HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection

BackgroundDecreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4⁺ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.MethodsWe measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.ResultsIn acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8⁺ T cells from monoinfected individuals enhanced their function although CD8⁺ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.ConclusionsThese data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.     

Effect of UVM induction on mutation fixation at non-pairing and mispairing DNA lesions

Mutation fixation at an ethenocytosine (εC) residue borne on transfected M13 single-stranded DNA is significantly enhanced in response to pretreatment of Escherichia coli cells with UV, alkylating agents or hydrogen peroxide, a phenomenon that we have called UVM for UV modulation of mutagenesis. The UVM response does not require the E. coli SOS or adaptive responses, and is observed in cells defective for oxyR , an oxidative DNA damage-responsive regulatory gene. UVM may represent either a novel DNA-repair phenomenon, or an unrecognized feature of DNA replication in damaged cells that affects a specific class of non-coding DNA lesions. To explore the range of DNA lesions subject to the UVM effect, we have examined mutation fixation at 3, N  ⁴-ethenocytosine and 1, N  ⁶-ethenoadenine, as well as at O⁶-methylguanine (O⁶mG). M13 viral single-stranded DNA constructs bearing a single mutagenic lesion at a specific site were transfected into cells pretreated with UV or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Survival of transfected viral DNA was measured as transfection efficiency, and mutagenesis at the lesion site was analysed by a quantitative multiplex sequence analysis technology. The results suggest that the UVM effect modulates mutagenesis at the two etheno lesions, but does not appear to significantly affect mutagenesis at O⁶mG. Because the modulation of mutagenesis is observed in cells incapable of the SOS response, these data are consistent with the notion that UVM may represent a previously unrecognized DNA damage-inducible response that affects the fidelity of DNA replication at certain mutagenic lesions in Escherichia coli .     

Influence of doxycycline administration on rat embryonic development during organogenesis

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty‐one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day‐fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.     

Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion

The mitochondrial DNA (mtDNA) depletion syndrome is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication of mtDNA. Markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase, was found in muscle mitochondria of patients with encephalomyopathy and mtDNA depletion. Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase; hence, we propose that a defect in the last step of mitochondrial dNTP salvage is a novel cause of the mtDNA depletion syndrome.     

In vitro kinetics and antifungal activity of various extracts of Terminalia chebula seeds against plant pathogenic fungi

The aim of the present study was to examine the efficacy of various seed extracts of Terminalia chebula as an antifungal potential against certain important plant pathogenic fungi. The organic extracts of methanol, ethyl acetate and chloroform at the used concentration of 1500 ppm/disc revealed remarkable antifungal effect as a fungal mycelial growth inhibitor against Fusarium oxysporum, Fusarium solani, Phytophthora capsici and Botrytis cinerea, in the range of 41.6–61.3%, along with MIC values ranging from 62.5 to 500 μg/ml. Also, the extracts had a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of B. cinerea. The results obtained from this study suggest that the natural products derived from Terminalia chebula could become an alternative to synthetic fungicides for controlling such important plant pathogenic fungi.     

A new thermostable and organic solvent-tolerant lipase from Aneurinibacillus thermoaerophilus strain HZ

A thermostable and organic solvent-tolerant lipase produced by Aneurinibacillus thermoaerophilus strain HZ was purified and characterised. The lipase was purified to apparent homogeneity with two steps: anion exchange chromatography on Q-Sepharose and gel filtration on Sephadex-G75. A final specific activity of 43.5 U/mg was obtained with an overall recovery of 19.7% and 15.6 purification fold. The molecular mass of the HZ lipase was estimated to be 50 kDa. The optimum pH for the activity of the purified HZ lipase was 7.0. The stability showed a broad range of pH values between pH 4.0 and 9.0 at 30 °C. The purified HZ lipase exhibited an optimum temperature of 65 °C with a half-life of 3 h and 10 min at 65 °C. The activity of the purified HZ lipase was stimulated in the presence of Ca²⁺. Organic solvents such as dimethyl sulfoxide (DMSO), methanol, n-tetradecane and n-hexadecane enhanced the lipase activity. Studies on the effect of oil showed that the lipase preferred natural oil, such as sunflower oil, over synthetic substrates.     

Mapping the Progress in Surface Plasmon Resonance Analysis of Phytogenic Silver Nanoparticles with Colorimetric Sensing Applications

Nanotechnology is gaining enormous attention as the most dynamic research area in science and technology. It involves the synthesis and applications of nanomaterials in diverse fields including medical, agriculture, textiles, food technology, cosmetics, aerospace, electronics, etc. Silver nanoparticles (AgNPs) have been extensively used in such applications due to their excellent physicochemical, antibacterial, and biological properties. The use of plant extract as a biological reactor is one of the most promising solutions for the synthesis of AgNPs because this process overcomes the drawbacks of physical and chemical methods. This review article summarizes the plant-mediated synthesis process, the probable reaction mechanism, and the colorimetric sensing applications of AgNPs. Plant-mediated synthesis parameters largely affect the surface plasmon resonance (SPR) characteristic due to the changes in the size and shape of AgNPs. These changes in the size and shape of plant-mediated AgNPs are elaborately discussed here by analyzing the surface plasmon resonance characteristics. Furthermore, this article also highlights the promising applications of plant-mediated AgNPs in sensing applications regarding the detection of mercury, hydrogen peroxide, lead, and glucose. Finally, it describes the future perspective of plant-mediated AgNPs for the development of green chemistry.     

Biomechanical Energy‐Driven Hybridized Generator as a Universal Portable Power Source for Smart/Wearable Electronics

The fast growth of smart electronics requires novel solutions to power them sustainably. Portable power sources capable of harvesting biomechanical energy are a promising modern approach to reduce battery dependency. Herein, a novel elastic impact‐based nonresonant hybridized generator (EINR‐HG) is reported to effectively harvest biomechanical energy from diverse human activities outdoors. Through the rational integration of a nonlinear electromagnetic generator with two contact‐mode triboelectric nanogenerators, the proposed EINR‐HG generates hybrid electrical output simultaneously under the same mechanical excitations. By introducing a flux‐concentrator with a nanowire‐nanofiber surface modification, significant improvement in the energy harvesting efficiency of the EINR‐HG is achieved. After optimizing using simulations and vibration tests, the as‐fabricated EINR‐HG delivers an outstanding normalized power density of 3.13 mW cm^?3 g^?2 across a matching resistance of 1.5 kΩ at 6 Hz under 1 g acceleration. Under human motion testing, the EINR‐HG generates an optimal output power of 131.4 mW with horizontal handshaking. With a customized power management circuit, the EINR‐HG serves as a universal power source that successfully drives commercial smart electronics, including smart bands and smartphones. This work shows the massive potential of biomechanical energy‐driven hybridized generators for powering personal electronics and portable healthcare monitoring devices.     

A New Cold-Adapted,Organic Solvent Stable Lipase from Mesophilic Staphylococcus epidermidis AT2

The gene encoding a cold-adapted, organic solvent stable lipase from a local soil-isolate, mesophilic Staphylococcus epidermidis AT2 was expressed in a prokaryotic system. A two-step purification of AT2 lipase was achieved using butyl sepharose and DEAE sepharose column chromatography. The final recovery and purification fold were 47.09 % and 3.45, respectively. The molecular mass of the purified lipase was estimated to be 43 kDa. AT2 lipase was found to be optimally active at pH 8 and stable at pH 6–9. Interestingly, this enzyme demonstrated remarkable stability at cold temperature (<30 °C) and exhibited optimal activity at a temperature of 25 °C. A significant enhancement of the lipolytic activity was observed in the presence of Ca²⁺, Tween 60 and Tween 80. Phenylmethylsulfonylfluoride, a well known serine inhibitor did not cause complete inhibition of the enzymatic activity. AT2 lipase exhibited excellent preferences towards long chain triglycerides and natural oils. The lipolytic activity was stimulated by dimethylsulfoxide and diethyl ether, while more than 50 % of its activity was retained in methanol, ethanol, acetone, toluene, and n-hexane. Taken together, AT2 lipase revealed highly attractive biochemical properties especially because of its stability at low temperature and in organic solvents.     

Surrogate Production of Eggs and Sperm by Intrapapillary Transplantation of Germ Cells in Cytoablated Adult Fish

Germ cell transplantation (GCT) is a promising assisted reproductive technology for the conservation and propagation of endangered and valuable genetic resources. In teleost fish, GCT in adult gonads has been achieved only in male recipients, limiting greatly the usefulness of this technique in situations where both sexes need equal and timely attention for conservation and/or propagation. Here we describe a simplified GCT approach that ultimately leads to production of donor-derived eggs and sperm in considerably short time. Donor germ cells isolated from young pejerrey Odontesthes bonariensis (Atherinopsidae) were transplanted non-surgically through the genital papilla into the sexually mature gonads of Patagonian pejerrey O. hatcheri recipients whose gonads have been depleted of endogenous GCs by heat (26°C) and chemical treatment (four doses of Busulfan at 30 mg/kg and 40 mg/kg for females and males, respectively). Transplanted spermatogonial and oogonial cells were able to recolonize the recipients'' gonads and produce functional donor origin eggs and sperm within 7 months from the GCT. We confirmed the presence of donor-derived gametes by PCR in 17% and 5% of the surrogate O. hatcheri fathers and mothers, respectively. The crosses between surrogate fathers and O. bonariensis mothers yielded 12.6–39.7% pure O. bonariensis and that between a surrogate mother and an O. bonariensis father yielded 52.2% pure O. bonariensis offspring. Our findings confirm that transplantation of germ cells into sexually competent adult fish by non-surgical methods allows the production of functional donor-derived eggs and sperm in a considerably short time. The methods described here could play a vital role in conservation and rapid propagation of endangered fish genetic resources.