Metabolic impact assessment for heterologous protein production in Streptomyces lividans based on genome-scale metabolic network modeling

The metabolic impact exerted on a microorganism due to heterologous protein production is still poorly understood in Streptomyces lividans. In this present paper, based on exometabolomic data, a proposed genome-scale metabolic network model is used to assess this metabolic impact in S. lividans. Constraint-based modeling results obtained in this work revealed that the metabolic impact due to heterologous protein production is widely distributed in the genome of S. lividans, causing both slow substrate assimilation and a shift in active pathways. Exchange fluxes that are critical for model performance have been identified for metabolites of mouse tumor necrosis factor, histidine, valine and lysine, as well as biomass. Our results unravel the interaction of heterologous protein production with intracellular metabolism of S. lividans, thus, a possible basis for further studies in relieving the metabolic burden via metabolic or bioprocess engineering.     

Two Novel Missense Mutations in the Connexin 26 Gene in Turkish Patients with Nonsyndromic Hearing Loss

Most nonsyndromic hearing losses are caused by mutations in the GJB2 gene, and studies have revealed that the forms and frequencies of these mutations are largely dependent on ethnic origin. In the present study, we aimed to characterize the mutation profiles of 151 patients with hearing loss in Turkey. The entire coding region of the GJB2 was directly sequenced in all patients. We found 35 (23.2%) individuals carrying GJB2 mutations. Seven different mutations were identified, five of which were previously known (35delG, delE120, R184P, M163V, L90P), the remaining two being novel variants (M34V, L205V). The most common mutation was 35delG followed by delE120. The 35delG mutation was homozygous in 22 cases (14.5%) and heterozygous in 4 cases (2.6%). Compound heterozygosity for 35delG was also observed. The delE120 mutation was found in three patients in homozygous form. A homozygous L90P and heterozygous mutations M163V and M34V were found in single cases.     

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.     

The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Guérin immunization

Bacille Calmette–Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n = 53) and cellular (n = 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml⁻¹ [3300–11 050] in cord blood) and six weeks (0.00 ng ml⁻¹ [0–288]). Frequencies of PPD-specific IFN-γ-expressing CD4⁺T cells increased at one week and declined between one and six weeks (p = 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4⁺T cells increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one week, the frequency of PPD-specific CD4⁺T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI −0.041% (−0.082, −0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study.     

Sleep disturbances and excessive daytime sleepiness in migraine: A comparison between comorbidities and disability

Sleep and Biological Rhythms - Many studies have investigated the association between headache and sleep disorders, but few have focused on migraine. The goal of this study was to evaluate sleep...     

Dietary restriction of amino acids other than methionine prevents oxidative damage during aging: involvement of telomerase activity and telomere length

AimsIt has been suggested that variations in the proportions of some dietary amino acids can slow down aging. In this study, the influence of amino acids other than methionine on aging was investigated.Main methodsRats were fed either with normal (ND) or except methionine, protein restricted diet (PREMD) for 4 months and oxygen radical production, oxidative protein and DNA damage along with telomere length and telomerase activity were evaluated in the liver.Key findingsExcept mitochondrial superoxide production rate, feeding with PREMD significantly decreased the oxygen radical production rate and protein carbonyl levels in the homogenate and mitochondria of 16-month-old rats. Feeding with PREMD prevented 8-OHdG formation in mitochondrial DNA but not in the genomic DNA. Although liver telomerase activities of rats receiving either ND or PREMD seemed to have some variations, these did not reach a statistical significance. Feeding with PREMD conserved the telomere length in the liver. The telomere length of 8- and 16-month-old rats fed PREMD was similar, 16-month-old rats fed ND had telomeres shortened by 36% (p < 0.05).SignificanceLong-term restriction of the amino acids other than methionine may decrease oxygen radical generation and oxidative damage of cellular constituents, and may also prevent telomere shortening in rat liver.