Sleep‐disordered breathing and poststroke outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150527/1/ana25515_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150527/2/ana25515.pd

Structural and Functional Diversity of the Microbial Kinome

The eukaryotic protein kinase (ePK) domain mediates the majority of signaling and coordination of complex events in eukaryotes. By contrast, most bacterial signaling is thought to occur through structurally unrelated histidine kinases, though some ePK-like kinases (ELKs) and small molecule kinases are known in bacteria. Our analysis of the Global Ocean Sampling (GOS) dataset reveals that ELKs are as prevalent as histidine kinases and may play an equally important role in prokaryotic behavior. By combining GOS and public databases, we show that the ePK is just one subset of a diverse superfamily of enzymes built on a common protein kinase–like (PKL) fold. We explored this huge phylogenetic and functional space to cast light on the ancient evolution of this superfamily, its mechanistic core, and the structural basis for its observed diversity. We cataloged 27,677 ePKs and 18,699 ELKs, and classified them into 20 highly distinct families whose known members suggest regulatory functions. GOS data more than tripled the count of ELK sequences and enabled the discovery of novel families and classification and analysis of all ELKs. Comparison between and within families revealed ten key residues that are highly conserved across families. However, all but one of the ten residues has been eliminated in one family or another, indicating great functional plasticity. We show that loss of a catalytic lysine in two families is compensated by distinct mechanisms both involving other key motifs. This diverse superfamily serves as a model for further structural and functional analysis of enzyme evolution

Parental and infant characteristics and childhood leukemia in Minnesota

<p>Abstract</p> <p>Background</p> <p>Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL), few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology.</p> <p>Methods</p> <p>We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML) diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>Male sex (HR = 1.41, 95% CI 1.16–1.70), white race (HR = 2.32, 95% CI 1.13–4.76), and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70) increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47). Higher birth weights (>3798 grams) (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65), and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60) increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education.</p> <p>Conclusion</p> <p>We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.</p

Periprosthetic osteolysis after total hip replacement: molecular pathology and clinical management

Periprosthetic osteolysis is a serious complication of total hip replacement (THR) in the medium to long term. Although often asymptomatic, osteolysis can lead to prosthesis loosening and periprosthetic fracture. These complications cause significant morbidity and require complex revision surgery. Here, we review advances in our understanding of the cell and tissue response to particles produced by wear of the articular and non-articular surfaces of prostheses. We discuss the molecular and cellular regulators of osteoclast formation and bone resorptive activity, a better understanding of which may lead to pharmacological treatments for periprosthetic osteolysis. We describe the development of imaging techniques for the detection and measurement of osteolysis around THR prostheses, which enable improved clinical management of patients, provide a means of evaluating outcomes of non-surgical treatments for periprosthetic osteolysis, and assist in pre-operative planning for revision surgery. Finally, there have been advances in the materials used for bearing surfaces to minimise wear, and we review the literature regarding the performance of these new materials to date.Donald W. Howie, Susan D. Neale, David R. Haynes, Oksana T. Holubowycz, Margaret A. McGee, Lucian B. Solomon, Stuart A. Callary, Gerald J. Atkins, David M. Findla

A Model of an Optimum Currency Area

This paper develops a model of the circumstances under which it is beneficial to participate in a currency area. The proposed two-country monetary model of trade with nominal rigidities encompasses the real and monetary arguments suggested by the optimum currency area literature: correlation of real and monetary shocks, international factor mobility, fiscal adjustment, openness, difference in national inflationary biases, and transactions costs. The effect of openness on the net benefits is ambiguous, contrary to the usual argument that more open economies are better candidates for a currency area. Also, prospective member countries do not necessarily agree on whether a given currency union should be created

Prediction of Yield for Flip-Chip Solder Assemblies

A model has been developed to predict the yield of solder flip-chip assemblies. Yield was found in relation to the mean and the standard deviation of the solder volume distribution, the assembly warpage, and the chip size. In this study, solder volume was represented by the diameters of the solder balls. The model identified failed joints using the Surface Evolver and a regression model. The results showed that the volume variation corresponding to a diameter variance of 25m for solder balls produced very low yields. Warpage greatly decreased the maximum variance allowed for 100% yields. For example, the diameter variance is +/- 11m for 150m solder balls; it is reduced to 7.6m with a warpage of 6.6m across the diagonal of a 1x1cm chip. In addition to volume variation and warpage, the pad radius also had an effect on the assembly yield. However, this effect is non-linear. In some cases, larger solder balls could result in lower yields than smaller solder ball sizes with the same pad rad..

Do Family Meetings Really Matter? Their Relationship to Planning and Performance Outcomes in Small Family Businesses

This empirical research focused on examining the relationship between family meetings and the characteristics of those family meetings (who participated and issues discussed), planning processes (succession planning, estate planning, family mission and business mission) and performance measures (revenues and number of generations survived). Small family businesses in a midwestern state were surveyed with 241 useable responses. Significant differences were found in the planning processes between businesses that held family meetings and those that did not. No differences were found for the performance measures. Significant relationships between family meetings and both planning processes and performance measures were found when comparing family businesses based on who participated in the family meetings - just holding meetings does not matter, but inclusiveness of those meetings does matter

Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.

Fetal alcohol spectrum disorder (FASD) describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol) and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6). The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, p<0.05, N = 8–9) (cell line: 5% at 20 mM and 40 mM, p<0.05, N = 6). Acetaldehyde also reduced Ki67-positive cells in both experiments (explants at 40 µM p<0.05; N = 6) (cell line at 10 µM and 40 µM; p<0.05; N = 7). Only in the cell line at 20 µM acetaldehyde demonstrated increased apoptosis (p<0.05; N = 6). Alcohol inhibited taurine transport in BeWo cells at 10 mM and 40 mM (p<0.05; N = 6), and in placenta at 40 mM (p<0.05; N = 7). Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6). Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6). Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of FASD by reducing placental growth. Alcohol also reduces the transport of taurine, which is vital for developmental neurogenesis

Effect of alcohol and acetaldehyde on system β and System A activity in BeWo cells.

<p>Na⁺-dependent ³H taurine uptake (system β activity) and Na⁺-dependent ¹⁴C-MeAIB uptake (system A activity) of BeWo cells over time. (a) system β activity and (b) system A activity, over 10, 20 and 30 minutes (Mean 23282±4809, SE = 2151, N = 6). The least squares linear regression shows that uptake was linearly related to time in all cases (p≤0.05). (c) System β activity of BeWo cells at 30 minutes. Ethanol treatment at 10 mM and 40 mM significantly decreased transporter activity (p<0.05; N = 6). (d) Acetaldehyde exposure did not change system β activity after 30 minutes (N = 6; p>0.05). (e) System A activity was not affected by ethanol or (f) acetaldehyde (N = 6; p>0.05). Statistical analysis with Wilcoxon signed-rank. <b>*</b>p<0.05 vs control.</p