LC3s are canonical proteins necessary for the formation of autophagosomes. We have previously established that two paralogs, LC3B and LC3C, have opposite activities in renal cancer, with LC3B playing ...an oncogenic role and LC3C a tumor-suppressing role. LC3C is an evolutionary late gene present only in higher primates and humans. Its most distinct feature is a C-terminal 20-amino acid peptide cleaved in the process of glycine 126 lipidation. Here, we investigated mechanisms of LC3C-selective autophagy. LC3C autophagy requires noncanonical upstream regulatory complexes that include ULK3, UVRAG, RUBCN, PIK3C2A, and a member of ESCRT, TSG101. We established that postdivision midbody rings (PDMBs) implicated in cancer stem-cell regulation are direct targets of LC3C autophagy. LC3C C-terminal peptide is necessary and sufficient to mediate LC3C-dependent selective degradation of PDMBs. This work establishes a new noncanonical human-specific selective autophagic program relevant to cancer stem cells.
The extragalactic background light (EBL) is an important avenue to understanding cosmological history. Made of radiation by stars, dust, and other objects, it traces both Galactic and stellar ...evolution. Upper and lower limits have been set through direct integration and galaxy counting methods, but there is still a gap between them. An alternative way of measuring the EBL is through its attenuation of gamma-ray signals from extragalactic sources.The High Altitude Water Cherenkov (HAWC) observatory has been fully operational since March 2015 and observing two-thirds of the sky in survey mode. Two nearby extragalactic blazars, Markarian 421 and Markarian 501, have been significantly detected by HAWC. In this dissertation, a constraint was placed on the EBL density using these two sources and HAWC’s sensitivity to > 1 TeV sources. A minimum chi-squared analysis was employed using a Fermi-LAT spectral fit taken from the Third Catalog of Hard Fermi-Lat Sources and HAWC quasi-differential flux points. The EBL models of Gilmore (2012) and Franceschini (2017) were used, scaled by an Overdensity Parameter (OP). An OP value of 1.22 was found to be preferred for the Gilmore model and 1.24 for the Franceschini model.
The well-known field of engineering psychology, also known as human factors engineering, utilizes psychologists to solve Engineering's problems that concern the behavior of humans in their operation ...and control of engineering systems such as military aircraft. To limit psychology's relation to engineering this way is, however, counterproductive. Psychology requires a broader conceptualization of engineering psychology, a subfield of psychology, within which the psychologist's major concern is with the behavior of psychoengineering systems that affect the reliability, validity and safety of psychological research and practice. In contrast with human-factor systems, the psychoengineering systems include healthy and unhealthy, human and animal subjects. The affiliated problems are not those of the engineering industry. This study in engineering psychology concerned the safety of two electrical stimulation systems that are used on animals, chiefly dogs, in punishment and escape/avoidance conditioning procedures of psychology. The study referenced two safety questions. First, is the electricity, when applied externally to the ventral neck of the animal, capable of stimulating carotide sinus and vagus nerves to the point of dangerously disrupting systemic blood pressure and sinus rhythm? Second, is the electricity capable of damaging the epidermis when it is applied repeatedly to the same two points of contact? Of forty-two anesthetized dogs, half were tested with a punishment system; the remainder were tested with an escape/avoidance system. Each was stimulated for five seconds, five times, at each of five intensities. Inter-stimulus interval was about thirty seconds. Systemic blood pressures and electrocardiograms (ECG) were recorded. Control and experimental biopsies were taken for histological examinations of electrified and unelectrified specimens. Each animal's neck was examined grossly each day for ten days following the stimulation runs. None of the gross examination reports was positive. An exact binomial test supported the hypothesis that tissue samples from control and experimental biopsies did not differ histologically. Repeated measure ANOVAs were used to detect significant differences in systolic pressures, diastolic pressures, and R to R intervals of the ECG throughout stimulation runs. While there were some statistically significant results, there was no clinical significance, especially with regard to safety hazards.
BOARD REVIEW Newbold, Michael W
Hoosier Banker,
08/2009, Letnik:
93, Številka:
8
Trade Publication Article
Early in life, I learned three basic lessons: Do what's right; do your best; and treat people the way you would want to be treated. The man who taught me these concepts was my hero - my father. ...Living in Indiana, I am immersed in a culture of these same guiding principles. Every day, it is my privilege to work with and interact with fine people who embody basic Midwestern values. I serve the banking community as president of the central Indiana region of The Huntington National Bank. In that capacity, I have day-to-day responsibility for Huntington's Indiana operations which includes $2 billion in deposits, $1.5 billion in loans, and 600 employees.
The well-known field of engineering psychology, also known as human factors engineering, utilizes psychologists to solve Engineering's problems that concern the behavior of humans in their operation ...and control of engineering systems such as military aircraft. To limit psychology's relation to engineering this way is, however, counterproductive. Psychology requires a broader conceptualization of engineering psychology, a subfield of psychology, within which the psychologist's major concern is with the behavior of psychoengineering systems that affect the reliability, validity and safety of psychological research and practice. In contrast with human-factor systems, the psychoengineering systems include healthy and unhealthy, human and animal subjects. The affiliated problems are not those of the engineering industry. This study in engineering psychology concerned the safety of two electrical stimulation systems that are used on animals, chiefly dogs, in punishment and escape/avoidance conditioning procedures of psychology. The study referenced two safety questions. First, is the electricity, when applied externally to the ventral neck of the animal, capable of stimulating carotide sinus and vagus nerves to the point of dangerously disrupting systemic blood pressure and sinus rhythm? Second, is the electricity capable of damaging the epidermis when it is applied repeatedly to the same two points of contact? Of forty-two anesthetized dogs, half were tested with a punishment system; the remainder were tested with an escape/avoidance system. Each was stimulated for five seconds, five times, at each of five intensities. Inter-stimulus interval was about thirty seconds. Systemic blood pressures and electrocardiograms (ECG) were recorded. Control and experimental biopsies were taken for histological examinations of electrified and unelectrified specimens. Each animal's neck was examined grossly each day for ten days following the stimulation runs. None of the gross examination reports was positive. An exact binomial test supported the hypothesis that tissue samples from control and experimental biopsies did not differ histologically. Repeated measure ANOVAs were used to detect significant differences in systolic pressures, diastolic pressures, and R to R intervals of the ECG throughout stimulation runs. While there were some statistically significant results, there was no clinical significance, especially with regard to safety hazards.
Background: The assessment of air pollution exposure using only community average concentrations may lead to measurement error that lowers estimates of the health burden attributable to poor air ...quality. To test this hypothesis, we modeled the association between air pollution and mortality using small-area exposure measures in Los Angeles, California. Methods: Data on 22,905 subjects were extracted from the American Cancer Society cohort for the period 1982-2000 (5,856 deaths). Pollution exposures were interpolated from 23 fine particle ($\text{PM}_{2.5}$) and 42 ozone (O₃) fixed-site monitors. Proximity to expressways was tested as a measure of traffic pollution. We assessed associations in standard and spatial multilevel Cox regression models. Results: After controlling for 44 individual covariates, all-cause mortality had a relative risk (RR) of 1.17 (95% confidence interval = 1.05-1.30) for an increase of 10 μg/m³ $\text{PM}_{2.5}$ and a RR of 1.11 (0.99-1.25) with maximal control for both individual and contextual confounders. The RRs for mortality resulting from ischemic heart disease and lung cancer deaths were elevated, in the range of 1.24-1.6, depending on the model used. These PM results were robust to adjustments for O₃ and expressway exposure. Conclusion: Our results suggest the chronic health effects associated with within-city gradients in exposure to $\text{PM}_{2.5}$ may be even larger than previously reported across metropolitan areas. We observed effects nearly 3 times greater than in models relying on comparisons between communities. We also found specificity in cause of death, with $\text{PM}_{2.5}$ associated more strongly with ischemic heart disease than with cardiopulmonary or all-cause mortality.
Lotic ecosystems such as rivers and streams are unique in that they represent a continuum of both space and time during the transition from headwaters to the river mouth. As microbes have very ...different controls over their ecology, distribution and dispersion compared with macrobiota, we wished to explore biogeographical patterns within a river catchment and uncover the major drivers structuring bacterioplankton communities. Water samples collected across the River Thames Basin, UK, covering the transition from headwater tributaries to the lower reaches of the main river channel were characterised using 16S rRNA gene pyrosequencing. This approach revealed an ecological succession in the bacterial community composition along the river continuum, moving from a community dominated by Bacteroidetes in the headwaters to Actinobacteria-dominated downstream. Location of the sampling point in the river network (measured as the cumulative water channel distance upstream) was found to be the most predictive spatial feature; inferring that ecological processes pertaining to temporal community succession are of prime importance in driving the assemblages of riverine bacterioplankton communities. A decrease in bacterial activity rates and an increase in the abundance of low nucleic acid bacteria relative to high nucleic acid bacteria were found to correspond with these downstream changes in community structure, suggesting corresponding functional changes. Our findings show that bacterial communities across the Thames basin exhibit an ecological succession along the river continuum, and that this is primarily driven by water residence time rather than the physico-chemical status of the river.
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