New Frontiers: Umbilical Cord Mesenchymal Stem Cells Uncover Developmental Roots and Biological Underpinnings of Obesity Susceptibility.

Purpose Of Review: To review evidence supporting human umbilical cord mesenchymal stem cells (UC-MSC) as an innovative model system advancing obesity precision medicine.

Recent Findings: Obesity prevalence is increasing rapidly and exposures during fetal development can impact individual susceptibility to obesity. UC-MSCs exhibit heterogeneous phenotypes associated with maternal exposures and predictive of child cardiometabolic outcomes.

The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice.

Targeting the cardiomyocyte cell cycle is a promising strategy for heart repair following injury. Here, we identify a cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) as a regulator of cardiomyocyte proliferation. Genetic ablation or antagomir-mediated knockdown of CRAPIR in mice impairs cardiomyocyte proliferation and reduces heart regenerative potential.

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

The clinical effect of bone perforations in periodontal regeneration and alveolar socket preservation: a systematic review with meta-analysis.

Objectives: The present systematic review aimed to evaluate if cortical bone perforation is effective in enhancing periodontal surgery and guided bone regeneration (GBR) in humans.

Materials And Methods: Electronic search was performed in PubMed, Scopus and Cochrane CENTRAL up to October 31st, 2023. Grey literature was also searched.

Neural mechanisms of relational learning and fast knowledge reassembly in plastic neural networks.

Humans and animals have a striking ability to learn relationships between items in experience (such as stimuli, objects and events), enabling structured generalization and rapid assimilation of new information. A fundamental type of such relational learning is order learning, which enables transitive inference (if A > B and B > C, then A > C) and list linking (A > B > C and D > E > F rapidly 'reassembled' into A > B > C > D > E > F upon learning C > D). Despite longstanding study, a neurobiologically plausible mechanism for transitive inference and rapid reassembly of order knowledge has remained elusive.

"They knew the same struggles": perceptions of a group coping skills intervention in patients with chronic graft-versus-host disease.

Purpose: Chronic graft-versus-host-disease (cGVHD), an inflammatory condition affecting allogeneic hematopoietic cell transplantation (HCT) survivors, is associated with a range of debilitating physical and psychological sequela. Yet HCT recipients with cGVHD are virtually absent from survivorship intervention research. We conducted a randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multidisciplinary group coping skills intervention (Horizons) tailored to meet these patients' unique needs.

Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis.

Sepsis is a leading cause of death worldwide, with most patient mortality stemming from lingering immunosuppression in sepsis survivors. This is due in part to immune dysfunction resulting from monocyte exhaustion, a phenotype of reduced antigen presentation, altered CD14/CD16 inflammatory subtypes, and disrupted cytokine production. Whereas previous research demonstrated improved sepsis survival in Ticam2 mice, the contribution of TICAM2 to long-term exhaustion memory remained unknown.

Modeling the impact of extreme weather events and future climate on the radiologically contaminated sites of Enewetak Atoll.

Enewetak Atoll underwent 43 historical nuclear tests from 1948 to 1958, including the first hydrogen bomb test, resulting in a substantial nuclear material fallout contaminating the Atoll and the lagoon waters. The radionuclide fallout material deposited in lagoon sediments and soil on the islands will remain for decades to come. With intensifying climate and extreme weather events, the possibility of redistribution of deposited radionuclide material has become a great concern.

Environmental gradients shape genetic variation in the desert moss, Syntrichia caninervis Mitt. (Pottiaceae).

The moss Syntrichia caninervis Mitt. is distributed throughout drylands globally, and often anchors ecologically significant communities known as biological soil crusts (biocrusts). The species occupies a variety of dryland habitats with varying levels of drought and temperature stress, suggesting the potential for ecological specialization within S.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC).

Asymmetric sensitivity of boreal forest resilience to forest gain and loss.

Forest gains and losses may have unequal effects on forest resilience, particularly given their distinct temporal dynamics. Here, we quantify the sensitivities of boreal forest resilience to forest cover gain and loss using a resilience indicator derived from the temporal autocorrelation (TAC) of the kernel normalized difference vegetation index from 2000 to 2020. Our findings unveil pronounced asymmetric sensitivities, with stronger sensitivity to forest loss (-4.

Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

Continental influx and pervasive matrilocality in Iron Age Britain.

Roman writers found the relative empowerment of Celtic women remarkable. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male.

Methane emissions from the Nord Stream subsea pipeline leaks.

The amount of methane released to the atmosphere from the Nord Stream subsea pipeline leaks remains uncertain, as reflected in a wide range of estimates. A lack of information regarding the temporal variation in atmospheric emissions has made it challenging to reconcile pipeline volumetric (bottom-up) estimates with measurement-based (top-down) estimates. Here we simulate pipeline rupture emission rates and integrate these with methane dissolution and sea-surface outgassing estimates to model the evolution of atmospheric emissions from the leaks.

Structural insights into RNA cleavage by PIWI Argonaute.

Argonaute proteins are categorized into AGO and PIWI clades. Across most animal species, AGO-clade proteins are widely expressed in various cell types, and regulate normal gene expression. By contrast, PIWI-clade proteins predominantly function during gametogenesis to suppress transposons and ensure fertility.

Illuminating the multidimensional contributions of small-scale fisheries.

Sustainable development aspires to "leave no one behind". Even so, limited attention has been paid to small-scale fisheries (SSF) and their importance in eradicating poverty, hunger and malnutrition. Through a collaborative and multidimensional data-driven approach, we have estimated that SSF provide at least 40% (37.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Targeting protein-ligand neosurfaces with a generalizable deep learning tool.

Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.