Structure, Organization, and Expression of the lct Gene for Lacticin 481, a Novel Lantibiotic Produced by Lactococcus lactis

The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 61-residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in β-methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry.

Dynamical ultrafast all-optical switching of planar GaAs/AlAs photonic microcavities

The authors study the ultrafast switching-on and -off of planar GaAs/AlAs microcavities. Up to 0.8% refractive index changes are achieved by optically exciting free carriers at 1720 nm and a pulse energy of 1.8 micro Joules. The cavity resonance is dynamically tracked by measuring reflectivity versus time delay with tunable laser pulses, and is found to shift by as much as 3.3 linewidths within a few picoseconds. The switching-off occurs with a decay time of around 50 ps. The authors derive the dynamic behavior of the carrier density and of the complex refractive index. They propose that the inferred 10 GHz switching rate may be tenfold improved by optimized sample growth.Comment: 1.) Replaced figure 1 (linear reflectivity) with a more recent and improved measurement 2.) Included a Figure of Merit for switching and compared to other recent contributions 3.) Explained more precisely the effect of embedded Quantum Dots (namely no effect on measurement) 4.) Changed wording in a few place

Associations of 24 h urinary excretions of alpha- and gamma-carboxyethyl hydroxychroman with plasma alpha- and gamma-tocopherol and dietary vitamin E intake in older adults:the Lifelines-MINUTHE Study

Background Urinary metabolites of vitamin E, i.e., alpha- and gamma-carboxyethyl hydroxychroman (alpha- and gamma-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma alpha-tocopherol and gamma-tocopherol and dietary vitamin E intake with 24 h urinary excretions of alpha- and gamma-CEHC. Objectives We aimed to (1) investigate the associations of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC with plasma alpha- and gamma-tocopherol, respectively; (2) investigate the associations of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of alpha- and gamma-CEHC will better correlate with vitamin E intake than urinary alpha- and gamma-CEHC/creatinine ratios. Design 24 h Urine and plasma samples were collected from 1519 participants (60-75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary alpha- and gamma-CEHC/creatinine ratios and 24 h urinary excretions of alpha- and gamma-CEHC, and plasma alpha- and gamma-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma alpha- and gamma-tocopherol, dietary vitamin E intake, with urinary alpha- and gamma-CEHC were assessed using multivariate linear regressions. Results 24 h Urinary excretion of alpha-CEHC (median (IQR): 0.9 (0.3-2.4) mu mol) was less than that of gamma-CEHC (median (IQR): 1.5 (0.5-3.5) mu mol). After adjustment for covariates, we found that 24 h urinary alpha-CEHC excretion and urinary alpha-CEHC/creatinine ratio were both positively associated with plasma alpha-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary alpha- and gamma-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary alpha- and gamma-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma alpha- and gamma-tocopherol and dietary vitamin E intake, nor between urinary gamma-CEHC and plasma gamma-tocopherol. Conclusion Our study confirmed our hypothesis that 24 h urinary alpha- and gamma-CEHC excretions would be a better marker for dietary vitamin E intake than urinary alpha- and gamma-CEHC/creatinine ratios. Considering that both 24 h urinary alpha- and gamma-CEHC excretions and alpha- and gamma-CEHC/creatinine ratios were also associated with plasma alpha-tocopherol status, we suggest that 24 h urinary alpha- and gamma-CEHC excretions could be used to assess overall vitamin E status

Observation of a stronger-than-adiabatic change of light trapped in an ultrafast switched GaAs-AlAs microcavity

We study the time-resolved reflectivity spectrum of a switched planar GaAs-AlAs microcavity. Between 5 and 40 ps after the switching (pump) pulse we observe a strong excess probe reflectivity and a change of the frequency of light trapped in the cavity up to 5 linewidths away from the cavity resonance. This frequency change does not adiabatically follow the fast-changing cavity resonance. The frequency change is attributed to an accumulated phase change due to the time-dependent refractive index. An analytical model predicts dynamics in qualitative agreement with the experiments, and points to crucial parameters that control future applications.Comment: Discussed effect of probe bandwidth. Included functional forms of n(z) and R(z

Specific protein homeostatic functions of small heat-shock proteins increase lifespan

During aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat-shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress-denatured substrates and/or to prevent aggregation of disease-associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70-dependent refolding of stress-denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70-independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo

Hypomagnesaemia and its determinants in a contemporary primary care cohort of persons with type 2 diabetes

AIMS: Among persons with type 2 diabetes mellitus (T2DM) hypomagnesaemia has been reported in 14-48% of patients. This may be of significance given the emerging associations of hypomagnesaemia with glucometabolic disturbances and possibly even complications. We assessed the prevalence of hypomagnesaemia and its determinants, in a well-defined cohort of persons with T2DM treated in primary care. METHODS: Observational cohort study among persons with T2DM treated in primary care in the Northeast of the Netherlands. Magnesium was measured using a colorimetric endpoint assay (Roche). Hypomagnesaemia was defined as a serum magnesium level <0.70 mmol/L. Pearson correlations were performed to correlate variables with serum magnesium. Next, a stepwise backward regression model was made. RESULTS: Data of 929 persons (55% male) with a mean age of 65 (± 10) years, diabetes duration 6.5 [3.0-10.1] years, and HbA1c concentration 6.7 (± 0.7)% (50 (± 9) mmol/mol) were analysed. Serum magnesium was 0.79 (± 0.08) mmol/L. The percentage of persons with magnesium deficiency was 9.6%. Age, diabetes duration, BMI, HbA1c, use of metformin, sulfonylurea derivatives, and DPP4 inhibitors were negatively associated with magnesium concentrations. In contrast, LDL cholesterol and serum creatinine were positively associated serum magnesium. CONCLUSIONS: Hypomagnesaemia was present in 9.6% of T2DM patients treated in primary care. This percentage is remarkably lower than reported previously, possibly due to the unselected nature of our population. Concerning T2DM-related factors, only BMI, HbA1c and the use of metformin, sulfonylurea derivatives and DPP4 inhibitors correlated negatively with magnesium concentrations

Rationale and design of the CORE (COrticosteroids REvised) study:protocol

Introduction Corticosteroids are an important pillar in many anti-inflammatory and immunosuppressive treatment regimens and are available in natural and synthetic forms, which are considered equipotent if clinical bioequivalence data are used. Current clinical bioequivalence data are however based on animal studies or studies with subjective endpoints. Furthermore, advancement in steroid physiology with regard to metabolism, intracellular handling and receptor activation have not yet been incorporated. Therefore, this study aims to re-examine the clinical bioequivalence and dose effects of the most widely used synthetic corticosteroids, prednisolone and dexamethasone. Methods and analysis In this double-blind, randomised cross-over clinical trial, 24 healthy male and female volunteers aged 18-75 years, will be included. All volunteers will randomly receive either first a daily dose of 7.5 mg prednisolone for 1 week, immediately followed by a daily dose of 30 mg prednisolone for 1 week, or first a presumed clinical bioequivalent dose of 1.125 mg dexamethasone per day, immediately followed by 4.5 mg of dexamethasone per day for 1 week. After a wash-out period of 4-8 weeks, the other treatment will be applied. The primary study endpoint is the difference in free cortisol excretion in 24 hours urine. Secondary endpoints will include differences in immunological parameters, blood pressure and metabolic measurements. Ethics and dissemination This study has been approved by the Medical Ethics Committee of the University Medical Center Groningen (METC 2020.398). The results of this study will be submitted for publication in peer-reviewed journals

Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled with a mixture of gas and oil, for the local delivery of lipophilic drugs

Predicting success of vagus nerve stimulation (VNS) from interictal EEG

AbstractPurposeVagus nerve stimulation (VNS) has shown to be an effective treatment for drug resistant epilepsy in numerous patients, however, not in all. It is still not possible to predict which patients will profit from VNS. In this pilot study, we explore predictive interictal EEG features for seizure reduction after VNS.Methods19 Patients with medically refractory epilepsy and an implanted VNS system were included. Interictal EEG registrations, recorded before implantation, were retrospectively analysed. A quantative symmetry measure, the pair wise derived brain symmetry index (pdBSI), was tested to predict VNS outcome. Reduction in seizure frequency was used to define the responders.Results10 Patients did respond to VNS, of whom 7 patients had a seizure reduction of at least 50% in a follow-up period of 2 years. On average, we find higher pdBSI values for delta, theta, alpha and beta bands for non-responders than for responders. The average pdBSI of the theta and alpha bands could significantly discriminate between responders and non-responders.ConclusionIn this study, quantifying EEG symmetry using the pdBSI shows promising results in predicting the reduction of seizure frequency after VNS treatment