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41.
Notch signaling as a therapeutic target   总被引:7,自引:0,他引:7  
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42.
Podocarpus falcatus is an indigenous evergreen conifer species of tropical mountain forests in southeastern Ethiopia, showing potential tree ages of around 500 years. To study the influence of seasonal climate on the growth pattern of P. falcatus, we combined high-resolution electronic dendrometer measurements with wood anatomical investigations of microcores from the outermost stem parts collected in monthly intervals. At any time of the year sufficient rain events are able to cause cambial activity in P. falcatus. This permanent growing readiness leads to irregular wood formation with the formation of intra-annual density fluctuations and missing rings. Wood anatomical studies of microcores collected around the circumference of a mature P. falcatus revealed locally different activity status of the cambium on different lobes of the stem. Tree-ring width measurements of stem disks resulted in tentative tree ages that were confirmed by radiocarbon dating of selected wood samples. Although our efforts to cross-date ring-width series from several stem disks were not successful, further sampling in areas with different rainfall regimes, additional radiocarbon dating and measurements of stable isotopes hopefully would enable the establishment of a multi-century-long tree-ring series for climate reconstruction.  相似文献   
43.
Tigray, the northernmost state of Ethiopia, has a population of 3.5 million, 86% rural, and 56% living in malarious areas. In 1992 a Community-Based Malaria Control Programme was established to provide region-wide and sustained access to early diagnosis and treatment of malaria at the village level. 735 volunteer community health workers (CHWs) serve 2,327 villages with a population of 1.74 million, treating an average of 489,378 patients yearly from 1994 to 1997. Recognition of clinical malaria is similar for CHWs and health staff at clinics where there is no access to microscopy. In 1996 a pilot community-financing scheme of insecticide-treated bednets was well accepted, but re-impregnation rates fell in 1998 because of war-related social upheaval. Indicators from health institutions show a progressive increase in malaria morbidity from 1994 to 1998. Repeated mortality surveys show a 40% reduction in death rates in under-5 children from 1994 to 1996 and a 10% increase from 1996 to 1998. These trends may be related to increased malaria transmission with water resources development, increased seasonal labour migration to malarious lowlands, prolongation of the transmission season with climate changes, and increasing chloroquine resistance throughout Ethiopia. Progressive extension of CHW services to ensure better coverage of women, children, migrant workers and communities near water development projects, change to first-line treatment with sulfadoxine-pyrimethamine, extension of the impregnated bednet initiative, and development of a regional warning system for epidemics should result in a greater impact on morbidity and mortality.  相似文献   
44.

Key message

The paper demonstrates the prospects and applications of dendrochronology for understanding climate change effects on riparian forests in the savanna landscape. 

Abstract

Riparian trees in savannas have a potential for dendro-climatic studies, but have been neglected hitherto. We examined ring-width series of Afzelia africana (evergreen) and Anogeissus leiocarpus (deciduous) to study the influence of climatic factors on the growth of riparian trees in the humid (HS) and dry (DS) savanna zones of the Volta basin in Ghana. A total of 31 stem discs belonging to A. africana and A. leiocarpus were selected from HS and DS to establish species-specific local chronologies of tree growth. Each individual of A. africana and A. leiocarpus from the two savanna sites showed distinct growth rings. Cross-dating of individual tree-ring patterns was successful using standard dendrochronological techniques. The mean annual growth rates of A. africana in the HS (1.38 ± 0.09) and DS (1.34 ± 0.08) were not statistically different. Furthermore, mean annual growth rate of A. leiocarpus in the DS (3.75 ± 0.27) was higher than in the HS (2.83 ± 0.16) suggesting that species in drier environment can have higher growth rates when sufficient soil moisture is available. The growth rates of both species at the same sites were different, which might indicate different water use strategies. High correlations of individual tree-ring series of A. africana and A. leiocarpus trees at HS and DS suggest a strong climatic forcing controlled by the seasonal movement of the inter-tropical convergence zone. The annual growth of A. africana and A. leiocarpus at both the HS and DS was significantly correlated with local temperature and precipitation. The negative correlations of the growth of the two tree species to global sea surface temperatures were however, indications that the growth of riparian forests can be impacted during El Niño-Southern Oscillation years. The result of our study shows that riparian trees in the humid and dry savanna zones of West Africa can be successfully used for dendrochronological studies.
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45.
While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.  相似文献   
46.
Possible immunogenic heterogeneity of the HLA-Bw44 antigen was investigated using cytotoxic T lymphocytes (CTL) generated between donors identical for HLA-A2,3,-B7,w44. Highly discriminatory CTL combinations were identified that defined two subgroups of Bw44, designated 44.1 and 44.2. Out of 47 Bw44-positive donors tested in a population study, 30 were lysed by the CTL defining 44.1, and 19 were lysed by the CTL defining 44.2. All Bw44 cells could be typed as either 44.1 or 44.2, except two Bw44-positive cells that were phenotypically homozygous for the serologically defined Bw44 antigen and were lysed by both CTL. No Bw44-negative donors (zero out of 37) expressed either 44.1 or 44.2, although cold target blocking was required to eliminate a contaminating reactivity of one CTL population on Bw35 and some Bw45 cells. CTL were also raised between responder/stimulator combinations mismatched for Bw44. These CTL lysed all Bw44-positive target cells, indicating a CML antigen shared by all Bw44 cells. But clear discrimination of the 44.1 and 44.2 subgroups was obtained when appropriate cold target blocking cells were added. All donors with 44.2 expressed high levels of serologically detectable Bw44 on their platelets, and all with 44.1 expressed low levels (p less than 0.005). Furthermore, population studies indicate that 44.1 is in positive linkage disequilibrium with HLA-A2 and possibly DR4, whereas 44.2 is in positive linkage disequilibrium with HLA-DR7 and possibly HLA-A23, -A26, and -A29. These data suggest the existence of two genetically and functionally different subgroups of Bw44 antigens.  相似文献   
47.
EcoHealth - Bats are important hosts of zoonotic viruses with pandemic potential, including filoviruses, MERS-Coronavirus (CoV), SARS-CoV -1, and likely SARS-CoV-2. Viral infection and transmission...  相似文献   
48.
mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series.  相似文献   
49.
The biting cycle of the malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) was assessed by hourly light trap collections in three villages in Tigray, northern Ethiopia. Hourly catches were conducted in two houses in each village, for four consecutive nights. Light traps were set from 18.00 hours to 07.00 hours in houses in which people slept under untreated bednets. Anopheles arabiensis showed early biting activities, which peaked between 19.00 hours and 20.00 hours in the three villages; over 70% of biting activity occurred before 22.00 hours, when people typically retire to bed. This early biting activity may have a negative impact on the efficiency of bednets to control malaria.  相似文献   
50.
NOTCH1 is a large type I transmembrane receptor that regulates normal T-cell development via a signaling pathway that relies on regulated proteolysis. Ligand binding induces proteolytic cleavages in NOTCH1 that release its intracellular domain (ICN1), which translocates to the nucleus and activates target genes by forming a short-lived nuclear complex with two other proteins, the DNA-binding factor CSL and a Mastermind-like (MAML) coactivator. Recent work has shown that human T-ALL is frequently associated with C-terminal NOTCH1 truncations, which uniformly remove sequences lying between residues 2524 and 2556. This region includes the highly conserved sequence WSSSSP (S4), which based on its amino acid content appeared to be a likely site for regulatory serine phosphorylation events. We show here that the mutation of the S4 sequence leads to hypophosphorylation of ICN1; increased NOTCH1 signaling; and the stabilization of complexes containing ICN1, CSL, and MAML1. Consistent with these in vitro studies, mutation of the WSSSSP sequence converts nonleukemogenic weak gain-of-function NOTCH1 alleles into alleles that cause aggressive T-ALLs in a murine bone marrow transplant model. These studies indicate that S4 is an important negative regulatory sequence and that the deletion of S4 likely contributes to the development of human T-ALL.  相似文献   
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