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New data-driven 3D chromosome model reveals structural and dynamic features of DNA

Chromosomes are masters of organization. These long strings of DNA fold down into an ensemble of compact structures that keep needed parts of the genome accessible while tucking away those that aren’t used as often. Understanding the complexity of these structures has been challenging; chromosomes are large systems, and deciphering the structure and dynamics requires a combination of experimental data and theoretical approaches. The FI-Chrom method, shared in a recent PNAS publication by Rice’s José Onuchic and Vinícius Contessoto, is a new and effective approach for creating 3D maps of chromosomes from real-world data.

FI-Chrom uses data from chromosome Hi-C maps. These maps break out the chromosome into units of length called beads — about 500,000 linear DNA bases each — and show how frequently each bead is close to other beads. This information shows only probabilities of any two beads being neighbors and no direct three-dimensional information. Imagine it as a logic puzzle where the rules, or parameters, read something like this: Bead A is 99% likely to be close to Bead B, 36% likely to be close to Bead C and 62% likely to be close to Bead D. A 3D model, the researchers knew, could be built by placing every bead in a space that didn’t violate any of the Hi-C map’s parameters. The only problem is that in Hi-C maps, there are hundreds of thousands of beads and tens of millions of mapped interactions showing bead closeness.

“We had chromosome maps that gave us, theoretically, 3D information, but we were really reading them in 2D space,” explains Onuchic, the Harry C. and Olga K. Wiess Chair of Physics and a corresponding author of the study. “Now, we have created FI-Chrom, an open-access program that can turn these Hi-C maps into 3D models of chromosomes.”

A targeted protein degrader that doubles as a cancer vaccine

Cells routinely present peptide fragments from their proteome for immune surveillance, using major histocompatibility complex (MHC) proteins as a display window. In this study, researchers introduced viral peptides to be processed and displayed on cancer cells.


One molecule combines two approaches to waken dormant immunity against tumors by .

Recently, variable length dystrophin constructs have been characterized in models of Duchenne muscular dystrophy (DMD)

Here, Hichem Tasfaout & team describe a new method for using proteomics to evaluate the efficacy of three dystrophin-replacement approaches using AAV vectors.


1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota — Twin Cities, Minneapolis, Minnesota, USA.

2Department of Neurology.

3Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, and.

4Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington, USA.

Atorvastatin and Aortic Stiffness During Anthracycline-Based Chemotherapy

Statin therapy before and during anthracycline-based chemotherapy resulted in fewer cases of elevated pulse wave velocity and reduced aortic distensibility compared with placebo. The results suggest a potential protective effect of atorvastatin against vascular dysfunction in cancer survivors.


Question Does 12 months of treatment with atorvastatin mitigate anthracycline-associated increased aortic stiffness, an important factor associated with adverse cardiovascular outcomes?

Findings In this secondary analysis of 300 participants with lymphoma enrolled in the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) randomized clinical trial, atorvastatin was associated with significantly lower odds of an increase (≥0.8 m per second) in magnetic resonance imaging–derived aortic arch pulse wave velocity, compared with placebo. The proportion of participants meeting this primary exploratory end point was significantly lower with atorvastatin (5%), compared with placebo (50%).

Meaning These findings suggest that pretreatment with atorvastatin is associated with preserved vascular function in patients undergoing anthracycline treatment.

PIKFYVE inhibition mitigates disease in models of diverse forms of ALS

Now online! (Cell 186786–802.e1–e15; February 16, 2023)


Now online! (Cell 186, 786–802.e1–e15; February 16, 2023)

In our original published article, we performed western blots and imaging of induced motor neurons (iMNs) to elucidate the mechanism through which PIKFYVE inhibition causes secretion and clearance of aggregation-prone proteins such as phosphorylated TDP-43 (pTDP-43). Since publication, we have become aware of 3 errors in figure legends or images that we are now correcting.

What Are the Roles of Mitochondrial Stress Responses and Mitohormesis in Neurodegenerative Disorders?

Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.


Zhao et al. report cryo-EM structures of human KCNQ2 in complex with QO-58 and QO-83 in multiple conformations, with or without PIP2. Together with electrophysiological and computational analyses, these structures provide insight into the channel’s activation mechanism and support the rational design of targeted anti-epileptic therapies.

Rim Lesions and Development of MS in Radiologically Isolated Syndrome

In #RadiologicallyIsolatedSyndrome, greater paramagnetic rim lesion burden on MRI was associated with increased risk and earlier development of clinical MultipleSclerosis.


Question Are paramagnetic rim lesions (PRLs) and central vein sign–positive white matter lesions (CVS+L) associated with developing clinical symptoms of multiple sclerosis (MS) in people with radiologically isolated syndrome (RIS)?

Findings In this cohort of 36 people with RIS, a higher PRL count was associated with a shorter time to developing clinical symptoms of MS and was an independent predictor of symptom onset; these findings were validated in an independent cohort of 43 people with RIS.

Meaning Results show that PRLs may have prognostic utility for risk stratification and help guide treatment decisions in people with RIS, the earliest detectable stage of MS.

Complement C5 Inhibitor Ameliorates a Case of Dysferlinopathy

Complement inhibition showed promising clinical improvement in this single case of dysferlinopathy.


Dysferlinopathy is a rare autosomal recessively inherited myopathy, presenting as several phenotypes, including a proximal weakness dominant limb-girdle muscular dystrophy R2 phenotype and a distal weakness dominant Miyoshi distal myopathy phenotype.1,2 Muscle weakness usually emerges in young adulthood, followed by a progressive motor decline over the first decade, which tends to be more rapid in individuals with earlier onset.3 Dysferlinopathy is caused by pathogenic variants of the DYSF gene that impair function of dysferlin, a protein that cooperates with others to repair membranes and restore skeletal muscle integrity after injury.4

To date, no effective treatment for dysferlinopathy has been clinically validated. Promising approaches, including exon skipping and gene editing targeting the DYSF gene, as well as myoblast transplantation, are still under investigation in preclinical models.5 Although dysferlinopathy often presents with inflammatory features on muscle pathology and is prone to misdiagnosis as myositis, it is characterized by the absence of focal MHC-I expression and complement C5b-9 deposition on nonnecrotic sarcolemma, which help distinguish it from other muscular dystrophies and inflammatory myopathies.6,7 Specially, complement C3 gene knockout in dysferlin-deficient mice has been demonstrated being able to reverse muscle pathology and improve motor function in the previous animal research.

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