Galaxies grow inefficiently, with only a small percentage of the available gas converted into stars each free-fall time. Feedback processes, such as outflowing winds driven by radiation pressure, ...supernovae, or supermassive black hole accretion, can act to halt star formation if they heat or expel the gas supply. We report a molecular outflow launched from a dust-rich star-forming galaxy at redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities up to 800 kilometers per second relative to the galaxy, is resolved into multiple clumps, and carries mass at a rate within a factor of 2 of the star formation rate. Our results show that molecular outflows can remove a large fraction of the gas available for star formation from galaxies at high redshift.
We report the discovery and constrain the physical conditions of the interstellar medium of the highest-redshift millimeter-selected dusty star-forming galaxy to date, SPT-S J031132−5823.4 (hereafter ...SPT0311−58), at . SPT0311−58 was discovered via its 1.4 mm thermal dust continuum emission in the South Pole Telescope (SPT)-SZ survey. The spectroscopic redshift was determined through an Atacama Large Millimeter/submillimeter Array 3 mm frequency scan that detected CO(6-5), CO(7-6), and (2-1), and subsequently was confirmed by detections of CO(3-2) with the Australia Telescope Compact Array and with APEX. We constrain the properties of the ISM in SPT0311−58 with a radiative transfer analysis of the dust continuum photometry and the CO and line emission. This allows us to determine the gas content without ad hoc assumptions about gas mass scaling factors. SPT0311−58 is extremely massive, with an intrinsic gas mass of . Its large mass and intense star formation is very rare for a source well into the epoch of reionization.
The coronavirus disease 2019 (Covid-19) pandemic intensified the already catastrophic drug overdose and substance use disorder (SUD) epidemic, signaling a syndemic as social isolation, economic and ...mental health distress, and disrupted treatment services disproportionally impacted this vulnerable population. Along with these social and societal factors, biological factors triggered by intense stress intertwined with incumbent overactivity of the immune system and the resulting inflammatory outcomes may impact the functional status of the central nervous system (CNS). We review the literature concerning SARS-CoV2 infiltration and infection in the CNS and the prospects of synergy between stress, inflammation, and kynurenine pathway function during illness and recovery from Covid-19. Taken together, inflammation and neuroimmune signaling, a consequence of Covid-19 infection, may dysregulate critical pathways and underlie maladaptive changes in the CNS, to exacerbate the development of neuropsychiatric symptoms and in the vulnerability to develop SUD.
This article is part of the special Issue on ‘Vulnerabilities to Substance Abuse’.
•Co-morbidities contribute to severe Covid-19, potentially due to inflammation.•Inflammation and the kynurenine pathway during SUD may add to Covid-19 severity.•Neuroimmune signaling during Covid-19 dysregulates tryptophan metabolism.•Increased levels of kynurenine destabilize normal neurotransmitter levels.•Altered neurotransmitters are related to drug use and misuse and increased SUDs.
The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of ...Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2–ERIC–PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.
Abstract Serotonin 2C receptors (5-HT2C R) appear to exert tonic inhibitory influence over dopamine (DA) neurotransmission in the ventral tegmental area (VTA), the origin of the mesolimbic DA system, ...thought to be important in psychiatric disorders including addiction and schizophrenia. Current literature suggests that the inhibitory influence of 5-HT2C R on DA neurotransmission occurs via indirect activation of GABA inhibitory neurons, rather than via a direct action of 5-HT2C R on DA neurons. The present experiments were performed to establish the distribution of 5-HT2C R protein on DA and GABA neurons in the VTA of male rats via double-label immunofluorescence techniques. The 5-HT2C R protein was found to be co-localized with the GABA synthetic enzyme glutamic acid decarboxylase (GAD), confirming the presence of the 5-HT2C R on GABA neurons within the VTA. The 5-HT2C R immunoreactivity was also present in cells that contained immunoreactivity for tyrosine hydroxylase (TH), the DA synthetic enzyme, validating the localization of 5-HT2C R to DA neurons in the VTA. While the degree of 5-HT2C R+GAD co-localization was similar across the rostro-caudal levels of VTA subnuclei, 5-HT2C R+TH co-localization was highest in the middle relative to rostral and caudal levels of the VTA, particularly in the paranigral, parabrachial, and interfascicular subnuclei. The present results suggest that the inhibitory influence of the 5-HT2C R over DA neurotransmission in the VTA is a multifaceted and complex interplay of 5-HT2C R control of the output of both GABA and DA neurons within this region.
Moving academic research forward during COVID-19 Wigginton, N S; Cunningham, R M; Katz, R H ...
Science (American Association for the Advancement of Science),
06/2020, Letnik:
368, Številka:
6496
Journal Article
Recenzirano
Odprti dostop
A gradual, stepwise approach to reopening, informed by public health expertise, will be essential
The coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented disruption of society. ...Institutions of higher education have been no exception. To preserve the safety of their communities and adhere to public health guidance, universities and colleges around the world have rapidly pivoted to fully online teaching and learning models, implemented remote work for the majority of employees, and shuttered countless public spaces and programs. Most “on-site” research activities—in laboratories, in clinics, or in the field—also ground to a halt. Many institutions are now planning or implementing a ramp-up of on-site research activities, which offers an opportunity to begin implementing policies and practices that will lay the groundwork for the eventual reopening of additional onsite academic programming, including teaching. To ramp up safely, institutions are working with stakeholder groups—such as public health experts, as well as faculty, staff, and students—to develop guiding principles that will help inform and drive decision-making over the coming months. We synthesized several risk and decision-making frameworks under development at our universities to develop a set of criteria informed by public health expertise that institutions should consider before and during the first stages of restoring research activities and less certain factors to consider for subsequent phases.
Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC ...regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.
This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.
This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).
NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Serotonin (5-HT) action via the 5-HT2C receptor (5-HT2C R) provides an important modulatory influence over neurons of the prefrontal cortex (PFC), which is critically involved in disorders ...of executive function including substance use disorders. In the present study, we investigated the distribution of the 5-HT2C R in the rat prelimbic prefrontal cortex (PrL), a subregion of the medial prefrontal cortex (mPFC), using a polyclonal antibody raised against the 5-HT2C R. The expression of 5-HT2C R immunoreactivity (IR) was highest in the deep layers (layers V/VI) of the mPFC. The 5-HT2C R-IR was typically most intense at the periphery of cell bodies and the initial segment of cell processes. Approximately 50% of the 5-HT2C R-IR detected was found in glutamate decarboxylase, isoform 67 (GAD 67)-positive neurons. Of the subtypes of GABA interneurons identified by expression of several calcium-binding proteins, a significantly higher percentage of neurons expressing IR for parvalbumin also expressed 5-HT2C R-IR than did the percentage of neurons expressing calbindin-IR or calretinin-IR that also expressed 5-HT2C R-IR. Since parvalbumin is located in basket and chandelier GABA interneurons which project to cell body and initial axon segments of pyramidal cells, respectively, these results raise the possibility that the 5-HT2C R in the mPFC acts via the parvalbumin-positive GABAergic interneurons to regulate the output of pyramidal cells in the rat mPFC.
The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an ...oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1–20ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts. There were also effects on multiple organ systems, cardiac function and oxidative status. External oiling affected flight patterns and time spent during flight tasks indicating that migration may be affected by short-term repeated exposure to oil. Feather damage also resulted in increased heat loss and energetic demands. The papers in this special issue indicate that the combined effects of oil toxicity and feather effects in avian species, even in the case of relatively light oiling, can significantly affect the overall health of birds.
•Deepwater Horizon (DWH) Natural Resource Damage Assessment (NRDA) initiated within a week of DWH oil spill.•Avian toxicity studies conducted to inform NRDA damage assessment.•Studies included oral dosing studies, external dosing study, metabolic and flight performance studies and field-based flight studies.•Studies indicated combined effects of oil toxicity and feather effects in avian species can significantly affect the overall health of birds.
Along the Gulf of Mexico (GoM) coast, natural resource managers continually struggle with managing coastal uplands due to front-end costs, prolonged maintenance, and habitat-specific ecological ...needs. Prescribed fire, mechanical removal, and chemical treatments are common habitat management techniques used to remove invasive species, clear understory, and achieve other management goals. However, rapid development and changing climate exacerbate the difficulty in using these techniques. A potential alternative or complementary technique is using livestock for habitat management (i.e., targeted or controlled grazing). In other regions of the world, using livestock for conservation or restoration of managed lands has shown to be a less intrusive and more financially viable alternative. To better understand the research needs, logistical, and environmental concerns related to using livestock for habitat management in the coastal uplands of the GoM, we developed and distributed a survey to three groups of land users, including natural resource managers, researchers, and livestock producers in the region. Survey results show that over 96% of respondents are interested in using livestock for habitat management, but less than 10% of respondents were aware of any information that could be used to inform grazing practices for coastal upland habitat management along the Gulf of Mexico coast. There were differences among surveyed groups, but generally small-sized cattle breeds and goats were identified as the livestock with the most potential for environmental benefit and ease of containment. General concerns and areas for further investigation were implementation (e.g., which livestock type to use and grazing intensity), logistical considerations (e.g., fencing and rotational frequency), impacts of grazing on water quality, wildlife, vegetation, and livestock nutrition. Survey respondents overwhelmingly (at least 75% of each group) indicated that livestock grazing ideally would not be a standalone management practice and should be used in conjunction with other habitat management techniques such as prescribed burns, mechanical clearing, or chemical treatments. The results of the survey could be used to develop applied research projects and guidance documents that directly address informational needs related to using livestock for habitat management of coastal uplands along the Gulf of Mexico coast.
•There is interest in exploring livestock grazing for coastal habitat management.•Few resources exist to inform livestock grazing for coastal habitat management.•Cattle and goats were identified as the most beneficial livestock in coastal uplands.•Research to inform livestock type and grazing frequency in coastal uplands is needed.
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