Global genetic diversity of Aedes aegypti

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co‐occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub‐Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans‐Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations.     

Widespread environmental contamination in agricultural soils and human health risk at the vicinity of an oil refinery site

In this research, carcinogenic and non-carcinogenic human health risks due to polycyclic aromatic hydrocarbons (PAHs) were investigated via three exposure pathways: accidental ingestion of soil, dermal contact of soils, and contaminated vegetable ingestion. To determine the contaminant concentrations in soil, samples were collected from areas adjacent to the Tehran oil refinery, located in Shahr-e-Ray city, Iran. Analyses of the samples indicated that the average of PAHs concentration in the soil samples were greater than clean-up level guidelines. Cancer risk of contaminants due to ingestion of cultivated vegetables that are sold in Tehran markets was significant in comparison with other exposure pathways. Moreover, the total cancer risk for 5th percentile, 95 upper confidence limit, and 95th percentile concentration of contaminants were 5.69E-04, 8.78E-02, and 2.13E-01, classifying the site as having a significant cancer risk potential. Furthermore, non-carcinogenic health risk analyses for the contaminants demonstrated hazard index of less than 1. Remediation of the soils is highly recommended to eliminate the potential cancer risks and prevent the contamination of the food chain for approximately 10 million Tehran residents.     

Ordering the Cytochrome c–initiated Caspase Cascade: Hierarchical Activation of Caspases-2, -3, -6, -7, -8, and -10 in a Caspase-9–dependent Manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1–mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c–inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.     

Anxiety,depression-like behaviors and biochemistry disorders induced by cannabis extract in female mice

Cannabis is an annual herbaceous plant sometimes grown for decoration and used as bird food that looks like flax. The study wanted to determine if a Cannabis extract may have an effect on how anxious and depressed the female mice behaved. forty healthy female mice were divided into four groups. Tap water was administered to the first group (control). Ethanol was administered to second group (positive control). The third and four groups were given 1 and 2 mg/kg cannabis extract respectively. Treatment continued for 14 days. After therapy, the light–dark chamber, forced swimming, tail suspension, plus lamb and open field tests were done to assess anxiety and depressive behavior. The results indicated that the anxiety and depression were increased in treated females significantly compared to control. Biochemical results showed that DA,5-HT, AChE, GSH, GST, CAT and SOD were decreased while TBARS, corticosterone and cortisol were increased. In conclusion, cannabis effects this kind of females’ behavior but the mechanisms are not clear yet. We need more researches on this trend.     

A comparison of H-reflex in the triceps surae muscle group in patients with S1 radiculopathy

Despite differences in the anatomical and physiological characteristics of the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles, it is common practice to investigate them as single triceps surae H-reflex recordings. The aim of this study was to compare the latencies of H-reflex recordings from the Sol, MG, and LG in patients with explicit magnetic resonance imaging (MRI) evidence of unilateral S1 radiculopathy and also compare their diagnostic yield in varied clinical characteristics (i.e., symptom duration and severity of involvement). We found a significant difference between H-reflex latencies of Sol and the two others (p?相似文献   

Stem cell biology in thyroid cancer: Insights for novel therapies

Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.     

Coupling of Calcium and Substrate Binding through Loop Alignment in the Outer-Membrane Transporter BtuB

In Gram-negative bacteria, TonB-dependent outer-membrane transporters bind large, scarce organometallic substrates with high affinity preceding active transport. The cobalamin transporter BtuB requires the additional binding of two Ca²⁺ ions before substrate binding can occur, but the underlying molecular mechanism is unknown. Using the crystallographic structures available for different bound states of BtuB, we have carried out extended molecular dynamics simulations of multiple functional states of BtuB to address the role of Ca²⁺ in substrate recruitment. We find that Ca²⁺ binding both stabilizes and repositions key extracellular loops of BtuB, optimizing interactions with the substrate. Interestingly, replacement by Mg²⁺ abolishes this effect, in accordance with experiments. Using a set of new force-field parameters developed for cyanocobalamin, we also simulated the substrate-bound form of BtuB, where we observed interactions not seen in the crystal structure between the substrate and loops previously found to be important for binding and transport. Based on our results, we suggest that the large size of cobalamin compared to other TonB-dependent transporter substrates explains the requirement of Ca²⁺ binding for high-affinity substrate recruitment in BtuB.     

Bio-shielding <Emphasis Type="Italic">In Situ</Emphasis> Forming Gels (BSIFG) Loaded With Lipospheres for Depot Injection of Quetiapine Fumarate: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

Quetiapine fumarate (QF), an anti-schizophrenic drug, suffers from rapid elimination and poor bioavailability due to extensive first-pass effect. Intramuscularly (IM) injected lipospheres were designed to enhance the drug’s bioavailability and extend its release. A central composite design was applied to optimize the liposphere preparation by a melt dispersion technique using Compritol® 888 ATO or glyceryl tristearate as lipid component and polyvinyl alcohol as surfactant. Lipospheres were evaluated for their particle size, entrapment efficiency, and in vitro release. The optimized QF lipospheres were prepared using a Compritol® 888 ATO fraction of 18.88% in the drug/lipid mixture under a stirring rate of 3979 rpm. The optimized lipospheres were loaded into a thermoresponsive in situ forming gel (TRIFG) and a liquid crystalline in situ forming gel (LCIFG) to prevent in vivo degradation by lipases. The loaded gels were re-evaluated for their in vitro release and injectability. Bioavailability of QF from liposphere suspension and bio-shielding in situ gels loaded with QF lipospheres were assessed in rabbits compared to drug suspension. Results revealed that the AUC_0–72 obtained from the liposphere-loaded TRIFG was ～3-fold higher than that obtained from the aqueous drug suspension indicating the bio-shielding effect of Poloxamer® 407 gel to inhibit the biodegradation of the lipospheres prolonging the residence of the drug in the muscle for higher absorption. Our results propose that bio-shielding in situ Poloxamer® 407 gels loaded with lipospheres is promising for the development of IM depot injection of drugs having extensive first-pass metabolism and rapid elimination.