A computational model for early events in B cell antigen receptor signaling: analysis of the roles of Lyn and Fyn

BCR signaling regulates the activities and fates of B cells. BCR signaling encompasses two feedback loops emanating from Lyn and Fyn, which are Src family protein tyrosine kinases (SFKs). Positive feedback arises from SFK-mediated trans phosphorylation of BCR and receptor-bound Lyn and Fyn, which increases the kinase activities of Lyn and Fyn. Negative feedback arises from SFK-mediated cis phosphorylation of the transmembrane adapter protein PAG1, which recruits the cytosolic protein tyrosine kinase Csk to the plasma membrane, where it acts to decrease the kinase activities of Lyn and Fyn. To study the effects of the positive and negative feedback loops on the dynamical stability of BCR signaling and the relative contributions of Lyn and Fyn to BCR signaling, we consider in this study a rule-based model for early events in BCR signaling that encompasses membrane-proximal interactions of six proteins, as follows: BCR, Lyn, Fyn, Csk, PAG1, and Syk, a cytosolic protein tyrosine kinase that is activated as a result of SFK-mediated phosphorylation of BCR. The model is consistent with known effects of Lyn and Fyn deletions. We find that BCR signaling can generate a single pulse or oscillations of Syk activation depending on the strength of Ag signal and the relative levels of Lyn and Fyn. We also show that bistability can arise in Lyn- or Csk-deficient cells.     

Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation

Chemerin is an adipokine associated with metabolic syndrome, systemic inflammation and innate immune system. It has been suggested recently that the decrease in renal function may cause an increase in serum chemerin concentration. In this paper we investigated the effect of kidney transplantation on elevated serum chemerin concentration in dialyzed patients with end stage renal disease (ESRD). Twenty five ESRD patients were tested before and 3months after the kidney transplantation. The control group was comprised of twenty one healthy subjects. Serum chemerin concentrations were measured using commercial ELISA kit, and were related to clinical status, and biomarkers of renal function. We have shown that the kidney transplantation resulted in the decrease of the serum chemerin concentration. Concomitantly, serum creatinine, blood urea nitrogen, phosphate and C-reactive protein concentrations were significantly reduced, while estimated glomerular filtration rate (eGFR), calcium and hemoglobin substantially increased. Univariate regression analysis showed that serum chemerin concentration was positively correlated with serum creatinine and phosphate concentrations and negatively correlated with eGFR. The results presented here indicate that the serum chemerin concentration in patients with ESRD normalizes after the kidney transplantation, and provide additional evidence that serum chemerin concentration is related to renal function.     

Discrepancy between clinical and histological effects of DHA supplementation in a rat model of pouchitis

Docosahexaenoic acid (DHA) potentially modulates inflammatory processes. Therefore, the aim of this study was to determine the influence of DHA supplementation on the expression of intestinal inflammation and nutritional status in rats which have undergone restorative proctocolectomy. Twenty-four Wistar rats were operated. After the induction of pouchitis, animals were randomly divided into a control group (CG) and supplementation groups receiving respectively a semi-synthetic diet without or with DHA (in a lower or higher dose, respectively known as the lower dose, LD, and higher dose, HD, groups) for six weeks. Selected nutritional parameters were assessed. Histopathological and immunohistochemical analysis of pouch mucosa specimens was also performed. The effectiveness of feeding and quality of stools were significantly better in the HD group than in the CG. The intensity of inflammation (Moskovitz scale) was higher in HD and LD than in CG (p = 0.03 and p = 0.0006, respectively). Nevertheless, pouch adaptation (Laumonier scale) was more significant in LD than in CG (p = 0.007). On the other hand, tissue expression of IL-1α and IL-10 was higher in HD and LD than in CG (IL-1α, p = 0.009 and p = 0.05, respectively; IL-10, p = 0.04 for both). DHA supplementation has no impact on body weight gain. Yet it seems that it may improve the effectiveness of nutrition and stool quality in rats which have undergone restorative proctocolectomy. Simultaneously, it increases the intensity of pouch adaptation and inflammation. The specificity of observed changes is not clear. However, it may imply potential modulation of inflammatory processes of pouch mucosa.     

The relationship between seedling growth and grain yield under drought conditions in maize and triticale genotypes

The effects of drought stress on seedlings?? growth and grain yield of 13 single cross maize hybrids and 11 breeding lines and cultivars of spring triticale were studied in greenhouse and field experiments. In the field experiment, the drought susceptibility index (DSI_GY) was calculated by determining the change in grain yield (GY) in conditions with two soil moisture levels (IR, irrigated; D, drought). In the greenhouse experiment the response to soil drought was evaluated using DSI_DW, by determining changes in the dry weight (DW) of vegetative plant parts. Marked variations in GY and DW were observed among the studied genotypes. In control conditions, the GY and DW in drought-sensitive genotypes were higher compared to the drought-resistant ones; but in drought conditions, the decreases in GY and DW in resistant genotypes were smaller than in drought-sensitive ones. DSI_GY and DSI_DW revealed variations in the degree of drought tolerance among the examined maize and triticale genotypes. The values of DSI_GY in the field experiment and DSI_DW in the greenhouse experiment enabled a division of the studied genotypes into drought-resistant or -sensitive groups. A close correlation between DSI_GY and DSI_DW was found. The positive linear correlation and determination coefficients between DSI_GY and DSI_DW were statistically significant (P?=?0.05), being equal to R ²?=?0.614 (maize) and R ²?=?0.535 (triticale). The ranking of the studied genotypes based on DSI_GY was in most cases consistent with the ranking based on DSI_DW, which indicates that genetically conditioned drought tolerance is similar for plants in the seedling and reproductive growth stages or may at least partly have a common genetic background.     

The landscape of mitochondrial DNA variation in human colorectal cancer on the background of phylogenetic knowledge

Recently, an increasing number of studies indicate that mutations in mitochondrial genome may contribute to cancer development or metastasis. Hence, it is important to determine whether the mitochondrial DNA might be a good, clinically applicable marker of cancer. This review describes hereditary as well as somatic mutations reported in mitochondrial DNA of colorectal cancer cells. We showed here that the entire mitochondrial genome mutational spectra are different in colorectal cancer and non-tumor cells. We also placed the described mutations on the phylogenetic context, which highlighted the recurrent problem of data quality. Therefore, the most important rules for adequately assessing the quality of mitochondrial DNA sequence analysis in cancer have been summarized. As follows from this review, neither the reliable spectrum of mtDNA somatic mutations nor the association between hereditary mutations and colorectal cancer risk have been resolved. This indicates that only high resolution studies on mtDNA variability, followed by a proper data interpretation employing phylogenetic knowledge may finally verify the utility of mtDNA sequence (if any) in clinical practice.     

Ectomycorrhizal fungal communities of native and non-native Pinus and Quercus species in a common garden of 35-year-old trees

Non-native tree species have been widely planted or have become naturalized in most forested landscapes. It is not clear if native trees species collectively differ in ectomycorrhizal fungal (EMF) diversity and communities from that of non-native tree species. Alternatively, EMF species community similarity may be more determined by host plant phylogeny than by whether the plant is native or non-native. We examined these unknowns by comparing two genera, native and non-native Quercus robur and Quercus rubra and native and non-native Pinus sylvestris and Pinus nigra in a 35-year-old common garden in Poland. Using molecular and morphological approaches, we identified EMF species from ectomycorrhizal root tips and sporocarps collected in the monoculture tree plots. A total of 69 EMF species were found, with 38 species collected only as sporocarps, 18 only as ectomycorrhizas, and 13 both as ectomycorrhizas and sporocarps. The EMF species observed were all native and commonly associated with a Holarctic range in distribution. We found that native Q. robur had ca. 120% higher total EMF species richness than the non-native Q. rubra, while native P. sylvestris had ca. 25% lower total EMF species richness than non-native P. nigra. Thus, across genera, there was no evidence that native species have higher EMF species diversity than exotic species. In addition, we found a higher similarity in EMF communities between the two Pinus species than between the two Quercus species. These results support the naturalization of non-native trees by means of mutualistic associations with cosmopolitan and novel fungi.     

Detection of disordered regions in globular proteins using 13C‐detected NMR

Characterization of disordered regions in globular proteins constitutes a significant challenge. Here, we report an approach based on ¹³C‐detected nuclear magnetic resonance experiments for the identification and assignment of disordered regions in large proteins. Using this method, we demonstrate that disordered fragments can be accurately identified in two homologs of menin, a globular protein with a molecular weight over 50 kDa. Our work provides an efficient way to characterize disordered fragments in globular proteins for structural biology applications.     

Complete mitochondrial DNA analysis of eastern Eurasian haplogroups rarely found in populations of northern Asia and eastern Europe

With the aim of uncovering all of the most basal variation in the northern Asian mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and 149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of northern and central Asia has been revealed, reflecting both influences of central Asian inhabitants and essential genetic interaction with the Altai region indigenous populations. Statistical analyses data demonstrate a close positioning of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their origin from a common maternal ancestral gene pool. In order to achieve a thorough coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we have completely sequenced the mtDNA of 55 samples representing haplogroups R11b, B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive collection (over 5000 individuals) of northern and eastern Asian, as well as European control region mtDNA sequences. Applying the newly updated mtDNA tree to the previously reported northern Asian and eastern Asian mtDNA data sets has resolved the status of the poorly classified mtDNA types and allowed us to obtain the coalescence age estimates of the nodes of interest using different calibrated rates. Our findings confirm our previous conclusion that northern Asian maternal gene pool consists of predominantly post-LGM components of eastern Asian ancestry, though some genetic lineages may have a pre-LGM/LGM origin.     

The evaluation of knee bone mineral density following open-wedge high tibial osteotomy

Examinations of bone density changes in selected knee bone ends were evaluated prospectively in a randomized group of 28 patients, aged from 41 to 65 (mean: 55.3 years), who had varus deformations of their mechanic limb axes, mean 8 degrees. The examinations were conducted during the preoperative period, 10 days, 3, 6, and 12 weeks, as well as 6 and 12 months after the procedure. A statistically significant increase in bone density was observed in the medial tibial condyle area, while a statistically insignificant decrease of bone density was noted in the medial femoral condyles. Bone density increased in the lateral tibial condyle area, whereas there were no density changes in the area of the lateral femoral condyles. The research results demonstrate that the relief achieved in ailments after high tibial osteotomies does not directly correspond to the bone density of the affected areas.