Influence of oxygen concentration on the metabolism of Penicillium chrysogenum.

In large-scale bioreactors, there is often insufficient mixing and as a consequence, cells experience uneven substrate and oxygen levels that influence product formation. In this study, the influence of dissolved oxygen (DO) gradients on the primary and secondary metabolism of a high producing industrial strain of Penicillium chrysogenum was investigated. Within a wide range of DO concentrations, obtained under chemostat conditions, we observed different responses from P. chrysogenum: (i) no influence on growth or penicillin production (>0.025 mmol L-1); (ii) reduced penicillin production, but no growth limitation (0.013-0.025 mmol L-1); and (iii) growth and penicillin production limitations (<0.013 mmol L-1). In addition, scale down experiments were performed by oscillating the DO concentration in the bioreactor. We found that during DO oscillation, the penicillin production rate decreased below the value observed when a constant DO equal to the average oscillating DO value was used. To understand and predict the influence of oxygen levels on primary metabolism and penicillin production, we developed a black box model that was linked to a detailed kinetic model of the penicillin pathway. The model simulations represented the experimental data during the step experiments; however, during the oscillation experiments the predictions deviated, indicating the involvement of the central metabolism in penicillin production.

A Strengths-Based Longitudinal Career Intervention for Junior Secondary School Students with Special Educational Needs: a Mixed-method Evaluation.

The mixed-method study reported here was designed to evaluate a strengths-based career intervention program for secondary school students with mild special educational needs (SEN). A sample of 32 SEN students (19 boys: 13 girls) from 5 inclusive schools in Hong Kong were recruited to a treatment group. An additional 32 SEN students (19 boys: 13 girls) were selected to form the control group matched for age, gender and parents' education level. The special needs exhibited by both groups were in areas of literacy and numeracy, attention deficits, and social-emotional problems, but did not include severe or complex disabilities. Participants in both groups responded to pre- and post-intervention questionnaires covering career development self-efficacy, personal and social development self-efficacy, and meaning in life. As a follow-up, two teachers and three social workers providing support to SEN students, and the 32 participants were interviewed several months after the intervention. Interviews also took place with teachers, social workers and students to evaluate the perceived effects of the intervention. Findings indicated significant interactions between Time 1 and Time 2, and between groups (control vs. treatment) in personal goal-setting, career goal-setting, and the presence of meaning in life. Additionally, several themes were identified from the interviews suggesting that the intervention did have positive effects on SEN students' career, personal and social development self-efficacy, and acquisition of meaning in life.

Systematic Review of Guidelines on Managing Patients with Harmful Use of Alcohol in Primary Healthcare Settings.

AIM: To appraise existing alcohol guidelines for identifying and managing harmful alcohol use in primary healthcare settings. METHODS: Seven databases and 18 health organization or medical society websites were systematically searched from inception to 31 October 2016. Guidelines in English language, developed by a national or international medical specialty society, government or health organization, and containing recommendations for identifying and managing harmful use of alcohol in primary healthcare settings, were included. The Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument was used to appraise the guidelines. RESULTS: Of the 970 literature identified, 17 were included for review, with 13 guidelines developed for use in Western countries and 4 for international use. The AGREE II scores ranged from 2.0 to 5.3, out of 7. Variations in terminology of harmful alcohol use were seen, with 'harmful drinking' and 'problem drinking' being mostly used. All guidelines were in favor of screening and brief interventions due to their effectiveness and cost-effectiveness. Potential benefits and costs of applying screening and brief interventions were found, but there was a lack of evidence for long-term effects or specific populations. CONCLUSIONS: All 17 guidelines recommended screening and brief interventions due to its associated health and financial benefits. Policy makers are highly encouraged to integrate these practices into primary healthcare settings taking the drinking status, culture and resources into account. SHORT SUMMARY: Screening and brief interventions were recommended by all 17 guidelines on managing patients with harmful use of alcohol in primary healthcare settings. Policy makers and healthcare practitioners are highly encouraged to implement these recommendations.

Diet quality and eating behavioural patterns in preschool children in Hong Kong.

BACKGROUND AND OBJECTIVES: To assess the diet quality and eating behaviour of preschool children, investigate parents' feeding practices, and obtain information on the kindergarten nutrition environment of Hong Kong children aged 30-60 months. METHODS AND STUDY DESIGN: Dietary information was obtained using multiple 24-hour recalls. Questionnaires were developed to obtain information on children' seating behaviour, parents' feeding practices and preschool nutrition environment. RESULTS: A total of 302 children and 23 local kindergartens from three regions of Hong Kong were surveyed. The results showed consumption of vegetable and fruit were adequate; however, consumption of grain and meat were excessive, while milk and dairy intakes were inadequate. On average, the children consumed 1,280 kcal per day, or 92% of the Chinese Nutrition Society's energy recommendation. For macronutrients, the mean percentages of energy from carbohydrate, protein and fat were 55%, 17% and 28%, respectively, which are within the United States Acceptable Macronutrient Distribution Ranges. The mean intakes of carbohydrate and protein were 175 g and 53.4 g, respectively. For micronutrients, the mean intakes of vitamin D, calcium, iron and zinc were significantly lower than the reference nutrient intake or adequate intake (p<0.05), but those of sodium and niacin were significantly higher than the tolerable upper intake levels (p<0.05). CONCLUSION: This study showed that diet quality among children in Hong Kong needs to be improved, as some nutrients are consumed in excess whereas others are consumed in inadequate amounts. Other results on children's eating behaviour, parent's feeding practices and school nutrition environment are also reported.

Murine Inhibin α-Subunit Haploinsufficiency Causes Transient Abnormalities in Prepubertal Testis Development Followed by Adult Testicular Decline.

Activin production and signaling must be strictly regulated for normal testis development and function. Inhibins are potent activin inhibitors; mice lacking the inhibin-α gene (Inha-/- mice) cannot make inhibin and consequently have highly elevated activin and FSH serum concentrations and excessive activin signaling, resulting in somatic gonadal tumors and infertility. Dose-dependent effects of activin in testicular biology have been widely reported; hence, we hypothesized that male mice lacking one copy of the Inha gene would produce less inhibin and have an abnormal reproductive phenotype. To test this, we compared hormone concentrations, testis development, and sperm production in Inha+/+ and Inha+/- mice. Serum and testicular inhibin-α concentrations in adult Inha+/- mice were approximately 33% lower than wild type, whereas activin A, activin B, FSH, LH, and T were normal. Sixteen-day-old Inha+/- mice had a mixed phenotype, with tubules containing extensive germ cell depletion juxtaposed to tubules with advanced Sertoli and germ cell development. This abnormal phenotype resolved by day 28. By 8 weeks, Inha+/- testes were 11% larger than wild type and supported 44% greater daily sperm production. By 26 weeks of age, Inha+/- testes had distinct abnormalities. Although still fertile, Inha+/- mice had a 27% reduction in spermatogenic efficiency, a greater proportion of S-phase Sertoli cells and lower Leydig cell CYP11A1 expression. This study is the first to identify an intratesticular role for inhibin/inhibin-α subunit, demonstrating that a threshold level of this protein is required for normal testis development and to sustain adult somatic testicular cell function.

A conformationally mobile cysteine residue (Cys-561) modulates Na+ and H+ activation of human CNT3.

In humans, the SLC28 concentrative nucleoside transporter (CNT) protein family is represented by three Na+-coupled members; human CNT1 (hCNT1) and hCNT2 are pyrimidine and purine nucleoside-selective, respectively, whereas hCNT3 transports both purine and pyrimidine nucleosides and nucleoside drugs. Belonging to a phylogenetic CNT subfamily distinct from hCNT1/2, hCNT3 also mediates H+/nucleoside cotransport. Using heterologous expression in Xenopus oocytes, we have characterized a cysteineless version of hCNT3 (hCNT3C-). Processed normally to the cell surface, hCNT3C- exhibited hCNT3-like transport properties, but displayed a decrease in apparent affinity specific for Na+ and not H+. Site-directed mutagenesis experiments in wild-type and hCNT3C- backgrounds identified intramembranous Cys-561 as the residue responsible for this altered Na+-binding phenotype. Alanine at this position restored Na+ binding affinity, whereas substitution with larger neutral amino acids (threonine, valine, and isoleucine) abolished hCNT3 H+-dependent nucleoside transport activity. Independent of these findings, we have established that Cys-561 is located in a mobile region of the hCNT3 translocation pore adjacent to the nucleoside binding pocket and that access of p-chloromercuribenzene sulfonate to this residue reports a specific H+-induced conformational state of the protein ( Slugoski, M. D., Ng, A. M. L., Yao, S. Y. M., Smith, K. M., Lin, C. C., Zhang, J., Karpinski, E., Cass, C. E., Baldwin, S. A., and Young, J. D. (2008) J. Biol. Chem. 283, 8496-8507 ). The present investigation validates hCNT3C- as a template for substituted cysteine accessibility method studies of CNTs and reveals a pivotal functional role for Cys-561 in Na+- as well as H+-coupled modes of hCNT3 nucleoside transport.