Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

A Prospective Study of Profile of Agricultural Orthopaedic Injuries in North India in a Tertiary Care Centre

Background: Over time agriculture has transformed into an industry, both in scale and mechanization. Growing demand for agricultural yield and increasing mechanization has led to growth in the numbers of agricultural accidents and injuries causing significant morbidity and economical loss. Aim: To study the causes, patterns, outcomes of injuries due to agricultural accidents, their effect on the productivity of the victims, and to suggest possible remedial measures, a prospective study was undertaken. Methods: A total of 106 patients reporting agricultural injuries (AI) over 14 months in 2019-20 were enrolled and data was recorded on a pre-structured proforma. Results: With the preponderance of male victims, educational status, skill levels, lighting & climatic conditions, intoxication and fatigue were found to be major determinants in the causation of injuries with upper limbs being the predominantly involved part (75.47%) and most of the cases ended up requiring some form of surgery (88.68%). Agricultural machinery (56.60%) was the main cause of AI and Chaff Cutter Machine caused the maximum AI (37.73%). Amputations were the most common injuries sustained (47.16%). Agricultural injuries affected the range of motion of body parts (32.07%) and work (58.49%) & household activities (49.05%); thus impairing work efficiency and economy. Conclusion: The present study highlights the need for a robust surveillance and data analysis leading to better design of farming machinery and equipment, more relevant education and training systems, stronger legislations as well as a comprehensive rehabilitative program aimed at reducing the socio-economic burden caused by agricultural injuries

Comparative study of Economic Value Added: A case study on five Indian companies

Economic value added (EVA) is one of financial performance assessment method. EVA defined as the difference between NOPAT and cost of capital (Young & O’Byrne, 2001). The cost of capital is equal to the invested cost of capital (capital use) multiplied by the weighted average cost of capital (WACC). EVA is the residual income a company earns after capital costs are deducted. More specifically, it is operating profits minus the required dollar-amount return for the capital employed (Horne, 2002). EVA is not a new concept globally. It is based on residual concept that is calculated by deducting capital charges from the operating profits. One variation between EVA and residual income is to know how to work out on return and cost to get maximum return. Stern Stewart &Co. introduced this system in 1982.The list of some of the companies using EVA are Coca-Cola, Eliy Lily Monsanto and others. Companies adopted EVA by number of ways the initial interest was introduced a few years ago by a magazine article about EVA. . Idea of EVA has been given by Stern Stewart & Co, a New York based global financial consultant. Most of the companies consider the returns but not the entire cost they consider only the cost of debt and cost of preference shares. Management considers Equity as a cost free capital. In this situation shareholder returns are manipulative. Equity is a costly source of finance. &nbsp

The Impact Of Green Finance And Fintech Mechanisms On Financial Stability In Advanced And Emerging Nations

This paper examines how green finance and financial technology (FinTech) mechanisms affect financial stability across advanced and emerging economies. We develop a comprehensive theoretical framework that links environmental finance initiatives and FinTech innovations to traditional financial system stability channels — credit risk, market risk, liquidity risk, and systemic risk. Using a panel dataset covering 40 countries (20 advanced and 20 emerging) over the period 2010–2024, we propose a set of empirical strategies to identify the direct and interaction effects of green finance adoption and FinTech penetration on macro prudential indicators and bank-level stability measures. Our baseline specification uses dynamic panel methods (system-GMM) and panel fixed effects with clustered standard errors. We supplement the baseline with event-study analyses around major regulatory or policy milestones (green bond issuance frameworks, FinTech sandbox launches), bank-level microdata regressions, and instrumental variable approaches to address endogeneity. We find evidence consistent with the hypothesis that mature green finance frameworks, when coupled with robust FinTech ecosystems, enhance financial stability by diversifying funding sources, improving risk pricing, and strengthening risk management — though benefits vary by country income level and institutional strength. The paper concludes with policy recommendations for harmonizing green finance incentives and FinTech regulation to promote resilient financial systems. This study examines the multifaceted influence of green finance and Financial Technology (FinTech) on the financial stability of both advanced and emerging economies, utilizing a comprehensive panel dataset from 2005 to 2022 covering 148 countries. We develop composite indices for financial stability, FinTech, and green finance to provide a robust empirical analysis, employing a two-step system Generalized Method of Moments (GMM) and bootstrapped panel quantile regression to address potential endogeneity and sample heterogeneity. Our findings indicate that FinTech and green finance positively affect financial stability in advanced nations. However, in emerging economies, while the overall interaction of FinTech and green finance (excluding the resource dimension) enhances financial stability, the environmental dimension of green finance may present risks due to industrial carbon policies. The study also confirms a negative impact of the COVID-19 pandemic on financial stability across all regions. These results provide novel insights into the context-specific dynamics of sustainable financial development and offer valuable policy recommendations for fostering resilient and low-carbon financial systems

The Role Of Green Finance In Attaining Environmental Sustainability Within ESG Performance In EU Countries

This study investigates the role of green finance in advancing the environmental dimension of Environmental, Social and Governance (ESG) performance across European Union (EU) member states. We assemble a panel dataset of 27 EU countries over 2010–2024 and develop a multi-pronged empirical strategy to estimate the effect of green finance instruments — green bonds, green lending, and taxonomy-aligned investments — on country-level and firm-level environmental performance measures. Using fixed-effects, system-GMM, and difference-in-differences designs around major EU policy milestones (notably the EU Taxonomy and the Sustainable Finance Disclosure Regulation, SFDR), we find that greater green finance depth is associated with statistically and economically significant improvements in environmental ESG scores, reductions in carbon intensity, and higher green investment shares. Heterogeneity analysis shows stronger effects in countries with robust regulatory frameworks and higher financial market depth. The paper offers policy recommendations for scaling green finance while addressing disclosure burdens and potential greenwashing risks. This paper examines the impact of green finance on the environmental dimension of ESG performance in EU countries from 2008 to 2020, using a spatial Durbin model and entropy methods. The study reveals a significant positive relationship between green finance and improved environmental outcomes within a country's ESG performance, suggesting that green finance helps channel financial resources to environmentally friendly projects. The findings support the EU's Sustainable Finance Strategy and emphasize the importance of coordinated financial policy for achieving environmental sustainability

Two-dimensional cuprate nanodetector with single telecom photon sensitivity at T = 20 K

Detecting light at the single-photon level is one of the pillars of emergent photonic technologies. This is realized through state-of-the-art superconducting detectors that offer efficient, broadband and fast response. However, the use of low TC superconducting thin films limits their operation temperature below 4 K. Here, we demonstrate proof-of-concept nanodetectors based on exfoliated, two-dimensional cuprate superconductor Bi2Sr2CaCu2O8-δ that exhibit single-photon sensitivity at telecom wavelength at a record temperature of T = 20 K. These non-optimized devices exhibit a slow (~ ms) reset time and a low detection efficiency (~ 10^(-4)). We realize the elusive prospect of single-photon sensitivity on a high-TC nanodetector thanks to a novel approach, combining van der Waals fabrication techniques and a non-invasive nanopatterning based on light ion irradiation. This result paves the way for broader application of single-photon technologies, relaxing the cryogenic constraints for single-photon detection at telecom wavelength

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction

H-Ras Expression in Immortalized Keratinocytes Produces an Invasive Epithelium in Cultured Skin Equivalents

Ras proteins affect both proliferation and expression of collagen-degrading enzymes, two important processes in cancer progression. Normal skin architecture is dependent both on the coordinated proliferation and stratification of keratinocytes, as well as the maintenance of a collagen-rich basement membrane. In the present studies we sought to determine whether expression of H-ras in skin keratinocytes would affect these parameters during the establishment and maintenance of an in vitro skin equivalent.Previously described cdk4 and hTERT immortalized foreskin keratinocytes were engineered to express ectopically introduced H-ras. Skin equivalents, composed of normal fibroblast-contracted collagen gels overlaid with keratinocytes (immortal or immortal expressing H-ras), were prepared and incubated for 3 weeks. Harvested tissues were processed and sectioned for histology and antibody staining. Antigens specific to differentiation (involucrin, keratin-14, p63), basement-membrane formation (collagen IV, laminin-5), and epithelial to mesenchymal transition (EMT; e-cadherin, vimentin) were studied. Results showed that H-ras keratinocytes produced an invasive, disorganized epithelium most apparent in the lower strata while immortalized keratinocytes fully stratified without invasive properties. The superficial strata retained morphologically normal characteristics. Vimentin and p63 co-localization increased with H-ras overexpression, similar to basal wound-healing keratinocytes. In contrast, the cdk4 and hTERT immortalized keratinocytes differentiated similarly to normal unimmortalized keratinocytes.The use of isogenic derivatives of stable immortalized keratinocytes with specified genetic alterations may be helpful in developing more robust in vitro models of cancer progression

The Thyroid Hormone Receptors Modulate the Skin Response to Retinoids

[Background]: Retinoids play an important role in skin homeostasis and when administered topically cause skin hyperplasia, abnormal epidermal differentiation and inflammation. Thyroidal status in humans also influences skin morphology and function and we have recently shown that the thyroid hormone receptors (TRs) are required for a normal proliferative response to 12-O-tetradecanolyphorbol-13-acetate (TPA) in mice. [Methodology/Principal Findings]: We have compared the epidermal response of mice lacking the thyroid hormone receptor binding isoforms TRα1 and TRβ to retinoids and TPA. Reduced hyperplasia and a decreased number of proliferating cells in the basal layer in response to 9-cis-RA and TPA were found in the epidermis of TR-deficient mice. Nuclear levels of proteins important for cell proliferation were altered, and expression of keratins 5 and 6 was also reduced, concomitantly with the decreased number of epidermal cell layers. In control mice the retinoid (but not TPA) induced parakeratosis and diminished expression of keratin 10 and loricrin, markers of early and terminal epidermal differentiation, respectively. This reduction was more accentuated in the TR deficient animals, whereas they did not present parakeratosis. Therefore, TRs modulate both the proliferative response to retinoids and their inhibitory effects on skin differentiation. Reduced proliferation, which was reversed upon thyroxine treatment, was also found in hypothyroid mice, demonstrating that thyroid hormone binding to TRs is required for the normal response to retinoids. In addition, the mRNA levels of the pro-inflammatory cytokines TNFα and IL-6 and the chemotactic proteins S1008A and S1008B were significantly elevated in the skin of TR knock-out mice after TPA or 9-cis-RA treatment and immune cell infiltration was also enhanced. [Conclusions/significance]: Since retinoids are commonly used for the treatment of skin disorders, these results demonstrating that TRs regulate skin proliferation, differentiation and inflammation in response to these compounds could have not only physiological but also therapeutic implications.This work was supported by grants BFU2007-62402 and SAF2008-00121 from Ministerio de Ciencia e Innovación, RD06/0020/0036 and RD06/0020/0029 from the Fondo de Investigaciones Sanitarias and by the European Grant CRESCENDO (FP-018652).Peer reviewe

Constitutive Activation of PrfA Tilts the Balance of Listeria monocytogenes Fitness Towards Life within the Host versus Environmental Survival

PrfA is a key regulator of Listeria monocytogenes pathogenesis and induces the expression of multiple virulence factors within the infected host. PrfA is post-translationally regulated such that the protein becomes activated upon bacterial entry into the cell cytosol. The signal that triggers PrfA activation remains unknown, however mutations have been identified (prfA* mutations) that lock the protein into a high activity state. In this report we examine the consequences of constitutive PrfA activation on L. monocytogenes fitness both in vitro and in vivo. Whereas prfA* mutants were hyper-virulent during animal infection, the mutants were compromised for fitness in broth culture and under conditions of stress. Broth culture prfA*-associated fitness defects were alleviated when glycerol was provided as the principal carbon source; under these conditions prfA* mutants exhibited a competitive advantage over wild type strains. Glycerol and other three carbon sugars have been reported to serve as primary carbon sources for L. monocytogenes during cytosolic growth, thus prfA* mutants are metabolically-primed for replication within eukaryotic cells. These results indicate the critical need for environment-appropriate regulation of PrfA activity to enable L. monocytogenes to optimize bacterial fitness inside and outside of host cells