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Biology subjects

Wall, C.

Publications and source records attributed to Wall, C..

3 recordsLinked to original sources

Epipelagic to mesopelagic variability of acoustic backscatter in the California Current

Mid-Trophic Level (MTL) organisms--including krill, forage fish, and mesopelagic fish-- are abundant in the California Current System (CCS) and play an essential role in transferring energy and biomass from primary producers to top predators. However, their spatiotemporal distribution and variability remain poorly understood, particularly with respect to vertical structure across epipelagic and mesopelagic habitats and coastal-offshore gradients. This lack of understanding emerges from both the complexity of MTL interactions with a heterogeneous environment and the challenges associated with sampling these organisms at high spatial and temporal resolution. To address this gap, we analyze 11 years of fisheries acoustic observations in the CCS (2006-2016) to characterize the spatiotemporal dynamics of MTLs as inferred from acoustic backscatter. Acoustic observations at 38 and 120 kHz, collected during day and night across depth strata from 15 to 495 m, reveal consistent cross-shore, seasonal, and latitudinal patterns in the backscatter of acoustically defined zooplankton, epipelagic fish, and mesopelagic fish communities. These patterns include: (1) weaker cross-shore gradients in mesopelagic relative to epipelagic communities; (2) a temporal succession among communities associated with seasonal upwelling; and (3) a multimodal latitudinal distribution with distinct coastal backscatter peaks. We further investigate relationships between acoustic backscatter and co-located environmental variables from in situ, remote sensing, and reanalysis products to elucidate plausible mechanisms underlying MTL dynamics. HighlightsO_LIFisheries acoustics resolve variability in mid-trophic communities C_LIO_LIEleven years of backscatter reveal consistent patterns in the California Current C_LIO_LIEpipelagic backscatter declines faster from the coast to offshore than mesopelagic C_LIO_LISeasonal changes in community composition are linked to upwelling dynamics C_LIO_LIBackscatter exhibits multimodal latitudinal distributions with distinct peaks C_LI

ecology↗

NNMT promotes tubular senescence and fibrosis in chronic kidney disease

Chronic kidney disease (CKD) is a major global health issue, projected to become the fifth leading cause of mortality by 2040. Renal tubular cell senescence is a key driver of kidney fibrosis, the final manifestation of CKD. However, current treatment strategies, do not target senescent cells, as the underlying mechanisms driving this dysfunctional phenotype remain poorly described. Here, we identify nicotinamide-N-methyltransferase (NNMT), as a critical mediator of tubular senescence and fibrosis in CKD. Using human RNAseq profiles of CKD, we show that NNMT expression in the renal tubulointerstitium is strongly associated with CKD pathology and transcriptional signatures of cellular senescence. In human diabetic kidney disease biopsies, NNMT levels correlate with the senescence marker p21, kidney function decline, and fibrosis. Spatial transcriptomics further highlights that NNMT-positive tubules are senescent, fibrotic, and surrounded by a pro-inflammatory microenvironment. Preclinical models of early-stage CKD, show upregulation of NNMT and association with senescence. Overexpression of NNMT in TGF-{beta}-stimulated tubular epithelial cells promotes senescence and partial epithelial-to-mesenchymal transition (EMT), while inhibition of NNMT in kidney cells and organoids is protective. Altogether, we identify NNMT as a novel therapeutic target in the early stages of CKD with the potential to reduce tubular senescence, fibrosis and significantly slow disease progression.

cell biology↗

The Flexible, Versatile and Fast GreGT Platform of Fully Deleted Helper-Virus Independent Adenoviral Vectors

Gene transfer (GT) vectors have diverse applications. They have been used to restore cellular activities by reconstituting normal cellular functions, by delivering therapeutic compounds, and by priming immune responses as genetic vaccines. Viruses, natures gene delivery vehicles, have formed the basis of most GT vectors. The biology of the underlying virus may, however, hamper their use. For instance, retroviral vectors with their ability to integrate into the genome, may cause malignant transformations. Vectors designed as minor variants of the relatively benign, yet complex adenovirus (Ad) excite vigorous immune responses, thus limiting their therapeutic effects. Deleting Ad vectors of all endogenous Ad genes brought their beneficial features to the front, such as their ability to transduce cells of many types with high efficiency and to deliver large genetic payloads. Earlier production schemes of fully deleted Ad (fdAd) vectors depended on helper virus constructs to deliver the vector production information in trans. They suffered from contaminations with the helper virus or the recombination of replication competent adenoviruses (RCA). We previously developed a novel transfection-based helper virus-independent Ad vector encapsidation technology that avoided these pitfalls. It was built on a vector genome and a vector packaging module. We have now optimized our approach into the GreGT plug-and-play platform so that a new vector can be delivered in about four weeks. The GreGT system is built upon a set of base vector genome modules that can be quickly loaded with a new application, and a set of packaging modules that allow their encapsidation into capsids of different Ad serotypes. As both components can be freely combined, the GreGT platform is endowed with high degrees of flexibility and versatility. Finally, the deletion of all endogenous Ad genes from the vector genome limits the interference by anti-Ad immune responses. It also increases the genetic payload capacity to levels unique to this system.

molecular biology↗