Trees as a metaphor to understand relationships in biology.

The phylogenetic tree has been a core conceptual tool for evolutionary biology for nearly 200 years. This editorial explores the role of the tree as a metaphor, discussing two new PLOS Biology Essays that look to the future.

How Do Students Critically Evaluate Outdated Language That Relates to Gender in Biology?

Cisheteronormative ideologies are infused into every aspect of society, including undergraduate science. We set out to identify the extent to which students can identify cisheteronormative language in biology textbooks by posing several hypothetical textbook questions and asking students to modify them to make the language more accurate (defined as "correct; precise; using language that applies to all people"). First, we confirmed that textbooks commonly use language that conflates or confuses sex and gender. We used this information to design two sample questions that used similar language. We examined what parts of the questions students modified, and the changes they recommended. When asked to modify sample textbook questions, we found the most common terms or words that students identified as inaccurate were related to infant gender identity. The most common modifications that students made were changing gender terms to sex terms. Students' decisions in this exercise differed little across three large biology courses or by exam performance. As the science community strives to promote inclusive classrooms and embrace the complexity of human gender identities, we provide foundational information about students' ability to notice and correct inaccurate language related to sex and gender in biology.

A CURE Lab in Introductory Biology at a Regional Comprehensive University Negatively Impacts Student Success in the Associated Lecture Course Among Students from Groups Underrepresented in Science.

Course-based undergraduate research experiences (CUREs) have been proposed as a mechanism to democratize access to the benefits of apprentice-style scientific research to a broader diversity of students, promoting inclusivity and increasing student success and retention. As we evaluate CUREs, it is essential to explore their effectiveness within the environments of regional comprehensive universities and community colleges, because they are important access points for a wide variety of students. It is also important to address the potential influence of volunteer bias, where students can opt to enroll in either the CURE or a traditional lab, on the outcomes of CUREs. We evaluated a CURE at a regional comprehensive university under conditions both with and without volunteer bias. We find that nonvolunteer students report a lower sense of discovery and relevance of the CURE compared with students who volunteered for the course. Importantly, we also find that our replacement of the traditional lab class with a CURE resulted in lower scores on exams in the associated lecture course among students who are both BIPOC and Pell eligible. We call for additional research on the effects of CUREs at nonresearch-intensive institutions and without volunteer bias, to better understand the impact of these classes.

A Road Map for Planning Course Transformation Using Learning Objectives.

The Vision and Change report called for biology educators to transform undergraduate biology education. The report recommended educators transparently state what students should know and be able to do and create assessments to measure student learning. Using backward design, learning objectives (LOs) can serve as the basis for course transformation. In this essay, we present a roadmap for planning successful course transformations synthesized from the literature. We identified three categories of critical features for successful course transformation. First, establishing a sense of urgency and offering faculty incentives to engage in this time-consuming work creates a needed climate for change. Second, departments are empowered in this process by including key stakeholders, building faculty teams to work collaboratively to identify LOs used to drive pedagogical change, develop assessment strategies, and engage in professional development efforts to support the process. Third, there must be intentional effort to manage resistance and ensure academic freedom and creativity in the classroom. General recommendations as well as areas for further research are discussed.

Label-free Brillouin endo-microscopy for the quantitative 3D imaging of sub-micrometre biology.

This report presents an optical fibre-based endo-microscopic imaging tool that simultaneously measures the topographic profile and 3D viscoelastic properties of biological specimens through the phenomenon of time-resolved Brillouin scattering. This uses the intrinsic viscoelasticity of the specimen as a contrast mechanism without fluorescent tags or photoacoustic contrast mechanisms. We demonstrate 2 µm lateral resolution and 320 nm axial resolution for the 3D imaging of biological cells and Caenorhabditis elegans larvae. This has enabled the first ever 3D stiffness imaging and characterisation of the C. elegans larva cuticle in-situ. A label-free, subcellular resolution, and endoscopic compatible technique that reveals structural biologically-relevant material properties of tissue could pave the way toward in-vivo elasticity-based diagnostics down to the single cell level.

Focusing on mitochondria in the brain: from biology to therapeutics.

Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to the physiology and pathology of many organs and tissues, among which the brain is particularly prominent. The brain demands 20% of the resting metabolic rate and holds highly active mitochondrial activities. Considerable research shows that mitochondria are closely related to brain function, while mitochondrial defects induce or exacerbate pathology in the brain. In this review, we provide comprehensive research advances of mitochondrial biology involved in brain functions, as well as the mitochondria-dependent cellular events in brain physiology and pathology. Furthermore, various perspectives are explored to better identify the mitochondrial roles in neurological diseases and the neurophenotypes of mitochondrial diseases. Finally, mitochondrial therapies are discussed. Mitochondrial-targeting therapeutics are showing great potentials in the treatment of brain diseases.

Future opportunities in solute carrier structural biology.

Solute carriers (SLCs) control the flow of small molecules and ions across biological membranes. Over the last 20 years, the pace of research in SLC biology has accelerated markedly, opening new opportunities to treat metabolic diseases, cancer and neurological disorders. Recently, new families of atypical SLCs, with roles in organelle biology, metabolite signaling and trafficking, have expanded their roles in the cell. This Perspective discusses work leading to current advances and the emerging opportunities to target and modulate SLCs to uncover new biology and treat human disease.

From covalent transition states in chemistry to noncovalent in biology: from ß- to Φ-value analysis of protein folding.

Solving the mechanism of a chemical reaction requires determining the structures of all the ground states on the pathway and the elusive transition states linking them. 2024 is the centenary of Brønsted's landmark paper that introduced the ß-value and structure-activity studies as the only experimental means to infer the structures of transition states. It involves making systematic small changes in the covalent structure of the reactants and analysing changes in activation and equilibrium-free energies. Protein engineering was introduced for an analogous procedure, Φ-value analysis, to analyse the noncovalent interactions in proteins central to biological chemistry. The methodology was developed first by analysing noncovalent interactions in transition states in enzyme catalysis. The mature procedure was then applied to study transition states in the pathway of protein folding - 'part (b) of the protein folding problem'. This review describes the development of Φ-value analysis of transition states and compares and contrasts the interpretation of ß- and Φ-values and their limitations. Φ-analysis afforded the first description of transition states in protein folding at the level of individual residues. It revealed the nucleation-condensation folding mechanism of protein domains with the transition state as an expanded, distorted native structure, containing little fully formed secondary structure but many weak tertiary interactions. A spectrum of transition states with various degrees of structural polarisation was then uncovered that spanned from nucleation-condensation to the framework mechanism of fully formed secondary structure. Φ-analysis revealed how movement of the expanded transition state on an energy landscape accommodates the transition from framework to nucleation-condensation mechanisms with a malleability of structure as a unifying feature of folding mechanisms. Such movement follows the rubric of analysis of classical covalent chemical mechanisms that began with Brønsted. Φ-values are used to benchmark computer simulation, and Φ and simulation combine to describe folding pathways at atomic resolution.

Library size confounds biology in spatial transcriptomics data.

Spatial molecular data has transformed the study of disease microenvironments, though, larger datasets pose an analytics challenge prompting the direct adoption of single-cell RNA-sequencing tools including normalization methods. Here, we demonstrate that library size is associated with tissue structure and that normalizing these effects out using commonly applied scRNA-seq normalization methods will negatively affect spatial domain identification. Spatial data should not be specifically corrected for library size prior to analysis, and algorithms designed for scRNA-seq data should be adopted with caution.

Biology and Toxicology of Gametes, Embryos, and Cancer Cells in Reproductive Systems.

Reproduction is the important process of transmitting one's genetic information to the next generation [...].

Biology of neurofibrosis with focus on multiple sclerosis.

Tissue damage elicits a wound healing response of inflammation and remodeling aimed at restoring homeostasis. Dysregulation of wound healing leads to accumulation of effector cells and extracellular matrix (ECM) components, collectively termed fibrosis, which impairs organ functions. Fibrosis of the central nervous system, neurofibrosis, is a major contributor to the lack of neural regeneration and it involves fibroblasts, microglia/macrophages and astrocytes, and their deposited ECM. Neurofibrosis occurs commonly across neurological conditions. This review describes processes of wound healing and fibrosis in tissues in general, and in multiple sclerosis in particular, and considers approaches to ameliorate neurofibrosis to enhance neural recovery.

[Application and optimization of CRISPRi to the biology of Mycobacterium tuberculosis].

Tuberculosis, caused by infection with Mycobacterium tuberculosis (MTB), remains a global public health challenge. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains make tuberculosis more difficult to control. New tools to study the biology of MTB can identify novel targets for drug discovery. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) combined with next-generation sequencing has provided many novel insights into the physiology and genetics of MTB. This review summarizes the application and optimization of CRISPRi in MTB biology.

Symbiosis takes a front and center role in biology.

All animals and plants likely require interactions with microbes, often in strong, persistent symbiotic associations. While the recognition of this phenomenon has been slow in coming, it will impact most, if not all, subdisciplines of biology.

Undergraduate Biology Lecture Courses Predominantly Test Facts about Science Rather than Scientific Practices.

Scientific practices are the skills used to develop scientific knowledge and are essential for careers in science. Despite calls from education and government agencies to cultivate scientific practices, there remains little evidence of how often students are asked to apply them in undergraduate courses. We analyzed exams from biology courses at 100 institutions across the United States and found that only 7% of exam questions addressed a scientific practice and that 32% of biology exams did not test any scientific practices. The low occurrence of scientific practices on exams signals that undergraduate courses may not be integrating foundational scientific skills throughout their curriculum in the manner envisioned by recent national frameworks. Although there were few scientific practices overall, their close association with higher-order cognitive skills suggests that scientific practices represent a primary means to help students develop critical thinking skills and highlights the importance of incorporating a greater degree of scientific practices into undergraduate lecture courses and exams.

An Endodontology Icon Who Fostered an Appreciation for Pulpal Biology and Its Relevance to Restorative Dentistry and Periodontics: Dr. Kaare Langeland.

The impact of ground-breaking research on the dental pulp and its response to dental procedures, materials and associated diseases significantly influenced the evolution and scope of Endodontics, creating a science of Endodontology. While there were scattered studies in the early 20th century in this regard, the clarification and codification of these concepts took a major leap forward in the late 1950s due to the academic prowess and in-depth research endeavors of Dr. Kaare Langeland. The story begins during World War I in Norway.

Brachytherapy on-a-chip: a clinically-relevant approach for radiotherapy testing in 3d biology.

We describe the first microfluidic device for in vitro testing of brachytherapy (BT), with applications in translational cancer research. Our PDMS-made BT-on-chip system allows highly precise manual insertion of clinical BT seeds, reliable dose calculation using standard clinically-used TG-43 formalism and easy culture of naturally hypoxic spheroids in less than 3 days, thereby increasing the translational potential of the device. As the BT-on-chip platform is designed to be versatile, we showcase three different gold-standard post-irradiation bioassays and recapitulate, for the first time on-chip, key clinical observations such as dose rate effect and hypoxia-induced radioresistance. Our results suggest that BT-on-chip can be used to safely and efficiently integrate BT and radiotherapy to translational research and drug development pipelines, without expensive equipment or complex workflows.