This essay explores the amazing phenomenon that in Europe since ca. 1700 most diseases have shown a pattern of 'rise-and-fall'. It argues that the rise of so many diseases indicates that their ultimate cause is not to be sought within the body, but in the interaction between humans and their environment. In their tireless pursuit of a better life, Europeans have constantly engaged in new activities which exposed them to new health risks, at a pace that evolution could not keep up with. Fortunately, most diseases have also declined again, mainly as a result of human interventions, in the form of public health interventions or improvements in medical care. The virtually continuous succession of diseases starting to fall in the 18th, 19th and 20th centuries suggests that the concept of an "epidemiological transition" has limited usefulness.
  The expansion of CAG (glutamine; Q) trinucleotide repeats (TNRs) predominantly occurs through male lineage in Huntington's disease (HD). As a result, offspring will have larger CAG repeats compared to their fathers, which causes an earlier onset of the disease called genetic anticipation. This study aims to develop a novel in vitro model to replicate CAG repeat instability in early spermatogenesis and demonstrate the biological process of genetic anticipation by using the HD stem cell model for the first time.
 
  HD rhesus monkey embryonic stem cells (rESCs) were cultured in vitro for an extended period. Male rESCs were used to derive spermatogenic cells in vitro with a 10-day differentiation. The assessment of CAG repeat instability was performed by GeneScan and curve fit analysis.
 
  Spermatogenic cells derived from rESCs exhibit progressive expansion of CAG repeats with high daily expansion rates compared to the extended culture of rESCs. The expansion of CAG repeats is cell type-specific and size-dependent.
 
  Here, we report a novel stem cell model that replicates genome instability and CAG repeat expansion in in vitro derived HD monkey spermatogenic cells. The in vitro spermatogenic cell model opens a new opportunity for studying TNR instability and the underlying mechanism of genetic anticipation, not only in HD but also in other TNR diseases.
 Here, we report a novel stem cell model that replicates genome instability and CAG repeat expansion in in vitro derived HD monkey spermatogenic cells. The in vitro spermatogenic cell model opens a new opportunity for studying TNR instability and the underlying mechanism of genetic anticipation, not only in HD but also in other TNR diseases.
  To identify the genetic factors responsible for asthenozoospermia, which is a major cause of male infertility characterized by immotile and malformed spermatozoa.
 
  Whole-exome sequencing was performed in two brothers from a family with asthenozoospermia to identify pathogenic variants.  https://www.selleckchem.com/products/bardoxolone.html  The functional effect of the identified variant was investigated in HEK293T cells using a minigene assay.
 
  We identified a novel homozygous splicing variant c.6311-2A>G in DNAH8 from two affected brothers belonging to the same consanguineous family. The splicing variant altered a consensus splice acceptor site of DNAH8 intron 44, which led to the deletion of exon 45 and resulted in a frameshift and a predicted truncated protein (p.G2104Efs*19). Although most spermatozoa from the patients presented with reduced sperm motility, intracytoplasmic sperm injection was able to overcome the inability of the spermatozoa to reach the ovum and thus produce a healthy child for the proband.
 
  This finding expands the mutational spectrum of DNAH8, making it a potential genetic diagnostic marker for those suffering from primary male infertility.
 This finding expands the mutational spectrum of DNAH8, making it a potential genetic diagnostic marker for those suffering from primary male infertility.Rheumatoid arthritis (RA) is a highly relevant public health problem. RA fibroblast-like synoviocytes (RAFLSs) play an important role in RA progression. Long non-coding RNA growth arrest-specific transcript 5 (GAS5) could improve RA by inducing RAFLSs apoptosis. However, the mechanism of GAS5 in RA remains unclear. RT-qPCR detected the expressions of GAS5, microRNA-128-3p (miR-128-3p), and histone deacetylase 4 (HDAC4) in RA synovial tissues and RAFLSs. Proliferation, apoptosis, migration, and invasion were measured by Cell Counting Kit-8 assay (CCK-8), flow cytometry, and transwell assays, severally. The protein levels of B-cell lymphoma-2 (Bcl-2), C-caspase 3, Bcl-2 related X protein (Bax), Tumor Necrosis factor-α (TNF-α), Interleukin 6 (IL-6), Interleukin 17 (IL-17), HDAC4, phosphorylation-protein kinase B (p-AKT), AKT, a phosphorylation-mechanistic target of rapamycin (p-mTOR), and mTOR were assessed by western blot assay. The interaction between miR-128-3p and GAS5 or HDAC4 was predicted by ENCORI or TargetScan Human and verified by the dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. GAS5 and HDAC4 were downregulated, and miR-128-3p was upregulated in RA synovial tissues and RAFLSs. Function analysis indicated that GAS5 curbed proliferation, migration, invasion, inflammation, and facilitated apoptosis of RAFLSs. Rescue assay confirmed that miR-128-3p overexpression or HDAC4 knockdown weakened the inhibitory effect of GAS5 or anti-miR-128-3p on RA development. GAS5 acted as a miR-128-3p sponge to upregulate HDAC4 expression. Besides, GAS5/miR-128-3p/HDAC4 axis regulated RA progression partially through the AKT/mTOR pathway. Our studies disclosed that GAS5 restrained inflammation in synovial tissue partly through regulating HDAC4 via miR-128-3p, suggesting a potential lncRNA-targeted therapy for RA treatment.Biological invasion, whereby populations of motile and proliferative individuals lead to moving fronts that invade vacant regions, is routinely studied using partial differential equation models based upon the classical Fisher-KPP equation. While the Fisher-KPP model and extensions have been successfully used to model a range of invasive phenomena, including ecological and cellular invasion, an often-overlooked limitation of the Fisher-KPP model is that it cannot be used to model biological recession where the spatial extent of the population decreases with time. In this work, we study the Fisher-Stefan model, which is a generalisation of the Fisher-KPP model obtained by reformulating the Fisher-KPP model as a moving boundary problem. The nondimensional Fisher-Stefan model involves just one parameter, [Formula see text], which relates the shape of the density front at the moving boundary to the speed of the associated travelling wave, c. Using numerical simulation, phase plane and perturbation analysis, we construct approximate solutions of the Fisher-Stefan model for both slowly invading and receding travelling waves, as well as for rapidly receding travelling waves.