Oligodendrocyte Precursor Cells Synthesize Neuromodulatory Factors

NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling.     

Cholesterol-related gene variants are associated with diabetes in coronary artery disease patients

Molecular Biology Reports - Coronary artery disease (CAD) which is a complex cardiovascular disease is the leading cause of death worldwide. The changing prevalence of the disease in different...     

E. coli RNase I exhibits a strong Ca2+-dependent inherent double-stranded RNase activity

Since its initial characterization, Escherichia coli RNase I has been described as a single-strand specific RNA endonuclease that cleaves its substrate in a largely sequence independent manner. Here, we describe a strong calcium (Ca²⁺)-dependent activity of RNase I on double-stranded RNA (dsRNA), and a Ca²⁺-dependent novel hybridase activity, digesting the RNA strand in a DNA:RNA hybrid. Surprisingly, Ca²⁺ does not affect the activity of RNase I on single stranded RNA (ssRNA), suggesting a specific role for Ca²⁺ in the modulation of RNase I activity. Mutation of a previously overlooked Ca²⁺ binding site on RNase I resulted in a gain-of-function enzyme that is highly active on dsRNA and could no longer be stimulated by the metal. In summary, our data imply that native RNase I contains a bound Ca²⁺, allowing it to target both single- and double-stranded RNAs, thus having a broader substrate specificity than originally proposed for this traditional enzyme. In addition, the finding that the dsRNase activity, and not the ssRNase activity, is associated with the Ca²⁺-dependency of RNase I may be useful as a tool in applied molecular biology.     

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

Human cytomegalovirus can cause a diverse range of diseases in different immunocompromised hosts. The pathogenic mechanisms underlying these diseases have not been fully elucidated, though the maximal viral load during infection is strongly correlated with the disease. However, concentrating on single viral load measures during infection ignores valuable information contained during the entire replication history up to the onset of disease. We use a statistical model that allows all viral load data sampled during infection to be analysed, and have applied it to four immunocompromised groups exhibiting five distinct cytomegalovirus-related diseases. The results show that for all diseases, peaks in viral load contribute less to disease progression than phases of low virus load with equal amount of viral turnover. The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases.     

Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish

Bone morphogenetic protein 1 (BMP1) is an astacin metalloprotease with important cellular functions and diverse substrates, including extracellular-matrix proteins and antagonists of some TGFβ superfamily members. Combining whole-exome sequencing and filtering for homozygous stretches of identified variants, we found a homozygous causative BMP1 mutation, c.34G>C, in a consanguineous family affected by increased bone mineral density and multiple recurrent fractures. The mutation is located within the BMP1 signal peptide and leads to impaired secretion and an alteration in posttranslational modification. We also characterize a zebrafish bone mutant harboring lesions in bmp1a, demonstrating conservation of BMP1 function in osteogenesis across species. Genetic, biochemical, and histological analyses of this mutant and a comparison to a second, similar locus reveal that Bmp1a is critically required for mature-collagen generation, downstream of osteoblast maturation, in bone. We thus define the molecular and cellular bases of BMP1-dependent osteogenesis and show the importance of this protein for bone formation and stability.     

The cultural contagion of conflict

Anecdotal evidence abounds that conflicts between two individuals can spread across networks to involve a multitude of others. We advance a cultural transmission model of intergroup conflict where conflict contagion is seen as a consequence of universal human traits (ingroup preference, outgroup hostility; i.e. parochial altruism) which give their strongest expression in particular cultural contexts. Qualitative interviews conducted in the Middle East, USA and Canada suggest that parochial altruism processes vary across cultural groups and are most likely to occur in collectivistic cultural contexts that have high ingroup loyalty. Implications for future neuroscience and computational research needed to understand the emergence of intergroup conflict are discussed.     

House dust mite fauna in western Anatolia, Turkey

House dust mites play an important role in the pathogenesis of allergic diseases. Many factors may influence mite growth. The presence of mites is related to mean temperature and humidity as well as altitude. The aim of this study was to analyze the mite fauna in 5 regions of western Anatolia, Turkey, that have similar climatic properties with low mean temperature and humidity, but differ in altitude. During the period October-November 2004, house dust was collected from 290 homes in 5 different cities. House dust mites were isolated in 67 (23.1%) of 290 samples. The family Pyroglyphidae (Astigmata) was present in all positive samples. This study suggests that the selected western Anatolian regions that share similar environmental conditions host similar dust mite populations.     

Axial pattern composite prefabrication of high-density porous polyethylene: experimental and clinical research

Currently, various alloplastic materials are being used for reconstruction of three-dimensional structures, and high-density porous polyethylene is so far the best and the most commonly used material. Various indications for high-density porous polyethylene have been defined for closure of craniofacial defects, correction of congenital anomalies, and aesthetic augmentations. A common property of various studies published so far is that after being fixed to the bone or underlying structures, high-density porous polyethylene has been covered primarily or by skin flaps. For reconstruction of complex three-dimensional structures such as the ear and nose, the success of current methods is limited by the thinness and pliability of the skin flap. In this study, the authors' aim was to investigate the graftability of high-density porous polyethylene after prefabrication with an axial pedicle and to explore possible clinical applications in light of the new data obtained. In the experimental study, three-dimensional implants (rectangular prism) carved from high-density porous polyethylene were prefabricated using bilateral superficial epigastric arteries and veins of 25 New Zealand rabbits. After a waiting period of 2 to 6 weeks in five groups, control samples were obtained and the prefabricated implants that had been left in place were directly grafted. The results showed that high-density porous polyethylene was vascularized 75 percent after 4 weeks and 90 percent after 5 weeks, and 95 percent of the grafts had survived after 8 weeks. In the clinical study, three nose defects, three ear defects, and one hard palate defect in seven patients ranging in age from 21 to 72 years were reconstructed using the same method. High-density porous polyethylene has been prefabricated and directly grafted for the very first time on a clinical basis. No serious complications have been observed, except for minimal graft loss in two patients. It is obvious that full-thickness skin grafts that are thinner than flaps will adapt better to the fine details of high-density porous polyethylene and will highly increase the detail obtained in the reconstruction of three-dimensional defects.