Concomitant Effects Research Articles

DMSO potentiates the suppressive effect of dronabinol on sleep apnea and REM sleep in rats

IntroductionDimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations of dronabinol, a cannabinoid, dissolved in DMSO demonstrated decreased sleep apnea frequency and time spent in REM sleep in rats. Here, we tested the effects of dronabinol dissolved in 25% DMSO diluted in phosphate-buffered saline (PBS) to rule out potentiating effects of DMSO.MethodsSprague–Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections separated by three days: vehicle (25% DMSO/PBS); vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol (CB1/CB2 agonist); dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonists. Sleep was manually scored into NREM and REM stages, and sleep apneas were quantified.ResultsDronabinol dissolved in 25% DMSO did not suppress sleep apneas or modify sleep efficiency compared to vehicle controls, in contrast to previously published results. However, dronabinol did suppress REM sleep, which is in line with previously published results.ConclusionsDronabinol in 25% DMSO partially potentiated dronabinol’s effects, suggesting a concomitant biological effect of DMSO on breathing during sleep.

Electrochemical Crosslinking of Alginate-Towards Doped Carbons for Oxygen Reduction.

Electrochemical crosslinking of alginate strands by in situ iron oxidation was explored using a potentiostatic regime. Carbon-based materials co-doped with iron, nitrogen, and/or sulfur were prepared via electrolyte composition variation with a nitrogen-rich compound (rivanol) or through post-treatments with sodium sulfide. Nanometer-sized iron particles were confirmed by transmission and field emission scanning electron microscopy in all samples as a consequence of the homogeneous dispersion of iron in the alginate scaffold and its concomitant growth-limiting effect of alginate chains. Raman spectra confirmed a rise in structural disorder with rivanol/Na2S treatment, which points to more defect sites and edges known to be active sites for oxygen reduction. Fourier transform infrared (FTIR) spectra confirmed the presence of different iron, nitrogen, and sulfur species, with a marked difference between Na2S treated/untreated samples. The most positive onset potential (-0.26 V vs. saturated calomel electrode, SCE) was evidenced for the sample co-doped with N, S, and Fe, surpassing the activity of those with single and/or double doping. The mechanism of oxygen reduction in 0.1 M KOH was dominated by the 2e- reduction pathway at low overpotentials and shifted towards complete 4e- reduction at the most negative explored values. The presented results put forward electrochemically formed alginate gels functionalized by homogeneously dispersed multivalent cations as an excellent starting point in nanomaterial design and engineering.

The effect of vitamin D supplementation on the brain mapping and behavioral performance of children with ADHD: a double-blinded randomized controlled trials

ABSTRACT Background Attention deficit hyperactivity disorder (ADHD) is one of the common neurodevelopmental diseases that are accompanied with EEG pattern changes and Low levels of 25-hydroxyvitamin D [25(OH)D]. Neurofeedback provides a feedback signal to alleviate brain wave abnormalities and offers an alternative therapy for ADHD. This study aimed to investigate the concomitant effects of Vitamin D3 supplementation and Neurofeedback on children with ADHD. Method This study was implemented on children with an established diagnosis of ADHD who received multisession Neurofeedback therapy. The intervention and control groups received 50000 IU vitamin D3 capsules and placebo respectively once a week for 2 months. The background rhythm was measured using quantitative EEG both before and at the end duration of the therapy. Results All of the vitamin D3 treated children showed a significant increase in the 25(OH)D (46 ± 18, 28 ± 10 (ng/ml), p = 0.001) and serum calcium level (9.5 ± 0.5, 9.8 ± 0.3 (mg/dl), p = 0.003) compared to the baseline. There were a statistically significant decrease in the treatment group about theta relative power, theta/beta, and theta/alpha power ratios within two eyes conditions (p = 0.004). All the changes were significant within eye open state in the treatment group (2.4 ± 1.2, 1.7 ± 0.5, p = 0.01). There is a significant relationship between Connors scores and some brain waves improvement (in relative theta (r = 0.998) and theta-to-beta power difference score (r = 0.56) (p < 0.001). Conclusion Concomitant use of vitamin D3 supplementation and neurofeedback, increases the serum level of this vitamin and reveal favorable electrophysiological results in children with ADHD. Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20200922048802N1..

Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management.

Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need to continually screen natural products for effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due to their structural diversity, constitute a reserve for the discovery of lead compounds with interesting pharmacological activities. Several in vitro studies and a few in vivo findings have documented various cytotoxic and antiproliferative properties of alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin and neferine, which belong to different alkaloid classes with antineoplastic properties and have been identified recently from plants. Despite their low solubility and bioavailability, plant-derived alkaloids have viable prospects as sources of viable lead antitumor agents. This potential can be achieved if more research on these chemical compounds is directed toward investigating ways of improving their delivery in an active form close to target cells, preferably with no effect on neighboring normal tissues.

Appraisal of Fizzling Features of Hausa Vernacular Architecture (HVA) in Selected Areas of Jos (cikin gari) City Centre, Plateau State, Nigeria.

Dakali is a unique feature that plays a functional role in the Hausa Vernacular Architecture (HVA). However, events have revealed a gradual extinction from the streetscape due to contemporary changes in the cityscapes and the general physical development with the concomitant effect of reduction in the performance of the expected function in buildings. This paper focuses on the enumeration and documentation of buildings with or without this significant feature. It also appraises the attendant contemporary architectural design-shift. The paper adopts quantitative research approach; purposive sampling and Content analysis method in the selection of potential respondents and review of related literature respectively. This was complimented with the conduct of field survey, selective interviews and observation. Information extracted therefrom was descriptively presented. Findings revealed that out of the total of 235 selected samples, 50 buildings (about 21%) reflects the HVA features; only 14 buildings (about 5.95%), though with retained feature HVA like the Dakali, but have significantly lost the features and transiting towards the contemporary/modern trends; while, 171 (about 72.7%) of the buildings in the study area have completely been transformed. The paper concludes that there is the need for the identification and comprehensive documentation other HVA features for posterity, so as not to allow their total loss without any form of record of their historical existence, due to fast changes been experienced arising from the advent of innovative design, challenges of rapid rate of global urbanization and the trending break-through in technological advancement within our urban/city settings.

Neuroprotective effects of estetrol in combined oral contraceptives: A review

One of the most effective contraception methods is combined hormonal contraceptives. According to the current prescribing information, in addition to their primary effect, they have several concomitant positive effects on the female body non-contraceptive effects. These include a well-predictable and controlled "menstrual cycle" (menstrual-like reaction), anti-androgenic effect, anti-anemic effect due to reduced menstrual blood loss, reducing the severity of dysmenorrhea and premenstrual syndrome, reducing the risk of pelvic inflammatory diseases, ectopic pregnancy, and some benign and malignant tumors of the reproductive system. Combined oral contraceptives (COCs) also have effects on the central nervous system, hypothalamic-pituitary structures that regulate sex hormones, and the psycho-emotional health of women. For a long time, the main estrogen component of COCs remained ethinylestradiol. Although not well-studied, its mechanisms of action on the nervous system are similar, regardless of the progestogen component. However, the effect was not entirely positive: taking contraceptives containing ethinylestradiol can lead to increased emotional lability, anxiety, and depressive disorders. It drives researchers to search for new estrogen without these adverse properties. Such is the long-known but overlooked esthetrol. Numerous studies indicate a pronounced neuroprotective effect of esthetrol, which can increase patients' satisfaction with hormonal contraceptives and their compliance. It also opens up great opportunities for the use of this drug beyond gynecological practice.

Acid suppressants reduce the therapeutic effect of immune checkpoint inhibitors and increase the risk of acute kidney injury: a meta-analysis.

Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses. We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs. The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21-1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21-1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81-1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74-2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS. It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI.

Social Support and Commitment to Life and Living: Bidirectional Associations in Late Life over Time.

This study aims to enhance the understanding of longitudinal associations between two important facets of well-being in late life: social support and commitment to life and living (CTL). Structured home interviews were conducted with 824 Israelis ≥75 years of age, with three annual data collection timepoints. We hypothesized and tested a cross-lagged, longitudinal structural equation model (SEM) in which CTL and social support were assumed to predict each other over time, covarying for previously reported CTL and social support. Social support has a positive, contemporaneous effect, predicting commitment to living at T1 and T3, while CTL predicts social support the following year (i.e., T1-T2 & T2-T3). Satisfaction with relationships significantly contributes to measurement of both latent constructs at each point of data collection. Commitment to life and living and social support are intertwined phenomena. Whereas social support has a concomitant effect on CTL, the effect of CTL on social support emerges over time. This suggests that greater social support fosters greater CTL, leading older adults to nurture social networks and relationships; the effect of which is greater social support in the future. The implications of these results warrant further research over longer periods and across cultures.

Phenologically Targeted Grazing: A Potential Sustainable Strategy for Native Bees in Semiarid Rangelands

Rangelands may offer valuable habitat for invertebrate wildlife, helping conserve ecologically and economically significant organisms, like native bees. In some systems, livestock may affect bees by consuming or trampling blooming plants that bees rely on for food. One potential way to reduce potential negative effects of livestock on bees is to delay grazing on floristically rich parts of the landscape until after peak bloom (i.e., phenologically targeted grazing). To test the outcome of this method, we collected bees using pan traps and counted blooming stems from May to September in grazed and ungrazed sites. Our sites were located in two experimental cattle grazing systems in the Pacific Northwest, United States, in which cattle turnout did not occur until after peak forb bloom. One system was located in bunchgrass prairie, and the other was located in riparian meadows. Our objectives were to 1) quantify seasonal variation in bee and blooming plant communities and 2) measure how or if these communities responded to grazing. In both systems, bee and bloom species richness peaked in June and bloom abundance and diversity were highest in May and June. Bee abundance and diversity were more variable throughout the season. We observed significantly lower abundance, richness, and diversity of blooming species in the riparian system in response to grazing, potentially decreasing floral resource availability for bees, but did not detect a concomitant negative effect on bees. In the bunchgrass system, we observed no significant negative effects of grazing on bees or blooming plants. This suggests that for areas with high-quality bee habitat, site-specific, phenologically targeted grazing may moderate negative effects of livestock on bee and plant communities. Range managers could use alternative grazing locations (e.g., old fields, early senescing sites, more intensively managed pastures), if available, during peak bloom to mitigate potential herbivory effects on bees and blooms.

Surrounding landscape, habitat and hybridization dynamics drive population structure and genetic diversity in the Saltmarsh Sparrow

Abstract Determining factors that shape a species’ population genetic structure is beneficial for identifying effective conservation practices. We assessed population structure and genetic diversity for Saltmarsh Sparrow (Ammospiza caudacuta), an imperiled tidal marsh specialist, using 13 microsatellite markers and 964 individuals sampled from 24 marshes across the breeding range. We show that Saltmarsh Sparrow populations are structured regionally by isolation-by-distance, with gene flow occurring among marshes within ~110 to 135 km of one another. Isolation-by-resistance and isolation-by-environment also shape genetic variation; several habitat and landscape features are associated with genetic diversity and genetic divergence among populations. Human development in the surrounding landscape isolates breeding marshes, reducing genetic diversity, and increasing population genetic divergence, while surrounding marshland and patch habitat quality (proportion high marsh and sea-level-rise trend) have the opposite effect. The distance of the breeding marsh to the Atlantic Ocean also influences genetic variation, with marshes farther inland being more divergent than coastal marshes. In northern marshes, hybridization with Nelson’s Sparrow (A. nelsoni) strongly influences Saltmarsh Sparrow genetic variation, by increasing genetic diversity in the population; this has a concomitant effect of increasing genetic differentiation of marshes with high levels of introgression. From a conservation perspective, we found that the majority of population clusters have low effective population sizes, suggesting a lack of resiliency. To conserve the representative breadth of genetic and ecological diversity and to ensure redundancy of populations, it will be important to protect a diversity of marsh types across the latitudinal gradient of the species range, including multiple inland, coastal, and urban populations, which we have shown to exhibit signals of genetic differentiation. It will also require maintaining connectivity at a regional level, by promoting high marsh habitat at the scale of gene flow (~130 km), while also ensuring “stepping stone” populations across the range.

The Igarapé Weir decelerated transport of contaminated sediment in the Paraopeba River after the failure of the B1 tailings dam (Brumadinho)

The B1 dam of Córrego do Feijão Mine, owned by Vale, S.A. mining company and located on the Ferro-Carvão stream, collapsed and injected 2.8 Mm3 of clayey, silty, and sandy iron- and manganese-rich tailings into the Paraopeba River (Minas Gerais state, Brazil). The accident occurred on 25 January 2019 and the tailings have been co-transported with coarser natural sediment since then, being partly trapped in the Igarapé Weir reservoir located on the Paraopeba River nearly 45 km downstream the injection point. The general purpose of the current study was to model suspended sediment transport in the vicinity of the Igarapé Weir aiming to assess the concomitant barrier effect imposed by this structure. Specifically, the spatial distributions of suspended clay, silt, and very fine-grained sand fractions (CSS) of sediment were mapped around the Igarapé Weir under low-flow (16 m3/s) and high-flow (5 to 10,000 years return period stream discharge; 699–2,699 m3/s) regimes, using RiverFlow2D as the modelling tool. The concentrations of the various grain materials in the upstream and downstream sectors were quantified linking the barrier effect to concentration reductions in the direction of stream flow. It was also a study goal to calculate differences of iron and manganese concentrations in the sediment + tailings mixtures along the Paraopeba River. The study results showed reductions in the CSS between 6.6% and 18%, from upstream to downstream of the Igarapé Weir, related with backwater effects, free and submerged hydraulic jumps, bank sedimentation in periods of high flow, and streambed sedimentation controlled by channel sinuosity and tailings density. These reductions were accompanied by drops in the concentrations of iron and manganese present in the clay and silt fractions, which varied between 6% and 42% under low flows and between 16% and 44% under high flows. Bank sedimentation was viewed as a potential threat to the riparian vegetation in the long-term. Dredging is the potentially most effective mitigation measure to help lead the Paraopeba River to a pre-rupture condition. The retention of sediment + tailings transported in suspension is less effective than the trapping of bedload sediment + tailings behind the Igarapé weir. The efficacy of sediment trapping is expected to be larger for natural sediment because it is much coarser than the tailings. In that context, the simulations revealed for the low-flow period that 33.6% of the sediment deposition comprised suspended transport of natural sediment (thus, was comprised 66.4% of bedload transport), this proportion rose to 86.9% for mixtures of natural sediment + tailings, a result that did not differ much for the high-flow periods.

Phosphoinositide and redox dysregulation by the anticancer methylthioadenosine phosphorylase transition state inhibitor

Methylthio-DADMe-immucillin-A (MTDIA) is an 86 picomolar inhibitor of 5′-methylthioadenosine phosphorylase (MTAP) with potent and specific anti-cancer efficacy. MTAP salvages S-adenosylmethionine (SAM) from 5′-methylthioadenosine (MTA), a toxic metabolite produced during polyamine biosynthesis. Changes in MTAP expression are implicated in cancer growth and development, making MTAP an appealing target for anti-cancer therapeutics. Since SAM is involved in lipid metabolism, we hypothesised that MTDIA alters the lipidomes of MTDIA-treated cells. To identify these effects, we analysed the lipid profiles of MTDIA-treated Saccharomyces cerevisiae using ultra-high resolution accurate mass spectrometry (UHRAMS). MTAP inhibition by MTDIA, and knockout of the Meu1 gene that encodes for MTAP in yeast, caused global lipidomic changes and differential abundance of lipids involved in cell signaling. The phosphoinositide kinase/phosphatase signaling network was specifically impaired upon MTDIA treatment, and was independently validated and further characterised via altered localization of proteins integral to this network. Functional consequences of dysregulated lipid metabolism included a decrease in reactive oxygen species (ROS) levels induced by MTDIA that was contemporaneous with changes in immunological response factors (nitric oxide, tumour necrosis factor-alpha and interleukin-10) in mammalian cells. These results indicate that lipid homeostasis alterations and concomitant downstream effects may be associated with MTDIA mechanistic efficacy.

0032 ADA Functional Polymorphism Modulates REM Sleep Following Total Sleep Deprivation

Abstract Introduction Adenosine Deaminase (ADA) regulates extracellular levels of adenosine, a brain correlate of sleep homeostasis. A single nucleotide polymorphism (SNP) of the ADA gene (rs73598374) is known to be associated with increased homeostatic pressure for NREM sleep after total sleep deprivation (TSD). Whether this genotype effect also impacts REM sleep after TSD has not been systematically investigated. The limit cycle reciprocal interaction model posits that NREM/REM cycles are regulated by cholinergic and GABAergic neurotransmitter systems. While NREM/REM regulation is also thought to be mediated by sleep homeostatic state, evidence of an association with adenosine levels has not been reported. Here we investigate the influence of ADA on REM sleep at baseline and following TSD. Methods N=48 healthy, normal sleepers (ages 27.7 + 5.3, 23 females) participated in one of three in-laboratory TSD studies. Following 10h baseline sleep (22:00–08:00), participants underwent 38h TSD, with subsequent 10h recovery sleep (22:00–08:00). Sleep periods were recorded polysomnographically and scored visually according to AASM criteria. Genomic DNA was extracted from whole blood, and the ADA SNP was assayed using real-time PCR. Sleep stages were analyzed using mixed-effect ANOVA with fixed effects of ADA genotype, night (baseline vs. recovery), and their interaction, controlling for study, with a random effect over subject on the intercept. Results The frequency of genotypes (G/G: 42, A/G: 6) did not vary from Hardy-Weinberg equilibrium. There was no genotype effect on total sleep time and no genotype by night interaction (p&amp;gt;0.7). However, A allele carriers spent more time in REM during baseline and less during recovery compared to G/G homozygotes (genotype by night interaction: F[1,46]=8.13, p=0.007). Conversely, while not statistically significant (p&amp;gt;0.1), A allele carriers spent less time in NREM during baseline and more during recovery compared to G/G homozygotes. Conclusion ADA genotype was associated with a shift in balance between REM and NREM at baseline, as well as changes therein after TSD, without concomitant effect on total sleep time. This suggests a role for adenosine in mediating REM sleep regulation, possibly through a sleep homeostatic effect on the reciprocal interaction between NREM and REM. Support (if any) CDMRP W81XWH-05-1-0099; ONR N00014-13-C-0063; NIH R21CA16769; ARO W911NF2210223.

Irritable bowel syndrome: shifts in point of view

The main symptom of irritable bowel syndrome (IBS), a recurrent functional GI disorder, is abdominal pain associated with defecation, a change in the frequency of bowel movements and a change in the consistency of stool. Until recently, it was the only specific disease that was included in the international classification of the 10th revision. Another 53 functional disorders will be included in the classification of the 11th revision and receive the status of ICD diseases. There are four main variants of IBS: IBS with constipation, IBS with diarrhea, IBS with mixed bowel habit and IBS unclassified. The very concept of IBS was fast-changing. The latest Rome IV (2016) guidelines suggested a mechanism of intraepithelial contact disruption as one of the pathogenetic mechanisms, which activates a minor intramucosal inflammation. It could be relevant to the chronicity of the process and require the use of anti-inflammatory drugs and agents in the treatment that restore intraepithelial contacts, which increases the percentage of patients with a positive treatment effect. The report provides data on the pharmacotherapy of drugs that have a combination (concomitant) effect of action, for example, Meteospasmyl®, which is superior to drugs with antispastic action or action that restores impaired motility in terms of the final effect of the action. The author of this report invites to participate in the discussion about the feasibility of introducing a new IBS variant, which may have a chronic course, and the inclusion of anti-inflammatory drugs in the combination treatment (if drugs that affect motor disorders have insufficient effect).

A Transnational Legacy: André van de Plas and International Folk Dancing in Australia

ABSTRACT Each week in Australia, hundreds of people attend classes in international folk dancing (IFD), eagerly learning and practising dances from around the globe. The existence of FDA and the popularity of IFD must be accorded to André van de Plas from The Netherlands, who visited Australia every year for over three decades. This article examines the practice of IFD in Australia, analysing recreational dance as a leisure pursuit, tracing its historical narrative and describing the foundation of the transnational relationship between van de Plas and Australian IFD practitioners. It focuses on the unique pedagogical methodologies employed, including the intimate relationship between choreography and musical accompaniment as reinforced by van de Plas. Description of the Teacher Training Course and the concomitant effect on IFD and the peak body, Folk Dance Australia. Finally, IFD practitioners comment following the passing of van de Plas in 2019 and interpersonal connectivity and an inherited enthusiasm for learning and teaching dance are revealed. Overall, the persistent influence of van de Plas on FDA and all IFD aficionados in Australia is recognized and celebrated as a tribute to his life and work.

CHOOSING A TURBOCOMPRESSOR MODEL FOR CONVERTING FREE INLET DIESELS TO TURBOCHARGED DIESELS

The use of supercharged diesel engines improves the combustion process, increases the efficiency of the engine and the overall efficiency of its operation. As a concomitant beneficial effect, there is an increase in the environmental performance of the engine. All of the above factors are particularly relevant for solving the problem of converting so-called "atmospheric" diesel engines into turbocharged engines, and the objects of conversion can be a fleet of old engine models that have not exhausted their resource. The results of the research of this article can be used for the implementation of the association agreement between Ukraine, on the one hand, and the European Union, the European Atomic Energy Community and their member states, on the other hand, in particular, Chapter 6 and Chapter 17 of Chapter V. The purpose of the article is creation of a methodology for determining turbocharger parameters, based on engine intake process parameters and selection, based on these parameters, of a turbocharger model for conversion of "atmospheric" turbocharged diesels. The research methods are based on the thermal calculation of the Hrynevetsky-Mazing engine, the calculation of the regulatory characteristic of the engine according to the cubic trinomial equation, the determination of the characteristic modes of the engine according to the regulatory characteristic, the calculation of the air consumption by the engine depending on the speed of rotation of the crankshaft in different modes of operation of the engine and the superimposition of the obtained results of the air consumption on the "turbo card" of the turbocharger, which allows you to establish the correspondence of the turbocharger model to the engine brand. Calculations were carried out using the mathematical editor Mathcad and Microsoft Excel spreadsheets. The results of the obtained calculations and the methodology can be the basis for the development of recommendations for the choice of a turbocharger when converting "atmospheric" diesel engines with turbocharging. Such recommendations will be useful to agricultural producers, in which the tractor fleet has old brands of tractors with non-supercharged engines that have not exhausted their resource.

Effects of sea cucumber fishing on tropical seagrass productivity

AbstractFishing can drive major ecological change in coastal ecosystems and is typically examined through top‐down trophic impacts. However, the massive removal of biomass can also disrupt key ecological bottom‐up processes, though how these effects shape ecosystems is poorly understood. Here, we examined the ecological roles of two species of commercially exploited sea cucumbers thought to promote primary productivity in nutrient‐poor environments through nutrient provisioning and sediment processing. Using a large‐scale field experiment, we tested whether simulated sea cucumber fishing affected seagrass productivity in a natural system comprising reef and seagrass patches that varied in abundance of vertebrate nutrient providers (i.e., fishes). Our findings were scale‐ and metric‐specific: while we could not detect a change in patch‐level seagrass productivity in response to simulated sea cucumber fishing, individual leaf extension rates were ~15% lower at sites where all sea cucumbers were removed, relative to the highest density, unfished sites. Interestingly, there was no concomitant effect of nutrients from the more abundant reef‐associated fishes, which contribute far more nutrients overall than sea cucumbers. This suggests that sea cucumbers are likely mediating seagrass growth through mechanisms other than direct nutrient provisioning, perhaps through processes associated with sediment processing. Our study demonstrates the potential consequences of under‐regulated and unmonitored sea cucumber fishing on foundation species like seagrasses, while highlighting the importance of taking a community‐based approach to these types of field experiments.

Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect

Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36–3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Multi-Responsive Supercapacitors from Chiral Nematic Cellulose Nanocrystal-Based Activated Carbon Aerogels.

The development of long-lived electrochemical energy storage systems based on renewable materials is integral for the transition toward a more sustainable society. Supercapacitors have garnered considerable interest given their impressive cycling performance, low cost, and safety. Here, the first example of a chiral nematic activated carbon aerogel is shown. Specifically, supercapacitor materials are developed based on cellulose, a non-toxic and biodegradable material. The chiral nematic structure of cellulose nanocrystals (CNCs) is harnessed to obtain free-standing hierarchically ordered activated carbon aerogels. To impart multifunctionality, iron- and cobalt-oxide nanoparticles are incorporated within the CNC matrix. The hierarchical structure remains intact even at nanoparticle concentrations of ≈70 wt%. The aerogels are highly porous, with specific surface areas up to 820 m2 g-1 . A maximum magnetization of 17.8 ± 0.1 emu g-1 with superparamagnetic behavior is obtained, providing a base for actuator applications. These materials are employed as symmetric supercapacitors; owing to the concomitant effect of the hierarchically arranged carbon skeleton and KOH activation, a maximum Cp of 294 F g-1 with a capacitance retention of 93% after 2500 cycles at 50 mV s-1 is achieved. The multifunctionality of the composite aerogels opens new possibilities for the use of biomass-derived materials in energy storage and sensing applications.

The Antinociceptive Activity of (E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide in Mice Is Reduced by (E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide Through Opposing Modulatory Mechanisms at the α7 Nicotinic Acetylcholine Receptor.

The primary objective of this study was to characterize the pharmacological and behavioral activity of 2 novel compounds, DM497 [(E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide] and DM490 [(E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide], structural derivatives of PAM-2, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (nAChR). A mouse model of oxaliplatin-induced neuropathic pain (2.4 mg/kg, 10 injections) was used to test the pain-relieving properties of DM497 and DM490. To assess possible mechanisms of action, the activity of these compounds was determined at heterologously expressed α7 and α9α10 nAChRs, and voltage-gated N-type calcium channel (Ca V 2.2) using electrophysiological techniques. Cold plate tests indicated that 10 mg/kg DM497 was able to decrease neuropathic pain in mice induced by the chemotherapeutic agent oxaliplatin. In contrast, DM490 induced neither pro- nor antinociceptive activity but inhibited DM497's effect at equivalent dose (30 mg/kg). These effects are not a product of changes in motor coordination or locomotor activity. At α7 nAChRs, DM497 potentiated whereas DM490 inhibited its activity. In addition, DM490 antagonized the α9α10 nAChR with >8-fold higher potency than that for DM497. In contrast, DM497 and DM490 had minimal inhibitory activity at the Ca V 2.2 channel. Considering that DM497 did not increase the mouse exploratory activity, an indirect anxiolytic mechanism was not responsible for the observed antineuropathic effect. The antinociceptive activity of DM497 and the concomitant inhibitory effect of DM490 are mediated by opposing modulatory mechanisms on the α7 nAChR, whereas the involvement of other possible nociception targets such as the α9α10 nAChR and Ca V 2.2 channel can be ruled out.