Mechanisms of Choice in X-Chromosome Inactivation

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation.

The Current Understanding of Precision Medicine and Personalised Medicine in Selected Research Disciplines: Study Protocol of a Systematic Concept Analysis

Introduction. The terms "precision medicine" and "personalised medicine" have become key terms in health-related research, and in science-related public communication. However, the application of these two concepts and their interpretation in various disciplines are heterogeneous, which also affects research translation and public awareness. This leads to confusion regarding the use and distinction of the two concepts. Methods and analysis. Our study aims at using Rodger's concept analysis method to systematically examine and distinguish the current understanding of the concepts "precision medicine" and "personalised medicine" in clinical medicine, biomedicine (incorporating genomics and bioinformatics), health services research; physics, chemistry, engineering; machine learning, and artificial intelligence, and to identify their respective attributes (clusters of characteristics) and surrogate and related terms. We will analyse similarities and differences in definitions in the respective disciplines and across different (sub)disciplines. The analysis procedure will include (1) a concept identification, (2) a setting, sample, and data source selection, (3) data collection, (4) data analysis and data summary, (5) identification of examples, and (6) identification of implications for further concept development. Ethics and dissemination. Following ethical and research standards, we will comprehensively report the methodology for a systematic analysis following Roger's[1] concept analysis method. Our systematic concept analysis will contribute to the clarification of the two concepts and distinction in their application in given settings and circumstances. Such a broader concept analysis will contribute to non-systematic syntheses of the concepts, or occasional systematic reviews on one of the concepts that have been published in specific disciplines, in order to facilitate interdisciplinary communication, translational medical research, and implementation science.

Current Understanding of the Pathogenesis of Porcine Circovirus 3

Circoviruses are closed, circular, single-stranded DNA viruses belonging to the family Circoviridae and the genus Circovirus. To date, at least four porcine circoviruses (PCVs) have been recognized, including PCV1 to PCV4, respectively. Similar to PCV2 pathogenesis, PCV3 has been reported worldwide with myriad clinical and pathological presentations such as reproductive disorders, respiratory diseases, diarrhea etc. Current understanding of PCV3 pathogenesis is very limited since the majority of studies were mostly field observations. Interpretation of the results from such studies is not always simple. Various confounding factors affect the clinical appearance and pathological changes of the infected pigs. Recently, several experimental PCV3 infection studies have been reported, providing a better understanding of its pathogenesis. In this review, we focused on novel findings regarding PCV3 pathogenesis from both field observation and experimental infection studies. Possible factors involved in the conflicting results among the experimental infection studies are also discussed. This review article provides important insight into the current knowledge on PCV3 pathogenesis which would aid in prioritizing research in order to fill the knowledge gaps.

Endometriosis in Mare; What the Mare Can Teach Us When Dealing with Endometriosis in the Woman

Endometriosis is a serious, often irreversible disease of the mare. Often associated with endometritis, this chapter will review our current understanding of pathophysiology, etiology, diagnosis and possible treatments. Endometriosis is a disease complex typically seen in our older mare population. It is important that we understand that although the same term is used to describe a condition in our human patients, it is, however, not the same medical condition as seen in our equine patients. As this disease profile is irreversible with limited treatment options, it causes significant economic strain in our broodmare population.

I’m Only Human: A New E-road to Advancing Social Equity Through a Humanist Approach to Mentoring in Public Service

This research reviews how mentoring has manifested in public service and how it can evolve to be better positioned to address key diversity, equity, and inclusion objectives. This work inventories the current understanding of public sector mentoring, highlighting the contrast between the classical mentoring approach of functionalism with the emerging humanist approach. Barriers to implementing meaningful humanist mentoring are reviewed, and e-mentoring is presented as a modality well situated to overcome these obstacles. The humanist e-mentoring model provides a process and modality to advance social equity by removing existing barriers to opportunities. Finally, best practices and outcomes for successfully implementing e-mentoring humanist and relationships in public service are presented and an updated model of critical outcomes is advanced. A brief agenda for future scholarship on this topic is presented.

Deciphering the Immune–Tumor Interplay During Early-Stage Lung Cancer Development via Single-Cell Technology

Lung cancer is the leading cause of cancer-related death worldwide. Cancer immunotherapy has shown great success in treating advanced-stage lung cancer but has yet been used to treat early-stage lung cancer, mostly due to lack of understanding of the tumor immune microenvironment in early-stage lung cancer. The immune system could both constrain and promote tumorigenesis in a process termed immune editing that can be divided into three phases, namely, elimination, equilibrium, and escape. Current understanding of the immune response toward tumor is mainly on the “escape” phase when the tumor is clinically detectable. The detailed mechanism by which tumor progenitor lesions was modulated by the immune system during early stage of lung cancer development remains elusive. The advent of single-cell sequencing technology enables tumor immunologists to address those fundamental questions. In this perspective, we will summarize our current understanding and big gaps about the immune response during early lung tumorigenesis. We will then present the state of the art of single-cell technology and then envision how single-cell technology could be used to address those questions. Advances in the understanding of the immune response and its dynamics during malignant transformation of pre-malignant lesion will shed light on how malignant cells interact with the immune system and evolve under immune selection. Such knowledge could then contribute to the development of precision and early intervention strategies toward lung malignancy.

Chemoproteomic Profiling Reveals Celastrol as a Potential Modulator of Cholesterol Signaling

We report a quantitative chemoproteomic approach that utilizes a clickable photoreactive probe for global profiling of celastrol targets, which may significantly improve the current understanding of celastrol’s mode of action.