A protocol for the use of cloud-based quantum computers for logical network analysis of biological systems.

Boolean networks are commonly used in systems biology to dynamically model gene regulatory interactions. Here, we present a protocol for implementing Boolean network dynamics as quantum circuits. We describe steps for accessing cloud-based quantum processing units offered by IBM and IonQ and downloading and parsing logic for gene regulatory networks.

Evolutionary paths to mammalian longevity through the lens of gene expression.

The natural variation in mammalian longevity and its underlying mechanisms remain an active area of aging research. In the latest issue of The EMBO Journal, Liu et al (2023) analyze gene expression levels in 103 mammalian species across three tissues, revealing tissue-specific associations between gene expression patterns and longevity. Remarkably, the study suggests that methionine restriction, a strategy shown to increase lifespan, may extend beyond artificial interventions and is similarly employed by natural selection.

Extensive pedigrees reveal the social organization of a Neolithic community.

Social anthropology and ethnographic studies have described kinship systems and networks of contact and exchange in extant populations. However, for prehistoric societies, these systems can be studied only indirectly from biological and cultural remains. Stable isotope data, sex and age at death can provide insights into the demographic structure of a burial community and identify local versus non-local childhood signatures, archaeogenetic data can reconstruct the biological relationships between individuals, which enables the reconstruction of pedigrees, and combined evidence informs on kinship practices and residence patterns in prehistoric societies.

Turquoise killifish: A natural model of age-dependent brain degeneration.

Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that display a wide range of spontaneous age-related changes, including onset of cancer, reduced mobility, and cognitive decline. Here, we focus on describing the phenotypic spectrum of the aging killifish brain. As turquoise killifish age, their dopaminergic and noradrenergic neurons undergo a significant decline in number.

A dysfunctional miR-1-TRPS1-MYOG axis drives ERMS by suppressing terminal myogenic differentiation.

Rhabdomyosarcoma is the most common pediatric soft tissue tumor, comprising two major subtypes: the PAX3/7-FOXO1 fusion-negative embryonal and the PAX3/7-FOXO1 fusion-positive alveolar subtype. Here, we demonstrate that the expression levels of the transcriptional repressor TRPS1 are specifically enhanced in the embryonal subtype, resulting in impaired terminal myogenic differentiation and tumor growth. During normal myogenesis, expression levels of TRPS1 have to decrease to allow myogenic progression, as demonstrated by overexpression of TRPS1 in myoblasts impairing myotube formation.

2019 Association of Biomolecular Resource Facilities Multi-Laboratory Data-Independent Acquisition Proteomics Study.

Despite the advantages of fewer missing values by collecting fragment ion data on all analytes in the sample as well as the potential for deeper coverage, the adoption of data-independent acquisition (DIA) in proteomics core facility settings has been slow. The Association of Biomolecular Resource Facilities conducted a large interlaboratory study to evaluate DIA performance in proteomics laboratories with various instrumentation. Participants were supplied with generic methods and a uniform set of test samples.

Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity.

Streptomyces polyketides mediate bacteria-fungi interactions across soil environments.

Although the interaction between prokaryotic and eukaryotic microorganisms is crucial for the functioning of ecosystems, information about the processes driving microbial interactions within communities remains scarce. Here we show that arginine-derived polyketides (arginoketides) produced by Streptomyces species mediate cross-kingdom microbial interactions with fungi of the genera Aspergillus and Penicillium, and trigger the production of natural products. Arginoketides can be cyclic or linear, and a prominent example is azalomycin F produced by Streptomyces iranensis, which induces the cryptic orsellinic acid gene cluster in Aspergillus nidulans.

Membrane shapers from two distinct superfamilies cooperate in the development of neuronal morphology.

Membrane-shaping proteins are driving forces behind establishment of proper cell morphology and function. Yet, their reported structural and in vitro properties are noticeably inconsistent with many physiological membrane topology requirements. We demonstrate that dendritic arborization of neurons is powered by physically coordinated shaping mechanisms elicited by members of two distinct classes of membrane shapers: the F-BAR protein syndapin I and the N-Ank superfamily protein ankycorbin.

Protecting RNA quality for spatial transcriptomics while improving immunofluorescent staining quality.

In comparison to bulk sequencing or single cell sequencing, spatial transcriptomics preserves the spatial information in tissue slices and can even be mapped to immunofluorescent stainings, allowing translation of gene expression information into their spatial context. This enables to unravel complex interactions of neighboring cells or to link cell morphology to transcriptome data. The 10× Genomics Visium platform offers to combine spatial transcriptomics with immunofluorescent staining of cryo-sectioned tissue slices.

Evolution, mechanism and limits of dietary restriction induced health benefits & longevity.

Dietary restriction (DR) is the most powerful intervention to enhance health and lifespan across species. However, recent findings indicate that DR started in late life has limited capacity to induce health benefits. Age-dependent changes that impair DR at old age remain to be delineated.

Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a severe and frequent complication of sepsis causing delirium, coma, and long-term cognitive dysfunction. We identified microglia and C1q complement activation in hippocampal autopsy tissue of patients with sepsis and increased C1q-mediated synaptic pruning in a murine polymicrobial sepsis model. Unbiased transcriptomics of hippocampal tissue and isolated microglia derived from septic mice revealed an involvement of the innate immune system, complement activation, and up-regulation of lysosomal pathways during SAE in parallel to neuronal and synaptic damage.

Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration.

Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process.

ABRAXAS1 orchestrates BRCA1 activities to counter genome destabilizing repair pathways-lessons from breast cancer patients.

It has been well-established that mutations in BRCA1 and BRCA2, compromising functions in DNA double-strand break repair (DSBR), confer hereditary breast and ovarian cancer risk. Importantly, mutations in these genes explain only a minor fraction of the hereditary risk and of the subset of DSBR deficient tumors. Our screening efforts identified two truncating germline mutations in the gene encoding the BRCA1 complex partner ABRAXAS1 in German early-onset breast cancer patients.

The African killifish: A short-lived vertebrate model to study the biology of sarcopenia and longevity.

Sarcopenia, the age-related decline in muscle function, places a considerable burden on health-care systems. While the stereotypic hallmarks of sarcopenia are well characterized, their contribution to muscle wasting remains elusive, which is partly due to the limited availability of animal models. Here, we have performed cellular and molecular characterization of skeletal muscle from the African killifish-an extremely short-lived vertebrate-revealing that while many characteristics deteriorate with increasing age, supporting the use of killifish as a model for sarcopenia research, some features surprisingly reverse to an "early-life" state in the extremely old stages.

Microbiome and immuno-metabolic dysregulation in patients with major depressive disorder with atypical clinical presentation.

Depression is highly prevalent (6% 1-year prevalence) and is the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This is most likely related to a heterogeneous clinical presentation of major depression disorder (MDD), suggesting different manifestations of underlying pathophysiological mechanisms.

Molecular-defined clonal evolution in patients with classical myeloproliferative neoplasms.

Classical myeloproliferative neoplasms (MPNs) are characterized by distinct clinical phenotypes. The discovery of driver mutations in JAK2, CALR and MPL genes provided new insights into their pathogenesis. Next-generation sequencing (NGS) identified additional somatic mutations, most frequently in epigenetic modulator genes.

A computational framework for testing hypotheses of the minimal mechanical requirements for cell aggregation using early annual killifish embryogenesis as a model.

Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface.

UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells.

Nonsense-mediated mRNA decay (NMD) is a highly conserved regulatory mechanism of post-transcriptional gene expression in eukaryotic cells. NMD plays essential roles in mRNA quality and quantity control and thus safeguards multiple biological processes including embryonic stem cell differentiation and organogenesis. UPF3A and UPF3B in vertebrate species, originated from a single gene in yeast, are key factors in the NMD machinery.

Epidermal Growth Factor Receptor in Hepatic Endothelial Cells Suppresses MCP-1-Dependent Monocyte Recruitment in Diabetes.

Insulin resistance is a compromised response to insulin in target tissues such as liver. Emerging evidence shows that vascular endothelial cells (ECs) are critical in mediating glucose metabolism. However, how liver ECs can regulate inflammation in the setting of insulin resistance is still unknown.