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We point out that the hypothesis of an SU ( 5 ) -like supersymmetric Grand Unified Theory (GUT) implies a generic relation within the flavour structure of up-type squarks. Contrary to other well-known SU ( 5 ) relations between the down-quark and charged lepton sectors, this relation remains exact in the presence of any corrections and extra operators. Moreover it remains valid to a good precision at the electroweak scale, and opens thus new possibilities for testing SU ( 5 ) -like GUTs. We derive the low-energy effective theory of observable light up-type squarks, that also constitutes a useful tool for squark phenomenology. We use this effective theory to determine how to test SU ( 5 ) relations at the LHC. Focusing on scenarios with light stops, compatible with Natural SUSY, it appears that simple tests involving ratios of event rates are sufficient to test the hypothesis of an SU ( 5 ) -like GUT theory. The techniques of charm-tagging and top-polarimetry are a crucial ingredient of these tests. [ABSTRACT FROM AUTHOR]

Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30 mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30 mg for 20 min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240 min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30 mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (C max : 29.4 vs 15.2 ng/mL; AUC: 45.7 vs 22.1 ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30 mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30 mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30 mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mallock-Ohnesorg, Rabenstein, Stoll, Gertzen, Rieder, Malke, Burgmann, Laux, Pieper, Schulz, Franzen, Luch and Rüther.)

Heated tobacco products (HTPs) produce aerosol using a different mechanism than tobacco cigarettes, leading to lower emissions of some harmful substances, but also of nicotine as reported by some independent studies. Lower nicotine delivery could lead to compensatory puffing when product use does not sufficiently satisfy cravings. Thus, this three-arm crossover study was conducted to characterize the potential of two different HTPs to deliver nicotine and satisfy cravings compared with conventional cigarettes in users who had already switched to HTPs. Fifteen active, non-exclusive HTP users consumed the study products according to a pre-directed puffing protocol. At predetermined time points, venous blood was sampled and the subjective effects of consumption were assessed. Nicotine delivery by both HTPs was comparable, but significantly lower than that by conventional cigarettes, suggesting a lower addictive potential. Cravings were reduced by all products, with no statistically significant differences between them, despite the different nicotine deliveries. This indicated that HTPs do not necessarily need high nicotine deliveries with high addictive potential, as are characteristic of tobacco cigarettes. These results were followed up on with an ad libitum use study.

Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions ("ad libitum"). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2-5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users.

Functional gamma-aminobutyric acid type B (GABA(B)) receptors are normally only observed upon coexpression of GABA(B1) with GABA(B2) subunits. A C-terminal arginine-based endoplasmic reticulum (ER) retention/retrieval signal, RSRR, prevents escape of unassembled GABA(B1) subunits from the ER and restricts surface expression to correctly assembled heteromeric receptors. The RSRR signal in GABA(B1) is proposed to be shielded by C-terminal coiled-coil interaction of the GABA(B1) with the GABA(B2) subunit. Here, we investigated whether the RSRR motif in GABA(B1) remains functional when grafted to ectopic sites. We found that the RSRR signal in GABA(B1) is inactive in any of the three intracellular loops but remains functional when moved within the distal zone of the C-terminal tail. C-terminal deletions that position the RSRR signal closer to the plasma membrane drastically reduce its effectiveness, supporting that proximity to the membrane restricts access to the RSRR motif. Functional ectopic RSRR signals in GABA(B1) are efficiently inactivated by the GABA(B2) subunit in the absence of coiled-coil dimerization, supporting that coiled-coil interaction is not critical for release of the receptor complex from the ER. The data are consistent with a model in which removal of RSRR from its active zone rather than its direct shielding by coiled-coil dimerization triggers forward trafficking. Because arginine-based intracellular retention signals of the type RXR, where X represents any amino acid, are used to regulate assembly and surface transport of several multimeric complexes, such a mechanism may apply to other proteins as well.