Characterization of the

The isotope ^{163}Ho is in many ways the best candidate to perform experiments to investigate the value of the electron neutrino mass. It undergoes an electron capture process to ^{163}Dy with an energy available to the decay, Q_{EC}, of about 2.8 keV. According to the present knowledge, this is the lowest Q_{EC} value for such transitions. Here we discuss a newly obtained spectrum of ^{163}Ho, taken by cryogenic metallic magnetic calorimeters with ^{163}Ho implanted in the absorbers and operated in anticoincident mode for background reduction. For the first time, the atomic deexcitation of the ^{163}Dy daughter atom following the capture of electrons from the 5s shell in ^{163}Ho, the OI line, was observed with a calorimetric measurement. The peak energy is determined to be 48 eV. In addition, a precise determination of the energy available for the decay Q_{EC}=(2.858±0.010_{stat}±0.05_{syst}) keV was obtained by analyzing the intensities of the lines in the spectrum. This value is in good agreement with the measurement of the mass difference between ^{163}Ho and ^{163}Dy obtained by Penning-trap mass spectrometry, demonstrating the reliability of the calorimetric technique.

What do windsurfers and kitesurfers in Germany know about surfer's ear and how is it influenced by protective measures?

OBJECTIVE: This study investigated the frequency of ear canal protection use and looked at its influence on external auditory exostosis severity and knowledge about external auditory exostosis among windsurfers and kitesurfers on the German coast. METHOD: This retrospective cross-sectional study interviewed 130 windsurfers and kitesurfers along the German coast on knowledge of external auditory exostosis, exposure time, use of neoprene hoods and earplugs, and otological complaints. Participants underwent bilateral video-otoscopic examination. RESULTS: Knowledge of external auditory exostosis was 'good' or 'excellent' in 78 of 130 (60 per cent) individuals and 'poor' or non-existent in 52 of 130 (40 per cent) individuals. Knowledge was positively correlated with hours of exposure, otological complaints and frequency of ear canal protection use. A significant negative influence of neoprene hood use on external auditory exostosis severity was shown. CONCLUSION: The positive effect of external auditory exostosis knowledge on the frequency of ear canal protection and the reduction of external auditory exostosis risk implies a need for health education on this topic.

SOX10 mutations in patients with Waardenburg-Hirschsprung disease.

Waardenburg syndrome (WS; deafness with pigmentary abnormalities) and Hirschsprung's disease (HSCR; aganglionic megacolon) are congenital disorders caused by defective function of the embryonic neural crest. WS and HSCR are associated in patients with Waardenburg-Shah syndrome (WS4), whose symptoms are reminiscent of the white coat-spotting and aganglionic megacolon displayed by the mouse mutants Dom (Dominant megacolon), piebald-lethal (sl) and lethal spotting (ls). The sl and ls phenotypes are caused by mutations in the genes encoding the Endothelin-B receptor (Ednrb) and Endothelin 3 (Edn3), respectively. The identification of Sox10 as the gene mutated in Dom mice (B.H. et al., manuscript submitted) prompted us to analyse the role of its human homologue SOX10 in neural crest defects. Here we show that patients from four families with WS4 have mutations in SOX10, whereas no mutation could be detected in patients with HSCR alone. These mutations are likely to result in haploinsufficiency of the SOX10 product. Our findings further define the locus heterogeneity of Waardenburg-Hirschsprung syndromes, and point to an essential role of SOX10 in the development of two neural crest-derived human cell lineages.

Effect of different vaccination programs on production parameters, carcass, leg bones, and digestive system characteristics of broilers.

The purpose of the present study was to compare the effects of two commercial vaccination programs using Prevexxion or Vaxxitek vaccines on production parameters, carcass weight and composition, and selected anatomical characteristics of Ross 308 broiler chickens. During the rearing period of broiler chickens, body weights were determined at 1, 10, 35, and 42 d of age, and feed intake and mortality of birds were recorded each day. On d 42 of the rearing period, 20 chickens were selected for dissection, 10 birds from each group. After slaughtering, the weight of the eviscerated carcass and the proportion of carcass elements, the lengths and diameters of individual intestinal segments, the weight of selected internal organs, and the dimensions of the femur and tibia were determined. The Prevexxion vaccination program had a positive significant effect on eviscerated carcass yield, dressing percentage, breast meat, wing and carcass remains content, as well as duodenum length, proventriculus content of slaughter weight and smallest breadth of the corpus of tibia bone. Broiler chickens treated with Prevexxion vaccines had higher European Production Index. The results indicate that Prevexxion vaccines have a more favorable effect on the production performance and slaughter characteristics of Ross 308 broiler chickens than with the use of Vaxxitek vaccines.

Sox11 regulates survival and axonal growth of embryonic sensory neurons.

Sensory neurons transduce various stimuli including temperature, pain, and touch from the periphery to the central nervous system. Sensory neuron development is governed by a combination of extracellular cues and specific gene expression. We demonstrated that the transcription factor Sox11 was highly expressed in the developing sensory neurons. To test the function of Sox11, we used a knockin mouse model where the entire coding region of Sox11 was replaced by a LacZ reporter. The ablation of Sox11 caused severe reduction in sensory neuron survival in the trigeminal and dorsal root ganglia, although it did not affect migration of neural crest cells or acquisition of major sensory neuron subtypes. We further demonstrated that ablating Sox11 caused an arrest of axonal outgrowth in vivo and in vitro. This defect could not be fully rescued by blocking cell death. Our data suggest that Sox11 is a key regulator of sensory neuron development.

POU-domain proteins: structure and function of developmental regulators.

POU-domain proteins are a group of developmental regulators found in organisms as distant as worm and man. The sequence conservation of the POU-domain has allowed the characterization of increasing numbers of proteins containing the domain, many of which act to control the generation and maintenance of differentiated cell phenotypes in organs as diverse as skin and brain. Analysis of the means by which POU-domain proteins regulate transcription has led to a further understanding of how this group initiates specific developmental programs.

A system to measure seat-human interaction parameters which might be comfort relevant.

In this paper a measurement tool is described and tested to evaluate the characteristics of different elements of a seat. Many studies report a relationship between discomfort and pressure distribution, but it is unknown what exactly is happening in the interaction. The purpose of this study is to present a measuring device, which records the comfort relevant seat parameters pressure and elongation while loading a seat. The results of the study, including the repeatability, reproducibility and detectability show that the measurement method is appropriate for our purpose, although the reproducibility has to be improved by operator experience or by a more intuitive assembling of the measurement setup. An application example illustrates that the interaction of the seat components highly affect the resulting comfort relevant parameters. The question is whether this objectively recorded differences are also experienced by seat occupants, which is interesting to study in future research.

Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta.

Alterations in intracellular calcium levels activate several signal transduction pathways resulting in distinct patterns of gene expression. Here, a pathway for calcium-mediated signals is demonstrated that involves C/EBP beta, a member of the bZip family of transcription factors. In pituitary cells C/EBP beta was phosphorylated in response to increased intracellular calcium concentrations as a consequence of the activation of a calcium-calmodulin-dependent protein kinase. Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.

Variable effects of phosphorylation of Pit-1 dictated by the DNA response elements.

Pit-1, a tissue-specific POU domain transcription factor, is required for the activation of the prolactin, growth hormone, and Pit-1 promoters that confer regulation by epidermal growth factor, adenosine 3',5'-monophosphate (cAMP), and phorbol esters. Pit-1 is phosphorylated in pituitary cells at two distinct sites in response to phorbol esters and cAMP. Phosphorylation of Pit-1 modifies its conformation on DNA recognition elements and results in increased binding at certain sites and decreased binding at other sites, dependent on DNA sequences adjacent to the core Pit-1 binding motif. One residue (Thr220), located in the POU homeodomain within a sequence conserved throughout the POU-domain family, confers these responses.

Surface properties of lunar samples.

Fine-grained samples disrupted after exposure to oxygen and oxygen with 3.5 percent water above 2 torr. Chemical etching revealed plastic deformation in some samples, adhesion due to impact melting in others, dislocations in crystalline phases and evidence that some glasses were partially devitrified. Specimens of rock that were fractured in ultrahigh vacuum exhibited a time-dependent adhesion and a network of localized electrostatically charged areas.

Bone morphogenetic proteins are required in vivo for the generation of sympathetic neurons.

Bone morphogenetic proteins (BMPs) induce autonomic neurogenesis in neural crest cultures and stimulate sympathetic neuron development when overexpressed in vivo. We demonstrate that inhibition of BMPs in the chick embryo bythe BMP antagonist Noggin prevents sympathetic neuron generation. In Noggin-treated embryos, the noradrenergic marker genes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), panneuronal neurofilament 160 (NF160) and SCG10 genes, and the transcriptional regulators Phox2b and Phox2a are not expressed in sympathetic ganglia. Whereas initial ganglion development is not affected, the expression of the basic helix-loop-helix transcription factor Cash-1 is strongly reduced. These results demonstrate that BMPs are essential for sympathetic neuron development and establish Cash-1 and Phox2 genes as downstream effectors of BMPs in this lineage.

The first detection of Senecavirus A in pigs in Thailand, 2016.

We report the first detection of Senecavirus A (SVA) in nine of 12 (75%) pigs in Thailand in 2016. The full-length genome demonstrated that Thai SVA isolates were closely related to the first Canada strain (11-55910-3) than the recent strains causing outbreaks in Brazil, the United States and China in 2015-2016.

Chronicles of a switch hunt: gcm genes in development.

Co-conservation of sequence and function is an important principle during evolution. As a consequence, sequence-related genes often have similar functions in evolutionarily distant species. Enter the 'glial cells missing' (gcm) genes. They code for a small family of novel transcription factors that share DNA-binding properties and domain structure. However, no evolutionarily conserved function is apparent as yet. The prototypical gcm from Drosophila dominates nervous system development as a fate switch and master regulator of gliogenesis, whereas mammalian gcm genes have roles in placental morphogenesis and development of the parathyroid gland. Apparently, structure and function sometimes can go separate ways.

The J domain of papovaviral large tumor antigen is required for synergistic interaction with the POU-domain protein Tst-1/Oct6/SCIP.

Large T antigens from polyomaviruses are multifunctional proteins with roles in transcriptional regulation, viral DNA replication, and cellular transformation. They have been shown to enhance the activity of various cellular transcription factors. In the case of the POU protein Tst-1/Oct6/SCIP, this enhancement involves a direct physical interaction between the POU domain of the transcription factor and the amino-terminal region of large T antigen. Here we have analyzed the structural requirements for synergistic interaction between the two proteins in greater detail. Tst-1/Oct6/SCIP and the related POU protein Brn-1 were both capable of direct physical interaction with large T antigen. Nevertheless, only Tst-1/Oct6/SCIP functioned synergistically with large T antigen. This differential behavior was due to differences in the amino-terminal regions of the proteins, as evident from chimeras between Tst-1/Oct6/SCIP and Brn-1. Synergy was specifically observed for constructs containing the amino-terminal region of Tst-1/Oct6/SCIP. Large T antigen, on the other hand, functioned synergistically with Tst-1/Oct6/SCIP only when the integrity of its J-domain-containing amino terminus was maintained. Mutations that disrupted the J domain concomitantly abolished the ability to enhance the function of Tst-1/Oct6/SCIP. The J domain of T antigen was also responsible for the physical interaction with Tst-1/Oct6/SCIP and could be replaced in this property by other J domains. Intriguingly, a heterologous J domain from a human DnaJ protein partially substituted for the amino terminus of T antigen even with regard to the synergistic enhancement of Tst-1/Oct6/SCIP function. Given the general role of J domains, we propose chaperone activity as the underlying mechanism for synergy between Tst-1/Oct6/SCIP and large T antigens.

Idiopathic weight reduction in mice deficient in the high-mobility-group transcription factor Sox8.

Sox8, Sox9, and Sox10 constitute subgroup E within the Sox family of transcription factors. Many Sox proteins are essential regulators of development. Sox9, for instance, is required for chondrogenesis and male sex determination; Sox10 plays key roles in neural crest development and peripheral gliogenesis. The function of Sox8 has not been studied so far. Here, we generated mice deficient in this third member of subgroup E. In analogy to the case for the related Sox9 and Sox10, we expected severe developmental defects in these mice. Despite strong expression of Sox8 in many tissues, including neural crest, nervous system, muscle, cartilage, adrenal gland, kidney, and testis, homozygous mice developed normally in utero, were born at Mendelian frequencies, and were viable. A substantial reduction in weight was observed in these mice; however, this reduction was not attributable to significant structural deficits in any of the Sox8-expressing tissues. Because of frequent coexpression with either Sox9 or Sox10, the mild phenotype of Sox8-deficient mice might at least in part be due to functional redundancy between group E Sox proteins.

Protein zero gene expression is regulated by the glial transcription factor Sox10.

Myelinating glia express high levels of a unique set of genes which code for structural proteins of the myelin sheath. Few transcription factors have so far been implicated in the regulation of any myelin gene. Here we show that the protein zero (P(0)) gene, a myelin gene exclusively expressed in the Schwann cell lineage of the peripheral nervous system, is controlled in its expression by the high-mobility-group domain protein Sox10 both in tissue culture and in vivo. Induction of wild-type Sox10, but not of other transcription factors or Sox10 mutants, strongly increased endogenous P(0) expression in tissue culture. This activation was mediated by the P(0) promoter, which was stimulated by Sox10 in transient transfections. Detailed analyses revealed the involvement of a proximal and a distal promoter region. The distal region functioned only in conjunction with the proximal one and contained a single Sox consensus binding site, which accounted for most of its activity. In contrast, the proximal region mediated Sox10 responsiveness on its own. It contained multiple binding sites for Sox proteins, with two high-affinity sites being the most significant. P(0) expression also depended on Sox10 in vivo, as evident from the analysis of Schwann cell precursors in mouse embryos with Sox10 mutation at day 12.5 of embryogenesis. To our knowledge this is the most conclusive link to date between a glial transcription factor and cell-specific activation of myelin gene expression.

Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y.

The POU domain protein Tst-1/Oct-6 is a transcriptional activator of human papovavirus JC virus in transient transfections. Because of its endogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. Activation of viral early and late genes depends on the ability of Tst-1/Oct-6 to interact with an AT-rich element within the viral regulatory region. Here, we show that this element not only is bound by Tst-1/Oct-6 but, in addition, serves as a binding site for the high-mobility-group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct-6 binding was observed on a site that did not allow binding of HMG-I/Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. These results point to an accessory role for HMG-I/Y in the activation of JC viral gene expression by the POU domain protein Tst-1/Oct-6. In agreement with such a role, HMG-Y synergistically supported the function of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y.

Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa.

The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, with mice dying between 9.5 and 10 days postcoitum. At the time of death, no abnormalities were apparent in the embryo proper. Nervous system development, in particular, was not impaired, as might have been expected in analogy to Drosophila GCM. Instead, placental failure was the cause of death. In agreement with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood. Only a few fetal blood vessels entered the placenta, and these failed to thrive and branch normally. Labyrinthine trophoblasts did not differentiate. All other layers of the placenta, including spongiotrophoblast and giant cell layer, formed normally. Our results indicate that mGCMa plays a critical role in trophoblast differentiation and the signal transduction processes required for normal vascularization of the placenta.

Improving community knowledge of obstetric fistula prevention and treatment.

In recent years, information has emerged in the scientific literature regarding the experience of physicians and clinical staff who try to prevent and treat obstetric fistulas at health facilities in developing countries. However, little is known about attempts to match the services they provide with policy and programmatic interventions in the communities they serve. To determine what is known about community involvement in the prevention and treatment of obstetric fistulas, the authors inquired into experiments carried out by EngenderHealth and partners in 15 African and Asian countries. From raw data, gray literature, and personal communications with those working in the field, they learned that engaging the community may be the keystone in the eradication of fistulas in low-resource settings, and they learned how to engage the community.