliminated from light density marrow cells by a single incubation with monoclonal antibody 6-19 and complement. The growth and composition of granulocytic and erythroid colonies were unaffected. Specific complement mediated cytotoxicity of the antibody was confirmed on passaged human fibroblasts derived from marrow (more than 99.6% of fibroblasts are killed by a single treatment). Similar results were obtained with human umbilical cord endothelial cells. In addition, such treatment abolished the initiation of Dexter culture stroma. Incubation of bone marrow cell suspensions with this antibody and complement will allow the study of stroma-free marrow cells in long- term liquid cultures.     

Young siblings of children with cancer deserve care and a personalized approach

The youngest siblings may be both emotionally vulnerable and often neglected members of the family of a childhood cancer patient. The prompt identification of signs of distress in these subjects allows trained caregivers to intervene with personalized, age-appropriate, attention, and care. A narrative approach, based on personalized listening, writings, and spontaneous drawings, can provide the means to elicit markers of psychological maladjustment in even the youngest of siblings. Two exemplary cases are reported to illustrate this approach.     

新疆维吾尔族、汉族变应性鼻炎表观遗传现象IL-4、IFN-γ基因甲基化的比较研究

目的:探讨变应性鼻炎(AR)患者IL-4、IFN-γ基因启动子区甲基化在新疆维吾尔族、汉族不同人群AR中的差异。方法:选择维吾尔族、汉族AR患者各50例,用甲基化特异性PCR(MSP)检测IL-4、IFN-γ基因的甲基化。结果:维吾尔族、汉族AR患者IL-4基因启动子区完全甲基化率为44%(22/50)和48%(24/50),未甲基化率为26%(13/50)和22%(11/50),甲基化与未甲基化共存率为30%(15/50)和30%(15/50);维吾尔族、汉族AR患者IFN-γ基因启动子区完全甲基化率为12%(6/50)和16%(8/50),未甲基化率8%(4/50)和10%(5/50),甲基化与未甲基化共存率为80%(40/50)和74%(37/50)。维吾尔族与汉族AR患者IL-4基因甲基化分布状态相比差异无统计学意义(P>0.05)。维吾尔族与汉族AR患者IFN-γ基因甲基化分布状态相比差异无统计学意义(P>0.05)。结论:IL-4、IFN-γ基因甲基化程度在汉族与维吾尔族患者中均无差异。     

Targeting emotional regulation using an Internet-delivered psychological intervention for cancer survivors: A randomized controlled trial

Objectives

This trial assessed the efficacy of an emotion-focused, modular, Internet-delivered adaptation of the Unified Protocol (UP) in improving cancer survivors' emotion regulation strategies.

Design

A two-arm randomized controlled trial (1:1) was used to compare the efficacy of two Internet-based interventions: UP-adapted CanCope Mind (CM) and lifestyle-focused active control CanCope Lifestyle (CL).

Methods

N = 224 cancer survivors randomized to CM or CL were assessed at baseline, between-modules, at post-intervention and 3-month follow-up on emotion regulation outcomes targeted by each CM module (Module 1: beliefs about emotions; Module 2: mindfulness; Module 3: cognitive reappraisal skills, catastrophizing, refocus on planning; Module 4: experiential avoidance). Primary analyses were intention-to-treat linear regressions using Fisher randomization tests for p-values and intervals were used to compare groups with standardized mean difference (SMD) effect sizes.

Results

CanCope Mind participants (n = 61 completers) experienced moderate-to-large improvements (SMDs from .44–.88) across all outcomes at post-intervention. CM's effects were larger than CL's (n = 75 completers) immediately post-intervention and at 3-month follow-up for beliefs about emotions, mindfulness, cognitive reappraisals and experiential avoidance (all p's < .05). CM experienced greater improvements in catastrophizing immediately post-intervention, with a trending effect at follow-up. However, we could not reject the null hypothesis of identical between-group effects for refocusing on planning both immediately post-intervention and at follow-up. Exploratory analyses revealed inconsistent between-module effects.

Conclusions

In its entirety, CM is a promising intervention for improving and maintaining cancer survivors' adaptive emotion regulation, especially for mindfulness and experiential avoidance. This may have important clinical implications for promoting cancer survivors’ emotional functioning and general well-being.     

Marginal Food Security Predicts Earlier Age at Menarche Among Girls From the 2009-2014 National Health and Nutrition Examination Surveys

Study ObjectiveThis study analyzed the relationship between household food security and variation in age at menarche, as well as the connections between food insecurity, nutritional status, and allostatic load, among girls aged 12-15 years from the 2009-2014 United States National Health and Nutrition Examination Survey (NHANES).MethodsData analysis included mean comparisons of age at menarche among household food security groups (high, marginal, low, and very low) as well as categorical variables known to associate with age at menarche (ethnicity, poverty status, body mass index [BMI], allostatic load, and milk consumption). χ² Analyses were used to test the associations between household food security and additional categorical variables. Univariate and multivariate regression models were used to test the relationship between variation in age at menarche and household food security, ethnicity, BMI, and allostatic load categories while controlling for age.ResultsNon-Hispanic Black and Hispanic/Mexican American girls had earlier mean ages at menarche, higher mean BMIs, and disproportionately experienced household food insecurity when compared to non-Hispanic White-identifying girls. In the univariate analyses, marginal household food security, Hispanic/Mexican American and Black ethnicities, overweight and obese BMI categories, and marginal-high allostatic load were each associated with lower age at menarche compared to reference categories. These associations were maintained in the multivariate analysis, although only Hispanic/Mexican American ethnicity predicted earlier menarche when compared to that of non-Hispanic White girls.ConclusionsMarginal household food security, particularly for girls who identified as non-White, predicted earlier age at menarche independent of nutritional status and allostatic load. At the same time, having more energetic resources (ie, higher BMI) also significantly predicted earlier menarche.     

Genetic association of an alpha2-macroglobulin (Val1000lle) polymorphism and Alzheimer's disease

alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/Ile1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in Abeta burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway.      

Hereditary lymphedema: evidence for linkage and genetic heterogeneity

Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at straight theta = 0. 0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor ( FLT4 ) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.      

The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay

Human gonadotrophins undergo metabolic transformations which result in the presence of several smaller, structurally and immunologically related forms of gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment (LHbeta cf) has been isolated from the pituitary and characterized. The corresponding urinary fragment is inferred from mass spectral and immunochemical analysis of chromatographically separated urinary forms. Physicochemical characteristics, primarily mass spectral and chromatographic, indicate that the pituitary and urinary forms of LHbeta cf have a different structure, probably in the carbohydrate moieties. This communication characterizes the expression of LHbeta cf in the urine of both reproductive and post-reproductive age women and in men, employing assays highly specific for the pituitary form of the fragment. It was found that LHbeta cf is the predominant LH associated molecular form in the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher than either LH or LH free beta subunit. Corresponding concentrations of human chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross-reaction with some LH or LHbeta monoclonal antibodies may well interfere with the accurate estimation of the day of the LH surge when urinary tests are utilized.