Why does paternal death accelerate the transition to first marriage in the C18-C19 Krummhörn population?

Among the population of the Krummhörn region (Ostfriesland, Germany) in the 18th and 19th centuries, the death of the father in the family led on average to the accelerated marriage of his children. Three evolutionary explanations are offered for this “paternal absence” effect in the literature: namely, (i) the assumption of an adaptive “psychosocial acceleration” of the children with prepubertal experience of uncertainty; (ii) an opportunistic adjustment of life and reproduction decisions as an adaptive reaction to the personal cost–benefit balances that are changed by the father's death; and (iii) given the genetic parent–offspring conflict, an increase in the reproductive autonomy of offspring after the loss of the dominant father figure. Our models, which are based on the analyses of the vital statistics data derived from church registers and tax rolls and compiled into a family reconstitution study, attribute the greatest explanatory power for the patterns found in the Krummhörn to the opportunistic adjustment approach (ii).     

普罗布考联合家庭心脏康复训练对冠心病患者射血分数、血脂的影响分析

目的 探讨普罗布考联合家庭康复训练对冠心病患者射血分数及血脂水平的影响.方法 选择2018年6月 ～2020年6月我院收治的冠心病患者110例,按随机数字表法分成对照组和实验组,对照组给予瑞舒伐他汀治疗,实验组在对照组的基础上联合应用普罗布考及家庭康复训练.对两组患者治疗前及治疗后3个月的心功能指标、血脂水平进行检测比...     

TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.     

Hyperthermophilic α-L-arabinofuranosidase from Thermotoga maritima MSB8: molecular cloning, gene expression, and characterization of the recombinant protein

A putative -L-arabinofuranosidase (AFase) gene belonging to family 51 of glycosyl hydrolases of a hyperthermophilic bacterium Thermotoga maritima MSB8 was cloned, sequenced, and overexpressed in Escherichia coli. The recombinant protein (Tm-AFase) was purified to apparent homogeneity by heat treatment (80°C, 30 min), followed by hydrophobic interaction, anion-exchange, and gel permeation column chromatography. Tm-AFase had a molecular mass of 55,284 Da on matrix assisted laser desorption ionization time-of-flight mass spectrometry and ~332 kDa on gel permeation column chromatography. Therefore, Tm-AFase comprised six identical subunits as in the case of homologous AFase from Geobacillus stearothermophilus. Regarding substrate specificity, Tm-AFase was active with p-nitrophenyl -L-arabinofuranoside but not with p-nitrophenyl -L-arabinopyranoside. Regarding polysaccharides, Tm-AFase hydrolyzed arabinan and debranched arabinan but not arabinoxylan, arabinogalactan, and carboxymethyl cellulose. Tm-AFase was extremely thermophilic, displaying an optimal reaction temperature of 90°C in a 10 min assay. When Tm-AFase was heated at 90°C, no loss of activity was observed for at least 24 h. At 100°C, the activity dropped to ~50% in 20 min; thereafter, inactivation occurred very slowly exhibiting a half-life of ~2.7 h, characterizing the enzyme to be the most thermophilic AFase reported thus far.     

The prevalence of male homosexuality: the effect of fraternal birth order and variations in family size

The prevalence of male homosexuality probably varies over time and across societies. One reason for this variation may be the joint effect of two factors: (1) variations in fertility rate or family size; and (2) the fraternal birth order effect, the finding that the odds of male homosexuality increases with each additional older brother. Because of these effects, the rate of male homosexuality may be relatively high (at least in terms of sexual attraction if not behavior) in societies that have a high fertility rate, but this rate has probably declined somewhat in some, particularly western, societies. Thus, even if accurately measured in one country at one time, the rate of male homosexuality is subject to change and is not generalizable over time or across societies.     

TRIM50 Protein Regulates Vesicular Trafficking for Acid Secretion in Gastric Parietal Cells

Of the TRIM/RBCC family proteins taking part in a variety of cellular processes, TRIM50 is a stomach-specific member with no defined biological function. Our biochemical data demonstrated that TRIM50 is specifically expressed in gastric parietal cells and is predominantly localized in the tubulovesicular and canalicular membranes. In cultured cells ectopically expressing GFP-TRIM50, confocal microscopic imaging revealed dynamic movement of TRIM50-associated vesicles in a phosphoinositide 3-kinase-dependent manner. A protein overlay assay detected preferential binding of the PRY-SPRY domain from the TRIM50 C-terminal region to phosphatidylinositol species, suggesting that TRIM50 is involved in vesicular dynamics by sensing the phosphorylated state of phosphoinositol lipids. Trim50 knock-out mice retained normal histology in the gastric mucosa but exhibited impaired secretion of gastric acid. In response to histamine, Trim50 knock-out parietal cells generated deranged canaliculi, swollen microvilli lacking actin filaments, and excess multilamellar membrane complexes. Therefore, TRIM50 seems to play an essential role in tubulovesicular dynamics, promoting the formation of sophisticated canaliculi and microvilli during acid secretion in parietal cells.     

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Proteins of the Rho family of small GTPases are central regulators of the cytoskeleton, and control a large variety of cellular processes, including cell migration, gene expression, cell cycle progression and cell adhesion ¹. Rho proteins are molecular switches that are active in GTP-bound and inactive in GDP-bound state. Their activation is mediated by a family of Guanine-nucleotide Exchange Factor (GEF) proteins. Rho-GEFs constitute a large family, with overlapping specificities ². Although a lot of progress has been made in identifying the GEFs activated by specific signals, there are still many questions remaining regarding the pathway-specific regulation of these proteins. The number of Rho-GEFs exceeds 70, and each cell expresses more than one GEF protein. In addition, many of these proteins activate not only Rho, but other members of the family, contributing further to the complexity of the regulatory networks. Importantly, exploring how GEFs are regulated requires a method to follow the active pool of individual GEFs in cells activated by different stimuli. Here we provide a step-by-step protocol for a method used to assess and quantify the available active Rho-specific GEFs using an affinity precipitation assay. This assay was developed a few years ago in the Burridge lab ^3,4 and we have used it in kidney tubular cell lines ^5,6,7. The assay takes advantage of a "nucleotide free" mutant RhoA, with a high affinity for active GEFs. The mutation (G17A) renders the protein unable to bind GDP or GTP and this state mimics the intermediate state that is bound to the GEF. A GST-tagged version of this mutant protein is expressed and purified from E. coli, bound to glutathione sepharose beads and used to precipitate active GEFs from lysates of untreated and stimulated cells. As most GEFs are activated via posttranslational modifications or release from inhibitory bindings, their active state is preserved in cell lysates, and they can be detected by this assay⁸. Captured proteins can be probed for known GEFs by detection with specific antibodies using Western blotting, or analyzed by Mass Spectrometry to identify unknown GEFs activated by certain stimuli.     

Japan’s Hidden Youths: Mainstreaming the Emotionally Distressed in Japan

One of the most talked-about social issues in Japan in recent years has been the problem of the nation's purportedly one million "hidden" youths, known as hikikomori (literally, "the withdrawn"). Most observers agree that the category of hikikomori encompasses a wide range of problems and provocations. The fact that these various dilemmas lead to the shared outcome of shutting oneself away at home is the point of departure here. The article explores the spheres of mental health care, education and family, focusing on the reluctance to highlight underlying psychological dimensions of hikikomori and the desire on the part of schools and families to "mainstream" Japanese children, accommodating as many as possible within standardized public education. Hikikomori can perhaps be seen as a manifestation of Japanese democracy, in which the good society is imagined as cohesive, protective and secure, rather than one in which the individual can freely exercise the right to be different. Schools, families and the sphere of mental health care have focused on producing social inclusion but have discouraged citizens from being labeled as "different" -- even when such a distinction might help them. The dearth of facilities and discourse for caring for the mentally ill or learning disabled is, in many respects, the darker side of Japan's successes. Those who cannot adjust are cared for through the institutions of families, companies and various other spheres that offer spaces to rest and to temporarily "drop out"; however, the expectation is that rest will eventually lead to a re-entry into mainstream society. Often the psychological problem or disability that led to the problem goes unnamed and untreated (hikikomori, psychiatry, special education, youth, family, Japan).