Mutations in Multidomain Protein MEGF8 Identify a Carpenter Syndrome Subtype Associated with Defective Lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed.     

Contribution of the putative heparan sulfate-binding motif BBXB of RANTES to transendothelial migration

The chemokines are a family of small chemoattractant proteins that have a range of functions, including activation and promotion of vectorial migration of leukocytes. Regulation on activation, normal T cell expressed and secreted (RANTES; CCL5), a member of the CC-chemokine subfamily, has been implicated in a variety of immune responses. In addition to the interaction of CC-chemokines with their cognate cell-surface receptors, it is known that they also bind to glycosaminoglycans (GAGs), including heparan sulfate. This potential for binding to GAG components of proteoglycans on the cell surface or within the extracellular matrix might allow formation of the stable chemokine concentration gradients necessary for leukocyte chemotaxis. In this study, we created a panel of mutant RANTES molecules containing neutral amino acid substitutions within putative, basic GAG-binding domains. Despite showing reduced binding to GAGs, it was found that each mutant containing a single amino acid substitution induced a similar leukocyte chemotactic response within a concentration gradient generated by free solute diffusion. However, we found that the mutant K45A had a significantly reduced potential to stimulate chemotaxis across a monolayer of microvascular endothelial cells. Significantly, this mutant bound to the CCR5 receptor and showed a potential to mobilize Ca(2+) with an affinity similar to the wild-type protein. These results show that the interaction between RANTES and GAGs is not necessary for specific receptor engagement, signal transduction, or leukocyte migration. However, this interaction is required for the induction of efficient chemotaxis through the extracellular matrix between confluent endothelial cells.     

Quasiperiodic Route to Chaos for the Dust Ion Acoustic Waves in Magnetized Dusty Plasmas

Plasma Physics Reports - Quasiperiodic and chaotic features of the dust ion acoustic (DIA) waves in a magnetized dusty plasma is studied. Reductive perturbation technique (RPT) is used to derive...     

Global patterns of geographic range size in birds

Large-scale patterns of spatial variation in species geographic range size are central to many fundamental questions in macroecology and conservation biology. However, the global nature of these patterns has remained contentious, since previous studies have been geographically restricted and/or based on small taxonomic groups. Here, using a database on the breeding distributions of birds, we report the first (to our knowledge) global maps of variation in species range sizes for an entire taxonomic class. We show that range area does not follow a simple latitudinal pattern. Instead, the smallest range areas are attained on islands, in mountainous areas, and largely in the southern hemisphere. In contrast, bird species richness peaks around the equator, and towards higher latitudes. Despite these profoundly different latitudinal patterns, spatially explicit models reveal a weak tendency for areas with high species richness to house species with significantly smaller median range area. Taken together, these results show that for birds many spatial patterns in range size described in geographically restricted analyses do not reflect global rules. It remains to be discovered whether global patterns in geographic range size are best interpreted in terms of geographical variation in species assemblage packing, or in the rates of speciation, extinction, and dispersal that ultimately underlie biodiversity.     

9,10-seco-9,19-Cyclolanostane arabinosides from the roots of Actaea podocarpa

Seven 9,10-seco-9,19-cyclolanostane arabinosides, named podocarpasides A-G (1-7), were isolated from the roots of Actaea podocarpa DC., a species closely related to black cohosh (a well known dietary supplement). Their structures were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The isolates were found inactive, when tested for cytotoxic, estrogenic, and antioxidant activities in cell based assays. They were also tested for anticomplement activity against the classical pathway of complement system and only podocarpaside C (3) inhibited modest complement activity with an IC50 value of 200 microM.     

A new sighting of the Mediterranean Monk Seal,Monachus monachus (Hermann, 1779), in the Marmara Sea (Turkey)

Rhagodes Pocock, 1897 is the most speciose genus within the family Rhagodidae and species diagnosis is often very difficult. We found Rhagodes eylandti (Walter, 1889) for the first time again since the 1930s and redescribe some morphological features of the male and compare them with the literature. The main diagnostic characters are illustrated.     

Leishmania species: Detection and identification by nested PCR assay from skin samples of rodent reservoirs

Many rodent species act as reservoir hosts of zoonotic cutaneous leishmaniasis in endemic areas. In the present study a simple and reliable assay based on nested PCR was developed for the detection and identification of Leishmania parasites from rodent skin samples. We designed Leishmania-specific primers that successfully amplified ITS regions of Leishmania major, Leishmania gerbilli and Leishmania turanica using nested PCR. Out of 95 field collected Rhombomys opimus, 21 were positive by microscopic examination and 48 by nested PCR. The percentage of gerbils infected with L. major, L. gerbilli and L. turanica was 3.2%, 1.1% and 27.4%, respectively. In 15.8% of the rodents, we found mixed natural infections by L. major and L. turanica, 1.1% by L. major and L. gerbilli, and 2.1% by the three species. We concluded that this method is simple and reliable for detecting and identifying Leishmania species circulating in rodent populations.     

Inter-Segmental Coordination Pattern in Patients with Anterior Cruciate Ligament Deficiency during a Single-Step Descent

Anterior cruciate ligament injury is a debilitating pathology which may alter lower limb coordination pattern in both intact and affected lower extremities during activities of daily living. Emerging evidence supports the notion that kinematic variables may not be a good indicator to differentiate patients with anterior cruciate ligament deficiency during step descent task. The aim of the present study was to examine alterations in kinematics as well as coordination patterns and coordination variability of both limbs of these patients during a single step descent task. Continuous relative phase technique was used to measure coordination pattern and coordination variability between a group of anterior cruciate ligament deficient (n = 23) and a healthy control group (n = 23). A third order polynomial Curve fitting was utilized to provide a curve that best fitted to the data points of coordination pattern and coordination variability of the healthy control group. This was considered as a reference to compare to that of patient group using nonlinear regression analysis. The results of the present study demonstrated an altered coordination pattern of the supporting shank-thigh and the stepping foot-shank couplings in anterior cruciate ligament deficient subjects. It was further noticed that there was an increased coordination variability in foot-shank and shank-thigh couplings of both supporting and stepping legs. There was no significant difference in the hip, knee and ankle joints kinematics in either side of these patients. Anterior cruciate ligament deficient individuals showed altered strategies in both intact and affected legs, with increased coordination variability. Kinematic data did not indicate any significant difference between the two groups. It could be concluded that more sophisticated dynamic approach such as continuous relative phase would uncover discrepancies between the healthy and anterior cruciate ligament deficient individuals.