Investigating Factors Affecting Unit-to-Unit Variability in Non-Systemic Pesticide Residues by Stochastic Simulation Modelling

The estimation of acute dietary intake plays a key role in the safety assessment of pesticide residues and needs knowledge of the unit-to-unit variability in residues. There is limited knowledge of contributions of factors to often observed large unit-to-unit variability in residues. A stochastic simulation study was conducted to investigate the effects of sample size and heterogeneity in factors driving residue dissipation of non-systemic pesticides on the unit-to-unit variability among individual apples. The heterogeneity in driving factors was expressed in terms of variability in three dissipation parameters. The variability factor (VF), calculated as the ratio of residues in individual fruit at the 97.5th percentile and the mean residue, was used to represent the unit-to-unit variability. As the rate of dissipation increased, the variability in the corresponding parameter led to larger increases in the variability VF of residues over time. Thus, under field conditions, the relative in pesticide residues is expected to increase with time although the absolute level of residues decreases. The coefficient of variation (CV) was used to describe residue variability in samples of small sizes (5, 10, 20, 40, and 80). When sample size was fewer than 40 fruit, the sample CV increased steeply with decreasing sample size. Measuring residues as concentrations, instead of per fruit, also led to an average 4–8% increase in the CV of residues because of variability in fruit expansion.     

Anaemia, Folate, Zinc and Copper Deficiencies Among Adolescent Schoolgirls in Eastern Sudan

Anaemia is a widespread problem especially in the tropics. Among adolescent girls, it has negative consequences on growth, school performance, morbidity and reproductive performance. A cross-sectional study was conducted to investigate the prevalence of anaemia, iron, folate, zinc and copper deficiencies amongst adolescent schoolgirls in New Halfa, eastern Sudan, and to examine the relationship of these micronutrients with haemoglobin (Hb) levels. Out of 187 adolescent schoolgirls, 181 (96.8%) had anaemia (Hb?<?12 g/dl); 21% had mild anaemia (Hb 11.0–11.9 g/dl); 66.8.1% had moderate anaemia (Hb 8.0–10.9 g/dl), and 12.1% had severe anaemia (Hb?<?8 g/dl), respectively. Iron deficiency (S-ferritin?<?12 μg/l), iron deficiency anaemia (<12 m/dl and S- ferritin?<?12 μg/l) and folate deficiency (S-folate?<?3 ng/ml) were prevalent in 17.6%, 16.5% and 69% of these girls, respectively. Nine percent and 5.9% of these girls had zinc (<75 μg/ml) and copper deficiency (<75 μg/ml), respectively. Twenty-six (14%) girls had ≥2 micronutrient deficiencies. S-ferritin and zinc were significantly lower in patients with severe anaemia. Haemoglobin levels were significantly positively correlated with zinc levels (r?=?0.161, P?=?0.03) and with copper levels (r?=?0.151, P?=?0.03). Thus, interventions are required to prevent and control anaemia in this setting. Further research is needed.     

Toll‐like receptor 9 protects non‐immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2

Toll‐like receptor 9 (TLR9) has a key role in the recognition of pathogen DNA in the context of infection and cellular DNA that is released from damaged cells. Pro‐inflammatory TLR9 signalling pathways in immune cells have been well investigated, but we have recently discovered an alternative pathway in which TLR9 temporarily reduces energy substrates to induce cellular protection from stress in cardiomyocytes and neurons. However, the mechanism by which TLR9 stimulation reduces energy substrates remained unknown. Here, we identify the calcium‐transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway. TLR9 stimulation reduces SERCA2 activity, modulating Ca²⁺ handling between the SR/ER and mitochondria, which leads to a decrease in mitochondrial ATP levels and the activation of cellular protective machinery. These findings reveal how distinct innate responses can be elicited in immune and non‐immune cells—including cardiomyocytes—using the same ligand‐receptor system.     

Use of signal quality measurements to gain efficiency in the analysis of cDNA microarray data

This research provides a new way to measure error in microarray data in order to improve gene expression analysis.Microarray data contains many sources of error.In order to glean information about mRNA expression levels,the true signal must first be segregated from noise.This research focuses on the variation that can be captured at the spot level in cDNA microarray images.Variation at other levels,due to differences at the array,dye,and block levels,can be corrected for by a variety of existing normalizati...     

Technological innovations in the recreational fishing sector: implications for fisheries management and policy

Reviews in Fish Biology and Fisheries - Technology that is developed for or adopted by the recreational fisheries sector (e.g., anglers and the recreational fishing industry) has led to rapid and...     

High-performance hydrophobic interaction chromatography of estrogen receptors and magnesium dependent protein kinase(s): detection of two molecular forms of estrogen receptors in the presence and absence of sodium molybdate

The separation characteristics of estrogen receptors (ER) from human breast cancer were evaluated based on their hydrophobic properties. Results show that (1) two distinct hydrophobic isoforms of ER exist either in the presence of sodium molybdate (peaks MI and MII with retention times of 15-17 min and 24-26 min) or in its absence (peaks I and II with retention times of 25-27 min and 34-36 min respectively); (2) this is observed whether molybdate (MoO2-4) is added to prepared cytosol or to the buffer prior to homogenization; (3) isoform MII and I separated with similar retention times suggesting they are the same ER species; and (4) isoform MI (Rt = 15-17 min) is a distinct ER species from either MII/I (Rt = 25-28 min) or II (Rt = 34-36 min). The latter isoform represents a highly hydrophobic species seen only in the absence of MoO2-4. Finally, (5) MoO2-4 ions appear to interconvert the most hydrophobic species (II) into the least hydrophobic isoform (MI) with virtually no change in the quantity of isoform(s) MII/I. However, it cannot be ascertained if the II----MI interconversion proceeds via isoform MII/I. Isoform II may result from the interaction with the stationary phase via its DNA binding site since MoO2-4, which is suggested to directly interact with this site, selectively interacts with peak II. These results imply the usefulness of inclusion of receptor stabilizing reagents in the mobile phase for preserving receptor integrity and in elucidating the interrelationships of ER isoforms and associated macromolecules.     

Pluripotency Gene Expression and Growth Control in Cultures of Peripheral Blood Monocytes during Their Conversion into Programmable Cells of Monocytic Origin (PCMO): Evidence for a Regulatory Role of Autocrine Activin and TGF-β

Previous studies have shown that peripheral blood monocytes can be converted in vitro to a stem cell-like cell termed PCMO as evidenced by the re-expression of pluripotency-associated genes, transient proliferation, and the ability to adopt the phenotype of hepatocytes and insulin-producing cells upon tissue-specific differentiation. However, the regulatory interactions between cultured cells governing pluripotency and mitotic activity have remained elusive. Here we asked whether activin(s) and TGF-β(s), are involved in PCMO generation. De novo proliferation of PCMO was higher under adherent vs. suspended culture conditions as revealed by the appearance of a subset of Ki67-positive monocytes and correlated with down-regulation of p21^WAF1 beyond day 2 of culture. Realtime-PCR analysis showed that PCMO express ActRIIA, ALK4, TβRII, ALK5 as well as TGF-β1 and the β_A subunit of activin. Interestingly, expression of ActRIIA and ALK4, and activin A levels in the culture supernatants increased until day 4 of culture, while levels of total and active TGF-β1 strongly declined. PCMO responded to both growth factors in an autocrine fashion with intracellular signaling as evidenced by a rise in the levels of phospho-Smad2 and a drop in those of phospho-Smad3. Stimulation of PCMO with recombinant activins (A, B, AB) and TGF-β1 induced phosphorylation of Smad2 but not Smad3. Inhibition of autocrine activin signaling by either SB431542 or follistatin reduced both Smad2 activation and Oct4A/Nanog upregulation. Inhibition of autocrine TGF-β signaling by either SB431542 or anti-TGF-β antibody reduced Smad3 activation and strongly increased the number of Ki67-positive cells. Furthermore, anti-TGF-β antibody moderately enhanced Oct4A/Nanog expression. Our data show that during PCMO generation pluripotency marker expression is controlled positively by activin/Smad2 and negatively by TGF-β/Smad3 signaling, while relief from growth inhibition is primarily the result of reduced TGF-β/Smad3, and to a lesser extent, activin/Smad2 signaling.     

Sickle cell disease in mice is associated with sensitization of sensory nerve fibers

The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5 Hz to stimulate preferentially Aβ, Aδ, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5 Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD.     

Use of spatiotemporal analysis of laboratory submission data to identify potential outbreaks of new or emerging diseases in cattle in Great Britain

Background  

New and emerging diseases of livestock may impact animal welfare, trade and public health. Early detection of outbreaks can reduce the impact of these diseases by triggering control measures that limit the number of cases that occur. The aim of this study was to investigate whether prospective spatiotemporal methods could be used to identify outbreaks of new and emerging diseases in scanning surveillance data. SaTScan was used to identify clusters of unusually high levels of submissions where a diagnosis could not be reached (DNR) using different probability models and baselines. The clusters detected were subjected to a further selection process to reduce the number of false positives and a more detailed epidemiological analysis to ascertain whether they were likely to represent real outbreaks.