Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea.

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections.

Hematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer.

Clonal hematopoiesis (CH) is defined as clonal expansion of mutant hematopoietic stem cells absent diagnosis of a hematologic malignancy. Presence of CH in solid tumor patients, including colon cancer, correlates with shorter survival. We hypothesized that bone marrow-derived cells with heterozygous loss-of-function mutations of DNMT3A, the most common genetic alteration in CH, contribute to the pathogenesis of colon cancer.

Western diet influences on microbiome and carcinogenesis.

The intestinal microbiota composition and associated bioactivities are sensitive to various modifier cues such as stress, inflammation, age, life-style and nutrition, which in turn are associated with susceptibility to developing cancer. Among these modifiers, diet has been shown to influence both microbiota composition as well as being an important source of microbial-derived compounds impacting the immunological, neurological and hormonal systems. Thus, it is necessary to take a holistic view when considering effect of diet on health and diseases.

Resolving Cross-modal Semantic Interference among Object Concepts Requires Medial Temporal Lobe Cortex.

The ability to flexibly categorize object concepts is essential to semantic cognition because the features that make two objects similar in one context may be irrelevant and even constitute interference in another. Thus, adaptive behavior in complex and dynamic environments requires the resolution of feature-based interference. In the current case study, we placed visual and functional semantic features in opposition across object concepts in two categorization tasks.

A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults.

The act of remembering an everyday experience influences how we interpret the world, how we think about the future, and how we perceive ourselves. It also enhances long-term retention of the recalled content, increasing the likelihood that it will be recalled again. Unfortunately, the ability to recollect event-specific details and reexperience the past tends to decline with age.

Intestinal microbiota modulates pancreatic carcinogenesis through intratumoral natural killer cells.

Preclinical data demonstrate that the gut microbiota can promote pancreatic ductal adenocarcinoma (PDAC), but mechanisms remain unclear. We hypothesized that intestinal microbiota alters anti-tumor innate immunity response to facilitate PDAC progression. Human PDAC L3.

Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort.

Background: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored.

Methods: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria.

The microbiome, gastrointestinal cancer, and immunotherapy.

The gastrointestinal tract greatly contributes to global cancer burden and cancer-related deaths. The microbiota represents the population of microorganisms that live in and around the body, located primarily in the gastrointestinal tract. The microbiota has been implicated in colorectal cancer development and progression, but its role in cancer therapy for the gastrointestinal tract is less defined, especially for extra-intestinal cancers.

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort.

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA.

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors.

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines.

Amending microbiota by targeting intestinal inflammation with TNF blockade attenuates development of colorectal cancer.

Intestinal inflammation and microbiota are two important components of colorectal cancer (CRC) etiology. However, it is not clear how tuning inflammation using clinically relevant anti-inflammatory treatment impacts microbiota or whether this consequently influences CRC outcome. Here, using chemically induced (DSS/ ) and spontaneous ( ) mouse CRC models colonized by colibactin-producing , we established the role of microbiota in mediating the antitumorigenic effect of anti-tumor necrosis factor (TNF) therapy.

Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer.

Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing on colon tissues and 16S and small RNA sequencing on stools from germfree (GF) and gnotobiotic ; mice associated with microbes from biofilm-positive human CRC tumor (BF+T) and biofilm-negative healthy (BF-bx) tissues.

Existing semantic knowledge provides a schematic scaffold for inference in early cognitive decline, but not in amnestic MCI.

Healthy older adults show impaired relational learning, but improved transitive expression when inferences are made across pre-experimentally known premise relations. Here, we used the transitivity paradigm to ask whether the organizational structure within schemas facilitates the bridging of relations for novel inference for otherwise healthy older adults who are exhibiting early signs of cognitive decline ("at-risk" older adults), and individuals with single- or multiple-domain amnestic mild cognitive impairment (aMCI). Relational learning was impaired in the two older adult groups, but transitive expression was facilitated by prior semantic knowledge of relations.

Microbial Colonization Coordinates the Pathogenesis of a Klebsiella pneumoniae Infant Isolate.

Enterobacteriaceae are among the first colonizers of neonate intestine. Members of this family, such as Escherichia and Klebsiella, are considered pathobionts and as such are capable of inducing local and systemic disease under specific colonization circumstances. Interplay between developing microbiota and pathogenic function of pathobionts are poorly understood.

promotes colorectal tumorigenesis through the action of cytolethal distending toxin.

Objective: produces a genotoxin, cytolethal distending toxin (CDT), which has DNAse activity and causes DNA double-strand breaks. Although infection has been shown to promote intestinal inflammation, the impact of this bacterium on carcinogenesis has never been examined.

Design: Germ-free (GF) mice, fed with 1% dextran sulfate sodium, were used to test tumorigenesis potential of CDT-producing .

Integrative and distinctive coding of visual and conceptual object features in the ventral visual stream.

A significant body of research in cognitive neuroscience is aimed at understanding how object concepts are represented in the human brain. However, it remains unknown whether and where the visual and abstract conceptual features that define an object concept are integrated. We addressed this issue by comparing the neural pattern similarities among object-evoked fMRI responses with behavior-based models that independently captured the visual and conceptual similarities among these stimuli.

Dissociable contributions of thalamic nuclei to recognition memory: novel evidence from a case of medial dorsal thalamic damage.

The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments in hippocampal-dependent tasks.

ClbM is a versatile, cation-promiscuous MATE transporter found in the colibactin biosynthetic gene cluster.

Multidrug transporters play key roles in cellular drug resistance to toxic molecules, yet these transporters are also involved in natural product transport as part of biosynthetic clusters in bacteria and fungi. The genotoxic molecule colibactin is produced by strains of virulent and pathobiont Escherichia coli and Klebsiella pneumoniae. In the biosynthetic cluster is a multidrug and toxic compound extrusion protein (MATE) proposed to transport the prodrug molecule precolibactin across the cytoplasmic membrane, for subsequent cleavage by the peptidase ClbP and cellular export.

MATE transport of the E. coli-derived genotoxin colibactin.

Various forms of cancer have been linked to the carcinogenic activities of microorganisms(1-3). The virulent gene island polyketide synthase (pks) produces the secondary metabolite colibactin, a genotoxic molecule(s) causing double-stranded DNA breaks(4) and enhanced colorectal cancer development(5,6). Colibactin biosynthesis involves a prodrug resistance strategy where an N-terminal prodrug scaffold (precolibactin) is assembled, transported into the periplasm and cleaved to release the mature product(7-10).

Examining the Role of the Human Hippocampus in Approach-Avoidance Decision Making Using a Novel Conflict Paradigm and Multivariate Functional Magnetic Resonance Imaging.

Unlabelled: Rodent models of anxiety have implicated the ventral hippocampus in approach-avoidance conflict processing. Few studies have, however, examined whether the human hippocampus plays a similar role. We developed a novel decision-making paradigm to examine neural activity when participants made approach/avoidance decisions under conditions of high or absent approach-avoidance conflict.