MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A.

Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1β from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent

Cognitive Bias in Ambiguity Judgements:Using Computational Models to Dissect the Effects of Mild Mood Manipulation in Humans

Positive and negative moods can be treated as prior expectations over future delivery of rewards and punishments. This provides an inferential foundation for the cognitive (judgement) bias task, now widely-used for assessing affective states in non-human animals. In the task, information about affect is extracted from the optimistic or pessimistic manner in which participants resolve ambiguities in sensory input. Here, we report a novel variant of the task aimed at dissecting the effects of affect manipulations on perceptual and value computations for decision-making under ambiguity in humans. Participants were instructed to judge which way a Gabor patch (250ms presentation) was leaning. If the stimulus leant one way (e.g. left), pressing the REWard key yielded a monetary WIN whilst pressing the SAFE key failed to acquire the WIN. If it leant the other way (e.g. right), pressing the SAFE key avoided a LOSS whilst pressing the REWard key incurred the LOSS. The size (0-100 UK pence) of the offered WIN and threatened LOSS, and the ambiguity of the stimulus (vertical being completely ambiguous) were varied on a trial-by-trial basis, allowing us to investigate how decisions were affected by differing combinations of these factors. Half the subjects performed the task in a 'Pleasantly' decorated room and were given a gift (bag of sweets) prior to starting, whilst the other half were in a bare 'Unpleasant' room and were not given anything. Although these treatments had little effect on self-reported mood, they did lead to differences in decision-making. All subjects were risk averse under ambiguity, consistent with the notion of loss aversion. Analysis using a Bayesian decision model indicated that Unpleasant Room subjects were ('pessimistically') biased towards choosing the SAFE key under ambiguity, but also weighed WINS more heavily than LOSSes compared to Pleasant Room subjects. These apparently contradictory findings may be explained by the influence of affect on different processes underlying decision-making, and the task presented here offers opportunities for further dissecting such processes

Elevated integration within the reward network underlies vulnerability to distress.

Distress tolerance (DT), the capability to persist under negative circumstances, underlies a range of psychopathologies. It has been proposed that DT may originate from activity and connectivity in diverse neural networks orchestrated by the reward system. To test this hypothesis, we examined the link between DT, and integration and segregation in the reward network as derived from resting state functional connectivity data. DT was measured in 147 healthy participants, using the Behavioral Indicator of Resiliency to Distress task. We found that distress intolerant participants demonstrated heightened reward network integration relative to distress tolerant subjects. In addition, these differences in integration were higher relative to the rest of the brain and, more specifically, the somatomotor network, which has been implicated in impulsive behavior. These findings support the notion that increased integration in large-scale brain networks may constitute a risk for distress intolerance and its psychopathology correlates

Applying a COVID-19 Sample-pooling Technique to Forensics Identification of Illicit Drugs

This paper presents a method for materially speeding up the identification process of suspect illicit drugs by pooling samples that require GC-MS analysis. This method can be applied to samples seized from a single suspect that are similar in appearance and therefore meet the Israeli Dangerous Drug Ordinance requirements for sampling. A complementary test (GC, TLC, or FTIR) conducted separately on each of the sampled units can prove conclusively that all units contain the same drug. This study shows that even with large differences in relative weight of mixes in a pool, each drug is easily identifiable by GC-MS and dominant peaks do not overshadow minority substances. By using this method, a narcotics lab can improve its throughput of expert opinions in narcotics cases, and at the same time save resources, extend instrument life, and be more environment-friendly

Applying a COVID-19 Sample-pooling Technique to Forensics Identification of Illicit Drugs

This paper presents a method for materially speeding up the identification process of suspect illicit drugs by pooling samples that require GC-MS analysis. This method can be applied to samples seized from a single suspect that are similar in appearance and therefore meet the Israeli Dangerous Drug Ordinance requirements for sampling. A complementary test (GC, TLC, or FTIR) conducted separately on each of the sampled units can prove conclusively that all units contain the same drug. This study shows that even with large differences in relative weight of mixes in a pool, each drug is easily identifiable by GC-MS and dominant peaks do not overshadow minority substances. By using this method, a narcotics lab can improve its throughput of expert opinions in narcotics cases, and at the same time save resources, extend instrument life, and be more environment-friendly

Settler-Colonialism, Memoricide and Indigenous Toponymic Memory: The Appropriation of Palestinian Place Names by the Israeli State

Cartography, place-naming and state-sponsored explorations were central to the modern European conquest of the earth, empire building and settler-colonisation projects. Scholars often assume that place names provide clues to the historical and cultural heritage of places and regions. This article uses social memory theory to analyse the cultural politics of place-naming in Israel. Drawing on Maurice Halbwachs’ study of the construction of social memory by the Latin Crusaders and Christian medieval pilgrims, the article shows Zionists’ toponymic strategies in Palestine, their superimposition of Biblical and Talmudic toponyms was designed to erase the indigenous Palestinian and Arabo-Islamic heritage of the land. In the pre-Nakba period Zionist toponymic schemes utilised nineteenth century Western explorations of Biblical ‘names’ and ‘places’ and appropriated Palestinian toponyms. Following the ethnic cleansing of Palestine in 1948, the Israeli state, now in control of 78 percent of the land, accelerated its toponymic project and pursued methods whose main features were memoricide and erasure. Continuing into the post-1967 occupation, these colonial methods threaten the destruction of the diverse historical cultural heritage of the land