Complement activation induces excessive T cell cytotoxicity in severe COVID-19.

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. Proportions of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

Potential Involvement of the South American Lungfish Intelectin-2 in Innate-Associated Immune Modulation.

Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about its structural characteristics and carbohydrate interaction properties is available. This study investigated an intelectin transcript identified in RNA-seq data obtained from the South American lungfish (Lepidosiren paradoxa), namely LpITLN2-B. The structural analyses predicted LpITLN2-B to be a homo-trimeric globular protein with the fibrinogen-like functional domain (FReD), exhibiting a molecular mass of 57 kDa. The quaternary structure is subdivided into three monomers, A, B, and C, and each domain comprises 11 ß-sheets: an anti-parallel ß-sheet, a ß-hairpin, and a disordered ß-sheet structure. Molecular docking demonstrates a significant interaction with disaccharides rather than monosaccharides. The preferential interaction with disaccharides highlights the potential interaction with pathogen molecules, such as LPS and Poly(I:C). The hemagglutination assay inhibited lectins activity, especially maltose and sucrose, highlighting lectin activity in L. paradoxa samples. Overall, our results show the potential relevance of LpITLN2-B in L. paradoxa immune defense against pathogens.

Molecular Changes in the Brain of the Wintering Calidris pusilla in the Mangroves of the Amazon River Estuary.

Migrant birds prepare differently to fly north for breeding in the spring and for the flight to lower latitudes during autumn, avoiding the cold and food shortages of the Northern Hemisphere's harsh winter. The molecular events associated with these fundamental stages in the life history of migrants include the differential gene expression in different tissues. Semipalmated sandpipers (Calidris pusilla) are Arctic-breeding shorebirds that migrate to the coast of South America during the non-breeding season. In a previous study, we demonstrated that between the beginning and the end of the wintering period, substantial glial changes and neurogenesis occur in the brain of C. pusilla. These changes follow the epic journey of the autumn migration when a 5-day non-stop transatlantic flight towards the coast of South America and the subsequent preparation for the long-distance flight of the spring migration takes place. Here, we tested the hypothesis that the differential gene expressions observed in the brains of individuals captured in the autumn and spring windows are consistent with the previously described cellular changes. We searched for differential gene expressions in the brain of the semipalmated sandpiper, of recently arrived birds (RA) from the autumnal migration, and that of individuals in the premigratory period (PM) in the spring. All individuals were collected in the tropical coastal of northern Brazil in the mangrove region of the Amazon River estuary. We generated a de novo neurotranscriptome for C. pusilla individuals and compared the gene expressions across libraries. To that end, we mapped an RNA-Seq that reads to the C. pusilla neurotranscriptome in four brain samples of each group and found that the differential gene expressions in newly arrived and premigratory birds were related with neurogenesis, metabolic pathways (ketone body biosynthetic and the catabolic and lipid biosynthetic processes), and glial changes (astrocyte-dopaminergic neuron signaling, astrocyte differentiation, astrocyte cell migration, and astrocyte activation involved in immune response), as well as genes related to the immune response to virus infections (Type I Interferons), inflammatory cytokines (IL-6, IL-1ß, TNF, and NF-κB), NLRP3 inflammasome, anti-inflammatory cytokines (IL-10), and cell death pathways (pyroptosis- and caspase-related changes).

Prevalence of comorbidities and concomitant medication use in acromegaly: analysis of real-world data from the United States.

PURPOSE: Patients receiving treatment for acromegaly often experience significant associated comorbidities for which they are prescribed additional medications. We aimed to determine the real-world prevalence of comorbidities and concomitant medications in patients with acromegaly, and to investigate the association between frequency of comorbidities and number of concomitantly prescribed medications. METHODS: Administrative claims data were obtained from the IBM® MarketScan® database for a cohort of patients with acromegaly, identified by relevant diagnosis codes and acromegaly treatments, and a matched control cohort of patients without acromegaly from January 2010 through April 2020. Comorbidities were identified based on relevant claims and assessed for both cohorts. RESULTS: Overall, 1175 patients with acromegaly and 5875 matched patients without acromegaly were included. Patients with acromegaly had significantly more comorbidities and were prescribed concomitant medications more so than patients without acromegaly. In the acromegaly and control cohorts, respectively, 67.6% and 48.4% of patients had cardiovascular disorders, the most prevalent comorbidities, and 89.0% and 68.3% were prescribed > 3 concomitant medications (p < 0.0001). Hypopituitarism and hypothalamic disorders, sleep apnea, malignant neoplasms and cancer, and arthritis and musculoskeletal disorders were also highly prevalent in the acromegaly cohort. A moderate, positive correlation (Spearman correlation coefficient 0.60) was found between number of comorbidities and number of concomitant medications in the acromegaly cohort. CONCLUSION: Compared with patients without acromegaly, patients with acromegaly have significantly more comorbidities and are prescribed significantly more concomitant medications. Physicians should consider the number and type of ongoing medications for individual patients before prescribing additional acromegaly treatments.

A global perspective on evolving bioinformatics and data science training needs.

Bioinformatics is now intrinsic to life science research, but the past decade has witnessed a continuing deficiency in this essential expertise. Basic data stewardship is still taught relatively rarely in life science education programmes, creating a chasm between theory and practice, and fuelling demand for bioinformatics training across all educational levels and career roles. Concerned by this, surveys have been conducted in recent years to monitor bioinformatics and computational training needs worldwide. This article briefly reviews the principal findings of a number of these studies. We see that there is still a strong appetite for short courses to improve expertise and confidence in data analysis and interpretation; strikingly, however, the most urgent appeal is for bioinformatics to be woven into the fabric of life science degree programmes. Satisfying the relentless training needs of current and future generations of life scientists will require a concerted response from stakeholders across the globe, who need to deliver sustainable solutions capable of both transforming education curricula and cultivating a new cadre of trainer scientists.

A new pan-European Train-the-Trainer programme for bioinformatics: pilot results on feasibility, utility and sustainability of learning.

Demand for training life scientists in bioinformatics methods, tools and resources and computational approaches is urgent and growing. To meet this demand, new trainers must be prepared with effective teaching practices for delivering short hands-on training sessions-a specific type of education that is not typically part of professional preparation of life scientists in many countries. A new Train-the-Trainer (TtT) programme was created by adapting existing models, using input from experienced trainers and experts in bioinformatics, and from educational and cognitive sciences. This programme was piloted across Europe from May 2016 to January 2017. Preparation included drafting the training materials, organizing sessions to pilot them and studying this paradigm for its potential to support the development and delivery of future bioinformatics training by participants. Seven pilot TtT sessions were carried out, and this manuscript describes the results of the pilot year. Lessons learned include (i) support is required for logistics, so that new instructors can focus on their teaching; (ii) institutions must provide incentives to include training opportunities for those who want/need to become new or better instructors; (iii) formal evaluation of the TtT materials is now a priority; (iv) a strategy is needed to recruit, train and certify new instructor trainers (faculty); and (v) future evaluations must assess utility. Additionally, defining a flexible but rigorous and reliable process of TtT 'certification' may incentivize participants and will be considered in future.

Establishing a distributed national research infrastructure providing bioinformatics support to life science researchers in Australia.

EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distributed national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia's capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs. The activities of EMBL-ABR are focussed in six key areas, aligning with comparable international initiatives such as ELIXIR, CyVerse and NIH Commons. These key areas-Tools, Data, Standards, Platforms, Compute and Training-are described in this article.

A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. METHODS: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. RESULTS: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. CONCLUSION: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.

TLR4 and TLR8 variability in Amazonian and West Indian manatee species from Brazil.

Amazonian (Trichechus inunguis) and West Indian (Trichechus manatus) manatees are aquatic mammals vulnerable to extinction found in the Amazon basin and the coastal western Atlantic. Toll-like receptors (TLR) play a key role in recognizing pathogen-associated molecular patterns using leucine-rich repeats (LRRs). We described the diversity of TLR4 and TLR8 genes in these two species of manatee. Amazonian manatee showed seven SNPs in TLR4 and the eight in TLR8, while West Indian manatee shared four and six of those SNPs, respectively. In our analysis, TLR4 showed one non-conservative amino acid replacement substitution in LRR7 and LRR8, on the other hand, TLR8 was less variable and showed only conserved amino acid substitutions. Selection analysis showed that only one TLR4 site was subjected to positive selection and none in TLR8. TLR4 in manatees did not show any evidence of convergent evolution compared to species of the cetacean lineage. Differences in TLR4 and TLR8 polymorphism may be related to distinct selection by pathogens, population reduction of West Indian manatees, or an expected consequence of population expansion in Amazonian manatees. Future studies combining pathogen association and TLR polymorphism may clarify possible roles of these genes and be used for conservation purposes of manatee species.

A systematic literature review of leptospirosis outbreaks worldwide, 1970-2012.

OBJECTIVE: This review describes the geographic and temporal distribution of, detection methods for, and other epidemiological features of published leptospirosis outbreaks, with the aim of informing efforts to standardize outbreak-reporting practices. METHODS: We conducted a systematic review of leptospirosis outbreaks reported in the scientific literature and ProMED during 1970-2012. Predefined criteria were used to identify and classify outbreaks and a standard form was used to extract information. RESULTS: During 1970-2012, we identified 318 outbreaks (average: 7 outbreaks/year; range: 1-19). Most outbreaks were reported in the Latin America and the Caribbean region (36%), followed by Southern Asia (13%), and North America (11%). Most outbreaks were located in tropical and subtropical ecoregions (55%). Quality classification showed that there was clear description of laboratory-confirmed cases in 40% of outbreaks. Among those, the average outbreak size was 82 cases overall (range: 2-2 259) but reached 253 cases in tropical/subtropical ecoregions. Common risk factors included outdoor work activities (25%), exposure to floodwaters (23%), and recreational exposure to water (22%). Epidemiologic investigation was conducted in 80% of outbreaks, mainly as case interviews. Case fatality was 5% overall (range: 0%-60%). CONCLUSIONS: Outbreak reporting increased over the study period with outbreaks covering tropical and non-tropical regions. Outbreaks varied by size, setting, and risk factors; however, data reviewed often had limited information regarding diagnosis and epidemiology. Guidelines are recommended to develop standardized procedures for diagnostic and epidemiological investigations during an outbreak and for reporting.

OBJETIVO: Describir la distribución geográfica y temporal, los métodos de detección y otras características epidemiológicas de los brotes de leptospirosis publicados con el fin de fundamentar los esfuerzos tendientes a estandarizar las prácticas empleadas en la notificación de brotes. MÉTODOS: Se llevó a cabo una revisión sistemática de los brotes de leptospirosis notificados en la bibliografía científica y en ProMED entre 1970 y 2012. Se utilizaron criterios predefinidos para identificar y clasificar los brotes y se empleó un formulario estándar para extraer la información. RESULTADOS: Entre 1970 y 2012 se identificaron 318 brotes (promedio: 7 brotes/año; rango: 1-19), la mayoría de ellos en América Latina y el Caribe (36%), región seguida por Asia meridional (13%) y América del Norte (11%). La mayoría de los brotes se localizaron en ecorregiones tropicales y subtropicales (55%). La clasificación cualitativa reveló que en el 40% de los brotes había una clara descripción de los casos confirmados por laboratorio. Entre ellos, el tamaño promedio del brote fue de 82 casos (rango: 2-2259 casos) pero alcanzó los 253 casos en ecorregiones tropicales o subtropicales. Entre los factores de riesgo frecuentes figuraban las actividades laborales al aire libre (25%), la exposición a agua proveniente de inundaciones (23%) y la exposición a agua con fines recreativos (22%). En el 80% de los brotes se realizaron investigaciones epidemiológicas, principalmente entrevistas de casos. La mortalidad específica de los casos fue del 5% (rango: 0%-60%). CONCLUSIONES: La notificación de brotes aumentó durante el período de estudio, y los brotes abarcaron regiones tropicales y no tropicales. Los brotes fueron diferentes en cuanto a su tamaño, el entorno y los factores de riesgo; sin embargo, los datos examinados con frecuencia incluían una información limitada respecto del diagnóstico y la epidemiología. Se recomiendan directrices para elaborar procedimientos estandarizados para las investigaciones diagnósticas y epidemiológicas durante un brote y para su notificación.

Determination of Volatile Organic Compounds and Antibacterial Activity of the Amazonian Cyanobacterium Synechococcus sp. Strain GFB01.

Cyanobacteria exhibit great biotechnological potential due to their capacity to produce compounds with various applicability. Volatile organic compounds (VOCs) possess low molecular weight and high vapor pressure. Many volatiles produced by microorganisms have biotechnological potential, including antimicrobial activity. This study aimed to investigate the VOCs synthesized by cyanobacterium Synechococcus sp. strain GFB01, and the influence of nitrate and phosphate on its antibacterial potential. The strain was isolated from the surface of the freshwater lagoon Lagoa dos Índios, Amapá state, in Northern Brazil. After cultivation, the VOCs were extracted by a simultaneous distillation-extraction process, using a Likens-Nickerson apparatus (2 h), and then identified by GC-MS. The extracts did not display inhibitory activity against the Gram-positive bacteria tested by the disk-diffusion agar method. However, the anti-Salmonella property in both extracts (methanol and aqueous) was detected. The main VOCs identified were heptadecane (81.32%) and octadecyl acetate (11.71%). To the best of our knowledge, this is the first study of VOCs emitted by a cyanobacterium from the Amazon that reports the occurrence of 6-pentadecanol and octadecyl acetate in cyanobacteria.

Seasonal changes in the song control nuclei of the Rufous-bellied Thrush, Turdus rufiventris (Oscine, Passeriformes, and Turdidae).

In vocal learning birds, memorization and song production rely on a set of telencephalic nuclei referred to as the song control system. Seasonal changes in song production are correlated with changes in the volume of the song control nuclei and are influenced by photoperiodic conditions and hormonal cues. The seasonal volume changes in the avian brain that controls singing are thought to involve regulation of neuronal replacement, which is a striking example of neuronal plasticity. The Rufous-bellied Thrush (Turdus rufiventris) is a seasonally breeding bird that actively sings during the spring and summer (breeding season) and is relatively silent in the fall, yet possible mechanisms behind the periodic changes in song production remain unknown. Here, we have examined two song control nuclei: High vocal center (HVC) and robust nucleus of arcopallium (RA) in fall males, spring males, and fall females of Rufous-bellied Thrush. The cytoarchitectonic organization was analyzed and quantified from Nissl-stained sections, and gene expression of song nuclei markers was examined by in situ hybridization during breeding and nonbreeding seasons. We observed a reduction in HVC volume and reductions in parvalbumin, and RGS4 expression in HVC and RA in males during the nonbreeding season. These findings provide evidence of seasonal changes in the song system of a representative tropical-breeding Turdidae species that does not maintain territories or mate bonding, setting the histological and molecular groundwork for future studies aimed at better understanding of song nuclei changes in seasonally breeding songbirds.

Structure of Hierridin C, Synthesis of Hierridins B and C, and Evidence for Prevalent Alkylresorcinol Biosynthesis in Picocyanobacteria.

Small, single-celled planktonic cyanobacteria are ubiquitous in the world's oceans yet tend not to be perceived as secondary metabolite-rich organisms. Here we report the isolation and structure elucidation of hierridin C, a minor metabolite obtained from the cultured picocyanobacterium Cyanobium sp. LEGE 06113. We describe a simple, straightforward synthetic route to the scarcely produced hierridins that relies on a key regioselective halogenation step. In addition, we show that these compounds originate from a type III PKS pathway and that similar biosynthetic gene clusters are found in a variety of bacterial genomes, most notably those of the globally distributed picocyanobacteria genera Prochlorococcus, Cyanobium and Synechococcus.

Cardiac Extracellular Vesicles (EVs) Released in the Presence or Absence of Inflammatory Cues Support Angiogenesis in Different Manners.

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs are involved, we isolated them by differential centrifugation from the conditioned medium derived either in the presence or absence of a pro-inflammatory cytokine cocktail. Murine recipient cells internalized CardAP-EVs as determined by an intracellular detection of human proteins, such as CD63, by a novel flow cytometry method for studying EV-cell interaction. Moreover, endothelial cells treated for 24 h with either unstimulated or cytokine stimulated CardAP-EVs exhibited a higher tube formation capability on Matrigel. Interestingly, unstimulated CardAP-EVs caused endothelial cells to release significantly more vascular endothelial growth factor and interleukin (IL)-6, while cytokine stimulated CardAP-EVs significantly enhanced the release of IL-6 and IL-8. By nCounter® miRNA expression assay (NanoString Technologies) we identified microRNA 302d-3p to be enhanced in unstimulated CardAP-EVs compared to their cytokine stimulated counterparts, which was verified by quantitative polymerase chain reaction. This study demonstrates that both CardAP-EVs are pro-angiogenic by inducing different factors from endothelial cells. This would allow to select potent targets for a safe and efficient therapeutic application.

Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with acromegaly naïve to somatostatin-receptor ligands: analysis of three multicenter clinical trials.

PURPOSE: In clinical research involving acromegalic patients naïve to somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs octreotide LAR and pasireotide LAR, respectively, achieved GH < 2.5 ng/mL + normalized IGF-1 concentrations. The proportions achieving control appeared higher in the post-surgery compared with the de-novo setting with pasireotide, but more similar with octreotide. Using pooled data from multicenter clinical trials, we examined the biochemical efficacy of lanreotide depot/Autogel in similar settings. METHODS: Inclusion criteria: Ipsen-sponsored, 48-52-week trials in SRL-naïve acromegalic populations receiving lanreotide depot (60-120 mg); patients were included if de novo (no prior acromegaly treatment) or post-surgery (no medical treatment; radiotherapy allowed unless within previous 3 years). Efficacy endpoints included normalized IGF-1 levels and GH < 2.5 ng/mL + normalized IGF-1 at study end/last value available. ANALYSES: all patients (analysis #1) and subset with baseline GH > 5 ng/mL (analysis #2). RESULTS: Three studies were included. Analysis #1: normalized IGF-1 was achieved by 42% (71/171) of patients overall (post-surgery, 46% [21/46]; de-novo, 40% [50/125]); GH < 2.5 ng/mL + normalized IGF-1 was achieved by 35% (59/171) (39% [18/46] and 33% [41/125], respectively). Analysis #2: normalized IGF-1 levels, 39% (46/118) (post-surgery, 40% [10/25]; de-novo, 39% [36/93]); GH < 2.5 ng/mL + normalized IGF-1, 31% (36/118) (28% [7/25] and 31% [29/93], respectively). CONCLUSION: In these pooled analyses of SRL-naïve patients receiving lanreotide depot, 39-42% achieved IGF-1 control and 31-35% achieved GH and IGF-1 control. Control rates within post-surgery cohorts did not differ markedly from those in corresponding de-novo cohorts.

A road map for leptospirosis research and health policies based on country needs in Latin America.

This report summarizes the presentations, discussions and the recommendations coming from the Oswaldo Cruz Institute/FIOCRUZ International Workshop for Leptospirosis Research Based on Country Needs and the 5th Global Leptospirosis Environmental Action Network meeting, which was held in the city of Rio de Janeiro, Brazil, 10-12 November 2015. The event focused on health policy and worked to develop a road map as a consensus document to help guide decision-making by policymakers, funding bodies, and health care professionals. The direction that leptospirosis research should take in the coming years was emphasized, taking into account the needs of countries of Latin America, as well as experiences from other world regions, as provided by international experts. The operational concepts of "One Health" and translational research underlaid the discussions and the resulting recommendations. Despite the wide geographic distribution of leptospirosis and its impact in terms of incidence, morbidity, and mortality, leptospirosis is not yet considered a "tool-ready" disease for global initiatives. Surveillance programs need new tools and strategies for early detection, prevention, and follow-up. The major recommendations developed at the Rio meeting cover both health policy and research. The health policy recommendations should be taken into account by decisionmakers, government officials, and the Pan American Health Organization. The priorities for research, technological development, and innovation should be considered by research institutions, universities, and stakeholders.

Towards a Novel Patch Material for Cardiac Applications: Tissue-Specific Extracellular Matrix Introduces Essential Key Features to Decellularized Amniotic Membrane.

There is a growing need for scaffold material with tissue-specific bioactivity for use in regenerative medicine, tissue engineering, and for surgical repair of structural defects. We developed a novel composite biomaterial by processing human cardiac extracellular matrix (ECM) into a hydrogel and combining it with cell-free amniotic membrane via a dry-coating procedure. Cardiac biocompatibility and immunogenicity were tested in vitro using human cardiac fibroblasts, epicardial progenitor cells, murine HL-1 cells, and human immune cells derived from buffy coat. Processing of the ECM preserved important matrix proteins as demonstrated by mass spectrometry. ECM coating did not alter the mechanical characteristics of decellularized amniotic membrane but did cause a clear increase in adhesion capacity, cell proliferation and viability. Activated monocytes secreted less pro-inflammatory cytokines, and both macrophage polarization towards the pro-inflammatory M1 type and T cell proliferation were prevented. We conclude that the incorporation of human cardiac ECM hydrogel shifts and enhances the bioactivity of decellularized amniotic membrane, facilitating its use in future cardiac applications.

Comparative mitogenomic analyses of Amazona parrots and Psittaciformes.

Amazon parrots are long-lived birds with highly developed cognitive skills, including vocal learning. Several parrot mitogenomes have been sequenced, but important aspects of their organization and evolution are not fully understood or have limited experimental support. The main aim of the present study was to describe the mitogenome of the blue-fronted Amazon, Amazona aestiva, and compare it to other mitogenomes from the genus Amazona and the order Psittaciformes. We observed that mitogenomes are highly conserved among Amazon parrots, and a detailed analysis of their duplicated control regions revealed conserved blocks. Population level analyses indicated that the specimen analyzed here seems to be close to A. aestiva individuals from Bahia state. Evolutionary relationships of 41 Psittaciformes species and three outgroups were inferred by BEAST. All relationships were retrieved with high support.