Transport and accumulation of litter in submarine canyons: a geoscience perspective

Marine litter is one of the most pervasive and fast-growing aspects of contamination in the global ocean, and has been observed in every environmental setting, including the deep seafloor where little is known about the magnitude and consequences of the problem. Submarine canyons, the main conduits for the transport of sediment, organic matter and water masses from shallow to abyssal depths, have been claimed to be preferential pathways for litter transport and accumulation in the deep sea. This is supported by ongoing evidence of large litter piles at great water depths, highlighting efficient transfer via canyons. The aim of this article is to present an overview of the current knowledge about marine litter in submarine canyons, taking a geological, process-based point of view. We evaluate sources, transport mechanisms and deposition of litter within canyons to assess the main factors responsible for its transport and accumulation in the deep sea. Few studies relate litter distribution to transport and depositional processes; nevertheless, results from available literature show that canyons represent accumulation areas for both land-based and maritime-based litter. Particularly, accumulation of fishing-related debris is mainly observed at the canyon heads and walls and is related to fishing activities carried out in and adjacent to canyons, while transport and accumulation of general waste and plastic along canyon axes can be related to different mechanisms, encompassing enhanced bottom currents, dense water cascading and turbidity currents, and is related to the proximity of canyons to shore. Global assessment of canyons exposure to riverine plastic inputs and fishing-related debris indicates varying susceptibility of canyons to litter, also highlighting that most of the canyons prone to receive large amounts of anthropogenic debris have not yet been surveyed. Considering that litter research in canyons is still in its infancy, several knowledge gaps need to be filled before the role of canyons as litter traps and the implication for benthic ecosystems can be fully understood

Dynamics of Sleep-Wake Transitions During Sleep

We study the dynamics of the awakening during the night for healthy subjects and find that the wake and the sleep periods exhibit completely different behavior: the durations of wake periods are characterized by a scale-free power-law distribution, while the durations of sleep periods have an exponential distribution with a characteristic time scale. We find that the characteristic time scale of sleep periods changes throughout the night. In contrast, there is no measurable variation in the power-law behavior for the durations of wake periods. We develop a stochastic model which agrees with the data and suggests that the difference in the dynamics of sleep and wake states arises from the constraints on the number of microstates in the sleep-wake system.Comment: Final form with some small corrections. To be published in Europhysics Letters, vol. 57, issue no. 5, 1 March 2002, pp. 625-63

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

Submarine canyon dynamics - Executive Summary

Discussing submarine canyons dynamics through a multidisciplinary approach allowed to identify both advances in knowledge and remaining gaps concerning the controlling factors underlying the formation, development, ecological functioning and vulnerability of canyons at various time scales. As a result, we identified a number of recommendations for future research and actions that the interested reader will discover in this synthetic chapter, drafted as a collective effort in the months following our meeting. The subsequent chapters, each written by a workshop participant, detail the specificities and dynamics of of submarine canyons within and beyond the Mediterranean domain

A translational framework for public health research

<p><b>Background</b></p> <p>The paradigm of translational medicine that underpins frameworks such as the Cooksey report on the funding of health research does not adequately reflect the complex reality of the public health environment. We therefore outline a translational framework for public health research.</p> <p><b>Discussion</b></p> <p>Our framework redefines the objective of translation from that of institutionalising effective interventions to that of improving population health by influencing both individual and collective determinants of health. It incorporates epidemiological perspectives with those of the social sciences, recognising that many types of research may contribute to the shaping of policy, practice and future research. It also identifies a pivotal role for evidence synthesis and the importance of non-linear and intersectoral interfaces with the public realm.</p> <p><b>Summary</b></p> <p>We propose a research agenda to advance the field and argue that resources for 'applied' or 'translational' public health research should be deployed across the framework, not reserved for 'dissemination' or 'implementation'.</p&gt

Cyclin-dependent kinase 9 as a potential target for anti-TNF resistant inflammatory bowel disease

BACKGROUND AND AIMS: Resistance to single cytokine blockade, namely anti-TNF therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines IFN-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically. In this study, we evaluate the effect of targeting the transactivation function of T-bet using inhibitors of P-TEFb (CDK9-cyclin T), a transcriptional elongation factor downstream of T-bet. METHODS: Using an adaptive immune-mediated colitis model, human colonic lymphocytes from IBD patients and multiple large clinical datasets, we investigate the effect of CDK9 inhibitors on cytokine production and gene expression in colonic CD4+ T cells and link these genetic modules to clinical response in patients with IBD. RESULTS: Systemic CDK9 inhibition led to histological improvement of immune-mediated colitis and was associated with targeted suppression of colonic CD4+ T cell-derived IFN-γ and IL-17A. In colonic lymphocytes from IBD patients, CDK9 inhibition potently repressed genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targeted genes that were highly expressed in anti-TNF resistant IBD and that predicted non-response to anti-TNF therapy. CONCLUSION: Collectively, our findings reveal CDK9 as a potential target for anti-TNF resistant IBD, which has the potential for rapid translation to the clinic

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

ACR Appropriateness Criteria® Spinal Bone Metastases

The spine is a common site of involvement in patients with bone metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive tumor can result in neurologic deterioration caused by spinal cord compression or cauda equina involvement. The treatment of spinal bone metastases depends on histology, site of disease, extent of epidural disease, extent of metastases elsewhere, and neurologic status. Treatment recommendations must weigh the risk-benefit profile of external beam radiation therapy (EBRT) for the particular individual's circumstance, including neurologic status, performance status, extent of spinal disease, stability of the spine, extra-spinal disease status, and life expectancy. Patients with spinal instability should be evaluated for surgical intervention. Research studies are needed that evaluate the combination or sequencing of localized therapies with systemic therapies including chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in the management of spinal oligometastasis, radioresistant spinal metastasis, and previously irradiated but progressive spinal metastasis are emerging, but more research is needed to validate the findings from retrospective studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140115/1/jpm.2012.0376.pd

Transport and accumulation of litter in submarine canyons: a geoscience perspective

Marine litter is one of the most pervasive and fast-growing aspects of contamination in the global ocean, and has been observed in every environmental setting, including the deep seafloor where little is known about the magnitude and consequences of the problem. Submarine canyons, the main conduits for the transport of sediment, organic matter and water masses from shallow to abyssal depths, have been claimed to be preferential pathways for litter transport and accumulation in the deep sea. This is supported by ongoing evidence of large litter piles at great water depths, highlighting efficient transfer via canyons. The aim of this article is to present an overview of the current knowledge about marine litter in submarine canyons, taking a geological, process-based point of view. We evaluate sources, transport mechanisms and deposition of litter within canyons to assess the main factors responsible for its transport and accumulation in the deep sea. Few studies relate litter distribution to transport and depositional processes; nevertheless, results from available literature show that canyons represent accumulation areas for both land-based and maritime-based litter. Particularly, accumulation of fishing-related debris is mainly observed at the canyon heads and walls and is related to fishing activities carried out in and adjacent to canyons, while transport and accumulation of general waste and plastic along canyon axes can be related to different mechanisms, encompassing enhanced bottom currents, dense water cascading and turbidity currents, and is related to the proximity of canyons to shore. Global assessment of canyons exposure to riverine plastic inputs and fishing-related debris indicates varying susceptibility of canyons to litter, also highlighting that most of the canyons prone to receive large amounts of anthropogenic debris have not yet been surveyed. Considering that litter research in canyons is still in its infancy, several knowledge gaps need to be filled before the role of canyons as litter traps and the implication for benthic ecosystems can be fully understood