The ice-covered central Arctic Ocean is characterized by low primary productivity due to light and nutrient limitations. The recent reduction in ice cover has the potential to substantially increase ...phytoplankton primary production, but little is yet known about the fate of the ice-associated primary production and of the nutrient supply with increasing warming. This study presents results from the central Arctic Ocean collected during summer 2012, when sea-ice extent reached its lowest ever recorded since the onset of satellite observations. Net primary productivity (NPP) was measured in the water column, sea ice and melt ponds by 14CO2 uptake at different irradiances. Photosynthesis vs. irradiance (PI) curves were established in laboratory experiments and used to upscale measured NPP to the deep Eurasian Basin (north of 78° N) using the irradiance-based Central Arctic Ocean Primary Productivity (CAOPP) model. In addition, new annual production has been calculated from the seasonal nutrient drawdown in the mixed layer since last winter. Results show that ice algae can contribute up to 60% to primary production in the central Arctic Ocean at the end of the productive season (August–September). The ice-covered water column has lower NPP rates than open water due to light limitation in late summer. As indicated by the nutrient ratios in the euphotic zone, nitrate was limiting primary production in the deep Eurasian Basin close to the Laptev Sea area, while silicate was the main limiting nutrient at the ice margin near the Atlantic inflow. Although sea-ice cover was substantially reduced in 2012, total annual new production in the Eurasian Basin was 17 ± 7 Tg C yr−1, which is within the range of estimates of previous years. However, when adding the contribution by sub-ice algae, the annual production for the deep Eurasian Basin (north of 78° N) could double previous estimates for that area with a surplus of 16 Tg C yr−1. Our data suggest that sub-ice algae are an important component of the productivity in the ice-covered Eurasian Basin of the central Arctic Ocean. It remains an important question whether their contribution to productivity is on the rise with thinning ice, or whether it will decline due to overall sea-ice retreat and be replaced by phytoplankton.
•Egocentric and allocentric memory were assessed with a card placing test.•Gender differences were observed in Egocentric and Allocentric spatial memory.•Spatial memory was associated with ...visuospatial span and working memory.•Women achieved better scores on the Allocentric test than on the Egocentric test.
Spatial memory allows us to locate objects and organisms in space and move through the environment. We frequently use two strategies for this purpose: egocentric, related to the viewer’s perspective, and allocentric, associated with environmental cues. This ability is usually assessed by 2D or virtual reality-based tasks. Gender differences have been reported on these tasks. We designed two card-placing tasks with the aim of assessing egocentric and allocentric spatial memory in a real environment. This task makes it possible to separately compare egocentric and allocentric strategies, providing participants with 3D information naturally present in daily orientation activities. We will assess the performance of male and female young adults on the two strategies. Ninety-four subjects were recruited and performed egocentric and allocentric spatial memory card placing tasks. Spatial Span, forward and backward, was also assessed using the Cambridge Neuropsychological Assessment Battery (CANTAB), and the brief version of Benton’s Judge of Line Orientation Test (JoLO) was used to evaluate the ability to judge spatial relations. Our results show that men outperformed women on both spatial memory tasks. Women performed better on Allocentric tasks than on Egocentric tasks, whereas men’s scores did not show differences between strategies. Spatial memory performance on the card placing tasks was significantly correlated with performance on the backward visuospatial span from the CANTAB. This study supports the existence of gender differences in spatial memory functioning, and it provides novel tools for the neuropsychological assessment of spatial memory.
The fundamental properties of neutron stars provide a direct test of the equation of state of cold nuclear matter, a relationship between pressure and density that is determined by the physics of the ...strong interactions between the particles that constitute the star. The most straightforward method of determining these properties is by measuring the gravitational redshift of spectral lines produced in the neutron star photosphere. The equation of state implies a mass-radius relation, while a measurement of the gravitational redshift at the surface of a neutron star provides a direct constraint on the mass-to-radius ratio. Here we report the discovery of significant absorption lines in the spectra of 28 bursts of the low-mass X-ray binary EXO0748-676. We identify the most significant features with the Fe xxvi and xxv n = 2-3 and O viii n = 1-2 transitions, all with a redshift of z = 0.35, identical within small uncertainties for the respective transitions. For an astrophysically plausible range of masses (M 1.3-2.0 solar masses; refs 2-5), this value is completely consistent with models of neutron stars composed of normal nuclear matter, while it excludes some models in which the neutron stars are made of more exotic matter.
SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor ...suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.
Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0–7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how ...those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression.
Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury.
HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: −46%, CXB: −30%, HLU + CXB: −35% relative to vehicle GC at day 28).
These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.
The present work relates to a method for determining the degree of freshness of fish by monitoring the production of spoilage products. This method comprises the global detection of the spoilage ...products including biogenic amines resulting from the degradation of fish by using arrays of voltammetric sensors chemically modified with phthalocyanines. The performance of an array of screen-printed electrodes (SPE) has been compared with that of an array formed by classic carbon paste electrodes (CPE). The sensors have shown good sensitivity towards model solutions of biogenic amines (ammonia, dimethylamine, trimethylamine, cadaverine and histamine). It has been evidenced that the electroactivity and basic character of amines influences considerably the electrochemical behaviour of the electrodic material.
The pattern of responses provided by the array has been successfully used to evaluate fish freshness and to determine the post-mortem period. An increase of the signals associated to biogenic amines and other spoilage products is observed with increasing storage days. Signals provided by classical CPE are better resolved and show better sensor-to-sensor reproducibility than SPE. However, the modification of SPE enables simple mass-production of low-cost and miniaturised sensing units with good sensibility and repeatability. The capability of discrimination demonstrated by Principal Component Analysis (PCA) and the capability of prediction of fish freshness calculated by Partial Least Squares-Discriminant Analysis (PLS-DA) is similar in both cases.
AML holds a unique place in the history of immunotherapy by virtue of being among the first malignancies in which durable remissions were achieved with “adoptive immunotherapy,” now known as ...allogeneic stem cell transplantation. The successful deployment of unselected adoptive cell therapy established AML as a disease responsive to immunomodulation. Classification systems for AML have been refined and expanded over the years in an effort to capture the variability of this heterogeneous disease and risk-stratify patients. Current systems increasingly incorporate information about cytogenetic alterations and genetic mutations. The advent of next generation sequencing technology has enabled the comprehensive identification of recurrent genetic mutations, many with predictive power. Recurrent genetic mutations found in AML have been intensely studied from a cell intrinsic perspective leading to the genesis of multiple, recently approved targeted therapies including IDH1/2-mutant inhibitors and FLT3-ITD/-TKD inhibitors. However, there is a paucity of data on the effects of these targeted agents on the leukemia microenvironment, including the immune system. Recently, the phenomenal success of checkpoint inhibitors and CAR-T cells has re-ignited interest in understanding the mechanisms leading to immune dysregulation and suppression in leukemia, with the objective of harnessing the power of the immune system via novel immunotherapeutics. A paradigm has emerged that places crosstalk with the immune system at the crux of any effective therapy. Ongoing research will reveal how AML genetics inform the composition of the immune microenvironment paving the way for personalized immunotherapy.
•We performed a travel survey in the Mediterranean city of Barcelona, Spain.•Our study recruitment design surveyed a relatively-high proportion of bicyclists.•We ascertained urban environmental ...determinants for bicycle commuting using GIS.•Bicycle sharing stations and greenness were motivators for bicycle commuting.•Public transport stations and elevation were deterrents for bicycle commuting.
Bicycle use for commuting is being encouraged not only to address physical inactivity, but also vehicular congestion, air pollution and climate change. The current study aimed to ascertain the urban environmental correlates and determinants of bicycle use for commuting (bicycle commuting) among the working or studying population in Barcelona, Spain.
Adults (n=769; 52% females) recruited whilst commuting within Barcelona (Spain) responded to a comprehensive telephone survey concerning their travel behaviour. Based upon responses collected from June 2011 to May 2012, participants were categorised into four groups: frequent bicyclists, infrequent bicyclists, willing non-bicyclists, and unwilling non-bicyclists. The determinants of frequency and willingness (propensity) to commute by bicycle were assessed by multinomial logistic regression models adjusted for potential confounders and covariates.
The number of public bicycle stations surrounding the home address and amount of greenness surrounding the work/study address were significant positive determinants of bicycle commuting propensity. On the other hand, the number of public transport stations surrounding the home address and elevation of the work/study address were significant negative determinants of bicycle commuting propensity. Individual age, education level, gender, nationality, physical activity level and commute distance significantly affected this propensity.
Greater availability of public bicycle stations and higher levels of urban greenness may increase bicycle use by adults commuting within a city such as Barcelona, Spain. Electrically-assisted public bicycles may address the challenge of elevation, making this system a more competitive mode against traditional motorised public transport.
Since their first synthesis back in the early 20th century, 1,2,4-triazolo1,5- apyrimidines have aroused increasing interest in very diverse areas ranging from chemotherapy to agriculture or even ...photography. Their similarity to purines confers a potential bioactivity and this feature has been wisely exploited for therapeutic use, including antifungal, antipyretic, analgesic, antiinflammatory, antitumoral and antiparasitic properties. In this review, we focus on the compounds that these nitrogen heterocycles form with metal ions and their antiparasitic activity and therapeutic potential against two neglected diseases of tropical prevalence, leishmaniasis and Chagas disease.
Gallbladder cancer (GBC) is one of the deadliest malignancy and treatment options are deplorably limited. Better strategies of prevention are urgently needed but knowledge on risk factors remains ...scarce. Recent data suggested that arsenic (As) may be involved in GBC carcinogenesis but the question remains debated. To date, there are no data on As measurement in GBC samples. This pilot study aimed to measure As concentrations in tissue samples from patients with GBC compared to non-cancerous gallbladder (NCGB). Included patients underwent cholecystectomy at Hospital Clinico Universidad de Chile, Santiago in Chile, a country with high As exposure, between 2001 and 2020. Tissue samples were preserved in formalin-fixed, paraffin-embedded blocks. Selected samples were retrieved, processed and submitted to inductively coupled plasma mass spectrometry (ICP-MS) to determine As concentrations. A total of 77 patients were included, including 35 GBC and 42 NCGB. The two groups were comparable, except for age (68 vs. 49 years, p < 0.001). Measured in 11 GBC and 38 NCGB, total As was detected in 5 GBC (14%) compared to 0 NCGB samples (p < 0.001). GBC group also showed higher median values of As compared to NCGB (p < 0.001). This pilot study provided a proof-of-concept to measure As concentrations in gallbladder samples and showed higher level of As in GBC samples compared to NCGB, paving the way for future studies aiming to investigate the impact of As on GBC, which may contribute to the prevention of this deadly disease.
•Gallbladder cancer (GBC) is one of the deadliest malignancy and its determinants remain unclear.•Recent studies suggested that arsenic (As) may contribute to the carcinogenesis of gallbladder cancer (GBC), but data remain scant.•The present pilot study aimed to measure and compare As in GBC and in non-cancerou gallbladder (NCGB) samples.•Higher levels of As were detected in GBC samples, suggesting that As may by an determinant of this aggressive cancer and underscoring the importance to further investigate this association.