SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD,RBD, and S2

1. Download : Download high-res image (157KB)
2. Download : Download full-size image

     

CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous system

CXCL9 and CXCL10 mediate the recruitment of T lymphocytes and NK cells known to be important in viral surveillance. The relevance of CXCL10 in comparison to CXCL9 in response to genital HSV-2 infection was determined using mice deficient in CXCL9 (CXCL9-/-) and deficient in CXCL10 (CXCL10-/-) along with wild-type (WT) C57BL/6 mice. An increased sensitivity to infection was found in CXCL10-/- mice in comparison to CXCL9-/- or WT mice as determined by detection of HSV-2 in the CNS at day 3 postinfection. However, by day 7 postinfection both CXCL9-/- and CXCL10-/- mice possessed significantly higher viral titers in the CNS in comparison to WT mice consistent with mortality (18-35%) of these mice within the first 7 days after infection. Even though CXCL9-/- and CXCL10-/- mice expressed elevated levels of CCL2, CCL3, CCL5, and CXCL1 in the spinal cord in comparison to WT mice, there was a reduction in NK cell and virus-specific CD8+ T cell mobilization to this tissue, suggesting CXCL9 and CXCL10 are critical for recruitment of these effector cells to the spinal cord following genital HSV-2 infection. Moreover, leukocytes from the spinal cord but not from draining lymph nodes or spleens of infected CXCL9-/- or CXCL10-/- mice displayed reduced CTL activity in comparison to effector cells from WT mice. Thus, the absence of CXCL9 or CXCL10 expression significantly alters the ability of the host to control genital HSV-2 infection through the mobilization of effector cells to sites of infection.     

Prey and tigers on the forgotten trail: high prey occupancy and tiger habitat use reveal the importance of the understudied Churia habitat of Nepal

Tigers are globally threatened and their conservation relies on intact habitat that supports key large prey. The Churia habitat is relatively unknown even though it occupies a significant portion of the forested landscape of the Terai Arc, which stretches over 1000 km in a narrow band across Nepal and India, parallel to the Himalayas. To address this lack of detailed information relevant to tiger conservation, we used sign surveys to estimate occupancy probability for 5 focal prey species of tigers (gaur, sambar, chital, wild pig, and barking deer), and assess tiger habitat use within 537 km² of the understudied Churia habitat in Chitwan National Park (CNP), Nepal. Multi-season occupancy models allowed us to make seasonal (winter vs. summer) inferences regarding changes in occupancy or habitat use based on covariates influencing occupancy and detection. We found that sambar had the largest spatial distribution occupying 431–437 km², while chital had the smallest at 100–158 km² across both seasons. The gaur population showed the most seasonal variation occupying from 413 to 318 km², suggesting their migration out of the Churia in summer and moving in during winter. Wild pigs showed the opposite trend occupying from 444 to 383 km²; suggesting moving into Churia in summer and out in winter. Barking deer were widespread in both seasons (329–349 km²). Tiger habitat use (\({{\hat{\varPsi } }}({\text{SE}})\)) was higher in winter 0.63 (0.11) than in summer 0.54 (0.21), but confidence intervals overlapped and area used was similar across seasons, 337 km² (winter) to 291 km² (summer). Available habitat, distribution of water sources, and human disturbance were the most common variables influencing spatial distribution of prey and habitat use of tigers at different spatial scales. Overall, we found high prey occupancy and tiger habitat use, suggesting the Churia is valuable habitat for ungulates and tigers. Given that this habitat accounts for 639 km² within CNP and 7642 km² across the entire Terai Arc, the Churia should no longer be neglected in global tiger conservation planning.     

2,4,6-Trisubstituted pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship

Designed and synthesized were a series of pyridines substituted at 2, 4, and 6 positions with various 5- or 6-memberd heteroaromatics as antitumor agents. They were evaluated their topoisomerase I and II inhibitory activities along with cytotoxicities against several human cancer cell lines. Among the prepared compounds, 10-20 showed significant topoisomerase I or II inhibitory activities, and 21-26 showed considerable cytotoxicities against several human cancer cell lines. Structure-activity relationship study indicates that 4'-pyridine at 6-position of central pyridine plays a key role in biological activity.     

No silver bullet? Snow leopard prey selection in Mt. Kangchenjunga,Nepal

In this study, we investigated the impact of domestic and wild prey availability on snow leopard prey preference in the Kangchenjunga Conservation Area of eastern Nepal—a region where small domestic livestock are absent and small wild ungulate prey are present. We took a comprehensive approach that combined fecal genetic sampling, macro‐ and microscopic analyses of snow leopard diets, and direct observation of blue sheep and livestock in the KCA. Out of the collected 88 putative snow leopard scat samples from 140 transects (290 km) in 27 (4 × 4 km²) sampling grid cells, 73 (83%) were confirmed to be from snow leopard. The genetic analysis accounted for 19 individual snow leopards (10 males and 9 females), with a mean population size estimate of 24 (95% CI: 19–29) and an average density of 3.9 snow leopards/100 km² within 609 km². The total available prey biomass of blue sheep and yak was estimated at 355,236 kg (505 kg yak/km² and 78 kg blue sheep/km²). From the available prey biomass, we estimated snow leopards consumed 7% annually, which comprised wild prey (49%), domestic livestock (45%), and 6% unidentified items. The estimated 47,736 kg blue sheep biomass gives a snow leopard‐to‐blue sheep ratio of 1:59 on a weight basis. The high preference of snow leopard to domestic livestock appears to be influenced by a much smaller available biomass of wild prey than in other regions of Nepal (e.g., 78 kg/km² in the KCA compared with a range of 200–300 kg/km² in other regions of Nepal). Along with livestock insurance scheme improvement, there needs to be a focus on improved livestock guarding, predator‐proof corrals as well as engaging and educating local people to be citizen scientists on the importance of snow leopard conservation, involving them in long‐term monitoring programs and promotion of ecotourism.     

Fire and forage quality: Postfire regrowth quality and pyric herbivory in subtropical grasslands of Nepal

Fire is rampant throughout subtropical South and Southeast Asian grasslands. However, very little is known about the role of fire and pyric herbivory on the functioning of highly productive subtropical monsoon grasslands lying within the Cwa climatic region. We assessed the temporal effect of fire on postfire regrowth quality and associated pyric‐herbivory in the subtropical monsoon grasslands of Bardia National Park, Nepal. Every year, grasslands are burned as a management intervention in the park, especially between March and May. Within a week after fire, at the end of March 2020, we established 60 m × 60 m plots within patches of burned grassland in the core area of the Park. We collected grass samples from the plots and determined physical and chemical properties of the vegetation at regular 30‐day intervals from April to July 2020, starting from 30 days after fire to assess postfire regrowth forage quality. We counted pellet groups of cervids that are abundant in the area for the same four months from 2 m × 2 m quadrats that were permanently marked with pegs along the diagonal of each 60 m × 60 m plot to estimate intensity of use by deer to the progression of postfire regrowth. We observed strong and significant reductions in crude protein (mean value 9.1 to 4.1 [55% decrease]) and phosphorus (mean value 0.2 to 0.11 [45% decrease]) in forage collected during different time intervals, that is, from 30 days to 120 days after fire. Deer utilized the burned areas extensively for a short period, that is, up to two months after fire when the burned areas contained short grasses with a higher level of crude protein and phosphorus. The level of use of postfire regrowth by chital (Axis axis) differed significantly over time since fire, with higher intensity of use at 30 days after fire. The level of use of postfire regrowth by swamp deer (Rucervus duvaucelii) did not differ significantly until 90 days after fire, however, decreased significantly after 90 days since fire. Large‐scale single event fires, thus, may not fulfil nutritional requirements of all species in the deer assemblage in these subtropical monsoon grasslands. This is likely because the nutritional requirements of herbivores differ due to differences in body size and physiological needs—maintenance, reproduction, and lactation. We recommend a spatiotemporal manipulation of fire to reinforce grazing feedback and to yield forage of high quality for the longest possible period for a sustainable high number of deer to maintain a viable tiger population within the park.     

Tumor immune cell clustering and its association with survival in African American women with ovarian cancer

New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME. Therefore, we have developed a framework for the spatial analysis of the TIME using Ripley’s K, coupled with a permutation-based framework to estimate and measure the departure from complete spatial randomness (CSR) as a measure of the interactions between immune cells. This approach was then applied to epithelial ovarian cancer (EOC) using mIF collected on intra-tumoral regions of interest (ROIs) and tissue microarrays (TMAs) from 160 high-grade serous ovarian carcinoma patients in the African American Cancer Epidemiology Study (AACES) (94 subjects on TMAs resulting in 263 tissue cores; 93 subjects with 260 ROIs; 27 subjects with both TMA and ROI data). Cox proportional hazard models were constructed to determine the association of abundance and spatial clustering of tumor-infiltrating lymphocytes (CD3+), cytotoxic T-cells (CD8+CD3+), and regulatory T-cells (CD3+FoxP3+) with overall survival. Analysis was done on TMA and ROIs, treating the TMA data as validation of the findings from the ROIs. We found that EOC patients with high abundance and low spatial clustering of tumor-infiltrating lymphocytes and T-cell subsets in their tumors had the best overall survival. Additionally, patients with EOC tumors displaying high co-occurrence of cytotoxic T-cells and regulatory T-cells had the best overall survival. Grouping women with ovarian cancer based on both cell abundance and spatial contexture showed better discrimination for survival than grouping ovarian cancer cases only by cell abundance. These findings underscore the prognostic importance of evaluating not only immune cell abundance but also the spatial contexture of the immune cells in the TIME. In conclusion, the application of this spatial analysis framework to the study of the TIME could lead to the identification of immune content and spatial architecture that could aid in the determination of patients that are likely to respond to immunotherapies.     

Peroxiredoxin IV plays a critical role in cancer cell growth and radioresistance through the activation of the Akt/GSK3 signaling pathways

High levels of redox enzymes have been commonly observed in various types of human cancer, although whether and how the enzymes contribute to cancer malignancy and therapeutic resistance have yet to be understood. Peroxiredoxin IV (Prx4) is an antioxidant with bona fide peroxidase and molecular chaperone functions. Here, we report that Prx4 is highly expressed in prostate cancer patient specimens, as well as established prostate cancer cell lines, and that its levels can be further stimulated through the activation of androgen receptor signaling. We used lentivirus-mediated shRNA knockdown and CRISPR-Cas9 based KO techniques to establish Prx4-depleted prostate cancer cells, which showed delayed cell cycle progression, reduced rate of cell proliferation, migration, and invasion compared to control cells. In addition, we used proteome profiler phosphokinase arrays to identify signaling changes in Prx4-depleted cells; we found that loss of Prx4 results in insufficient phosphorylation of both Akt and its downstream kinase GSK3α/β. Moreover, we demonstrate that Prx4-depleted cells are more sensitive to ionizing radiation as they display compromised ability to scavenge reactive oxygen species and increased accumulation of DNA damage. In mouse xenograft models, we show depletion of Prx4 leads to significant suppression of tumor growth, and tumors formed by Prx4-depleted cells respond more effectively to radiation therapy. Our findings suggest that increased levels of Prx4 contribute to the malignancy and radioresistance of prostate cancer through the activation of Akt/GSK3 signaling pathways. Therefore, strategies targeting Prx4 may be utilized to potentially inhibit tumor growth and overcome radioresistance in prostate cancer.     

Production of bioethanol and biodiesel using instant noodle waste

Instant noodle manufacturing waste was used as feedstock to convert it into two products, bioethanol and biodiesel. The raw material was pretreated to separate it into two potential feedstocks, starch residues and palm oil, for conversion to bioethanol and biodiesel, respectively. For the production of bioethanol, starch residues were converted into glucose by α-amylase and glucoamylase. To investigate the saccharification process of the pretreated starch residues, the optimal pretreatment conditions were determined. The bioethanol conversion reached 98.5 % of the theoretical maximum by Saccharomyces cerevisiae K35 fermentation after saccharification under optimized pretreatment conditions. Moreover, palm oil, isolated from the instant noodle waste, was converted into valuable biodiesel by use of immobilized lipase (Novozym 435). The effects of four categories of alcohol, oil-to-methanol ratio, reaction time, lipase concentration and water content on the conversion process were investigated. The maximum biodiesel conversion was 95.4 %.