Publications by authors named "Cuthbert B"

Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood.

View Article and Find Full Text PDF

(Mtb) is the causative agent of tuberculosis, the world's deadliest infectious disease. Mtb uses a variety of mechanisms to evade the human host's defenses and survive intracellularly. Mtb's oxidative stress response enables Mtb to survive within activated macrophages, an environment with reactive oxygen species and low pH.

View Article and Find Full Text PDF
Article Synopsis
  • Advanced glycation end-products (AGE) are harmful protein modifications linked to serious health issues like neurodegenerative diseases, heart disease, and diabetes, caused by toxic byproducts of glucose metabolism.
  • Research reveals that AGE crosslinking activates a specific antibacterial enzyme in the bacteria Enterobacter cloacae, which is linked through a unique interaction between two amino acids.
  • The study highlights that glycation can stabilize protein structures, especially in environments where traditional stabilizing methods (like disulfide bonds) are not effective, suggesting broader implications for protein engineering.
View Article and Find Full Text PDF
Article Synopsis
  • Current mental disorder classifications are based on convention and symptom clusters rather than biological mechanisms, leading to significant overlap and variability in diagnoses.
  • There is a need for a new diagnostic framework that incorporates neurobiology to enhance treatment options and help patients better understand their illnesses.
  • The ECNP New Frontiers Meeting 2024 aims to establish a roadmap for improved precision diagnostics by focusing on innovative technologies, the biology of mental illness, and translating this knowledge into effective treatment strategies.*
View Article and Find Full Text PDF

Whole-report working memory tasks provide a measure of recall for all stimuli in a trial and afford single-trial analyses that are not possible with single-report delayed estimation tasks. However, most whole-report studies assume that trial stimuli are encoded and reported independently, and they do not consider the relationships between stimuli presented and reported within the same trial. Here, we present the results of two independently conducted whole-report experiments.

View Article and Find Full Text PDF

The tuberculosis (TB) emergency has been a pressing health threat for decades. With the emergence of drug-resistant TB and complications from the COVID-19 pandemic, the TB health crisis is more serious than ever. Mycobacterium tuberculosis (Mtb), the causative agent of TB, requires iron for its survival.

View Article and Find Full Text PDF
Article Synopsis
  • Mycobacterium tuberculosis (Mtb) is a major health threat, especially with rising drug-resistant strains, making it crucial to find new treatments targeting its iron acquisition mechanisms.
  • This study investigates the roles of two periplasmic binding proteins, FecB and FecB2, in Mtb's ability to acquire iron, finding that FecB specifically binds to the Mtb siderophore and has a crucial interaction with the iron acquisition system.
  • The researchers determined the 3D structures of FecB and FecB2, revealing different binding features, and identified key interactions that suggest FecB is important for both siderophore and heme uptake in Mtb.
View Article and Find Full Text PDF

Many Gram-negative bacteria use CdiA effector proteins to inhibit the growth of neighboring competitors. CdiA transfers its toxic CdiA-CT region into the periplasm of target cells, where it is released through proteolytic cleavage. The N-terminal cytoplasm-entry domain of the CdiA-CT then mediates translocation across the inner membrane to deliver the C-terminal toxin domain into the cytosol.

View Article and Find Full Text PDF

The integration of developmental processes is essential for a full understanding of psychopathology. The National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) provide a scaffold on which to organize the components and processes of psychopathology and to detail behavioral and biological disruptions in developmental processes gone awry. This special section on Integrating Developmental Psychopathology With the RDoC Framework provides the opportunity to comment on five extraordinary developmental psychopathology articles that report results and theory integral to RDoC.

View Article and Find Full Text PDF

Background: In 2013, a few years after the launch of the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative, Cuthbert and Insel published a paper titled "Toward the future of psychiatric diagnosis: the seven pillars of RDoC." The RDoC project is a translational research effort to encourage new ways of studying psychopathology through a focus on disruptions in normal functions (such as reward learning or attention) that are defined jointly by observable behavior and neurobiological measures. The paper outlined the principles of the RDoC research framework, including emphases on research that acquires data from multiple measurement classes to foster integrative analyses, adopts dimensional approaches, and employs novel methods for ascertaining participants and identifying valid subgroups.

View Article and Find Full Text PDF

The National Institute of Mental Health (NIMH) addressed in its 2008 Strategic Plan an emerging concern that the current diagnostic system was hampering translational research, as accumulating data suggested that disorder categories constituted heterogeneous syndromes rather than specific diseases. However, established practices in peer review placed high priority on extant disorders in evaluating grant applications for mental illness. To provide guidelines for alternative study designs, NIMH included a goal to develop new ways of studying psychopathology based on dimensions of measurable behavior and related neurobiological measures.

View Article and Find Full Text PDF

Bacteria live in complex communities and environments, competing for space and nutrients. Within their niche habitats, bacteria have developed various inter-bacterial mechanisms to compete and communicate. One such mechanism is contact-dependent growth inhibition (CDI).

View Article and Find Full Text PDF

Posttraumatic stress disorder (PTSD) is marked by alterations in emotional functioning, physiological reactivity, and attention. Neural reactivity to acoustic startle stimuli can be used to understand brain functions related to these alterations. Investigations of startle reactivity in PTSD have yielded inconsistent findings, which may reflect the heterogeneity of the disorder.

View Article and Find Full Text PDF

Several trends intersecting over the past two decades have generated increasing debate as to how the concepts of schizophrenia, the schizophrenia spectrum, and the psychotic disorders spectrum should be regarded. These trends are reflected in various areas of research such as genomics, neuroimaging, and data-driven computational studies of multiple response systems. Growing evidence suggests that schizophrenia represents a broad and heterogenous syndrome, rather than a specific disease entity, that is part of a multi-faceted psychosis spectrum.

View Article and Find Full Text PDF

Background: Schizophrenia (SCZ) is a neurodevelopmental disorder that leads to poor social function. Oxytocin (OXT), a neuropeptide involved in social cognition, is a potential therapeutic agent for alleviating social dysfunction. Therefore, we investigated the effects of intranasal oxytocin (IN-OXT) on emotional processes in experimental interactive social contexts in individuals with SCZ.

View Article and Find Full Text PDF

Tuberculosis (TB) is the most lethal bacterial infectious disease worldwide. It is notoriously difficult to treat, requiring a cocktail of antibiotics administered over many months. The dense, waxy outer membrane of the TB-causing agent, (Mtb), acts as a formidable barrier against uptake of antibiotics.

View Article and Find Full Text PDF

Chronic infection with (TOXO) results in microcysts in the brain that are controlled by inflammatory activation and subsequent changes in the kynurenine pathway. TOXO seropositivity is associated with a heightened risk of schizophrenia (SCZ) and with cognitive impairments. Latency of the acoustic startle response, a putative index of neural processing speed, is slower in SCZ.

View Article and Find Full Text PDF

Background: Schizophrenia (SCZ) is a severe, chronic illness characterized by psychotic symptoms and impairments in many cognitive domains. Dysregulation of brain derived neurotrophic factor (BDNF) is associated with the cognitive impairments seen in patients with SCZ. Given the growing literature supporting a positive effect of aerobic exercise on cognition in other populations, we hypothesized that a structured aerobic exercise program would improve cognitive and functional outcomes in subjects with SCZ, potentially mediated by increases in BDNF.

View Article and Find Full Text PDF

The Research Domain Criteria (RDoC) project constitutes a translational framework for psychopathology research, initiated by the National Institute of Mental Health in an attempt to provide new avenues for research to circumvent problems emerging from the use of symptom-based diagnostic categories in diagnosing disorders. The RDoC alternative is a focus on psychopathology based on dimensions simultaneously defined by observable behavior (including quantitative measures of cognitive or affective behavior) and neurobiological measures. Key features of the RDoC framework include an emphasis on functional dimensions that range from normal to abnormal, integration of multiple measures in study designs (which can foster computational approaches), and high priority on studies of neurodevelopment and environmental influences (and their interaction) that can contribute to advances in understanding the etiology of disorders throughout the lifespan.

View Article and Find Full Text PDF

Patients with schizophrenia exhibit psychomotor deficits that are associated with poor functional outcomes. One pathway that may be associated with psychomotor slowing is inflammation. Inflammatory markers have been shown to be elevated in patients with schizophrenia and are associated with psychomotor deficits in both animal and human studies.

View Article and Find Full Text PDF

Tissues and organs are composed of diverse cell types, which poses a major challenge for cell-type-specific profiling of gene expression. Current metabolic labeling methods rely on exogenous pyrimidine analogs that are only incorporated into RNA in cells expressing an exogenous enzyme. This approach assumes that off-target cells cannot incorporate these analogs.

View Article and Find Full Text PDF

In this article we aim at conceptual reconstruction of the historical background behind RDoC project. It incorporates some elements that have not heretofore been included in frameworks for psychopathology research. At the same time, however, RDoC - like any approach to mental illness - must grapple with longstanding challenges in addressing issues about the roles and relationships of mind, brain, and patients' reports in considering the nature of disorder.

View Article and Find Full Text PDF

The PRISM (Psychiatric Ratings using Intermediate Stratified Markers) project was funded under the auspices of the European Union Innovative Medicine Initiative (EU-IMI) to explore quantitative approaches to the biological and behavioral aspects of neuropsychiatric disorders. PRISM focuses specifically on social withdrawal, although its principles are applicable to a wide range of disorders. This commentary explores some of the major aspects of the PRISM design from the perspective of the Research Domain Criteria (RDoC) project initiated by the National Institute of Mental Health.

View Article and Find Full Text PDF