Robust bursting to the origin: heteroclinic cycles with maximal symmetry equilibria

Preprint version of an article published in International Journal of Bifurcation and Chaos, 15, 9, 2005, pp. 2819-2832. DOI: 10.1142/S0218127405013708 © copyright World Scientific Publishing Company. http://www.worldscinet.com/ijbc/ijbc.shtmlRobust attracting heteroclinic cycles have been found in many models of dynamics with symmetries. In all previous examples, robust heteroclinic cycles appear between a number of symmetry broken equilibria. In this paper we examine the first example where there are robust attracting heteroclinic cycles that include the origin, ie a point with maximal symmetry. The example we study is for vector fields on R3 with (Z2)3 symmetry. We list all possible generic (codimension one) local and global bifurcations by which this cycle can appear as an attractor; these include a resonance bifurcation from a limit cycle, direct bifurcation from a stable origin and direct bifurcation from other and more familiar robust heteroclinic cycles

Genetic Testing for Breast and Ovarian Cancer: Implications for Life Insurance

As the science of genetic testing progresses, the debate surrounding the uses of genetic information intensifies. In February, President Clinton signed an executive order prohibiting federal agencies from using such information to make hiring, promotion, or placement decisions. Concerns about privacy and discrimination have led many states to propose or enact statutes that prohibit health insurers from using genetic test results in their underwriting decisions. However, few statutes address access to these results by the life insurance industry. This Issue Brief summarizes the current debate on whether life insurers should have access to genetic testing information for breast and ovarian cancer, and provides actuarial insight into the potential effect of such testing on the voluntary term insurance market

ttm-1 encodes CDF transporters that excrete zinc from intestinal cells of C. elegans and act in a parallel negative feedback circuit that promotes homeostasis

Zinc is an essential metal involved in a wide range of biological processes, and aberrant zinc metabolism is implicated in human diseases. The gastrointestinal tract of animals is a critical site of zinc metabolism that is responsible for dietary zinc uptake and distribution to the body. However, the role of the gastrointestinal tract in zinc excretion remains unclear. Zinc transporters are key regulators of zinc metabolism that mediate the movement of zinc ions across membranes. Here, we identified a comprehensive list of 14 predicted Cation Diffusion Facilitator (CDF) family zinc transporters in Caenorhabditis elegans and demonstrated that zinc is excreted from intestinal cells by one of these CDF proteins, TTM-1B. The ttm-1 locus encodes two transcripts, ttm-1a and ttm-1b, that use different transcription start sites. ttm-1b expression was induced by high levels of zinc specifically in intestinal cells, whereas ttm-1a was not induced by zinc. TTM-1B was localized to the apical plasma membrane of intestinal cells, and analyses of loss-of-function mutant animals indicated that TTM-1B promotes zinc excretion into the intestinal lumen. Zinc excretion mediated by TTM-1B contributes to zinc detoxification. These observations indicate that ttm-1 is a component of a negative feedback circuit, since high levels of cytoplasmic zinc increase ttm-1b transcript levels and TTM-1B protein functions to reduce the level of cytoplasmic zinc. We showed that TTM-1 isoforms function in tandem with CDF-2, which is also induced by high levels of cytoplasmic zinc and reduces cytoplasmic zinc levels by sequestering zinc in lysosome-related organelles. These findings define a parallel negative feedback circuit that promotes zinc homeostasis and advance the understanding of the physiological roles of the gastrointestinal tract in zinc metabolism in animals

Obesity and COVID-19 Outcomes in a Primarily Black Population

ABSTRACT Background: Studies have noted higher COVID-19 mortality with more severe obesity in populations that included a small percentage of Black patients. Methods: We retrospectively analyzed COVID-19 outcomes associated with obesity in our largely African American patient population. A total of 1101 symptomatic patients with a positive COVID-19 laboratory test March 5 to June 3, 2020, were categorized into weight groups based on body mass index (BMI). Of these patients, 679 (61.7%) were Black. A total of 355 (32.2%) patients had overweight and 516 (46.9%) had obesity. Results: BMI was an independent risk factor for intubation and an independent predictor for ICU length of stay and intubation days. An unexpected observation was favorable outcomes in mild obesity compared with normal weight and more severe obesity, likely a result of older age and higher Charlson comorbidity index in patients with normal BMI compared with patients with mild obesity. Conclusions: In a diverse primarily Black population, comorbidities were a concern for adverse COVID-19 outcomes and COVID-19 outcomes were significantly worse with moderate and severe obesity

Computational Studies of the Mechanical Stability for Single-Strand Break DNA.

The stability of DNA is crucial for the existence of most living organisms. Even a single DNA break can lead to serious problems, including cell death. In this work the position specificity of single strand breaks (SSB) and the stability of short DNA fragments of various lengths and sequence repetitions (d(AT)30, d(ATGC)15, d(GC)30, d(TTAGG)12, d(TTAGGG)10, and d(TTTAGGG)9 with SSBs and d(GC) with 2-60 repetitions without SSBs) were examined, by performing a series of steered molecular dynamics simulations using the coarse-grained NARES-2P force field. Our results show that the stability of DNA with a SSB strongly depends on the position of the break, and that the minimum length of DNA required for stability is sequence dependent. d(GC)30 with an SSB in position x was found to be less resistant to stretching than d(GC) x without SSB, where x is the number of d(GC) repetitions. DNA sequences with longer repeated fragments (such as telomeres) exhibit greater stability in the presence of breaks positioned at the beginning of the chain, which could constitute a cellular defense mechanism against DNA damage

Value within otolaryngology: Assessment of the cost-utility analysis literature

AbstractObjectiveTo assess the characteristics and quality of cost utility analyses (CUA) related to otolaryngology within the CEA registry and to summarize their collective results.MethodsAll cost-utility analyses published between 1976 and 2011 contained in the Cost-Effectiveness Analysis Registry (CEA Registry) were evaluated. Topics that fall within the care of an otolaryngologist were included in the review regardless of the presence of an otolaryngologist author. Potential associations between various study characteristics and CEA registry quality scores were evaluated using the Pearson product moment correlation coefficient.ResultsSixty-one of 2913 (2.1%) total CUA publications screened were related to otolaryngology. Eighteen of 61 (29.5%) publications included an otolaryngologist as an author. Fourteen studies agreed on the cost effectiveness of at least unilateral cochlear implantation and six of seven (85.7%) studies demonstrated the cost effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). Forty-six percent (28 of 61) of all manuscripts were published between 2008 and 2011. A more recent publication year was associated with a higher CEA registry quality score while the presence of an otolaryngologist author and journal impact factor had no significant correlation with the quality of the CUA.ConclusionBased on current evidence in the CEA registry, unilateral cochlear implantation for hearing loss and CPAP for OSA are both cost-effective therapeutic interventions. Although CUAs in otolaryngology have increased in quantity and improved in quality in more recent years, there is a relative lack of CUAs in otolaryngology in comparison to other subspecialties

Weight loss, exercise, or both and physical function in obese older adults

BACKGROUND: Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. METHODS: In this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weightmanagement (diet) group, an exercise group, or a weight-management-plus-exercise (diet–exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life. RESULTS: A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet–exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet–exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet–exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet–exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet–exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet–exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet–exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries. CONCLUSIONS: These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Background

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al