Semiquantitative analysis of rabbit knee articular surfaces based on stereomicroscopic examination of the cartilage

A semiquantitative stereomicroscopic method was devised in order to examine rabbit knee articular surfaces. With the aid of a drawing tube mounted on a stereomicroscope, enlarged pictures (magnification of X 14-19) of ink-stained or SEM specimens of joint surfaces were drawn and the structural details classified. The point-counting method or a computer-coupled analyzer was used to analyze the pictures. The data thus obtained underwent statistical evaluation. The method proved to be very useful for the quantitation of experimentally induced changes on cartilage surfaces.     

Awareness of Climate Change and the Dietary Choices of Young Adults in Finland: A Population-Based Cross-Sectional Study

Climate change is a major public health threat that is exacerbated by food production. Food items differ substantially in the amount of greenhouse gases their production generates and therefore individuals, if willing, can mitigate climate change through dietary choices. We conducted a population-based cross-sectional study to assess if the understanding of climate change, concern over climate change or socio-economic characteristics are reflected in the frequencies of climate-friendly food choices. The study population comprised 1623 young adults in Finland who returned a self-administered questionnaire (response rate 64.0%). We constructed a Climate-Friendly Diet Score (CFDS) ranging theoretically from −14 to 14 based on the consumption of 14 food items. A higher CFDS indicated a climate-friendlier diet. Multivariate linear regression analyses on the determinants of CFDS revealed that medium concern raised CFDS on average by 0.51 points (95% confidence interval (CI) 0.03, 0.98) and high concern by 1.30 points (95% CI 0.80, 1.80) compared to low concern. Understanding had no effect on CFDS on its own. Female gender raised CFDS by 1.92 (95% CI 1.59, 2.25). Unemployment decreased CFDS by 0.92 (95% CI −1.68, −0.15). Separate analyses of genders revealed that high concern over climate change brought about a greater increase in CFDS in females than in males. Good understanding of climate change was weakly connected to climate-friendly diet among females only. Our results indicate that increasing awareness of climate change could lead to increased consumption of climate-friendly food, reduction in GHG emissions, and thus climate change mitigation.     

dj-1β regulates oxidative stress,insulin-like signaling and development in Drosophila melanogaster

DJ-1 (or PARK-7) is a multifunctional protein implicated in numerous pathologies including cancer, sterility and Parkinson disease (PD). The popular genetic model Drosophila melanogaster has two orthologs, dj-1: α and β. Dysfunction of dj-1β strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1β mutant phenotype. Mitochondrial hydrogen peroxide production, but not superoxide production, was increased in mutant flies. An increase in peroxide leak from mitochondria causes oxidative damage elsewhere and explains the strong reduction in mobility caused by dj-1β mutation. However, at the same time, increased levels of hydrogen peroxide activated a pro-survival program characterized by (1) an alteration in insulin-like signaling, (2) an increase in mitochondrial biogenesis and (3) an increase in the de-acetylase activity of sirtuins. The activation of this pro-survival program was associated with increased longevity under conditions of moderate oxidative stress. Additionally, the dj-1β mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1β in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster.     

Brain Correlates of Non-Symbolic Numerosity Estimation in Low and High Mathematical Ability Children

Previous studies have implicated several brain areas as subserving numerical approximation. Most studies have examined brain correlates of adult numerical approximation and have not considered individual differences in mathematical ability. The present study examined non-symbolic numerical approximation in two groups of 10-year-olds: Children with low and high mathematical ability. The aims of this study were to investigate the brain mechanisms associated with approximate numerosity in children and to assess whether individual differences in mathematical ability are associated with differential brain correlates during the approximation task. The results suggest that, similarly to adults, multiple and distributed brain areas are involved in approximation in children. Despite equal behavioral performance, there were differences in the brain activation patterns between low and high mathematical ability groups during the approximation task. This suggests that individual differences in mathematical ability are reflected in differential brain response during approximation.     

Mice with Tissue Inhibitor of Metalloproteinases 4 (Timp4) Deletion Succumb to Induced Myocardial Infarction but Not to Cardiac Pressure Overload

Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated in human cardiovascular diseases. It controls extracellular matrix remodeling by inhibiting matrix metalloproteinases (MMPs) and is implicated in processes including cell proliferation, apoptosis, and angiogenesis. Timp4-deficient mice (Timp4^−/−) were generated to assess TIMP4 function in normal development and in models of heart disease. We deleted exons 1–3 of the Timp4 gene by homologous recombination. Timp4^−/− mice are born healthy, develop normally, and produce litters of normal size and gender distribution. These mice show no compensation by overexpression of Timp1, Timp2, or Timp3 in the heart. Following cardiac pressure overload by aortic banding, Timp4^−/− mice have comparable survival rate, cardiac histology, and cardiac function to controls. In this case, Timp4 deficiency is compensated by increased cardiac Timp2 expression. Strikingly, the induction of myocardial infarction (MI) leads to significantly increased mortality in Timp4^−/− mice primarily due to left ventricular rupture. The post-MI mortality of Timp4^−/− mice is reduced by administration of a synthetic MMP inhibitor. Furthermore, combining the genetic deletion of Mmp2 also rescues the higher post-MI mortality of Timp4^−/− mice. Finally, Timp4^−/− mice suffer reduced cardiac function at 20 months of age. Timp4 is not essential for murine development, although its loss moderately compromises cardiac function with aging. Timp4^−/− mice are more susceptible to MI but not to pressure overload, and TIMP4 functions in its capacity as a metalloproteinase inhibitor after myocardial infarction.     

Quantitative genetic studies of antisocial behaviour

This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental influences varies for different types of AB; the environmental risk factors are truly environmental; and genetic vulnerability influences susceptibility to environmental risk. While the current data are not yet directly translatable for prevention and treatment programmes, quantitative genetic research has concrete translational potential. Quantitative genetic research can supplement neuroscience research in informing about different subtypes of AB, such as AB coupled with callous-unemotional traits. Quantitative genetic research is also important in advancing the understanding of the mechanisms by which environmental risk operates.     

Following nature's roadmap: folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae

Therapeutic protein production in yeast is a reality in industry with an untapped potential to expand to more complex proteins, such as full‐length antibodies. Despite numerous engineering approaches, cellular limitations are preventing the use of Saccharomyces cerevisiae as the titers of recombinant antibodies are currently not competitive. Instead of a host specific approach, the possibility of adopting the features from native producers of antibodies, plasma cells, to improve antibody production in yeast. A subset of mammalian folding factors upregulated in plasma cells for expression in yeast and screened for beneficial effects on antibody secretion using a high‐throughput ELISA platform was selected. Co‐expression of the mammalian chaperone BiP, the co‐chaperone GRP170, or the peptidyl‐prolyl isomerase FKBP2, with the antibody improved specific product yields up to two‐fold. By comparing strains expressing FKBP2 or the yeast PPIase Cpr5p, the authors demonstrate that speeding up peptidyl‐prolyl isomerization by upregulation of catalyzing enzymes is a key factor to improve antibody titers in yeast. The findings show that following the route of plasma cells can improve product titers and contribute to developing an alternative yeast‐based antibody factory.     

Specimen preparation and quantification of collagen birefringence in unstained sections of articular cartilage using image analysis and polarizing light microscopy

To establish an optimal method for analysis of the collagen structures from unstained tissue sections, a computerized image analysis system using a charge coupled device camera coupled to a polarizing light microscope was used. Retardation values of birefringence, which are proportional to the content and fibril orientation of collagen in the extracellular matrix of articular cartilage, were determined from sections prepared in different ways. In the superficial zone of articular cartilage, the highest retardation values were recorded from sections cut parallel to the so-called split lines indicating the anisotropic arrangement of collagen. Complete digestion of glycosaminoglycans reduced the retardation value by approximately 6.0%, suggesting a minor, but not insignificant, contribution of glycosaminoglycans to the birefringence of the matrix. The use of a mounting medium with a refractive index close to that of the collagen (e.g. DPX) increased the specificity of the method, since the optical anisotropy of collagen derives predominantly from the intrinsic (structural) birefringence. In conclusion, analysis of unstained sections after careful removal of paraffin and glycosaminoglycans from the tissues provides a sensitive and rapid quantitative assessment of oriented collagen structures in articular cartilage     

N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors

A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.