N-terminal truncation of antiapoptotic MCL1, but not G2/M-induced phosphorylation, is associated with stabilization and abundant expression in tumor cells

The antiapoptotic BCL2 family member MCL1 is normally up- and down-modulated in response to environmental signals and conditions, but is constitutively expressed in cancer where it promotes cell survival and drug resistance. A post-translational modification identified here, truncation at the N terminus, was found to act along with previously described ERK- and GSK3-induced phosphorylation events to regulate the turnover of the MCL1 protein and thus its availability for antiapoptotic effects. Although both N-terminally truncated and full-length MCL1 contain sequences enriched in proline, glutamic acid, serine, and threonine and were susceptible to proteasomal degradation, the truncated form decayed less rapidly and was maintained for an extended period in the presence of ERK activation. This was associated with extended cell survival because the truncated form of MCL1 (unlike those of BCL2 and BCLX) retained antiapoptotic activity. N-terminal truncation slightly increased the electrophoretic mobility of MCL1 and differed from the phosphorylation/band shift to decreased mobility, which occurs in the G2/M phase and was not found to affect MCL1 turnover. The N-terminally truncated form of MCL1 was expressed to varying extents in normal lymphoid tissues and was the predominant form present in lymphomas from transgenic mice and human tumor lines of B-lymphoid origin. The degradation versus stabilized expression of antiapoptotic MCL1 is thus controlled by N-terminal truncation as well as by ERK- and GSK3 (but not G2/M)-induced phosphorylation. These modifications may contribute to dysregulated MCL1 expression in cancer and represent targets for promoting its degradation to enhance tumor cell death.     

Gender-specific links between hepatic 11beta reduction of cortisone and adipokines

Objective: Reduction of cortisone to cortisol is mediated by 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1), a putative key enzyme in obesity‐related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor‐α (TNF‐α), are of importance for 11βHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender‐specific and associated with circulating levels of leptin and TNF‐α receptors and/or sex hormones. Research Methods and Procedures: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11βHSD1 enzyme activity was estimated by the conversion of orally‐ingested cortisone to cortisol. Results: Hepatic 11βHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF‐α receptors also after adjustment of BMI and waist circumference. In contrast, 11β reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. Discussion: Hepatic 11β reduction shows different links to circulating adipocyte‐derived hormones in males and females. This emphasizes the need for further studies on tissue‐specific regulation of 11βHSD1 in both genders.     

An exploratory study of cardiac function and oxygen uptake during cycle ergometry in overweight children

Objective: Obesity has been proposed to negatively impact cardiac function in overweight (OW) individuals. The relationship between diastolic dysfunction and oxygen uptake (V?o ₂) kinetics is equivocal. This exploratory investigation evaluated the relationship between resting left ventricular function and V?o ₂ kinetics during cycle ergometry in OW and non‐overweight (NO) children and adolescents. Research Methods and Procedures: Fourteen OW (>85 percentile for BMI for age and gender) children, 10 boys and 4 girls (age, 11.7 ± 1.9 years; body mass, 80.6 ± 45.5 kg) and 10 NO children (4 boys, 6 girls) volunteered to participate in the study (age, 12.5 ± 2.1 years; body mass, 45.8 ± 13.8 kg). Resting cardiovascular structure and function were assessed using spectral Doppler echocardiography. All subjects underwent two sub‐maximal exercise stages on a cycle ergometer (3 minutes unloaded and 5 minutes at 50 W, both at a cadence of 50 rpm). Respiratory data were measured on a breath‐by‐breath basis at both workloads and the mean response time (MRT) was calculated. Results: Analysis of the MRT data demonstrated that there were no significant differences between OW and NO (OW, 52.6 ± 11.7 seconds vs. NO, 45.6 ± 7.4 seconds). Significant correlations (p < 0.05) were obtained between MRT V?o ₂ and echocardiographic‐derived mitral valve inflow pressure half‐time (r = 0.55) and between MRT V?o ₂, and mitral valve inflow deceleration time (r = 0.55). Discussion: The evidence from this research suggests a possible link between left ventricular diastolic function at rest and oxygen uptake kinetics during sub‐maximal exercise in OW and NO children and adolescents.     

The validity of obesity based on self-reported weight and height: Implications for population studies

Objective: To validate self‐reported information on weight and height in an adult population and to find a useful algorithm to assess the prevalence of obesity based on self‐reported information. Research Methods and Procedures: This was a cross‐sectional survey consisting of 1703 participants (860 men and 843 women, 30 to 75 years old) conducted in the community of Vara, Sweden, from 2001 to 2003. Self‐reported weight, height, and corresponding BMI were compared with measured data. Obesity was defined as measured BMI ≥ 30 kg/m². Information on education, self‐rated health, smoking habits, and physical activity during leisure time was collected by a self‐administered questionnaire. Results: Mean differences between measured and self‐reported weight were 1.6 kg (95% confidence interval, 1.4; 1.8) in men and 1.8 kg (1.6; 2.0) in women (measured higher), whereas corresponding differences in height were ?0.3 cm (?0.5; ?0.2) in men and ?0.4 cm (?0.5; ?0.2) in women (measured lower). Age and body size were important factors for misreporting height, weight, and BMI in both men and women. Obesity (measured) was found in 156 men (19%) and 184 women (25%) and with self‐reported data in 114 men (14%) and 153 women (20%). For self‐reported data, the sensitivity of obesity was 70% in men and 82% in women, and when adjusted for corrected self‐reported data and age, it increased to 81% and 90%, whereas the specificity decreased from 99% in both sexes to 97% in men and 98% in women. Discussion: The prevalence of obesity based on self‐reported BMI can be estimated more accurately when using an algorithm adjusted for variables that are predictive for misreporting.     

Sexually dimorphic SCAMP1 expression in the forebrain motor pathway for song production of juvenile zebra finches

Mechanisms regulating sexual differentiation of the zebra finch song system are not well understood. The present study was designed to more fully characterize secretory carrier membrane protein 1 (SCAMP1), which was identified in a cDNA microarray screen as showing increased expression in the forebrains of developing male compared with female zebra finches. We completed the sequence of the open reading frame and used in situ hybridization to compare mRNA in song control regions of juvenile (25-day-old) individuals. Expression was significantly greater in the HVC (used as a proper name) and robust nucleus of the arcopallium (RA) in males than in females. Immunohistochemistry revealed that SCAMP1 protein is also expressed in these two brain regions, and qualitatively appears greater in males. Western analysis confirmed that the protein is increased in the telencephalon of males when compared with females at 25 days of age. These results are consistent with the idea that SCAMP1 is involved in masculinization of these brain areas, perhaps facilitating the survival of cells within them.     

Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings

Our previous studies on scalp-recorded event-related potentials (ERPs) showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA) to the ERP data, we found independent components (ICs) located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC) and the primary somatosensory cortex (SI). The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex) that are involved in sensation and perception of various stimuli.     

Endless Hide-and-Seek： Dynamic Co-evolution in Plant-Bacterium Warfare

Plants possess innate Immune systems to prevent most potential Infections. The ancient and conserved innate immune responses are triggered by microbe-associated molecular patterns （MAMPs） and play important roles in broad-spectrum defenses. However, successful bacterial pathogens evolved type Ⅲ virulence effectors to suppress MAMP-medlated immunity. To survive, plants further developed highly specific resistance （R） genes to trigger gene-for-gene-mediated immunity and turn the virulent pathogens into avirulent ones. We summarize here the very recent advances in this dynamic coevolution of plantbacterium interaction.     

Astaxanthin Accumulation in the Green Alga Haematococcus pluvialis： Effects of Cultivation Parameters

The green alga, Haematococcus pluvlalis Flotow is used as a source of the ketocarotenoid astaxanthin for application in fish aquaculture, pharmaceutical and cosmetic industries. Ceils of the green alga were induced by the application of different light and starvation conditions to evaluate the effect in astaxanthin accumulate. The conditions used for the Induction were high light intensity （170 μmol·m^-2·s^-1）, iron starvation, sulfur starvation and phosphate starvation. The results show that stresses applied in culture, which interfere with cell division, trigger the accumulation of astaxanthin. Notably, sulfur starvation results in a massive accumulation of this commercially important carotenoid.