Aristotle Said “Happiness is a State of Activity” — Predicting Mood Through Body Sensing with Smartwatches

We measure and predict states of Activation and Happiness using a body sensing application connected to smartwatches. Through the sensors of commercially available smartwatches we collect individual mood states and correlate them with body sensing data such as acceleration, heart rate, light level data, and location, through the GPS sensor built into the smartphone connected to the smartwatch. We polled users on the smartwatch for seven weeks four times per day asking for their mood state. We found that both Happiness and Activation are negatively correlated with heart beats and with the levels of light. People tend to be happier when they are moving more intensely and are feeling less activated during weekends. We also found that people with a lower Conscientiousness and Neuroticism and higher Agreeableness tend to be happy more frequently. In addition, more Activation can be predicted by lower Openness to experience and higher Agreeableness and Conscientiousness. Lastly, we find that tracking people’s geographical coordinates might play an important role in predicting Happiness and Activation. The methodology we propose is a first step towards building an automated mood tracking system, to be used for better teamwork and in combination with social network analysis studies.     

Ca<Superscript>2+</Superscript> signals,cell membrane disintegration,and activation of TMEM16F during necroptosis

Activated receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like (MLKL) are essential components of the necroptotic pathway. Phosphorylated MLKL (pMLKL) is thought to induce membrane leakage, leading to cell swelling and disintegration of the cell membrane. However, the molecular identity of the necroptotic membrane pore remains unclear, and the role of pMLKL for membrane permeabilization is currently disputed. We observed earlier that the phospholipid scramblase and ion channel TMEM16F/anoctamin 6 cause large membrane currents, cell swelling, and cell death when activated by a strong increase in intracellular Ca²⁺. We, therefore, asked whether TMEM16F is also central to necroptotic cell death and other cellular events during necroptosis. Necroptosis was induced by TNFα, smac mimetic, and Z-VAD (TSZ) in NIH3T3 fibroblasts and the four additional cell lines HT₂₉, 16HBE, H441, and L929. Time-dependent changes in intracellular Ca²⁺, cell morphology, and membrane currents were recorded. TSZ induced a small and only transient oscillatory rise in intracellular Ca²⁺, which was paralleled by the activation of outwardly rectifying Cl^? currents, which were typical for TMEM16F/ANO6. Ca²⁺ oscillations were due to Ca²⁺ release from endoplasmic reticulum, and were independent of extracellular Ca²⁺. The initial TSZ-induced cell swelling was followed by cell shrinkage. Using typical channel blockers and siRNA-knockdown, the Cl^? currents were shown to be due to the activation of ANO6. However, the knockdown of ANO6 or inhibitors of ANO6 did not inhibit necroptotic cell death. The present data demonstrate the activation of ANO6 during necroptosis, which, however, is not essential for cell death.     

Switch from protective to adverse inflammation during influenza: viral determinants and hemostasis are caught as culprits

Influenza viruses cause acute respiratory infections, which are highly contagious and occur as seasonal epidemic and sporadic pandemic outbreaks. Innate immune response is activated shortly after infection with influenza A viruses (IAV), affording effective protection of the host. However, this response should be tightly regulated, as insufficient inflammation may result in virus escape from immunosurveillance. In contrast, excessive inflammation may result in bystander lung tissue damage, loss of respiratory capacity, and deterioration of the clinical outcome of IAV infections. In this review, we give a comprehensive overview of the innate immune response to IAV infection and summarize the most important findings on how the host can inappropriately respond to influenza.     

Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior–posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal–epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal–epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal–epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.     

Cellular mechanisms responsible for cell-to-cell spreading of prions

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrP^Sc). These abnormal aggregated PrP^Sc species multiply in infected cells by recruiting and converting the host PrP^C protein into new PrP^Sc. How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrP^Sc-containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrP^Sc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases.     

Updating the mechanisms of common fragile site instability: how to reconcile the different views?

Common fragile sites (CFSs) are large chromosomal regions long identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs came from their key role in the formation of DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was notably correlated with the appearance of genome instability in precancerous lesions and during tumor progression. Identification of the molecular mechanisms responsible for their instability therefore represents a major challenge. A number of data show that breaks result from mitotic entry before replication completion but the mechanisms responsible for such delayed replication of CFSs and relaxed checkpoint surveillance are still debated. In addition, clues to the molecular events leading to breakage just start to emerge. We present here the results of recent reports addressing these questions.     

Ube3a,the E3 ubiquitin ligase causing Angelman syndrome and linked to autism,regulates protein homeostasis through the proteasomal shuttle Rpn10

Ubiquitination, the covalent attachment of ubiquitin to a target protein, regulates most cellular processes and is involved in several neurological disorders. In particular, Angelman syndrome and one of the most common genomic forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during brain development. We have now devised a protocol to screen for substrates of this particular ubiquitin ligase. In a neuronal cell system, we find direct ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is targeted for degradation upon ubiquitination by Ube3a, indicating that degradation might not be the only effect of Ube3a on its substrates. Furthermore, we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of ubiquitinated proteins, further supporting the biochemical evidence of interaction obtained in neuronal cells.     

Inflammation and repeated infections in CGD: two sides of a coin

Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals. It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells (neutrophils, eosinophils, monocytes, and macrophages). This “respiratory burst” involves the catalytic conversion of molecular oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients.     

Origin of AIDS: contaminated polio vaccine theory refuted

Despite strong evidence to the contrary, speculation continues that the AIDS virus, human immunodeficiency virus type 1 (HIV-1), may have crossed into humans as a result of contamination of the oral polio vaccine (OPV). This 'OPV/AIDS theory' claims that chimpanzees from the vicinity of Stanleyville--now Kisangani in the Democratic Republic of Congo--were the source of a simian immunodeficiency virus (SIVcpz) that was transmitted to humans when chimpanzee tissues were allegedly used in the preparation of OPV. Here we show that SIVcpz is indeed endemic in wild chimpanzees of this region but that the circulating virus is phylogenetically distinct from all strains of HIV-1, providing direct evidence that these chimpanzees were not the source of the human AIDS pandemic.