Protein phosphorylation is an important post-translational modification that is an integral part of cellular function. The O-phosphorylated amino-acid residues, such as phosphoserine (pSer), ...phosphothreonine (pThr) and phosphotyrosine (pTyr), have dominated the literature while the acid labile N-linked phosphorylated amino acids, such as phosphohistidine (pHis), have largely been historically overlooked because of the acidic conditions routinely used in amino-acid detection and analysis. This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems. Particular emphasis is placed on pHis isomerization and the hybrid functionality for both pHis and pTyr of the proposed τ-pHis analogue bearing the triazole residue.
Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular ...carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log hazard ratio, -0.27; 95% CI, -0.46 to -0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for "other" treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran's Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients' hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.
This paper describes a data preprocessing algorithm that can be used to mitigate the effects of interfering spectral components when the goal is to detect the spectrum of unknown components in a ...mixture of known components or to verify the presence of suspected components in the spectrum of a mixture of known components. The algorithm is both relatively simple and applicable to a wide range of problems in spectroscopy. The range of applicability can be increased by combining the method with other data preprocessing methods, for example derivative spectra, and can also accommodate variability in the spectra of one or more of the known components. Examples of the application of the algorithm to real problems are given for near-infrared analysis of antibiotic drug formulations inside gelatin capsules and mid-infrared analysis of atmospheric pollutants.
Graphical Abstract
Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over ...recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).
Optimal mobility, defined as relative ease and freedom of movement in all of its forms, is central to healthy aging. Mobility is a significant consideration for research, practice, and policy in ...aging and public health. We examined the public health burdens of mobility disability, with a particular focus on leading public health interventions to enhance walking and driving, and the challenges and opportunities for public health action. We propose an integrated mobility agenda, which draws on the lived experience of older adults. New strategies for research, practice, and policy are needed to move beyond categorical promotion programs in walking and driving to establish a comprehensive program to enhance safe mobility in all its forms.
Many clinical studies have been carried out to determine the health benefits of soy protein and the isoflavones contained in soy. S‐equol is not present in soybeans but is produced naturally in the ...gut of certain individuals, particularly Asians, by the bacterial biotransformation of daidzein, a soy isoflavone. In those intervention studies in which plasma S‐equol levels were determined, a concentration of >5–10 ng/mL has been associated with a positive outcome for vasomotor symptoms, osteoporosis (as measured by an increase in bone mineral density), prostate cancer, and the cardiovascular risk biomarkers low‐density lipoprotein cholesterol and C‐reactive protein. These studies suggest that S‐equol may provide therapeutic benefits for a number of medical needs.
Early BEH research addressed influences of toxic environmental exposures, zoning laws, building codes, and healthy housing and communities on asthma, injury, violence, healthy and unhealthy food ...consumption, mental health, social capital, and health inequities.1 Awareness increased regarding the benefits of denser, more walkable, and less automobile-dependent settings, as well as the accessibility, mobility, and livability needs ofthe growing aging population. Work on automobile dependence, traffic safety, walking and biking, commuting, and sedentary time was primarily driven by the Robert Wood Johnson Foundation's Active Living Research initiative to promote active living via environment, policy, and practice improvements3,4 Research linked specific building and community features to health outcomes, enabling more effective interventions such as appealing stairways, ample sidewalks, and vibrant activity centers.5 The business case for healthpromoting, walkable places was documented.6 Unintended consequences, including gentrification and displacement, of interventions aimed at improving health among people from racial and ethnic minority groups and of lower incomes were increasingly recognized, resulting in more research focused on how to mitigate these risks.7 The history of structural racism, segregation, redlining, neighborhood disinvestment, health inequities, and disparities in walkability, housing, and greenspace access was only recently widely acknowledged.8 Numerous books (Table E, available as a supplement to the online version of this article at http://www.ajph.org) and dozens of BEH measures (e.g., walkability https://www.wal kscore. com, access to parks https://www.tpl. org/ParkScore, livability http://www. livabilitylndex.AARP.org, and brain health https://cognability.isr.umich. edu) were also published, reflecting the growth and maturation ofthe field. The effects of these evolving technologies on land use, housing, economic and community development, traffic patterns, transportation planning and infrastructure, air quality, and associated health outcomes require further research and evaluation (Table G, reference 3).10 PRACTICE Professional organizations across disciplines established BEH committees and working groups (Table F, available as a supplement to the online version of this article at http://www.ajph.org), promoting healthy building and community design through conferences, reports, training, and advocacy (e.g., https://www. Health impact assessments (HIAs) were used to consider potential health impacts of proposed projects and programs and identify disproportionately affected populations as well as howto mitigate adverse effects9,11,12 HIAs improved collaboration, amplified community member voices, increased awareness of health issues, and informed decision makers, but the time and resources required to complete HIAs limited their success.12 Cross-disciplinary public health, planning, policy, real estate, architecture, engineering, transportation, and public-private partnership efforts, along with Complete Streets approaches (https://highways.dot.gov/ complete-streets), improved pedestrian infrastructure and safety.
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