Consuming addictive drugs is often initially pleasurable, but escalating drug intake eventually recruits physiological anti-reward systems called opponent processes that cause tolerance and withdrawal symptoms. Opponent processes are fundamental for the addiction process, but their physiological basis is not fully characterized. Here, we propose an opponent processes mechanism centered on the endocrine stress response, the hypothalamic-pituitary-adrenal (HPA) axis. We focus on alcohol addiction, where the HPA axis is activated and secretes β-endorphin, causing euphoria and analgesia. Using a mathematical model, we show that slow changes in the functional mass of HPA glands act as an opponent process for β-endorphin secretion. The model explains hormone dynamics in alcohol addiction and experiments on alcohol preference in rodents. The opponent process is based on fold-change detection (FCD) where β-endorphin responses are relative rather than absolute; FCD confers vulnerability to addiction but has adaptive roles for learning. Our model suggests gland mass changes as potential targets for intervention in addiction.The Ganga basin includes some of the most densely populated areas in the world, in a region characterized by extremely high demographic and economic growth rates. Although anthropogenic pressure in this area is increasing, the pollution status of the Ganga is still poorly studied and understood. In the light of this, we have carried out a systematic literature review of the sources, levels and spatiotemporal distribution of organic pollutants in surface water and sediment of the Ganga basin, including for the first time emerging contaminants (ECs). We have identified 61 publications over the past thirty years, with data on a total of 271 organic compounds, including pesticides, industrial chemicals, and by-products, artificial sweeteners, pharmaceuticals, and personal care products (PPCPs). The most studied organic contaminants are pesticides, whereas knowledge of industrial compounds and PPCPs, among which some of the major ECs, is highly fragmentary. Most studies focus on the main channel of the Ganga, the Yamuna, the Gomti, and the deltaic region, while most of the Ganga's major tributaries, and the entire southern part of the catchment, have not been investigated. Hotspots of contamination coincide with major urban agglomerations, including Delhi, Kolkata, Kanpur, Varanasi, and Patna. Pesticides levels have decreased at most of the sites over recent decades, while potentially harmful concentrations of polychlorinated biphenyls (PCBs), organotin compounds (OTCs), and some PPCPs have been detected in the last ten years. Considering the limited geographical coverage of sampling and number of analyzed compounds, this review highlights the need for a more careful selection of locations, compounds and environmental matrices, prioritizing PPCPs and catchment-scale, source-to-sink studies.HIF1-alpha expression defines metabolic compartments in the developing heart, promoting glycolytic program in the compact myocardium and mitochondrial enrichment in the trabeculae. Nonetheless, its role in cardiogenesis is debated. To assess the importance of HIF1-alpha during heart development and the influence of glycolysis in ventricular chamber formation, herein we generated conditional knockout models of Hif1a in Nkx2.5 cardiac progenitors and cardiomyocytes. Deletion of Hif1a impairs embryonic glycolysis without influencing cardiomyocyte proliferation and results in increased mitochondrial number and transient activation of amino acid catabolism together with HIF2α and ATF4 upregulation by E12.5. Hif1a mutants display normal fatty acid oxidation program and do not show cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling and glycolysis are dispensable for mouse heart development and reveal the metabolic flexibility of the embryonic myocardium to consume amino acids, raising the potential use of alternative metabolic substrates as therapeutic interventions during ischemic events.Classically, hematopoietic stem cell (HSC) differentiation is assumed to occur via progenitor compartments of decreasing plasticity and increasing maturity in a specific, hierarchical manner. The classical hierarchy has been challenged in the past by alternative differentiation pathways. We abstracted experimental evidence into 10 differentiation hierarchies, each comprising 7 cell type compartments. By fitting ordinary differential equation models with realistic waiting time distributions to time-resolved data of differentiating HSCs from 10 healthy human donors, we identified plausible lineage hierarchies and rejected others. We found that, for most donors, the classical model of hematopoiesis is preferred. Surprisingly, multipotent lymphoid progenitor differentiation into granulocyte-monocyte progenitors is plausible in 90% of samples. An in silico analysis confirmed that, even for strong noise, the classical model can be identified robustly. Our computational approach infers differentiation hierarchies in a personalized fashion and can be used to gain insights into kinetic alterations of diseased hematopoiesis.An 82-year-old male was transferred for an abdominal CT scan for chronic cutaneous fistulation at the level of the right abdominal wall. Previous CT and ultrasound imaging described recurrent collections in the right abdominal wall, requiring CT guided abscess drainage. The abdominal CT scan revealed an abscess in between the internal oblique and transversus abdominis muscle layers of the right flank, with significant fat stranding and loss of the intermuscular fat planes ( Figure 1 ). Inside this abscess, we notice a spontaneous hyperdense nodular lesion (Hounsfield Units 130), which doesn't enhance after contrast injection ( Figure 1 arrow). Looking back at the previous CT scans we discern the presence of this hyperdense lesion, which tends to migrate over time over a small distance along the abdominal wall ( Figure 2 A-D arrow). We can trace this back on the numerous previous scans, with different local tissue reactions over time.  https://www.selleckchem.com/products/rvx-208.html  The first performed CT 8 years prior reveals a perforated calculous cholecystitis, containing multiple cholecystolithiases with the same density as our previously mentioned hyperdense lesion ( Figure 3 arrow).