Ecological and methodological drivers of non-stationarity in tree growth response to climate

Radial tree growth is sensitive to environmental conditions, making observed growth increments an important indicator of climate change effects on forest growth. However, unprecedented climate variability could lead to non-stationarity, that is, a decoupling of tree growth responses from climate over time, potentially inducing biases in climate reconstructions and forest growth projections. Little is known about whether and to what extent environmental conditions, species, and model type and resolution affect the occurrence and magnitude of non-stationarity. To systematically assess potential drivers of non-stationarity, we compiled tree-ring width chronologies of two conifer species, Picea abies and Pinus sylvestris, distributed across cold, dry, and mixed climates. We analyzed 147 sites across the Europe including the distribution margins of these species as well as moderate sites. We calibrated four numerical models (linear vs. non-linear, daily vs. monthly resolution) to simulate growth chronologies based on temperature and soil moisture data. Climate–growth models were tested in independent verification periods to quantify their non-stationarity, which was assessed based on bootstrapped transfer function stability tests. The degree of non-stationarity varied between species, site climatic conditions, and models. Chronologies of P. sylvestris showed stronger non-stationarity compared with Picea abies stands with a high degree of stationarity. Sites with mixed climatic signals were most affected by non-stationarity compared with sites sampled at cold and dry species distribution margins. Moreover, linear models with daily resolution exhibited greater non-stationarity compared with monthly-resolved non-linear models. We conclude that non-stationarity in climate–growth responses is a multifactorial phenomenon driven by the interaction of site climatic conditions, tree species, and methodological features of the modeling approach. Given the existence of multiple drivers and the frequent occurrence of non-stationarity, we recommend that temporal non-stationarity rather than stationarity should be considered as the baseline model of climate–growth response for temperate forests.     

Radiosensitivity and proliferative activity of vertebral CFU-S surviving in mice injected with oncogenic activities of 239Pu or 241Am

Survival, radiosensitivity and capability to produce differentiated progeny were followed in CFU-S from lumbar vertebrae of mice injected with 198.6 kBq 239Pu/kg or 208.6 kBq 241Am/kg. The CFU-S assay and 59Fe uptake into spleen colonies were used. The number of CFU-S from treated mice was significantly lower than in controls. Higher radiosensitivity of CFU-S from 239Pu- or 241Am-treated mice was demonstrated using additional exposure to 0.5 Gy X-rays 1, 24, 48, 72 hrs after cell transplantation and expressed more precisely by survival curves obtained 1 hr after the marrow cell injection. The effect of 239Pu on CFU-S was characterized by Do 0.58 Gy (n = 0.91) and that of 241Am by Do 0.64 Gy (n = 0.91); corresponding control values were Do 0.89 Gy, n = 1.11. Lower iron utilization due not only to the decreased CFU-S numbers, but also to the defective production of erythroid cells per one CFU-S was found. Complexity of radiation effect on hemopoietic stem cells was demonstrated by the present study.     

Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production

Inhibition of mitochondrial respiratory chain complex I by rotenone had been found to induce cell death in a variety of cells. However, the mechanism is still elusive. Because reactive oxygen species (ROS) play an important role in apoptosis and inhibition of mitochondrial respiratory chain complex I by rotenone was thought to be able to elevate mitochondrial ROS production, we investigated the relationship between rotenone-induced apoptosis and mitochondrial reactive oxygen species. Rotenone was able to induce mitochondrial complex I substrate-supported mitochondrial ROS production both in isolated mitochondria from HL-60 cells as well as in cultured cells. Rotenone-induced apoptosis was confirmed by DNA fragmentation, cytochrome c release, and caspase 3 activity. A quantitative correlation between rotenone-induced apoptosis and rotenone-induced mitochondrial ROS production was identified. Rotenone-induced apoptosis was inhibited by treatment with antioxidants (glutathione, N-acetylcysteine, and vitamin C). The role of rotenone-induced mitochondrial ROS in apoptosis was also confirmed by the finding that HT1080 cells overexpressing magnesium superoxide dismutase were more resistant to rotenone-induced apoptosis than control cells. These results suggest that rotenone is able to induce apoptosis via enhancing the amount of mitochondrial reactive oxygen species production.     

Prevalence,Types, Risk Factors and Clinical Correlates of Anaemia in Older People in a Rural Ugandan Population

Background

Studies conducted in high income countries have shown that anaemia is a common medical condition among older people, but such data are scarce in Africa. The objectives of this study were to estimate the prevalence, types, risk factors and clinical correlates of anaemia in older people.

Methods

Participants were aged (≥ 50) years recruited from a general population cohort from January 2012 to January 2013. Blood samples were collected for assessing hemoglobin, serum ferritin, serum vitamin B12, serum folate, C-reactive protein, malaria infection and stool samples for assessment of hookworm infection. HIV status was assessed using an algorithm for HIV rapid testing. Questionnaires were used to collect data on sociodemographic characteristics and other risk factors for anaemia.

Results

In total, 1449 people participated (response rate 72.3%). The overall prevalence of anaemia was 20.3 % (95% CI 18.2-22.3%), and this was higher for males (24.1%, 95% CI=20.7-27.7%) than females (17.5%, 95% CI=15.0-20.1%). In males, the prevalence of anaemia increased rapidly with age almost doubling between 50 and 65 years (p-trend<0.001). Unexplained anaemia was responsible for more than half of all cases (59.7%). Anaemia was independently associated with infections including malaria (OR 3.49, 95% CI 1.78-6.82), HIV (OR 2.17, 1.32-3.57) heavy hookworm infection (OR 3.45, 1.73-6.91), low fruit consumption (OR 1.55, 1.05-2.29) and being unmarried (OR 1.37 , 95% CI 1.01-1.89). However, the odds of anaemia were lower among older people with elevated blood pressure (OR 0.47, 95% CI 0.29-0.77).

Conclusion

Anaemia control programmes in Uganda should target older people and should include interventions to treat and control hookworms and educational programs on diets that enhance iron absorption. Clinicians should consider screening older people with HIV or malaria for anaemia. Further studies should be done on unexplained anaemia and serum ferritin levels that predict iron deficiency anaemia in older people.     

Neo-tropical felid activity patterns in relation to potential prey and intraguild competitors in the Calakmul Biosphere Reserve,Mexico

Predator behaviors influence, and are influenced by, prey and competitor behaviors. Jaguars (Panthera onca), pumas (Puma concolor), and ocelots (Leopardus pardalis) coexist throughout their geographic range as the three largest predators in a multi-predator community across diverse environments. This study tested for non-random segregation and overlap in the activity patterns of these felids and their shared prey in the southern buffer zone of the Calakmul Biosphere Reserve, in southern Mexico, using camera traps during February to August 2019. We detected little temporal segregation between the nocturnal activities of jaguars, pumas, and ocelots, although pumas were more active closer to dawn. Jaguars had low activity overlap with species likely to be common prey, whereas ocelots had high overlap with their potential prey. Pumas displayed finer-scale similarities in activity with species likely to be common prey. In an understudied area of conservation importance, this study shows that temporal segregation is an unlikely mechanism of coexistence. Further research should incorporate spatio-temporal avoidance and dietary differences to improve our understanding of the mechanisms that drive coexistence between generalist species in a diverse assemblage of threatened felids. Abstract in Spanish is available with online material.     

Long-term effects of low-level 239Pu contamination on murine bone-marrow stem cells and their progeny

The effects of long-term internal contamination with 13.3 kBq kg-1 239Pu injected intravenously were studied in 10-week-old ICR (SPF) female mice. Radiosensitivity of spleen colony-forming units (CFU-S) and 125IUdR incorporating into proliferating cells of vertebral bone marrow and spleens were determined in plutonium-treated and control animals one year after nuclide injection. The CFU-S in 239Pu-treated mice were more sensitive to X-rays (D0 = 0.52 +/- 0.01 Gy) than in controls (D0 = 0.84 +/- 0.02 Gy). 125IUdR incorporation into bone marrow and spleen cells was reduced after plutonium contamination. At one year following plutonium injection, the occurrence of chromosome aberrations was evaluated in metaphase figures of femoral bone marrow cells. The frequency of aberrations increased early after plutonium treatment, at later intervals it tended to decrease but not below the control level. While the relative numbers of vertebral marrow CFU-S decreased significantly, but only to 86 per cent of normal, cellularity of vertebral bone marrow, peripheral blood counts and survival of 239Pu-treated mice did not differ from the control data.     

G-protein-coupled receptors and asthma endophenotypes: the cysteinyl leukotriene system in perspective

Genetic variation in specific G-protein coupled receptors (GPCRs) is associated with a spectrum of respiratory disease predispositions and drug response phenotypes. Although certain GPCR gene variants can be disease-causing through the expression of inactive, overactive, or constitutively active receptor proteins, many more GPCR gene variants confer risk for potentially deleterious endophenotypes. Endophenotypes are traits, such as bronchiole hyperactivity, atopy, and aspirin intolerant asthma, which have a strong genetic component and are risk factors for a variety of more complex outcomes that may include disease states. GPCR genes implicated in asthma endophenotypes include variants of the cysteinyl leukotriene receptors (CYSLTR1 and CYSLTR2), and prostaglandin D2 receptors (PTGDR and CRTH2), thromboxane A2 receptor (TBXA2R), beta2-adrenergic receptor (ADRB2), chemokine receptor 5 (CCR5), and the G protein-coupled receptor associated with asthma (GPRA). This review of the contribution of variability in these genes places the contribution of the cysteinyl leukotriene system to respiratory endophenotypes in perspective. The genetic variant(s) of receptors that are associated with endophenotypes are discussed in the context of the extent to which they contribute to a disease phenotype or altered drug efficacy.     

Linkage of prostate cancer susceptibility loci to chromosome 1

Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease.     

A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases

During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6), a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3’ untranslated region (UTR) that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Here, we pursued how this protective RNA element functions to maintain mRNA stability. Using affinity purification and mass spectrometry, we identified a set of proteins that associate specifically with the protective element. Although multiple proteins contributed to the escape mechanism, depletion of nucleolin (NCL) most severely impacted protection. NCL was re-localized out of the nucleolus during lytic KSHV infection, and its presence in the cytoplasm was required for protection. After loading onto the IL-6 3’ UTR, NCL differentially bound to the translation initiation factor eIF4H. Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the RNA, suggesting that interactions between proteins bound to distant regions of the mRNA are important for escape. Finally, we found that the IL-6 3’ UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX. These findings highlight how a multitude of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA.     

Isolation and mapping of polymorphic cosmid clones used for sublocalization of the multiple endocrine neoplasia type 1 (MEN1) locus

Summary Multiple endocrine neoplasia type 1 (MEN1) is characterized by neoplasia of the parathyroids, the pancreas, and the pituitary. Tumorigenesis involves unmasking of a recessive mutation at the MEN1 locus, which has been mapped to the centromeric part of chromosomal region 11q. In order to localize the MEN1 gene further and to make its isolation possible, a number of new markers were isolated. Two radiation-reduced somatic cell hybrids were identified that only contained markers close to and flanking the MEN1 region. DNA from these hybrids was used for the construction of a cosmid library, and clones containing human inserts were isolated. In addition, cosmid clones were isolated for locus expansion of 7 other markers that were mapped to the 11q12–13.2 region. The 33 newly isolated clones together with 25 previously published markers from this region were analyzed in a panel of radiation-reduced somatic cell hybrids. From the hybridization pattern, the region was divided into 11 parts. New restriction fragment length polymorphisms were identified in 7 of the newly isolated cosmid clones and in one plasmid. These were then used to sublocalize meiotic cross-overs more precisely in two MEN1 families, thus refining the mapping of the disease gene.