A manually curated compendium of expression profiles for the microbial cell factory Corynebacterium glutamicum.

Corynebacterium glutamicum is the major host for the industrial production of amino acids and has become one of the best studied model organisms in microbial biotechnology. Rational strain construction has led to an improvement of producer strains and to a variety of novel producer strains with a broad substrate and product spectrum. A key factor for the success of these approaches is detailed knowledge of transcriptional regulation in C. glutamicum. Here, we present a large compendium of 927 manually curated microarray-based transcriptional profiles for wild-type and engineered strains detecting genome-wide expression changes of the 3,047 annotated genes in response to various environmental conditions or in response to genetic modifications. The replicates within the 927 experiments were combined to 304 microarray sets ordered into six categories that were used for differential gene expression analysis. Hierarchical clustering confirmed that no outliers were present in the sets. The compendium provides a valuable resource for future fundamental and applied research with C. glutamicum and contributes to a systemic understanding of this microbial cell factory. Measurement(s) Gene Expression Analysis Technology Type(s) Two Color Microarray Factor Type(s) WT condition A vs. WT condition B • Plasmid-based gene overexpression in parental strain vs. parental strain with empty vector control • Deletion mutant vs. parental strain Sample Characteristic - Organism Corynebacterium glutamicum Sample Characteristic - Environment laboratory environment Sample Characteristic - Location Germany.

Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.

BACKGROUND: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. OBJECTIVE: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. DESIGN: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery. SETTING: This single-centre study was conducted at an academic medical centre. PARTICIPANTS: In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD). INTERVENTION: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia. MAIN OUTCOMES AND MEASURES: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365. RESULTS: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery. CONCLUSION: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h. TRIAL REGISTRATION: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).

Questioning the long-term stability of the additive model in comorbid CTD+ADHD - The transition from childhood to adulthood.

BACKGROUND: A previous study (Roessner et al. 2007) found psychopathological evidence of an additive model of the comorbid group with Chronic Tic Disorders and Attention Deficit Hyperactivity Disorder (CTD+ADHD), which demanded clinical interventions aimed primarily at the factor ADHD. This 14-year follow-up study tested whether this childhood additive model can also be found in young adulthood and whether ADHD remains the most impairing factor. METHODS: 92 patients (22.8% girls) from Roessner et al. (2007) were re-investigated as young adults at the age of 24 years, broken down into four groups: CTD-only (n = 22), CTD+ADHD (n = 23), ADHD-only (n = 24), and controls (n = 23). The Adult Behavior Checklist (ABCL) was used as an equivalent parent-report instrument to the Child Behavior Checklist (CBCL) applied 14 years ago. Statistically, 2x2 factorial design was completed. RESULTS: From the point of view of parents, the factors CTD and ADHD in young adults contributed almost equally to psychopathological problems and showed many interactions, i.e. an interactive model was supported. In addition, the ADHD factor was no longer the leading problem for psychosocial impairment in the adult CTD+ADHD group. CONCLUSION: The additive model of CTD+ADHD seems to exist no longer in young adults, nor may the childhood predominance of the factor ADHD in comorbid CTD+ADHD. Thus, treatment priority should be decided by clinicians on a case-by-case basis depending on the most impairing disorder of each patient.

Influence of goal-directed therapy with balanced crystalloid-colloid or unbalanced crystalloid solution on base excess.

OBJECTIVE: To investigate changes in standard base excess (SBE) when administering two different infusion regimens for elective hip replacement within a goal-directed haemodynamic algorithm. METHODS: This prospective, double-blind, randomized, controlled study enrolled patients scheduled for primary hip replacement surgery, who were randomized to receive either an unbalanced crystalloid (chloride: 155.5 mmol/l) or a 1 : 1 mixture of a balanced crystalloid and a balanced colloid (6% w/v hydroxyethyl starch 130/0.42; chloride: 98 and 112 mmol/l, respectively). Fluid management was goal-directed to optimize stroke volume using oesophageal Doppler. RESULTS: A total of 40 patients (19 female/21 male) participated in the study. After surgery, median (25-75% percentiles) SBE was significantly lower in the unbalanced group compared with the balanced group: -2.0 mmol/l (-3.1 to -1.1) versus -0.4 mmol/l (-1.2 to 0.7), respectively. This difference was mainly due to greater plasma chloride concentrations in the unbalanced group. The amount of study medication required to reach haemodynamic stability (median 1200 ml) did not differ between the two groups. CONCLUSION: SBE decreased in the unbalanced group without influence on fluid requirements and haemodynamic stability.

Direct observation of microtubule pushing by cortical dynein in living cells.

Microtubules are under the influence of forces mediated by cytoplasmic dynein motors associated with the cell cortex. If such microtubules are free to move, they are rapidly transported inside cells. Here we directly observe fluorescent protein-labeled cortical dynein speckles and motile microtubules. We find that several dynein complex subunits, including the heavy chain, the intermediate chain, and the associated dynactin subunit Dctn1 (also known as p150glued) form spatially resolved, dynamic speckles at the cell cortex, which are preferentially associated with microtubules. Measurements of bleaching and dissociation kinetics at the cell cortex reveal that these speckles often contain multiple labeled dynein heavy-chain molecules and turn over rapidly within seconds. The dynamic behavior of microtubules, such as directional movement, bending, or rotation, is influenced by association with dynein speckles, suggesting a direct physical and functional interaction. Our results support a model in which rapid turnover of cell cortex-associated dynein complexes facilitates their search to efficiently capture and push microtubules directionally with leading plus ends.

Small-area analysis of incidence and localisation of vulvar cancer.

Objective. Vulvar cancer is a rare disease mainly in older women. HPV and non-HPV induced vulvar cancer reflect two types of oncogenesis. Controversies exist on most recent developments in vulvar cancer incidence, patients, and disease characteristics. Changes in incidence, age of disease onset, and tumor site in women treated for primary vulvar cancer in a single German university hospital unit will be described. Methods. A retrospective analysis of patient records of women treated between 1994 and 2008 was performed. The fifteen-year-spanning period was divided into three five year-spanning cohorts. Descriptive and statistical analyses were performed. Results. 104 patients were identified: cohort-1 from 1994 to 1998 (11 patients); cohort-2 from 1999 to 2003 (21 patients); cohort-3 from 2004 to 2008 (72 patients). Mean age (years) was 73.18 (confidence interval (CI): 64.04; 82.33), 58.9 (CI: 52.24; 65.57), and 61.19 (CI: 57.27; 65.12), respectively. Vulvar cancer confined to the region between clitoris and urethra was seen more often in cohort-3 (n = 20) compared to cohort-1 (n = 0) or cohort-2 (n = 1). Conclusion. This analysis supports the notion of rising incidence of vulvar cancer and a changing pattern of anatomical local extension. Disease onset is not restricted to older women.