VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes.

VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.

Prevalence of human leptospirosis in the Americas: a systematic review and meta-analysis.

Objective: To describe the prevalence of leptospirosis in the Americas. Methods: A systematic review and meta-analysis, in the period 1930 to 2017, performed on a search of six platforms: PubMed, Web of Science, Scopus, Lilacs, Embase, and Cochrane. Results: The search found 77 publications of which 53 (68%) were from the period 2000-2017. Of the 77, 62 studies were included in the analysis, from North America (11, 17%), Central America (9, 14%), and South America (42, 67%), and 22 studies were from urban areas. Leptospirosis prevalence in the 62 studies analyzed corresponded to 28% (95% CI [23, 32]). Countries with higher prevalence were United States of America (41%), Colombia (29%), and Brazil (21%). The most frequent serovars found were Icterohaemorrhagiae (43 of 77 publications, 55%), Canicola (35, 45%), Pomona (28, 36%), and Grippotyphosa (26, 33%). Conclusions: There is variability of Leptospira species and serovars with heterogenous distribution throughout the Americas, with high prevalence in some countries, highlighting the need for action to control the disease.

Dose-response effect of Montelukast on post-extraction dental socket repair and skeletal phenotype of mice.

Bone metabolism and repair are directly regulated by arachidonic acid metabolites. At present, we analyzed the dose-response effects of a selective cysteinyl leukotriene receptor type-1 antagonist during bone repair after tooth extraction and on non-injured skeleton. Sixty-three 129 Sv/Ev male mice composed the groups: C-Control (saline solution); MTK2-2 mg/Kg of Montelukast (MTK) and MTK4-4 mg/Kg of MTK, daily administered by mouth throughout all experimental periods set at 7, 14, and 21 days post-operative. Dental sockets were analyzed by computed microtomography (microCT), histopathology, and immunohistochemistry. Femurs, L5 vertebra and organs were also removed for observation. Blood was collected for plasma bone and liver markers. Histopathology and microCT analysis revealed early socket repair of MTK2 and MTK4 animals, with significant increased BV/TV at days 14 and 21 compared to C. Higher plasma calcium was detected at days 7 and 21 in MTK4 in comparison to C, while phosphate was significantly increased in MTK2 in the same periods in comparison to C and MTK4. No significant differences were found regarding plasma ALP and TRAP, neither for local TRAP and Runx2 immunolabeling at the healing sockets. Organs did not present histological abnormalities. Increased AST levels have been detected in distinct groups and periods. In general, femur phenotype was improved in MTK treated animals. Collectively, MTK promoted early bone formation after tooth extraction and increased bone quality of femurs and vertebra in a time-dose-dependent manner, and should be considered as an alternative therapy when improved post-extraction socket repair or skeleton preservation is required.

Seasonal dynamics of Amblyomma sculptum in two areas of the Cerrado biome midwestern Brazil, where human cases of rickettsiosis have been reported.

Amblyomma sculptum is a common human-biting tick in Brazil, where it plays an important role as a vector of Rickettsia rickettsii, the agent of the Brazilian spotted fever. Herein, we studied the seasonal dynamics of A. sculptum in an urban area of the Cerrado biome in midwestern Brazil, where human rickettsiosis is endemic. Ticks were collected in two sites located within the campus of Federal University of Goiás. The collections were done by dragging, flagging and visual search. In total, 117,685 ticks were collected, including 100,627 Amblyomma spp. larvae, 10,055 nymphs and 6977 adults of A. sculptum, and one nymph and 25 adults of Amblyomma dubitatum. The highest peak of larvae occurred in June 2018 and in July 2019, whereas nymphs peaked in July 2018 and September 2019. Adults reached their highest numbers in March 2018 and November 2019. These data suggest that A. sculptum develops one generation per year in this urban area of the Cerrado biome in midwestern Brazil. Interestingly, the peak of nymphs occurred during the same period of all confirmed cases of rickettsiosis in Goiás, suggesting a possible relationship between the seasonal dynamics of this tick stage and rickettsiosis transmission in this state.

Pre-pubertal exposure to ibuprofen impairs sperm parameters in male adult rats and compromises the next generation.

Ibuprofen is one of the most commonly prescribed anti-inflammatory drugs in pediatric practice. This drug inhibits the cyclooxygenase enzyme, reducing the production of prostaglandin, an important mediator on male reproductive function. We examined if pre-pubertal treatment with ibuprofen in male rats can affect the reproductive parameters of these animals in adult life and on their descendants. Male rats (23 days old) received ibuprofen (0; 2.4; 7.2 or 14.3 mg/kg/day), per gavage, from postnatal day (PND) 23 to 53. At sexual maturity, treated males were placed with untreated females for obtaining the next generation (F1). The highest dose of ibuprofen interfered in sexual behavior and reduced the fertility potential of these animals in adulthood. Additionally, the ibuprofen treatment altered the sperm quantity and quality, as evidenced by a decrease in sperm motility and in the daily sperm production in the testis. Testosterone levels were also reduced by pre-pubertal treatment. The paternal treatment with this drug also influenced the reproductive outcomes of progeny. The male offspring from males treated exhibited acceleration in sperm transit time in the epididymis and the number and volume of Leydig cell nuclei were decreased, while the estrous cyclicity was displayed and the fertility potential reduced in the female offspring. The pre-pubertal ibuprofen-treatment caused negative reproductive impacts in adulthood, compromising sperm quality and quantity, as well as interfered in the reproductive outcomes of the next generation.

High abdominal adiposity and low phase angle in overweight renal transplant recipients.

Obesity is associated with increased risk of cardiovascular disease (CVD). Body mass index (BMI) is the most used parameter for obesity screening. However, the evaluation of CVD risk in overweight individuals should include the assessment of body fat distribution and body composition. Renal transplant recipients (RTR) have a high CVD risk and frequently present weight gain and loss of lean mass. The aim of this study was to evaluate body fat distribution and body composition in overweight RTR. This cross-sectional study was conducted with 86 RTR and 86 hypertensive individuals (comparison group, CG) presenting BMI 25-35 Kg/m2 and 45-70 years. Anthropometric evaluation included BMI, waist circumference, waist-to-height ratio, and a body shape index. Body composition was evaluated with bioelectrical impedance analysis (BIA). Glomerular filtration rate was estimated (eGFR) by CKD-EPI equation. RTR group (RTRG) and CG presented similar age and BMI. RTRG when compared to CG presented lower percentage of women and eGFR; higher central adiposity; and lower values of reactance, intracellular water, body cell mass and phase angle, more consistently observed in women. This study suggests that overweight RTR present higher abdominal adiposity and impairment in BIA parameters that are sensitive indicators of impaired membrane integrity, water distribution, and body cell mass.

Sarcopenia and its components in adult renal transplant recipients: prevalence and association with body adiposity.

Sarcopenia is a progressive and generalised skeletal muscle disorder associated with adverse outcomes. Ageing causes primary sarcopenia, while secondary causes include chronic kidney disease (CKD), long-term use of glucocorticoids and obesity. The aim of the present study was to evaluate the prevalence of sarcopenia using guidelines recommended by the European Working Group on Sarcopenia in Older People (EWGSOP, 2010; EWGSOP2, 2018) and the Foundation of the National Institutes of Health (FNIH) and analyse the relationship between sarcopenia and body adiposity in adult renal transplant recipients (RTR). This was a cross-sectional study of adult RTR (BMI ≥ 18·5 kg/m2). Body composition was evaluated by dual-energy X-ray absorptiometry (DXA) and anthropometry. Glomerular filtration rate was estimated (eGFR) by CKD-Epidemiology Collaboration equation. The prevalence of sarcopenia in adult RTR (n 185; 57 % men, 50 (se 0·82) years and eGFR 55·80 (se 1·52) ml/min) was 7 % (FNIH), 11 % (EWGSOP2) and 17 % (EWGSOP). Low muscle mass, muscle function and physical performance affected, respectively, up to 28, 46 and 10 % of the participants. According to EWGSOP and EWGSOP2, body adiposity evaluated by anthropometry and DXA (percentage trunk fat) was lower in participants with sarcopenia. Conversely, according to the FNIH criteria, RTR with sarcopenia presented higher waist:height ratio. The present study suggests that adult RTR sarcopenia prevalence varies according to the diagnostic criteria; low muscle mass, low muscle function and low physical performance are common conditions; the association of body adiposity and sarcopenia depends on the criteria used to define this syndrome; and the FNIH criteria detected higher adiposity in individuals with sarcopenia.

Vitamin B12 status in kidney transplant recipients: association with dietary intake, body adiposity and immunosuppression.

The aim of the present study was to evaluate the prevalence of vitamin B12 (B12) deficiency in kidney transplant recipients (KTR) and its possible association with B12 dietary intake, body adiposity and immunosuppressive drugs. In this cross-sectional study, we included 225 KTR, aged 47·50 (sd 12·11) years, and 125 (56 %) were men. Serum levels of B12 were determined by chemiluminescent microparticle intrinsic factor assay and the cut-off of 200 pg/ml was used to stratify KTR into B12-sufficient or B12-deficient group. B12 dietary intake was evaluated by three 24 h dietary recalls and was considered adequate when ≥2·4 µg/d. Body adiposity was estimated after taking anthropometric measures and using the dual-energy X-ray absorptiometry (DXA) method. B12 deficiency was seen in 14 % of the individuals. B12-deficient group, compared with the B12-sufficient group, exhibited lower intake of B12 (median 2·42 (interquartile range (IQR) 1·41-3·23) v. 3·16 (IQR 1·94-4·55) µg/d, P = 0·04) and higher values of waist circumference (median 96·0 (IQR 88·0-102·5) v. 90·0 (IQR 82·0-100·0) cm, P = 0·04). When the analysis included only women, B12 deficiency was associated with higher total and central body adiposity measurements obtained with anthropometry (BMI, body adiposity index, waist and neck circumferences) and DXA (total and trunk body fat). Among individuals with adequate intake of B12, the deficiency of this vitamin was more frequently seen in those using mycophenolate mofetil (MMF) (17 %) v. azathioprine (2 %), P = 0·01. In conclusion, the prevalence of B12 deficiency in KTR was estimated as 14 % and was associated with reduced intake of B12 as well as higher adiposity, especially in women, and with the use of MMF.

EuPathDB: the eukaryotic pathogen genomics database resource.

The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host-pathogen interactions.

Growth hormone-releasing peptide 6 prevents cutaneous hypertrophic scarring: early mechanistic data from a proteome study.

Hypertrophic scars (HTS) and keloids are forms of aberrant cutaneous healing with excessive extracellular matrix (ECM) deposition. Current therapies still fall short and cause undesired effects. We aimed to thoroughly evaluate the ability of growth hormone releasing peptide 6 (GHRP6) to both prevent and reverse cutaneous fibrosis and to acquire the earliest proteome data supporting GHRP6's acute impact on aesthetic wound healing. Two independent sets of experiments addressing prevention and reversion effects were conducted on the classic HTS model in rabbits. In the prevention approach, the wounds were assigned to topically receive GHRP6, triamcinolone acetonide (TA), or vehicle (1% sodium carboxy methylcellulose [CMC]) from day 1 to day 30 post-wounding. The reversion scheme was based on the infiltration of either GHRP6 or sterile saline in mature HTS for 4 consecutive weeks. The incidence and appearance of HTS were systematically monitored. The sub-epidermal fibrotic core area of HTS was ultrasonographically determined, and the scar elevation index was calculated on haematoxylin/eosin-stained, microscopic digitised images. Tissue samples were collected for proteomics after 1 hour of HTS induction and treatment with either GHRP6 or vehicle. GHRP6 prevented the onset of HTS without the untoward reactions induced by the first-line treatment triamcinolone acetonide (TA); however, it failed to significantly reverse mature HTS. The preliminary proteomic study suggests that the anti-fibrotic preventing effect exerted by GHRP6 depends on different pathways involved in lipid metabolism, cytoskeleton arrangements, epidermal cells' differentiation, and ECM dynamics. These results enlighten the potential success of GHRP6 as one of the incoming alternatives for HTS prevention.

Vitamin D status in renal transplant recipients living in a low-latitude city: association with body fat, cardiovascular risk factors, estimated glomerular filtration rate and proteinuria.

Recent evidence suggests that vitamin D deficiency is associated with CVD, impaired kidney function and proteinuria. To date, no study has evaluated these associations in renal transplant recipients (RTR) adjusting for body adiposity assessed by a 'gold standard' method. This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum 25-hydroxyvitamin D (25(OH)D) concentration was used to define vitamin D status as follows: 10 % (n 19) had vitamin D deficiency (30 ng/ml). Percentage of body fat (DXA) was significantly associated with vitamin D deficiency independently of age, sex and eGFR. Lower 25(OH)D was associated with higher odds of the metabolic syndrome and dyslipidaemia after adjustment for age, sex and eGFR, but not after additional adjustment for body fat. Hypertension and diabetes were not related to 25(OH)D. Lower serum 25(OH)D was associated with increasing proteinuria and decreasing eGFR even after adjustments for age, sex and percentage of body fat. This study suggests that in RTR of a low-latitude city hypovitaminosis D is common, and is associated with excessive body fat, decreased eGFR and increased proteinuria.

EuPathDB: the eukaryotic pathogen database.

EuPathDB (http://eupathdb.org) resources include 11 databases supporting eukaryotic pathogen genomic and functional genomic data, isolate data and phylogenomics. EuPathDB resources are built using the same infrastructure and provide a sophisticated search strategy system enabling complex interrogations of underlying data. Recent advances in EuPathDB resources include the design and implementation of a new data loading workflow, a new database supporting Piroplasmida (i.e. Babesia and Theileria), the addition of large amounts of new data and data types and the incorporation of new analysis tools. New data include genome sequences and annotation, strand-specific RNA-seq data, splice junction predictions (based on RNA-seq), phosphoproteomic data, high-throughput phenotyping data, single nucleotide polymorphism data based on high-throughput sequencing (HTS) and expression quantitative trait loci data. New analysis tools enable users to search for DNA motifs and define genes based on their genomic colocation, view results from searches graphically (i.e. genes mapped to chromosomes or isolates displayed on a map) and analyze data from columns in result tables (word cloud and histogram summaries of column content). The manuscript herein describes updates to EuPathDB since the previous report published in NAR in 2010.

Ophthalmic Manifestations of Monkeypox Virus Infection: A Cases Series.

This retrospective case series aims to describe the ophthalmic manifestations of the Monkeypox virus infection in seven patients evaluated in two countries of South America (Colombia and Brazil). Two had skin lesions in the eyelid, and five had conjunctivitis. None had intraocular involvement. Three of seven patients had a history of Human Immunodeficiency Virus infection, and all patients had lesions in the genital region, suggesting sexual-contact transmission. In 6 of 7 cases, conjunctival RT-PCR was positive for the Monkeypox virus, including one case without conjunctival vesicles. In all cases, lesions resolved without complications, and just two required antiviral treatment. All patients demonstrated improvement without complications. RT-PCR positivity in conjunctiva demonstrated the presence of the Monkeypox virus, suggesting that ocular-mediated transmission could be plausible. Ophthalmologists should be aware of this ophthalmic manifestation.

Do Men and Women Differ in Hematological Adaptations to 24 Weeks of Crossfit® Training?

Regular exercise can modulate the immune system functioning through changes in the number and function of leukocytes as well as in red blood cells and other typical blood markers. High intensity exercise promotes increases in cytotoxic activity, phagocytic capacity, chemotaxis and cell apoptosis. The aim of the study was to compare the chronic effects of a 24-week training program using CrossFit® methodology on hematological variables of men vs. women. Twenty-nine CrossFit® athletes (35.3 ± 10.4 years, 175.0 ± 9.2 cm, 79.5 ± 16.4 kg) participated in the study. The blood count, the lipid profile and glucose markers were measured every two months during the study period. The erythrocyte count and hemoglobin concentrations increased in months 4 and 6 in men and women, respectively. Hematocrit levels increased in men in months 2, 4 and 6, while in women only in month 6. Red cell distribution width increased in men in month 6 when compared to the value in month 2. Segmented neutrophils increased in men in month 6 and eosinophil levels increased in women in month 6. Differences between the two sexes were observed in monocytes levels at baseline, as well as in months 2, 4 and 6. Cross-Fit® training increased red cell count indicators in both sexes, which may be related to increased erythropoiesis. Some white blood cell counts were altered and these differed between sexes. The number of lymphocytes remained stable throughout the experiment.

Systematic surveillance tools to reduce rodent pests in disadvantaged urban areas can empower communities and improve public health.

Rodents are notorious pests, known for transmitting major public health diseases and causing agricultural and economic losses. The lack of site-specific and national standardised rodent surveillance in several disadvantaged communities has rendered interventions targeted towards rodent control as often ineffective. Here, by using the example from a pilot case-study in the Bahamas, we present a unique experience wherein, through multidisciplinary and community engagement, we simultaneously developed a standardised national surveillance protocol, and performed two parallel but integrated activities: (1) eight days of theoretical and practical training of selected participants; and (2) a three-month post-training pilot rodent surveillance in the urban community of Over-the-Hill, Nassau, The Bahamas. To account for social and environmental conditions influencing rodent proliferation in the Bahamas, we engaged selected influential community members through a semi-structured interview and gathered additional site-specific information using a modified Centers for Diseases Control and Prevention (CDC) exterior and interior rodent evaluation form, along with other validated instruments such as tracking plates and snap trapping, to test and establish a standardised site-specific rodent surveillance protocol tailored for the Bahamas. Our engagement with community members highlighted poor disposal of animal and human food, irregular garbage collection, unapproved refuse storage, lack of accessible dumpsters, poor bulk waste management, ownership problems and structural deficiencies as major factors fuelling rodent proliferation in the study areas. Accordingly, results from our pilot survey using active rodent signs (that is, the presence of rodent runs, burrows, faecal material or gnawed material) as a proxy of rodent infestation in a generalized linear model confirmed that the variables earlier identified during the community engagement program as significantly correlated with rodent activities (and capturing) across the study areas. The successful implementation of the novel site-specific protocol by trained participants, along with the correlation of their findings with those recorded during the community engagement program, underscores its suitability and applicability in disadvantaged urban settings. This experience should serve as a reference for promoting a standardised protocol for monitoring rodent activities in many disadvantaged urban settings of the Global South, while also fostering a holistic understanding of rodent proliferation. Through this pilot case-study, we advocate for the feasibility of developing sustainable rodent control interventions that are acceptable to both local communities and public authorities, particularly through the involvement of a multidisciplinary team of professionals and community members.

Pharmacodynamic of Recombinant Human Interferon Alpha-2b Nasal Drops and Effective Prophylaxis Against SARS-COV-2 Infection.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

Progression of microalbuminuria in SHR is associated with lower expression of critical components of the apical endocytic machinery in the renal proximal tubule.

Cumulative epidemiological evidence indicates that the presence of microalbuminuria predicts a higher frequency of cardiovascular events, peripheral disease, and mortality in essential hypertension. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin by receptor-mediated endocytosis. This study aimed to evaluate the temporal pattern of urinary protein excretion and to test the hypothesis that progression of microalbuminuria is associated with decreased protein expression of critical components of the endocytic apparatus in the renal proximal tubule of spontaneously hypertensive rats (SHR). We found that urinary albumin excretion increased progressively with blood pressure in SHR from 6 to 21 wk of age. In addition, SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (<70 kDa), typical of tubular proteinuria. Moreover, the protein abundance of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 wk of age. Expression of the vacuolar H⁺-ATPase B2 subunit was also reduced in the renal cortex of 21-wk-old compared with both 6- and 14-wk-old SHR. Collectively, our study suggests that enhanced urinary protein excretion, especially of albumin, may be due, at least in part, to lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. Finally, one may speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may contribute to the development of microalbuminuria in essential hypertension.

AmoebaDB and MicrosporidiaDB: functional genomic resources for Amoebozoa and Microsporidia species.

AmoebaDB (http://AmoebaDB.org) and MicrosporidiaDB (http://MicrosporidiaDB.org) are new functional genomic databases serving the amoebozoa and microsporidia research communities, respectively. AmoebaDB contains the genomes of three Entamoeba species (E. dispar, E. invadens and E. histolityca) and microarray expression data for E. histolytica. MicrosporidiaDB contains the genomes of Encephalitozoon cuniculi, E. intestinalis and E. bieneusi. The databases belong to the National Institute of Allergy and Infectious Diseases (NIAID) funded EuPathDB (http://EuPathDB.org) Bioinformatics Resource Center family of integrated databases and assume the same architectural and graphical design as other EuPathDB resources such as PlasmoDB and TriTrypDB. Importantly they utilize the graphical strategy builder that affords a database user the ability to ask complex multi-data-type questions with relative ease and versatility. Genomic scale data can be queried based on BLAST searches, annotation keywords and gene ID searches, GO terms, sequence motifs, protein characteristics, phylogenetic relationships and functional data such as transcript (microarray and EST evidence) and protein expression data. Search strategies can be saved within a user's profile for future retrieval and may also be shared with other researchers using a unique strategy web address.

An Overview on Electrophysiological and Neuroimaging Findings in Dyslexia.

Objective: Dyslexia is a prevalent neurodevelopmental condition that is characterized by inaccurate and slow word recognition. This article reviews neural correlates of dyslexia from both electrophysiological and neuroimaging studies. Method : In this brief review, we provide electrophysiological and neuroimaging evidence from electroencephalogram (EEG) and magnetic resonance imaging (MRI) studies in dyslexia to understand functional and structural brain changes in this condition. Results: In both electrophysiological and neuroimaging studies, the most frequently reported functional impairments in dyslexia include aberrant activation of the left hemisphere occipito-temporal cortex (OTC), temporo-parietal cortex (TPC), inferior frontal gyrus (IFG), and cerebellar areas. EEG studies have mostly highlighted the important role of lower frequency bands in dyslexia, especially theta waves. Furthermore, neuroimaging studies have suggested that dyslexia is related to functional and structural impairments in the left hemisphere regions associated with reading and language, including reduced grey matter volume in the left TPC, decreased white matter connectivity between reading networks, and hypo-activation of the left OTC and TPC. In addition, neural evidence from pre-reading children and infants at risk for dyslexia show that there are abnormalities in the dyslexic brain before learning to read begins. Conclusion: Advances in comprehending the neural correlates of dyslexia could bring closer translation from basic to clinical neuroscience and effective rehabilitation for individuals who struggle to read. However, neuroscience still has great potential for clinical translation that requires further research.