An isochroman analog of CD3254 and allyl-, isochroman-analogs of NEt-TMN prove to be more potent retinoid-X-receptor (RXR) selective agonists than bexarotene

Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene

Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals

Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology

A mid-infrared Mueller ellipsometer with pseudo-achromatic optical elements

The purpose of this article is to present a new broadband Mueller ellipsometer designed to work in the mid-infrared range, from 3 to 14 microns. The Mueller ellipsometer, which can be mounted in reflection or in transmission configuration, consists of a polarization state generator (PSG), a sample holder, and a polarization state analyzer (PSA). The PSG consists in one linear polarizer and a retarder sequentially rotated to generate a set of four optimal polarization states. The retarder consists in a bi-prism made of two identical Fresnel rhombs disposed symmetrically and joined by optical contact, giving the ensemble a "V" shape. Retardation is induced by the four total internal reflections that the beam undergoes when it propagates through the bi-prism. Total internal reflection allows to generate a quasi-achromatic retardation. The PSA is identical to the PSG, but with its optical elements mounted in reverse order. After a measurement run, the instrument yields a set of sixteen independent values, which is the minimum amount of data required to calculate the Mueller matrix of the sample. The design of the Mueller ellipsometer is based on the optimization of an objective criterion that allows minimizing the propagation of errors from raw data to the Mueller matrix of the sample. The pseudo-achromatic optical elements ensure a homogeneous quality of the measurements for all wavelengths. The performance of the Mueller ellipsometer in terms of precision, and accuracy, is discussed and illustrated with a few examples

An engineered escherichia coli strain with synthetic metabolism for in‐cell production of translationally active methionine derivatives

In the last decades, it has become clear that the canonical amino acid repertoire codified by the universal genetic code is not up to the needs of emerging biotechnologies. For this reason, extensive genetic code re‐engineering is essential to expand the scope of ribosomal protein translation, leading to reprogrammed microbial cells equipped with an alternative biochemical alphabet to be exploited as potential factories for biotechnological purposes. The prerequisite for this to happen is a continuous intracellular supply of noncanonical amino acids through synthetic metabolism from simple and cheap precursors. We have engineered an Escherichia coli bacterial system that fulfills these requirements through reconfiguration of the methionine biosynthetic pathway and the introduction of an exogenous direct trans‐sulfuration pathway. Our metabolic scheme operates in vivo, rescuing intermediates from core cell metabolism and combining them with small bio‐orthogonal compounds. Our reprogrammed E. coli strain is capable of the in‐cell production of L‐azidohomoalanine, which is directly incorporated into proteins in response to methionine codons. We thereby constructed a prototype suitable for economic, versatile, green sustainable chemistry, pushing towards enzyme chemistry and biotechnology‐based production

The Impact of Sex, Circadian Disruption, and the Clock\u3csup\u3e∆19/∆19\u3c/sup\u3e Genotype on Alcohol Drinking in Mice

Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., Clock∆19/∆19 mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male Clock∆19/∆19 mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, Clock∆19/∆19 mice displayed increased alcohol consumption and preference. Sex differences were not apparent in Clock∆19/∆19 mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the Clock gene greatly increases alcohol consumption and abolishes sex differences present in WT animals

Oleanolic acid: A promising antidiabetic metabolite detected in Aglianico grape pomace

Grape pomace, a bulky component of winery waste, is a source of healthy compounds. So far, scientific research has mainly focused on its polyphenol content, but given the impressive number of bioactivities shown by grape pomace, it is not unlikely that, besides polyphenols, additional metabolites, so far undetected, may be involved. In order to verify such hypothesis, an in-depth chemical analysis of Aglianico (Vitis vinifera) grape pomace was conducted by NMR and LC-MS/MS. In addition to a number of polyphenols, a remarkable concentration of oleanolic acid (0.45 mg/g - fresh weight) was determined in the analyzed material. Oleanolic acid is a natural triterpenoid showing many bioactivities including antitumor, anti-inflammatory, antibiotic and antiviral properties. Also, it was proven a potential antidiabetic molecule in Type1 Diabetes rats. Hence, its influence on the mitochondrial and glucose uptake activities of C2C12 myoblast was here assessed, thus supporting oleanolic acid as a promising antidiabetic metabolite

Mesurer la fièvre palestinienne. Notes sur une expérience de monitoring pendant la deuxième Intifada, 2000-2006

Depuis l’automne 2000 et le début de la deuxième Intifada dans les Territoires palestiniens occupés (tpo), l’Unité de recherche sur la Palestine (urp) de l’Institut universitaire d’études du développement (iued) est engagée dans un projet portant sur le monitoring des conditions de vie de la population civile, ainsi que sur le rôle et les effets de l’aide internationale. Initialement financé sur le budget de l’aide humanitaire suisse, le projet est ensuite entré dans celui de la coopération a..