The semaphorins

Semaphorins are secreted, transmembrane, and GPI-linked proteins, defined by cysteine-rich semaphorin protein domains, that have important roles in a variety of tissues. Humans have 20 semaphorins, Drosophila has five, and two are known from DNA viruses; semaphorins are also found in nematodes and crustaceans but not in non-animals. They are grouped into eight classes on the basis of phylogenetic tree analyses and the presence of additional protein motifs. The expression of semaphorins has been described most fully in the nervous system, but they are also present in most, or perhaps all, other tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. More recently, they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. A common theme in the mechanisms of semaphorin function is that they alter the cytoskeleton and the organization of actin filaments and the microtubule network. These effects occur primarily through binding of semaphorins to their receptors, although transmembrane semaphorins also serve as receptors themselves. The best characterized receptors for mediating semaphorin signaling are members of the neuropilin and plexin families of transmembrane proteins. Plexins, in particular, are thought to control many of the functional effects of semaphorins; the molecular mechanisms of semaphorin signaling are still poorly understood, however. Given the importance of semaphorins in a wide range of functions, including neural connectivity, angiogenesis, immunoregulation, and cancer, much remains to be learned about these proteins and their roles in pathology and human disease.     

Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms

Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal Ags is a model for human uveitis. The immunosuppressive cytokine IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of endogenous IL-10 in the mouse model of EAU, we examined transgenic (Tg) mice expressing IL-10 either in activated T cells (inducible) or in macrophages (constitutive). These IL-10-Tg mice and non-Tg wild-type controls were immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein. Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in sera and in ocular extracts. In contrast, expression of IL-10 in activated T cells only partially protected from EAU and marginally reduced Ag-specific responses. All IL-10-Tg lines showed suppression of Ag-specific effector cytokines. APC from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naive T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10-Tg mice that received interphotoreceptor retinoid-binding protein-specific uveitogenic T cells from wild-type donors were protected from EAU. We suggest that constitutively produced endogenous IL-10 ameliorates the development of EAU by suppressing de novo priming of Ag-specific T cells and inhibiting the recruitment and/or function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye.     

High yield of cells committed to the photoreceptor-like cells from conjunctiva mesenchymal stem cells on nanofibrous scaffolds

Transplantation of stem cells using biodegradable and biocompatible nanofibrous scaffolds is a promising therapeutic approach for treating inherited retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. In this study, conjunctiva mesenchymal stem cells (CJMSCs) were seeded onto poly-l-lactic acid (PLLA) nanofibrous scaffolds and were induced to differentiate toward photoreceptor cell lineages. Furthermore, the effects of orientation of scaffold on photoreceptor differentiation were examined. Scanning electron microscopy (SEM) imaging, quantitative real time RT-PCR (qPCR) and immunocytochemistry were used to analyze differentiated cells and their expression of photoreceptor-specific genes. Our observations demonstrated the differentiation of CJMSCs to photoreceptor cells on nanofibrous scaffolds and suggested their potential application in retinal regeneration. SEM imaging showed that CJMSCs were spindle shaped and well oriented on the aligned nanofiber scaffolds. The expression of rod photoreceptor-specific genes was significantly higher in CJMSCs differentiated on randomly-oriented nanofibers compared to those on aligned nanofibers. According to our results we may conclude that the nanofibrous PLLA scaffold reported herein could be used as a potential cell carrier for retinal tissue engineering and a combination of electrospun nanofiber scaffolds and MSC-derived conjunctiva stromal cells may have potential application in retinal regenerative therapy.     

Compensatory growth in sub‐yearling Siberian sturgeon,Acipenser baerii Brandt, 1869: Effects of starvation and refeeding on growth,feed utilization and body composition

The capacity of sub‐yearling Siberian sturgeon (Acipenser baerii Brandt, 1869) (19.7 ± 0.8 g) to show compensatory growth was assessed for a 40‐day period for the effects of short‐term starvation and refeeding on growth, feeding performance and body composition. After acclimation, 25 experimental fish were randomly distributed among twelve 500‐L cylindrical fiberglass tanks with a flow‐through system. The fish were subjected to four different feeding regimes: control, which was fed four times daily to apparent satiation; T₁: four periods of 2 days starvation alternating with 8 days re‐feeding; T₂: two periods of 4 days starvation alternating with 16 days refeeding; T₃: an 8 days starvation period followed by 32 days refeeding. At the end of the experiment, the deprived fish attained body weights comparable to those attained by the control fish. There were no differences in growth and feeding performances between the deprived and the control fish. Total protein and lipid contents of the control fish were significantly higher than that of T₁ and T₂ fish at the end of the experiment (P < 0.05). A significant difference in the energy content was observed between T₂ and the control. Siberian sturgeon exhibited complete compensation, indicating a high ability of the deprived fish to grow sufficiently to fully compensate for weight loss during starvation. The results suggested that the feeding schedule involving starvation–refeeding cycles could be a promising feed management option for the culture of this species.     

Germacranolides related to chapliatrin from calea harleyi

The roots of Calea harleyi afforded four germacranolides closely related to chapliatrin and two derivatives of p-hydroxyacetophenone related to the acyloxycalefoliones.     

Genetic diversity of some wild almonds and related <Emphasis Type="Italic">Prunus</Emphasis> species revealed by SSR and EST-SSR molecular markers

Almond and its related wild species, which are widely distributed in Central and West Asia, have high genetic variation. This is an important source of genetic diversity for crop improvement. In this study a set of 32 SSR and 12 EST-SSR primer pairs were used to determine genetic diversity in 89 accessions of almond and other Prunus species. Most of the accessions (68) were collected from natural habitats of Iran. SSR primers amplified higher numbers of alleles than EST-SSR markers and discriminated genotypes more effectively. Results indicated high diversity among accessions. Observed heterozygosity (Ho) was 0.581. Nei’s index of diversity (He) and average number of alleles per locus (na) were 0.885 and 34, respectively. The mean value of polymorphism information content (PIC) was 0.874. The average Fst (F-statistics index) was 0.271 and the fixation index (Fis) was 0.151. Estimated variance among putative populations (AP) and individuals (AI) and within individuals (WI) were 5, 35, and 60%, respectively, which revealed that most of the variation was distributed among individuals rather than groups. Cultivated almonds were highly similar to P. fenzeliana, which is native to West Asia, supporting the importance of these regions in almond domestication. In the dendrogram of groups, minimum genetic distance was observed between Amygdalus and Orientalis groups from the Euamygdalus section. The Leptopus and Chameamygdalus sections were more distant from almonds than plums. The results also showed Dodecandra (Lycioides) series should be taxonomically classified closer to the section Euamygdalus.     

Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis

Proteinuria is an important cause of progressive tubulo-interstitial damage. Whether proteinuria could trigger a renal lymphangiogenic response has not been established. Moreover, the temporal relationship between development of fibrosis, inflammation and lymphangiogenesis in chronic progressive kidney disease is not clear yet. Therefore, we evaluated the time course of lymph vessel (LV) formation in relation to proteinuria and interstitial damage in a rat model of chronic unilateral adriamycin nephrosis. Proteinuria and kidneys were evaluated up to 30 weeks after induction of nephrosis. LVs were identified by podoplanin/VEGFR3 double staining. After 6 weeks proteinuria was well-established, without influx of interstitial macrophages and myofibroblasts, collagen deposition, osteopontin expression (tubular activation) or LV formation. At 12 weeks, a ∼3-fold increase in cortical LV density was found (p<0.001), gradually increasing over time. This corresponded with a significant increase in tubular osteopontin expression (p<0.01) and interstitial myofibroblast numbers (p<0.05), whereas collagen deposition and macrophage numbers were not yet increased. VEGF-C was mostly expressed by tubular cells rather than interstitial cells. Cultured tubular cells stimulated with FCS showed a dose-dependent increase in mRNA and protein expression of VEGF-C which was not observed by human albumin stimulation. We conclude that chronic proteinuria provoked lymphangiogenesis in temporal conjunction with tubular osteopontin expression and influx of myofibroblasts, that preceded interstitial fibrosis.     

Incidence of Chronic Kidney Disease and Its Risk Factors,Results of Over 10 Year Follow Up in an Iranian Cohort

To examine, the predictors of incident chronic kidney disease (CKD) in a community-based cohort of Middle East population, during a mean follow-up of 9.9 years. In a sample of 3313 non-CKD Iranian adults ≥20 years the estimated glomerular filtration rate (eGFR) was calculated at baseline and at three year intervals during three consecutive phases. The eGFR <60 mL/min/1.73 m2 was defined as CKD. Multivariate Logistic regression analysis was used to determine the independent variables associated with incident CKD. The incidence density rates of CKD were 285.3 and 132.6 per 10,000 person-year, among women and men, respectively. Female gender per se was associated with higher risk of CKD, compared with males. Among women, age, eGFR, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for CKD; however the intermediate degree of education and family history of diabetes decreased the risk by 40% (P<0.05). Among male subjects, independent predictors of developing CKD included aging and hypertension (with significantly higher risk than in women, P for interaction<0.05), eGFR, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of CKD about 30% which was marginally significant. In the Iranian population,>2% of individuals develops CKD each year. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident CKD.