Advances in diagnostic approaches to Fasciola infection in animals and humans: An overviews.

Fasciolosis, caused by Fasciola hepatica and F. gigantica, is an impediment to the livestock industry's expansion and has a massively negative socio-economic impact due to its widespread prevalence in livestock. It is a waterborne zoonosis affecting human populations in the countries where rural economies are associated with livestock rearing. Conventional diagnosis of Fasciola infection is done by detecting parasite eggs in the faeces of infected animals or by immunological methods. Accurate and quick immunodiagnosis of Fasciola infection in animals and humans is based on the detection of antibodies and specific antigens expressed in the prepatent stage of the parasite. Both molecular and serodiagnostic tests developed thus far have enhanced the reliability of Fasciola diagnosis in both man and animals but are not widely available in resource-poor nations. A pen-side diagnostic test based on a lateral flow assay or a DNA test like loop-mediated isothermal amplification (LAMP) would be simple, fast, and cost-effective, enabling clinicians to treat animals in a targeted manner and avoid the development of drug resistance to the limited flukicides. This review focuses on the recent advances made in the diagnosis of this parasite infection in animals and humans.

Air pollution tolerance index of Persea bombycina: Primary food plant of endemic muga silkworm (Antheraeaassamensis).

Air pollution poses a significant threat to human health, ecosystems, and the livelihood of tribal communities. This study focuses on understanding the impact of air pollution on the primary food plant som (Persea bombycina Kost.) of the endemic Muga silkworm (Antheraea assamensis) and its implications for muga silk production. The study was conducted at two sites in northeastern India, one free from atmospheric pollutants (FAP) and the other affected by pollution from an oil refinery (PAS). Various atmospheric pollutants, including particulate matter, hydrocarbons, and heavy metals, were found to be higher at the PAS site. The study investigated biochemical parameters like ascorbic acid, relative water content, total chlorophyll, and extractable pH in the leaves of P. bombycina to determine its air pollution tolerance index (APTI). Results showed that the ascorbic acid content in the leaves increased significantly at the PAS site (p < 0.05), indicating the plant's adaptation to air pollution stress. Similarly, the APTI values were higher during summer compared to winter, suggesting better tolerance during the former season. Positive correlations were found between APTI and ascorbic acid content (p < 0.05), emphasizing the role of ascorbic acid as an antioxidant in mitigating the effects of air pollution. The study highlights the importance of understanding the tolerance levels of P. bombycina to develop protective measures for sustaining Muga silk production in the face of rapid industrialization and increasing pollution. This research can aid policymakers in balancing economic growth with environmental conservation and protecting traditional practices of tribal communities.

A Comparison of the Modified Alvarado Score and the Raja Isteri Pengiran Anak Saleha Appendicitis (Ripasa) Score in a Southeast Asian Population With Histopathology as the Gold Standard.

Background The diagnosis of acute appendicitis has remained difficult despite it being one of the most common surgical emergencies in the world. One of the most frequently used scoring systems is the Modified Alvarado Score (MAS). However, the MAS has been known to be less efficient in Asian populations. To overcome this issue, the Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score has been specifically developed to improve the diagnosis of acute appendicitis in Asian populations. This study aimed to evaluate the accuracy of the RIPASA score compared to the MAS for the diagnosis of acute appendicitis in a Southeast Asian population keeping histopathology as the gold standard. Methodology The study group comprised 150 patients. Data were collected from each patient using a simple proforma to ascertain both the MAS and the RIPASA score for each patient at the time of presentation. The patients then underwent open appendectomy and histopathology was used as the gold standard to determine the presence or absence of acute appendicitis in the excised specimens. Results The RIPASA score had a sensitivity and specificity of 89.83% and 59.38%, respectively, compared to 64.41% and 53.12%, respectively, for the MAS. Diagnostic accuracy was similarly higher for the RIPASA score at 83.33% versus 62.00% for the MAS. Conclusions The RIPASA score is superior to the MAS for the diagnosis of acute appendicitis. Using the RIPASA score instead of the MAS in Southeast Asian populations can lead to a more accurate and timely clinical diagnosis of patients with suspected acute appendicitis and help improve patient outcomes.

Plummeting toxic contaminates from water through phycoremediation: Mechanism, influencing factors and future outlook to enhance the capacity of living and non-living algae.

Freshwater habitats hold a unique role in the survival of all living organisms and supply water for drinking, irrigation, and life support activities. In recent decades, due to anthropogenic activities, deterioration in the water quality has been a long-lasting problem and challenge to the scientific fraternity. Although, these freshwater bodies have a bearable intrinsic capacity for pollution load however alarming increase in pollution limits the intrinsic capacities and requires additional technological interventions. The release of secondary pollutants from conventional interventions further needs revisiting the existing methodologies and asking for green interventions. Green interventions such as phycoremediation are natural, eco-friendly, economic, and energy-efficient alternatives and provide additional benefits such as nutrient recovery, biofuel production, and valuable secondary metabolites from polluted freshwater bodies. This systemic review in a nut-shell comprises the recent research insights on phycoremediation, technological implications, and influencing factors, and further discusses the associated mechanisms of metal ions biosorption by living and non-living algae, its advantages, and limitations. Besides, the article explores the possibility of future research prospects for applicability at a field scale that will help in the efficient utilization of resources, and improved ecological and health risks.

The gut ecosystem and immune tolerance.

The gastrointestinal tract is home to the largest microbial population in the human body. The gut microbiota plays significant roles in the development of the gut immune system and has a substantial impact on the maintenance of immune tolerance beginning in early life. These microbes interact with the immune system in a dynamic and interdependent manner. They generate immune signals by presenting a vast repertoire of antigenic determinants and microbial metabolites that influence the development, maturation and maintenance of immunological function and homeostasis. At the same time, both the innate and adaptive immune systems are involved in modulating a stable microbial ecosystem between the commensal and pathogenic microorganisms. Hence, the gut microbial population and the host immune system work together to maintain immune homeostasis synergistically. In susceptible hosts, disruption of such a harmonious state can greatly affect human health and lead to various auto-inflammatory and autoimmune disorders. In this review, we discuss our current understanding of the interactions between the gut microbiota and immunity with an emphasis on: a) important players of gut innate and adaptive immunity; b) the contribution of gut microbial metabolites; and c) the effect of disruption of innate and adaptive immunity as well as alteration of gut microbiome on the molecular mechanisms driving autoimmunity in various autoimmune diseases.

Clinical performance and Willingness To Pay for soft toric contact lenses in low and moderate astigmats.

PURPOSE: To determine clinical performance and the 'Willingness To Pay' for toric vs. spherical soft contact lenses in an astigmatic population. METHODS: In the clinical study, subjects with binocular low to moderate astigmatism (-0.75DC to -1.50DC) wore pairs of soft toric (Biofinity toric) and spherical (Biofinity) contact lenses in random sequence. Visual acuity (high and low contrast, monocular and binocular), subjective comfort and subjective vision were recorded. In the economics study, first subjects who had participated in the clinical study were presented with a series of randomised economic scenarios in order to determine their Willingness To Pay a premium (i.e. an increase) for toric lenses. Then, a similar set of scenarios were presented to a much larger group of online respondents and again, Willingness To Pay was established. RESULTS: For the four measures of visual acuity, the Biofinity toric lens out-performed the Biofinity spherical lens by 0.6 to 1.1 lines.. Subjective vision performance was statistically significantly better with the toric lens for the distance task only. Comfort scores were not significantly different. Similar findings for Willingness To Pay were established for the clinical subjects and for the online respondents. The Willingness To Pay premium (additional fee) for a monthly supply of toric lenses (over spherical lenses) was between £13 and £16, if a toric lens provides better vision and similar comfort, as shown in the clinical study. CONCLUSION: Consumers are willing to pay a monthly premium of around 50% to benefit from the typical experience of better vision and similar comfort for toric vs. spherical lenses. The level of additional cost for toric lenses compared to their spherical equivalents is less than this in the market, so eye care professionals should consider that toric lenses are delivering a greater clinical return than anticipated by wearers for the relatively small increase in price.

Spontaneous development of an autoimmune hepatitis - primary biliary cholangitis overlap syndrome in dnTGFßRII Aire-/- mice.

Autoimmune regulator (Aire) and TGF-ß signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFßRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)-like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFßRII Aire-/- mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA-seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFßRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T-cell-mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland.

3D printing of hollow geometries using blocking liquid substitution stereolithography.

Micrometer scale arbitrary hollow geometries within a solid are needed for a variety of applications including microfluidics, thermal management and metamaterials. A major challenge to 3D printing hollow geometries using stereolithography is the ability to retain empty spaces in between the solidified regions. In order to prevent unwanted polymerization of the trapped resin in the hollow spaces-known as print-through-significant constraints are generally imposed on the primary process parameters such as resin formulation, exposure conditions and layer thickness. Here, we report on a stereolithography process which substitutes the trapped resin with a UV blocking liquid to mitigate print-through. We investigate the mechanism of the developed process and determine guidelines for the formulation of the blocking liquid. The reported method decouples the relationship between the primary process parameters and their effect on print-through. Without having to optimize the primary process parameters to reduce print-through, hollow heights that exceed the limits of conventional stereolithography can be realized. We demonstrate fabrication of a variety of complex hollow geometries with cross-sectional features ranging from tens of micrometer to hundreds of micrometers in size. With the framework presented, this method may be employed for 3D printing functional hollow geometries for a variety of applications, and with improved freedom over the printing process (e.g. material choices, speed and resulting properties of the printed parts).

A Systematic Review of Whether the Use of N95 Respirator Masks Decreases the Incidence of Cardiovascular Disease in the General Population.

The usage of masks such as the N95 has increased exponentially worldwide. With the ever-increasing global rates of cardiovascular disease, it is vital that preventative measures are adopted to help tackle this crisis. N95 masks have been promoted as health prevention odysseys in the battle against viruses such as COVID-19. A systematic review was conducted on whether the N95 masks could help improve our cardiovascular health. Our data sources included PubMed, Medline and Scopus. Eleven studies met the eligibility criteria to be included in the review. N95 mask usage led to increased reports of dyspnoea, however, no significant effect was seen on blood pressure. N95 masks also showed improvement in aortic parameters. While encouraging results were yielded, further focussed studies on the use of N95 masks and the effect on various cardiovascular parameters would help strengthen the association.

Accounting on silk for reducing microplastic pollution from textile sector: a viewpoint.

Microplastic pollution is the emerging issue in the recent past and has been identified in the remotely located ecosystems. The textile sector is one of the key contributors in the microplastic pollution. Keeping this in view, the present viewpoint has been planned to address the systematic possible reduction of microplastic pollution. It has been observed through the literature that silk is having a promising material to reduce the microplastic problems and its associated environmental risk due to its non-persistent nature.

Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression.

The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation. We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis. To study this hypothesis, ARE-Del+/- mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied. JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage, associated with a significant reduction in splenic and hepatic CD4+ T cells and CD8+ T cells. Functionally, ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγ and TNF from splenic CD4+ T cells. Additionally, ruxolitinib treatment also decreased the frequencies of germinal center B (GC B) cells and T follicular helper (Tfh) cells and led to lower serological AMA levels. Of note, liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment. Mechanistically, ruxolitinib inhibited the secretion of IL-6, TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro, indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway. Our data highlight the significance, both immunologically and clinically, of the JAK/STAT signaling pathway in autoimmune cholangitis.

Single-Cell Characterization of Hepatic CD8+ T Cells in a Murine Model of Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC), an organ-specific autoimmune disease, is characterized by injury to small bile ducts, inflammatory cell infiltrates within the liver, progressive cholestasis, and in some cases, cirrhosis with unclear pathogenesis. We aimed to clarify the importance role of hepatic immunce cells in the pathogenesis of human and experimental PBC.The dominant-negative TGFß receptor type II transgenic (dnTGFßRII) mice, a well-studied and established murine model of PBC were used to identify changes of immune cells, especially the pathogenic CD8+ T cells. The high-throughput single-cell RNA sequencing technology were applied and found functional heterogeneity among the hepatic CD8+ T cells subsets in dnTGFßRII mice. CD8+ T cells were confirmed the key cells leading to the pathogenesis of PBC in dnTGFßRII mice, and identified the terminally differentiated CD8αα T cells and CD8αß T cell subsets in the liver of dnTGFßRII mice. While terminally differentiated CD8αα T cells have higher cytokine production ability and cytotoxicity, the terminally differentiated CD8αß T cells retain their proliferative profile. Our work suggests that there are developmental and differentiated trajectories of pathogenic CD8+ T cell subsets in the pathogenesis of PBC. A further clarification of their roles would be helpful to our understanding of the pathogenesis of PBC and may potentially lead to identifying novel therapeutic modalities.

E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants.

BACKGROUND AND AIMS: The increased frequency of urinary tract infections in patients with primary biliary cholangitis (PBC) and the cross-reactivity between the lipoyl domains (LD) of human pyruvate dehydrogenase complex (hPDC-E2) and Escherichia coli PDC-E2 (ePDC-E2) have long suggested a role of E. coli in causality of PBC. This issue, however, has remained speculative. We hypothesized that by generating specific constructs of human and E. coli PDC-E2, we would be able to assess the specificity of autoantibody responses and define whether exposure to E. coli in susceptible hosts is the basis for the antimitochondrial antibody (AMA) response. APPROACH AND RESULTS: Importantly, the reactivity of hPDC-E2 LD (hPDC-E2LD) affinity-purified antibodies against hPDC-E2LD could only be removed by prior absorption with hPDC-E2LD and not ePDC-E2, suggesting the presence of unique human PDC-E2 epitopes distinct from E. coli PDC-E2. To identify the autoepitope(s) present in hPDC-E2LD, a more detailed study using a variety of PDC-E2 constructs was tested, including the effect of lipoic acid (LA) on ePDC-E2 conformation and AMA recognition. Individual recombinant ePDCE2 LD domains LD1, LD2 and LD3 did not react with either AMA or antibodies to LA (anti-LA), but in contrast, anti-LA was readily reactive against purified recombinant LD1, LD2, and LD3 expressed in tandem (LP); such reactivity increased when LP was precultured with LA. Moreover, when the three LD (LD1, LD2, LD3) domains were expressed in tandem in pET28a or when LD1 was expressed in another plasmid pGEX, they were lipoylated and reactive to PBC sera. CONCLUSIONS: In conclusion, our data are consistent with an exposure to E. coli that elicits specific antibody to ePDC-E2 resulting in determinant spreading and the classic autoantibody to hPDC-E2LD. We argue this is the first step to development of human PBC.

Kinetic Changes of Peripheral Blood Monocyte Subsets and Expression of Co-Stimulatory Molecules during Acute Dengue Virus Infection.

Monocytes, one of the main target cells for dengue virus (DENV) infection, contribute to the resolution of viremia and to pathogenesis. We performed a longitudinal study by a detailed phenotypic comparison of classical (CD14++CD16-, non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocyte subsets in blood samples from dengue fever (DF) to the severe dengue hemorrhagic fever (DHF) and healthy individuals. Various costimulatory molecules of CD40, CD80, CD86 and inducible costimulatory ligand (ICOSL) expressed on these three monocyte subsets were also analyzed. DENV-infected patients showed an increase in the frequency of intermediate monocytes and a decrease in the classical monocytes when compared to healthy individuals. Although these differences did not correlate with disease severity, changes during the early phase of infection gradually returned to normal in the defervescence phase. Moreover, decreased frequency of classical monocytes was associated with a significant up-regulation of co-stimulatory molecules CD40, CD86 and ICOSL. Kinetics of these co-stimulatory molecule-expressing classical monocytes showed different patterns throughout the sampling times of acute DENV infection. Different distribution of monocyte subsets and their co-stimulatory molecules in the peripheral blood during acute infection might exacerbate immune responses like cytokine storms and ADE, and future studies on intracellular molecular pathways utilized by these monocyte linages are warranted.

Myco-remediation: A mechanistic understanding of contaminants alleviation from natural environment and future prospect.

Industrialization and modernization of agricultural systems contaminated lithosphere, hydrosphere, and biosphere of the Earth. Sustainable remediation of contamination is essential for environmental sustainability. Myco-remediation is proposed to be a green, economical, and efficient technology over conventional remediation technologies to combat escalating pollution problems at a global scale. Fungi can perform remediation of pollutants through several mechanisms like biosorption, precipitation, biotransformation, and sequestration. Myco-remediation significantly removes or degrades metal metals, persistent organic pollutants, and other emerging pollutants. The current review highlights the species-specific remediation potential, influencing factors, genetic and molecular control mechanism, applicability merits to enhance the bioremediation efficiency. Structure and composition of fungal cell wall is crucial for immobilization of toxic pollutants and a subtle change on fungal cell wall structure may significantly affect the immobilization efficiency. The utilization protocol and applicability of enzyme engineering and myco-nanotechnology to enhance the bioremediation efficiency of any potential fungus was proposed. It is advocated that the association of hyper-accumulator plants with plant growth-promoting fungi could help in an effective cleanup strategy for the alleviation of persistent soil pollutants. The functions, activity, and regulation of fungal enzymes in myco-remediation practices required further research to enhance the myco-remediation potential. Study of the biotransformation mechanisms and risk assessment of the products formed are required to minimize environmental pollution. Recent advancements in molecular "Omic techniques"and biotechnological tools can further upgrade myco-remediation efficiency in polluted soils and water.

Facile Electrochemical Determination of Methotrexate (MTX) Using Glassy Carbon Electrode-Modified with Electronically Disordered NiO Nanostructures.

Recently, the oxidative behavior of methotrexate (MTX) anticancer drug is highly demanded, due to its side effects on healthy cells, despite being a very challenging task. In this study, we have prepared porous NiO material using sodium sulfate as an electronic disorder reagent by hydrothermal method and found it highly sensitive and selective for the oxidation of MTX. The synthesized NiO nanostructures were characterized by scanning electron microscope (SEM) and X-ray diffraction (XRD) techniques. These physical characterizations delineated the porous morphology and cubic crystalline phase of NiO. Different electrochemical approaches have been utilized to determine the MTX concentrations in 0.04 M Britton-Robinson buffer (BRB) at pH 2 using glassy carbon electrode (GCE)-modified with electronically disordered NiO nanostructures. The linear range for MTX using cyclic voltammetry (CV) was found to be from 5 to 30 nM, and the limit of detection (LOD) and limit of quantification (LOQ) were 1.46 nM and 4.86 nM, respectively, whereas the linear range obtained via linear sweep voltammetry (LSV) was estimated as 15-90 nM with LOD and LOQ of 0.819 nM and 2.713 nM, respectively. Additionally, amperometric studies revealed a linear range from 10 to70 nM with LOD and LOQ of 0.1 nM and 1.3 nM, respectively. Importantly, MTX was successfully monitored in pharmaceutical products using the standard recovery method. Thus, the proposed approach for the synthesis of active metal oxide materials could be sued for the determination of other anticancer drugs in real samples and other biomedical applications.

Viremia controls Env-specific antibody-secreting cell responses in simian immunodeficiency virus infected macaques pre and post-antiretroviral therapy.

OBJECTIVE: The aim of this study was to investigate the kinetics of Env (gp140)-specific antibody-secreting cells (ASCs) during acute and early chronic simian immunodeficiency virus (SIV) infection, and prior to and postantiretroviral therapy (ART) in rhesus macaques. DESIGN AND METHODS: At week 0, rhesus macaques were inoculated intravenously with SIVmac239 and the viral loads were allowed to develop. Daily ART was initiated at week 5 post infection until week 18, though the animals were monitored until week 28 for the following parameters: enumeration of SIV gp140-specific ASCs by ELISPOT; quantification of viremia and SIV gp140-specific IgG titres through qRT-PCR and ELISA, respectively; estimation of monocytes, follicular helper T cells (Tfh) and memory B cell frequencies using polychromatic flow cytometry. RESULTS: Direct correlations were consistently found between blood SIV gp140-specific ASC responses and viremia or SIV Env-specific IgG titres. In contrast, SIV gp140-specific ASC responses showed inverse correlations with the percentage of total memory B cells in the blood. In lymph nodes, the magnitude of the SIV gp140-specific ASC responses also followed the viral load kinetics. In contrast, the number of SIV gp140-specific ASCs presented did not correlate with frequencies of circulating activated monocyte (CD14+CD16+) or Tfh cells. CONCLUSION: Blood and/or lymph node viral loads may regulate the onset and magnitude of SIV gp140-specific ASCs during SIV infection and following ART in rhesus macaques.

A Review of the Evidence Base for Nutrition and Nutritional Supplements in Older Adults with Bipolar Disorder: A report from the OABD task force.

OBJECTIVES: To better understand the role of nutrition in older adults (aged 50 years or older) with bipolar disorders (OABD), we conducted a systematic review of the literature and appraise existing evidence. METHODS: Following PRISMA guidelines, we searched databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Register, FDA website, and clinical trial registries through 2019 for eligible reports. The search string combined MeSH terms for bipolar disorder, nutrition and older adults. This was supplemented by snowball searching of references in relevant studies and authors were contacted to request their work where necessary. All included studies were rated with the National Institutes of Health Study Quality Assessment Tools based on study designs. RESULTS: Of 2280 papers screened, ten studies including eight observational and two interventional studies. The topic foci of the papers examined several nutrients, (including vitamin B12, vitamin D, coenzyme Q10, homocysteine, and folate), nutritional deficiencies and biochemical correlates. The prevalence rates of deficiencies varied with specific nutrients (3.7% to 71.6% for Vitamin B12 and 34.6% for Vitamin D), and between inpatient versus outpatient populations. While nutritional interventions appeared to be associated with improvement in both affective and cognitive outcomes, the sample sizes of OABD varied and were generally small. CONCLUSION: While there is evidence for the benefits of nutritional interventions on affective, cognitive and overall outcome in OABD, the quality of the evidence is limited. Our findings underscore the need for high quality studies to inform evidence-based guidelines for nutritional assessment and supplemention in OABD.

Mechanistic basis of post-treatment control of SIV after anti-α4ß7 antibody therapy.

Treating macaques with an anti-α4ß7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4ß7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4ß7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4ß7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4ß7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed-some animals exhibited large fluctuations in viral load after cART cessation-the model suggests that anti-α4ß7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

Nickel in terrestrial biota: Comprehensive review on contamination, toxicity, tolerance and its remediation approaches.

Nickel (Ni) has been a subject of interest for environmental, physiological, biological scientists due to its dual effect (toxicity and essentiality) in terrestrial biota. In general, the safer limit of Ni is 1.5 µg g-1 in plants and 75-150 µg g-1 in soil. Litreature review indicates that Ni concentrations have been estimated up to 26 g kg-1 in terrestrial, and 0.2 mg L-1 in aquatic resources. In case of vegetables and fruits, mean Ni content has been reported in the range of 0.08-0.26 and 0.03-0.16 mg kg-1. Considering, Ni toxicity and its potential health hazards, there is an urgent need to find out the suitable remedial approaches. Plant vascular (>80%) and cortical (<20%) tissues are the major sequestration site (cation exchange) of absorbed Ni. Deciphering molecular mechanisms in transgenic plants have immense potential for enhancing Ni phytoremediation and microbial remediation efficiency. Further, it has been suggested that integrated bioremediation approaches have a potential futuristic path for Ni decontamination in natural resources. This systematic review provides insight on Ni effects on terrestrial biota including human and further explores its transportation, bioaccumulation through food chain contamination, human health hazards, and possible Ni remediation approaches.