The present study utilized an ensemble modelling approach to predict the distribution of Diospyros melanoxylon under present, past (last glacial maximum (LGM), ~ 22 000 years BP, middle Holocene (MH) ...~ 6000 years BP) and future climate change scenarios (RCP 2.6 and 8.5 for 2050s and 2070s). The annual mean temperature, mean temperature of the wettest quarter and annual precipitations were the most critical parameters that chiefly influence the distribution of D. melanoxylon. The ensemble model rendered high accuracy with AUC = 0.93, TSS = 0.74 and Kappa = 0.71. Past projections of D. melanoxylon indicated a widespread distribution during LGM and MH suggesting its adaptability to semi‐dry as well as warm and humid climate, respectively. Presence of fossil pollen evidence of D. melanoxylon in the suitable habitats derived through past projections in this study complements the model results and marks occurrences of the species during LGM and MH. By 2050s and 2070s (RCP 8.5), there would be a decline in the distribution by only 0.4% (13 622 km2) and 0.2% (6842 km2) of the extremely suitable habitats, respectively. The main factor leading to reduced habitat suitability is the anticipated rise in temperature and variations in seasonal precipitation patterns. Our findings, help in identifying the parts of the country which would be severely affected by future climate change scenarios and plan conservation strategies for this commercially important species to facilitate its growth in suitable habitats which are likely to sustain under future climatic conditions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for ...TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8+PD-1hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies.
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•The human pancreas contains CD8+ TRMs exhibiting tissue-specific molecular signatures•Pancreas TRMs express high levels of PD-1 yet maintain strong effector function•During homeostasis, pancreas TRMs are regulated by PD-L1+ tissue macrophages•In chronic pancreatitis, TRM PD-1 levels and PD-L1+ macrophage density are reduced
Non-recirculating tissue-resident memory T cells (TRMs) mediate immune responses in non-lymphoid tissues. Using a human organ donor tissue resource, Weisberg et al. reveal that PD-1hi pancreas TRMs are regulated by PD-L1+ macrophages during homeostasis. Comparison with chronic pancreatitis patient samples shows how pancreas TRM regulation is altered during inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sepsis is one of the leading causes of morbidity and mortality worldwide, and culture-negative sepsis, despite its prevalence, is largely understudied. The current study intends to examine clinical ...characteristics and biomarkers in culture-positive and culture-negative sepsis, focusing on 30-day mortality and duration of hospital stay in both groups. Materials and methods: A prospective observational comparative cohort study was done on 150 patients admitted to the intensive care unit (ICU) and wards of Jaipur Golden Hospital. Patients with documented fungal, viral, or parasitic infections, as well as those who had undergone surgery or experienced trauma, were excluded. Results: The mean age of the patients was 51.31±18.94 years. Of 150 patients, 95 (63.3%) were culture-negative, whereas 55 (36.7%) were culture-positive, with more men in the former and more women in the latter. Patients with negative cultures had fewer comorbidities. The levels of procalcitonin (PCT), C-reactive protein (CRP), and serum lactate were within the prescribed limit for both culture-negative and positive patients. A higher proportion (87.3%) of the organisms isolated from culture-positive individuals were gram-negative, with
(
) having the highest prevalence (27.3%), followed by
(20%). There were 12.7% gram-positive isolates. The culture-negative patients had significantly better outcomes (P=0.003) as well as the duration of hospital stay (P<0.001) than the culture-positive patients. Culture-positive patients had a more severe illness, a higher incidence of septic shock, and a higher fatality rate than culture-negative patients.
It can be concluded that CRP and PCT can be used as clinically reliable sepsis biomarkers in both culture-positive and culture-negative patients. The study found that culture-negative sepsis is more prevalent and that there are substantial differences between culture-negative and culture-positive sepsis, with the former group having fewer comorbidities, less severe illness, a shorter duration of hospital stays, lower death rates, and better outcomes.
Toxoplasma gondii is a widespread protozoan parasite that infects humans and other animals. Previous studies indicate some genotypes of T. gondii are more frequently isolated in wildlife than ...agricultural animals, suggesting a wild/feral animal diversity model. To determine seroprevalence and genetic diversity of T. gondii in southeastern US wildlife, we collected sera from 471 wild animals, including 453 mammals and 18 birds, between 2011 and 2014. These serum samples were assayed for T. gondii infection using the modified agglutination test (MAT). Heart or tongue tissues from 66 seropositive animals were bioassayed in mice and 19 isolates were obtained. The isolated parasites were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method employing 10 genetic markers.
One hundred and ninety-six of 471 samples (41.6%) had a titer ≥1:32 and were considered positive for T. gondii infection. Of 453 mammals, 195 (43%) were seropositive, whereas only one (5.6%) of 18 birds was seropositive. The seroprevalence in mammals was significantly higher than in the birds. Mammalian hosts with adequate samples size (≥ 20) comprised white-tailed deer (n = 241), feral hogs (n = 100), raccoons (n = 34) and coyotes (n = 22), with seroprevalences of 41.0%, 51.0%, 50.0% and 72.7%, respectively. Coyotes had significantly higher seroprevalence than the white-tailed deer. Genotyping revealed five distinct genotypes, including the ToxoDB PCR-RFLP genotype #5 (a.k.a type 12) for 15 isolates, genotype #3 (a.k.a. type II) for 1 isolate, and genotypes #154, #167 and #216, each for 1 isolate. The results showed moderate to high infection rates of T. gondii in white-tailed deer, feral hogs, raccoons and coyotes. Genotyping results indicated limited genetic diversity and a dominance of genotype #5, which has been reported as a major type in wildlife in North America.
We conclude that T. gondii infection is common in game animals (white-tailed deer and feral hogs) in the southeastern US, which may pose a food safety risk to humans. Further research is necessary to understand T. gondii transmission from wildlife to farm animals and humans.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Radiation-induced gastrointestinal syndrome (RIGS) results from the acute loss of intestinal stem cells (ISC), impaired epithelial regeneration, and subsequent loss of the mucosal barrier, resulting ...in electrolyte imbalance, diarrhea, weight loss, sepsis, and mortality. The high radiosensitivity of the intestinal epithelium limits effective radiotherapy against abdominal malignancies and limits the survival of victims of nuclear accidents or terrorism. Currently, there is no approved therapy to mitigate radiation toxicity in the intestine. Here we demonstrate that BCN057, an anti-neoplastic small molecular agent, induces ISC proliferation and promotes intestinal epithelial repair against radiation injury.
BCN057 (90 mg/kg body weight, subcutaneously) was injected into C57Bl6 male mice (JAX) at 24 h following abdominal irradiation (AIR) and was continued for 8 days post-irradiation. BCN057-mediated rescue of Lgr5-positive ISC was validated in Lgr5-EGFP-Cre-ERT2 mice exposed to AIR. The regenerative response of Lgr5-positive ISC was examined by lineage tracing assay using Lgr5-EGFP-ires-CreERT2-TdT mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from surgical specimens of human colon or from mice jejunum and were used to examine the radio-mitigating role of BCN057 on ISC ex vivo. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test.
Treatment with BCN057 24 h after a lethal dose of AIR rescues ISC, promotes regeneration of the intestinal epithelium, and thereby mitigates RIGS. Irradiated mice without BCN057 treatment suffered from RIGS, resulting in 100% mortality within 15 days post-radiation. Intestinal organoids developed from mice jejunum or human colon demonstrated a regenerative response with BCN057 treatment and mitigated radiation toxicity. However, BCN057 did not deliver radio-protection to mouse or human colon tumor tissue.
BCN057 is a potential mitigator against RIGS and may be useful for improving the therapeutic ratio of abdominal radiotherapy. This is the first report demonstrating that a small molecular agent mitigates radiation-induced intestinal injury by inducing ISC self-renewal and proliferation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Chronic kidney disease (CKD), characterized by progressive loss of kidney function, is a major cause of mortality in cats. Another complication is the formation of calcium oxalate (CaOx) ...uroliths in the bladder and kidneys of cats, where inflammation has a role in its pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs which bind to the target mRNA to reduce its function. Depending on the target mRNA, they regulate transcription of several pro-inflammatory genes. We assessed the expression profiles of circulating miRNAs in blood, collected at the natural end-of-life in colony cats, in a retrospective study, in healthy (n=10; 5.9-16 yr), CaOx (n=10, 8.6-13.4 yr), and CKD (n=10; 8.3-15.4 yr). Circulating concentrations of creatinine, symmetric dimethylarginine, and blood urea nitrogen were significantly greater in CaOx and CKD cats compared with controls, indicating kidney dysfunction. Expression of miRNAs, measured by qRT-PCR, was analyzed using the ΔΔCt method and normalized to U6. There was a significant upregulation of miR-155 in CaOx stone formers compared with controls (p< 0.05). miR-155 is increased in the serum and urine of human patients with nephrolithiasis. miR-155 can also promote oxalate-induced renal oxidative stress by suppressing MGP expression. In humans, miR-155 concentrations are negatively correlated with cytokines including IL-1β, IL-6, and TNF-α, suggesting the involvement of inflammation in nephrolithiasis. However, miR-155 was downregulated in CKD compared with controls. miR-16 was also downregulated in CKD cats. Consistent with this, there is downregulation of both the miRNAs in human patients with Stage 4 CKD. Further, miRNAs downregulated in CaOx, but not in CKD, included miR-17, miR-19b, miR-27a, and miR-27b, whereas let-7a, miR-15a, miR-16, miR-29b, and miR-200a were downregulated only in CKD cats. Taken together, the profile of circulating miRNAs in CaOx and CKD cats may serve as important biomarkers in the initiation and progression of renal dysfunction in cats.
The present study provides an assessment of the distribution of key Non-Timber Forest Product species in India, namely
Aegle marmelos
(L.) Correa,
Buchanania lanzan
Spreng.,
Madhuca longifolia
(J. ...Koenig ex L.) J. F. Macbr.,
Phyllanthus emblica
L. and
Terminalia bellirica
(Gaertn.) Roxb. The suitable habitat was analyzed under current climate scenarios and subsequently, the future distribution (2050s and 2070s) was mapped under RCP 2.6 and 8.5 scenarios, along with the past distribution (mid-Holocene, ~ 6000 cal year BP) using the MaxEnt species distribution model. The distribution of all species is primarily driven by key bioclimatic factors, including annual precipitation (Bio_12), mean annual temperature (Bio_1), isothermality (Bio_3) and precipitation of the coldest quarter (Bio_19). The results indicate that the present distribution of these species is mainly centred in the Western Ghats regions, Central Highlands, North-eastern India and Siwalik hills. The current study suggests that under the future climate change, the suitable habitat for
A. marmelos
and
T. bellirica
is expected to increase while for
B. lanzan
,
M. longifolia
and
P. emblica
, it is projected to decline.
A. marmelos
and
T. bellirica
are anticipated to exhibit resilience to future climate changes and are expected to be minimally affected, while
B. lanzan
,
M. longifolia
and
P. emblica
are highly sensitive to high temperature and alteration in rainfall pattern expected under future climate changes. The projections of habitat suitability areas can be used as a valuable foundation for developing conservation and restoration strategies aimed at alleviating the climate change impacts on NTFP species.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Toxoplasma gondii is one of the most successful pathogens on earth, capable of infecting an extremely broad range of mammals and birds and causing potentially fatal disease in humans. The house mouse ...(Mus musculus) has been used as the primary laboratory animal model for determining the virulence of T. gondii strains. Epidemiological evidence also suggests a potential association between virulence in mice and disease severity in human toxoplasmosis. However, many factors can affect virulence measurements, including route of infection, life stage of the parasite, number of passages of the parasite in mice or cell culture, and the mouse host line used. Variability among these factors makes it difficult to compare results between different studies in different laboratories. Here, we discuss important factors that should be considered when carrying out T. gondii murine virulence assays and propose a standardized methodology that should facilitate integration of T. gondii virulence data throughout the research community in future studies and thereby enable more efficient and effective analysis of genetic and virulence patterns for this important parasite.
•Life stages of Toxoplasma gondii affect parasite virulence in mice.•Continuous passages in mice and cell culture affect T. gondii virulence.•The routes of infection affect the outcome of T. gondii virulence in mice.•Different lines of laboratory mice vary in their resistance to T. gondii infection.•Proposed methodology in determining T. gondii virulence in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mangroves support numerous ecosystem services and help in reducing coastal ecological risks, yet they are declining rapidly due to climate change, sea level fluctuations and human activities. It is ...important to understand their responses to climate and sea level changes and identify conservation target areas at spatio-temporal scales, specifically in regions of rich mangrove biodiversity. In this study, we predicted the potential impact of past (Middle Holocene, ∼6000 years), current and future (2050s, 2070s; RCP 2.6 and RCP 8.5) climate change scenarios on the two dominant species in the coastal mangrove forest wetlands of India, i.e., Rhizophora mucronata and Avicennia officinalis through an ensemble species distribution modeling approach. The ensemble modeling has been carried out by integrating eight single algorithm methods. Based on the receiver operating characteristics of area under the curve (AUC) and true skill statistics (TSS) values the ensemble modeling has yielded the highest predictive performance for SVM for both the species and lowest by CART for R. mucronata and BIOCLIM for A. officinalis. The internal evaluation metrics of the resulting Species distribution models (SDMs) tested its robustness with AUC-0.97 and TSS-0.89 for A. officinalis and AUC-0.99 and TSS-0.90 for R. mucronata. Precipitation of Wettest Month (Bio 13) and Mean Temperature of Warmest Quarter (Bio 10) was the most important variable (54–67%) for the distribution of A. officinalis and Precipitation Seasonality (Bio 15) and Precipitation of Warmest Quarter (Bio 18) for R. mucronata. High precipitation and sea-level highstand during middle Holocene led to the maximum range expansion of suitable habitat for the mangrove species which is also validated in the present study by the fossil pollen datasets. Total mangrove habitat in current and future climatic scenarios decreased in 2.6 and 8.5 Representative Concentration Pathways (RCPs) for 2050 and 2070 which indicates the vulnerability of the species to climate change impacts. Mangrove species are projected to shift their ranges more towards land in future experiencing a decrease in the amount of suitable coastal area available to them throughout the Indian coastline. The plausible cause for this range shift may be due to higher precipitation that is usually associated with longer period of soil inundation and because of the rise in sea level. Our findings will assist in formulating species-specific restoration plans for these keystone species in context of climate change in the Indian Subcontinent.
•Past, current and future prediction of two mangrove species in Indian coastline.•Ensemble of eight algorithms mapped the species distribution since Mid Holocene.•Landward range shift in future due to decline in suitable habitats along the coast.•Maximum range expansion mapped in mid Holocene validated by fossil pollen data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. ...Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the Northern Hemisphere, many genotypes coexist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the Northern Hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii. Here, our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat/mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii. Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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