Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells.

A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by alterations in the redox state of critical thiols in the IP3R, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We found that under basal conditions, ∼5 of the 60 cysteines are oxidized in IP3R1. Cell treatment with 50 μm thimerosal altered gel shifts, indicating oxidation of ∼20 cysteines. By contrast, the shifts induced by 0.5 mm H2O2 or other oxidants were much smaller. Monitoring of biotin-maleimide attachment to IP3R1 by LC-MS/MS with 71% coverage of the receptor sequence revealed modification of two cytosolic (Cys-292 and Cys-1415) and two intraluminal cysteines (Cys-2496 and Cys-2533) under basal conditions. The thimerosal treatment modified an additional eleven cysteines, but only three (Cys-206, Cys-767, and Cys-1459) were consistently oxidized in multiple experiments. H2O2 also oxidized Cys-206 and additionally oxidized two residues not modified by thimerosal (Cys-214 and Cys-1397). Potentiation of IP3R channel function by oxidants was measured with cysteine variants transfected into a HEK293 IP3R triple-knockout cell line, indicating that the functionally relevant redox-sensitive cysteines are predominantly clustered within the N-terminal suppressor domain of IP3R. To our knowledge, this study is the first that has used proteomic methods to assess the redox state of individual thiols in IP3R in intact cells. © 2018 Joseph et al

Implementation of the Combined--Nonlinear Condensation Transformation

We discuss several applications of the recently proposed combined nonlinear-condensation transformation (CNCT) for the evaluation of slowly convergent, nonalternating series. These include certain statistical distributions which are of importance in linguistics, statistical-mechanics theory, and biophysics (statistical analysis of DNA sequences). We also discuss applications of the transformation in experimental mathematics, and we briefly expand on further applications in theoretical physics. Finally, we discuss a related Mathematica program for the computation of Lerch's transcendent.Comment: 23 pages, 1 table, 1 figure (Comput. Phys. Commun., in press

Habitat coupling in a large lake system: delivery of an energy subsidy by an offshore planktivore to the nearshore zone of Lake Superior

1. We hypothesised that the autumn spawning migration of Lake Superior cisco (Coregonus artedi) provides a resource subsidy, in the form of energy-rich cisco eggs, from the offshore pelagic to the nearshore benthic community over winter, when alternate prey production is likely to be low. 2. We tested this hypothesis using fish and macroinvertebrate surveys, fish population demographics, diet and stable isotope analyses, and bioenergetics modelling. 3. The benthic, congeneric lake whitefish (C. clupeaformis) was a clear beneficiary of cisco spawning. Cisco eggs represented 16% of lake whitefish annual consumption in terms of biomass, but 34% of energy (because of their high energy density: \u3e10 kJ g wet mass 1). Stable isotope analyses were consistent with these results and suggest that other nearshore fish species may also rely on cisco eggs. 4. The lipid content of lake whitefish liver almost doubled from 26 to 49% between November and March, while that of muscle increased from 14 to 26% over the same period, suggesting lake whitefish were building, rather than depleting, lipid reserves during winter. 5. In the other Laurentian Great Lakes, where cisco populations remain very low and rehabilitation efforts are underway, the offshore-to-nearshore ecological link apparent in Lake Superior has been replaced by non-native planktivorous species. These non-native species spawn in spring have smaller eggs and shorter incubation periods. The rehabilitation of cisco in these systems should reinstate the onshore subsidy as it has in Lake Superior

State Efforts to Deter Unauthorized Aliens: Legal Analysis of Arizona's S.B. 1070

This report discusses the major provisions of S.B.1070, as modified by H.B. 2162, and the legal and constitutional considerations possibly implicated by their implementation. The report focuses primarily on those provisions that require state enforcement of federal immigration law and impose criminal penalties for immigration-related conduct, and discusses preemption issues that might be raised by these measures

Evolutionary genomics of a cold-adapted diatom: Fragilariopsis cylindrus

The Southern Ocean houses a diverse and productive community of organisms1, 2. Unicellular eukaryotic diatoms are the main primary producers in this environment, where photosynthesis is limited by low concentrations of dissolved iron and large seasonal fluctuations in light, temperature and the extent of sea ice3, 4, 5, 6, 7. How diatoms have adapted to this extreme environment is largely unknown. Here we present insights into the genome evolution of a cold-adapted diatom from the Southern Ocean, Fragilariopsis cylindrus8, 9, based on a comparison with temperate diatoms. We find that approximately 24.7 per cent of the diploid F. cylindrus genome consists of genetic loci with alleles that are highly divergent (15.1 megabases of the total genome size of 61.1 megabases). These divergent alleles were differentially expressed across environmental conditions, including darkness, low iron, freezing, elevated temperature and increased CO2. Alleles with the largest ratio of non-synonymous to synonymous nucleotide substitutions also show the most pronounced condition-dependent expression, suggesting a correlation between diversifying selection and allelic differentiation. Divergent alleles may be involved in adaptation to environmental fluctuations in the Southern Ocean

Nutritional interventions in randomised clinical trials for people with incurable solid cancer:A systematic review

Background & aimsMalnutrition is highly prevalent in those with cancer and more so in those with incurable cancer. In incurable cancer, it is widely agreed that optimal nutritional care has the potential to positively impact patient and caregiver distress and oncological outcomes. The aim of this systematic review was to describe the diversity and frequency of nutritional interventions, whether given in isolation or as part of a multimodal intervention in those with incurable cancer, in randomised controlled trials. The secondary aims were to describe adherence and their efficacy.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The following databases were searched electronically: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulated Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL) with the time frame from January 2000 to 7th September 2023. Eligible studies included adult patients (≥18 years) diagnosed with incurable solid cancer with a sample size ≥40. Studies were to be primary research and delivered for at least 14 days to allow for efficacy. They were to include a nutritional intervention encompassing at least one of the following: dietary counselling, oral nutritional supplements (ONS), enteral tube feeding and/or parenteral nutrition (PN), given in isolation or as part of a multi-modal intervention. Studies were excluded if the population contained patients who had completed curative treatment or are being treated with curative intent, haematological cancers, or if they examined the effects of micronutrients, proteins, amino acids or fatty acids given in isolation. The quality of the included studies was assessed using the Cochrane risk of bias tool for randomised trials (RoB2). A balloon plot was produced to present the results in addition to a table with a narrative summary of the primary outcomes.ResultsA total of 7968 studies were identified, of which 18 met the eligibility criteria. This included 2720 study participants. The included studies comprised: multimodal interventions (n = 7), dietary counselling (n = 2), nutritional supplementation with or without dietary counselling (n = 7) and PN (n = 2). Primary outcomes included quality of life (QoL), body composition and nutritional status. For QoL, this was reported in 15 studies, 4 studies showed a significant improvement. Body composition was evaluated in 15 studies, 5 of which showed a significant improvement in body weight and two in fat-free mass (FFM). Nutritional status was reported in 6 studies with one showing a significant difference in Patient-Generated Subjective Global Assessment (PG-SGA) score. The risk of bias was deemed ‘low’ in 6 studies, with ‘some concerns’ in 10 studies and a ‘high risk’ in 2 studies. There was heterogeneity between the studies.ConclusionThis systematic review has highlighted some positive findings in regard to QoL, body weight and nutritional intake. Optimum nutritional intervention was not identified. Future studies should evaluate the effectiveness of earlier nutritional interventions at the point of diagnosis, including regular reviews and the impact this has on nutritional outcomes, QoL and overall survival (OS)

A Performance Evaluation of Vis/NIR Hyperspectral Imaging to Predict Curcumin Concentration in Fresh Turmeric Rhizomes

Hyperspectral image (HSI) analysis has the potential to estimate organic compounds in plants and foods. Curcumin is an important compound used to treat a range of medical conditions. Therefore, a method to rapidly determine rhizomes with high curcumin content on-farm would be of significant advantage for farmers. Curcumin content of rhizomes varies within, and between varieties but current chemical analysis methods are expensive and time consuming. This study compared curcumin in three turmeric (Curcuma longa) varieties and examined the potential for laboratory-based HSI to rapidly predict curcumin using the visible–near infrared (400–1000 nm) spectrum. Hyperspectral images (n = 152) of the fresh rhizome outer-skin and flesh were captured, using three local varieties (yellow, orange, and red). Distribution of curcuminoids and total curcumin was analysed. Partial least squares regression (PLSR) models were developed to predict total curcumin concentrations. Total curcumin and the proportion of three curcuminoids differed significantly among all varieties. Red turmeric had the highest total curcumin concentration (0.83 ± 0.21%) compared with orange (0.37 ± 0.12%) and yellow (0.02 ± 0.02%). PLSR models predicted curcumin using raw spectra of rhizome flesh and pooled data for all three varieties (R2c = 0.83, R2p = 0.55, ratio of prediction to deviation (RPD) = 1.51) and was slightly improved by using images of a single variety (orange) only (R2c = 0.85, R2p = 0.62, RPD = 1.65). However, prediction of curcumin using outer-skin of rhizomes was poor (R2c = 0.64, R2p = 0.37, RPD = 1.28). These models can discriminate between ‘low’ and ‘high’ values and so may be adapted into a two-level grading system. HSI has the potential to help identify turmeric rhizomes with high curcumin concentrations and allow for more efficient refinement into curcumin for medicinal purposes

Granular dampers in microgravity: sharp transition between modes of operation

Abstract When a container filled with granular material is subjected to sinusoidal vibration in microgravity, dependent on the amplitude of the oscillation, the granulate may exhibit one of two distinct dynamical modes: at low amplitude, a gas-like state is observed, where the particles are relatively homogeneously distributed within the container, almost independent of the phase of the oscillation. In contrast, for large amplitude, collective motion of the particles is favoured, termed collect-and-collide regime. Both regimes are characterized by very different dissipation characteristics. A recent model predicts that the regimes are separated by a sharp transition due to a critical amplitude of the vibration. Here we confirm this prediction of a sharp transition and also the numerical value of the critical amplitude by means of experiments performed under conditions of weightlessness

Triggered Surface Slips In The Salton Trough Associated With The 1999 Hector Mine, California, Earthquake

Surface fracturing occurred along the southern San Andreas, Superstition Hills, and Imperial faults in association with the 16 October 1999 (Mw 7.1) Hector Mine earthquake, making this at least the eighth time in the past 31 years that a regional earthquake has triggered slip along faults in the Salton Trough. Fractures associated with the event formed discontinuous breaks over a 39-km-long stretch of the San Andreas fault, from the Mecca Hills southeastward to Salt Creek and Durmid Hill, a distance from the epicenter of 107 to 139 km. Sense of slip was right lateral; only locally was there a minor (∼1 mm) vertical component of slip. Dextral slip ranged from 1 to 13 mm. Maximum slip values in 1999 and earlier triggered slips are most common in the central Mecca Hills. Field evidence indicates a transient opening as the Hector Mine seismic waves passed the southern San Andreas fault. Comparison of nearby strong-motion records indicates several periods of relative opening with passage of the Hector Mine seismic wave—a similar process may have contributed to the field evidence of a transient opening.Bulletin of the Seismological Society of America 92(4), 1300-1317. (2002)0037-110