Differentially expressed seed aging responsive heat shock protein OsHSP18.2 implicates in seed vigor, longevity and improves germination and seedling establishment under abiotic stress

Small heat shock proteins (sHSP) are a diverse group of proteins and are highly abundant in plant species. Although majority of these sHSPs were shown to express specifically in seed, their potential function in seed physiology remains to be fully explored. Our proteomic analysis revealed that OsHSP18.2, a class II cytosolic HSP is an aging responsive protein as its abundance significantly increased after artificial aging in rice seeds. OsHSP18.2 transcript was found to markedly increase at the late maturation stage being highly abundant in dry seeds and sharply decreased after germination. Our biochemical study clearly demonstrated that OsHSP18.2 forms homooligomeric complex and is dodecameric in nature and functions as a molecular chaperon. OsHSP18.2 displayed chaperone activity as it was effective in preventing thermal inactivation of Citrate Synthase. Further, to analyze the function of this protein in seed physiology, seed specific Arabidopsis overexpression lines for OsHSP18.2 were generated. Our subsequent functional analysis clearly demonstrated that OsHSP18.2 has ability to improve seed vigor and longevity by reducing deleterious ROS accumulation in seeds. In addition, transformed Arabidopsis seeds displayed better performance in germination and cotyledon emergence under adverse conditions as well. Collectively, our work demonstrates that OsHSP18.2 is an aging responsive protein which functions as a molecular chaperon and possibly protect and stabilize the cellular proteins from irreversible damage particularly during maturation drying, desiccation and aging in seeds by restricting ROS accumulation and thereby improves seed vigor, longevity and seedling establishment

p53 immunohistochemistry in endometrial cancer:clinical and molecular correlates in the PORTEC-3 trial

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n = 89, 68%), followed by null (n = 12, 9%) and cytoplasmic (n = 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLE mutations and/or MMRd (n = 22/27; p < 0.001). Agreement between p53 IHC and TP53 NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC)

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Abstract: Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Abstract: Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes

Hydrological inferences from watershed analysis for water resource management using remote sensing and GIS techniques

The present study highlights the importance of Digital Elevation Model (DEM) and satellite images for assessment of drainage and extraction of their relative parameters for the Orr watershed Ashok Nagar district, M.P., India. Hydrological parameters such as drainage analysis, topographic parameters and land use pattern were evaluated and interpreted for watershed management of the area. Hydrological module of ARC GIS software was utilized for calculation and delineation of the watershed and morphometric analysis of the watershed using SRTM DEM. The stream order of watershed ranges from first to sixth order showing dendritic type drainage network which is a sign of the homogeneity in texture and lack of structural control of the watershed. The drainage density in the area has been found to be low to medium which indicates that the area possesses highly permeable soils and low relief. The bifurcation ratio varies from 4.74 to 5 and the elongation ratio is 0.58 which reveals that the basin belongs to the elongated shaped basin category. The mean Rb of the entire basin is 4.62 which indicates that the drainage pattern is not much influenced by geological structures. Land use map of the watershed was generated from latest available multispectral satellite data and whole watershed covers under agricultural land, settlement, fallow land, forest, mining areas and water body. The present study reveals that SRTM DEM based hydrological evaluation at watershed scale is more applied and precise compared to other available techniques

Assessment of Landscape Change of Lesser Himalayan Road Corridor of Uttarakhand, India

The spatio-temporal monitoring and understanding of the pattern of land-use and land-cover (LULC) change in the Himalayas are essential for sustainable development, especially from environmental planning and management perspective. The increasing anthropogenic activities and climate change in the Siwalik and Lesser Himalayas have substantially experienced rapid change in the natural landscape; however, detailed investigation and documentation of such observed changes are limited. This study aims to assess the LULC changes along the Kalsi-Chakrata road corridor located in the Lesser Himalayan region of Uttarakhand state of India using remote sensing and geographic information system (GIS) for the periods 2000-2010 and 2010-2019. The LULC maps were generated from multi-temporal satellite images of the Landsat -7 Enhanced Thematic Mapper Plus (ETM+) series for 2000 and 2010, and the Linear Imaging Self-Scanning System IV (LISS IV) images from Resourcesat-1 for 2019. The extent of spatial landscape changes occurred in different LULC classes was performed through the cross-tabulation change matrix in the GIS module up to the individual village level. The results indicate that the forest cover of the area was intensively converted to open areas, sparse vegetation, and different land-use categories. These included agricultural land, built-up areas, and decreased from 47.27 % in 2000 to 36.66 % in 2019. During the same period, the open areas and agricultural areas were increased by 15.86 % and 4.49 %, respectively. Moreover, the built-up areas (both urban and rural settlements) were progressively increased from 0.33% in 2000 to 0.56 % in 2019. The conversion of forests and sparsely vegetative areas to agricultural land and rural settlements is closely associated with the increasing anthropogenic activities due to population growth, tourism, movement of heavy vehicles for mining and other economic activities. The changes in land-cover to land use classes are more prominent in Samalta Dadauli, Nithala, Bhugtari, and Udapalta villages located between Kalsi and Sahiya town. The reported maximum transition of forest areas into the open area, agricultural land, and sparse vegetation indicates the possible scarcity of water, which could link with the incidence of climatic or seasonal variation in the Lesser Himalayan terrain to the hydro-geomorphic and anthropogenic processes. The trend in LULC change at the village level gave the insight to help to prioritize future mitigation planning and sustainable development that are exceedingly convenient for the planners, policymakers, and local authorities for comprehensive forest management, biodiversity strategies, and necessary conservatio

Etiology, Clinical Features, and Diagnosis of Vulvar Lichen Sclerosus: A Scoping Review

Objective. Vulvar lichen sclerosus (VLS) is a chronic inflammatory disorder, which affects women of all ages. With numerous controversies as regards to the nomenclature, diagnosis and its association with neoplastic conditions, we decided to conduct a scoping review on this subject. Data Source. A review protocol was developed, and the Knowledge Resource Services website was used to do a search of articles pertaining to VLS with keywords “Vulvar,” “Vulval,” “diagnosis,” “lichen sclerosus et atrophicus,” “kraurosis,” “vulvar dystrophy,” and “Lichen Sclerosus”. Study Selection. The search was limited to published data from the last ten years, i.e., from July 2009 onwards and in the English language. A total of 338 articles pertaining to VLS were obtained. Older data were accessed if particular information was sought for. Results & Conclusion. The presentation is bimodal, i.e., one in prepubertal girls (average age: 7.6 years) and the other in peri- and postmenopausal women (average age: 52.6 years). However, many cases also present during reproductive years. Studies suggest a multifactorial origin as far as etiology is concerned, including a genetic, autoimmune, hormonal, and local infectious background. It affects the genital labial, perineal, and perianal areas and manifests as a patchy, thin, glistening, ivory-white area. Diagnosis is mainly based on clinical features. Biopsy is seldom required. It has been well established as a precursor lesion of dVIN and vulvar carcinoma

Landslide susceptibility assessment in a lesser Himalayan road corridor (India) applying fuzzy AHP technique and earth-observation data

The Kalsi-Chakrata road corridor, located in the Lesser Himalayas, experiences several landslides every year, resulting in a considerable amount of damage to roads, assets, and other infrastructure and even loss of lives. During the monsoon season (June–August), the disruption of routes due to landslide resulted in economic losses and barred villagers from accessing critical and essential facilities, thus impacting the livelihood of the communities residing along the road corridor. Hence immediate requirement was to systematically assess the landslide susceptibility for the study area that would support in the preparation of the planning and mitigation goal, both short and long term. The present study adopted the fuzzy analytic hierarchy process (fuzzy AHP) method integrated with geospatial technology that may be highly effective for landslide susceptibility assessment in the landslide-prone Lesser Himalayas. The use of validated landslide inventory data and high-resolution remote sensing images for selection and mapping of landslide conditioning factors gratifies the geospatial aspect of local variations across the Kalsi-Chakrata road corridor. For fuzzy AHP model setup, prominent landslide contributing factors viz., slope, aspect, altitude, lithology, proximity to road, fault & drainage, Stream Power Index (SPI), Topographical Wetness Index (TWI), rainfall, land use/land cover (LULC), soil, and seismicity, were mapped and classified into significant classes. The resultant landslide susceptibility map (LSM) shows that about 55% (45.23 km2) of the study area was categorized as a very high and high landslide susceptibility zone. Of this, about 21% (17.7 km2) was within very high LSM zone, while 33% (27.5 km2) fell under high landslide susceptibility categories. Approximately 17.6% (14.5 km2) areas fall within the moderately susceptible zone, where chances of future landslides may be amplified without periodic observation and prospective study. At the village level, it was observed that Jhutaya village, located nearer foothill of Lesser Himalayas, is most susceptible to landslide followed by Dhaira, Chapanu, and Sairi villages. The fuzzy AHP model shows 86.52% accuracy in landslide prediction evaluated through the ROC curve (at 95% confidence level). Hence, the output LSI may be referred by the planners and engineers for monitoring, prevention, and mitigation of landslide hazards and development of infrastructure in the Kalsi-Chakrata road corridor, and the fuzzy AHP methodology adopted may be applied in other areas of the Lesser Himalayas