<Emphasis Type="Italic">R-spondin1</Emphasis> and <Emphasis Type="Italic">FOXL2</Emphasis>act into two distinct cellular types during goat ovarian differentiation

Background  

Up to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4.     

Wear Behavior of Plasma Oxidized CoCrMo Alloy under Dry and Simulated Body Fluid Conditions

In this study, CoCrMo alloy was oxidized in plasma environment at the temperatures of 600 ℃ to 800 ℃ for 1 h to 5 h with 100% 02 gas and its tribological behavior was investigated. After the plasma oxidizing process, the compound and diffusion layers were formed on the surface. XRD results show that Cr203, a-Co and ε-Co phases diffracted from the modified layers after plasma oxidizing. The untreated and treated CoCrMo samples were subjected to wear tests both in dry and simulated body fluid conditions, and normal loads of 2 N and 10 N were used. For the sliding wear test, alumina balls were used as counter materials. It was observed that the wear resistance of CoCrMo alloy was increased after the plasma oxidizing process. The lowest wear rate was obtained from the samples that were oxidized at 800 ℃ for 5 h. It was detected that both wear environment and load have significant effects on the wear behavior of this alloy, and the wear resistance of oxidized CoCrMo alloy is higher when oxide-based counterface is used. The wear rates of both untreated and plasma oxidized samples increase under high loads.     

In silico investigation of PARP-1 catalytic domains in holo and apo states for the design of high-affinity PARP-1 inhibitors

The rational design of high-affinity inhibitors of poly-ADP-ribose polymerase-1 (PARP-1) is at the heart of modern anti-cancer drug design. While relevance of enzyme to DNA repair processes in cellular environment is firmly established, the structural and functional understanding of the main determinants for high-affinity ligands controlling PARP-1 activity is still lacking. The conserved active site of PARP-1 represents an ideal target for inhibitors and may offer a novel target at the treatment of breast cancer. To fill the gap in the structural knowledge, we report on the combination of molecular dynamics (MD) simulations, principal component analysis (PCA), and conformational analysis that analyzes in great details novel binding mode for a number of inhibitors at the PARP-1. While optimization of the binding affinity for original target is an important goal in the drug design, many of the promising molecules for treatment of the breast cancer are plagued by significant cardiotoxicity. One of the most common side-effects reported for a number of polymerase inhibitors is its off-target interactions with cardiac ion channels and hERG1 channel, in particular. Thus, selected candidate PARP-1 inhibitors were also screened in silico at the central cavities of hERG1 potassium ion channel.     

Paraoxonase and Arylesterase Levels in Behcet’s Disease and Their Relations with the Disease Activity

The aim of this study was to determine the paraoxonase (PON) and arylesterase (ARE) enzyme activity levels in Behcet’s disease (BD) and to investigate whether they are associated with the disease activity. Twenty-six patients (study group) with active BD and 28 healthy controls (control group) were included in this study. While the patients who had at least one of the symptoms related to genital ulcer, skin lesions, active uveitis, arthritis, thrombophlebitis, or central nervous system involvement in addition to oral ulcers were considered as the active group, the patients who did not show clinical symptoms in the last one month due to the medical treatment were considered as the inactive group in the clinical evaluation of patients with BD. The PON and ARE levels were found to be significantly lower in the study group than the control group (p < 0.05). The PON levels of the active and inactive groups were 96.23 ± 57.84 and 112.2 ± 65.14, respectively. The ARE levels of the active and inactive groups were 30.49 ± 5.81 and 30.85 ± 6.40, respectively. No significant correlations were found between clinical findings and the activity levels of PON and ARE in the active patient group (p > 0.05). The activities of the antioxidant PON and ARE enzymes are reduced in BD. Therefore, it may be useful to add antioxidant therapy to the conventional treatment of the disease.     

Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties,differentiation potential and immunophenotypic markers

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into many lineages. Although the growing interest in BM-MSCs has led to a number of characterization studies, some important biochemical and immunohistochemical properties are still lacking. In this study, morphological and immunophenotypic properties of BM-MSCs were examined in detail. Differentiation potential and growth kinetics of adult rat BM-MSCs were also determined. Immunohistochemistry and RT-PCR results indicated that BM-MSCs expressed myogenic (desmin, myogenin, myosin IIa, and α-SMA), neurogenic (γ-enolase, MAP2a,b, c-fos, nestin, GFAP and beta III tubulin), and osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, BMP-2, BMP-4 and type I collagen) markers without stimulation towards differentiation. These expression patterns indicated why these cells can easily differentiate into multiple lineages both in vitro and in vivo. Ultrastructural characteristics of rBM-MSCs showed more developed and metabolically active cells.     

Purification and mass spectrometry based characterization of a pediocin produced by Pediococcus acidilactici 13

Bacteriocins are antimicrobial peptides produced by several bacterial species. Among the bacteriocins pediocin-like bacteriocins have a significant inhibitory activity on the foodborne pathogens especially on Listeria monocytogenes. This study aims to select a simple and usable purification method to purify/concentrate the antimicrobial peptide and characterization of the bacteriocin produced by Pediococcus acidilactici 13 by using proteomic approaches which is a recent omic technology. For purification dialysis, ultrafiltration method was used, and as a result of this study the bacteriocin activity reached 819,200 AU/mL from 102,400 AU/mL initially. Two dimensional gel electrophoresis and then matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) analysis were carried out to identify the current bacteriocin and related proteins. Obtained data revealed similarity to pediocin PA-1 transport/processing ATP-binding protein PedD (accession number: P36497), pediocin operon PedC (accession number: Q68GC4) and bacteriocin pediocin PA-1 (accession number: P29430) from UniProtKB/Swiss-Prot databank, thus the bacteriocin produced by P. acidilactici 13 is considered similar to pediocin PA-1.     

Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.     

The Effects of Chromium Histidinate on Mineral Status of Serum and Tissue in Fat-Fed and Streptozotocin-Treated Type II Diabetic Rats

The present study was conducted to investigate the effects of chromium histidinate (CrHis) against experimentally induced type II diabetes and on chromium (Cr), zinc (Zn), selenium (Se), manganese (Mn), iron (Fe), and copper (Cu) in serum, liver, and kidney of diabetic rats. The male Wistar rats (n = 60, 8 weeks old) were divided into four groups. Group I received a standard diet (12% of calories as fat); group II were fed standard diet and received CrHis (110 mcg CrHis/kg body weight per day); group III received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg i.p.; HFD/STZ); group IV were treated as group III (HFD/STZ) but supplemented with 110 mcg CrHis/kg body weight per day. The mineral concentrations in the serum and tissue were determined by atomic absorption spectrometry. Compared to the HFD/STZ group, CrHis significantly increased body weight and reduced blood glucose in diabetic rats (p < 0.001). Concentrations of Cr, Zn, Se, and Mn in serum, liver, and kidney of the diabetic rats were significantly lower than in the control rats (p < 0.0001). In contrast, higher Fe and Cu levels were found in serum and tissues from diabetic versus the non-diabetic rats (p < 0.001). Chromium histidinate supplementation increased serum, liver, and kidney concentrations of Cr and Zn both in diabetic and non-diabetic rats (p < 0.001). Chromium supplementation increased Mn and Se levels in diabetic rats (p < 0.001); however, it decreased Cu levels in STZ-treated group (p < 0.001). Chromium histidinate supplementation did not affect Fe levels in both groups (p > 0.05). The results of the present study conclude that supplementing Cr to the diet of diabetic rats influences serum and tissue Cr, Zn, Se, Mn, and Cu concentrations.     

Alkaloids from Haplophyllum buxbaumii

In addition to the known alkaloids kokusaginine, skimmianine, γ-fagarine and a lignan, justicin B, the aerial parts of Haplophyllum buxbaumii afforded three new alkaloids: 4,5,6-trimethoxyfuroquinoline, 4,5,7-trimethoxyfuroquinoline and N-hydroxymethylflindersine. The structures of the known and the new compounds were assigned by spectral methods.