There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

/pdf/ampk-and-mtor-regulate-autophagy-through-direct-14wqsz16ke.pdf

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to card...

https://cdr.lib.unc.edu/downloads/p2676x621

Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

CA : A Cancer Journal for Clinicians

Many health care facilities have developed electronic reporting systems for identifying and reporting adverse events (AEs), so that measures can be taken to improve patient safety. Although several studies have examined AEs in surgical settings, there has not previously been a systematic assessment of the variations in adverse event rates among different types of surgery, nor an identification of the particular types of AEs that are most common within each surgical category. Additionally, this study will identify the AE severity level associated with each of the AE category types. This retrospective observational study was conducted at three Midwestern hospitals that are part of a large integrated healthcare system. Data from 2006 through 2009 were analyzed to determine the rates of reported adverse events (per 1,000 hospitalizations involving a surgical procedure) for 96 categories of surgery as classified according to the ICD-9-CM procedural coding system. Univariate and bivariate summary statistics were compiled for AEs by type, severity, and patient age. During the four-year study period, there was a total of 82,784 distinct hospitalizations involving at least one surgical procedure at these three hospitals. At least one adverse event was reported at 5,368 (6.5%) of those hospitalizations. The mean rate of AEs among all surgical procedure groups was 82.8 AEs per 1,000 hospitalizations. Adverse event rates varied widely among surgical categories with a high of 556.7 AEs per 1,000 hospitalizations for operations on the heart and pericardium. The most common type of adverse event involved care management, followed by medication events and events related to invasive procedures. Detecting variations in AEs among surgical categories can be useful for surgeons and for hospital quality assurance personnel. Documenting the specific AE incidence rates among the most common types of surgical categories, and determining AE severity and age distributions within surgical categories will enable officials to better identify specific patient safety needs and develop appropriately targeted interventions for improvement.

/pdf/incidence-of-adverse-events-in-an-integrated-us-healthcare-2i6hyhk6dp.pdf

Incidence of adverse events in an integrated US healthcare system: a retrospective observational study of 82,784 surgical hospitalizations

Effectiveness of varenicline for smoking cessation: a 1-year follow-up study.

// Joo-Young Jung 1,2,* , Do-Kun Yoon 1,* , Brendan Barraclough 2,3 , Heui Chang Lee 3,4 , Tae Suk Suh 1 and Bo Lu 2 1 Department of Biomedical Engineering and Research Institute of Biomedical Engineering, College of Medicine, Catholic University of Korea, Seoul, Korea 2 Department of Radiation Oncology, University of Florida, Gainesville, FL, USA 3 Department of Biomedical Engineering, J. Crayton Pruitt Family, University of Florida, Gainesville, FL, USA 4 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA * These authors have contributed equally to this work Correspondence to: Tae Suk Suh, email: // Keywords : proton boron fusion therapy, boron neutron capture therapy, Monte Carlo simulation, bragg-peak Received : November 23, 2016 Accepted : February 13, 2017 Published : February 25, 2017 Abstract The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

/pdf/comparison-between-proton-boron-fusion-therapy-pbft-and-5dwy7m4m2z.pdf

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study

Objectives. We examined medically treated injuries among US workers with disability.Methods. Using 2006–2010 National Health Interview Survey data, we compared 3-month rates of nonoccupational and occupational injuries to workers with disability (n = 7729) and without disability (n = 175 947). We fitted multivariable logistic regression models to calculate odds ratios and 95% confidence intervals of injuries by disability status, controlling for sociodemographic variables. We also compared leading causes of injuries by disability status.Results. In the 3-month period prior to the survey, workers with disability were more likely than other workers to have nonoccupational injuries (odds ratio [OR] = 2.35; 95% confidence interval [CI] = 2.04, 2.71) and occupational injuries (OR = 2.39; 95% CI = 1.89, 3.01). For both groups, the leading cause was falls.Conclusions. Disability status was strongly associated with risk of nonoccupational and occupational injuries among US workers. The safety issues facing US wor...

Nonoccupational and Occupational Injuries to US Workers With Disabilities

Lung cancer is the leading cause of cancer-related deaths worldwide. The relatively poor cure rate in lung cancer patients has been associated with a resistance to chemotherapy and radiation that is at least in part related to defects in cellular apoptotic machinery. Exploitation of another form of cell death, autophagy, has the capacity to improve the therapeutic gain of current therapies. In an effort to develop novel treatment strategies to enhance the therapeutic ratio for lung cancer, we wish to better understand the role of autophagic cell death for the sensitization of lung cancer. This text reviews the most up to date protocols and techniques for the study of autophagic cell death in lung cancer models. Others may use these techniques as a framework for study within their experimental models.

Bo Lu

Papers

Incidence of adverse events in an integrated US healthcare system: a retrospective observational study of 82,784 surgical hospitalizations

Effectiveness of varenicline for smoking cessation: a 1-year follow-up study.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study

Nonoccupational and Occupational Injuries to US Workers With Disabilities

Autophagy in lung cancer.