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Hierarchical Phase-Contrast Tomography Imaging: Applicability in biomedical research

Objectives Hierarchical Phase-Contrast Tomography (HiP-CT) enables non-destructive, multi-scale imaging of whole human organs. We describe how HiP-CT is utilized for biomedical research within the Human Organ Atlas Hub through three case studies: mapping the enteric nervous system (ENS) of the human colon, analysing myocardial and AV conduction architecture in Tetralogy of Fallot (TOF), and characterizing ductal organization in breast carcinoma. The challenges we faced with this novel biomedi...

— Docter, D., Brunet, J., Sabarigirivasan, V., Lemmens, G., Tielemans, B., Sporring, J., Dejea, H., Urban, T., Purzycka, J., Gorter, R., Huirne, J., Michels, V., Hanemaaijer-van der Veer, J., Bellier, A., Stansby, D., Ackermann, M., D. Buelow, R., Jonigk, D., Jacob, J., Hagoort, J., Verleden, S., Cook, A., Walsh, C., Tafforeau, P., Lee, P., de Bakker, B. 2026-01-19 00:00:00

dgiLIT: A Method for Prioritization and AI Curation of Drug-Gene Interactions

IMPORTANCE: The Drug-Gene Interaction Database (DGIdb) has a long history of driving hypothesis generation for biomedical research through the careful curation of drug-gene interaction data from primary and secondary sources with supporting literature. Recent advances in large-language model (LLM) and artificial intelligence (AI) technologies have enabled new paradigms for knowledge extraction and biocuration. The accelerating growth of biomedical literature presents a significant challenge f...

— Cannon, M. J., Bratulin, A., Stevenson, J. S., Perry, K., Coffman, A., Kiwala, S., Schimmelpfennig, L., Costello, H., McMichael, J. F., Griffith, M., Griffith, O. L., Wagner, A. H. 2026-01-19 00:00:00

Deconvolved tumor adipocyte proportions and high grade serous ovarian carcinoma survival

Background Single-cell-based analyses of high-grade serous ovarian carcinoma (HGSOC) survival have largely ignored adipocytes, which are fragile and under-represented in single-cell references. Adipocytes are known active components of the tumor microenvironment in many cancers, and HGSOC tumors frequently metastasize to the omentum, a lining of adipose tissue. Methods We created a composite reference that combines single-nucleus adipose profiles with published HGSOC single-cell data to deco...

— Ivich, A., Grieshober, L., Davidson, N. R., Akatsu, G. Y., Peres, L. C., Hicks, S. C., Marks, J. R., Schildkraut, J. M., Doherty, J. A., Greene, C. S. 2026-01-19 00:00:00

Iron Deficiency Drives Sarcopenia in the Elderly: HIF-1α-Mediated Fibro-Adipogenic Progenitor Differentiation Induces Fat Infiltration and Impairs Muscle Function

Abnormal iron metabolism is closely linked to sarcopenia; however, the specific iron metabolism features of fat-infiltrating sarcopenia remain poorly understood. Proteomic sequencing revealed that in skeletal muscle with severe fat infiltration, the expression of iron utilization-related proteins was significantly downregulated, whereas that of iron uptake and storage proteins was markedly upregulated, thereby presenting an abnormal iron deficiency (ID) phenotype. Nevertheless, the mechanism ...

— Ren, Q., Yang, G., Wang, D., Wu, W., Wang, Y., Feng, J., Ma, K., Guo, A., Fan, M., Sun, Y., Lang, Z., Jiang, X., Liu, Y., Wang, L., Wang, R. 2026-01-19 00:00:00

Phosphorylation of Cyclophilin-D is Not Required for Regulation of The Mitochondrial Permeability Transition Pore by GSK3β

Genetic inhibition of cyclophilin D (CypD) delays the opening of the mitochondrial permeability transition pore (MPTP) and therefore reduces necrotic cell death. Elucidation of factors that impact CypD activity is therefore key to understanding the regulation of MPTP opening. Glycogen synthase kinase-3{beta} (GSK3{beta}) is a serine/threonine kinase that has been shown to modulate MPTP and cell death, potentially through phosphorylation of CypD. Therefore, we hypothesized that the mitochondri...

— Alex, L., Klutho, P., Song, L., Gutierrez-Aguilar, M., Baines, C. 2026-01-19 00:00:00

Species Identification and Antimicrobial Susceptibility of Mycobacterial Isolates from Dogs and Cats

Nontuberculous Mycobacterium (NTM) species are increasingly recognized as opportunistic pathogens in companion animals, yet data on species distribution and antimicrobial resistance remain limited. The goal of this study was to evaluate species identification methods and determine antimicrobial susceptibility profiles of NTM isolates from cats and dogs submitted to the University of Tennessee veterinary diagnostic laboratory. Twenty-nine NTM isolates (25 feline, 4 canine) collected between 20...

— Rajeev, S., Azelby, J., Reed, P., Jones, R., Nair, R. V., Johnson, B. 2026-01-19 00:00:00

Uncovering Conceptual Biases in DNA Stabilization: A Student-Led Investigation

Deoxyribonucleic acid (DNA) stands as one of the most foundational concepts in life sciences, essential for students to master. However, when surveyed about the forces that stabilize the double-stranded DNA structure, many students exhibited a conceptual bias, favouring base pairing as the primary stabilizing force, while overlooking the equally critical role of base stacking interactions. To investigate the origins of this misconception, students conducted a comprehensive analysis of 35 wide...

— Polo, C., Thandi, A., Chandler, O., Lugert, P., Hammond, A., Madhi, T., Ayala, M., Berrigan, A. J., Chen, A., Gillett, K., Sareen, M., Yu, S., Xiong, S., Zuo, Y.-y., Sanjeev, S. 2026-01-19 00:00:00

Beyond Deficit and Coexistence: Modeling the Knowledge-Conspiracy-Mistrust Configuration in Public Understanding of Science

Debates about public trust in science often contrast deficit-based models, which emphasize the role of scientific knowledge, with constructivist perspectives that highlight the coexistence of multiple epistemologies. However, both approaches tend to overlook the mechanisms that link scientific knowledge, alternative epistemic orientations, and mistrust in science. To address this gap, the study applies a multilevel structural equation model within a multidimensional framework to examine consp...

— Süerdem, A., Zdravkov, S., Ivanov, M. J. 2026-01-19 00:00:00

Rigor and Transparency in two neurotrauma-publishing journals: editorial policies improve transparent reporting.

Preclinical research in traumatic brain injury (TBI) continues to significantly increase knowledge and yield a large number of peer-reviewed studies, but translation of these results to the clinical setting has been minimal. Rigor and transparency factors such as concealment of group allocation (e.g., blinding) or ensuring that reagents are identifiable are critical in ensuring that scientific studies are replicable and translatable. Yet, nearly all efforts aimed at measuring these factors ha...

— Bandrowski, A. E., Namburi, A., Ferguson, A. R., Floyd, C. L., Martone, M. E., PRECISE-TBI Authors, T. 2026-01-19 00:00:00

Identity-resolved vocal exchanges in multi-marmoset settings

Acoustic communication is tightly coupled to collective behaviour and social network structure in many animal societies. Yet continuous, identity-resolved recordings of multiple concurrent signalers are challenging. We evaluated a commercial acoustic camera for marmoset (Callithrix jacchus) vocal behavior across controlled bench tests and naturalistic family interactions. Spectral characterization showed the system is closest to neutral and most sensitive in 5 - 10 kHz, supporting reliable de...

— Cabrera-Moreno, J., Burkart, J., Mircheva, M. 2026-01-19 00:00:00

Array-CNCC: precise aggregation and arrayed plating facilitate quantitative phenotyping of human cranial neural crest cells and craniofacial disease modelling

Facial development is highly sensitive to genetic and environmental perturbation, with craniofacial malformation associated with over one-third of congenital birth defects. The face arises during an early and largely inaccessible window of embryonic development, with a large contribution from transient and multipotent cranial neural crest cells (CNCCs). Assessment of the molecular and cellular mechanisms driving normal and disordered human facial development therefore relies greatly on the us...

— Ozga, E., Milto, K. M., Demurtas, M., Bates, L. E., Grimes, G., Azami, T., Su, J., De Angelis, C., Trizzino, M., Nichols, J., Long, H. K. 2026-01-18 00:00:00

Genomic signatures of reproductive isolation are decoupled from floral divergence in a long-standing hybrid zone

A central goal in evolutionary biology is to understand how species boundaries are maintained in the face of gene flow. While gene flow between species often accompanies the formation of hybrids, the genome-wide effects of hybridization depend on the presence and nature of reproductive isolating barriers. Two North American wildflower species with divergent floral syndromes, [I]Penstemon davidsonii[/I] (bee syndrome) and [I]P. newberryi[/I] (bird syndrome), have formed hybrid zones in the eas...

— Stone, B. W., Williams, N. H., Depatie, T. H., Radford, Z. J., Mosley, A. M., Wessinger, C. A. 2026-01-18 00:00:00

PRECISION EVOLUTIONARY MEDICINE: A COMPUTATIONAL GRAPH-THEORETICAL FRAMEWORK FOR PATHOGEN-SPECIFIC ANTIBIOTIC CYCLING IN MULTI-DRUG-RESISTANT GRAM-NEGATIVE INFECTIONS

Background: The Proliferation of Multi-drug resistant (MDP) ESKAPE pathogens threatens to compromise the efficacy of standard antibiotic pharmacopoeia. Current antimicrobial stewardship strategies predominantly rely on reactive antibiograms selecting therapeutic agents based on immediate phenotypic susceptibility. This approach, while clinically expedient, often inadvertently selects for cross-resistance, driving the evolutionary trajectory toward pan-drug resistance. A paradigm shift is requ...

— Shuaibu, I. I., Khan, M. A., Alkhamis, D., Alkhamis, A., Ahmad, M. I. 2026-01-18 00:00:00

Modular mRNA LNP design integrates RNA, lipid, and antigen engineering for protective vaccination

mRNA lipid nanoparticle (LNP) vaccines are programmable, multicomponent systems in which immune outcomes emerge from coupled control of nanoparticle chemistry, RNA regulatory architecture, and antigen design. Here we establish an integrated engineering framework that quantitatively maps how ionizable lipid identity, untranslated region (UTR) configuration, and 5' cap structure shape innate activation landscapes and thereby tune the magnitude, cellular distribution, and polarization of adaptiv...

— Farzani, T., Espinoza, N., M. Manafi, M., R. Welch, S., D. Coleman-McCray, J., Aida-Ficken, V., R. Spengler, J., Bergeron, E., F. Spiropoulou, C., Borges, C., Bielecki, K., Li, L., Shah, D., Paye, M., Rojas, E., N. Spector, S., Samani, P., E. Hensley, L., Ozonoff, A., Sabeti, P. 2026-01-18 00:00:00

Genetic biosensor for optimizing double-stranded RNA production by bacterial symbionts

There is growing interest in engineering animal and plant microbiomes to deliver double-stranded RNA (dsRNA) for RNA interference (RNAi) applications. We developed a genetically encoded biosensor that uses bimolecular fluorescence complementation to monitor dsRNA levels within bacterial cells to accelerate the symbiont-mediated RNAi design-build-test cycle. We validated performance of the sensor in Escherichia coli and demonstrated enhanced dsRNA accumulation in engineered strains of the aphi...

— Navarro-Escalante, L., VanDieren, A. J., Barrick, J. E. 2026-01-18 00:00:00

An Adenine-Based Molecular Rotor as a Universal Fluorescent Nucleobase with High Brightness

Chemically modified nucleic acids have become a powerful platform for basic research and applied technologies. Universal nucleobases are used in PCR,sequencing, and the design of nanodevices and aptamers. Fluorescent universal nucleobases have an even wider range of applications, including the development of nucleic acid-based sensors, switches, and relay logic gates. However, few such nucleobases have been proposed to date, and most of them have suboptimal optical properties. Here, we propos...

— Pushkarevskaya, A. A., Kamzeeva, P. N., Belyaev, E. S., Brylev, V. A., Lomzov, A. A., Aralov, A. V. 2026-01-18 00:00:00

Snapshots of Internal Protein Crystal Architecture at the Nanoscale

Macromolecular crystallography has historically inferred models of internal crystal architecture from reciprocal-space measurements of Bragg reflections. Nevertheless, direct real-space visualization of crystallographic disorder remains elusive, particularly at the nanoscale. Using a 15-nanometer probe, here we apply both ambient-temperature and cryogenic four-dimensional scanning transmission electron microscopy (4D-STEM) to map the topography of coherently diffracting domains (CDDs) in lyso...

— Nia, S. S., Saha, A., Cho, J., Zhou, Z. H., Ercius, P., Mecklenburg, M. 2026-01-18 00:00:00

Amino acid variants at the P94 position in Staphylococcus aureus class A sortase modulate substrate binding and enzyme activity

The surface of gram-positive bacteria is a highly regulated environment with specific attachment of proteins required for viability. Sortase enzymes are cysteine transpeptidases that recognize and ligate substrates to the peptidoglycan layer in these microorganisms, which can be highly pathogenic (e.g., Staphylococcus aureus, Streptococcus pyogenes, etc.). As such, sortases represent a potentially novel target for antibiotic development. In addition, the catalytic activity of sortase enzymes ...

— Cox-Tigre, N., Stewart, M. E., Tucker, J., Walkenhauer, E. G., Wilce, C. S., Antos, J. M., Amacher, J. F. 2026-01-18 00:00:00

An integrated, scaled approach to resolve TSC2 variants of uncertain significance

Obtaining a precise genetic tuberous sclerosis diagnosis is a challenge as many missense TSC2 variants are variants of uncertain significance (VUS). VUS in TSC2 have been resolved by one-at-a-time functional assays, but these assays cannot scale to the 3,634 TSC2 missense VUS observed so far. To address this challenge, we used massively parallel sequencing to measure the steady-state abundance of almost 9,000 TSC2 missense variants and also developed an mTOR pathway activity assay using genom...

— Biar, C. G., Wang, Z. R., Camp, N. D., Holmes, D. L., Wheelock, M. K., Pendyala, S., McGee, A. V., Gupta, P., McEwen, A. E., Tejura, M., Richardson, M. E., Weyandt, J. D., Coleman, T., Stewart, R., Zeiberg, D., Vandi, A. J., Dawson, S., Radivojac, P., Starita, L. M., Carvill, G. L., James, R. G., Fowler, D. M., Calhoun, J. D. 2026-01-18 00:00:00

Revisiting the genetics of Lake Constance Coregonids using lake-wide whole genome sequencing

Anthropogenic pressures can have detrimental impacts on fish populations, with their effective management and conservation requiring accurate monitoring tools. Yet, this is not straightforward for closely-related, co-existing species that are difficult to distinguish using simple phenotypic or genetic approaches. Coregonids are of cultural and economic importance across Europe but have faced a multitude of pressures over the last century. Yet genomic management tools are lacking. In Lake Cons...

— Jacobs, A., Roch, S., Roberts, B., Capstick, M., Brinker, A. 2026-01-18 00:00:00

Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models

Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses: rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics, replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo. All four viruses demonst...

— Nooruzzaman, M., Buccholz, D. W., Rani, R., de Oliveira, P. S. B., Adeleke, R. A., Feng, C., Demeter, E. A., Aguilar, H. C., Diel, D. 2026-01-18 00:00:00

Recombinant influenza A H5N1 viruses expressing fluorescent and luminescent reporter proteins

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses present a broad host range, with recent spillover and sustained transmission in dairy cattle in the United States. Replication-competent reporter viruses are critical tools that enable real-time monitoring of virus replication facilitating high-throughput antiviral and serological screens. In this study, we engineered three recombinant H5N1 clade 2.3.4.4b reporter viruses expressing nanoluciferase (NLuc) and two fluorescent ...

— Nooruzzaman, M., de Oliveira, P. S. B., Feng, C., Diel, D. 2026-01-18 00:00:00

Engineering Cybergenetic Cell-Based Therapies

Adaptive, closed-loop control of cellular behavior is essential for next-generation therapies, yet most current treatments operate in an open-loop manner and lack robustness to patient variability and disease dynamics. Here, we establish a control-theoretic platform for rational engineering of closed-loop cell-based therapies that achieve precise and robust regulation. First, we introduce multi-dimensional nullgram profiling, a high-throughput approach that enables quantitative prediction and...

— Chang, C.-H., Arampatzis, A., Balula, S., Hou, M., Filo, M. G., Chen, M., Cella, F., Khammash, M. 2026-01-18 00:00:00

A reconfigurable DNA memory architecture for hierarchical data management via programmable phase transitions

DNA has emerged as a promising medium for the post-silicon era of information storage due to its ultrahigh density and longevity. However, current systems are bifurcated, with solid-state systems providing robust cold archival but lacking accessibility, while fluidic molecular computing systems offer dynamic processing but suffer from low density and instability. This mutual exclusivity has hindered the development of hierarchical memory, a standard in modern computing, within molecular stora...

— Ye, J., Liu, A., Wang, F., Zhang, H., Zhang, H., Fan, C. 2026-01-18 00:00:00

Fundamental limitations of genomic language models for realistic sequence generation

Large language models (LLMs) have shown remarkable success in natural language processing, prompting interest in their application to genomic sequence analysis. Genomic Language Models based on similar architectures offer a promising avenue for synthetic genome generation and characterization. However, their effectiveness for biological sequence modeling remains poorly characterized. We present a comprehensive evaluation of a state-of-the-art genomic Language Model (gLM), Evo 2, on multiple g...

— Tzanakakis, A., Mouratidis, I., Georgakopoulos-Soares, I. 2026-01-18 00:00:00

STRUCT2SEQ: RNA INVERSE FOLDING WITH DEEP Q-LEARNING

RNA molecules play critical roles in biology and therapeutics, with their function intimately tied to their secondary structure. Designing RNA sequences that reliably fold into desired secondary structures, especially those with complex pseudoknots, remains a fundamental challenge. Here, we present Struct2SeQ, a reinforcement learning framework that leverages deep Q-learning to generate RNA sequences conditioned on target secondary structures and SHAPE reactivity constraints. By formulating R...

— He, S., Sun, Q. 2026-01-18 00:00:00

SSNA1 mechanically reinforces the damaged microtubule lattice

SSNA1 (Sjogren's Syndrome Nuclear Autoantigen 1) is a microtubule-associated protein involved in key cellular processes, including cell division, intraflagellar transport, and axonal branching. SSNA1 specifically localizes to sites of damage along the microtubule lattice, thus acting as a microtubule damage sensor. However, the effects of SSNA1 on microtubule mechanics or on the process of microtubule self-repair, which involves the incorporation of soluble tubulin dimers into lattice damage ...

— Richardson, L. B., Lawrence, E. J., Pinjakan, A., Zanic, M. 2026-01-18 00:00:00

SE3Bind: SE(3)-equivariant model for antibody-antigen binding affinity prediction

Predicting antibody-antigen binding affinity is critical for therapeutic development, but machine learning-based approaches to the problem are typically hampered by the small amount of available structural and affinity data. We introduce SE3Bind, an SE(3)-equivariant architecture trained on two related tasks: re-docking of an antibody structure to its matching antigen structure, and antibody-antigen binding free energy prediction. Both tasks encourage the model to learn an energy function for...

— Subedy, A., Bhadra-Lobo, S., Lamoureux, G. 2026-01-18 00:00:00

Structural characterization of a minimal KLC2/Nup358/BicD2 complex

Cellular transport processes along microtubules are often facilitated by multi-motor complexes, which are connected by adapter proteins and cargoes. The nuclear pore protein Nup358, for example, interacts with the dynein adapter Bicaudal D2 (BicD2), which in turn recruits minus-end directed dynein motors and plus-end directed kinesin-1 motors for a nuclear positioning pathway that is essential for brain development. How motor recruitment is regulated by interactions of BicD2 with Nup358 is no...

— Noell, C. R., Solmaz, S. R. 2026-01-18 00:00:00

Characterization of novel cytoplasmic roles for the N-terminal methyltransferase NRMT1

N-terminal methylation of proteins by the trimethylase NRMT1 plays important roles in oncogenesis, development, and aging. As N-terminal methylation has frequently been shown to regulate protein-DNA interactions, and many NRMT1 substrates are transcription factors or regulators of chromatin structure, previous research has focused on how transcriptional regulation by NRMT1 affects cell growth and differentiation. However, we have recently identified a new, cytoplasmic role for NRMT1, inhibiti...

— Tooley, J. G., Zhou, G., Obeidat, S., Arbel, A., Jones, C., Tedeschi, F., Schaner Tooley, C. 2026-01-18 00:00:00