Effect of weather on asthmatic children in the Eastern part of the Netherlands

A biometeorological analysis of the daily asthma complaints, classified in 5 degrees of severity, of 50 boys and 25 girls, 7 to 16 years old, at the asthma center Eykeloord (Eastern Netherlands), during 1964 has shown that in winter and early spring the number of asthma attacks in both sexes increased during periods of cooling. The total rise in asthma attacks increased with the length of the cooling period and decreased in relation to the length of the period of warming up. During the summer months June and August these meteorotropic effects were not statistically significant. The observations confirmed the previous findings at an asthma center in the Western Netherlands.

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Zusammenfassung Eine biometeorologische Analyse der täglichen Asthmabeschwerden, die in 5 Schweregraden klassifiziert wurden, bei 50 Knaben und 25 Mädchen im Alter von 7 bis 16 Jahren in der Asthmaklinik Eykeloord (Ost-Holland)während des Jahres 1964 hat gezeigt, dass im Winter und Vorfrühling die Anzahl der Asthmaanfälle bei Kälteeinbrüchen zunimmt. Asthmaanfälle nehmen an Zahl mit der Länge der Kälteperioden zu und mit der Länge der Wärmeperioden ab.Während der Sommermonate Juni bis August waren diese Beziehungen zwar auch nachweisbar aber nicht signifikant. Die Beobachtungen bestätigten früheren Ergebnisse in einer Asthmaklinik in West-Holland.

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Resume Une analyse biométéorologique des accès d'asthme a montré qu'en hiver et au début du printemps le nombre des dits accès augmente au moment d'une advection d'air froid. Pour ce faire, on s'est basé sur l'observation de 50 garçons et de 25 fillettes de 7 à 16 ans répartis en 5 classes d'acuité de la maladie. Tous étaient en traitement durant l'année 1964 à la clinique pour asthmatiques d'Eykeloord(Hollande orientale). Les accès d'asthme sont d'autant plus nombreux que la période froide est plus longue et leur nombre diminue parallèlement à la durée des périodes plus chaudes. La même relation a pu être établie durant les mois d'été (de juin à août), mais pas de façon significative. Ces observations confirment celles qui avaient été faites antérieurement dans une clinique pour asthmatiques de l'ouest de la Hollande.

     

Spatial Heterogeneity in Ecologically Important Climate Variables at Coarse and Fine Scales in a High-Snow Mountain Landscape

Climate plays an important role in determining the geographic ranges of species. With rapid climate change expected in the coming decades, ecologists have predicted that species ranges will shift large distances in elevation and latitude. However, most range shift assessments are based on coarse-scale climate models that ignore fine-scale heterogeneity and could fail to capture important range shift dynamics. Moreover, if climate varies dramatically over short distances, some populations of certain species may only need to migrate tens of meters between microhabitats to track their climate as opposed to hundreds of meters upward or hundreds of kilometers poleward. To address these issues, we measured climate variables that are likely important determinants of plant species distributions and abundances (snow disappearance date and soil temperature) at coarse and fine scales at Mount Rainier National Park in Washington State, USA. Coarse-scale differences across the landscape such as large changes in elevation had expected effects on climatic variables, with later snow disappearance dates and lower temperatures at higher elevations. However, locations separated by small distances (∼20 m), but differing by vegetation structure or topographic position, often experienced differences in snow disappearance date and soil temperature as great as locations separated by large distances (>1 km). Tree canopy gaps and topographic depressions experienced later snow disappearance dates than corresponding locations under intact canopy and on ridges. Additionally, locations under vegetation and on topographic ridges experienced lower maximum and higher minimum soil temperatures. The large differences in climate we observed over small distances will likely lead to complex range shift dynamics and could buffer species from the negative effects of climate change.     

Protein lipoylation in mitochondria requires Fe–S cluster assembly factors NFU4 and NFU5

Plants have evolutionarily conserved NifU (NFU)-domain proteins that are targeted to plastids or mitochondria. “Plastid-type” NFU1, NFU2, and NFU3 in Arabidopsis (Arabidopsis thaliana) play a role in iron–sulfur (Fe–S) cluster assembly in this organelle, whereas the type-II NFU4 and NFU5 proteins have not been subjected to mutant studies in any plant species to determine their biological role. Here, we confirmed that NFU4 and NFU5 are targeted to the mitochondria. The proteins were constitutively produced in all parts of the plant, suggesting a housekeeping function. Double nfu4 nfu5 knockout mutants were embryonic lethal, and depletion of NFU4 and NFU5 proteins led to growth arrest of young seedlings. Biochemical analyses revealed that NFU4 and NFU5 are required for lipoylation of the H proteins of the glycine decarboxylase complex and the E2 subunits of other mitochondrial dehydrogenases, with little impact on Fe–S cluster-containing respiratory complexes or aconitase. Consequently, the Gly-to-Ser ratio was increased in mutant seedlings and early growth improved with elevated CO₂ treatment. In addition, pyruvate, 2-oxoglutarate, and branched-chain amino acids accumulated in nfu4 nfu5 mutants, further supporting defects in the other three mitochondrial lipoate-dependent enzyme complexes. NFU4 and NFU5 interacted with mitochondrial lipoyl synthase (LIP1) in yeast 2-hybrid and bimolecular fluorescence complementation assays. These data indicate that NFU4 and NFU5 have a more specific function than previously thought, most likely providing Fe–S clusters to lipoyl synthase.

A pair of evolutionarily conserved proteins involved in iron–sulfur cofactor assembly have a specific role in lipoate biosynthesis for mitochondrial dehydrogenases.     

A two-gene strategy increases iron and zinc concentrations in wheat flour,improving mineral bioaccessibility

Dietary deficiencies of iron and zinc cause human malnutrition that can be mitigated by biofortified staple crops. Conventional breeding approaches to increase grain mineral concentrations in wheat (Triticum aestivum L.) have had only limited success, and our understanding of the genetic and physiological barriers to altering this trait is incomplete. Here we demonstrate that a transgenic approach combining endosperm-specific expression of the wheat VACUOLAR IRON TRANSPORTER gene TaVIT2-D with constitutive expression of the rice (Oryza sativa) NICOTIANAMINE SYNTHASE gene OsNAS2 significantly increases the total concentration of zinc and relocates iron to white-flour fractions. In two distinct bread wheat cultivars, we show that the so called VIT-NAS construct led to a two-fold increase in zinc in wholemeal flour, to ∼50 µg g⁻¹. Total iron was not significantly increased, but redistribution within the grain resulted in a three-fold increase in iron in highly pure, roller-milled white flour, to ∼25 µg g⁻¹. Interestingly, expression of OsNAS2 partially restored iron translocation to the aleurone, which is iron depleted in grain overexpressing TaVIT2 alone. A greater than three-fold increase in the level of the natural plant metal chelator nicotianamine in the grain of VIT-NAS lines corresponded with improved iron and zinc bioaccessibility in white flour. The growth of VIT-NAS plants in the greenhouse was indistinguishable from untransformed controls. Our results provide insights into mineral translocation and distribution in wheat grain and demonstrate that the individual and combined effects of the two transgenes can enhance the nutritional quality of wheat beyond what is possible by conventional breeding.

Targeted expression of a vacuolar iron transporter and increased nicotianamine levels have combinatorial effects on iron and zinc levels and their distribution in wheat grain.     

Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion

Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37°C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.     

Incorporation of mineral nitrogen into the soil food web as affected by plant community composition

Although nitrogen (N) deposition is increasing globally, N availability still limits many organisms, such as microorganisms and mesofauna. However, little is known to which extent soil organisms rely on mineral‐derived N and whether plant community composition modifies its incorporation into soil food webs. More diverse plant communities more effectively compete with microorganisms for mineral N likely reducing the incorporation of mineral‐derived N into soil food webs. We set up a field experiment in experimental grasslands with different levels of plant species and functional group richness. We labeled soil with ¹⁵NH₄ ¹⁵NO₃ and analyzed the incorporation of mineral‐derived ¹⁵N into soil microorganisms and mesofauna over 3 months. Mineral‐derived N incorporation decreased over time in all investigated organisms. Plant species richness and presence of legumes reduced the uptake of mineral‐derived N into microorganisms. In parallel, the incorporation of mineral‐derived ¹⁵N into mesofauna species declined with time and decreased with increasing plant species richness in the secondary decomposer springtail Ceratophysella sp. Effects of both plant species richness and functional group richness on other mesofauna species varied with time. The presence of grasses increased the ¹⁵N incorporation into Ceratophysella sp., but decreased it in the primary decomposer oribatid mite Tectocepheus velatus sarekensis. The results highlight that mineral N is quickly channeled into soil animal food webs via microorganisms irrespective of plant diversity. The amount of mineral‐derived N incorporated into soil animals, and the plant community properties affecting this incorporation, differed markedly between soil animal taxa, reflecting species‐specific use of food resources. Our results highlight that plant diversity and community composition alter the competition for N in soil and change the transfer of N across trophic levels in soil food webs, potentially leading to changes in soil animal population dynamics and community composition. Sustaining high plant diversity may buffer detrimental effects of elevated N deposition on soil biota.     

Two novel loci underlie natural differences in Caenorhabditis elegans abamectin responses

Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes.     

Availability of Volunteer-Led Home-Based Care System and Baseline Factors as Predictors of Clinical Outcomes in HIV-Infected Patients in Rural Zambia

Background

We assessed the impact of home-based care (HBC) for HIV+ patients, comparing outcomes between two groups of Zambians receiving antiretroviral therapy (ART) who lived in villages with and without HBC teams.

Methods

We conducted a retrospective cohort study using medical charts from Macha Mission Hospital, a hospital providing HIV care in Zambia''s rural Southern Province. Date of birth, date of ART initiation, place of residence, sex, body mass index (BMI), CD4+ cell count, and hemoglobin (Hgb) were abstracted. Logistic regression was used to test our hypothesis that HBC was associated with treatment outcomes.

Results

Of 655 patients, 523 (80%) were eligible and included in the study. There were 428 patients (82%) with favorable outcomes (alive and on ART) and 95 patients (18%) with unfavorable outcomes (died, lost to follow-up, or stopped treatment). A minority of the 523 eligible patients (n = 84, 16%) lived in villages with HBC available. Living in a village with HBC was not significantly associated with treatment outcomes; 80% of patients in a village with HBC had favorable outcomes, compared to 82% of patients in a village without HBC (P = 0.6 by χ²). In bivariable analysis, lower BMI (P<0.001), low CD4+ cell count (P = 0.02), low Hgb concentration (P = 0.02), and older age at ART initiation (P = 0.047) were associated with unfavorable outcomes. In multivariable analysis, low BMI remained associated with unfavorable outcomes (P<0.001).

Conclusions

We did not find that living in a village with HBC available was associated with improved treatment outcomes. We speculate that the ART clinic''s rigorous treatment preparation before ART initiation and continuous adherence counseling during ART create a motivated group of patients whose outcomes did not improve with additional HBC support. An alternative explanation is that the quality of the HBC program is suboptimal.