How traumatic brain injury (TBI) mechanistically contributes to neurodegenerative disease remains poorly understood. Marco et al. find that therapeutic viral vector-based delivery of VEGFC recuperates meningeal lymphatic drainage deficits post-TBI and protects against severe development of tauopathy, neurodegeneration, and cognitive decline in the PS19 mouse model of tauopathy.
This study used a novel multiplex 20-gene panel with Cas9-targeted, amplification-free long-read sequencing and optical genome mapping to elucidate ATXN10 repeat motif patterns and investigated genotype-phenotype correlations in index cases of 6 multigenerational spinocerebellar ataxia type 10 kindreds from Peru.
Spinocerebellar ataxia type 10 (SCA10, Online Mendelian Inheritance in Man (OMIM)# 603516) is a rare autosomal-dominant disorder caused by an expanded pentanucleotide repeat in the ATXN10 gene on chromosome 22q13.3.1 Although rare globally, SCA10 accounts for 45% of spinocerebellar ataxia cases in Peru, where the population is approximately 70% Amerindian.2,3
A typical ATXN10 allele has 10–32 ATTCT repeats. Intermediate alleles from 280 to 850 repeats may have reduced penetrance4 while alleles over 850 repeats result in full disease penetrance.5 In our recent study on ATXN10 expansions in healthy Peruvians, we found expanded alleles in 3.7% of Mestizos and 9.9% of Indigenous American nonataxic individuals.6
Conventional methods fail to accurately determine ATXN10 repeat size and structure: Southern blot often overestimates repeats while repeat-primed PCR cannot measure repeats over 1,250 bp or detect alternate repeats without specific repeat primers.7
The human brain is a fascinating and complex organ that supports numerous sophisticated behaviors and abilities that are observed in no other animal species. For centuries, scientists have been trying to understand what is so unique about the human brain and how it develops over the human lifespan.
Recent technological and experimental advances have opened new avenues for neuroscience research, which in turn has led to the creation of increasingly detailed descriptions of the brain and its underlying processes. Collectively, these efforts are helping to shed new light on the underpinnings of various neuropsychiatric and neurodevelopmental disorders.
Researchers at Beijing Normal University, the Changping Laboratory and other institutes have recently set out to study both the human and macaque brain, comparing their development over time using various genetic and molecular analysis tools. Their paper, published in Nature Neuroscience, highlights some key differences between the two species, with the human pre-frontal cortex (PFC) developing slower than the macaque PFC.
In a major step toward understanding how the physical form of DNA shapes human biology, researchers at Northwestern University working with the 4D Nucleome Project have created the most comprehensive maps yet of the genome’s three-dimensional organization over time and space. The work is described in a new study published in Nature.
The research, based on experiments in human embryonic stem cells and fibroblasts, provides an expansive picture of how genes interact with one another, fold into complex structures, and shift their positions as cells carry out normal functions and divide. The study was co-led by Feng Yue, the Duane and Susan Burnham Professor of Molecular Medicine in the Department of Biochemistry and Molecular Genetics.
“Understanding how the genome folds and reorganizes in three dimensions is essential to understanding how cells function,” said Yue, who is also director of the Center for Advanced Molecular Analysis and founding director of the Center for Cancer Genomics at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “These maps give us an unprecedented view of how genome structure helps regulate gene activity in space and time.”
A new study suggests that dementia may be driven in part by faulty blood flow in the brain. Researchers found that losing a key lipid causes blood vessels to become overactive, disrupting circulation and starving brain tissue. When the missing molecule was restored, normal blood flow returned. This discovery opens the door to new treatments aimed at fixing vascular problems in dementia.
CTAs, immune-privileged and aberrantly expressed in HNSCC tumors, were consistently undetectable in normal oral mucosa but highly enriched in malignant tissue. These findings inform the development of targeted adoptive cell therapies with minimized risk for off-tumor effects.
Question Can cancer-testis antigens (CTAs) be leveraged as precision immuno-oncologic targets for head and neck cancer?
Findings In this cross-sectional study including 33 samples from patients with head and neck squamous cell carcinoma (HNSCC), 23 testis-restricted and 44 testis-selective CTAs with tumor-specific expression were identified in both de novo and radiation-recurrent HNSCCs, validated across transcriptomic, genomic, and proteomic analyses. Of these, a core set of 14 CTAs were consistently detected across all datasets analyzed.
Meaning The CTAs identified in this study in both de novo and recurrent HNSCCs represent potential precision immuno-oncologic targets for adoptive cell therapeutics, such as T-cell receptor–engineered T-cell therapy.
The authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.
Imaging technology has transformed how we observe the universe—from mapping distant galaxies with radio telescope arrays to unlocking microscopic details inside living cells. Yet despite decades of innovation, a fundamental barrier has persisted: capturing high-resolution, wide-field images at optical wavelengths without cumbersome lenses or strict alignment constraints.
A new study by Guoan Zheng, a biomedical engineering professor and the director of the UConn Center for Biomedical and Bioengineering Innovation (CBBI), and his research team at the UConn College of Engineering, was published in Nature Communications, introducing a breakthrough solution that could redefine optical imaging across science, medicine, and industry.
“At the heart of this breakthrough is a longstanding technical problem,” said Zheng. “Synthetic aperture imaging—the method that allowed the Event Horizon Telescope to image a black hole—works by coherently combining measurements from multiple separated sensors to simulate a much larger imaging aperture.”