Production of ordered silicon nanocrystals by low-energy ion sputtering

We report on the production of ordered assemblies of silicon nanostructures by means of irradiation of a Si(100) substrate with 1.2 keV Ar ions at normal incidence. Atomic Force and High-Resolution Transmission Electron microscopies show that the silicon structures are crystalline, display homogeneous height, and spontaneously arrange into short-range hexagonal ordering. Under prolonged irradiation (up to 16 hours) all dot characteristics remain largely unchanged and a small corrugation develops at long wavelengths. We interpret the formation of the dots as a result of an instability due to the sputtering yield dependence on the local surface curvatureComment: 4 two-column pages (revtex4), 3 figures (higher quality copies in the printed jrnl. version

Combination of qualitative and quantitative methods for developing a new Health Related Quality of Life measure for patients with anogenital warts

BACKGROUND: Anogenital warts are the most easily recognized sign of genital Human Papilloma Virus infection. The objective was to develop a short, valid and reliable questionnaire to measure Health Related Quality of Life (HRQL) in patients with anogenital warts. METHODS: First a literature review was performed to identify relevant papers describing the impact of anogenital warts in HRQL; second the main domains were identified by some experts in a focus group, and third in-depth-semi-structured interviews were conducted in patients with anogenital warts to identify the initial set of items. A qualitative reduction of the initial set of items was performed based on the mean scoring of the experts for the three scales: clarity, frequency and importance. The initial questionnaire was pilot tested in 135 patients. Rasch analysis was performed with the results of the questionnaire in order to refine the instrument. Spearman's correlation was calculated between the initial questionnaire and the reduced version. Additionally the measurement properties (validity and reliability) of the resulting final questionnaire were tested and compared using standard procedures (Cronbach's Alpha and item-total correlation). RESULTS: the main domains identified as affected in patient's life were: sexual, colleagues and partner relationships. After a proper qualitative reduction the initial set of 134 items was reduced to 22. The questionnaire was pilot tested in 135 patients and two dimensions were identified after the multifactorial analysis: emotional dimension and sexual activity dimension. As a result of the Rasch analysis the questionnaire was reduced to 10 items. High correlation was found between the initial and the reduced version for the two dimensions. Cronbach's alpha values were acceptable (0.86). CONCLUSION: The initial 22 items questionnaire was reduced by Rasch analysis to a version of 10 items, with two dimensions: emotional and sexual. The results suggest the adequacy of the 10 items to evaluate HRQL of patients with anogenital warts in a valid and reliable way

Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction

The following are available online at https://www.mdpi.com/article/ 10.3390/genes14040831/s1A.A.M.S. received a scholarship from the Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Devel- opment Program. O.A.K. was supported by the US National Institutes of Health (NIH)—National Institute on Deafness and Other Communication Disorders (NIDCD) grant T32 DC012280 (to Sue C. Kinnamon and Herman A. Jenkins). This work was supported by the NIH through the NIDCD grants R01 DC019642 (to R.L.P.S.-C. and Ivana V. Yang) and R01 DC013912 (to S.P.G.); and the National Insti- tute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR068292 (to N.H.-M.). Funding was also provided by Junta de Andalucia, grant Retos en Investigacion PY20_00303 (to J.A.L.-E.).Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere’s disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere’s disease, and 38 European–American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere’s disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease.Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Development ProgramUS National Institutes of Health (NIH)-National Institute on Deafness and Other Communication Disorders (NIDCD) T32 DC012280NIH through the NIDCD R01 DC019642, R01 DC013912United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01 AR068292Junta de Andalucia PY20_0030

G6PD overexpression protects from oxidative stress and age-related hearing loss

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: MINECO/FEDER SAF2017-86107-R; Comunidad de Madrid, Grant/Award Number: FEDER/CM-B2017/BMD-368

Inhibition of granulomatous inflammation and prophylactic treatment of schistosomiasis with a combination of edelfosine and Praziquantel

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Background]: Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. This parasitic disease is due to immunologic reactions to Schistosoma eggs trapped in tissues. Egg-released antigens stimulate tissue-destructive inflammatory and granulomatous reactions, involving different immune cell populations, including T cells and granulocytes. Granulomas lead to collagen fibers deposition and fibrosis, resulting in organ damage. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. [Methodology/Principal Findings]: Using in vitro and in vivo approaches, we have found that the alkylphospholipid analog edelfosine kills schistosomula, and displays anti-inflammatory activity. The combined treatment of PZQ and edelfosine during a few days before and after cercariae infection in a schistosomiasis mouse model, simulating a prophylactic treatment, led to seven major effects: a) killing of Schistosoma parasites at early and late development stages; b) reduction of hepatomegaly; c) granuloma size reduction; d) down-regulation of Th1, Th2 and Th17 responses at late post-infection times, thus inhibiting granuloma formation; e) upregulation of IL-10 at early post-infection times, thus potentiating anti-inflammatory actions; f) down-regulation of IL-10 at late post-infection times, thus favoring resistance to re-infection; g) reduction in the number of blood granulocytes in late post-infection times as compared to infected untreated animals. [Conclusions/Significance]: Taken together, these data suggest that the combined treatment of PZQ and edelfosine promotes a high decrease in granuloma formation, as well as in the cellular immune response that underlies granuloma development, with changes in the cytokine patterns, and may provide a promising and effective strategy for a prophylactic treatment of schistosomiasis.This work was supported by grants from the Junta de Castilla y León (SA342U13, CSI052A11-2, and CSI221A12-2), Real Federación Española de Fútbol-Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013), Spanish Ministerio de Economía y Competitividad (SAF2011-30518, SAF2014-59716-R, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), and European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS).Peer Reviewe

Visual acuity of pseudophakic patients predicted from in-vitro measurements of intraocular lenses with different design

Postprint (published version

Mammal and tree diversity accumulate different types of soil organic matter in the northern Amazon

Diversity of plants and animals influence soil carbon through their contributions to soil organic matter (SOM). However, we do not know whether mammal and tree communities affect SOM composition in the same manner. This question is relevant because not all forms of carbon are equally resistant to mineralization by microbes and thus, relevant to carbon storage. We analyzed the elemental and molecular composition of 401 soil samples, with relation to the species richness of 83 mammal and tree communities at a landscape scale across 4.8 million hectares in the northern Amazon. We found opposite effects of mammal and tree richness over SOM composition. Mammal diversity is related to SOM rich in nitrogen, sulfur and iron whereas tree diversity is related to SOM rich in aliphatic and carbonyl compounds. These results help us to better understand the role of biodiversity in the carbon cycle and its implications for climate change mitigation.Xunta de Galicia | ED481D 2019/024Xunta de Galicia | ED431C2021/32European Commission | Ref. H2020, n. 947921National Science Foundation (NSF) | BE/CNH 05 0809

Bases genéticas, moleculares y bioquímicas del envejecimiento auditivo ¿Qué nos enseñan los modelos experimentales

Age-related hearing loss (ARHL) affects one in three people older than 65 years and is the most prevalent sensorineural deficit. This type of hearing loss precedes and accelerates the onset of cognitive impairment and is associated with an increased risk for neurodegenerative diseases such as dementia and Alzheimer disease. The onset and progression of ARHL is influenced by genetic factors, which are still poorly understood, and environmental factors, which in particular include exposure to excessive noise and ototoxic substances. At present, no effective drug treatments are available for ARHL prevention or treatment, and therefore research in this field is a priority. In the research field, animal models offer a crucial tool for i) identifying new genes associated with ARHL, ii) understanding the cellular and molecular basis of auditory ageing and iii) defining new therapeutic targets and evaluating candidate treatments.La presbiacusia afecta a una de cada tres personas mayores de 65 años y constituye el déficit neurosensorial más prevalente. Antecede a la aparición de la fragilidad cognitiva, la acelera y se asocia con un mayor riesgo de padecer enfermedades neurodegenerativas como la demencia o el Alzheimer. La aparición y evolución de la presbiacusia están influidas por factores genéticos, todavía poco conocidos, y ambientales, entre los que destacan la exposición a ruido excesivo o a sustancias ototóxicas. En la actualidad no disponemos de tratamientos farmacológicos eficaces para prevenir o tratar la presbiacusia, por lo que la investigación en este campo es prioritaria. En este contexto, los modelos animales son una herramienta esencial para: a) identificar nuevos genes de presbiacusia, b) comprender las bases celulares y moleculares del envejecimiento auditivo, y c) definir nuevas dianas terapéuticas y evaluar posibles tratamientos