Overview of ribosomal and non-ribosomal antimicrobial peptides produced by Gram positive bacteria.

The increasing incidence of antimicrobial resistance bacterial infection and decreasing effectiveness of conventional antibiotics to treatment have caused serious problems worldwide. The demand for new generationantibiotics to combat microbial pathogens is imperative. Cationic antimicrobial peptides (AMPs) with different sources from prokaryotic to complex eukaryotic organisms, with variable length, amino acid composition and secondary structure, have been consideredduring the past decades.  The advantages of large number of AMPs are related to broad spectrum and morphogenetic activities, low resistance rate among microorganismswithout side effect on human cells, rapid killing of bacteria via membrane damage and intracellular targets,and their critical roles in anti-inflammatory. Ribosomal synthesized peptides of Gram positive bacteria with various post translational modificationsrepresent extended types of antimicrobial peptide with different structural and functional diversity. These types of peptides have been considered as new therapeutic agents for pharmaceutical development .In addition, non- ribosomal synthesized peptides are a wide range of peptides , an extremely extensive range of biological activities and pharmacological properties that are not synthesized by ribosomes,  show interesting biological properties ranging from antibiotic to bio surfactants. This review focused on genetics, mechanism of action and modifications, resistance mode of Gram positive bacteria to AMPs and the biotechnological application of ribosomally and non-ribosomally synthesized peptides derived from Gram positive bacteria.

Isolation of multipotent adult stem cells from the dermis of mammalian skin.

We describe here the isolation of stem cells from juvenile and adult rodent skin. These cells derive from the dermis, and clones of individual cells can proliferate and differentiate in culture to produce neurons, glia, smooth muscle cells and adipocytes. Similar precursors that produce neuron-specific proteins upon differentiation can be isolated from adult human scalp. Because these cells (termed SKPs for skin-derived precursors) generate both neural and mesodermal progeny, we propose that they represent a novel multipotent adult stem cell and suggest that skin may provide an accessible, autologous source of stem cells for transplantation.

Molecular dynamics simulation study of association in trifluoroethanol/water mixtures.

Mixtures of Trifluoroethanol (TFE) and water with different proportions are studied using molecular dynamics simulations. The radial and spatial distribution functions, as well as the size distribution of TFE clusters are obtained from the trajectories. The variation of radial and spatial distribution functions with composition show that the addition of TFE enhances the water structure, but the hydrogen bonds between TFE molecules are broken as TFE is diluted with water. The TFE-rich solutions have stronger TFE-water hydrogen bonds. The clustering of TFE molecules in low concentration region is attributed to the hydrophobic interactions between CF(3) groups. The distribution of cluster sizes in solution supports these conclusions.

Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups.

The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. Also we found that the rat pups whose mother was submitted to forced-swimming during pregnancy had significantly higher brain, liver, heart and kidney weights compared with their sedentary counterparts. On the other hand we estimated the cell number of different regions of the hippocampus in the rat pups. We found that both exercise models during pregnancy increased the cell number in cornus ammonis subregion 1 (CA1) and dentate gyrus of the hippocampus in rat pups. To determine the role that noradrenergic and serotonergic neurotransmission and N-methyl-D-aspartate (NMDA) receptors hold in mediation of the maternal exercise in offspring, we used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), p-chloroamphetamine (PCA) and MK-801 to eliminate or block the above systems, respectively. Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.

Maternal voluntary exercise ameliorates learning deficit in rat pups exposed, in utero, to valproic acid; role of BDNF and VEGF and their receptors.

In utero exposure to therapeutic doses of valproic acid (VPA) during pregnancy can produce physical malformation and CNS abnormalities in the offspring. There is evidence indicating that even lower doses of VPA during pregnancy could cause cognitive impairment in offspring. It has been demonstrated that maternal exercise has positive effects on offspring's cognitive function. In this study we evaluated the preventive potential of maternal voluntary exercise on cognitive deficits induced by in utero exposure to VPA, in rat pups. Furthermore, the alteration of hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) and their respective receptors were measured. In treatment groups, pregnant rats received VPA (10 and 20 mg/kg) daily on the gestation days (GD) 7 for twelve days with or without access to a running wheel. In control groups, rats received saline with or without access to a running wheel. On postnatal day (PND) 30, learning and memory of rat pups were assessed using the Morris Water Maze (MWM) task. Also, on PND 30, hippocampal BDNF and VEGF were measured by ELISA and western blot analysis respectively. VEGFR (VEGF receptor) and TrkB (Tyrosine receptor kinase B, the receptor for BDNF) expressions were assessed using immunofluorescence staining. Results revealed that maternal voluntary exercise enhanced learning in offspring but had little effect on memory retention. Exposure to VPA during pregnancy disturbed learning and memory in rat pups. Maternal voluntary exercise could ameliorate some aspects of cognitive deficit induced by VPA. TrkB and VEGFR2 expression were enhanced in pups from running mothers. VPA, at both doses, suppressed exercise induced expression of these two receptors. Voluntary exercise and to a much greater extent VPA administration increased hippocampal BDNF. Voluntary exercise of mothers caused an enhance expression of VEGF in rat pups as did VPA administration, although to a smaller amount.

Outcome Determinants of Patients with Traumatic Pelvic Fractures: A Cohort Study in a Level I Trauma Center in Southern Iran.

Pelvic fracture is a result of devastating injuries and is usually encountered in conjunction with other life-threatening injuries. The aim of the current study was to determine the outcome determinants of patients with pelvic fractures referred to a large trauma center in southern Iran. This retrospective cross-sectional study was conducted in a level I trauma center over a period of three years from 2012 to 2015. We included all patients with pelvic fractures whose medical records had sufficient data. Data were compared between good condition and poor conditions. A total of 327 patients with mean age of 40.1 ± 19.7 years were included. Poor condition was defined as being associated with higher heart rate (p=0.002), lower systolic blood pressure (p<0.001), lower diastolic blood pressure (p=0.002) lower Glasgow Coma Scale (GCS) on admission (p<0.001) and higher Injury Severity Score (ISS) (p<0.001). Those with poor conditions had significantly higher admission to ICU (p<0.001), higher rate of surgical interventions (p<0.001) and higher mortality (p<0.001). The hospital length of stay (p<0.001) and ICU length of stay (p=0.025) were also longer in those with poor condition. Lower hemoglobin, lower pH, higher heart rate, lower systolic blood pressure, lower GCS on admission and higher ISS were important outcome determinants of traumatic pelvic fractures.

Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.

The ability of exercise to benefit neuronal and cognitive plasticity is well recognized. This study reveals that the effects of exercise on brain neuronal and cognitive plasticity are in part modulated by a central source of insulin-like growth factor-I. Exercise selectively increased insulin-like growth factor-I expression without affecting insulin-like growth factor-II expression in the rat hippocampus. To determine the role that insulin-like growth factor-I holds in mediating exercise-induced neuronal and cognitive enhancement, a specific antibody against the insulin-like growth factor-I receptor was used to block the action of insulin-like growth factor-I in the hippocampus during a 5-day voluntary exercise period. A two-trial-per-day Morris water maze was performed for five consecutive days, succeeded by a probe trial 2 days later. Blocking hippocampal insulin-like growth factor-I receptors did not significantly attenuate the ability of exercise to enhance learning acquisition, but abolished the effect of exercise on augmenting recall. Blocking the insulin-like growth factor-I receptor significantly reversed the exercise-induced increase in the levels of brain-derived neurotrophic factor mRNA and protein and pro-brain-derived neurotrophic factor protein, suggesting that the effects of insulin-like growth factor-I may be partially accomplished by modulating the precursor to the mature brain-derived neurotrophic factor. A molecular analysis revealed that exercise significantly elevated proteins downstream to brain-derived neurotrophic factor activation important for synaptic function, i.e. synapsin I, and signal transduction cascades associated with memory processes, i.e. phosphorylated calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein kinase II. Blocking the insulin-like growth factor-I receptor abolished these exercise-induced increases. Our results illustrate a possible mechanism by which insulin-like growth factor-I interfaces with the brain-derived neurotrophic factor system to mediate exercise-induced synaptic and cognitive plasticity.

Utility of a short-term 25% carbohydrate diet on improving glycemic control in type 2 diabetes mellitus.

OBJECTIVE: To determine if introduction of a low carbohydrate diet might be a useful option for type 2 diabetic patients who do not achieve glucose target levels despite conventional treatment. METHODS: Subjects with type 2 diabetes, either treated with diet alone (n=9) or second generation sulfonylurea agents (n= 19), which were discontinued, were placed on a diet based on ideal body weight and comprised of 25% carbohydrate. After a mean of 8 weeks, they were then switched to a caloricly equivalent diet, but composed of 55% carbohydrate. RESULTS: Compared to baseline diet, after 8 weeks of a 25% diet, subjects showed significantly improved glycemia as evidenced by fasting blood glucose values (p<0.005) and hemoglobin A1c levels (p<0.05). Those previously treated with oral hypoglycemic agents showed, in addition, a significant decrease in weight and diastolic blood pressure despite the discontinuation of the oral agent. When then placed on a 55% carbohydrate diet, the hemoglobin A1c rose significantly over the ensuing next 12 weeks (p<0.05). CONCLUSION: A low carbohydrate, caloricly-restricted diet has beneficial short-term effects in subjects with type 2 who have failed either diet or sulfonylurea therapy and may obviate the necessity for insulin. Our study also affirms the need for reassessing the role of diet whenever type 2 diabetic patients manifests hyperglycemia, despite conventional oral treatment or diet management.

Studies on human alpha(s)- and kappa-casein fractions and human caseinoglycomacropeptide.

1. Fractions have been obtained from human whole casein closely resembling the alpha(s)- and kappa-fractions of cow casein. 2. The alpha(s)-fraction (human alpha(s)-casein) is calcium-sensitive, heterogeneous in zone analysis and inert towards rennin. 3. The kappa-fraction (human kappa-casein) is calcium-insensitive, heterogeneous in zone analysis, and forms a soluble glycopeptide when acted upon by rennin. 4. Human kappa-casein stabilizes human alpha(s)-casein in the presence of Ca(2+) ions. 5. The glycopeptides released by rennin from human casein and from cow casein have been compared. There are important differences in both the peptide and non-peptide structures of the two compounds. 6. In both human and bovine glycopeptides some of the carbohydrate residues are joined to the peptide by O-glycosidic links with threonine, and possibly with serine.

Effects of diltiazem and verapamil on ADP-induced rabbit platelet shape change and aggregation.

1. The effects of diltiazem and verapamil (two structurally different calcium channel blockers) were examined on the rabbit platelets shape change and aggregation induced by adenosine-5'-diphosphate (ADP). 2. ADP was a much more potent stimulator on inducing platelet shape change (ED50 = 1 x 10(-7)) than platelet aggregation (ED50 = 1.78 x 10(-6)). 3. Both drugs similarly inhibited ADP-induced platelet shape change and aggregation at concentrations more than 300 microM. 4. There were no significant differences in inhibitory effects of either diltiazem or verapamil on ADP-induced platelet shape change and aggregation. 5. The inhibitory effects of diltiazem and verapamil on ADP-induced platelet shape change and aggregation at high concentrations may be due to their non specific properties.

Orthodontic, genetic, and periodontal considerations in the treatment of impacted maxillary central incisors: A study of twins.

Treatment of twins each with one impacted maxillary central incisor and a mesiodens is described. Treatment included rapid expansion, extraction of the mesiodens, surgical exposure of the impacted central incisor, and its forced eruption. The impacted incisor was brought into functional position in one patient but was lost in the other because of insufficient root length and high mobility. Orthodontic, genetic, and periodontal considerations of these 2 cases are evaluated.

Hemoglobin Wayne: a frameshift mutation detected in human hemoglobin alpha chains.

Hemoglobin Wayne is an alpha chain variant which manifests itself as two minor hemoglobin (Hb) components that migrate more rapidly than Hb A on electrophoresis at pH 8.6. It has been found in a child with Fanconi's anemia and in three generations of the child's family. Each of the minor components yields an alpha chain in which the carboxyl-terminal tripeptide sequence, Lys-Tyr-Arg, has been replaced by the octapeptide sequence Asx-Thr-Val-Lys-Leu-Glu-Pro-Arg. In alpha Wayne I, the slower of the pair, Asx is asparagine, whereas in alpha Wayne II it is aspartic acid. Comparison of the alpha Wayne sequences with the amino-acid sequences of alpha A and alpha Constant Spring leads to the conclusion that Hb Wayne I is the result of a -1 frameshift mutation in the alpha chain and that Hb Wayne II is formed secondarily by spontaneous deamidation of the new asparagine residue. A frameshift is consistent with a single mRNA base sequence for the last eight codons involved and supports the view of Clegg, Weatherall, and Milner [Nature (1971) 234, 337-341] that Hb Constant Spring is the result of a terminator mutation leading to translation of 31 codons not normally translated.