School Water,Sanitation, and Hygiene,Soil-Transmitted Helminths,and Schistosomes: National Mapping in Ethiopia

BackgroundIt is thought that improving water, sanitation, and hygiene (WASH) might reduce the transmission of schistosomes and soil-transmitted helminths, owing to their life cycles. However, few large-scale studies have yet assessed the real extent of associations between WASH and these parasites.Conclusions/SignificanceImproving school WASH may reduce transmission of these parasites. However, different forms of WASH appear to have different effects on infection with the various parasites, with our analysis finding the strongest associations between water and S. mansoni, sanitation and A. lumbricoides, and hygiene and hookworm.     

Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder

Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MBD5 coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders.     

A system for accurate immunolocalization of Tamm-Horsfall protein in renal biopsies

Summary The distribution of Tamm-Horsfall protein (THP) was studied in the human kidney using formalin-fixed, paraffin-embedded sections with a monoclonal antibody specific for human THP applied in conjunction with a modified dinitrophenyl hapten sandwich staining (DHSS) procedure.The method was found to be highly sensitive producing very strong specific staining at antibody dilations up to 1 in 64 000. Counterstaining with Haematoxylin and Eosin was possible without significant masking of the specific staining. This provided excellent structural definition of the background tissue, which proved especially important in the study of THP localization in randomly oriented biopsy material. THP was found in all segments of the thick ascending limbs of loops of Henle, most segments of distal convoluted tubules and occasionally in distended collecting ducts and in the glomerular capsular space. Maculae densae did not contain THP.The combination of the modified DHSS procedure and the human THP specific antibody represents a highly sensitive and reliable method for specific staining of the THP in kidney sections.     

W. Montague Cobb (1904–1990): Physical Anthropologist, Anatomist, and Activist

William Montague Cobb's life and work reflect a profound integration of art, literature, social activism, and science. This article presents some of the highlights of his academic development and professional contributions. We have considered his early academic development within the contexts of the formative years of American physical anthropology, Howard University Medical School, and the social issues in American society that influenced Cobb. His approaches to teaching, anatomical and anthropological research, and medicine are unique, and yet are closely reasoned and creative reflections of the major currents of academe and the broader society with which he dealt. Imbued with a sense of social responsibility, Cobb's applied anthropology involved the accumulation of extensive data on the one hand, and the formation of organizations for social activism on the other. It was directed toward solving problems of health care and racism. His work thereby served to balance the widespread distortion and neglect of medical and racial problems facing A fro-America between 1930 and the present day. He was also a principal builder of black medical and scientific institutions, and he preserved the record of his coworkers' contributions through his many biographies. This work represents no more than a sketch of his rich and prolific career (during which he produced more than 1,100 publications); the emphasis of this biographical study has been to ascertain the circumstances and attitudes that helped mold the first Afro-American Ph.D. in physical anthropology.     

Structure of cyanide methemoglobin

X-ray difference Fourier analysis at 2.8 Å resolution shows that the tertiary structures of horse cyanide methemoglobin and methemoglobin differ significantly. The conformations of the heme groups and their interactions with the globin are altered. Short contacts with globin side chains affect cyanide binding to the hemes, and the changes in globin-ligand contact upon substitution of cyanide for water in turn directly affect globin structure. Although the ligand peaks lie off the heme axes, the atoms FeCN may still lie on a straight line (as they do in small iron cyanide complexes), with this line not normal to the mean heme plane. This linear binding configuration is consistent with the observed motion and deformation of the porphyrin. Although motion of the iron atoms is not directly apparent, there is evidence that some changes in tertiary structure are induced by shortening of the iron-pyrrol nitrogen bond lengths. This and other studies suggest that the structural changes responsible for co-operativity in hemoglobin may be initiated not merely by an alteration in the covalent porphyrin-proximal histidine linkage, but by changes in the noncovalent interactions of the globin with the ligand and porphyrin as well.