Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

"Попівська академія" як культурно-просвітницький осередок на Слобожанщині

У статті аналізується діяльність культурного осередку на х. Попівка (тепер Сумщина), який зіграв істотну роль у розвитку освіти й духовності на Слобожанщині.This article analyzes the activities of the cultural center at village Popovci (now Sumy region), which played a significant role in the development of education and spirituality in Slobozhanshina

Necessary fictions: indigenous claims and the humanity of rights

Indigenous right insistently challenges the surpassing arrogations of sovereign right. In so doing, it affirms dimensions of being-together denied or stunted in sovereign modes of political formation. This force of Indigenous right is amplified here through legal and literary instantiations. These, in turn, uncover the continuously created and fictional quality of rights, revealing them to be necessary fictions

Pre-service science teachers’ understanding of science and engineering practices, engineering design process, and scientific method

This study examined secondary pre-service science teachers’ understanding of science and engineering practices, the engineering design process, and the scientific method before and after an intervention. Participants were ten pre-service science teachers. Data were collected through a survey and semi-structured interviews. Results show that after the intervention pre- service science teachers developed understanding of science and engineering practices and used more engineering-specific language when describing them. They also developed an understanding that both engineering design process and scientific method are cyclical and iterative and that the two processes share many practices, but the biggest difference between them is in their purposes. Pre-service teachers also said that the redesign process in engineering design, and the repetition of steps can occur at any point in engineering design process and scientific method. These findings have implications for science teacher education, and teaching and learning of science and engineering design in schools

Risk and Protective Factors for Well-Being in Latinx Immigrants in Removal Proceedings

Recent figures estimate roughly 12 million undocumented immigrants live in the U.S. (Baker, 2018; Capps, Fix, & Zong, 2016), 1,101,061 of which have pending immigration court cases, and over 80% of which are Latinx (TRAC, 2020a). Despite legal protections in other areas of the U.S. justice system, there is little opportunity for relief for adults going through deportation proceedings (Koh, 2017a) and no right to government-funded representation (Hausman & Srikantiah, 2016). There is little research on the effect of immigration court on the well-being of immigrants, and no empirical data on risk and protective factors in the court context. Against this background, this study aimed to examine how hopelessness and helplessness (i.e., risk factors) and social, religious, and legal support (i.e., protective factors) relate to the emotional and physical well-being of Latinx individuals facing removal proceedings. All participants (n = 157; 31.2% male) were adult (18 to 69 years old) respondents with an active immigration court case. Overall, results indicated higher levels of hopelessness and helplessness (individually and cumulatively) were associated with poorer outcomes, while social and religious aggregate support did not serve as a protective factor attenuating the relation between risk and outcome variables. Finally, contrary to hypotheses, legal support served as a risk factor for individuals high on helplessness, such that more legal support was associated with worse outcomes. Several explanations for results are offered. While findings inform immigration-related policy, results also have implications for our nation’s economy, healthcare system, and citizens

The microbiome and lung cancer: microbial effects on host immune responses and treatment outcomes

The human microbiome plays a critical role in shaping physiological processes, immune system function, metabolism, and disease development. Recent research has highlighted the microbiome’s profound cancer impact, particularly on lung cancer. This review explores how microbial communities in lung and gut influence tumor progression, immune responses, and treatment outcomes as well as describing the interactions between the microbiome and the host immune system in modulating the efficacy of cancer therapies. Emerging evidence from preclinical and clinical studies investigating the role of the lung and gut microbiome in lung cancer focus on alterations in the microbiota that influence the tumor microenvironment, modulate immune responses, and potentially enhance/hinder treatment effectiveness such as chemotherapy, targeted therapies, and immunotherapy. Microbial diversity plays a significant role in immune regulation, and specific microbial species may activate/suppress immune cells such as T-cells, dendritic cells, and macrophages. Furthermore, this review examines the therapeutic implications of microbiome modulation, including the use of probiotics, antibiotics, and fecal microbiota transplantation in enhancing cancer therapies. Alterations in the lung and gut microbiome and their interaction in the recently described gut-lung axis with its bidirectional communication significantly influence the tumor microenvironment and systemic immune responses. These findings suggest that microbial diversity can regulate immune functions, with specific species capable of activating or suppressing immune cell activity. Furthermore, microbiome-targeted interventions show potential in improving the effectiveness of treatments including chemotherapy, targeted therapies, and immunotherapy, underscoring the importance of the microbiome as a key factor in lung cancer pathogenesis and treatment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts