Hydrolysis efficiency of β‐galactosidases is affected due to a strong inhibition by galactose, hampering the complete lactose hydrolysis. One alternative to reduce this inhibition is to perform ...mutations in the enzyme's active site. The aim of this study was to evaluate the effect of point mutations on the active site of different microbial β‐galactosidases, using computational techniques. The enzymes of Aspergillus niger (AnβGal), Aspergillus oryzae (AoβGal), Bacillus circulans (BcβGal), Bifidobacterium bifidum (BbβGal), and Kluyveromyces lactis (KlβGal) were used. The mutations were carried out in all residues that were up to 4.5 Å from the galactose/lactose molecules and binding energy was computed. The mutants Tyr96Ala (AnβGal), Asn140Ala and Asn199Ala (AoβGal), Arg111Ala and Glu355Ala (BcβGal), Arg122Ala and Phe358Ala (BbβGal), Tyr523Ala, Phe620Ala, and Trp582Ala (KlβGal) had the best results, with higher effect on galactose binding energy and lower effect on lactose affinity. To maximize enzyme reactions by reducing galactose affinity, double mutations were proposed for BcβGal, BbβGal, and KlβGal. The double mutations in BcβGal and BbβGal caused the highest reduction in galactose affinity, while no satisfactory results were observed to KlβGal. Using computational tools, mutants that reduced galactose affinity without significantly affecting lactose binding were proposed. The mutations proposed can be used to reduce the negative feedback process, improving the catalytic characteristics of β‐galactosidases and rendering them promising for industrial applications.
Different types of extragalactic objects are known to produce TeV gamma-rays. Some of these objects are the most probable candidates to accelerate cosmic rays up to 10 super(20) eV. It is very well ...known that gamma-rays can be produced as a result of the cosmic ray propagation through the intergalactic medium. These gamma-rays contribute to the total flux observed in the direction of the source. In this paper we propose a new method to derive an upper limit on the cosmic-ray luminosity of an individual source based on the measured upper limit on the integral ux of GeV-TeV gamma-rays. We show how it is possible to calculate an upper limit on the cosmic-ray luminosity of a particular source and we explore the parameter space in which the current GeV-TeV gamma-ray measurements can offer a useful determination. We study in detail two particular sources, Pictor A and NGC 7469, and we calculate the upper limit on the proton luminosity of each source based on the upper limit on the integral gamma-ray flux measured by the H.E.S.S. telescopes.
Phytosulfokine (PSK) is a phytohormone responsible for cell-to-cell communication in plants, playing a pivotal role in plant development and growth. The binding of PSK to its cognate receptor, PSKR1, ...is modulated by the formation of a binding site located between a leucine-rich repeat (LRR) domain of PSKR1 and the loop located in the receptor's island domain (ID). The atomic resolution structure of the extracellular PSKR1 bound to PSK has been reported, however, the intrinsic dynamics of PSK binding and the architecture of the PSKR1 binding site remain to be understood. In this work, we used atomistic molecular dynamics (MD) simulations and free energy calculations to elucidate how the PSKR1 island domain (ID) loop forms and binds PSK. Moreover, we report a novel "druggable" binding site which could be exploited for the targeted modulation of the PSKR1-PSK binding by small molecules. We expect that our results will open new ways to modulate the PSK signalling cascade via small molecules, which can result in new crop control and agricultural applications.
The development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis. Herein, we ...report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with organic anions as chemical adjuvants. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride (MFLHCl) and several organic acid sodium salts in high yields. One of the salts, mefloquine mesylate (MFLHMsO), presented increased water solubility in comparison with MFLHCl. Moreover, all salts with the exception of mefloquine docusate (MFLHAOT) showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with MFLHCl, particularly mefloquine camphorsulfonates (MFLH(1R)-CSA, MFLH(1S)-CSA) and mefloquine HEPES (MFLHHEPES).
To verify if acute intake of beetroot juice potentiates post-exercise hypotension (PEH) in hypertensive postmenopausal women.
Thirteen hypertensive postmenopausal women (58.1 ± 4.62 years and 27.4 ± ...4.25 kg/m²) were recruited to participate in three experimental sessions, taking three different beverages: Beetroot juice (BJ), placebo nitrate-depleted BJ (PLA), and orange flavored non-caloric drink (OFD). The participants performed moderate aerobic exercise training on a treadmill, at 65-70% of heart rate reserve (HRR), for 40 min. After an overnight fast, the protocol started at 07h when the first resting blood pressure (BP) was measured. The beverage was ingested at 07h30 and BP was monitored until the exercise training started, at 09h30. After the end of the exercise session, BP was measured every 15 min over a 90-min period. Saliva samples were collected at rest, immediately before and after exercise, and 90 min after exercise for nitrite (NO
) analysis.
There was an increase in salivary NO
with BJ intake when compared to OFD and PLA. A slight increase in salivary NO
was observed with PLA when compared to OFD (
< 0.05), however, PLA resulted in lower salivary NO
when compared to BJ (
< 0.001). There were no changes in salivary NO
with the OFD. Systolic and diastolic BP decreased (
< 0.001) on all post exercise time points after all interventions, with no difference between the three beverages.
Acute BJ intake does not change PEH responses in hypertensive postmenopausal women, even though there is an increase in salivary NO
.
Objective
To estimate the incidence of epilepsy in children with Zika‐related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to ...summarize the treatment responses.
Methods
We followed a cohort of children, born during the 2015‐2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months.
Results
We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin.
Significance
Zika‐related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.
This study tested the effect of isoflavone supplementation in addition to combined exercise training in salivary oxidative stress markers in non-obese postmenopausal women. Thirty-two postmenopausal ...women without hormone therapy were randomly assigned to exercise + placebo (n = 15) or exercise + isoflavone supplementation (n = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Saliva samples were collected after an overnight fast. Superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, catalase, total protein and nitrite were determined before and after ten weeks of the intervention. The ANOVA two-way analysis of variance was applied with α of 5%. Both groups increase (p<0.05) superoxide dismutase activity and decrease catalase levels. There was interaction (time × group) in both nitrite and thiobarbituric acid reactive substances results, with increase (p<0.05) in placebo group and decrease (p<0.05) in isoflavone group. No difference was found for total antioxidant capacity or total protein. The combination of isoflavone supplementation and exercise training can promote an antioxidant effect through reduction of lipid peroxidation and concentrations of salivary nitrite.
Amphiphilic copolymers have a wide variety of medical and biotechnological applications, including DNA transfection in eukaryotic cells. Still, no polymer-primed transfection of prokaryotic cells has ...been described. The reversible addition-fragmentation chain transfer (RAFT) polymer synthesis technique and the reversible deactivation radical polymerization variants allow the design of polymers with well-controlled molar mass, morphology, and hydrophilicity/hydrophobicity ratios. RAFT was used to synthesize two amphiphilic copolymers containing different ratios of the amphiphilic poly2-(dimethyl-amino) ethyl methacrylate and the hydrophobic poly methyl methacrylate. These copolymers bound to pUC-19 DNA and successfully transfected non-competent Escherichia coli DH5α, with transformation efficiency in the range of 103 colony-forming units per µg of plasmid DNA. These results demonstrate prokaryote transformation using polymers with controlled amphiphilic/hydrophobic ratios.
By harnessing the chirality of the DNA double helix, chemists have been able to obtain new, reliable, selective, and environmentally friendly biohybrid catalytic systems with tailor-made functions. ...Nonetheless, despite all the advances made throughout the years in the field of DNA-based asymmetric catalysis, many challenges still remain to be faced, in particular when it comes to designing a “universal” catalyst with broad reactivity and unprecedented selectivity. Rational design and rounds of selection have allowed us to approach this goal. We report here the development of a DNA/RNA hybrid catalytic system featuring a covalently attached bipyridine ligand, which exhibits unmatched levels of selectivity throughout the current DNA toolbox and opens new avenues in asymmetric catalysis.
In cellular systems, information signals must be transmitted at high rates and with high reliability. One of the possible solutions to meet such criteria is the use of systems with multiple ...transmitting and/or receiving antenna arranged in the form of a multiple-input, multiple-output (MIMO) system. However, signal processing techniques in MIMO systems are developed under the assumption of transmission on Gaussian channels, which may lead to the decrease of efficiency in non-Gaussian communication scenarios. In this context, the widespread use of MIMO systems in recent years has motivated the development of new processing techniques that can be employed in scenarios that also consider the presence of non-Gaussian noise in communication channels. This work proposes a novel signal detection technique for MIMO systems, which is called maximum correntropy detector (MCD), being adequate to environments characterized by Gaussian and non-Gaussian noise. The introduced approach is based on complex correntropy function and can be seen as a generalization of the maximum likelihood detector (MLD) concept. The MCD is evaluated on Gaussian and non-Gaussian channels, where superior performance is achieved when compared with the classic detectors, without significant increase of the computational complexity.
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