Intrinsic and extrinsic control impact motivation and outcome sensitivity: the role of anhedonia, stress, and anxiety.

Background: Motivated behaviors vary widely across individuals and are controlled by a range of environmental and intrinsic factors. However, due to a lack of objective measures, the role of intrinsic extrinsic control of motivation in psychiatric disorders remains poorly understood.

Methods: We developed a novel multi-factorial behavioral task that separates the distinct contributions of intrinsic extrinsic control, and determines their influence on motivation and outcome sensitivity in a range of contextual environments.

Ventral tegmental area integrity measured with high-resolution 7-Tesla MRI relates to motivation across depression and anxiety diagnoses.

The ventral tegmental area (VTA) is one of the major sources of dopamine in the brain and has been associated with reward prediction, error-based reward learning, volitional drive and anhedonia. However, precise anatomical investigations of the VTA have been prevented by the use of standard-resolution MRI, reliance on subjective manual tracings, and lack of quantitative measures of dopamine-related signal. Here, we combine ultra-high field 400 µm quantitative MRI with dopamine-related signal mapping, and a mixture of machine learning and supervised computational techniques to delineate the VTA in a transdiagnostic sample of subjects with and without depression and anxiety disorders.

An Early Examination: Psychological, Health, and Economic Correlates and Determinants of Social Distancing Amidst COVID-19.

Federal and local government agencies were quick to issue orders for residents to shelter-in-place in response to the COVID-19 outbreak. This study utilized data collected from Unacast Inc., spanning observations of 3,142 counties across 50 states and the District of Columbia ( = 230,846) from March 8, 2020 to April 13, 2020 ( = 104,930) and from April 14, 2020 to May 24, 2020 ( = 131,912) in a 3-level multilevel model to examine the correlates of social distancing behavior, as measured by the relative reduction in (1) distance traveled and (2) non-essential visitations since baseline pre-COVID-19 times.

Combinatorial CRISPR-Cas9 Metabolic Screens Reveal Critical Redox Control Points Dependent on the KEAP1-NRF2 Regulatory Axis.

The metabolic pathways fueling tumor growth have been well characterized, but the specific impact of transforming events on network topology and enzyme essentiality remains poorly understood. To this end, we performed combinatorial CRISPR-Cas9 screens on a set of 51 carbohydrate metabolism genes that represent glycolysis and the pentose phosphate pathway (PPP). This high-throughput methodology enabled systems-level interrogation of metabolic gene dispensability, interactions, and compensation across multiple cell types.

ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination.

Mitochondria as biosynthetic factories for cancer proliferation.

Unchecked growth and proliferation is a hallmark of cancer, and numerous oncogenic mutations reprogram cellular metabolism to fuel these processes. As a central metabolic organelle, mitochondria execute critical biochemical functions for the synthesis of fundamental cellular components, including fatty acids, amino acids, and nucleotides. Despite the extensive interest in the glycolytic phenotype of many cancer cells, tumors contain fully functional mitochondria that support proliferation and survival.

Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.

The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the epithelium are poorly understood. Here we show that p62 levels were reduced in the stroma of several tumors and that its loss in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism, resulting in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment.

Loss of myoferlin redirects breast cancer cell motility towards collective migration.

Cell migration plays a central role in the invasion and metastasis of tumors. As cells leave the primary tumor, they undergo an epithelial to mesenchymal transition (EMT) and migrate as single cells. Epithelial tumor cells may also migrate in a highly directional manner as a collective group in some settings.