An interim exploratory proteomics biomarker analysis of a phase 2 clinical trial to assess the impact of CT1812 in Alzheimer's disease.

CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer's disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aß) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment. To elucidate the mechanism of action in AD patients and pharmacodynamic biomarkers of CT1812, the present study reports exploratory cerebrospinal fluid (CSF) biomarker data from 18 participants in an interim analysis of the first set of patients in SHINE (part A). Untargeted mass spectrometry-based discovery proteomics detects >2000 proteins in patient CSF and has documented utility in accelerating the identification of novel AD biomarkers reflective of diverse pathophysiologies beyond amyloid and tau, and enabling identification of pharmacodynamic biomarkers in longitudinal interventional trials. We leveraged this technique to analyze CSF samples taken at baseline and after 6 months of CT1812 treatment. Proteome-wide protein levels were detected using tandem mass tag-mass spectrometry (TMT-MS), change from baseline was calculated for each participant, and differential abundance analysis by treatment group was performed. This analysis revealed a set of proteins significantly impacted by CT1812, including pathway engagement biomarkers (i.e., biomarkers tied to S2R biology) and disease modification biomarkers (i.e., biomarkers with altered levels in AD vs. healthy control CSF but normalized by CT1812, and biomarkers correlated with favorable trends in ADAS-Cog11 scores). Brain network mapping, Gene Ontology, and pathway analyses revealed an impact of CT1812 on synapses, lipoprotein and amyloid beta biology, and neuroinflammation. Collectively, the findings highlight the utility of this method in pharmacodynamic biomarker identification and providing mechanistic insights for CT1812, which may facilitate the clinical development of CT1812 and enable appropriate pre-specification of biomarkers in upcoming clinical trials of CT1812.

Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Comparison of the performance of SWAT and hybrid M5P tree models in rainfall-runoff simulation.

Stream flow forecasting is a crucial aspect of hydrology and water resource management. This study explores stream flow forecasting using two distinct models: the Soil and Water Assessment Tool (SWAT) and a hybrid M5P model tree. The research specifically targets the daily stream flow predictions at the MH Halli gauge stations, located along the Hemvati River in Karnataka, India. A 14-year dataset spanning from 2003 to 2017 is divided into two subsets for model calibration and validation. The SWAT model's performance is evaluated by comparing its predictions to observed stream flow data. Residual time series values resulting from this comparison are then resolved using the M5P model tree. The findings reveal that the hybrid M5P tree model surpasses the SWAT model in terms of various evaluation metrics, including root-mean-square error, coefficient of determination (R2), Nash-Sutcliffe efficiency, and degree of agreement (d) for the MH Halli stations. In conclusion, this study shows the effectiveness of the hybrid M5P tree model in stream flow forecasting. The research contributes valuable insights into improved water resource management and underscores the importance of selecting appropriate models based on their performance and suitability for specific hydrological forecasting tasks.

Effects of UV radiation on natural and synthetic materials.

The deleterious effects of solar ultraviolet (UV) radiation on construction materials, especially wood and plastics, and the consequent impacts on their useful lifetimes, are well documented in scientific literature. Any future increase in solar UV radiation and ambient temperature due to climate change will therefore shorten service lifetimes of materials, which will require higher levels of stabilisation or other interventions to maintain their lifetimes at the present levels. The implementation of the Montreal Protocol and its amendments on substances that deplete the ozone layer, controls the solar UV-B radiation received on Earth. This current quadrennial assessment provides a comprehensive update on the deleterious effects of solar UV radiation on the durability of natural and synthetic materials, as well as recent innovations in better stabilising of materials against solar UV radiation-induced damage. Pertinent emerging technologies for wood and plastics used in construction, composite materials used in construction, textile fibres, comfort fabric, and photovoltaic materials, are addressed in detail. Also addressed are the trends in technology designed to increase sustainability via replacing toxic, unsustainable, legacy additives with 'greener' benign substitutes that may indirectly affect the UV stability of the redesigned materials. An emerging class of efficient photostabilisers are the nanoscale particles that include oxide fillers and nanocarbons used in high-performance composites, which provide good UV stability to materials. They also allow the design of UV-shielding fabric materials with impressive UV protection factors. An emerging environmental issue related to the photodegradation of plastics is the generation of ubiquitous micro-scale particles from plastic litter exposed to solar UV radiation.

Dissipation kinetics, food safety evaluation and decontamination of chlorantraniliprole in cowpea.

Cowpea is known for its high protein content (18-25%) and also chiefly raised for green fodder. The infesting pests, pod borer and aphids are the most destructive ones. To control these pests, chlorantraniliprole emerges as a promising molecule. Thus, its needs to assess the dissipation nature of the chlorantraniliprole. Hence, a trial was conducted at IIVR, Varanasi, India. The residue analysis was done through solid phase extraction method followed by gas chromatoghraphy analysis. The analytical method was standardized and validated according to international standard. The half-life of chlorantraniliprole in cowpea pods was estimated in the range of 2.79- 2.33 days in the year-I and 2.51-2.32 days in the year-II for single dose (SD) and double dose (DD) respectively. Similarly, half-life of the chlorantraniliprole in leaves 2.43-2.27 days whereas, 1.94-1.70 days in case of soil. The exposure of the residues in pods were less than maximum permissible intake (MPI). The RQ values revealed that there could be negligible risk to earthworms and arthropods. Washing with boiling water was found the most effective decontamination treatment to remove residue from cowpea pods. Thus, it could be concluded that chlorantraniliprole does not pose any significant threat when uses in cowpea in a particular dose.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021.

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

Dendritic cell engineered cTXN as new vaccine prospect against L. donovani.

Dendritic cells (DCs), as antigen-presenting cells, can reportedly be infected withLeishmaniaparasites and hence provide a better option to trigger T-cell primary immune responses and immunological memory. We consistently primed DCs during culture with purified recombinant cytosolic tryparedoxin (rcTXN) and then evaluated the vaccine prospect of presentation of rcTXN against VL in BALB/c mice. We reported earlier the immunogenic properties of cTXN antigen derived fromL. donovani when anti-cTXN antibody was detected in the sera of kala-azar patients. It was observed that cTXN antigen, when used as an immunogen with murine DCs acting as a vehicle, was able to induce complete protection against VL in an infected group of immunized mice. This vaccination triggered splenic macrophages to produce more IL-12 and GM-CSF, and restricted IL-10 release to a minimum in an immunized group of infected animals. Concomitant changes in T-cell responses against cTXN antigen were also noticed, which increased the release of protective cytokine-like IFN-γ under the influence of NF-κß in the indicated vaccinated group of animals. All cTXN-DCs-vaccinated BALB/c mice survived during the experimental period of 120 days. The results obtained in our study suggest that DCs primed with cTXN can be used as a vaccine prospect for the control of visceral leishmaniasis.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

The Double Burden of COVID-19 and Dengue in Nepal: The challenges ahead.

Coronavirus disease 2019 (COVID-19) pandemic has caused significant impact on the health care system. As a consequence, diagnosis and treatment of vector borne diseases including dengue has been equally affected. Nepal is no exception to this, where COVID-19 cases is exponentially increased and all resources are concentrated on its prevention, control and management. Dengue, one of the major vector-borne diseases in Nepal, is apparently overlooked despite approaching the peak season of the disease. The aim of this paper is to describe the double burden of COVID-19 and dengue in Nepal, particularly highlighting the co-circulation and possible coinfections. This has posed higher risk of increased severity, more severe cases and deaths in Nepal. Moreover, potential misdiagnosis of these viral diseases may lead to delayed or, inappropriate treatment and poor allocation of resources.

Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019.

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Pressure-Induced Amorphization of Diisopropylammonium Perchlorate Studied by Raman Spectroscopy and X-ray Diffraction.

Diisopropylammonium salts have drawn attention in recent years due to their room-temperature ferroelectric properties. Triclinic diisopropylammonium perchlorate (DIPAP) exhibits ferroelectricity at room temperature. We have carried out density functional theory calculations to assign the phonon modes in DIPAP. High-pressure Raman spectra of DIPAP are recorded up to ∼3 GPa. Discontinuity in the NH2 bending and stretching mode frequencies and the appearance of new bands at 0.7 GPa suggest a phase transition by a rearrangement in the hydrogen network. Broadening of lattice modes at 1.3-1.7 GPa indicates a loss of crystalline nature above 1.7 GPa. High-pressure synchrotron X-ray diffraction of DIPAP shows an isostructural phase transition at 0.6 GPa and confirms amorphization at 1.5 GPa that may lead to a loss of ferroelectricity above this pressure. The ambient phase becomes reversible after releasing the pressure. The bulk modulus of DIPAP is determined to be 16.5 GPa.

Visceral leishmaniasis: A novel nuclear envelope protein 'nucleoporins-93 (NUP-93)' from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response.

The shift of macrophage and T-cell repertoires towards proinflammatory cytokine signalling ensures the generation of host-protective machinery that is otherwise compromised in cases of the intracellular Leishmania parasite. Different groups have attempted to restore host protective immunity. These vaccine candidates showed good responses and protective effects in murine models, but they generally failed during human trials. In the present study, we evaluated the effect of 97 kDa recombinant nucleoporin-93 of Leishmania donovani (rLd-NUP93) on mononuclear cells in healthy and treated visceral leishmaniasis (VL) patients and on THP-1 cell lines. rLd-NUP93 stimulation increased the expression of the early lymphocyte activation marker CD69 on CD4+ and CD8+ T cells. The expression of the host protective pro-inflammatory cytokines IFN-γ, IL-12 and TNF-α was increased, with a corresponding down-regulation of IL-10 and TGF-ß upon rLd-NUP93 stimulation. This immune polarization resulted in the up-regulation of NF-κB p50 with scant expression of SMAD-4. Augmenting lymphocyte proliferation upon priming with rLd-NUP93 ensured its potential for activation and generation of strong T-cell mediated immune responses. This stimulation extended the leishmanicidal activity of macrophages by releasing high amounts of reactive oxygen species (ROS). Further, the leishmanicidal activity of macrophages was intensified by the elevated production of nitric oxide (NO). The fact that this antigen was earlier reported in circulating immune complexes of VL patients highlights its antigenic importance. In addition, in silico analysis suggested the presence of MHC class I and II-restricted epitopes that proficiently trigger CD8+ and CD4+ T-cells, respectively. This study reported that rLd-NUP93 was an effective immunoprophylactic agent that can be explored in future vaccine design.

Interactive effects of solar UV radiation and climate change on material damage.

Solar UV radiation adversely affects the properties of organic materials used in construction, such as plastics and wood. The outdoor service lifetimes of these materials are influenced by their rates of degradation under solar UV radiation as well as by other climate factors such as temperature, moisture, and atmospheric pollutants. While recovery of the stratospheric ozone layer is expected, local increases in UV radiation are still likely to occur, especially in the tropics, but also elsewhere because of climate change effects. Such increases, when taken together with an increased ambient temperature due to climate change, can significantly shorten the service lifetimes of organic building materials. Several proven technologies, including the use of UV stabilisers, surface treatments or coatings have been developed over the years to mitigate these adverse effects. While these technologies should be able to compensate for any realistic future UV radiation and climate change scenarios, they will also add significantly to the lifetime cost of material in relevant products. Shorter outdoor lifetime of the plastic components in photovoltaic (PV) modules is a serious concern in the solar energy industry. To ensure module durability over the full service-lifetime (of about ∼20 years) of the light-harvesting PV components, better stabilisation technologies are being investigated. The present trend towards more environmentally sustainable materials in building, and environmental impact of additives such as stabilisers, need to be considered in addition to their engineering performance. This may require the phasing out of some conventional additives used in plastics as well as substituting wood or other materials in place of plastics in buildings. Depending on the relative costs of mitigation, substituting more UV-stable materials for conventional ones in outdoor products may also be a viable option with some categories of products. Neither the global cost of mitigation of the effects of climate change on materials nor the long-term sustainability of the technologies available for the purpose, have been estimated. Plastic waste and litter exposed outdoors to solar UV radiation over extended periods undergo cracking and fragmentation into small pieces (of micro- and nano-scale size). Release of these fragments into the environment, particularly in the aquatic environment, poses a potential threat to marine biota. Already several hundred of species are known to ingest these fragments that can potentially accumulate additives and pollutants from water. This is a potential threat to humans because 25% of fish marketed for human consumption have been reported to contain microplastics in their digestive systems. The focus of this assessment is on recent advances in understanding the mechanisms of UV-radiation-induced degradation in materials and in assessing emerging technologies for their stabilisation against outdoor UV-degradation. A better understanding of the mechanisms of degradation will allow for innovative stabilisation approaches to be developed. Also assessed is information on the sustainability of the available and emerging UV stabilisation technologies.

Doping effect on the local structure of metamagnetic Co doped Ni/NiO:GO core-shell nanoparticles using X-ray absorption spectroscopy and the pair distribution function.

Core-shell nanoparticles of Co (0%, 3%, and 5%) doped Ni/NiO and incorporated (5 mg) graphene oxide (GO) sheets were synthesized by a sol-gel auto-combustion method. X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and pair distribution function measurements were employed for the determination of the local structure and structural properties of the samples. Due to the effect of Co doping the bond lengths of all coordinate atoms were varied. The microstructural features in the core-shell structured particles were evaluated with high-resolution transmission electron microscopy (HRTEM). Magnetic properties of the samples revealed that both the interface of Ni/Co and NiO crystal lattices and the weight fraction of Ni have significant impact on their magnetic properties at 5 K to 300 K. Experimental results show that Co doping and GO incorporation into Ni/NiO suppress the antiferromagnetic charge ordering and lead to a spin-flop metamagnetic behavior at 5 K to 300 K temperatures. Above 5 K, the step-like transitions transform into broad ones. This step-like feature is correlated with the collapse of the balance between the magnetic energy and elastic energy at the core-shell interface. It is confirmed from M-T measurements that the blocking temperature of Ni/NiO was reduced with Co content.

Magnitude of unreported kala-azar cases in a highly endemic district of Bihar, India: A positive impact of Indian elimination programme.

BACKGROUND & OBJECTIVES: In India, kala-azar surveillance is weak and no public-private partnership exists for disease containment. Estimate of disease burden is not reliably available and still cases are going to private providers for the treatment. The present study aimed to assess the magnitude of kala-azar cases actually detected and managed at private set-up and unreported to existing health management information system. METHODS: Institution based cross-sectional prospective pilot study was conducted. List of facilities was created with the help of key informants. The information about incidence of kala-azar cases were captured on monthly basis from July 2010 to June 2011. Rapid diagnostic strip test (rk-39) or bone marrow/splenic puncture were applied as laboratory methods for the diagnosis of kala-azar. Descriptive statistics as well as chi-square test for comparison between proportions was conducted. RESULTS: Overall availability of private practitioners (PPs) was 4.59/1,00,000 population and maximum PPs (46; 93.9%) were from qualified category. The median years of medical practice was 25 yr (inter quartile-range [18, 28]). Interestingly, only a small proportion (240; 19%) of cases was managed by PPs. Amongst the PPs, only low proportion (32; 18.2%) managed >2 cases per month. The mean number of kala-azar suspects and cases identified varied significantly between different PPs' professions with p <0.048 and p <0.032, respectively. A highly significant difference (p <0.0001) was observed for kala-azar case load between qualified and unqualified practitioners. A small proportion (38; 15.8%) of kala-azar cases was not present in the public health system record. INTERPRETATION & CONCLUSION: Still sizeable proportions of cases are going to PPs and unrecorded into government surveillance system. A mechanism need to be devised to involve at least qualified PPs in order to reduce treatment delay and increase case detection in the region.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

New High Pressure Phases of Energetic Material TEX: Evidence from Raman Spectroscopy, X-ray Diffraction, and First-Principles Calculations.

Samples of energetic material TEX (C6H6N4O8) are studied using Raman spectroscopy and X-ray diffraction (XRD) up to 27 GPa pressure. There are clear changes in the Raman spectra and XRD patterns around 2 GPa related to a conformational change in the TEX molecule, and a phase transformation above 11 GPa. The molecular structures and vibrational frequencies of TEX are calculated by density functional theory based Gaussian 09W and CASTEP programs. The computed frequencies compare well with Raman spectroscopic results. Mode assignments are carried out using the vibrational energy distribution analysis program and are also visualized in the Materials Studio package. Raman spectra of the high pressure phases indicate that the sensitivity of these phases is more than that of the ambient phase.

Actinomycetes: an unexplored microorganisms for plant growth promotion and biocontrol in vegetable crops.

Actinomycetes, a Gram positive bacteria, well reported as a source of antibiotics, also possess potential to control various plant pathogens, besides acting as plant growth promoting agent. Chemicals in different forms are extensively being used in vegetable farming, adversely affecting the environment and consumer health. Microbial agent like actinomycetes can substantially replace these harmful chemicals, and have now started finding a place as an important input in to farming practices. Only selected vegetable crops belonging to 11 different families have been explored with use of actinomycetes as biocontrol and plant growth promoting agent till now. It provides ample opportunities to vegetable researchers, to further explore with use of this very important group of microorganisms, in order to achieve even higher production level of safe vegetables. Mycostop and Actinovate are two actinomycetes based formulations globally available for use in vegetable farming as a substitute for chemical formulations. Present review article has summarized the literature available on use of actinomycetes in vegetable farming. Existing wide gap in knowledge, and potential thrust areas for future research have also been projected.

Vaccine potential of HLA-A2 epitopes from Leishmania Cysteine Protease Type III (CPC).

Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8+ T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8+ T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3+ T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.

Bismuth(III) Complexes with Bis(dimethylphenyl) Dithiophosphates: Synthesis, Characterization and Crystal Structure of [{(3,5-CH3)2C6H3O}2PS2]3Bi.

This work presents four complexes with general formula [(ArO)2PS23Bi] (1-4), where Ar = 2,4-(CH3)2C6H3, 2,5-(CH3)2C6H3, 3,4-(CH3)2C6H3 and 3,5-(CH3)2C6H3, respectively. Reaction of [(ArO)2PS2Na] with Bi(NO3)3 · 5H2O in toluene in 3:1 molar stoichiometry afforded the complexes [(ArO)2PS23Bi]. These newly synthesized complexes have been characterized by elemental analysis, FT-IR and multinuclear NMR (1H, 13C and 31P) NMR. The crystal structure of [(3,5-CH3)2C6H3O2PS2]3Bi (4) has been determined by X-ray crystallography. The compound crystallizes in monoclinic P21/c space group and Bi(III) centre is surrounded by six sulfur atoms from three symmetrically chelating bidentate diphenyl dithiophosphate ligands in a distorted octahedron environment. Screening these complexes for their antifungal activity against Pencillium chrysogenum gave positive results.