CYP19A1 mediates severe SARS-CoV-2 disease outcome in males.

Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n = 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment.

Measuring water holding capacity in pork meat images using deep learning.

Water holding capacity (WHC) plays an important role when obtaining a high-quality pork meat. This attribute is usually estimated by pressing the meat and measuring the amount of water expelled by the sample and absorbed by a filter paper. In this work, we used the Deep Learning (DL) architecture named U-Net to estimate water holding capacity (WHC) from filter paper images of pork samples obtained using the press method. We evaluated the ability of the U-Net to segment the different regions of the WHC images and, since the images are much larger than the traditional input size of the U-Net, we also evaluated its performance when we change the input size. Results show that U-Net can be used to segment the external and internal areas of the WHC images with great precision, even though the difference in the appearance of these areas is subtle.

The proprotein convertase SKI-1/S1P is a critical host factor for Nairobi sheep disease virus infectivity.

Nairobi sheep disease virus (NSDV) belongs to the Orthonairovirus genus in the Bunyavirales order and is genetically related to human-pathogenic Crimean-Congo hemorrhagic fever virus (CCHFV). NSDV is a zoonotic pathogen transmitted by ticks and primarily affects naïve small ruminants in which infection leads to severe and often fatal hemorrhagic gastroenteritis. Despite its veterinary importance and the striking similarities in the clinical picture between NSDV-infected ruminants and CCHFV patients, the molecular pathogenesis of NSDV and its interactions with the host cell are largely unknown. Here, we identify the membrane-bound proprotein convertase site-1 protease (S1P), also known as subtilisin/kexin-isozyme-1 (SKI-1), as a host factor affecting NSDV infectivity. Absence of S1P in SRD-12B cells, a clonal CHO-K1 cell variant with a genetic defect in the S1P gene (MBTPS1), results in significantly decreased NSDV infectivity while transient complementation of SKI-1/S1P rescues NSDV infection. SKI-1/S1P is dispensable for virus uptake but critically required for production of infectious virus progeny. Moreover, we provide evidence that SKI-1/S1P is involved in the posttranslational processing of the NSDV glycoprotein precursor. Our results demonstrate the role of SKI-1/S1P in the virus life cycle of NSDV and suggest that this protease is a common host factor for orthonairoviruses and may thus represent a promising broadly-effective, indirect antiviral target.

Hydrocephalus and Intracranial Hypertension by an Odontogenic Brain Abscess.

Brain abscesses are rare and severe infections with high mortality, corresponding to neurosurgical emergencies. 12% of all abscesses are caused by odontogenic etiologies, either an infectious process or a dental procedure. This paper describes a case of a patient who underwent tooth extraction, presenting days later with hydrocephalus and intracranial hypertension due to a brain abscess, whose isolated pathogen is the same identified in the oral cavity.

Secretive fish diversity: A new species of Listrura (Siluriformes, Trichomycteridae) from a supposedly well-known river in south-eastern Brazil.

The trichomycterid catfish Listrura menezesi, new species, is described from a flooded area adjacent to Rio das Panelas, Rio São João basin, Cachoeiras de Macacu municipality, Rio de Janeiro State, Brazil. It represents a most valuable remnant of Atlantic Forest biome that still resists the devastation of Brazilian coastlands. Listrura menezesi can be distinguished from its congeners, except L. boticario and L. depinnai, by the absence of a dorsal fin. It mainly differs from L. boticario and L. depinnai by a continuous midlateral dark stripe along the entire body (vs. discontinuous) and a longitudinal row of irregular dots along the dorsal limit of the abdomen extending for nearly the entire body (vs. only on the posterior half of the body in L. boticario and not forming a distinct row in L. depinnai). Although the new species shares with L. boticario and L. depinnai the absence of dorsal fin, recent phylogenetic analyses show a close relationship between L. menezesi and L. macaensis, the latter having a dorsal fin. A putative apomorphic condition for this clade is presented: the abrupt widening on the mesethmoid axis starting posteriorly on the horizontal through the middle region of the autopalatine (vs. anteriorly, on the horizontal through the anterior region of the autopalatine). Listrura menezesi comes as an addition to the ichthyofauna of the Rio São João drainage, a region extensively sampled for the past 20 years and supposedly well known. This paper also highlights the vulnerability of this species and the possibility of its disappearance in the near future.

Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life.

Influenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring.

αVß3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells.

The Flavivirus genus includes a number of important viruses that are pathogenic to humans and animals and are responsible for outbreaks across the globe. Integrins, a family of heterodimeric transmembrane molecules expressed in all nucleated cells mediate critical functions of cell physiology and cell cycle. Integrins were previously postulated to be involved in flavivirus entry and to modulate flavivirus replication efficiency. In the present study, mouse embryonic fibroblasts (MEF), lacking the expression of αVß3 integrin (MEF-αVß3-/-), were infected with four different flaviviruses, namely yellow fever virus (YFV), West Nile virus (WNV), Usutu virus (USUV) and Langat virus (LGTV). The effects of the αVß3 integrin absence in double-knockout MEF-αVß3-/- on flavivirus binding, internalization and replication were compared to the respective wild-type cells. Binding to the cell surface for all four flaviviruses was not affected by the ablation of αVß3 integrin, whereas internalization of USUV and WNV was slightly affected by the loss of αVß3 integrin expression. Most interestingly, the deletion of αVß3 integrin strongly impaired replication of all flaviviruses with a reduction of up to 99% on virus yields and a strong reduction on flavivirus anti-genome RNA synthesis. In conclusion, our results demonstrate that αVß3 integrin expression in flavivirus-susceptible cell lines enhances the flavivirus replication.

Iterative taxonomy reveals a new species of Trichomycterus Valenciennes 1832 (Siluriformes, Trichomycteridae) widespread in Rio Doce basin: a pseudocryptic of T. immaculatus.

This paper reports on a new species of Trichomycterus from the Rio Doce basin. Unusually for new taxa in the genus during the past few decades, the new species is not narrowly endemic but instead widely distributed in its major drainage, the Rio Doce. The species has been collected and deposited in scientific collections for some years, but has been systematically misidentified as the more abundant Trichomycterus immaculatus or, to a lesser degree, as other morphologically similar species from south-eastern Brazil such as T. nigricans and T. pradensis. A combination of several morphological characteristics, such as vertebral number, pectoral-fin ray counts, pigmentation pattern and barcoding distance, were iteratively used and unambiguously distinguish the new species from all congeners. The present case reveals a pattern of diversity-discovery in which rare and narrowly endemic morphologically conspicuous species are discovered and described before visually inconspicuous taxa, even when the latter are more abundant and widespread. The morphological similarities among south-eastern Brazilian species with a uniform dark-grey color serve as basis for a brief discussion about the concepts of cryptic and pseudo-cryptic species in Trichomycterus and their consequences for potentially hidden diversity in the genus.

ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response.

Deciphering complex virus-host interactions is crucial for pandemic preparedness. In this study, we assessed the impact of recently postulated cellular factors ANP32A and ANP32B of influenza A virus (IAV) species specificity on viral pathogenesis in a genetically modified mouse model. Infection of ANP32A-/- and ANP32A+/+ mice with a seasonal H3N2 IAV or a highly pathogenic H5N1 human isolate did not result in any significant differences in virus tropism, innate immune response or disease outcome. However, infection of ANP32B-/- mice with H3N2 or H5N1 IAV revealed significantly reduced virus loads, inflammatory cytokine response and reduced pathogenicity compared to ANP32B+/+ mice. Genome-wide transcriptome analyses in ANP32B+/+ and ANP32B-/- mice further uncovered novel immune-regulatory pathways that correlate with reduced pathogenicity in the absence of ANP32B. These data show that ANP32B but not ANP32A promotes IAV pathogenesis in mice. Moreover, ANP32B might possess a yet unknown immune-modulatory function during IAV infection. Targeting ANP32B or its regulated pathways might therefore pose a new strategy to combat severe influenza.

The type specimens of Trichomycterus alternatus (Eigenmann, 1917) and Trichomycterus zonatus (Eigenmann, 1918), with elements for future revisionary work (Teleostei: Siluriformes: Trichomycteridae).

The trichomycterid catfish species Trichomycterus alternatus (Eigenmann, 1917) and Trichomycterus zonatus (Eigenmann, 1918) are reportedly among the most pervasive species in mid- to high-elevation coastal streams of Southeastern Brazil. Despite their apparent abundance and ecological ubiquity, the applicability of their names is still uncertain. Examination of the type material of the two species reveals that part of the confusion stems from a mixing of species in the T. zonatus type series. Other issues relate to reports of character conditions in the respective species that do not actually correspond to the situation in their type specimens. Such situation triggered a long-lasting chain of taxonomic misinterpretations and erroneous identification protocols and traditions so that even the taxonomic distinctiveness of the two species is nebulous. That situation is disentangled in detail on the basis of new information on the holotypes and remaining type specimens of each species by classical and new (stereo triplet radiography) morphology analyses for data acquisition. Results show that the type specimens of T. alternatus and T. zonatus differ pronouncedly in several traits of internal and external morphology and represent markedly distinct taxa. The latter species does not correspond to most identifications in the literature and is, in fact, endemic to the region of its type locality. We also clarify and map the reported localities of the type material and offer comments on the validity of T. alternatus and T. zonatus, along with that of possibly related forms.

A new species of Trichomycterus Valenciennes 1832 (Trichomycteridae: Siluriformes) from the Rio Doce drainage with remarkable similarities with Bullockia and a CT-scan survey.

A new species of Trichomycterus is described from rocky and psammic sectors near the main channel of the middle and upper Rio Doce basin in Southeastern Brazil. Trichomycterus astromycterus n. sp., is distinguished from all congeners by a number of autapomorphic characters, such as the distally expanded maxilla; the short and thick mesethmoid cornua; and the elongated anterior process of the vomer. Additional characters (short barbels, large head, 33 vertebrae, ii+8 or ii+9 dorsal-fin rays, nine dorsal-fin pterygiophores, markedly enlarged lips, narrow caudal peduncle, bilobed caudal fin with the lower lobe longer than the upper one) also distinguish the new species from all its congeners in Southeastern Brazil and from most congeners anywhere. Examination of internal anatomy reveals that T. astromycterus shares some intriguing characteristics with the austral genus Bullockia Arratia et al., 1978. However, the phylogenetic significance of such similarities is still uncertain and will require further comparative study. For this reason, the new species is provisionally included in the all-encompassing genus Trichomycterus. An osteological description is presented on the basis of CT-scan imaging and cleared and stained specimens.

Distribution, morphological notes and conservation status of the psammophilus Microcambeva catfishes (Siluriformes: Trichomycteridae).

Sarcoglanidinae and Glanapteryginae catfishes are among the most unusual elements of the Neotropical freshwater fish fauna. Microcambeva ribeirae, M. barbata and M. draco are miniaturized Sarcoglanidinae known to occur in sandy microhabitats in drainages of the Brazilian Atlantic Forest. Due to their specific habitats, specimens of Microcambeva are rare in fish collections, and new records are considered noteworthy to warrant report. Recently, specimens of this genus were newly found in the Rio Doce basin in Minas Gerais and Espírito Santo States. Such new records expand the known geographic distribution of Microcambeva. Further records of Microcambeva for Rio Peruípe in south Bahia State are also reported. Comments on the distribution of Microcambeva species along the Atlantic Forest coastal basins and suggestions on its conservation status are also offered.

Indirect ELISA based on Hendra and Nipah virus proteins for the detection of henipavirus specific antibodies in pigs.

Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus in the family Paramyxoviridae. Henipavirus infections were first reported in the 1990's causing severe and often fatal outbreaks in domestic animals and humans in Southeast Asia and Australia. NiV infections were observed in humans in Bangladesh, India and in the first outbreak in Malaysia, where pigs were also infected. HeV infections occurred in horses in the North-Eastern regions of Australia, with singular transmission events to humans. Bats of the genus Pteropus have been identified as the reservoir hosts for henipaviruses. Molecular and serological indications for the presence of henipa-like viruses in African fruit bats, pigs and humans have been published recently. In our study, truncated forms of HeV and NiV attachment (G) proteins as well as the full-length NiV nucleocapsid (N) protein were expressed using different expression systems. Based on these recombinant proteins, Enzyme-linked Immunosorbent Assays (ELISA) were developed for the detection of HeV or NiV specific antibodies in porcine serum samples. We used the NiV N ELISA for initial serum screening considering the general reactivity against henipaviruses. The G protein based ELISAs enabled the differentiation between HeV and NiV infections, since as expected, the sera displayed higher reactivity with the respective homologous antigens. In the future, these assays will present valuable tools for serosurveillance of swine and possibly other livestock or wildlife species in affected areas. Such studies will help assessing the potential risk for human and animal health worldwide by elucidating the distribution of henipaviruses.

A new species of Copionodon representing a relictual occurrence of the Copionodontinae (Siluriformes: Trichomycteridae), with a CT-scan imaging survey of key subfamilial features

A new species of the Copionodontinae genus Copionodon is described from the riacho do Mosquito, tributary to rio Santo Antônio, rio Paraguaçu basin in the Diamantina Plateau, Bahia State, northeastern Brazil. This species represents the northernmost occurrence of the subfamily yet known and is a relictual population, apparently restricted to an underground sector of the stream and its immediate downstream exit. The new species can be readily recognized by the combination of the presence of opercular odontodes, the mostly uniform coloration of the body, and the lack of a free orbital rim. Despite several troglomorphic traits shared between the new species and Glaphyropoma spinosum, the two species are not closest relatives and all such similarities are convergent adaptations to the subterranean habitat. A CT-Scan study of the holotype of the new species is presented and allows a view into the details of copionodontine anatomy with unprecedented clarity.(AU)

Uma nova espécie de Copionodon (Copionodontinae) é descrita do riacho do Mosquito, tributário do rio Santo Antônio, bacia do rio Paraguaçu, Chapada Diamantina, Bahia, Brasil. Essa espécie representa a ocorrência mais ao norte da subfamília até então conhecida como uma população relictual, aparentemente restrita a um setor subterrâneo do riacho e sua saída à jusante. A nova espécie pode ser reconhecida pela combinação de odontódeos presentes no opérculo, coloração uniforme do corpo e ausência de margem orbital livre. Apesar de alguns caracteres troglomórficos compartilhados entre a nova espécie e Glaphyropoma spinosum, as duas espécies não são proximamente relacionadas e todas essas similaridades são interpretadas como adaptações convergentes ao ambiente subterrâneo. É apresentado um estudo de tomografia computadorizada do holótipo da nova espécie que permite a visualização de detalhes da anatomia interna de copionodontinae com clareza sem precedentes.(AU)

Bat Astroviruses: Towards Understanding the Transmission Dynamics of a Neglected Virus Family.

Bats belong to the order Chiroptera that represents the second largest order of mammals with more than 1200 species and an almost global distribution. Environmental changes and deforestation have severely influenced many ecosystems, intensifying the contact between wildlife and humans. In recent years, bats have been found to harbor a number of different viruses with zoonotic potential, as well as a great diversity of astroviruses, for which the question of zoonotic potential remains unanswered to date. Human astroviruses have been identified as the causative agent for diarrhea in children and immunocompromised patients. For a long time, astroviruses have been considered to be strictly species-specific. However, a great genetic diversity has recently been discovered among animal and human astroviruses that might indicate the potential of these viruses to cross species barriers. Furthermore, our knowledge about the tissue tropism of astroviruses has been expanded to some neurotropic strains that have recently been shown to be responsible for encephalitis in humans and livestock. This review gives an overview on what is known about astroviruses in bats, humans and livestock, especially bovines and pigs. Future research activities are suggested to unravel astrovirus infection dynamics in bat populations to further assess the zoonotic potential of these viruses.

Closely Related Syntopic Cytotypes of Astyanax taeniatus (Jenyns, 1842) from the Upper Piranga River, Upper Doce Basin in Southeastern Brazil.

Astyanax taeniatus occurs in coastal areas of southeastern Brazil, and it is very abundant in the Upper Doce River Basin. Our objective was to study C-, argyrophilic nucleolar organizer region (Ag-NOR) and fluorescent in situ hybridization (FISH) banding patterns using 5S, 18S, CA(15), and GA(15) repetitive DNA probes on a population of A. taeniatus present in the Piranga River, in the Doce Basin. Two syntopic cytotypes were found, both with 2n = 50: cytotype A (14m + 12sm + 16st + 8t) and cytotype B (10m + 14sm + 18st + 8t). In both cytotypes, heterochromatic blocks occurred in all the chromosomes; Ag-NOR sites were multiple, ranging from four to eight. The 5S rDNA probe marked eight chromosomes in both cytotypes, a unique condition within Astyanax, suggesting a recent divergence between these cytotypes. The 18S rDNA probe differed between the cytotypes, marking 10 and 8 chromosomes in cytotypes A and B, respectively. CA(15) and GA(15) FISH patterns were mainly subtelomeric, but CA(15) showed centromeric markings that were diagnostic for each cytotype. Although overall cytogenetic evidence suggests that these cytotypes are closely related, morphological and molecular data in progress will provide further hypothesis test on their phylogenetic relationship.

Expression, characterisation and antigenicity of a truncated Hendra virus attachment protein expressed in the protozoan host Leishmania tarentolae.

Hendra virus (HeV) is an emerging zoonotic paramyxovirus within the genus Henipavirus that has caused severe morbidity and mortality in humans and horses in Australia since 1994. HeV infection of host cells is mediated by the membrane bound attachment (G) and fusion (F) glycoproteins, that are essential for receptor binding and fusion of viral and cellular membranes. The eukaryotic unicellular parasite Leishmania tarentolae has recently been established as a powerful tool to express recombinant proteins with mammalian-like glycosylation patterns, but only few viral proteins have been expressed in this system so far. Here, we describe the purification of a truncated, Strep-tag labelled and soluble version of the HeV attachment protein (sHeV G) expressed in stably transfected L. tarentolae cells. After Strep-tag purification the identity of sHeV G was confirmed by immunoblotting and mass spectrometry. The functional binding of sHeV G to the HeV cell entry receptor ephrin-B2 was confirmed in several binding assays. Generated polyclonal rabbit antiserum against sHeV G reacted with both HeV and Nipah virus (NiV) G proteins in immunofluorescence assay and efficiently neutralised NiV infection, thus further supporting the preserved antigenicity of the purified protein.

Avanços em cirurgia guiada e no planejamento virtual / Advances in guided surgery and virtual planning

Hoje em dia, encontra-se disponível uma literatura crescente sobre implantodontia assistida por computador. Os estudos relatam a respeito da precisão no posicionamento dos implantes, comparando as posições planejadas virtualmente com as posições reais obtidas e demonstrando os resultados clínicos das diferentes técnicas. Como muitas dessas técnicas já estão disponíveis na prática clínica ou encontram-se no caminho de se firmar como opções de tratamento rotineiras, é de grande importância analisar os diferentes sistemas atualmente disponíveis, discutindo as possibilidades e limitações da implantodontia assistida por computador e suas aplicações clínicas...

Serologic survey of West Nile virus in horses from Central-West, Northeast and Southeast Brazil.

Since the emergence of West Nile virus (WNV) in North America in 1999, there have been several reports of WNV activity in Central and South American countries. To detect WNV in Brazil, we performed a serological survey of horses from different regions of Brazil using recombinant peptides from domain III of WNV. Positive samples were validated with the neutralisation test. Our results showed that of 79 ELISA-positive horses, nine expressed WNV-specific neutralising antibodies. Eight of the infected horses were from the state of Mato Grosso do Sul and one was from the state of Paraíba. Our results provide additional evidence for the emergence of WNV in Brazil and for its circulation in multiple regions of the country.

Production and diagnostic application of recombinant domain III of West Nile envelope protein in Brazil.

INTRODUCTION: West Nile virus (WNV) is a flavivirus with a natural cycle involving mosquitoes and birds. Over the last 11 years, WNV has spread throughout the Americas with the imminent risk of its introduction in Brazil. METHODS: Envelope protein domain III of WNV (rDIII) was bacterially expressed and purified. An enzyme-linked immunosorbent assay with WNV rDIII antigen was standardized against mouse immune fluids (MIAFs) of different flavivirus. RESULTS: WNV rDIII reacted strongly with St. Louis encephalitis virus (SLEV) MIAF but not with other flaviviruses. CONCLUSIONS: This antigen may be a potentially useful tool for serologic diagnosis and may contribute in future epidemiological surveillance of WNV infections in Brazil.