Synthesis,Characterization and Lipophilicity Study of Brucella abortus’ Immunogenic Peptide Sequence That Can Be Used in the Future Vaccination Studies

International Journal of Peptide Research and Therapeutics - Brucellosis is primarily a zoonotic disease caused by members of the Brucella genus which consists of 11 recognized species based on...     

The Role of Arginine–Nitric Oxide Pathway in Patients with Alzheimer Disease

There is a reciprocal regulation of arginase and nitric oxide synthase in l-arginine-metabolizing pathways. There are various evidences of the role of nitric oxide in several neuropsychiatric disorders including Alzheimer’s disease. However, there is no study that has investigated the role of arginase as an important part of the arginine regulatory system affecting nitric oxide synthase activity in Alzheimer’s disease. This study aims to investigate arginase, manganese (a cofactor of arginase), and total nitrite levels (a metabolite of NO) and their relationship to the arginine–NO pathway in patients with Alzheimer’s disease. Arginase activities, Mn, and total nitrite levels were measured in plasma from 47 patients with Alzheimer’s disease and 43 healthy control subjects. Plasma arginase activities and manganese were found to be significantly lower and total nitrite level higher in patients with Alzheimer’s disease compared with controls. Our results suggest that the arginine–NO pathway is involved in the pathogenesis of Alzheimer’s disease.     

The clonogenic potential of hematopoietic stem cells and mesenchymal stromal cells in various hematologic diseases: a pilot study

Background aimsMesenchymal stromal cells (MSC) are the most popular cells used in regenerative medicine and biotechnology. The clonogenic potential of these cells is defined by colony-forming unit-fibroblasts (CFU-F). It is well known that there is an interaction between hematopoietic cells and stromal cells in disease formation pathogenesis. Therefore we hypothesized that there should be a quantitative and qualitative relationship between MSC colonies (CFU-F) and hematopoietic stem cell colonies (colony-forming unit-granulocyte-macrophages; CFU-GM) among patients with and without hematologic diseases.MethodsForty-two patients were included in this study. Patients were divided into three groups: group A, patients with hematologic malignancies (n = 20); group B, patients with bone marrow (BM) failure (n = 11); group C, patients without hematologic diseases (n = 11). BM aspirates were plated in different densities for CFU-F culture. The plating density was the same for CFU-GM culture.ResultsCFU-GM colonies grew in 90% of group A cells and all of group B and C cells (P = 0.0001). CFU-F colonies became visible on the ninth day of plating in group A and on the eight day in groups B and C. There was no statistically significant difference between the groups for the duration of CFU-F colony formation (P = 0.12). There were differences in the morphology of the colonies among the groups.ConclusionsThis is the first study that has compared the clonogenic potential of stromal cells and hematopoietic stem cells in the same subjects with and without hematologic diseases. No correlation was shown between the clonogenic potential of stromal cells and hematopoietic cells.     

Mortality and knockdown effects of imidacloprid and methomyl in house fly (Musca domestica L., Diptera: Muscidae) populations

In this study, the knockdown and mortality effects of imidacloprid and methomyl were investigated. The residual surface applications were carried out to determine the knockdown effects (KDt₅₀ and KDt₉₅) and mortality (LD₅₀ and LD₉₅) induced by each insecticide. For mortality comparisons, the susceptible house fly (Musca domestica L., Diptera: Muscidae) of a WHO population and three natural field‐collected M. domestica populations from Turkey were used. In conclusion, it was found that the resistance to imidacloprid and methomyl was significantly higher in the field populations when compared to the susceptible population from WHO. The results showed that applicators and pest management decision‐makers should control and conduct an integrated pest management strategy by including biological agents to prevent the development of high levels of resistance in the field populations.     

Dynamic mechanical response of bovine gray matter and white matter brain tissues under compression

Dynamic responses of brain tissues are needed for predicting traumatic brain injury (TBI). We modified a dynamic experimental technique for characterizing high strain-rate mechanical behavior of brain tissues. Using the setup, the gray and white matters from bovine brains were characterized under compression to large strains at five different strain rates ranging from 0.01 to 3000/s. The white matter was examined both along and perpendicular to the coronal section for anisotropy characterization. The results show that both brain tissue matters are highly strain-rate sensitive. Differences between the white matter and gray matter in their mechanical responses are recorded. The white matter shows insignificant anisotropy over all strain rates. These results will lead to rate-dependent material modeling for dynamic event simulations.     

The Ability to Generate Senescent Progeny as a Mechanism Underlying Breast Cancer Cell Heterogeneity

Background

Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, “normal-like”, and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity.

Methodology/Principal Findings

A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21^Cip1 correlated with senescence in these cell lines. p21^Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and “normal-like” tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice.

Conclusions/Significance

Luminal A and “normal-like” breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential.     

Mutation in exon 1f of PLEC, leading to disruption of plectin isoform 1f, causes autosomal-recessive limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of inherited muscular disorders manifesting symmetric, proximal, and slowly progressive muscle weakness. Using Affymetrix 250K SNP Array genotyping and homozygosity mapping, we mapped an autosomal-recessive LGMD phenotype to the telomeric portion of chromosome 8q in a consanguineous Turkish family with three affected individuals. DNA sequence analysis of PLEC identified a homozygous c.1_9del mutation containing an initiation codon in exon 1f, which is an isoform-specific sequence of plectin isoform 1f. The same homozygous mutation was also detected in two additional families during the analysis of 72 independent LGMD2-affected families. Moreover, we showed that the expression of PLEC was reduced in the patient's muscle and that there was almost no expression for plectin 1f mRNA as a result of the mutation. In addition to dystrophic changes in muscle, ultrastructural alterations, such as membrane duplications, an enlarged space between the membrane and sarcomere, and misalignment of Z-disks, were observed by transmission electron microscopy. Unlike the control skeletal muscle, no sarcolemmal staining of plectin was detected in the patient's muscle. We conclude that as a result of plectin 1f deficiency, the linkage between the sarcolemma and sarcomere is broken, which could affect the structural organization of the myofiber. Our data show that one of the isoforms of plectin plays a key role in skeletal muscle function and that disruption of the plectin 1f can cause the LGMD2 phenotype without any dermatologic component as was previously reported with mutations in constant exons of PLEC.     

Inhibition of in vitro and in vivo brown fat differentiation program by myostatin

Objective: Obesity arises mainly due to the imbalance between energy storage and its expenditure. Metabolically active brown adipose tissue (BAT) has recently been detected in humans and has been proposed as a new target for anti‐obesity therapy because of its unique capacity to regulate energy expenditure. Myostatin (Mst), a negative regulator of muscle mass, has been identified as a potential target to regulate overall body composition. Although the beneficial effects of Mst inhibition on muscle mass are well known, its role in the regulation of lipid metabolism, and energy expenditure is not very clear. Design and Methods: We tested the effects of Mst inhibition on the gene regulatory networks that control BAT differentiation using both in vivo and in vitro model systems. PRDM16 and UCP1, two key regulators of brown fat differentiation were significantly up regulated in levator‐ani (LA) and gastrocnemius (Gastroc) muscles as well as in epididymal (Epi) and subcutaneous (SC) fat pads isolated from Mst knock out (Mst KO) male mice compared with wild type (WT) mice. Results: Using mouse embryonic fibroblast (MEFs) primary cultures obtained from Mst KO group compared to the WT group undergoing adipogenic differentiation, we also demonstrate a significant increase in select genes and proteins that improve lipid metabolism and energy expenditure. Conclusion: Treatment of Mst KO MEFs with recombinant Mst protein significantly inhibited the gene expression levels of UCP1, PRDM16, PGC1‐α/β as well as BMP7. Future studies to extend these findings and explore the therapeutic potential of Mst inhibition on metabolic disorders are warranted.