Gas-phase Basicity of Glycine

The protonation thermochemistry of gaseous glycine is re-examined. The composite G3, G3MP2, G3B3, CBS-Q and CBS-QB3 methods have been used to estimate the enthalpy component i.e. the proton affinity of glycine, PA(Gly). The so called "protonation entropy", ΔpS(Gly) = S°(GlyH+) − S°(Gly), has been evaluated by calculating contributions to entropy of the internal rotations using the Pitzer hindered rotor model. The resulting theoretical gas-phase basicity, GB(Gly) = PA(Gly) – T[S°(H+) − ΔpS(Gly)] has been then calculated. These computations were done, either by considering only the most stable neutral and protonated conformers of glycine ("most stable conformer" values, denoted "msc") or a population of conformers based on a Boltzmann distribution at 298 K ("molar" values). An isodesmic procedure has been used by anchoring the computed data to the experimental proton affinities of isopropylamine. The results are the following: PAmsciso(Gly) = 889.2 kJ mol−1, PAmolar(Gly) = 890.9 kJ mol−1, ΔpSmsciso(Gly) = 2.3 J mol−1 K−1, ΔpSmolar(Gly) = 1.2 [−6.2] J mol−1 K−1, GBmsciso(Gly) = 857.5 kJ mol−1, GBmolar(Gly) = 858.9 [856.6] kJ mol−1 [values in brackets correspond to data obtained by including the entropy of mixing]. Evaluated values of PA(Gly)= 889 kJ mol−1 and GB(Gly)= 856 kJ mol−1, at 298 K, may be proposed after comparison with the available experimental data

Gas-Phase Lithium Cation Affinity of Glycine

International audienceThe gas-phase lithium cation binding thermochemistry of glycine has been determined theoretically by quantum chemical calculations at the G4 level and experimentally by the extended kinetic method using electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity of glycine, ∆ Li H° 298 (GLY), i.e. the ∆ Li H° 298 of the reaction GlyLi + ® Gly + Li + , given by the G4 method is equal to 241.4 kJ mol-1 if only the most stable conformer of glycine is considered or to 242.3 kJ mol-1 if the 298 K equilibrium mixture of neutral conformers is included in the calculation. The ∆ Li H° 298 (GLY) deduced from the extended kinetic method is obviously dependent on the choice of the Li + affinity scale; thus, ∆ Li H° 298 (GLY) is equal to 228.7 ± 0.9(2.0) kJ mol-1 if anchored to the recently re-evaluated lithium cation affinity scale, but shifted to 235.4 ± 1.0 kJ mol-1 if G4 computed lithium cation affinities of the reference molecules are used. This difference of 6.3 kJ mol-1 may originate from a compression of the experimental lithium affinity scale in the high ∆ Li H° 298 region. The entropy change associated with the reaction GlyLi + ® Gly + Li + reveals a gain of approximately 15 J mol-1 K-1 with respect to monodentate Li + acceptors. The origin of this excess entropy is attributed to the bidentate interaction between the Li + cation and both the carbonyl oxygen and the nitrogen atoms of glycine. The computed G4 Gibbs free energy, ∆ Li G° 298 (GLY), is equal to 205.3 kJ mol-1 ; a similar result, 201.0 ± 3.4 kJ mol-1 , is obtained from the experiment if the ∆ Li G° 298 of the reference molecules is anchored on the G4 results

IFIT2‐depleted metastatic oral squamous cell carcinoma cells induce muscle atrophy and cancer cachexia in mice

Abstract Background Interferon‐induced protein with tetratricopeptide repeat 2 (IFIT2) is a reported metastasis suppressor in oral squamous cell carcinoma (OSCC). Metastases and cachexia may coexist. The effect of cancer metastasis on cancer cachexia is largely unknown. We aimed to address this gap in knowledge by characterizing the cachectic phenotype of an IFIT2‐depleted metastatic OSCC mouse model. Methods Genetically engineered and xenograft tumour models were used to explore the effect of IFIT2‐depleted metastatic OSCC on cancer cachexia. Muscle and organ weight changes, tumour burden, inflammatory cytokine profiles, body composition, food intake, serum albumin and C‐reactive protein (CRP) levels, and survival were assessed. The activation of the IL6/p38 pathway in atrophied muscle was measured. Results IFIT2‐depleted metastatic tumours caused marked body weight loss (−18.2% vs. initial body weight, P < 0.001) and a poor survival rate (P < 0.01). Skeletal muscles were markedly smaller in IFIT2‐depleted metastatic tumour‐bearing mice (quadriceps: −28.7%, gastrocnemius: −29.4%, and tibialis: −24.3%, all P < 0.001). Tumour‐derived circulating granulocyte‐macrophage colony‐stimulating factor (+772.2‐fold, P < 0.05), GROα (+1283.7‐fold, P < 0.05), IL6 (+245.8‐fold, P < 0.001), IL8 (+616.9‐fold, P < 0.001), IL18 (+24‐fold, P < 0.05), IP10 (+18.8‐fold, P < 0.001), CCL2 (+439.2‐fold, P < 0.001), CCL22 (+9.1‐fold, P < 0.01) and tumour necrosis factor α (+196.8‐fold, P < 0.05) were elevated in IFIT2‐depleted metastatic tumour‐bearing mice. Murine granulocyte colony‐stimulating factor (+61.4‐fold, P < 0.001) and IL6 (+110.9‐fold, P < 0.01) levels were significantly increased in IFIT2‐depleted metastatic tumour‐bearing mice. Serum CRP level (+82.1%, P < 0.05) was significantly increased in cachectic shIFIT2 mice. Serum albumin level (−26.7%, P < 0.01) was significantly decreased in cachectic shIFIT2 mice. An assessment of body composition revealed decreased fat (−81%, P < 0.001) and lean tissue (−21.7%, P < 0.01), which was consistent with the reduced food intake (−19.3%, P < 0.05). Muscle loss was accompanied by a smaller muscle cross‐sectional area (−23.3%, P < 0.05). Muscle atrophy of cachectic IFIT2‐depleted metastatic tumour‐bearing mice (i.v.‐shIFIT2 group) was associated with elevated IL6 (+2.7‐fold, P < 0.05), phospho‐p38 (+2.8‐fold, P < 0.05), and atrogin‐1 levels (+2.3‐fold, P < 0.05) in the skeletal muscle. Neutralization of IL6 rescued shIFIT2 conditioned medium‐induced myotube atrophy (+24.6%, P < 0.01). Conclusions Our results suggest that the development of shIFIT2 metastatic OSCC lesions promotes IL6 production and is accompanied by the loss of fat and lean tissue, anorexia, and muscle atrophy. This model is appropriate for the study of OSCC cachexia, especially in linking metastasis with cachexia

Accelerated CREP - RRR: Turri, Buckwalter, &amp; Blouw (2015)

According to the Justified True Belief (JTB) account of knowledge, a person’s ability to know something is defined by having a belief that is both justified and true (i.e., knowledge is justified true belief). However, this account fails to consider the role of luck. In 1963, Gettier argued that JTB is insufficient because it does not account for certain situations, called Gettier cases, wherein a person is justified for believing something true but only because of luck. It is unclear whether lay people’s intuitions about knowledge lead them to agree with Gettier, such that lay people believe that individuals in these cases lack knowledge (referred to as Gettier intuitions). We attempt to provide a robust estimate of the Gettier intuition effect size by replicating Turri and colleagues’ (2015) Experiment 1. The Collaborative Replications and Education Project (CREP) selected this study for replication based on its undergraduate appeal, feasibility, and pedagogical value. However, in light of some inconsistent results, suboptimal designs, and inconsistent evidence for cultural variation (e.g., Machery et al., 2015; Nagel, et al., 2013; Seyedsayamdost et al., 2015; Starman &amp; Friedman, 2012; Weinberg et al., 2001), the improved methodology of Turri et al. (2015) make it an important study to replicate cross-culturally. Therefore, we propose a multisite collaborative preregistered replication of Turri and colleague's (2015) Experiment 1 (35 labs from 14 countries across 4 continents signed up at time of submission; expected minimum N = 1,500). Results of this study are expected to provide a clearer picture of the Gettier intuition effect size, lay people’s theory and practice of knowledge, and potentially cross-cultural similarities and differences. Preprint: [X] Pre-registered protocols: [X