Season of Birth and Exceptional Longevity: Comparative Study of American Centenarians, Their Siblings, and Spouses

This study explores the effects of month of birth (a proxy for early-life environmental influences) on the chances of survival to age 100. Months of birth for 1,574 validated centenarians born in the United States in 1880–1895 were compared to the same information obtained for centenarians' 10,885 shorter-lived siblings and 1,083 spouses. Comparison was conducted using a within-family analysis by the method of conditional logistic regression, which allows researchers to control for unobserved shared childhood or adulthood environment and common genetic background. It was found that months of birth have significant long-lasting effect on survival to age 100: siblings born in September–November have higher odds to become centenarians compared to siblings born in March. A similar month-of-birth pattern was found for centenarian spouses. These results support the idea of early-life programming of human aging and longevity

Sexuality and Cognitive Status: A U.S. Nationally Representative Study of Home‐Dwelling Older Adults

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146357/1/jgs15511.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146357/2/jgs15511_am.pd

Apofaattisuus ja houkkuus venäläisessä nykykirjallisuudessa

This article focuses on the question of the transformation of the Orthodox tradition in the postmodern context. Apophatic theology and the institute of Holy Fools (jurodstvo) are the most hermeneutic and mystical parts of the Byzantine and Russian Orthodox cultures. These practices have now become detached from their original sacral context and are used as rhetorical devices. The process and results of such transgression are studied using examples from the works of Dmitry Prigov and Vladimir Sorokin. In this article, I concentrate on three rhetorical figures that are used by these authors: logogriph, amplification and ostranenie.Artikkeli tarkastelee ortodoksisen tradition muutokseen liittyviä kysymyksiä postmodernistisen sanataiteen kontekstissa. Apofaattinen teologia ja Pyhien hullujen instituutio (jurodstvo) ovat kaikkein tulkinnallisin ja mystisin osa Bysantin ja Venäjän ortodoksista kulttuuria. Nämä käytännöt on nyt etäännytetty niiden alkuperäisestä sakraalista kontekstista ja otettu retoriseen käyttöön. Tätä prosessia ja sen vaikutusta tarkastellaan käyttäen esimerkkeinä Dmitry Prigovin ja Vladimir Sorokinin töitä. Analyysi keskittyy erityisesti kolmeen retoriseen keinoon, joita he käyttävät: logogryfi, amplifikaatio ja vieraannuttaminen

Adult mortality patterns in the former Soviet Union’s southern tier: Armenia and Georgia in comparative perspective

Background: While the health crisis in the former USSR has been well-documented in the case of Russia and other northern former Soviet republics, little is known about countries located in the southern tier of the region, i.e., the Caucasus and Central Asia. Objective: This paper presents new mortality information from two Caucasian countries, Georgia and Armenia. Results are compared with information from two relevant countries previously examined in the literature, Kyrgyzstan and Russia. Methods: Using official statistics (with adjustments when necessary), we compare adult mortality patterns in the four countries since 1979, for all causes and by cause for the recent period. For Kyrgyzstan results are presented by ethnicity, as its mortality levels have been impacted by its large Slavic population. Results: Adult mortality patterns in Armenia and Georgia have been more favorable than in Russia. This appears to be due to a large extent to lower mortality from alcohol-related causes. Mortality patterns in these Caucasian republics resemble those observed in Kyrgyzstan, especially when considering the native portion of the population. Conclusions: As far as mortality is concerned, Armenia and Georgia have weathered the collapse of the Soviet Union better than Russia. These results document a distinct southern tier pattern of adult mortality in the former Soviet Union. Contribution: This article enriches our understanding of the health crisis in the former Soviet Union by bringing new information from two lesser-known countries and further documenting the scale of heterogeneity in mortality experiences across this vast region

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.Keywords: Malabsorption, Mice, Differentiation, Common variable immunodeficiency, Homeostasis, System, Segmented filamentous bacteria, IGA response, Cells, NetworksKeywords: Malabsorption, Mice, Differentiation, Common variable immunodeficiency, Homeostasis, System, Segmented filamentous bacteria, IGA response, Cells, Network

Impairment of the mitochondrial one-carbon metabolism enzyme SHMT2 causes a novel brain and heart developmental syndrome

Inborn errors of metabolism cause a wide spectrum of neurodevelopmental and neurodegenerative conditions [15]. A pivotal enzyme located at the intersection of the amino acid and folic acid metabolic pathways is SHMT2, the mitochondrial form of serine hydroxymethyltransferase. SHMT2 performs the first step in a series of reactions that provide one-carbon units covalently bound to folate species in mitochondria: it transfers one-carbon units from serine to tetrahydrofolate (THF), generating glycine and 5,10-methylene-THF. Using whole exome sequencing (WES), we identified biallelic SHMT2 variants in five individuals from four different families. All identified variants were located in conserved residues, either absent or extremely rare in control databases (gnomAD, ExAC), and cosegregated based on a recessive mode of inheritance (pRec = 0.9918 for this gene). In family F1, a homozygous missense variant present in two affected siblings was located in a region without heterozygosity (~ 10 Mb, the only region > 1 Mb shared by both siblings) in which no other candidate variants were found, providing a strong genetic evidence of causality for these variants. The missense/in-frame deletion nature of these variants, and the absence of loss-of-function homozygous individuals in control databases, combined with the fact that complete loss of SHMT2 is embryonic lethal in the mouse, suggested that these variants may cause hypomorphic effects. Using 3D molecular dynamics models of the SHMT2 protein, we concluded that these candidate variants probably alter the SHMT2 oligomerization process, and/or disrupt the conformation of the active site, thus inducing deleterious effects on SHMT2 enzymatic function