Nuclear morphology is shaped by loop-extrusion programs.

It is well established that neutrophils adopt malleable polymorphonuclear shapes to migrate through narrow interstitial tissue spaces1-3. However, how polymorphonuclear structures are assembled remains unknown4. Here we show that in neutrophil progenitors, halting loop extrusion-a motor-powered process that generates DNA loops by pulling in chromatin5-leads to the assembly of polymorphonuclear genomes. Specifically, we found that in mononuclear neutrophil progenitors, acute depletion of the loop-extrusion loading factor nipped-B-like protein (NIPBL) induced the assembly of horseshoe, banded, ringed and hypersegmented nuclear structures and led to a reduction in nuclear volume, mirroring what is observed during the differentiation of neutrophils. Depletion of NIPBL also induced cell-cycle arrest, activated a neutrophil-specific gene program and conditioned a loss of interactions across topologically associating domains to generate a chromatin architecture that resembled that of differentiated neutrophils. Removing NIPBL resulted in enrichment for mega-loops and interchromosomal hubs that contain genes associated with neutrophil-specific enhancer repertoires and an inflammatory gene program. On the basis of these observations, we propose that in neutrophil progenitors, loop-extrusion programs produce lineage-specific chromatin architectures that permit the packing of chromosomes into geometrically confined lobular structures. Our data also provide a blueprint for the assembly of polymorphonuclear structures, and point to the possibility of engineering de novo nuclear shapes to facilitate the migration of effector cells in densely populated tumorigenic environments.

The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

Preparation and characterization of poly(vinyl pyrrolidone)/cellulose nanofiber/Aloe Vera composites as a biocompatible hydrating facial mask.

This study aimed to enhance the properties of polyvinylpyrrolidone (PVP) for use as biocompatible facial masks. To achieve this, nanofibers were developed by blending PVP with cellulose nanofibers (CNFs) and Aloe vera (AV) powder using electrospinning. The results showed that incorporating CNFs and AV into the PVP matrix led to the formation of smooth and uniform nanofibers. In particular, adding 3-6 wt% AV powder in PVP/CNF composites improved fiber diameter distribution and uniformity compared to pure PVP. The PVP/CNF/AV nanofibers exhibited desirable properties for facial mask applications. They displayed 86-93 % porosity, which allowed for efficient moisture absorption capacity of up to 1829 %, and excellent water vapor permeability rate of 3.92 g/m2h. The mechanical properties of the electrospun nanofiber composites were evaluated through tensile testing. The results showed that Young's modulus values decreased progressively with the addition of CNFs and AV powder to the PVP polymer matrix, indicating a plasticizing effect that enhances flexibility. The fracture strain remained similar across all composites, suggesting that CNFs and AV did not significantly weaken the PVP matrix. The tensile strength initially increased with CNF addition but decreased with incremental AV loading. Biocompatibility studies revealed that all nanofibers exhibited excellent fibroblast viability, surpassing 98 %. This indicates that incorporating CNFs and AV did not compromise cell viability, further highlighting the suitability of the PVP/CNF/AV composites for facial mask applications.