Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.

Secondary bile acid derivatives are contributors to the fecal bile acid pool and associated with bile acid modulating nutrients.

Objective: Accumulation of hydrophobic bile acids is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic bile acids. The impact of diet on secondary bile acid (BA) derivative production has not been determined.

Cycle Effects Are Not Universal: A Case Study of Urinary C-Reactive Protein Concentrations in Rural Polish and Polish American Samples.

Objectives: We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent.

Single-Cell Peptide Profiling to Distinguish Stickleback Ecotypes with Divergent Breeding Behavior.

Variation in parenting behavior is widespread across the animal kingdom, both within and between species. There are two ecotypes of the three-spined stickleback fish () that exhibit dramatic differences in their paternal behavior. Males of the common ecotype are highly attentive fathers, tending to young from eggs to fry, while males of the white ecotype desert offspring as eggs.

A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.

An abnormal expansion of a GGGGCC (GC) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the GC repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits.

Yerba mate () genome provides new insights into convergent evolution of caffeine biosynthesis.

Yerba mate (YM, ) is an economically important crop marketed for the elaboration of mate, the third-most widely consumed caffeine-containing infusion worldwide. Here, we report the first genome assembly of this species, which has a total length of 1.06 Gb and contains 53,390 protein-coding genes.

Epistatic hotspots organize antibody fitness landscape and boost evolvability.

The course of evolution is strongly shaped by interaction between mutations. Such epistasis can yield rugged sequence-function maps and constrain the availability of adaptive paths. While theoretical intuition is often built on global statistics of large, homogeneous model landscapes, mutagenesis measurements necessarily probe a limited neighborhood of a reference genotype.

Egg shape and color mediate acceptance thresholds in diverse avian host species with different rates of antiparasitic egg rejection.

Eggshell recognition in parental birds is vital for nest management, defense against brood parasitism, optimal embryonic development, and minimizing disease and predation risks. This process relies on acceptance thresholds balancing the risk of rejecting own eggs against the benefit of excluding foreign ones, following signal detection theory. We investigated the role of object shape in egg rejection decisions among three host species of the brown-headed cowbird (Molothrus ater), each with a varying known response to parasitic eggs.

Incidence of alternative splicing associated with sex and opioid effects in the axon guidance pathway.

The alternative splicing of a gene results in distinct transcript isoforms that can result in proteins that differ in function. Alternative splicing processes are prevalent in the brain, have varying incidence across brain regions, and can present sexual dimorphism. Exposure to opiates and other substances of abuse can also alter the type and incidence of the splicing process and the relative abundance of the isoforms produced.

Enhanced detection for antibiotic resistance genes in wastewater samples using a CRISPR-enriched metagenomic method.

The spread of antibiotic resistance genes (ARGs) in the environment is a global public health concern. To date, over 5000 genes have been identified to express resistance to antibiotics. ARGs are usually low in abundance for wastewater samples, making them difficult to detect.

Trojan horse peptide conjugates remodel the activity spectrum of clinical antibiotics.

Infections caused by gram-negative pathogens continue to be a major risk to human health because of the innate antibiotic resistance endowed by their unique cell membrane architecture. Nature has developed an elegant solution to target gram-negative strains, namely by conjugating toxic antibiotic warheads to a suitable carrier to facilitate the active import of the drug to a specific target organism. Microcin C7 (McC) is a Trojan horse peptide-conjugated antibiotic that specifically targets enterobacteria by exploiting active import through oligopeptide transport systems.

Integration of metabolomics and other omics: from microbes to microbiome.

Metabolomics is a cutting-edge omics technology that identifies metabolites in organisms and their environments and tracks their fluctuations. This field has been extensively utilized to elucidate previously unknown metabolic pathways and to identify the underlying causes of metabolic changes, given its direct association with phenotypic alterations. However, metabolomics inherently has limitations that can lead to false positives and false negatives.

Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants.

Organoids are multicellular structures formed from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system.

Increasing Rubisco as a simple means to enhance photosynthesis and productivity now without lowering nitrogen use efficiency.

Global demand for food may rise by 60% mid-century. A central challenge is to meet this need using less land in a changing climate. Nearly all crop carbon is assimilated through Rubisco, which is catalytically slow, reactive with oxygen, and a major component of leaf nitrogen.

Seasonal influenza a virus lineages exhibit divergent abilities to antagonize interferon induction and signaling.

The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells is responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection.

Photosynthetic directed endosymbiosis to investigate the role of bioenergetics in chloroplast function and evolution.

Cyanobacterial photosynthesis (to produce ATP and NADPH) might have played a pivotal role in the endosymbiotic evolution to chloroplast. However, rather than meeting the ATP requirements of the host cell, the modern-day land plant chloroplasts are suggested to utilize photosynthesized ATP predominantly for carbon assimilation. This is further highlighted by the fact that the plastidic ADP/ATP carrier translocases from land plants preferentially import ATP.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Chemoenzymatic Synthesis Planning Guided by Reaction Type Score.

Thanks to the growing interest in computer-aided synthesis planning (CASP), a wide variety of retrosynthesis and retrobiosynthesis tools have been developed in the past decades. However, synthesis planning tools for multistep chemoenzymatic reactions are still rare despite the widespread use of enzymatic reactions in chemical synthesis. Herein, we report a reaction type score (RTscore)-guided chemoenzymatic synthesis planning (RTS-CESP) strategy.

Differential antigenic imprinting effects between influenza H1N1 hemagglutinin and neuraminidase in a mouse model.

Unlabelled: Understanding how immune history influences influenza immunity is essential for developing effective vaccines and therapeutic strategies. This study examines the antigenic imprinting of influenza hemagglutinin (HA) and neuraminidase (NA) using a mouse model with sequential infections by H1N1 virus strains exhibiting substantial antigenic differences in HA. In our pre-2009 influenza infection model, we observed that mice with more extensive infection histories produced higher levels of functional NA-inhibiting antibodies (NAI).

Late Pleistocene onset of mutualistic human/canid ( spp.) relationships in subarctic Alaska.

Large canids (wolves, dogs, and coyote) and people form a close relationship in northern (subarctic and arctic) socioecological systems. Here, we document the antiquity of this bond and the multiple ways it manifested in interior Alaska, a region key to understanding the peopling of the Americas and early northern lifeways. We compile original and existing genomic, isotopic, and osteological canid data from archaeological, paleontological, and modern sites.

The low enoyl-acyl carrier protein reductase activity of FabI2 is responsible for the high unsaturated fatty acid composition in Sinorhizobium meliloti.

Background: Sinorhizobium meliloti is noted for its exceptional capacity to produce unsaturated fatty acids (UFAs). Earlier studies have indicated that S. meliloti primarily employs the FabA-FabB pathway for UFA synthesis, however, the mechanisms remain elusive.