Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors

Background  

The tear film is a thin layer of fluid that covers the ocular surface and is involved in lubrication and protection of the eye. Little is known about the protein composition of tear fluid but its deregulation is associated with disease states, such as diabetic dry eyes. This makes this body fluid an interesting candidate for in-depth proteomic analysis.     

Persistent nuclear ribosomal DNA sequence polymorphism in the Amelanchier agamic complex (Rosaceae)

Individual plants of several Amelanchier taxa contain many polymorphic nucleotide sites in the internal transcribed spacers (ITS) of nuclear ribosomal DNA (nrDNA). This polymorphism is unusual because it is not recent in origin and thus has resisted homogenization by concerted evolution. Amelanchier ITS sequence polymorphism is hypothesized to be the result of gene flow between two major North American clades resolved by phylogenetic analysis of ITS sequences. Western North American species plus A. humilis and A. sanguinea of eastern North America form one clade (A), and the remaining eastern North American Amelanchier make up clade B. Five eastern North American taxa are polymorphic at many of the nucleotide sites where clades A and B have diverged and are thought to be of hybrid origin, with A. humilis or A. sanguinea as one parent and various members of clade B as the other parent. Morphological evidence suggests that A. humilis is one of the parents of one of the polymorphic taxa, a microspecies that we refer to informally as A. "erecta." Sequences of 21 cloned copies of the ITS1- 5.8S gene-ITS2 region from one A. "erecta" individual are identical to A. humilis sequence or to the clade B consensus sequence, or they are apparent recombinants of A. humilis and clade B ITS repeats. Amelanchier "erecta" and another polymorphic taxon are suspected to be relatively old because both grow several hundred kilometers beyond the range of one of their parents. ITS sequence polymorphisms have apparently persisted in these two taxa perhaps because of polyploidy and/or agamospermy (asexual seed production), which are prevalent in the genus.      

The ameliorative effects of vinpocetine on apoptosis and HSP-70 expression in testicular torsion in rats

Vinpocetine is a potent antioxidant and free radical scavenger. We investigated the effects of vinpocetine on torsion/detorsion (T/D) induced testicular damage, HSP-70 expression and germ cell apoptosis in rats. Sixty Wistar albino adult male rats were divided into five groups of 12. The groups comprised a control group, a sham treated group, a T/D group, a vinpocetine treated group, and a T/D plus vinpocetine treated group. The left testis of each rat was subjected to unilateral torsion followed by detorsion after 2 h. Vinpocetine was administered intraperitoneally immediately and for 10 days following detorsion. At the end of the study, the rats were sacrificed and their testes removed and processed. HSP-70 expression, apoptosis and histopathological damage scores were determined for each group. Testicular T/D caused significant increases in apoptosis and HSP-70 expression, and a significant decrease in Johnsen’s testicular biopsy scores and mean seminiferous tubule diameter. Vinpocetine ameliorated testicular histopathology and HSP-70 expression in the T/D + vinpocetine group. Consequently, vinpocetine may prevent testicular injury following testicular torsion owing to its antioxidant effects.     

The art of strain improvement of industrial lactic acid bacteria without the use of recombinant DNA technology

The food industry is constantly striving to develop new products to fulfil the ever changing demands of consumers and the strict requirements of regulatory agencies. For foods based on microbial fermentation, this pushes the boundaries of microbial performance and requires the constant development of new starter cultures with novel properties. Since the use of ingredients in the food industry is tightly regulated and under close scrutiny by consumers, the use of recombinant DNA technology to improve microbial performance is currently not an option. As a result, the focus for improving strains for microbial fermentation is on classical strain improvement methods. Here we review the use of these techniques to improve the functionality of lactic acid bacteria starter cultures for application in industrial-scale food production. Methods will be described for improving the bacteriophage resistance of specific strains, improving their texture forming ability, increasing their tolerance to stress and modulating both the amount and identity of acids produced during fermentation. In addition, approaches to eliminating undesirable properties will be described. Techniques include random mutagenesis, directed evolution and dominant selection schemes.     

Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats

Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.     

细胞周期与细胞凋亡

从海洋生物胚胎细胞到哺乳动物的细胞周期,主要是在其细胞周期基因产物周期素及Ｐ３４的调控下启动,运行和脱出周期的;某些原癌基因或抑癌基因的产物如ｐ５３,ｐＲＢ也直接调控着细胞周期。     

Granuloma Due to Oxidized Regenerated Cellulose in an Aged Rhesus Macaque (Macaca mulatta)

Bioabsorbable hemostatic agents such as oxidized regenerated cellulose are widely used to control intraoperative diffuse capillary bleeding. Compared with electrocautery or ligation, oxidized regenerated cellulose has the advantage of controlling bleeding without occluding the vessel lumen or causing thermal injuries to adjacent tissue. Although the manufacturer recommends removal of the material once hemostasis is achieved, oxidized regenerated cellulose is a bioabsorbable hemostatic agent and is often left in the surgical bed to prevent subsequent bleeding after surgical closure. However, noninvasive imaging techniques have revealed granulomatous foreign-body reactions that mimic infection or tumor recurrence. We present a case report of sterile peritonitis and granuloma formation secondary to the presence of oxidized regenerated cellulose after intestinal resection to excise a colonic adenocarcinoma in an aged rhesus macaque.Bioabsorbable hemostatic agents such as oxidized regenerated cellulose (for example, Surgicel) are widely used to control intraoperative diffuse capillary bleeding. Compared with electrocautery or ligation, oxidized regenerated cellulose has the advantage of controlling bleeding without occluding the vessel lumen or causing thermal injuries to adjacent tissue.¹⁶Oxidized regenerated cellulose is formed by dissolving the α-cellulose of decomposed wood pulp in an alkaline solution and subsequently regenerating it as a continuous fiber. This fiber is then woven into a gauze and oxidized.^17,22 Oxidized regenerated cellulose is supplied as a substrate that is flexible, malleable, and trimable.¹⁶The mechanism of hemostasis of oxidized regenerated cellulose is reportedly associated with its caustic activity.² The oxidation of cellulose produces a low-pH organic acid that reacts with blood, thus forming an artificial clot and causing platelet aggregation.¹⁸Although the manufacturer recommends the removal of oxidized regenerated cellulose once hemostasis is achieved,⁸ the product, a bioabsorbable hemostatic agent, is often left in situ within the surgical bed to prevent bleeding after surgical procedures. The biodegradation and elimination of oxidized regenerated cellulose from the tissue occurs in 2 phases.¹⁴ Polyanhydroglucuronic acid, the major functional unit of oxidized regenerated cellulose, is readily soluble. This acid is degraded extracellulary and systematically cleared from the system approximately 18 h after implantation.^13,14 The remaining fibrous residue, however, requires macrophage phagocytosis for clearance and can be observed within macrophages for at least 48 h after implantation.¹³ Unfortunately, these fibrous residues have a prolonged degradation, and their persistence for as long as 7 mo after surgery has been confirmed histologically.⁷Despite the biocompatibility of oxidized regenerated cellulose, granulomatous foreign-body reactions that imitate infection or tumor recurrence have been revealed by using noninvasive imaging techniques.^{1,11,12,15,17,18,22} Here we describe a case of peritonitis and granuloma formation secondary to the presence of oxidized regenerated cellulose after an intestinal resection to excise a colonic adenocarcinoma in an aged rhesus macaque.     

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS₁₀) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10⁻¹¹; N = 467). A higher GRS₁₀ was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS₁₀ and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.