BACKGROUND AND PURPOSE Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present ...study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory‐related behaviour were investigated.
EXPERIMENTAL APPROACH Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age‐matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil.
KEY RESULTS Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperphosphorylation and a decrease in the activity of glycogen synthase kinase 3β (GSK3β) and of cyclin‐dependent kinase 5 (CDK5) (p25/p35 ratio). Moreover, sildenafil also increased levels of brain‐derived neurotrophic factor (BDNF) and the activity‐regulated cytoskeletal‐associated protein (Arc) in the hippocampus without any detectable modification of brain amyloid burden.
CONCLUSIONS AND IMPLICATIONS Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease.
Halite deposits from the hyperarid zone of the Atacama Desert reveal the presence of endolithic microbial colonization dominated by cyanobacteria associated with heterotrophic bacteria and archaea. ...Using the λ-scan confocal laser scanning microscopy (CLSM) option, this study examines the autofluorescence emission spectra produced by single cyanobacterial cells found inside halite rocks and by their photosynthetic pigments. Photosynthetic pigments could be identified according to the shapes of the emission spectra and wavelengths of fluorescence peaks. According to their fluorescence fingerprints, three groups of cyanobacterial cells were identified within this natural extreme microhabitat: (i) cells producing a single fluorescence peak corresponding to the emission range of phycobiliproteins and chlorophyll a, (ii) cells producing two fluorescence peaks within the red and green signal ranges, and (iii) cells emitting only low-intensity fluorescence within the nonspecific green fluorescence signal range. Photosynthetic pigment fingerprints emerged as indicators of the preservation state or viability of the cells. These observations were supported by a cell plasma membrane integrity test based on Sytox Green DNA staining and by transmission electron microscopy ultrastructural observations of cyanobacterial cells.
This study aimed to assess the role of multifocal visual-evoked potentials (mfVEPs) as a guiding factor for clinical conversion of radiologically isolated syndrome (RIS). We longitudinally followed a ...cohort of 15 patients diagnosed with RIS. All subjects underwent thorough ophthalmological, neurological and imaging examinations. The mfVEP signals were analysed to obtain features in the time domain (SNR
: amplitude, Lat
: monocular latency) and in the continuous wavelet transform (CWT) domain (b
: instant in which the CWT function maximum appears, N
: number of CWT function maximums). The best features were used as inputs to a RUSBoost boosting-based sampling algorithm to improve the mfVEP diagnostic performance. Five of the 15 patients developed an objective clinical symptom consistent with an inflammatory demyelinating central nervous system syndrome during follow-up (mean time: 13.40 months). The (SNR
) variable decreased significantly in the group that converted (2.74 ± 0.92 vs. 4.07 ± 0.95, p = 0.01). Similarly, the (b
) feature increased significantly in RIS patients who converted (169.44 ± 24.81 vs. 139.03 ± 11.95 (ms), p = 0.02). The area under the curve analysis produced SNR
and b
values of 0.92 and 0.88, respectively. These results provide a set of new mfVEP features that can be potentially useful for predicting prognosis in RIS patients.
A few small studies have reported increased prevalences of polycystic ovary syndrome (PCOS) and symptoms of androgen excess in women with type 1 diabetes.
We performed a systematic review and ...meta-analysis of studies evaluating androgen excess symptoms and PCOS in women with type 1 diabetes.
The Entrez-PubMed and Scopus electronic databases were used.
We selected studies addressing androgen excess signs, symptoms, and disorders in girls, adolescents, and adult women with type 1 diabetes.
The main outcome measures were prevalences of PCOS, hyperandrogenemia, hirsutism, menstrual dysfunction, and polycystic ovarian morphology (PCOM).
Nine primary studies involving 475 adolescent or adult women with type 1 diabetes were included. The prevalences of PCOS and associated traits in women with type 1 diabetes were 24% (95% CI 15-34) for PCOS, 25% (95% CI 17-33) for hyperandrogenemia, 25% (95% CI 16-36) for hirsutism, 24% (95% CI 17-32) for menstrual dysfunction, and 33% (95% CI 24-44) for PCOM. These figures are considerably higher than those reported earlier in the general population without diabetes.
The data collected in the original studies were heterogeneous in age, race, ethnicity, and criteria used for the diagnosis of PCOS; yet, we used a quality-effects model in the meta-analyses to overcome this limitation.
PCOS and its related traits are frequent findings in women with type 1 diabetes. PCOS may contribute to the subfertility of these women by a mechanism that does not directly depend on glycemic/metabolic control among other negative consequences for their health. Hence, screening for PCOS and androgen excess should be included in current guidelines for the management of type 1 diabetes in women.
Background
Previous research has demonstrated the efficacy of cognitive engagement in reducing concurrent pain. However, little is known about the role of individual differences in inhibitory control ...abilities and negative pain‐related cognitions in modulating the magnitude of this type of distraction from pain.
Methods
In a pain distraction paradigm, 41 participants completed a working memory task with both a demanding high load condition (2‐back) and an easy low load condition (0‐back), while receiving warm or painful thermal stimuli to their left forearm. To control for individual differences in sensitivity to pain and perceived task difficulty, nociceptive stimulus intensity and task speed were individually calibrated. Additionally, participants completed a set of cognitive inhibition tasks (flanker, go/nogo, Stroop) and questionnaires about negative pain‐related cognitions (fear of pain, pain catastrophizing) prior to the distraction paradigm.
Results
As expected, engaging in the high load condition significantly reduced perceived intensity and unpleasantness of nociceptive stimuli, compared to the low load condition. The size of the distraction effect correlated significantly with better cognitive inhibition and selective attention abilities, as measured by the flanker task. A moderation analysis revealed a significant interaction between pain catastrophizing and performance in the flanker task in predicting the distraction effect size: Participants who performed well on the flanker task showed more pain reduction, but only when they were average to high pain catastrophizers.
Conclusions
Selective attention abilities and pain catastrophizing seem to be important factors in explaining individual differences in the size of the analgesic response to a distractive task.
Significance
Understanding which factors influence the effectiveness of cognitive engagement in distracting from pain could help to optimize its therapeutic application in patient care. This study shows that a complex interplay of cognitive inhibition abilities, specifically selective attention, and negative pain‐related cognitions, such as pain catastrophizing, modulate the magnitude of the distraction effect.
We examined the role of the most important metabolic enzyme families in the detoxification of neurotoxic insecticides on adult males and females from susceptible populations of Cydia pomonella (L.), ...Grapholita molesta (Busck), and Lobesia botrana (Denis & Schiffermüller). The interaction between the enzyme families - carboxylesterases (EST), glutathione-S-transferases (GST), and polysubstrate monooxygenases (PSMO) - with the insecticides - chlorpyrifos, λ-cyhalothrin, and thiacloprid - was studied. Insect mortality arising from the insecticides, with the application of enzyme inhibitors - S,S,S-tributyl phosphorotrithioate (DEF), diethyl maleate (DEM), and piperonyl butoxide (PBO) - was first determined. The inhibitors' influence on EST, GST, and PSMO activity was quantified. EST and PSMO (the phase-I enzymatic activities) were involved in the insecticide detoxification in the three species for both sexes, highlighting the role of EST, whereas GST (phase-II enzymes) was involved only in G. molesta insecticide detoxification. L. botrana exhibited, in general, the highest level of enzymatic activity, with a significantly higher EST activity compared with the other species. It was the only species with differences in the response between sexes, with higher GST and PSMO activity in females than in males, which can be explained as the lower susceptibility of the females to the tested insecticides. A positive correlation between PSMO activity and the thiacloprid LD50s in the different species-sex groups was observed explaining the species-specific differences in susceptibility to the product reported in a previous study.
Global warming has a strong impact on the polar regions, in particular, the Antarctic Peninsula and nearby islands. Methane (CH
4
) is a major factor in climate change and mitigation of CH
4
...emissions can be accomplished through microbial oxidation by methanotrophic bacteria. Understanding this biological process is crucial given the shortage of research carried out in this geographical area. The aim of this study was to characterise psychrophilic enrichment cultures of aerobic methanotrophs obtained from lake sediments of the Fildes Peninsula (King George Island, South Shetland Islands) and revealing the distribution of the genus
Methylobacter
in different lake sediments of the peninsula. Four stable methanotrophic enrichment cultures were obtained and analysed by metagenome-assembled genomes (MAGs). The phylogeny of methanotroph MAGs recovered from these enrichment cultures based on the 16S rRNA gene showed that K-2018 MAG008 and D1-2020 MAG004
Ts
clustered within the
Methylobacter
clade 2, with high similarity to
Methylobacter tundripaludum
SV96
T
(97.88 and 98.56% respectively). However, the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values with
M. tundripaludum
were < 95% (84.8 and 85.0%, respectively) and < 70% (30.2 and 30.3%, respectively), suggesting that they represent a putative novel species for which the name ‘
Ca.
Methylobacter titanis’ is proposed. This is the first species of clade 2 of the genus
Methylobacter
obtained from Antarctica. The bacterial diversity assessed by 16S rRNA gene sequencing of 21 samples of different lakes (water column and sediments) revealed 54 ASVs associated with methanotrophs and the genus
Methylobacter
as the most abundant. These results suggest that aerobic methanotrophs belonging to the
Methylobacter
clade 2 would be the main responsible for CH
4
oxidation in these sediments.
Additively manufactured AISI 316 L stainless steel samples were heat treated at temperatures from 400 °C to 1100 °C, and the corrosion behavior in chloride environments was electrochemically studied. ...Heat treatments at 400 °C and 650 °C increased the grain size and the treatment at 1100 °C formed MnCr2O4 inclusions. Also, these postprocessing techniques reduce the hardness and increased the porosity. Heat treatment at 400 °C increased the polarization resistance and maintained the pitting corrosion mechanisms of the additively manufactured samples. Heat treatments at higher temperatures reduced the polarization resistance but changed the corrosion resistance mechanisms.
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•The influence of different heat treatments in the corrosion of the 316 L stainless steel manufactured by SLM was studied.•Heat treatments at low temperatures improve the polarization resistance and keep the pitting corrosion behavior.•Heat treatments at high temperatures worsen the polarization resistance and the pitting corrosion of this 316 L.•Heat treatments at high temperatures change the corrosion mechanism of the material shown in Nyquist and Bode’s plots.
Computational and experimental studies unravel the structural and electronic properties of a novel supramolecular liquid crystal built through a hierarchical assembly process resulting in an H‐bonded ...melamine rosette decorated with peripheral triphenylenes. The six‐fold symmetry of the mesogen facilitates the formation of a highly organized hexagonal columnar mesophase stable at room temperature. X‐ray diffraction and electron density maps confirm additional intra‐ and intercolumn segregation of functional subunits, and this paves the way for 1D charge transport. Indeed, hole mobility has been measured and found to be higher than for related mesogens. DFT calculations of HOMO and LUMO levels and parameters such as reorganization energy and transfer integral of the rosette structure have been achieved, and not only validate the columnar organization but also establish the way it translates into a favorable electronic architecture and molecular orbital interactions to promote charge carrier mobility.
Six‐fold semiconducting rosette: the unique hierarchical assembly of six melamines and six triphenylene‐containing acids through H‐bonding interactions self‐organizes into a highly‐ordered hexagonal columnar mesophase, with segregated regions for triphenylenes. The supramolecular architecture influences positively the electronic architecture in terms of favoring molecular‐orbital interactions that favor charge‐carrier mobility as theoretical calculations reveal and experimental measurements prove.
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