Meiotic recombination shapes the genetic diversity transmitted upon sexual reproduction. However, its non-random distribution along the chromosomes constrains the landscape of potential genetic combinations. For a variety of purposes, it is desirable to expand the natural repertoire by changing the distribution of crossovers in a wide range of eukaryotes. Toward this end, we report the local stimulation of meiotic recombination at a number of chromosomal sites by tethering the natural Spo11 protein to various DNA-binding modules: full-length DNA binding proteins, zinc fingers (ZFs), transcription activator-like effector (TALE) modules, and the CRISPR-Cas9 system. In the yeast Saccharomyces cerevisiae, each strategy is able to stimulate crossover frequencies in naturally recombination-cold regions. The binding and cleavage efficiency of the targeting Spo11 fusions (TSF) are variable, being dependent on the chromosomal regions and potential competition with endogenous factors. TSF-mediated genome interrogation distinguishes naturally recombination-cold regions that are flexible and can be warmed-up (gene promoters and coding sequences), from those that remain refractory (gene terminators and centromeres). These results describe new generic experimental strategies to increase the genetic diversity of gametes, which should prove useful in plant breeding and other applications.

Epigenetic deregulation contributes to diseases including cancer, neurodegeneration, osteodystrophy, cardiovascular defects, and obesity. For this reason, several inhibitors for histone deacetylases (HDACs) are being validated as novel anti-cancer drugs in clinical studies and display important anti-proliferative activities. While most inhibitors act on both class I, II, and IV HDACs, evidence is accumulating that class I is directly involved in regulation of cell growth and death, whereas class II members regulate differentiation processes, such as muscle and neuronal differentiation. Here, we show that the novel class II-selective inhibitor MC1568 interferes with the RAR- and peroxisome proliferator-activated receptor γ (PPARγ)-mediated differentiation-inducing signaling pathways. In F9 cells, this inhibitor specifically blocks endodermal differentiation despite not affecting retinoic acid-induced maturation of promyelocytic NB4 cells. In 3T3-L1 cells, MC1568 attenuates PPARγ-induced adipogenesis, while the class I-selective MS275 blocked adipogenesis completely thus revealing a different mode of action and/or target profile of the two classes of HDACs. Using in vivo reporting PPRE-Luc mice, we find that MC1568 impairs PPARγ signaling mostly in the heart and adipose tissues. These results illustrate how HDAC functions can be dissected by selective inhibitors.

Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with the Asia-Pacific (APAC) region bearing a disproportionate burden. This paper examines HCC challenges within seven APAC health systems, identifies key barriers at each stage of the patient journey, and proposes tailored, actionable solutions. To effectively address HCC challenges, a stepwise approach should prioritise high-impact solutions, focusing on prevention, early diagnosis, and expanding surveillance to maximise health outcomes and economic benefits, while tailoring strategies to each health system’s unique resources and constraints. Methods: A mixed-methods approach was used, including expert consultations from the 2024 HCC APAC Policy Forum, a literature review, and a review of Japan’s HCC management model. Data were collected through workshops and stakeholder feedback from healthcare professionals, policymakers, researchers and patient advocates across Australia, India, Malaysia, South Korea, Taiwan, Thailand, and Vietnam. Results: Key findings include significant disparities in HCC awareness, prevention, early detection, diagnosis, and access to treatment. Common challenges across APAC include limited public awareness, suboptimal surveillance infrastructure, and financial barriers to care. The integration of novel biomarkers and advanced surveillance modalities were identified as crucial priorities for improving early detection. Japan’s multi-faceted approach to HCC management serves as a successful model for the region. Conclusions: A customised and targeted approach is essential for reducing the HCC burden across APAC. The proposed recommendations, tailored to each health system’s needs, can significantly improve patient outcomes and reduce healthcare costs. Effective collaboration among stakeholders is necessary to drive these changes.

Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with the Asia-Pacific (APAC) region bearing a disproportionate burden. This paper examines HCC challenges within seven APAC health systems, identifies key barriers at each stage of the patient journey, and proposes tailored, actionable solutions. To effectively address HCC challenges, a stepwise approach should prioritise high-impact solutions, focusing on prevention, early diagnosis, and expanding surveillance to maximise health outcomes and economic benefits, while tailoring strategies to each health system’s unique resources and constraints. Methods: A mixed-methods approach was used, including expert consultations from the 2024 HCC APAC Policy Forum, a literature review, and a review of Japan’s HCC management model. Data were collected through workshops and stakeholder feedback from healthcare professionals, policymakers, researchers and patient advocates across Australia, India, Malaysia, South Korea, Taiwan, Thailand, and Vietnam. Results: Key findings include significant disparities in HCC awareness, prevention, early detection, diagnosis, and access to treatment. Common challenges across APAC include limited public awareness, suboptimal surveillance infrastructure, and financial barriers to care. The integration of novel biomarkers and advanced surveillance modalities were identified as crucial priorities for improving early detection. Japan’s multi-faceted approach to HCC management serves as a successful model for the region. Conclusions: A customised and targeted approach is essential for reducing HCC burden across APAC. The proposed recommendations, tailored to each health system’s needs can significantly improve patient outcomes and reduce healthcare costs. Effective collaboration among stakeholders is necessary to drive these changes.