Late glacial and Holocene vegetation,climate and fire history inferred from Lagoa Nova in the southeastern Brazilian lowland

The pollen and charcoal record of a 1,500-cm-long lake sediment core from Lagoa Nova allows a reconstruction of vegetation, climate and fire history in the Atlantic lowland of southeastern Brazil. Today the potential vegetation of the study region would be dense and tall semi-deciduous forest, related to a dry season of 4 months and 1,250 mm precipitation per year. The lowermost core section of Lagoa Nova is probably of late Glacial age and contains only few, poorly preserved pollen grains, indicating dry environmental conditions. Pollen preservation was good above 1,005-cm core depth. Extrapolating from four radiocarbon dates, this interval represents about the last 10,000 years. During the early Holocene (until about 8,500 b.p.), the landscape was dominated by savanna of the campo cerrado type (open shrub woodland), with frequent trees of Curatella americana and small areas of gallery forests along the drainage system. Savanna fires, probably natural, were frequent at that time. The palaeovegetation pattern is consistent with a long dry season of about 6 months and annual precipitation lower than today. Then, up to about 7,560 b.p., gallery forests expanded in the valleys, reflecting a shorter dry season of about 5 months and somewhat higher annual rainfall. Fire was less frequent during this wetter period. Between about 7,560 and 6,060 b.p., savanna expanded and gallery forests retreated, indicating a return to drier climatic conditions of probably between 5 and 6 months dry season and lower precipitation. Fire was again frequent, but not as frequent as during the early Holocene. During the mid to late Holocene period between about 6,060 and 2,180 b.p., the valleys were covered by semi-deciduous forest, but on the hills cerrado vegetation continued to grow. The dry season was probably around 5 months and rainfall was higher than in the preceding period. During the following period between about 2,810 and 600 b.p., the open cerrado on the hills changed to closed cerrado, reflecting wetter conditions with a shorter dry season than in the previous period. It was only after about 600 b.p. that dense semi-deciduous forests expanded throughout the study region, indicating the start of modern, wet climatic conditions with an annual dry season of about 4 months. Fire was nearly absent during this period. The reconstructed palaeoenvironment from the Lagoa Nova record is similar to that of Lago do Pires, indicating that changes in past vegetation, climate and fire frequency are regionally consistent in southeastern Brazil.     

Non-Invasive Bioluminescence Imaging to Monitor the Immunological Control of a Plasmablastic Lymphoma-Like B Cell Neoplasia after Hematopoietic Cell Transplantation

To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Igha^tm1(Myc)Janz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Igha^tm1(Myc)Janz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies.     

A Computational Model for Predicting Nanoparticle Accumulation in Tumor Vasculature

Vascular targeting of malignant tissues with systemically injected nanoparticles (NPs) holds promise in molecular imaging and anti-angiogenic therapies. Here, a computational model is presented to predict the development of tumor neovasculature over time and the specific, vascular accumulation of blood-borne NPs. A multidimensional tumor-growth model is integrated with a mesoscale formulation for the NP adhesion to blood vessel walls. The fraction of injected NPs depositing within the diseased vasculature and their spatial distribution is computed as a function of tumor stage, from 0 to day 24 post-tumor inception. As the malignant mass grows in size, average blood flow and shear rates increase within the tumor neovasculature, reaching values comparable with those measured in healthy, pre-existing vessels already at 10 days. The NP vascular affinity, interpreted as the likelihood for a blood-borne NP to firmly adhere to the vessel walls, is a fundamental parameter in this analysis and depends on NP size and ligand density, and vascular receptor expression. For high vascular affinities, NPs tend to accumulate mostly at the inlet tumor vessels leaving the inner and outer vasculature depleted of NPs. For low vascular affinities, NPs distribute quite uniformly intra-tumorally but exhibit low accumulation doses. It is shown that an optimal vascular affinity can be identified providing the proper balance between accumulation dose and uniform spatial distribution of the NPs. This balance depends on the stage of tumor development (vascularity and endothelial receptor expression) and the NP properties (size, ligand density and ligand-receptor molecular affinity). Also, it is demonstrated that for insufficiently developed vascular networks, NPs are transported preferentially through the healthy, pre-existing vessels, thus bypassing the tumor mass. The computational tool described here can effectively select an optimal NP formulation presenting high accumulation doses and uniform spatial intra-tumor distributions as a function of the development stage of the malignancy.     

Seasonal incidence of Ixodes ricinus ticks (Acari: ixodidae) on rodents in western France

Data collected from a longitudinal survey carried out over 2 years on four farms in western France were used to assess the incidence and infestation of Ixodes ricinus on rodents. Once a month, on each farm, 25 Sherman live traps were set in hedges bordering selected pastures. A total of 799 micromammals were examined, including Apodemus sylvaticus, Clethrionomys glareolus, Microtus agrestis, Microtus arvalis, and Crocidura spp. Larvae and nymphs of I. ricinus were found. Small numbers of Ixodes (Exopalpiger) trianguliceps were also recovered from each farm. The mean infestation rate of the I. ricinus larvae (1.6–5.9) among all animals examined varied between farms Most animals were infested by only a single tick, but one M. agrestis harboured 43 I. ricinus larvae. Larvae or nymphs were found throughout the year, with peaks from March to October.     

Norepinephrine effects on identified neurons of the rat dorsal motor nucleus of the vagus

The dorsal motor nucleus of the vagus (DMV) receives more noradrenergic terminals than any other medullary nucleus; few studies, however, have examined the effects of norepinephrine (NE) on DMV neurons. Using whole cell recordings in thin slices, we determined the effects of NE on identified gastric-projecting DMV neurons. Twenty-five percent of DMV neurons were unresponsive to NE, whereas the remaining 75% responded to NE with either an excitation (49%), an inhibition (26%), or an inhibition followed by an excitation (4%). Antrum/pylorus- and corpus-projecting neurons responded to NE with a similar percentage of excitatory (49 and 59%, respectively) and inhibitory (20% for both groups) responses. A lower percentage of excitatory (37%) and a higher percentage of inhibitory (36%) responses were, however, observed in fundus-projecting neurons. In all groups, pretreatment with prazosin or phenylephrine antagonized or mimicked the NE-induced excitation, respectively. Pretreatment with yohimbine or UK-14304 antagonized or mimicked the NE-induced inhibition, respectively. These data suggest that NE depolarization is mediated by alpha(1)-adrenoceptors, whereas NE hyperpolarization is mediated by alpha(2)-adrenoceptors. In 16 neurons depolarized by NE, amplitude of the action potential afterhyperpolarization (AHP) and its kinetics of decay (tau) were significantly reduced vs. control. No differences were found on the amplitude and tau of AHP in neurons hyperpolarized by NE. Using immunohistochemical techniques, we found that the distribution of tyrosine hydroxylase fibers within the DMV was significantly different within the mediolateral extent of DMV; however, distribution of cells responding to NE did not show a specific pattern of localization.     

A naturally occurring promoter polymorphism of the Arabidopsis FUM2 gene causes expression variation,and is associated with metabolic and growth traits

Fumarate and malate are known intermediates of the TCA cycle, a mitochondrial metabolic pathway generating NADH for respiration. Arabidopsis thaliana and other Brassicaceae contain an additional cytosolic fumarase (FUM2) that functions in carbon assimilation and nitrogen use. Here, we report the identification of a hitherto unknown FUM2 promoter insertion/deletion (InDel) polymorphism found between the Col‐0 and C24 accessions, which also divides a large number of Arabidopsis accessions carrying either the Col‐0 or the C24 allele. The polymorphism consists of two stretches of 2.1 and 3.8 kb, which are both absent from the promotor region of Col‐0 FUM2. By analysing mutants as well as mapping and natural populations with contrasting FUM2 alleles, the promotor insertion was linked to reduced FUM2 mRNA expression, reduced fumarase activity and reduced fumarate/malate ratio in leaves. In a large population of 174 natural accessions, the polymorphism was also found to be associated with the fumarate/malate ratio, malate and fumarate levels, and with dry weight at 15 days after sowing (DAS). The association with biomass production was confirmed in an even larger (251) accession population for dry weight at 22 DAS. The dominant Col‐0 allele that results in increased fumarate/malate ratios and enhanced biomass production is predominantly found in central/eastern European accessions, whereas the C24 type allele is prevalent on the Iberian Peninsula, west of the Rhine and in the British Isles. Our findings support the role of FUM2 in diurnal carbon storage, and point to a growth advantage of accessions carrying the FUM2 Col‐0 allele.     

Reduced hnRNPA3 increases C9orf72 repeat RNA levels and dipeptide‐repeat protein deposition

Intronic hexanucleotide (G₄C₂) repeat expansions in C9orf72 are genetically associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat RNA accumulates within RNA foci but is also translated into disease characterizing dipeptide repeat proteins (DPR). Repeat‐dependent toxicity may affect nuclear import. hnRNPA3 is a heterogeneous nuclear ribonucleoprotein, which specifically binds to the G₄C₂ repeat RNA. We now report that a reduction of nuclear hnRNPA3 leads to an increase of the repeat RNA as well as DPR production and deposition in primary neurons and a novel tissue culture model that reproduces features of the C9orf72 pathology. In fibroblasts derived from patients carrying extended C9orf72 repeats, nuclear RNA foci accumulated upon reduction of hnRNPA3. Neurons in the hippocampus of C9orf72 patients are frequently devoid of hnRNPA3. Reduced nuclear hnRNPA3 in the hippocampus of patients with extended C9orf72 repeats correlates with increased DPR deposition. Thus, reduced hnRNPA3 expression in C9orf72 cases leads to increased levels of the repeat RNA as well as enhanced production and deposition of DPR proteins and RNA foci.     

Clinical diagnostics and therapy monitoring in the congenital disorders of glycosylation

Abnormal protein glycosylation is observed in many common disorders like cancer, inflammation, Alzheimer’s disease and diabetes. However, the actual use of this information in clinical diagnostics is still very limited. Information is usually derived from analysis of total serum N-glycan profiling methods, whereas the current use of glycoprotein biomarkers in the clinical setting is commonly based on protein levels. It can be envisioned that combining protein levels and their glycan isoforms would increase specificity for early diagnosis and therapy monitoring. To establish diagnostic assays, based on the mass spectrometric analysis of protein-specific glycosylation abnormalities, still many technical improvements have to be made. In addition, clinical validation is equally important as well as an understanding of the genetic and environmental factors that determine the protein-specific glycosylation abnormalities. Important lessons can be learned from the group of monogenic disorders in the glycosylation pathway, the Congenital Disorders of Glycosylation (CDG). Now that more and more genetic defects are being unraveled, we start to learn how genetic factors influence glycomics profiles of individual and total serum proteins. Although only in its initial stages, such studies suggest the importance to establish diagnostic assays for protein-specific glycosylation profiling, and the need to look beyond the single glycoprotein diagnostic test. Here, we review progress in and lessons from genetic disease, and review the increasing opportunities of mass spectrometry to analyze protein glycosylation in the clinical diagnostic setting. Furthermore, we will discuss the possibilities to expand current CDG diagnostics and how this can be used to approach glycoprotein biomarkers for more common diseases.     

The role of summer precipitation and summer temperature in establishment and growth of dwarf shrub <Emphasis Type="Italic">Betula nana</Emphasis> in northeast Siberian tundra

It is widely believed that deciduous tundra-shrub dominance is increasing in the pan-Arctic region, mainly due to rising temperature. We sampled dwarf birch (Betula nana L.) at a northeastern Siberian tundra site and used dendrochronological methods to explore the relationship between climatic variables and local shrub dominance. We found that establishment of shrub ramets was positively related to summer precipitation, which implies that the current high dominance of B. nana at our study site could be related to high summer precipitation in the period from 1960 to 1990. The results confirmed that early summer temperature is most influential to annual growth rates of B. nana. In addition, summer precipitation stimulated shrub growth in years with warm summers, suggesting that B. nana growth may be co-limited by summer moisture supply. The dual controlling role of temperature and summer precipitation on B. nana growth and establishment is important to predict future climate-driven vegetation dynamics in the Arctic tundra.