Cyclooxygenase and 5-lipoxygenase inhibitory activity of 2,6 di-t-butylphenols linked by a sulfur atom to 1,3,4-thiadiazoles and 1,3,4-oxadiazoles

The preparation of a series of 1,3,4-thiadiazoles and 1,3,4-oxadizoles linked by a thioether to 2,6-di-t-butylphenol and the inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) by these compounds is dicussed.     

Treatment-resistant depression: definition,prevalence, detection,management, and investigational interventions

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.     

Spontaneous Activity in Crustacean Neurons

Single units which discharged with regular spontaneous rhythms without intentional stimulation were observed in the ventral nerve cord by intracellular recording close to the sixth abdominal ganglion. These units were divided into two groups: group A units in which interspike intervals varied less than 10 msec.; group B units in which interspike intervals varied within a range of 10 to 30 msec. Group A units maintained "constant" interspike intervals and could not be discharged by sensory inputs, while the majority of group B units could be discharged by appropriate sensory nerve stimulation. Both group A and B units discharged to direct stimulation when the stimulating and recording electrodes were placed in the same ganglionic intersegment, and directly evoked single spikes reset the spontaneous rhythm. In group B units, presynaptic volleys reset the spontaneous rhythm of some units; but in others, synaptically evoked spikes were interpolated within the spontaneous rhythm without resetting. The phenomenon of enhancement could also be demonstrated in spontaneously active units as a result of repetitive stimulation. It is concluded that endogenous pacemaker activity is responsible for much of the regular spontaneous firing observed in crayfish central neurons, and that interaction of evoked responses with such pacemaker sites can produce a variety of effects dependent upon the anatomical relationships between pacemaker and synaptic regions.     

Seasonal population dynamics of Paraquimpevia tenevvima (Linstow) (Nematoda) in the European eel Anguilla anguilla (Linnaeus) in three localities of southwest England

Seasonal population dynamics of Puraquzmperia tenerrima (Linstow) in the European eel Anguillu anguillu (Linnaeus) have been investigated in three localities in Devon, southwest England. The nematode is common and exhibits very similar seasonal patterns in changes of prevalence and abundance in the three localities. The population increases over winter through to late spring or early summer as the recruitment of the new generation occurs throughout this period. Reproduction of the nematode starts in spring. A sharp decrease of prevalence and abundance accompanies or follows reproduction, and infection levels are very low in autumn and early winter. The dispersion pattern of the nematode varies with the infection levels from over-dispersion in spring and early summer to almost random dispersion in autumn and winter. It is suggested that P. tenerrimu is a common specific parasite of eels, especially in small streams or rivers and that insect larvae or species of crustaceans might serve as intermediate hosts for the nematode.     

Landscape-scale patterns of biological invasions in shoreline plant communities

Little is known about the patterns and dynamics of exotic species invasions at landscape to regional spatial scales. We quantified the presence (identity, abundance, and richness) and characteristics of native and exotic species in estuarine strandline plant communities at 24 sites in Narragansett Bay, Rhode Island, USA. Our results do not support several fundamental predictions of invasion biology. Established exotics (79 of 147 recorded plant species) were nearly indistinguishable from the native plant species (i.e. in terms of growth form, taxonomic grouping, and patterns of spatial distribution and abundance) and essentially represent a random sub-set of the current regional species pool. The cover and richness of exotic species varied substantially among quadrats and sites but were not strongly related to any site-level physical characteristics thought to affect invasibility (i.e. the physical disturbance regime, legal status, neighboring habitat type, and substrate characteristics). Native and exotic cover or richness were not negatively related within most sites. Across sites, native and exotic richness were positively correlated and exotic cover was unrelated to native richness. The colonization and spread of exotics does not appear to have been substantially reduced at sites with high native diversity. Furthermore, despite the fact that the Rhode Island strandline system is one of the most highly-invaded natural plant communities described to date, exotic species, both individually and as a group, currently appear to pose little threat to native plant diversity. Our findings are concordant with most recent, large-scale investigations that do not support the theoretical foundation of invasion biology and generally contradict small-scale experimental work.     

Relationship between grass species richness and ecosystem stability in Kruger National Park, South Africa

The relationship between grass species richness and ecosystem stability was investigated in the Kruger National Park. A total of 135 489 individual grasses were identified from 189 sites spread across 19 485 km² of savanna biome, making this one of the largest studies of its kind. At each site, grass percentage abundance and standing crop were measured at one year intervals to provide an index of ecosystem function. A severe drought that affected the region between 1991 and 1993 provided a convenient perturbation. At the height of the drought, mean species richness declined by 12.7% while standing crop declined by 38.1%, from 3199 to 1979 kg ha^?1. Percentage grass abundance declined to 87.5% of its pre‐drought value. After the drought had passed species richness, standing crop and percentage abundance recovered to 92.1%, 113.8% and 92.8% of their pre‐perturbation values, respectively. Statistical analysis of these responses revealed that grass assemblages of low species richness were more resistant to drought than assemblages of high species richness. Species‐poor sites also showed better recovery from perturbation after the drought had passed. These findings suggest that ecosystem stability may be negatively related to grass species richness in South African savanna grasslands.     

Potential bias in inbreeding depression estimates when using pedigree relationships to assess the degree of homozygosity for loci under selection

A potential bias in estimation of inbreeding depression when using pedigree relationships to assess the degree of homozygosity for loci under selection is indicated. A comparison of inbreeding coefficients based on either pedigree or genotypic frequencies indicated that, as a result of selection, the inbreeding coefficient based on pedigree might not correspond with the random drift of allelic frequencies. Apparent differences in average levels of both inbreeding coefficients were obtained depending on the genetic model (additive versus dominance, initial allelic frequencies, heritability) and the selection system assumed (no versus mass selection). In the absence of selection, allelic frequencies within a small population change over generations due to random drift, and the pedigree-based inbreeding coefficient gives a proper assessment of the accompanying probability of increased homozygosity within a replicate by indicating the variance of allelic frequencies over replicates. With selection, in addition to random drift, directional change in allelic frequencies is not accounted for by the pedigree-based inbreeding coefficient. This result implies that estimation of inbreeding depression for traits under either direct or indirect selection, estimated by a regression of performance on pedigree-based coefficients, should be carefully interpreted.Deceased     

Soil microbial diversity and the sustainability of agricultural soils

Many world ecosystems are in various states of decline evidenced by erosion, low productivity, and poor water quality caused by forest clearing, intensive agricultural production, and continued use of land resources for purposes that are not sustainable. The biological diversity of these systems is being altered. Little research has been conducted to quantify the beneficial relationships between microbial diversity, soil and plant quality, and ecosystem sustainability. Ecosystem functioning is governed largely by soil microbial dynamics. Differences in microbial properties and activities of soils have been reported but are restricted to general ecological enumeration methods or activity levels, which are limited in their ability to describe a particular ecosystem. Microbial populations and their responses to stresses have been traditionally studied at the process level, in terms of total numbers of microorganisms, biomass, respiration rates, and enzyme activities, with little attention being paid to responses at the community or the organismal levels. These process level measurements, although critical to understanding the ecosystem, may be insensitive to community level changes due to the redundancy of these functions. As microbial communities comprise complex interactions between diverse organisms, they should be studied as such, and not as a black box into which inputs are entered and outputs are received at measured rates. Microbial communities and their processes need to be examined in relation to not only the individuals that comprise the community, but the effect of perturbations or environmental stresses on those communities.     

The relationship between a summer fry (0+) abundance index, derived from semi-quantitative electrofishing, and egg deposition of Atlantic salmon, in the River Bush, Northern Ireland

Atlantic salmon survival in the R. Bush (N. Ireland) from egg to summer 0+ was inversely density-dependent on egg deposition ( P <0.05). A stock-recruitment relationship derived from egg deposition and summer 0+ abundance index data was compared to that derived from adult and smolt counts based on total trapping. Fitted Ricker curves indicated maximum recruitment at around 2.35 million eggs and 2.46 million eggs for 0+ index and smolt count methods, respectively. Salmon 0+ abundance index data from semi-quantitative electrofishing could be obtained with relatively little effort, and used to derive whole-river stock-recruitment relationships on rivers where only adult count or some other estimator of parental stock is available. The derivation and expression of spawning targets from stock/recruitment relationships is discussed with reference to the R. Bush data.