Cannabinoid receptors expression in bone marrow trephine biopsy of chronic lymphocytic leukaemia patients treated with purine analogues

Background: Cannabinoid receptors CB1 and CB2 are part the endocannabinoid system that plays an important role in the process of proliferation and apoptosis of different neoplastic cells. B-cell chronic lymphocytic leukaemia is one of the diseases in which these processes are altered. Aim: The aim of our study was the assessment of cannabinoid receptor expression on the B-lymphocytes in bone marrow trephine biopsy from leukaemic patients at diagnosis and after purine analogue treatment. Methods: The biopsy was taken routinely and standard immunohistochemical staining procedure for paraffin embedded sections was applied. The cannabinoid receptors were detected using specific primary polyclonal antibody anti-CB1 and anti-CB2. Additionally, an existence of cannabinoid receptors was confirmed by flow cytometry. Results: The results showed that the expression of CB1 receptor on the surface of neoplastic cells was lower than that of CB2 (17.0 ± 3.1% and 92.1 ± 1.7% respectively, p < 0.001). Nine of the patients responded to applied treatment with a reduction in leukaemic infiltration (77.2 ± 6.9% to 30.2 ± 6.5%, p = 0.007) and CB1 receptor expression (24.4 ± 4.8% to 8.6 ± 2.9%, p = 0.01), but there was no change in CB2 expression (91.7 ± 2.7% vs 90.9 ± 2.8%, p = 0.69). Four patients without remission expressed even greater number of the receptors. In all of the cases both cannabinoid receptor types antibodies gave positive reaction. Furthermore, the existence of cannabinoid receptors on neoplastic lymphocytes was confirmed by flow cytometry. Conclusion: The study provides original evidence for the existence of cannabinoid receptors on B-lymphocytes in chronic lymphocytic leukaemia patients. The receptors are thought to be a new structure that can modify the course of the disease and may be considered as a new target in leukaemia treatment.Обоснование: рецепторы каннабиноидов CB1 и CB2 яв ляются частью системы эндоканнабиноидов, которая играет важную роль в процессах пролиферации и апоптоза различных неопластических клеток. Одним из заболеваний, при которых происходит нарушение этих процессов, является В-клеточный хронический лимфлейкоз. Цель: оценка экспрессии рецепторов каннабиноидов на В-лимфоцитах в трепанобиоптатах у больных лейкозом до и после проведения лечения с использованием пуриновых аналогов. Методы: биоптаты получили рутинными методами; иммуногистохимическое исследование депарафинизированных срезов проводили по стандартной процедуре. Рецепторы каннабиноидов определяли с использованием специфических моноклональных антител анти-CB1 и анти-CB2. Кроме того, наличие рецепторов подтверждено при по- мощи проточной цитофлуориметрии. Результаты: показано, что экспрессия рецептора CB1 на поверхности опухолевых клеток ниже, чем экспрессия CB2 (17,0  ± 3,1% и 92,1 1,7% твенно, p < 0,001). После проведенного лечения у 9 пациентов отмечалось уменьшение лейкозного инфильтрата (77,2 6,9% до 30,2 6,5%, p = 0,007) и снижение экспрессии рецептора CB1 (24,4 4,8% до 8,6 2,9%, p = 0,01), однако различий в экспрессии CB2 не отмечали (91,7 2,7% против 90,9 2,8%, p = 0,69). У 4 пациентов, у которых не удалось достичь ремиссии, определяли даже повышение экспрессии рецепторов. Во всех случаях маркировки антителами к обоим типам рецепторов каннабиноидов отмечали поло- жительную реакцию. Более того, присутствие рецепторов каннабиноидов на злокачественных клетках подтверждали при помощи проточной цитометрии. Выводы: в ходе исследования показано изначальное наличие рецепторов каннабиноидов на В-лимфоцитах у больных хроническим лимфолейкозом. Указанные рецепторы могут быть новой структурой, которая может быть модифицирована в течение болезни, и могут считаться новой мишенью при лечении больных лейкозом

Lake surface temperature [in “State of the Climate in 2017”]

Observed lake surface water temperature anomalies in 2017 are placed in the context of the recent warming observed in global surface air temperature by collating long-term in situ lake surface temperature observations from some of the world’s best-studied lakes and a satellite-derived global lake surface water temperature dataset. The period 1996–2015, 20 years for which satellite-derived lake temperatures are available, is used as the base period for all lake temperature anomaly calculations

Evidence for a general species time arearelationship

The species-area relationship (SAR) plays a central role in biodiversity research, and recent work has increased awareness of its temporal analog, the species-time relationship (STR). Here we provide evidence for a general species-time-area-relationship (STAR), in which species number is a function of the area and time span of sampling, as well as their interaction. For eight assemblages ranging from lake zooplankton to desert rodents, this model outperformed a sampling-based model and two simpler models in which area and time had independent effects. In every case the interaction term was negative, meaning that rates of species accumulation in space decreased with the time span of sampling, while species accumulation rates in time decreased with area sampled. Although questions remain about its precise functional form, the STAR provides a tool for scaling species richness across time and space, for comparing the relative rates of species turnover in space and time at different scales of sampling, and for rigorous testing of mechanisms proposed to drive community dynamics. Our results show that the SAR and STR are not separate relationships but two dimensions of one unified pattern. Keywords: community dynamics, spatiotemporal scaling, species diversity, turnover, speciesarea relationship, species-time relationshi

Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

Forest defoliator outbreaks alter nutrient cycling in northern waters.

Insect defoliators alter biogeochemical cycles from land into receiving waters by consuming terrestrial biomass and releasing biolabile frass. Here, we related insect outbreaks to water chemistry across 12 boreal lake catchments over 32-years. We report, on average, 27% lower dissolved organic carbon (DOC) and 112% higher dissolved inorganic nitrogen (DIN) concentrations in lake waters when defoliators covered entire catchments and reduced leaf area. DOC reductions reached 32% when deciduous stands dominated. Within-year changes in DOC from insect outbreaks exceeded 86% of between-year trends across a larger dataset of 266 boreal and north temperate lakes from 1990 to 2016. Similarly, within-year increases in DIN from insect outbreaks exceeded local, between-year changes in DIN by 12-times, on average. As insect defoliator outbreaks occur at least every 5 years across a wider 439,661 km2 boreal ecozone of Ontario, we suggest they are an underappreciated driver of biogeochemical cycles in forest catchments of this region.Natural Environment Research Council (NE/L006561/1) Ontario Centres of Excellence (OCE/27649) Natural Sciences and Engineering Research Council of Canada (NSERC/509182-17

GRID-PARAMETER OPTIMIZATION OF DISCRETE SYSTEMS WITH PHASE CONTROL

Solved the problem of determining the optimal values of the parameters of a discrete system with phase control, for which the minimum of a given functional quality. Obtain the solution in general and implemented on a specific example of a system that has a specified transfer function

The extent and variability of storm-induced temperature changes in lakes measured with long-term and high-frequency data

The intensity and frequency of storms are projected to increase in many regions of the world because of climate change. Storms can alter environmental conditions in many ecosystems. In lakes and reservoirs, storms can reduce epilimnetic temperatures from wind-induced mixing with colder hypolimnetic waters, direct precipitation to the lake's surface, and watershed runoff. We analyzed 18 long-term and high-frequency lake datasets from 11 countries to assess the magnitude of wind- vs. rainstorm-induced changes in epilimnetic temperature. We found small day-to-day epilimnetic temperature decreases in response to strong wind and heavy rain during stratified conditions. Day-to-day epilimnetic temperature decreased, on average, by 0.28°C during the strongest windstorms (storm mean daily wind speed among lakes: 6.7 ± 2.7 m s−1, 1 SD) and by 0.15°C after the heaviest rainstorms (storm mean daily rainfall: 21.3 ± 9.0 mm). The largest decreases in epilimnetic temperature were observed ≥2 d after sustained strong wind or heavy rain (top 5th percentile of wind and rain events for each lake) in shallow and medium-depth lakes. The smallest decreases occurred in deep lakes. Epilimnetic temperature change from windstorms, but not rainstorms, was negatively correlated with maximum lake depth. However, even the largest storm-induced mean epilimnetic temperature decreases were typically <2°C. Day-to-day temperature change, in the absence of storms, often exceeded storm-induced temperature changes. Because storm-induced temperature changes to lake surface waters were minimal, changes in other limnological variables (e.g., nutrient concentrations or light) from storms may have larger impacts on biological communities than temperature changes

Kemijski sastav endemske biljke Centaurea austro-anatolica i ispitivanje antimikrobnog djelovanja protiv multi-rezistentnih bakterija

Hexane, chloroform, ethyl acetate and ethanolic extracts of the aerial parts of C. austro-anatolica Hub.-Mor. (Asteraceae) were evaluated against microorganisms, including multi-resistant bacteria, using a paper disc diffusion method. The chloroform extract exhibited significant antibacterial activity toward all bacteria tested. The chemical composition of the chloroform extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The major compounds of the extract were caryophyllene oxide (21.32 %), spathulenol (10.86 %), n-tricosanol (9.58 %) and geranyl isovalerate (8.71 %).Heksanski, kloroformski, etil-acetatni i etanolni ekstrakti vršnih dijelova biljke C. austro-anatolica Hub.-Mor. (Asteraceae) ispitivani su na antimikrobno djelovanje protiv multi-rezistentnih bakterija, koristeći difuzijsku metodu na papirnom disku. Kloroformski ekstrakt pokazao je značajno antibakterijsko djelovanje protiv svih testiranih bakterija. Kemijski sastav tog ekstrakta određivan je plinskom kromatografijom (GC) i plinskom kromatografijom-spektrometrijom masa (GC-MS). Najvažniji sastojci ekstrakta bili su kariofilen oksid (21,32 %), spatulenol (10,86 %), n-trikozanol (9,58 %) i geranil izovalerat (8,71 %)

The jellification of north temperate lakes.

Calcium (Ca) concentrations are decreasing in softwater lakes across eastern North America and western Europe. Using long-term contemporary and palaeo-environmental field data, we show that this is precipitating a dramatic change in Canadian lakes: the replacement of previously dominant pelagic herbivores (Ca-rich Daphnia species) by Holopedium glacialis, a jelly-clad, Ca-poor competitor. In some lakes, this transformation is being facilitated by increases in macro-invertebrate predation, both from native (Chaoborus spp.) and introduced (Bythotrephes longimanus) zooplanktivores, to which Holopedium, with its jelly coat, is relatively invulnerable. Greater representation by Holopedium within cladoceran zooplankton communities will reduce nutrient transfer through food webs, given their lower phosphorus content relative to daphniids, and greater absolute abundances may pose long-term problems to water users. The dominance of jelly-clad zooplankton will likely persist while lakewater Ca levels remain low.This work was primarily supported by grants from the Natural Sciences and Engineering Research Council of Canada and funding from the Ontario Ministry of the Environment.This is the accepted manuscript. The final version is available at http://rspb.royalsocietypublishing.org/content/282/1798/20142449

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption