Influence of Clothing on Thermoregulation and Comfort During Exercise in the Heat.

Davis, JK, Laurent, CM, Allen, KE, Zhang, Y, Stolworthy, NI, Welch, TR, and Nevett, ME. Influence of clothing on thermoregulation and comfort during exercise in the heat. J Strength Cond Res 31(12): 3435-3443, 2017-Sport textiles of synthetic fiber have been proposed to have superior properties for keeping wearers cooler, drier, and more comfortable compared with natural fibers. The impact of various fiber content and fabric construction on thermoregulation and perceptual responses are not well understood. Eight male collegiate athletes performed 3 counterbalanced trials of 45-minute treadmill run at 60% of maximal oxygen uptake in an environmental chamber (32° C). Three different fibers, consisting of 100% cotton, a blend of natural fibers (50/50% cotton/soybean), and a synthetic fiber (100% polyester) with mesh loops to facilitate ventilation through the clothing, were tested. Heat strain indices, microenvironment temperature, ratings of perceived exertion (RPE), and clothing comfort were measured. Session RPE (S-RPE) and session thermal sensation (S-TS) were recorded 20 minutes after each trial. There was no effect of clothing on rectal, skin, and body temperatures, heart rate, RPE, or comfort measures (p ≥ 0.05). A significant effect was observed for synthetic fiber compared with cotton on S-RPE (p = 0.03), S-TS (p = 0.04), and the microenvironment temperature at the chest (p = 0.02). No significant difference was shown for any other fibers on S-RPE, S-TS, or other microenvironment areas (p ≥ 0.05). These results show that clothing fiber content and fabric construction had no effect on thermoregulation, RPE, or clothing comfort during moderate-intensity exercise in the heat; whereas synthetic fabric construction indeed effectively reduced regional microenvironment temperature and attenuated global exertion and TS, which may have important implications for exercise tolerance in the heat.

Influence of Dehydration on Intermittent Sprint Performance.

This study examined the effects of dehydration on intermittent sprint performance and perceptual responses. Eight male collegiate baseball players completed intermittent sprints either dehydrated (DEHY) by 3% body mass or euhydrated (EU). Body mass was reduced through exercise in the heat with controlled fluid restriction occurring 1 day before the trial. Participants completed twenty-four 30-m sprints divided into 3 bouts of 8 sprints with 45 seconds of rest between each sprint and 3 minutes between each bout. Perceived recovery status (PRS) scale was recorded before the start of each trial. Heart rate (HR), ratings of perceived exertion (RPE) (0-10 OMNI scale), and perceived readiness (PR) scale were recorded after every sprint, and session RPE (SRPE) was recorded 20 minutes after completing the entire session. A 2 (condition) × 3 (bout of sprints) repeated-measures ANOVA revealed a significant main effect of condition on mean sprint time (p = 0.03), HR (p < 0.01), RPE (p = 0.01), and PR (p = 0.02). Post hoc tests showed significantly faster mean sprint times for EU vs. DEHY during the second (4.87 ± 0.29 vs. 5.03 ± 0.33 seconds; p = 0.01) and third bouts of sprints (4.91 ± 0.29 vs. 5.12 ± 0.44 seconds; p = 0.02). Heart rate was also significantly lower (p ≤ 0.05) for EU during the second and third bouts. Post hoc measures also showed significantly impaired (p ≤ 0.05) feelings of recovery (PRS) before exercise and increased (p ≤ 0.05) perceptual strain before each bout (PR) during the second and third bouts of repeated sprint work (i.e., RPE and PR) and after the total session (SRPE) in the DEHY condition. Dehydration impaired sprint performance, negatively altered perception of recovery status before exercise, and increased RPE and HR response.

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27).

Trimethylation of histone H3 on lysine 27 (H3K27me3) is a repressive posttranslational modification mediated by the histone methyltransferase EZH2. EZH2 is a component of the polycomb repressive complex 2 and is overexpressed in many cancers. In B-cell lymphomas, its substrate preference is frequently altered through somatic mutation of the EZH2 Y641 residue. Herein, we identify mutation of EZH2 A677 to a glycine (A677G) among lymphoma cell lines and primary tumor specimens. Similar to Y641 mutant cell lines, an A677G mutant cell line revealed aberrantly elevated H3K27me3 and decreased monomethylated H3K27 (H3K27me1) and dimethylated H3K27 (H3K27me2). A677G EZH2 possessed catalytic activity with a substrate specificity that was distinct from those of both WT EZH2 and Y641 mutants. Whereas WT EZH2 displayed a preference for substrates with less methylation [unmethylated H3K27 (H3K27me0):me1:me2 k(cat)/K(m) ratio = 9:6:1] and Y641 mutants preferred substrates with greater methylation (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1:2:13), the A677G EZH2 demonstrated nearly equal efficiency for all three substrates (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1.1:0.6:1). When transiently expressed in cells, A677G EZH2, but not WT EZH2, increased global H3K27me3 and decreased H3K27me2. Structural modeling of WT and mutant EZH2 suggested that the A677G mutation acquires the ability to methylate H3K27me2 through enlargement of the lysine tunnel while preserving activity with H3K27me0/me1 substrates through retention of the Y641 residue that is crucial for orientation of these smaller substrates. This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EZH2.

Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer.

PURPOSE: This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history. EXPERIMENTAL DESIGN: Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC. Safety and activity were assessed every 4 and 8 weeks, respectively. Tumors were analyzed for EGFR and HER2 mutations and/or amplifications. RESULTS: Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of >or=24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of >or=24 weeks. No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in HER2 were found. One of two patients with HER2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. The most common adverse events were grade 1 or 2 diarrhea, rash, fatigue, nausea, and anorexia. Adverse events were similar across dosing regimens. CONCLUSIONS: Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC.

Frameshift events associated with the lysyl-tRNA and the rare arginine codon, AGA, in Escherichia coli: a case study involving the human Relaxin 2 protein.

Human Relaxin 2 is an insulin-related peptide hormone with a mass of 19,084 Da. The mRNA contains a number of arginine codons that are rarely used by Escherichia coli to produce highly expressed proteins. As a result, expressing this recombinant protein in E. coli is problematic. When human Relaxin 2 was expressed in E. coli BL21 (DE3), several forms of the protein were made. One species had the expected molecular weight (19,084 Da). A second species observed had a molecular weight of 21,244 Da. A third minor species had a molecular weight of 17,118 Da. These aberrant molecular weights can be explained as follows. First, a sequence CGA-AAA-AAG-AGA, containing the rare arginine codons CGA and AGA was the site of the +1 frameshift that generated the 21,244 Da species. Since there was a limited supply of this arginyl-tRNA, the peptidyl-tRNA moved +1 nucleotide to occupy the codon and resumed protein synthesis. Second, a -1 frameshift associated with 'slippery A' sequence XXA-AAA-AAG accounted for 10% of the product with a mass of 17,118 Da. Presumably, the shift to -1 also occurred because there was a paucity of the arginyl-tRNAArgucu. Introduction of a plasmid coding for the cognate tRNA for AGA and site directed mutagenesis prevented the formation of both frameshift species.