Myths of the High Medical Cost of Old Age and Dying

The rising costs of medical care in the United States are often erroneously linked to the growing population of older adults. Despite public perception, health care costs associated with aging are limited. Part of the ILC-USA's project on Ageism In America with generous support from the Open Society Institute, this report identifies and dispels seven myths about caring for older people at the end of life

Investigations into the mechanism for RNA structural remodeling by dead-box helicase proteins

textStructured RNAs and RNA-protein complexes (RNPs) are involved in many essential biological processes and the specific conformations of these RNAs are crucial to their various functions. However, in vitro studies have found that RNA has propensity for misfolding into inactive species that often consist of extensive secondary and tertiary interactions, which can be locally and globally stabilizing, resulting in long-lived non-native conformers. DEAD-box helicases are one class of proteins that have been found to accelerate folding and rearrangements of highly structured RNAs. While these proteins have been shown to use ATP to unwind short RNA helices, it is not known how they disrupt the tertiary interactions that often stabilize both native and misfolded RNA conformations. We used single molecule fluorescence to probe the mechanism by which DEAD-box proteins facilitate global unfolding of a structured RNA. DEAD-box protein CYT-19, a mitochondrial protein from Neurospora crassa, was found to destabilize a specific tertiary interaction with the Tetrahymena group I intron ribozyme using a helix capture mechanism. The protein molecule binds to a helix within the structured RNA only after the helix spontaneously loses its tertiary contacts, and then uses ATP to unwind the helix, liberating the product strands. Ded1, a multi-functional DEAD-box protein found in Saccharomyces cerevisiae, gives analogous results with small but reproducible differences that may reflect its in vivo roles. The requirement for spontaneous dynamics likely targets DEAD-box proteins toward less stable RNA structures, which are likely to experience greater dynamic fluctuations, and provides a satisfying explanation for previous correlations between RNA stability and CYT-19 unfolding efficiency. Biologically, the ability to sense RNA stability probably biases DEAD-box proteins to act preferentially on misfolded structures and thereby to promote native folding while minimizing spurious interactions with stable, natively-folded RNAs. In addition, this straightforward mechanism for RNA remodeling does not require any specific structural environment of the helicase core and is likely to be relevant for DEAD-box proteins that promote RNA rearrangements of RNP complexes including the spliceosome and ribosome.Biochemistr

Residency Exposures and Anticipated Future Involvement in Community Settings

Objective— To assess how exposures to community activities in residency impact anticipated future involvement in community child health settings. Methods— Prospective cohort study of pediatric residents from 10 programs (12 sites) who completed training between 2003 and 2009. Residents reported annual participation for ≥8 days in each of 7 community activities (eg, community settings, child health advocacy) in the prior year. At the start and end of residency, residents reported anticipated involvement in 10 years in 8 community settings (eg, school, shelter). Anticipated involvement was dichotomized: moderate/ substantial (“high”) versus none/limited (“low”). Logistic regression modeled whether residency exposures independently influenced anticipated future involvement at the end of residency. Results— A total of 683 residents completed surveys at the start and end of residency (66.8% participation). More than half of trainees reported ≥8 days’ of involvement in community settings (65.6%) or child health advocacy (53.6%) in residency. Fewer anticipated high involvement in at least 1 community setting at the end of residency than at the start (65.5% vs 85.6%, P < .001). Participation in each community activity mediated but did not moderate relations between anticipated involvement at the start and end of residency. In multivariate models, exposure to community settings in residency was associated with anticipated involvement at end of residency (adjusted odds ratio 1.5; 95% confidence interval 1.2, 2.0). No other residency exposures were associated. Conclusions— Residents who anticipate high involvement in community pediatrics at the start of residency participate in related opportunities in training. Exposure to community settings during residency may encourage community involvement after training

DEAD-Box Helicase Proteins Disrupt RNA Tertiary Structure Through Helix Capture

DEAD-box helicase proteins accelerate folding and rearrangements of highly structured RNAs and RNA–protein complexes (RNPs) in many essential cellular processes. Although DEAD-box proteins have been shown to use ATP to unwind short RNA helices, it is not known how they disrupt RNA tertiary structure. Here, we use single molecule fluorescence to show that the DEAD-box protein CYT-19 disrupts tertiary structure in a group I intron using a helix capture mechanism. CYT-19 binds to a helix within the structured RNA only after the helix spontaneously loses its tertiary contacts, and then CYT-19 uses ATP to unwind the helix, liberating the product strands. Ded1, a multifunctional yeast DEAD-box protein, gives analogous results with small but reproducible differences that may reflect its in vivo roles. The requirement for spontaneous dynamics likely targets DEAD-box proteins toward less stable RNA structures, which are likely to experience greater dynamic fluctuations, and provides a satisfying explanation for previous correlations between RNA stability and CYT-19 unfolding efficiency. Biologically, the ability to sense RNA stability probably biases DEAD-box proteins to act preferentially on less stable misfolded structures and thereby to promote native folding while minimizing spurious interactions with stable, natively folded RNAs. In addition, this straightforward mechanism for RNA remodeling does not require any specific structural environment of the helicase core and is likely to be relevant for DEAD-box proteins that promote RNA rearrangements of RNP complexes including the spliceosome and ribosome

Vegetation restoration in Northern China: A contrasted picture

China started a long- term effort to mitigate desertification and ensure the sustainability of its environment by implementing multiple large- scale national ecological restoration projects since 1978, but their success has been highly debated for a long time. Here, we estimated the change of vegetation fraction cover (VFC) in the Three- North Shelterbelt Programme (TNSP) region over the past three decades on the basis of the Normalized Difference Vegetation Index dataset from the Global Inventory Monitoring and Modeling System. We evaluate the national strategy of vegetation restoration in North China by comparing rainfall patterns, vegetation change, and national ecological restoration programs on the basis of the Global Meteorological Forcing Dataset and the China Forestry Statistical Yearbooks. We find that the western, central, and eastern parts of the TNSP region exhibited a distinct increase in vegetation coverage. The western region had the highest increase of annual precipitation, but this did not result in the highest VFC increase. We infer that ecological restoration activities are the factor leading to the observed increase in VFC in the eastern and central region compared with the western region. The low survival rate of planted trees in the forest of the TNSP region indicates that it is necessary to improve the mode of vegetation restoration to obtain optimal returns and avoid excessive investment. The success of new strategies, for example, natural restoration and quasinatural afforestation are promising as an alternative method. China’s experiences in reforestation will be very beneficial for other countries to promote land degradation mitigation and vegetation improvement in the arid and semiarid areas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154888/1/ldr3314_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154888/2/ldr3314.pd

Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014.

In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines

Molecular computations for reactions and phase transitions: applications to protein stabilization, hydrates and catalysis

In this work we have made significant contributions in three different areas of interest: therapeutic protein stabilization, thermodynamics of natural gas clathrate-hydrates, and zeolite catalysis. In all three fields, using our various computational techniques, we have been able to elucidate phenomena that are difficult or impossible to explain experimentally. More specifically, in mixed solvent systems for proteins we developed a statistical-mechanical method to model the thermodynamic effects of additives in molecular-level detail. It was the first method demonstrated to have truly predictive (no adjustable parameters) capability for real protein systems. We also describe a novel mechanism that slows protein association reactions, called the “gap effect.” We developed a comprehensive picture of methioine oxidation by hydrogen peroxide that allows for accurate prediction of protein oxidation and provides a rationale for developing strategies to control oxidation. The method of solvent accessible area (SAA) was shown not to correlate well with oxidation rates. A new property, averaged two-shell water coordination number (2SWCN) was identified and shown to correlate well with oxidation rates. Reference parameters for the van der Waals Platteeuw model of clathrate-hydrates were found for structure I and structure II. These reference parameters are independent of the potential form (unlike the commonly used parameters) and have been validated by calculating phase behavior and structural transitions for mixed hydrate systems. These calculations are validated with experimental data for both structures and for systems that undergo transitions from one structure to another. This is the first method of calculating hydrate thermodynamics to demonstrate predictive capability for phase equilibria, structural changes, and occupancy in pure and mixed hydrate systems. We have computed a new mechanism for the methanol coupling reaction to form ethanol and water in the zeolite chabazite. The mechanism at 400°C proceeds via stable intermediates of water, methane, and protonated formaldehyde.Singapore-MIT Alliance (SMA

Monocyte-Derived Macrophages Orchestrate Multiple Cell-Type Interactions To Repair Necrotic Liver Lesions in Disease Models

The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor 9+ (SOX9+) hepatocytes near the necrotic lesions, which acted as a barrier from further injury. Subsequently, necrotic environment (hypoxia and dead cells) induced a cluster of complement 1q-positive (C1q+) MoMFs that promoted necrotic removal and liver repair, while Pdgfb+ MoMFs activated hepatic stellate cells (HSCs) to express α-smooth muscle actin and induce a strong contraction signal (YAP, pMLC) to squeeze and finally eliminate the necrotic lesions. In conclusion, MoMFs play a key role in repairing the necrotic lesions, not only by removing necrotic tissues, but also by inducing cell death-resistant hepatocytes to form a perinecrotic capsule and by activating α-smooth muscle actin-expressing HSCs to facilitate necrotic lesion resolution

Greenhouse gas emissions from food systems: building the evidence base

New estimates of greenhouse gas (GHG) emissions from the food system were developed at the country level, for the period 1990–2018, integrating data from crop and livestock production, on-farm energy use, land use and land use change, domestic food transport and food waste disposal. With these new country-level components in place, and by adding global and regional estimates of energy use in food supply chains, we estimate that total GHG emissions from the food system were about 16 CO2eq yr−1 in 2018, or one-third of the global anthropogenic total. Three quarters of these emissions, 13 Gt CO2eq yr−1, were generated either within the farm gate or in pre- and post-production activities, such as manufacturing, transport, processing, and waste disposal. The remainder was generated through land use change at the conversion boundaries of natural ecosystems to agricultural land. Results further indicate that pre- and post-production emissions were proportionally more important in developed than in developing countries, and that during 1990–2018, land use change emissions decreased while pre- and post-production emissions increased. We also report results on a per capita basis, showing world total food systems per capita emissions decreasing during 1990–2018 from 2.9 to 2.2 t CO2eq cap−1, with per capita emissions in developed countries about twice those in developing countries in 2018. Our findings also highlight that conventional IPCC categories, used by countries to report emissions in the National GHG inventory, systematically underestimate the contribution of the food system to total anthropogenic emissions. We provide a comparative mapping of food system categories and activities in order to better quantify food-related emissions in national reporting and identify mitigation opportunities across the entire food system