Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients.

The efficacy of primary prophylaxis with atovaquone in preventing Toxoplasma reactivation and disease in hematopoietic cell transplant (HCT) recipients is unknown. We describe 2 cases of atovaquone prophylaxis failure in pre-HCT Toxoplasma-seropositive (pre-HCTSP) recipients who underwent allogeneic HCT (allo-HCT) and review the literature on atovaquone prophylaxis in HCT recipients.

Introduction and Establishment of Pissodes castaneus (Coleoptera: Curculionidae) in the Andean Patagonia of Argentina.

The pine weevils that occur in plantations of Pinus spp. in Andean Patagonia of Argentina belong to the species Pissodes castaneus (De Geer), a Eurasian endemic species, according to the identification based on molecular and morphological characters. Sequences of the mitochondrial Cytochrome oxidase subunit I and nuclear genes (28 S rDNA and ITS2) were obtained for individuals of 13 afforestations, covering the entire distribution area of the established populations in the Andean Patagonia of Argentina. Sequence comparison with representative species of the genus (European, North American, and Chinese species) shows that Patagonian specimens are conspecific to those of P. castaneus sequenced from Europe. Phylogenetic analyses indicate that all terminals from Patagonia form a monophyletic unit without evident subclades, eliminating the possibility of existence of more than one species of Pissodes Germar in this area, including cryptic ones. Moreover, the very low genetic divergence between the Patagonian populations suggests that it is plausible that P. castaneus was introduced into Patagonia from just one location. Mitochondrial DNA analysis shows that Patagonian terminals group together with a French haplotype and are clearly separated from other P. castaneus individuals represented in our sample, and reveal that established populations in Andean Patagonia originated via a limited introduction.

Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

Transgenic Citrange troyer rootstocks overexpressing antimicrobial potato Snakin-1 show reduced citrus canker disease symptoms.

Citrus canker is a major disease caused by Xanthomonas citri pv. citri. Snakin-1 is an antimicrobial peptide, which was previously shown to be effective against different bacterial and fungal diseases in potato, wheat and lettuce when expressed in transgenic plants. We generated transgenic Citrange Troyer citrus rootstocks constitutively expressing this peptide and 5 different transgenic lines were challenged against virulent X. citri isolates. Challenge assays conducted in vitro using detached leaves and in planta by infiltration revealed a significant reduction of the number and size of canker lesions in some of the transgenic lines.

G-protein signaling through tubby proteins.

Dysfunction of the tubby protein results in maturity-onset obesity in mice. Tubby has been implicated as a transcription regulator, but details of the molecular mechanism underlying its function remain unclear. Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxyl terminal "tubby domain." X-ray crystallography reveals the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidyl- inositol binding factors. Receptor-mediated activation of G protein alphaq (Galphaq) releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein 3 (TULP3) is similarly regulated. These data suggest that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G-protein signaling and the regulation of gene expression.

Effect of Chronic Consumption of Sweeteners on Microbiota and Immunity in the Small Intestine of Young Mice.

The consumption of sweeteners has increased as a measure to reduce the consumption of calories and thus combat obesity and diabetes. Sweeteners are found in a large number of products, so chronic consumption has been little explored. The objective of the study was to evaluate the effect of chronic sweetener consumption on the microbiota and immunity of the small intestine in young mice. We used 72 CD1 mice of 21 days old, divided into 3 groups: (i) No treatment, (ii) Group A (6 weeks of treatment), and (iii) Group B (12 weeks of treatment). Groups A and B were divided into 4 subgroups: Control (CL), Sucrose (Suc), Splenda® (Spl), and Svetia® (Sv). The following were determined: anthropometric parameters, percentage of lymphocytes of Peyer's patches and lamina propria, IL-6, IL-17, leptin, resistin, C-peptide, and TNF-α. From feces, the microbiota of the small intestine was identified. The BMI was not modified; the mice preferred the consumption of Splenda® and Svetia®. The percentage of CD3+ lymphocytes in Peyer's patches was increased. In the lamina propria, Svetia® increased the percentage of CD3+ lymphocytes, but Splenda® decreases it. The Splenda® and Svetia® subgroups elevate leptin, C-peptide, IL-6, and IL-17, with reduction of resistin. The predominant genus in all groups was Bacillus. The chronic consumption of sweeteners increases the population of lymphocytes in the mucosa of the small intestine. Maybe, Bacillus have the ability to adapt to sweeteners regardless of the origin or nutritional contribution of the same.

Effect of Supplementation with n-3 Fatty Acids Extracted from Microalgae on Inflammation Biomarkers from Two Different Strains of Mice.

BACKGROUND: Diabetes mellitus is considered a chronic noncommunicable disease in which inflammation plays a main role in the progression of the disease and it is known that n-3 fatty acids have anti-inflammatory properties. One of the most recent approaches is the study of the fatty acids of microalgae as a substitute for fish oil and a source rich in fatty acids EPA and DHA. OBJECTIVE: To analyze the effect of supplementation with n-3 fatty acids extracted from microalgae on the inflammatory markers from two different strains of mice. METHODS: Mice of two strains, db/db and CD1, were supplemented with n-3 fatty acids extracted from microalgae in lyophilized form and added to food; the experiment was carried out from week 8 to 16 of life. Flow cytometry was performed to determine the percentage of TCD4+ cells producing Th1 and Th2 cytokines. RESULTS: Supplementation with microalgae fatty acids decreased the percentage of TCD4+ cells producing IFN-γ and TNF-α and increased the ones producing IL-17A and IL-12 in both strains; on the other hand, supplementation decreased percentage of TCD4+ cells producing IL-4 and increased the ones producing TGF-ß. CONCLUSIONS: Microalgae n-3 fatty acids could be a useful tool in the treatment of diabetes as well as in the prevention of the appearance of health complications caused by inflammatory states.

In vivo acceleration of heart relaxation performance by parvalbumin gene delivery.

Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.

Mutations in conserved regions of the predicted RAG2 kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.

The V(D)J recombination reaction is composed of multiple nucleolytic processing steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence analysis has suggested that RAG2 contains six kelch repeat motifs that are predicted to form a six-bladed beta-propeller structure, with the second beta-strand of each repeat demonstrating marked conservation both within and between kelch repeat-containing proteins. Here we demonstrate that mutations G95R and DeltaI273 within the predicted second beta-strand of repeats 2 and 5 of RAG2 lead to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with the mutant proteins reveal appropriate localization to the nucleus. However, both mutations reduce the capacity of RAG2 to interact with RAG1 and block recombination signal cleavage, therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype. The present experiments, performed with an extensive panel of site-directed mutations within each of the six kelch motifs, further support the critical role of both hydrophobic and glycine-rich regions within the second beta-strand for RAG1-RAG2 interaction and recombination signal recognition and cleavage. In contrast, multiple mutations within the variable-loop regions of the kelch repeats had either mild or no effects on RAG1-RAG2 interaction and hence on the ability to mediate recombination. In all, the data demonstrate a critical role of the RAG2 kelch repeats for V(D)J recombination and highlight the importance of the conserved elements of the kelch motif.

Sexual risk behaviors among heterosexual HIV serodiscordant couples in the era of post-exposure prevention and viral suppressive therapy.

OBJECTIVES: To describe awareness and use of antiretroviral treatments, viral load monitoring, and post-exposure prevention; to assess changing concerns about HIV transmission; and to examine the effect of these advances on sexual behavior in HIV-serodiscordant heterosexual couples. METHODS: Cross-sectional analysis of a baseline sample of 104 couples (n = 208 individuals) from the California Partners Study II, an intervention trial for HIV-serodiscordant couples in California. Questions on sexual practices, viral load testing, HIV treatment, post-exposure prevention, and their effect on sexual behaviors, risk taking and transmission concerns were measured at intake. RESULTS: Over two-thirds of couple members surveyed reported unprotected sex with their partner in the past 6 months. Among seropositive respondents, 37% were taking protease inhibitor therapy, 92% had undergone viral load testing, and of those, 40% said it had ben undetectable at their most recent test. Most respondents, regardless of serostatus, said that viral load testing and awareness of post-exposure prevention had no effect on their condom use. In addition, perceiving that their partner had an undetectable viral load was associated with having protected sex among seronegative subjects (P < 0.05). Seropositive respondent taking protease inhibitors were 2.4 times less likely to report unprotected sex compared with those not taking protease inhibitors (P = 0.05). However, up to 33% of seropositive and 40% of seronegative respondents acknowledged decreased transmission concerns in the light of the new HIV treatments. In comparison with their seropositive partners, seronegative individuals were more likely to acknowledge increased risk taking and decreased HIV transmission concerns (P < 0.05). CONCLUSIONS: New medical advances were not associated with unprotected sex in HIV-serodiscordant couples. However, new treatment options may decrease concerns about HIV transmission, particularly among seronegative partners. Providers should discuss the effect of antiretroviral treatments on sexual transmission risk with their patients. The inclusion of seronegative partners in counseling interventions may decrease risk taking in serodiscordant couples.