Dynamic Opposition of Histone Modifications.

Gene transcription does not only require writers of active histone modifications; on-site opposition by erasers is essential for many genes. Here, we propose the concept of dynamic opposition of histone modifications to explain this conundrum. We highlight the requirement of HDACs for acetylation balance at superenhancers, and the requirement of KDM5A for H4K3me3 recycling at highly active gene promoters. We propose that histone post-translational modifications regulate charge balance for biomolecular condensate formation and nucleosome turnover and form a short-term memory that informs lock-and-step checkpoints for chromatin engagement by RNA polymerase II.

Public Engagement with Biotechnology Inside and Outside the Classroom: Community-Focused Approaches.

Biotechnology offers vast benefits to the environment, animals, and human health, and contributes to improving socioeconomic conditions for the public. However, biotechnology innovations continue to trigger public concern and opposition over their potential social, health, and ecological risks. There is an opportunity to increase knowledge and acceptance of biotechnology through engagement, education, and community participation. In this perspective, we highlight crucial factors that shape the public perception of biotechnology and present opportunities for scientists to effectively communicate their ideas while engaging with local and global communities. Initiatives that seek to involve communities in design, development, and adoption processes are crucial for the successful implementation of biotechnology-based solutions.

Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix.

Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome could degrade the host ECM and that bacteria-driven remodeling, in turn, could enhance colonic inflammation. Through a variety of in vitro assays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activity in vitro, compared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species that are capable of degrading human ECM accelerated inflammation in dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) that are potentially responsible for ECM degradation in vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECM in vitro and suggest that this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to elucidating some of the mechanisms underlying host-bacteria interactions in IBD and beyond. IMPORTANCE Healthy gut epithelial cells form a barrier that keeps bacteria and other substances from entering the blood or tissues of the body. Those cells sit on scaffolding that maintains the structure of the gut and informs our immune system about the integrity of this barrier. In patients with inflammatory bowel disease (IBD), breaks are formed in this cellular barrier, and bacteria gain access to the underlying tissue and scaffolding. In our study, we discovered that bacteria that normally reside in the gut can modify and disassemble the underlying scaffolding. Additionally, we discovered that changes to this scaffolding affect the onset of IBD in mouse models of colitis as well as the abilities of these mice to recover. We propose that this new information will reveal how breaks in the gut wall lead to IBD and will open up new avenues by which to treat patients with IBD.

Engaging Scientific Diasporas in STEAM Education: The Case of Science Clubs Colombia.

Currently, there is limited insight on the role that scientific diasporas can play in STEAM education in Latin America. Here, we present the Science Clubs Colombia (Clubes de Ciencia Colombia-SCC) program, a pioneering STEAM capacity-building initiative led by volunteer scientists to engage youth and children from underserved communities in science. The program brings together researchers based in Colombia and abroad to lead intensive project-based learning workshops for young students in urban and rural areas. These projects focus on channeling the students' technical and cognitive scientific aptitudes to tackle challenges of both local and global relevance. The program provides high-quality STEAM education adapted to communities' needs and articulates long-lasting international collaborations using the mobility of the Colombian diaspora. The program's success is tangible via its sustained growth and adaptability. Since its first version in 2015, 722 volunteer scientists living abroad or in Colombia have collaborated to create 364 clubs with the participation of 9,295 students. We describe elements of the SCC program that lead to a scalable and reproducible outcome to engage science diasporas in STEAM education. Additionally, we discuss the involvement of multiple stakeholders and the generation of international networks as potential science diplomacy outcomes. The SCC program strengthens the involvement of Latin American youth in science, demonstrates the potential of engaging scientific diasporas in science education, and enriches connections between the Global South and the Global North.

A microfluidic chip carrier including temperature control and perfusion system for long-term cell imaging.

Microfluidic devices are widely used for biomedical applications but there is still a lack of affordable, reliable and user-friendly systems for transferring microfluidic chips from an incubator to a microscope while maintaining physiological conditions when performing microscopy. The presented carrier represents a cost-effective option for sustaining environmental conditions of microfluidic chips in combination with minimizing the device manipulation required for reagent injection, media exchange or sample collection. The carrier, which has the outer dimension of a standard well plate size, contains an integrated perfusion system that can recirculate the media using piezo pumps, operated in either continuous or intermittent modes (50-1000 µl/min). Furthermore, a film resistive heater made from 37 µm-thick copper wires, including temperature feedback control, was used to maintain the microfluidic chip temperature at 37 °C when outside the incubator. The heater characterisation showed a uniform temperature distribution along the chip channel for perfusion flow rates up to 10 µl/min. To demonstrate the feasibility of our platform for long term cell culture monitoring, mouse brain endothelial cells (bEnd.3) were repeatedly monitored for a period of 10 days, demonstrating a system with both the versatility and the potential for long imaging in microphysiological system cell cultures.

Geographic differences in gut microbiota composition impact susceptibility to enteric infection.

Large-scale studies of human gut microbiomes have revealed broad differences in composition across geographically distinct populations. Yet, studies examining impacts of microbiome composition on various health outcomes typically focus on single populations, posing the question of whether compositional differences between populations translate into differences in susceptibility. Using germ-free mice humanized with microbiome samples from 30 donors representing three countries, we observe robust differences in susceptibility to Citrobacter rodentium, a model for enteropathogenic Escherichia coli infections, according to geographic origin. We do not see similar responses to Listeria monocytogenes infections. We further find that cohousing the most susceptible and most resistant mice confers protection from C. rodentium infection. This work underscores the importance of increasing global participation in microbiome studies related to health outcomes. Diverse cohorts are needed to identify both population-specific responses to specific microbiome interventions and to achieve broader-reaching biological conclusions that generalize across populations.

The internationalization of human microbiome research.

The human microbiome has now been linked with myriad diseases, yet most of this research has been conducted on American and European populations that make up only 1/6th of the world's population. With growing recognition that human microbiomes differ tremendously across global populations, it is especially important to understand how these compositional differences impact health outcomes. Recent advances in infectious disease and malnutrition research have demonstrated the potential for microbiome-based strategies to address the biggest challenges in global health. This review highlights major advances toward understanding microbiome diversity across the world and its contributions to disease, and outlines key questions, challenges, and opportunities to broaden the scope of and promote inclusivity within microbiome research.

Butenafine and analogues: An expeditious synthesis and cytotoxicity and antifungal activities.

The incidence of fungal infections is considered a serious public health problem worldwide. The limited number of antimycotic drugs available to treat human and animal mycosis, the undesirable side effects and toxicities of the currently available drugs, and the emergence of fungal resistance emphasizes the urgent need for more effective antimycotic medicines. In this paper, we describe a rapid, simple, and efficient synthetic route for preparation of the antifungal agent butenafine on a multigram scale. This novel synthetic route also facilitated the preparation of 17 butenafine analogues using Schiff bases as precursors in three steps or less. All the synthesized compounds were evaluated against the yeast, Cryptococcus neoformans/C. gattii species complexes and the filamentous fungi Trichophyton rubrum and Microsporum gypseum. Amine 4bd, a demethylated analogue of butenafine, and its corresponding hydrochloride salt showed low toxicity in vitro and in vivo while maintaining inhibitory activity against filamentous fungi.