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The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

Poor teat and udder structure, frequently associated with older cows, impact cow production and health as well as calf morbidity and mortality. However, producer culling, for reasons including age, production, feed availability, and beef markets, creates a bias in teat (TS) and udder scores (US) assessed and submitted to the Canadian Angus Association for genetic evaluations toward improved mammary structure. In addition, due to the infancy of the reporting program, repeated scores are rare. Prior to the adoption of genetic evaluations for TS and US in Canadian Angus cattle, it is imperative to verify that TS and US from young cows are the same traits as TS and US estimated on mature cows. Genetic parameters for TS and US from all cows (n = 4,192) and then from young cows (parities 1 and 2) and from mature cows (parity ≥ 4) were estimated using a single-trait animal model. Genetic correlations for the traits between the two cow age groups were estimated using a two-trait animal model. Estimates of heritability (posterior SD [PSD]) were 0.32 (0.07) and 0.45 (0.07) for young TS and US and 0.27 (0.07) and 0.31 (0.07) for mature TS and US, respectively. Genetic correlation (PSD) between the young and mature traits was 0.87 (0.13) for TS and 0.40 (0.17) for US. Genome-wide association studies were used to further explore the genetic and biological commonalities and differences between the two groups. Although there were no genes in common for the two USs, 12 genes overlapped for TS in the two cow age groups. Interestingly, there were also 23 genes in common between TS and US in mature cows. Based on these findings, it is recommended that producers collect TS and US on their cow herd annually.

Functional and enduring mammary structure is pivotal for producer profitability, and animal health and welfare in beef production. Genetic evaluations for teat and udder score in Canadian Angus cattle have previously been developed. The aim of this study was to identify genomic regions associated with teat and udder structure in Canadian Angus cows thereby enhancing knowledge of the biological architecture of these traits. Thus, we performed a weighted single-step genome wide association study (WssGWAS) to identify candidate genes for teat and udder score in 1,582 Canadian Angus cows typed with the GeneSeek® Genomic Profiler Bovine 130K SNP array. Genomically enhanced estimated breeding values (GEBVs) were converted to SNP marker effects using unequal variances for markers to calculate weights for each SNP over three iterations. At the genome wide level, we detected windows of 20 consecutive SNPs that explained more than 0.5% of the variance observed in these traits. A total of 35 and 28 windows were identified for teat and udder score, respectively, with two SNP windows in common for both traits. Using Ensembl, the SNP windows were used to search for candidate genes and quantitative trait loci (QTL). A total of 94 and 71 characterized genes were identified in the regions for teat and udder score, respectively. Of these, 7 genes were common for both traits. Gene network and enrichment analysis, using Ingenuity Pathway Analysis (IPA), signified key pathways unique to each trait. Genes of interest were associated with immune response and wound healing, adipose tissue development and morphology, and epithelial and vascular development and morphology. Genetic architecture from this GWAS confirms that teat and udder score are distinct, polygenic traits involving varying and complex biological pathways, and that genetic selection for improved teat and udder score is possible.

Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-min time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation because of chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.

In Arabidopsis thaliana, chromosomal rearrangements are commonly associated with compound T-DNA insertions due to endogenous double-stranded break and repair mechanisms. During the production of a double homozygous mutant for the CCCH zinc finger proteins, AtC3H6 and AtC3H68, we uncovered evidence for a reciprocal I-V chromosomal translocation in SALK_093620. Mapping the T-DNA borders in this insertion line confirmed an insertion site at the AtC3H6 locus on chromosome I and identified a second insertion in an intergenic region at the end of chromosome V. Our investigation of the progeny distribution and gamete transmission from reciprocal crosses indicated that male and female gametes are differentially affected by this predicted translocation. Male gametes with the haploid genotype AtC3H6(+);AtC3H68(+) had significantly higher transmission than female gametes with the same genotype. Our work highlights the importance of detailing T-DNA insertion events in transgenetic lines produced through Agrobacterium-mediated transformation, which can uncover novel chromosomal anomalies and imbalanced genome compositions.

Transposable elements (TEs) have the main role in shaping the evolution of genomes and host species, contributing to the creation of new genes and promoting rearrangements frequently associated with new regulatory networks. Support for these hypotheses frequently results from studies with model species, and Drosophila provides a great model organism to the study of TEs. Micropia belongs to the Ty3/Gypsy group of long terminal repeats (LTR) retroelements and comprises one of the least studied Drosophila transposable elements. In this study, we assessed the evolutionary history of Micropia within Drosophilidae, while trying to assist in the classification of this TE. At first, we performed searches of Micropia presence in the genome of natural populations from several species. Then, based on searches within online genomic databases, we retrieved Micropia-like sequences from the genomes of distinct Drosophilidae species. We expanded the knowledge of Micropia distribution within Drosophila species. The Micropia retroelements we detected consist of an array of divergent sequences, which we subdivided into 20 subfamilies. Even so, a patchy distribution of Micropia sequences within the Drosophilidae phylogeny could be identified, with incongruences between the species phylogeny and the Micropia phylogeny. Comparing the pairwise synonymous distance (dS) values between Micropia and three host nuclear sequences, we found several cases of unexpectedly high levels of similarity between Micropia sequences in divergent species. All these findings provide a hypothesis to the evolution of Micropia within Drosophilidae, which include several events of vertical and horizontal transposon transmission, associated with ancestral polymorphisms and recurrent Micropia sequences diversification.

Leigh syndrome is a fatal neurometabolic disorder caused by defects in mitochondrial function. mTOR inhibition with rapamycin attenuates disease progression in a mouse model of Leigh syndrome (Ndufs4 KO mouse); however, the mechanism of rescue is unknown. Here we identify PKC downregulation as a key event mediating the beneficial effects of rapamycin treatment of Ndufs4 KO mice. Assessing the impact of rapamycin on the brain proteome and phosphoproteome of Ndufs4 KO mice we find that rapamycin restores mitochondrial protein levels, inhibits signaling through both mTOR complexes, and reduces the abundance and activity of multiple protein kinase C (PKC) isoforms. Administration of PKC inhibitors increases survival, delays neurological deficits, prevents hair loss, and decreases inflammation in Ndufs4 KO mice. Thus, PKC may be a viable therapeutic target for treating severe mitochondrial disease. Reporting Summary Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Despite their heritability and influence on female productivity, there are currently no genetic evaluations for teat and udder structure in Canadian Angus cattle. The objective of this study was to develop optimal genetic evaluations for these traits in the Canadian Angus population. Guidelines recommended by Beef Improvement Federation (BIF) were used to score teat and udder structure in 1,735 Canadian Angus cows from 10 representative herds. Cows scored ranged in parity from 1 to 13; however, >70% of cows were parity ≤4. Scores ranged from 1 (large, bottle shaped) to 9 (very small) for teats and from 1 (very pendulous) to 9 (very tight) for udders. Consistent with parity distribution, >70% of teat and udder scores were ≥6. Teat and udder scores (TS9 and US9, respectively) were modeled using a multiple trait animal model with random effects of contemporary group (herd-year-season) and additive genetic effect, and fixed effects of breed, parity group, and days between calving and scoring. To test good versus poor structure, a binary classification of 1 or 2 (TS2, US2) [comprised of scores 1 to 5 = 1 (poor structure) and scores 6 to 9 = 2 (good structure)] was created. Further, to assess the impact of grouping less frequently observed poor scores, a 1 to 7 scale (TS7, US7) was created by combining teat and udder scores 1 to 3. Analyses for teat and udder scores on scales TS9, US9, TS7, US7, and TS2, US2 were compared. In addition, both threshold and linear animal models were used to estimate variance components for the traits. Data treatment and models were evaluated based on correlation of resulting estimated breeding value (EBV) with corrected phenotypes, Spearman’s rank correlation coefficient, average EBV accuracies (r), and deviance information criteria (DIC). TS9, US9 scales for teat and udder scores and linear models performed best. Estimates of heritability (SE) for teat and udder score were 0.32 (0.06) and 0.15 (0.04), respectively, indicating these traits were moderately heritable and that genetic improvement for teat and udder scores was possible. Estimates of phenotypic and genotypic correlations for teat and udder score were 0.46 (0.02) and 0.71 (0.09), respectively. Estimates of genotypic correlations with birth weight (BW), weaning weight (WW), and yearling weight (YW), ranged from −0.04 (0.10) to −0.20 (0.12), verifying the importance of selecting for improved teat and udder score as individual traits, alongside performance traits.

Leigh syndrome is a fatal neurometabolic disorder caused by defects in mitochondrial function. mTOR inhibition with rapamycin attenuates disease progression in a mouse model of Leigh syndrome (Ndufs4 KO mouse); however, the mechanism of rescue is unknown. Here we assessed the impact of rapamycin on the brain proteome and phosphoproteome of Ndufs4 KO mice. We report that rapamycin remodels the brain proteome to alter mitochondrial structure, inhibits signaling through both mTOR complexes, and inhibits multiple protein kinase C (PKC) isoforms. Administration of PKC inhibitors was sufficient to increase survival, delay neurological deficits, and prevent hair loss in Ndufs4 KO mice. Thus, PKC may be a viable therapeutic target for treating severe mitochondrial disease.One Sentence SummaryProteomic and phosphoproteomic analysis of mouse brain identifies PKC as a key target to treat mitochondrial disease

Background The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STAT-dependent genes (Srinivasan et al., 2016). Here, we revise that conclusion and report that α-actinin is far more potent than actin at inducing the same STAT response and can be found in trace amounts in actin preparations. Recombinant expression of actin or α-actinin in bacteria demonstrated that only α-actinin could drive the expression of STAT target genes in Drosophila. The response to injected α-actinin required the same signalling cascade that we had identified in our previous work using actin preparations. Taken together, these data indicate that α-actinin rather than actin drives STAT activation when injected into Drosophila.

In this work, calcium diglyceroxide (Ca-DG), was produced by reacting hydrated lime with glycerin varying reaction times and temperatures. The effect of removing the glycerin excess by a water washing and drying step was also considered. Samples’ purity and identification of the crystalline phases was determined by X-ray powder diffraction (XRD) and the purest sample was evaluated in the transesterification reaction of castor oil with methanol. Transesterification reaction products were characterized by 1H NMR and thin-layer chromatography analysis. The influence of the catalyst amount, methanol:oil ratio (vol.), reaction time, and reaction temperature was studied. From the XRD results it was evidenced that Ca-DG was obtained as the main crystalline phase although calcium hydroxide and calcite were identified in all samples. In this sense, the best reaction conditions for Ca-DG obtaining were achieved at 60 °C and 2 h. It was interesting that although in the first use full conversion of castor oil was achieved in the first recycling of spent catalyst, a conversion decrease was observed and the catalyst did not show any activity after the second reuse. In order to determine the reasons that caused catalyst’s deactivation the solid’s stability was tested immersing it in water, methanol, castor oil and biodiesel, respectively.

Hydrated lime (HL) and CaO were evaluated as solid base catalysts in the transesterification of castor oil and methanol. Castor oil and the alkyl esters produced after the transesterification reaction were characterized by 1H NMR and TLC analysis. Since full conversion of the raw materials into biodiesel (BD) was obtained with both HL and CaO, the influence of the catalyst amount, methanol:oil ratio, reaction time, and reaction temperature was studied employing HL due to the economic and process advantages of HL over CaO. The catalyst’s changes throughout reaction time and after the catalyst reutilization were analyzed by X-ray analysis of the recovered mixture of HL, raw materials and products. From the X-ray diffraction analysis it was corroborated that the crystalline phases after 10, 30, 60 and 120 min were Ca(OH)2 and CaCO3 as the main and secondary phases, respectively. From the results it was clear that the catalyst’s active phase after the first use was Ca(OH)2. However, when the catalyst was reused, calcium diglyceroxide was identified by X-ray analysis as the main crystalline phase and it remained up to the third reuse. The catalyst stability was determined and the results revealed that although a conversion decrease was observed after the first reuse, the catalyst increased its activity in the second reuse maintaining a conversion up to 84% after the third one. Room-temperature biodiesel production was also investigated. In this sense, 98% conversion was achieved at 14 h of reaction.

The search for alternative sources of energy is more important than ever as the extraction of petroleum, the greenhouse gas emissions and the climate changes are getting extremely complicated an unsafe for mankind. In order to find renewable, cheaper and easier methods to obtain energy, a hydrocalumite-type compound was synthesized by a green method here presented and evaluated in the transesterification of castor oil with methanol to obtain biodiesel. The pristine material and its thermally decomposed products were analyzed by X-ray powder diffraction, thermogravimetric analysis and Scanning Electron Microscopy. Biodiesel conversion was determined by 1 H NMR. The effect of the precursors’ thermal activation on biodiesel production was evaluated at 300, 500 and 700 °C. Similar results were obtained with the solids produced by a conventional method, demonstrating that the materials prepared by the new technique disclosed not only comparable physicochemical properties, but also analogous catalytic activity; revealing the feasibility of producing high active catalyst’s precursors by a simple, economic and environmentally-friendly method.

This work aims to present a study of the adsorption and photocatalytic reduction of Cr(VI) by ZnAl, MgZnAl and MgAl mixed oxides derived from layered double hydroxides (LDHs). The effect of variables like Zn content and pH (3 and 6.5) on Cr(VI) removal efficiency is presented. The catalysts were characterized by X-ray diffraction (XRD) and infrared spectroscopy (FTIR). The reaction progress was verified by UV/vis spectrophotometry with a colorimetric method. A maximum of 99.5% Cr(VI) was photocatalytically removed and this process was approximately two times faster than adsorption. In addition, it was found that the use of these materials does not imply the addition of further chemicals to regulate pH since the free basic pH of the catalyst-contaminant suspension positively affects both adsorption and photo-reduction kinetics.

Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity. DOI: http://dx.doi.org/10.7554/eLife.19662.001, eLife digest All animals must be able to detect and repair injuries quickly. To do this, the body triggers a process called inflammation at the site of injury to remove dead and damaged cells, keep the area free from infection and trigger repair. However, if an area becomes excessively inflamed, or remains inflamed for a long period of time, it can contribute to diseases like cancer and Alzheimer’s disease. Inflammation starts when the body detects molecules that are released when cells die or are damaged to the extent that they become leaky. Actin, which is a protein that usually provides structural support to the cell, is one molecule that is sensed by the immune system in mammals when released from dying cells. However, it is not clear whether released actin can also trigger reactions in simpler animals like fruit flies. To address this question, Srinivasan, Gordon et al. injected fruit flies with actin. These animals developed a widespread reaction reminiscent of inflammation seen in mammals. Further experiments showed that actin switches on a signalling pathway called JAK/STAT, which is known to become active when flies experience other types of stress. The JAK/STAT proteins activate a signalling pathway that leads to changes in gene activity. Srinivasan, Gordon et al. also showed that part of a cascade of signals triggered by released actin in mammals is shared in fruit flies. These findings suggest that this important response to actin evolved a long time ago. A future challenge is to find out how the body detects and mops up released actin, which may help us to understand how actin can contribute to various inflammatory diseases. DOI: http://dx.doi.org/10.7554/eLife.19662.002

O Pampa brasileiro (extremo sul do país) está, atualmente, vastamente modificado devido ao aumento das atividades agrícolas. Em muitos lugares, apenas pequenos fragmentos de campo permanecem em uma paisagem agrícola. Drosophilidae (Diptera) tem sido amplamente utilizadas como bioindicadores para monitorar os efeitos das mudanças antropogênicas em ambientes naturais. Porém, a fauna de Drosophilidae no Bioma Pampa de ambientes naturais ou perturbados, ainda permanece amplamente desconhecida. O presente estudo é uma das primeiras tentativas de preencher esta lacuna, apresentando resultados de coletas mensais no município de São Luiz Gonzaga (28º24'28"S, 54º57'39"W), no Pampa brasileiro. Um inventário de espécies foi conduzido em dois ambientes contrastantes, uma zona urbana e um remanescente de floresta (zona rural). Em ambos os locais, armadilhas com banana fermentada foram usadas para capturar drosofilideos adultos. A identificação foi feita através da morfologia externa e da terminália dos machos. No total, 13,379 drosofilideos foram analisados (zona rural: N = 8,812 and Sobs = 25; zona urbana: N = 4,567 and Sobs = 16). No presente estudo, 16 (60%) das 26 espécies coletadas foram encontradas exclusivamente ou preferencialmente no fragmento de mata. O período de maior riqueza foi entre os meses de junho a novembro (inverno-primavera), e o período de menor riqueza foi de dezembro a maio (verão-outono). Uma análise de cluster pelo Coeficiente de Jaccard mostrou que a composição da assembléia muda ligeiramente quando o período do ano com temperaturas mais elevadas (janeiro-maio) é comparado com o período de temperaturas menos elevadas (junho-outubro). A abundância das espécies foi também altamente afetada pela sazonalidade, como revelou o Índice de Morisita, onde as amostras foram agrupadas em períodos consecutivos dentro de uma mesma estação, mostrando a preferência sazonal de algumas espécies. O componente tempo foi determinante na diversidade da assembléia, superando o efeito espacial. A forte redução na diversidade na área urbana quando comparada com o pequeno fragmento de floresta, torna evidente a importância do ambiente natural para a preservação da diversidade no bioma Pampa, atualmente com sua paisagem altamente alterada. The Brazilian Pampa (the southernmost end of the country) is currently a highly modified environment because of increasing agricultural activities. In many places, only small parts of grasslands remain inside an agricultural landscape. Drosophilidae (Diptera) have been widely used as a potential bioindicators to monitor the effects of anthropogenic changes in natural environments. However, the fauna of Drosophilidae in the Pampa Biome from natural and disturbed environments, still remains largely unknown. The present study represents one of the first attempts to fill this gap, showing results from monthly collections in the municipality of São Luiz Gonzaga (28º24'28"S, 54º57'39"W), in the Brazilian Pampa. A species inventory was carried out in two contrasting environments, an urban zone and a forest remnant (rural zone). In both areas banana-baited traps were used to capture adult drosophilids. The identification was made using external morphology and male terminalia. In total, 13,379 drosophilids were analyzed (rural zone: N = 8,812 and Sobs = 25; urban zone: N = 4,567 and Sobs = 16). In the present study, 16 (60%) out of 26 species were found exclusively or preferentially in the forest. The period of highest richness was between the months of June to November (roughly winter and spring), and the period of lowest richness was from December to May (roughly summer and autumn). An analysis of cluster by the Coefficient of Jaccard showed that species composition slightly changes when the period of the year with higher temperatures (from January to May) is compared with the period with lower temperatures (from June to October). The species abundances were also highly affected by seasonality, as revealed by the Morisita Index, since the samples clustered into similar groups in consecutive periods and in the same season, showing the seasonal preference of some species. The time component was a determinant in the diversity of the assemblage, surpassing the spatial effect. The strong reduction in diversity in the urban area when compared to a small forest patch is evidence of the importance of the natural environments in maintaining the diversity in the Pampa biome, currently a highly disturbed landscape.

The objective of this work is to study, for the first time, the photodegradation of 4-chlorophenol (4CP) catalyzed by a calcined Mg–Zn–Al layered double hydroxides (MgAlZn LDHs) in a co-current downflow bubble column (CDBC) photoreactor at pilot scale. The effect of initial organic compound concentration (C4CP0), temperature (T), and mass catalyst over reaction rate (−r4CP) was elucidated. An intrinsic kinetic regime was established, and a single-site Langmuir–Hinshelwood mechanism was determined to occur during the organic compound oxidation. The catalyst was characterized by X-ray diffraction (XRD), inductively coupled plasma atomic emission spectrometry (ICP-AES), and ultraviolet–visible light (UV/vis) spectrophotometry. The reaction progress was verified by UV/vis spectrophotometry and total organic carbon (TOC) content. Degradation and mineralization rate were found to be dependent on T and 4CP concentration. In the range of studied operating conditions, a maximum of 94% 4CP was degraded, while 70% t...

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder of zinc (Zn) deficiency. AE is the clinical phenotype of Zn deficiency and is characterized by pustular and bullous dermatitis with an acral and periorificial distribution, frequently associated with pustular paronychia, angular stomatitis, glossitis, generalized alopecia and diarrhoea.1-4 Initially the term AE was used to describe the congenital form. This genetic defect has been mapped to 8q24 and the defective gene identified as SLC39A4, which encodes the zinc transporter4 Zip4. Nowadays, AE is also associated with the acquired form of Zn deficiency resulting from impaired intestinal absorption due to gastrointestinal diseases or by poor consumption of the mineral.1-3 In this case it has been denominated as AE like (AEL) disease. The diagnosis of AE is made by clinical presentation, dietary survey, laboratory tests, and histopathological findings (characteristic skin lesions). In some patients the differential diagnosis with other skin diseases is difficult and can generate delay in the correct diagnosis and appropriate treatment. In this report we present an infant with AEL probably secondary to an inadequate dietary management due to suspicious atopic dermatitis (AD) related to cow’s milk allergy.

OBJECTIVE To evaluate pharmacokinetics, recovery times, and recovery quality in horses anesthetized with 1.2 times the minimum alveolar concentration of sevoflurane or desflurane. ANIMALS 6 healthy adult horses. PROCEDURES Anesthesia was maintained with sevoflurane or desflurane for 2 hours at 1.2 times the minimum alveolar concentration. Horses recovered without assistance. During recovery, end-tidal gas samples were collected until horses spontaneously moved. Anesthetic concentrations were measured by use of gas chromatography. After a 1-week washout period, horses were anesthetized with the other inhalation agent. Video recordings of anesthetic recovery were evaluated for recovery quality on the basis of a visual analogue scale by investigators who were unaware of the anesthetic administered. Anesthetic washout curves were fit to a 2-compartment kinetic model with multivariate nonlinear regression. Normally distributed interval data were analyzed by means of paired Student t tests; ordinal or nonnormally distributed data were analyzed by means of Wilcoxon signed rank tests. RESULTS Horses recovered from both anesthetics without major injuries. Results for subjective recovery evaluations did not differ between anesthetics. Area under the elimination curve was significantly smaller and time to standing recovery was significantly less for desflurane than for sevoflurane, although distribution and elimination constants did not differ significantly between anesthetics. CONCLUSIONS AND CLINICAL RELEVANCE Differences in area under elimination the curve between anesthetics indicated more rapid clearance for desflurane than for sevoflurane in horses, as predicted by anesthetic blood solubility differences in this species. More rapid elimination kinetics was associated with faster recovery times, but no association with improved subjective recovery quality was detected.

This study describes the development and full validation of a stability-indicating HPLC method to quantify ritonavir (RTV) and lopinavir (LPV) in soft gelatin capsules. The method uses a LiChrospher® 100 RP-18 (250 mm × 4.6 mm, 5 µm, Merck) column and isocratic elution. The mobile phase consisted of a mixture of acetonitrile-water-methanol (53:37:10, v/v/v), pumped at a flow-rate of 1.0 mL min−1 and UV detection at 210 nm using a photodiode array detector. LPV and RTV were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. The response was linear over a range of 40-360 µg mL−1 for LPV and 10–90 µg mL−1 for RTV (r > 0,999 for both drugs). The mean recoveries were 99.46 and 100.81% for LPV and RTV, respectively. The RSD values for intra- and inter-day precision studies were < 0.70% for both drugs. Degradation studies showed that lopinavir is stable in thermal, alkaline and oxidative conditions, while ritonavir degraded under these conditions. The method was found to be stability-indicating and can be used for the routine analysis of the association LPV/RTV in soft gelatin capsules.

Até o momento, não só o lugar da fertilização em carrapatos é desconhecido, mas também não é claro como este mistério possa ser esclarecido. Sinais de fertilização podem ser observados ao longo do trato genital feminino e estes podem ser pistas para a elucidação das questões relacionadas à fertilização em ácaros. Em Boophilus microplus (Canestrini, 1887), os sinais mais importantes são os seguintes: a eversão final do canal acrossômico em fêmeas prestes à oviposição; a presença de pequenos túbulos assemelhando-se a processos subplasmalêmicos dos espermatozóides entre as células do oviduto; brotamentos nucleares ao longo do trato genital feminino e as duas áreas Feulgen e DAPI positivas nos ovócitos em processo de vitelogênese. Estas características morfológicas sugerem que a fertilização ocorra no cilindro interno, o qual se estende desde o útero até o ovário inclusive. At present not only is the site of fertilization in ticks still unknown but it is also unclear as to how this mystery can be solved. Signs of fertilization can be observed throughout the female genital tract and these can be clues for the elucidation of the unsolved questions relating to ticks fertilization. In Boophilus microplus (Canestrini, 1887) the most important signs are the following: the final eversion of the acrosomal canal in females ready for oviposition; the presence of small tubules, resembling the subplasmalemal process of the spermatozoon between the oviduct cells; budding nuclei throughout the female genital tract; and the two Feulgen and DAPI positive areas in the oocyte at vitelogenesis. These morphological characteristics suggest that fertilization takes place in the internal cylinder which extends from the uterus to the ovary itself.

Parsley is leafy herb highly susceptible to desiccation. Leaves from plain-leaf (Petroselinum crispum var. neapolitanum) and curled-leaf (P. crispum var. crispum) parsley were stored in open trays or into folded, unsealed, polyethylene bags, and stored at 22, 10, and 1°C. In another experiment the leaves were dry-stored at 20°C for 0, 6, 12, and 24 h after harvest, after which time their petioles were immersed in distilled water and transferred to 10°C. Curled and plain leaf parsley did not differ in storage life. Maximum storage life of about 6 weeks was achieved with wrapped leaves stored at 1°C. The rate of water loss was generally higher in curled than in plain leaf parsley. Cooling and plastic wrapping are effective means of reducing water loss. Should desiccation occur during postharvest handling, parsley leaves are able to recover from a 10% water loss once their petioles are placed in water, even though dehydration reduces the rate of water uptake and hastens senescence.

We used transcranial magnetic stimulation to evaluate cortical excitability in acute exacerbations of chronic obstructive pulmonary disease (COPD). Patients affected by COPD were studied during acute exacerbation that required hospital admission and 3-4 months after oxygen therapy. Their data were compared with those of age-matched healthy controls. Intracortical inhibition and cortical silent period duration were significantly reduced in patients during acute exacerbation of COPD. These findings could reflect impairment of GABAergic cortical circuits during hypoxia.

SummaryThe aim of this study was to estimate genetic associations between tem-perament and performance traits. Temperament was evaluated in yearlingmale and female Nellore cattle, using four traits: temperament score (TS),for assessing animals’ reactions in a corral pen (n = 25 691); movementscore (MOV), for animals’ movements recorded inside the crush; crushscore (CS), for animal’s general reactivity inside the crush; and flightspeed (FS), for the speed (in m/s) at which the animals exited the crush(n = 11 697, for the last three methods); for all the temperament traits,lower scores indicate animals with calmer temperament. Performancetraits were visual scores for conformation (C), finishing precocity (P) andmuscling (M) evaluated at yearlings, and average daily gain (ADG) wasestimated from weaning to yearling. Bayesian inference using Gibbs sam-pling was applied to estimate (co)variance components and genetic andphenotypic parameters. Heritability estimates for the temperament traitsranged from 0.07 (CS) to 0.28 (FS). Genetic correlations of the tempera-ment traits with ADG and C, P and M were negative and ranged from 0.02 to 0.31. Phenotypic correlations were negative and consistentlylower than the genetic, ranging from 0.08 to 0.02. It was concludedthat the temperament traits assessed had favourable genetic correlationestimates with the performance traits studied. However, indirectresponses in temperament when selecting for higher ADG and visual scor-ing system of C, P and M, will be low.IntroductionTemperament can be defined as individual differ-ences in behavioural responses which are persistentover time and across situations. Cattle temperamenttraits are usually assessed from behaviouralresponses of the animals under human influenceduring handling procedures (Fordyce et al. 1985)and related to cattle welfare, stockperson safety andefficiency of handling. Furthermore, there are severalreports where these traits are related to importantaspects of cattle production, for example reproductiveefficiency (Cooke et al. 2012), growth rate and meatquality (Petherick et al. 2002; Behrends et al. 2009).Despite the large number of studies addressing thistopic, there is no consensus about the extent towhich temperament traits may affect productiveperformance, as some authors reported strong rela-tionship (Petherick et al. 2002; Behrends et al.2009), whereas others reported only a weak associa-tion (Burrow & Corbet 2000; Burrow 2001).These varying results could partially be associatedwith different rearing conditions, which could affectthe expression of temperament traits and, conse-quently, the degree of their association with perfor-mance (Fordyce et al. 1985; Burrow & Corbet2000). To overcome this difficulty, it would berequired assessing the temperament of cattle from a

Temperature-dependent gonadal dysgenesis was shown to occur in the progeny of both inter- and intrastrain crosses involving two populations of Drosophila willistoni, one of which was an old laboratory stock, and the other, freshly collected from a natural population. We propose that the phenomenon observed was caused by the mobilization of transposable elements, as occurs in several other Drosophila species.Disgenesia gonadal dependente de temperatura foi encontrada na prole tanto de cruzamentos intra como interlinhagens, envolvendo duas populações de Drosophila willistoni. Uma delas é derivada de um velho estoque de laboratório e a outra, de uma amostra recentemente coletada de uma população natural. Tal fenômeno não havia ainda sido descrito em D. willistoni e nós sugerimos que a disgenesia gonadal encontrada seja causada por elementos transponíveis, como ocorre em muitas outras espécies de Drosophila.

Aims Three cases of chronic periapical periodontitis including focal areas with malakoplakia changes are reported. Methods and results These areas included both von Hansemann-type macrophages and periodic acid–Schiff-positive, iron- and calcium-containing concretions. Some concretions corresponded to spherules with a targetoid configuration, thus fitting the morphological criteria for classical Michaelis–Gutmann bodies. Conclusion The vast majority of the cases of malakoplakia that have been reported in the literature corresponded to a characteristic, fairly homogeneous lesion, but a few instances of focal malakoplakia have been described in various chronic conditions. These considerations support the opinion that the local conditions for the production of Michaelis–Gutmann bodies may occur focally in diseases characterized by macrophage accumulation.

This phase II study was designed to verify the activity and safety of an intensive epirubicin/ifosfamide schedule in untreated soft tissue sarcoma (STS) patients by using both the agents at the identified maximal tolerated doses. 39 adult patients were treated with epirubicin at 55 mg/m2, on days 1 and 2 (total dose per cycle 110 mg/m2) combined with ifosfamide at 2.5 g/m2 days 1-4 (total dose per cycle 10 g/m2), with equidose mesna uroprotection and G-CSF support. Treatment was given on an ambulatory basis, at 3-week intervals. The overall objective response (OR) rate was 59% (95% confidence interval, CI, 43-72%), with 5 complete responses (13%) at 18 partial responses (46%); 12 partial responders were rendered disease-free following surgery. The median survival time was 19 months, being 23 and 13 months, respectively, for responding and non-responding patients. The median time to response was 40 days (range 21-60). Treatment-related toxicity was overall acceptable. The OR of 59% was the highest ever reported in our consecutive studies in advanced STS, confirming that improved therapeutic efficacy can be obtained with intensified regimens in such a disease; both the response duration and survival were also longer. The observed activity proved to be interesting with regard to the high response rate in the lung (86%), as well as the proportion of patients rendered disease-free by early surgery after the achievement of a partial response (55%). Both these findings may be important in the multimodality approach to patients with lesions potentially resectable for cure.

Unintentional injury is the seventh leading cause of death among adults aged 65 and above. Falls are a serious health problem among older adults, the costs of fall-related injuries are significant. In 1994, the average direct cost for a fall injury was $1,400 for a person over age 65. In the United States the total direct cost of fall injuries in 1994 among people 65 and older was $20.2 billion (Englander et al., 1996). This sum does not include the costs of the long-term consequences of these injuries, such as disability and reduced quality of life. The purpose of this paper is to share characteristics and findings of a model program designed to prevent injuries from occurring in the home. Two trained injury-prevention counselors conducted environmental assessments to identify hazards, make safety recommendations and corrections, and encourage behavioral changes. Additionally, a community-based consortium served as a resource for referrals and promotion of injury-prevention awareness in the targe...

Microsatellite analysis is emerging as an important tool in the study of cancer. The addition of novel microsatellite alleles is referred as microsatellite instability (MSI) indicating possible mutations in cellular DNA repair mechanism. The detection of these genetic changes demonstrates the presence of a clonal population of cells that share altered genetic information, which is characteristic of cancer cells. In this study, we analyzed the five MSI markers: D2S123, D5S346, D17S250, BAT 25, BAT 26 recommended at the 1997 National Cancer Institute in a patient with suspicious familiar history of Non-Polyposic Hereditary Colorectal Cancer (NHPCC), Lynch syndrome, and high instability MSI-H was confirmed.

BACKGROUND: The combination of high PEEP and low tidal volume (VT) decreases some risks of mechanical ventilation, including pulmonary overdistention, damage due to cyclic opening and closing of the alveoli, and inflammatory responses that can lead to multiple-organ dysfunction. We hypothesized that high VT and high PEEP induce mesenteric microcirculatory disturbances and that those disturbances would be attenuated by pentoxifylline, which is anti-inflammatory. METHODS: We anesthetized (isoflurane 1.5%), tracheostomized, and mechanically ventilated 57 male Wistar rats with PEEP of 10 cm H2O and FIO2 of 0.21 for 2 hours. One group received low VT (7 mL/kg), another group received high VT (10 mL/kg), and a third group received high VT plus pentoxifylline (25 mg/kg). We measured mean arterial pressure, respiratory mechanics, mesenteric blood flow, and leukocyte-endothelial interactions. RESULTS: The mean arterial pressure was similar among the groups at baseline (108 mm Hg [IQR 94–118 mm Hg]) and after 2 hours of mechanical ventilation (104 mm Hg [IQR 90–114 mm Hg]). Mesenteric blood flow was also similar between the groups: low VT 15.1 mL/min (IQR 12.4–17.7 mL/min), high VT 11.3 mL/min (IQR 8.6– 13.8 mL/min), high-VT/pentoxifylline 12.4 mL/min (10.8–13.7 mL/min). Peak airway pressure after 2 hours was lower (P .03) in the low-VT group (10.4 cm H2O [IQR 10.2–10.4 cm H2O]) than in the high-VT group (12.6 cm H2O [10.2–14.9 cm H2O]) or the high-VT/pentoxifylline group (12.8 cm H2O [10.7–16.0 cm H2O]). There were fewer adherent leukocytes (P .005) and fewer migrated leukocytes (P .002) in the low-VT group (5 cells/100 m length [IQR 4–7 cells/100 m length] and 1 cell/5,000 m 2 [IQR 1–2 cells/5,000 m 2 ], respectively) and the high-V T /pentoxifylline group (5 cells/100 m length [IQR 3–10 cells/100 m length] and 1 cell/5,000 m 2 [IQR 1–3 cells/ 5,000 m 2 ], respectively) than in the high-V T group (14 cells/100 m length [IQR 11–16 cells/ 100 m length] and 9 cells/5,000 m 2 [IQR 8–12 cells/5,000 m 2 ], respectively). CONCLUSIONS

Acute respiratory distress syndrome (ARDS) is a quite common disease, with an annual incidence ranging from 1.5 to 8.3 cases for every 100000 patients and a mortality of 30–50% [1]. In 1994, the American European Consensus Conference defined ARDS as: ‘an acute and persistent lung disease characterized by an arterial hypoxemia (PaO2/FiO2

The change in size of peripheral organs is one indicator used to describe effects of an intervention in experimental studies, or in observational studies. It is common practice to express size in terms of organweight in relation to bodyweight. When effects on size as such are looked for, this can be misleading. The particular treatment may affect the weight of the organ, the total weight of body at the time for sacrifice and dissections, or affect the organ size and bodyweight. ‘Which’ bodyweight is used for reference will affect the results obtained. To illustrate this point the results are presented of a study on the effects on organ-weight of an anabolic androgenic steroid: Nandrolone decanoate. Twenty-four (330–470 g) male Wistar rats (Taconic M&B, Ry, Denmark) were randomly divided in four treatment groups of six rats. The rats in each group received injections of either the vehicle (Arachidis oleum) or Nandrolone decanoate in one of three doses (1, 5 or 10 mg/kg). The rats received a daily injection subcutaneously (s.c.) for 19 days. The rats were sacrificed on the day following the last injections. The rats were weighed at the onset and end of the study. The poster presents the weight of a selection of peripheral organs relative to individual pre-experimental and postexperimental weight, and relative to the dose given and growth over the treatment-period. The implications in each case are discussed in terms of effects on each target of the drugtreatment.

Follicular mucinosis is a rare chronic inflammatory disease of unknown aetiology, presenting as mucin deposits around the follicles and sebaceous glands. It can progress to alopecia of the scalp and other hairy areas. Follicular mucinosis may be a benign primary idiopathic disorder or secondary to malignant lymphoproliferative disorders. It can present with shiny papules or sharply marginated infiltrated erythematous scaling plaques, with follicular accentuation on the scalp, neck, trunk and limbs. There are many local and systemic treatments. This paper discusses the case of an adult with an uncommon acneiform follicular mucinosis controlled with systemic corticosteroids.