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This research paper article thoroughly investigates the tensile, tear, and abrasion properties of high-performance cotton denim fabrics incorporating para-aramid and ultrahigh molecular weight polyethylene (UHMWPE) fibers. It compares these high-performance blended denim fabrics with traditional 100 % cotton fabric material. The findings indicate that fabrics containing UHMWPE and para-aramid fibers demonstrate notably greater strength and durability compared with pure cotton fabrics. Factors such as yarn thickness, twist, fabric weight, cover factor, and the blend proportion of high-performance fibers contribute to enhanced tensile strength and abrasion resistance. Among the tested samples, the blend with 30 % cotton and 70 % UHMWPE fibers, weighing 430 g/m² (S9), exhibits the most superior performance in terms of tensile strength. These fabrics also exhibit remarkable tear resistance, even under extreme conditions. Sample S9 excels in abrasion resistance, qualifying it for Zone 3 Level 1 protection. The study underscores the potential of these fabrics to offer outstanding protection against abrasion in diverse applications. Additionally, it has been observed that fabrics generally display higher tensile strength and abrasion resistance along the warp direction, owing to a higher yarn density. The analysis of variance and Tukey Honestly Significant Difference (HSD) tests confirm the significant influence of fiber composition on fabric properties based on the statistical analyses that have been conducted. [ABSTRACT FROM AUTHOR]

The textile processing and finishing industry is the mainstay for the apparel segment. The textile processing and finishing industry consume an enormous amount of chemicals and release harmful substances to the environment. Therefore rethinking and refinement of the practice adopted and the techniques involved in processing and finishing are very much significant. The consciousness toward environmental protection, pollution control, and user-friendliness are the reasons for emerging trends with sustainable concepts where natural materials, plant ingredients, plant extracts can be used for textile finishing. This review paper discusses the exploratory qualitative study about the natural ingredients, extraction processes, finishing on textiles for various applications, its effects, and results. The applications of textile finishing processes covered in this article are fragrance finish, bio-polishing, bio-stone washing, insect repellent, and UV protection. This article also deals with the various methods of finishing textiles using natural products such as pad-dry-cure, microencapsulation, exhaust method, spraying technique, etc., and its implications. The finishing process using natural products has obtained satisfactory results with various tests for analyzing the properties of textiles after finishing. The critical analysis of this article has revealed that the textile finishing process using natural products seem to be economical, sustainable, have control over environmental and health hazard. [ABSTRACT FROM AUTHOR]

Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured. [ABSTRACT FROM AUTHOR]

Nearly 2 decades since its discovery as one of the genes responsible for the Wolf-Hirschhorn Syndrome (WHS), the primary function of the leucine-zipper EF-hand containing transmembrane 1 (LETM1) protein in the inner mitochondrial membrane (IMM) or the mechanism by which it regulates mitochondrial Ca2+ handling is unresolved. Meanwhile, LETM1 has been associated with the regulation of fundamental cellular processes, such as development, cellular respiration and metabolism, and apoptosis. This mini-review summarizes the diversity of cellular functions impacted by LETM1 and highlights the multiple roles of LETM1 in health and disease. [ABSTRACT FROM AUTHOR]

Mitochondrial Ca2+ handling is accomplished by balancing Ca2+ uptake, primarily via the Ru360-sensitive mitochondrial calcium uniporter (MCU), Ca2+ buffering in the matrix and Ca2+ efflux mainly via Ca2+ ion exchangers, such as the Na+/Ca2+ exchanger (NCLX) and the Ca2+/H+ exchanger (CHE). The mechanism of CHE in cardiac mitochondria is not well-understood and its contribution to matrix Ca2+ regulation is thought to be negligible, despite higher expression of the putative CHE protein, LETM1, compared to hepatic mitochondria. In this study, Ca2+ efflux via the CHE was investigated in isolated rat cardiac mitochondria and permeabilized H9c2 cells. Mitochondria were exposed to (a) increasing matrix Ca2+ load via repetitive application of a finite CaCl2 bolus to the external medium and (b) change in the pH gradient across the inner mitochondrial membrane (IMM). Ca2+ efflux at different matrix Ca2+ loads was revealed by inhibiting Ca2+ uptake or reuptake with Ru360 after increasing number of CaCl2 boluses. In Na+-free experimental buffer and with Ca2+ uptake inhibited, the rate of Ca2+ efflux and steady-state free matrix Ca2+ [mCa2+]ss increased as the number of administered CaCl2 boluses increased. ADP and cyclosporine A (CsA), which are known to increase Ca2+ buffering while maintaining a constant [mCa2+]ss, decreased the rate of Ca2+ efflux via the CHE, with a significantly greater decrease in the presence of ADP. ADP also increased Ca2+ buffering rate and decreased [mCa2+]ss. A change in the pH of the external medium to a more acidic value from 7.15 to 6.8∼6.9 caused a twofold increase in the Ca2+ efflux rate, while an alkaline change in pH from 7.15 to 7.4∼7.5 did not change the Ca2+ efflux rate. In addition, CHE activation was associated with membrane depolarization. Targeted transient knockdown of LETM1 in permeabilized H9c2 cells modulated Ca2+ efflux. The results indicate that Ca2+ efflux via the CHE in cardiac mitochondria is modulated by acidic buffer pH and by total matrix Ca2+. A mechanism is proposed whereby activation of CHE is sensitive to changes in both the matrix Ca2+ buffering system and the matrix free Ca2+ concentration. [ABSTRACT FROM AUTHOR]

Chinese Leishmania isolate MHOM/CN/90/SC10H2 (L. H2), which was obtained from the spinal cords of patients from the Sichuan province of China, is an uncharacterized, pathogenic species closely related to Leishmania tarentolae. The in vitro transformation rate of L. H2 promastigotes into amastigotes has not been studied. This study is the first to successfully define the in vitro life cycle of L. H2 by investigating the percent conversion of L.H2 promastigotes to amastigotes in vitro under 216 different culture conditions. The highest proportion of L. H2 amastigotes observed (94%) was significantly higher than that previously reported. After conversion, the axenic amastigotes remained viable as verified by the levels of stage-specific genes (Gp46, A2 and β-tubulin) detected by RT-PCR. Meanwhile, morphological and protein characterizations of these axenic amastigotes were carried out in order to confirm the successful conversion. Specific antibodies were only able to detect 46 kDa, 52 kDa and 75 kDa proteins in samples isolated from axenic amastigotes. Afterward, these converted axenic amastigotes were transformed into the promastigote form by altering the culture condition. These converted axenic promastigotes still have the ability to infect macrophages, and their morphology changed back to the amastigote form following infection. These findings will assist further investigations into the biological characteristics of the host-parasite relationship and the process of pathogenesis. [ABSTRACT FROM AUTHOR]

The outcome of visceral leishmaniasis, caused by parasite Leishmania donovani , depends on the recruitment of leishmanicidal Th1 cells. Chemokine receptor CXCR3, preferentially expressed by Th1 cells, is critical for migration of these T cells during infection. During chronic VL, there is a decrease in the presence of CXCR3-expressing CD4 + T cells in the spleen, which is associated with high parasitic burden in this organ. We therefore examined whether T cell-specific expression of CXCR3 in mice (CXCR3 Tg ) would promote resistance to VL. L. donovani infected CXCR3 Tg mice showed increased accumulation of T cells in the spleens compared to WT littermates (CXCR3 +/+ ). However, CXCR3 + T cells from CXCR3 Tg mice showed low CD69 expression and these mice developed fewer granulomas. Additionally, both groups of mice showed similar cytokine profiles and parasitic burdens during the course of infection. In summary, although T cell-specific expression of CXCR3 promoted the accumulation of CXCR3-expressing T cells during L. donovani infection, this did not enhance resistance to VL. [ABSTRACT FROM AUTHOR]

STAT4 is critical for the production of IFN-γ during the generation of Th1 immune responses. We investigated the role of STAT4 in mediating Th1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN-γ production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and Th2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KOderived splenocytes. Our observations for defective Th1 and Th2 responses in STAT4KO mice were further supported by the low levels of Th1-associated IgG2a and Th2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both Th1 and Th2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development. [ABSTRACT FROM AUTHOR]

Rapid technological advancement and relatively short life time of electronic goods have resulted in an alarming growth rate of electronic waste which often contains significant quantities of toxic and precious metals. Compared to conventional recovery methods, bioleaching is an environmentally friendly process for metal extraction. Gold was bioleached from electronic scrap materials (ESM) via gold–cyanide complexation using cyanide produced from pure and mixed cultures of cyanogenic bacteria Chromobacterium violaceum , Pseudomonas aeruginosa and Pseudomonas fluorescens . As ESM was toxic to the bacteria, a two-step bioleaching approach was adopted where the solid waste was added to the bacterial culture after it has reached maximum growth and cyanide production during early stationary phase. Pure culture of C. violaceum showed the highest cyanide production, yielding maximum gold recovery of 11.3% at 0.5% w/v pulp density of ESM in two-step bioleaching. At the same pulp density of ESM, spent medium bioleaching using bacterial cell-free metabolites achieved gold recovery of 18%. Recovery increased to 30% when the pH of the spent medium was increased to shift the equilibrium in favor of cyanide ions production. It is demonstrated for the first time that pH modification of spent medium further improved metal solubilization and yielded higher metal recovery (compared to two-step bioleaching). [ABSTRACT FROM AUTHOR]

Gold bioleaching from electronic scrap materials (ESM) was examined using the bacterium Chromobacterium violaceum which produces and detoxifies cyanide, one of the few lixiviants capable of leaching gold. Gold recovery by the wild-type C. violaceum and two genetically engineered strains (pBAD and pTAC) with an additional cyanide-producing operon were investigated and compared. The ESM was pretreated to remove metals competing for metal cyanide complexation with gold. The effect of pulp density on leaching performance by the various strains was also investigated. The pBAD strain produced the highest cyanide concentration, and achieved the highest gold recovery of 30% at 0.5% w/v pulp density, compared to 11% recovery by the wild-type bacteria. Our results demonstrated the application of lixiviant metabolic engineering in the construction of enhanced bioleaching microbes for the bioleaching of precious metals from electronic waste. [ABSTRACT FROM AUTHOR]

Previously, we showed that genetically modified live-attenuated Leishmania donovani parasite cell lines (LdCen-/- and Ldp27-/-) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. In this study, we explored the mechanism of cross-protection against cutaneous lesion-causing Leishmania mexicana. Upon challenge with wild-type L. mexicana, mice immunized either for short or long periods showed significant protection. Immunohistochemical analysis of ears from immunized/challenged mice exhibited significant influx of macrophages, as well as cells expressing MHC class II and inducible NO synthase, suggesting an induction of potent host-protective proinflammatory responses. In contrast, substantial inhibition of IL-10, IL-4, and IL-13 expression and the absence of degranulated mast cells and less influx of eosinophils within the ears of immunized/challenged mice suggested a controlled anti-inflammatory response. L. mexicana Ag-stimulated lymph node cell culture from the immunized/challenged mice revealed induction of IFN- secretion by the CD4 and CD8 T cells compared with non-immunized/challenged mice. We also observed suppression of Th2 cytokines in the culture supernatants of immunized/challenged lymph nodes compared with non-immunized/challenged mice. Adoptively transferred total T cells from immunized mice conferred strong protection in recipient mice against L. mexicana infection, suggesting that attenuated L. donovani can provide protection against heterologous L. mexicana parasites by induction of a strong T cell response. Furthermore, bone marrow-derived dendritic cells infected with LdCen-/- and Ldp27-/- parasites were capable of inducing a strong proinflammatory response leading to the proliferation of Th1 cells. These studies demonstrate the potential of live-attenuated L. donovani parasites as pan-Leishmania species vaccines. [ABSTRACT FROM AUTHOR]

Motorcycle protective clothing is designed to protect motorcyclists from injuries during accidents. It helps to protect the motorcyclist and pillion passengers during the collision and acts as a barrier between the rider's skin and tarmac surface. Soft tissue trauma is common in motorcycle accidents and protective clothing can protect the soft tissue of the riders up to a certain extent during accidents. Though there are many reasons for road accidents and injuries, the reasons such as uncomfortable clothing, thermally inefficient protective clothing during hot climatic conditions, and ineffective performance of the personal protective equipment (PPE) are also to be considered seriously. Motorcycle clothing is specially designed in such a way that it could give better protection against impact and abrasion during the collision. An increase in the usage of the motorcycle has also in turn increased the crash statistics. This paper deals with the significance of motorcycle clothing, materials, test standards, and their performance characteristics. As per the review results, most of the motorcycle protective clothing has failed to meet out the quality standard protocols. Impact resistance, abrasion resistance, thermal comfort, and ergonomics are the major areas where more focus is required. Design of appropriate fabrics assuring requisites of motorcycle clothing is very challenging and extensive research is still intended in these areas. [ABSTRACT FROM AUTHOR]

Regulation of mitochondrial free Ca2+ is critically important for cellular homeostasis. An increase in mitochondrial matrix free Ca2+ concentration ([Ca2+]m) predisposes mitochondria to opening of the permeability transition pore (mPTP). Opening of the pore can be delayed by cyclosporin A (CsA), possibly by inhibiting cyclophilin D (Cyp D), a key regulator of mPTP. Here, we report on a novel mechanism by which CsA delays mPTP opening by enhanced sequestration of matrix free Ca2+. Cardiac-isolated mitochondria were challenged with repetitive CaCl2 boluses under Na+-free buffer conditions with and without CsA. CsA significantly delayed mPTP opening primarily by promoting matrix Ca2+ sequestration, leading to sustained basal [Ca2+]m levels for an extended period. The preservation of basal [Ca2+]m during the CaCl2 pulse challenge was associated with normalized NADH, matrix pH (pHm), and mitochondrial membrane potential (ΔΨm). Notably, we found that in PO43− (Pi)-free buffer condition, the CsA-mediated buffering of [Ca2+]m was abrogated, and mitochondrial bioenergetics variables were concurrently compromised. In the presence of CsA, addition of Pi just before pore opening in the Pi-depleted condition reinstated the Ca2+ buffering system and rescued mitochondria from mPTP opening. This study shows that CsA promotes Pi-dependent mitochondrial Ca2+ sequestration to delay mPTP opening and, concomitantly, maintains mitochondrial function. [ABSTRACT FROM AUTHOR]

Ibrutinib, a BTK inhibitor, is currently used to treat various hematological malignancies. We evaluated whether ibrutinib treatment during development of murine bone marrow-derived dendritic cells (DCs) modulates their maturation and activation. Ibrutinib treatment increased the proportion of CD11c+DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs. Additionally, ibrutinib treatment led to an increase in MHC-II+, CD80+and CCR7+DCs but a decrease in CD86+DCs upon LPS stimulation. LPS/ibrutinib-treated DCs displayed increased IFNβ and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone. Finally, LPS/ibrutinib-treated DCs promoted higher rates of CD4+T cell proliferation and cytokine production compared to LPS only stimulated DCs. Taken together, our results indicate that ibrutinib enhances the maturation and activation of DCs to promote CD4+T cell activation which could be exploited for the development of DC-based cancer therapies. [ABSTRACT FROM AUTHOR]

Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide (NO) and higher induction of IL-6, TGF-β, IL-10 and IL-18. While ibrutinib dampened MHC-II and CD86 expression on DCs, CD80 expression was upregulated. Further, ibrutinib-treated DCs promoted T cell proliferation and enhanced IL-17 production upon co-culture with nylon wool enriched T cells. Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response. We describe a novel mode of action for ibrutinib on DCs which should be explored to treat other forms of cancer besides B cell malignancies. [ABSTRACT FROM PUBLISHER]

Objectives: Madhulai Manappagu - a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate ( Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats., Methods: The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed., Results: In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses., Conclusions: The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Mitochondrial Ca 2+ handling is accomplished by balancing Ca 2+ uptake, primarily via the Ru360-sensitive mitochondrial calcium uniporter (MCU), Ca 2+ buffering in the matrix and Ca 2+ efflux mainly via Ca 2+ ion exchangers, such as the Na + /Ca 2+ exchanger (NCLX) and the Ca 2+ /H + exchanger (CHE). The mechanism of CHE in cardiac mitochondria is not well-understood and its contribution to matrix Ca 2+ regulation is thought to be negligible, despite higher expression of the putative CHE protein, LETM1, compared to hepatic mitochondria. In this study, Ca 2+ efflux via the CHE was investigated in isolated rat cardiac mitochondria and permeabilized H9c2 cells. Mitochondria were exposed to (a) increasing matrix Ca 2+ load via repetitive application of a finite CaCl 2 bolus to the external medium and (b) change in the pH gradient across the inner mitochondrial membrane (IMM). Ca 2+ efflux at different matrix Ca 2+ loads was revealed by inhibiting Ca 2+ uptake or reuptake with Ru360 after increasing number of CaCl 2 boluses. In Na + -free experimental buffer and with Ca 2+ uptake inhibited, the rate of Ca 2+ efflux and steady-state free matrix Ca 2+ [mCa 2+ ] ss increased as the number of administered CaCl 2 boluses increased. ADP and cyclosporine A (CsA), which are known to increase Ca 2+ buffering while maintaining a constant [mCa 2+ ] ss , decreased the rate of Ca 2+ efflux via the CHE, with a significantly greater decrease in the presence of ADP. ADP also increased Ca 2+ buffering rate and decreased [mCa 2+ ] ss. A change in the pH of the external medium to a more acidic value from 7.15 to 6.8∼6.9 caused a twofold increase in the Ca 2+ efflux rate, while an alkaline change in pH from 7.15 to 7.4∼7.5 did not change the Ca 2+ efflux rate. In addition, CHE activation was associated with membrane depolarization. Targeted transient knockdown of LETM1 in permeabilized H9c2 cells modulated Ca 2+ efflux. The results indicate that Ca 2+ efflux via the CHE in cardiac mitochondria is modulated by acidic buffer pH and by total matrix Ca 2+ . A mechanism is proposed whereby activation of CHE is sensitive to changes in both the matrix Ca 2+ buffering system and the matrix free Ca 2+ concentration., (Copyright © 2020 Natarajan, Glait, Mishra, Stowe, Camara and Kwok.)

Introduction: Delaying care-seeking for tuberculosis (TB) symptoms is a major contributor to mortality, leading to worse outcomes and spread. To reduce delays, it is essential to identify barriers to care-seeking and target populations most at risk of delaying. Previous work identifies barriers only in people within the health system, often long after initial care-seeking., Methods: We conducted a community-based survey of 84 625 households in Chennai, India, to identify 1667 people with TB-indicative symptoms in 2018-2019. Cases were followed prospectively to observe care-seeking behaviour. We used a comprehensive survey to identify care-seeking drivers, then performed multivariate analyses to identify care-seeking predictors. To identify profiles of individuals most at risk to delay care-seeking, we segmented the sample using unsupervised clustering. We then estimated the per cent of the TB-diagnosed population in Chennai in each segment., Results: Delayed care-seeking characteristics include smoking, drinking, being employed, preferring different facilities than the community, believing to be at lower risk of TB and believing TB is common. Respondents who reported fever or unintended weight loss were more likely to seek care. Clustering analysis revealed seven population segments differing in care-seeking, from a retired/unemployed/disabled cluster, where 70% promptly sought care, to a cluster of employed men who problem-drink and smoke, where only 42% did so. Modelling showed 54% of TB-diagnosed people who delay care-seeking might belong to the latter segment, which is most likely to acquire TB and least likely to promptly seek care., Conclusion: Interventions to increase care-seeking should move from building general awareness to addressing treatment barriers such as lack of time and low-risk perception. Care-seeking interventions should address specific beliefs through a mix of educational, risk perception-targeting and social norms-based campaigns. Employed men who problem-drink and smoke are a prime target for interventions. Reducing delays in this group could dramatically reduce TB spread., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

CD4 + T helper 1 (Th1) cells producing interferon gamma (IFN-γ) are critical for the resolution of visceral leishmaniasis (VL). MicroRNA 155 (miR155) promotes CD4 + Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL. To determine the role of miR155 in VL, we monitored the course of Leishmania donovani infection in miR155 knockout (miR155KO) and wild-type (WT) C57BL/6 mice. miR155KO mice displayed significantly higher liver and spleen parasite loads than WT controls and showed impaired hepatic granuloma formation. However, parasite growth eventually declined in miR155KO mice, suggesting the induction of a compensatory miR155-independent antileishmanial pathway. Leishmania antigen-stimulated splenocytes from miR155KO mice produced significantly lower levels of Th1-associated IFN-γ than controls. Interestingly, at later time points, levels of Th2-associated interleukin-4 (IL-4) and IL-10 were also lower in miR155KO splenocyte supernatants than in WT mice. On the other hand, miR155KO mice displayed significantly higher levels of IFN-γ , iNOS , and TNF-α gene transcripts in their livers than WT mice, indicating that distinct organ-specific antiparasitic mechanisms were involved in control of L. donovani infection in miR155KO mice. Throughout the course of infection, organs of miR155KO mice showed significantly more PDL1-expressing Ly6C hi inflammatory monocytes than WT mice. Conversely, blockade of Ly6C hi inflammatory monocyte recruitment in miR155KO mice significantly reduced parasitic loads, indicating that these cells contributed to disease susceptibility. In conclusion, we found that miR155 contributes to the control of L. donovani but is not essential for infection resolution., (Copyright © 2019 American Society for Microbiology.)

Here, we present the draft genome sequence of an anaerobic ammonium-oxidizing bacterium (AnAOB), " Candidatus Brocadia," which was enriched in an anammox reactor. A 3.2-Mb genome sequence comprising 168 contigs was assembled, in which 2,765 protein-coding genes, 47 tRNAs, and one each of 5S, 16S, and 23S rRNAs were annotated. No evidence for the presence of a nitric oxide-forming nitrite reductase was found., (Copyright © 2018 Liu et al.)

STAT4 is critical for the production of IFN-γ during the generation of T h 1 immune responses. We investigated the role of STAT4 in mediating T h 1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN-γ production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and T h 2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KO-derived splenocytes. Our observations for defective T h 1 and T h 2 responses in STAT4KO mice were further supported by the low levels of T h 1-associated IgG2a and T h 2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both T h 1 and T h 2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development., (© The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide (NO) and higher induction of IL-6, TGF-β, IL-10 and IL-18. While ibrutinib dampened MHC-II and CD86 expression on DCs, CD80 expression was upregulated. Further, ibrutinib-treated DCs promoted T cell proliferation and enhanced IL-17 production upon co-culture with nylon wool enriched T cells. Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response. We describe a novel mode of action for ibrutinib on DCs which should be explored to treat other forms of cancer besides B cell malignancies.

Conventional leaching (extraction) methods for gold recovery from electronic waste involve the use of strong acids and pose considerable threat to the environment. The alternative use of bioleaching microbes for gold recovery is non-pollutive and relies on the secretion of a lixiviant or (bio)chemical such as cyanide for extraction of gold from electronic waste. However, widespread industrial use of bioleaching microbes has been constrained by the limited cyanogenic capabilities of lixiviant-producing microorganisms such as Chromobacterium violaceum. Here we show the construction of a metabolically-engineered strain of Chromobacterium violaceum that produces more (70%) cyanide lixiviant and recovers more than twice as much gold from electronic waste compared to wild-type bacteria. Comparative proteome analyses suggested the possibility of further enhancement in cyanogenesis through subsequent metabolic engineering. Our results demonstrated the utility of lixiviant metabolic engineering in the construction of enhanced bioleaching microbes for the bioleaching of precious metals from electronic waste.

Leishmania are obligate intracellular parasites that cause a wide spectrum of diseases ranging from cutaneous, mucocutaneous and the visceral kind. Persistence or resolution of leishmaniasis is governed by host immune response. Co-stimulation is an important secondary signal that governs the extent, strength and direction of the immune response that follows. Co-stimulation by CD40, B7 and OX40 family has been shown to influence the outcome following Leishmania infection and manipulation of these pathways has shown promise for use in immune therapy of leishmaniasis. In this review, we discuss the roles of CD40, B7 and OX40 co-stimulatory pathways in regulating immunity to Leishmania and their implications in the treatment of this disease.