A neotropical perspective on the uniqueness of the Holocene among interglacials.

Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.

Widespread reforestation before European influence on Amazonia.

An estimated 90 to 95% of Indigenous people in Amazonia died after European contact. This population collapse is postulated to have caused decreases in atmospheric carbon dioxide concentrations at around 1610 CE, as a result of a wave of land abandonment in the wake of disease, slavery, and warfare, whereby the attendant reversion to forest substantially increased terrestrial carbon sequestration. On the basis of 39 Amazonian fossil pollen records, we show that there was no synchronous reforestation event associated with such an atmospheric carbon dioxide response after European arrival in Amazonia. Instead, we find that, at most sites, land abandonment and forest regrowth began about 300 to 600 years before European arrival. Pre-European pandemics, social strife, or environmental change may have contributed to these early site abandonments and ecological shifts.

Maternal autoimmune thyroid disease and the fetal immune system.

OBJECTIVE: Several studies indicate that in utero exposure to maternal autoimmune diseases and transplacental passage of autoantibodies affect the risk of autoimmunity in the offspring, e. g., maternally derived GAD65 autoantibody correlates with decreased risk of type 1 diabetes, whereas thyroid peroxidase autoantibody (TPOAb) positivity at birth is associated with increased incidence of autoimmune thyroid disease later in life. The aim of this study was to identify immunological changes in children born to mothers with thyroid autoimmunity that may be related to in utero exposure to autoantibodies. DESIGN AND METHOD: Open label prospective analysis of cord blood lymphocytes and serum cytokines by Flow Cytometry in children born to mothers with autoimmune thyroiditis (AIT) (n=31) and to healthy mothers (n=76) and titers of thyroid autoantibodies were determined in cord blood and in maternal peripheral blood at delivery. RESULTS: We found an increase (almost 30%) in the frequency of cord blood natural killer (NK) cells (p=0.0016) and a minor increase in the subset of T cells expressing NK markers (p=0.028), in children born to AIT mothers. There were no detectable differences in the phenotype or frequency of cord blood memory/activated T cells, including CD4 (+)CD25 (+) T cells, between the 2 groups. The levels of pro-inflammatory cytokines TNF-α, IL-10, IL-12p70, IFN-γ and IL-1ß were significantly decreased in offspring of AIT mothers as compared to healthy controls. CONCLUSIONS: Maternal thyroid autoimmunity and transplacental passage of autoantibodies against thyroid antigens may affect the generation or expansion of cells with NK activity and the secretion of inflammatory cytokines.

Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency.

Approximately 10% of the patients diagnosed with type 2 diabetes (T2D) have detectable serum levels of glutamic acid decarboxylase 65 autoantibodies (GADA). These patients usually progress to insulin dependency within a few years, and are classified as being latent autoimmune diabetes in adults (LADA). A decrease in the frequency of peripheral blood natural killer (NK) cells has been reported recently in recent-onset T1D and in high-risk individuals prior to the clinical onset. As NK cells in LADA patients have been investigated scarcely, the aim of this study was to use multicolour flow cytometry to define possible deficiencies or abnormalities in the frequency or activation state of NK cells in LADA patients prior to insulin dependency. All patients were GADA-positive and metabolically compensated, but none were insulin-dependent at the time blood samples were taken. LADA patients exhibited a significant decrease in NK cell frequency in peripheral blood compared to healthy individuals (P=0.0018), as reported previously for recent-onset T1D patients. Interestingly, NKG2D expression was increased significantly (P<0.0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P<0.0001) within the NK cell population. These observations highlight a defect in both frequency and activation status of NK cells in LADA patients and suggest that this immunological alteration may contribute to the development of autoimmune diabetes by affecting peripheral tolerance. Indeed, recent evidence has demonstrated a regulatory function for NK cells in autoimmunity. Moreover, the decrease in NK cell number concords with observations obtained in recent-onset T1D, implying that similar immunological dysfunctions may contribute to the progression of both LADA and T1D.

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes.

Maternal transmission of islet autoantibodies to children born to mothers with type 1 diabetes (T1D) has been shown to protect from autoantibodies and diabetes development later in life. However, the factors conferring disease protection are poorly understood. The aim of this study was to evaluate comparatively proinflammatory cytokines, autoantibodies and lymphocyte subsets in cord blood (CB) of children born to mothers with either T1D (n = 13), gestational diabetes (GDM) (n = 32) or healthy mothers (n = 81) in relation to transplacental passage of autoantibodies. The results are consistent with early priming of the fetal immune system only in children born to mothers with T1D. Levels of interleukin (IL)-1beta (P = 0.022), tumour necrosis factor (TNF)-alpha (P = 0.002) and IL-8 (P = 0.0012), as well as the frequency of CD4(+) CD25(+) T cells (P < 0.01) were significantly increased, and the increased levels correlated positively with anti-GAD65 autoantibody (GADA) levels. Moreover, CD4(+) CD25(+) T cells of children born to T1D mothers exhibited a more pronounced memory phenotype with increased CCR4 expression and down-regulation of CD62L. These data suggest that early activation of the fetal immune system as a consequence of maternal autoimmunity and transplacental passage of GADA may influence the generation and expansion of fetal regulatory T cells. This might induce an early antigen-specific immunological tolerance that could protect against T1D later in life.

A high density RFLP linkage map of sugar beet.

A high density sugar beet RFLP map with an average distance of 1.5 cM between markers has been constructed. The map covers 621 cM and includes 413 markers distributed over the nine linkage groups of sugar beet. The map is based on two F2 populations representing two different pairs of parents. The two sets of data were integrated into a single map using 90 markers that were common to both data sets. The quality of the map was assessed in several ways. The common markers were used to investigate how often the loci had been mapped in the same order in the two F2 populations. For closely situated markers (<1.5 cM) the order specified in the map is uncertain, but for markers separated by more than 2 cM the locus order is highly reliable. The error rate of the overall process was estimated at 0.3% by independently repeating the analysis of 41 markers. The map is comparatively short, with a map length corresponding to approximately 1.4 crossovers per bivalent. Another feature of the map is a high degree of clustering of markers along the linkage groups. With the possible exception of linkage group 2, each linkage group shows one major cluster, which in most cases is situated in the centre of the linkage group. Our interpretation is that sugar beet, in comparison with most other species, has an extreme localization of recombination. Key words : sugar beet, linkage, RFLP, clustering.

Analysis of L-[methyl-11C]methionine and metabolites in human plasma by an automated solid-phase extraction and a high-performance liquid chromatographic procedure.

A fully automated method for separation of L-[methyl-11C]Methionine from metabolites in patient plasma was developed. L-[methyl-11C]Methionine was isolated from plasma by solid-phase extraction (SPE). The radioactivity retained on the SPE column was eluted and injected onto the HPLC system for separation of in vivo formed L-[methyl-11C]methionine radiolabeled metabolites. The yield through the isolation procedure and HPLC analysis was greater than 95% with a precision better than 5% (R.S.D.). The calculated rate of L-[methyl-11C]methionine transport into tumor tissue was markedly different with and without compensation for radiolabeled metabolites in patient plasma.

Separation of botulinum-positive and -negative fish samples by means of a pattern recognition method applied to headspace gas chromatograms.

A gas chromatographic headspace technique was used to analyze the gas produced during putrefaction of pond-raised, degutted trout, incubated in evacuated plastic pouches. The following samples were analyzed; 10 samples which, due to natural contamination with Clostridium botulinum, were toxic when injected into mice, 10 samples which were nontoxic when injected, and 9 samples inoculated with one strain of C. botulinum type E. The gas chromatograms showed the presence of 118 compounds in most samples. Quantitative differences among most chromatograms could be observed, but no compound was unique to any of the three groups. By means of a specific pattern recognition method, all negative samples were shown to fall into one group and were distinctly separated from the toxic samples. No differences could be observed between the two groups of inoculated and naturally contaminated trout samples. The results suggest that headspace analysis combined with pattern recognition analysis might prove to be a valuable method for screening studies of foods containing living cells of C. botulinum.

Toxicological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes.

The 2-n-propyl (pr) and 2-n-butyl (bu) methylenedioxyindenes (MDIs) developed in our laboratories are intracellular calcium antagonists with coronary dilating and antiarrhythmic actions. Acute toxicity studies resulted, in mice, in an iv LD50 of 40 and 32 mg/kg for pr-MDI and bu-MDI, respectively, and an ip LD50 of 185 mg/kg for both MDIs. In rats, the ip LD50 was 175 and 240 mg/kg for pr-MDI and bu-MDI, respectively. An iv dose of 16 mg/kg decreased motor activity and prolonged barbiturate sleeping time in mice, but did not affect conditioned avoidance behavior or motor coordination tests. In sub-acute toxicity studies, rats received daily for 4 weeks 26.25 or 52.5 mg/kg ip of either MDIs, while mice received 23.13 or 46.25 mg/kg ip of either MDIs. No alterations were observed in serum alkaline phosphatase, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, creatine phosphokinase, bilirubin, chloride, cholesterol, uric acid, prothrombin time, and bromsulphalein retention. Blood glucose was slightly lowered. Serum calcium was slightly lowered in male mice. The higher dose of pr-MDI elevated serum lactate dehydrogenase in rats. Both MDIs elevated serum isocitric dehydrogenase in male rats. Light microscopic examination of brain, kidney, liver, spleen, intestine, stomach, and myocardium showed no anomalies resulting from the 4-week MDI treatment, and electron microscopic examination of hepatocytes revealed no deleterious effects of either MDIs.