Epidermolysis bullosa dystrophica treated with vitamin E and oral corticosteroids

A 12-year-old boy with histologically proved epidermolysis bullosa dystrophica was treated daily with 10,000 IU of DL-alphatocopheryl acetate and prednisone 120 mg. Comparison of a control study period of seven weeks with the period during which vitamin E was given revealed no significant improvement. The same negative results were noted with the use of prednisone although the levels believed necessary to produce improvement were never attained owing to supervening infection.     

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.     

Population Genetics of the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) across Multiple Spatial Scales

Conservation genetics is a powerful tool to assess the population structure of species and provides a framework for informing management of freshwater ecosystems. As lotic habitats become fragmented, the need to assess gene flow for species of conservation management becomes a priority. The eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a large, fully aquatic paedamorphic salamander. Many populations are experiencing declines throughout their geographic range, yet the genetic ramifications of these declines are currently unknown. To this end, we examined levels of genetic variation and genetic structure at both range-wide and drainage (hierarchical) scales. We collected 1,203 individuals from 77 rivers throughout nine states from June 2007 to August 2011. Levels of genetic diversity were relatively high among all sampling locations. We detected significant genetic structure across populations (F_st values ranged from 0.001 between rivers within a single watershed to 0.218 between states). We identified two genetically differentiated groups at the range-wide scale: 1) the Ohio River drainage and 2) the Tennessee River drainage. An analysis of molecular variance (AMOVA) based on landscape-scale sampling of basins within the Tennessee River drainage revealed the majority of genetic variation (∼94–98%) occurs within rivers. Eastern hellbenders show a strong pattern of isolation by stream distance (IBSD) at the drainage level. Understanding levels of genetic variation and differentiation at multiple spatial and biological scales will enable natural resource managers to make more informed decisions and plan effective conservation strategies for cryptic, lotic species.     

Randomization Modeling to Ascertain Clustering Patterns of Human Papillomavirus Types Detected in Cervicovaginal Samples in the United States

Detection of multiple human papillomavirus (HPV) types in the genital tract is common. Associations among HPV types may impact HPV vaccination modeling and type replacement. The objectives were to determine the distribution of concurrent HPV type infections in cervicovaginal samples and examine type-specific associations. We analyzed HPV genotyping results from 32,245 cervicovaginal specimens collected from women aged 11 to 83 years in the United States from 2001 through 2011. Statistical power was enhanced by combining 6 separate studies. Expected concurrent infection frequencies from a series of permutation models, each with increasing fidelity to the real data, were compared with the observed data. Statistics were computed based on the distributional properties of the randomized data. Concurrent detection occurred more than expected with 0 or ≥3 HPV types and less than expected with 1 and 2 types. Some women bear a disproportionate burden of the HPV type prevalence. Type associations were observed that exceeded multiple hypothesis corrected significance. Multiple HPV types were detected more frequently than expected by chance and associations among particular HPV types were detected. However vaccine-targeted types were not specifically affected, supporting the expectation that current bivalent/quadrivalent HPV vaccination will not result in type replacement with other high-risk types.     

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study

Background  

The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS.     

Remnant populations of the regal fritillary (Speyeria idalia) in Pennsylvania: Local genetic structure in a high gene flow species

The Regal Fritillary butterfly, Speyeria idalia (Drury) (Lepidoptera: Nymphalidae), has been described as a high gene flow species. Supporting this assertion, previous studies in the Great Plains, where it is still relatively widespread, have found evidence of gene flow across hundreds of kilometers. Using mitochondrial and microsatellite loci, we examined the spatial genetic structure of a very isolated Pennsylvania population of these butterflies that occupies three separate meadows located within ten kilometers of each other. We found restricted gene flow and a distinct structure, with each meadow having a unique genetic signature. Our findings indicate that even a species that normally exhibits high gene flow may show fine-scale genetic subdivision in areas where populations have been largely extirpated.Authors contributed equally.     

A comparison between inosine- and guanosine-containing anticodons in ribosome-free codon-anticodon binding

Binding of the ribooligomers, AUC, AUU, AUA, AUCA, AUUA, and AUAA to the isoleucine-accepting tRNAs, tRNA${}_{\mathrm{<mtext>T.\; utilis</mtext>}}{}^{\mathrm{Ile}}$ (anticodon, -IAU-) and tRNA${}_{\mathrm{<mtext>E.\; coli</mtext>}}{}^{\mathrm{Ile}}$ (anticodon, -GAU-) was measured by equilibrium dialysis. With the aid of Scatchard plots, AUCA was shown to bind to one site per tRNA molecule, presumably the anticodon. AUA and AUAA did not measurably attach to either anticodon in the ribosome-free system. All other oligomers were bound to tRNA${}_{\mathrm{<mtext>E.\; coli</mtext>}}{}^{\mathrm{Ile}}$ about 5 to 13 times stronger than to tRNA${}_{\mathrm{<mtext>T.\; utilis</mtext>}}{}^{\mathrm{Ile}}$.     

The CD4+AT2R+ T cell subpopulation improves post‐infarction remodelling and restores cardiac function

Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4⁺ AT2R⁺ cells in the rat heart and spleen post‐infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4⁺ AT2R⁺ T cells in circulating blood, post‐infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4⁺ cells. CD4⁺ AT2R⁺ T cells within blood CD4⁺ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4⁺ AT2R⁺ T cells which expressed regulatory FoxP3, secreted interleukin‐10 and other inflammatory‐related cytokines. Furthermore, intramyocardial injection of MI‐induced splenic CD4⁺ AT2R⁺ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4⁺ AT2R⁺ cells as a T cell subset improving heart function post‐MI corresponding with reduced infarction size in a rat MI‐model. Our results indicate CD4⁺ AT2R⁺ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.     

Late Quaternary (Weichselian) alluvial history and neotectonic control on fluvial landscape development in the southern Körös plain,Hungary

Four drill cores and a clay pit section have been examined in the southern part of the Körös plain to understand the history and controls on alluvial sedimentation for the last ~ 40 ka. Four facies groups were identified, such as channel, channel margin, floodplain and floodbasin with seven distinctive facies. Magnetic susceptibility and mineralogy have further characterized the sedimentary facies indicating shifts in humidity conditions, variations in sediment flux and pedogenesis. Detailed pollen analysis of a 7.5 m thick clayey succession indicated climatic variability within the MIS 3 period. The spatial distribution of the different facies allowed outlining alluvial architecture of the study area. Three depositional units composed of various facies were identified based on OSL and radiocarbon data. These packages correspond to three major phases of channel activity: (F-I) pre-LGM period (> 30 ka to 24 ka), (F-II) post-LGM interstadial (18–16 ka), and (F-III) Late Glacial < 15 ka to ~ 10 ka). The pre-LGM and post-LGM “interstadial” phases are characterized by meandering river patterns, while the Late Glacial fluvial activity is characterized by a braided system in the area. Higher sediment supply feeding this braided river was probably caused by neotectonic uplift of the southern margin of the basin, documented by a significant stratigraphic gap between 25 and 14 ka.