The implications of K-Ar glauconite dating of the Diest Formation on the paleogeography of the Upper Miocene in Belgium

The glauconite-rich Diest Formation in central and north Belgium contains sands in the Campine subsurface and the hilly Hageland area that can be distinguished from each other. The Hageland Diest Sands member contains no stratigraphically relevant fossils while in the Campine subsurface dinoflagellate cysts are common and show a stratigraphic range covering the entire Tortonian stage. K-Ar dates were determined for glauconite from 13 selected samples spread over both areas. A glauconite date corresponding to the earliest Tortonian indicates newly formed glauconite was incorporated into a greensand at the base of the Diest Formation in the central Campine area. All other dates point at reworked glauconite and can be organized in two groups, one reflecting a Burdigalian age and another reflecting a Langhian age. These data and the thickness and glauconite content of the Diest Formation imply massive reworking of older Miocene deposits. The paleogeographic implications of these data lead to the tentative recognition of two Tortonian sedimentary sequences. An older one corresponding to dinoflagellate biochron DN8 comprises the Deurne Member, part of the Dessel Member, the Hageland Diest member, the eastern Campine Diest member and some basal sands of the Diest Formation in the central Campine. A younger sequence corresponding to dinoilagellate biochrons DN9 and 10 was strongly influenced by the prograding proto-Rhine delta front in the Roer Valley Graben to the northeast. The subsiding Campine basin was filled from east to west during this second cycle

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta.By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas.Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction

Peptide immobilisation on porous silicon surface for metal ions detection

In this work, a Glycyl-Histidyl-Glycyl-Histidine (GlyHisGlyHis) peptide is covalently anchored to the porous silicon PSi surface using a multi-step reaction scheme compatible with the mild conditions required for preserving the probe activity. In a first step, alkene precursors are grafted onto the hydrogenated PSi surface using the hydrosilylation route, allowing for the formation of a carboxyl-terminated monolayer which is activated by reaction with N-hydroxysuccinimide in the presence of a peptide-coupling carbodiimide N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide and subsequently reacted with the amino linker of the peptide to form a covalent amide bond. Infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy are used to investigate the different steps of functionalization

Attentional capture by alcohol-related stimuli may be activated involuntarily by top-down search goals

Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to Incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience, and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be congruent or incongruent with the current search goal. Applying a meta-analysis, we combined the results across the three experiments and found consistent evidence of goal-driven attentional capture; whereby alcohol distractors impeded target detection when the search goal was for alcohol. By contrast, alcohol distractors did not interfere with target detection while participants were searching for a non-alcoholic category. A separate experiment revealed that the goal-driven capture effect was not found when participants held alcohol features active in memory but did not intentionally search for them. These findings suggest a strong goal-driven account of attentional capture by alcohol cues in social drinkers

A pilot survey of post-deployment health care needs in small community-based primary care clinics

<p>Abstract</p> <p>Background</p> <p>Relatively little is known regarding to what extent community-based primary care physicians are encountering post-deployment health care needs among veterans of the Afghanistan or Iraq conflicts and their family members.</p> <p>Methods</p> <p>This pilot study conducted a cross-sectional survey of 37 primary care physicians working at small urban and suburban clinics belonging to a practice-based research network in the south central region of Texas.</p> <p>Results</p> <p>Approximately 80% of the responding physicians reported caring for patients who have been deployed to the Afghanistan or Iraq war zones, or had a family member deployed. Although these physicians noted a variety of conditions related to physical trauma, mental illnesses and psychosocial disruptions such as marital, family, financial, and legal problems appeared to be even more prevalent among their previously deployed patients and were also noted among family members of deployed veterans.</p> <p>Conclusions</p> <p>Community-based primary care physicians should be aware of common post-deployment health conditions and the resources that are available to meet these needs.</p

Effects of a single intraperitoneal administration of cadmium on femoral bone structure in male rats

<p>Abstract</p> <p>Background</p> <p>Exposure to cadmium (Cd) is considered a risk factor for various bone diseases in humans and experimental animals. This study investigated the acute effects of Cd on femoral bone structure of adult male rats after a single intraperitoneal administration.</p> <p>Methods</p> <p>Ten 4-month-old male Wistar rats were injected intraperitoneally with a single dose of 2 mg CdCl₂/kg body weight and killed 36 h after the Cd had been injected. Ten 4-month-old males served as a control group. Differences in body weight, femoral weight, femoral length and histological structure of the femur were evaluated between the two groups of rats. The unpaired Student's t-test was used for establishment of statistical significance.</p> <p>Results</p> <p>A single intraperitoneal administration of Cd had no significant effect on the body weight, femoral weight or femoral length. On the other hand, histological changes were significant. Rats exposed to Cd had significantly higher values of area, perimeter, maximum and minimum diameters of the primary osteons' vascular canals and Haversian canals. In contrast, a significant decrease in all variables of the secondary osteons was observed in these rats.</p> <p>Conclusions</p> <p>The results indicate that, as expected, a single intraperitoneal administration of 2 mg CdCl₂/kg body weight had no impact on macroscopic structure of rat's femora; however, it affected the size of vascular canals of primary osteons, Haversian canals, and secondary osteons.</p

Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients

<p>Abstract</p> <p>Background</p> <p>Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported.</p> <p>Methods</p> <p>We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008.</p> <p>Results</p> <p>Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) β were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively.</p> <p>Conclusions</p> <p>Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multidisciplinar therapeutic team is, however, essential to succeed in improving patients' outcome.</p

The Arabidopsis Resistance-Like Gene SNC1 Is Activated by Mutations in SRFR1 and Contributes to Resistance to the Bacterial Effector AvrRps4

The SUPPRESSOR OF rps4-RLD1 (SRFR1) gene was identified based on enhanced AvrRps4-triggered resistance in the naturally susceptible Arabidopsis accession RLD. No other phenotypic effects were recorded, and the extent of SRFR1 involvement in regulating effector-triggered immunity was unknown. Here we show that mutations in SRFR1 in the accession Columbia-0 (Col-0) lead to severe stunting and constitutive expression of the defense gene PR1. These phenotypes were temperature-dependent. A cross between srfr1-1 (RLD background) and srfr1-4 (Col-0) showed that stunting was caused by a recessive locus in Col-0. Mapping and targeted crosses identified the Col-0-specific resistance gene SNC1 as the locus that causes stunting. SRFR1 was proposed to function as a transcriptional repressor, and SNC1 is indeed overexpressed in srfr1-4. Interestingly, co-regulated genes in the SNC1 cluster are also upregulated in the srfr1-4 snc1-11 double mutant, indicating that the overexpression of SNC1 is not a secondary effect of constitutive defense activation. In addition, a Col-0 RPS4 mutant showed full susceptibility to bacteria expressing avrRps4 at 24°C but not at 22°C, while RLD susceptibility was not temperature-dependent. The rps4-2 snc1-11 double mutant showed increased, but not full, susceptibility at 22°C, indicating that additional cross-talk between resistance pathways may exist. Intriguingly, when transiently expressed in Nicotiana benthamiana, SRFR1, RPS4 and SNC1 are in a common protein complex in a cytoplasmic microsomal compartment. Our results highlight SRFR1 as a convergence point in at least a subset of TIR-NBS-LRR protein-mediated immunity in Arabidopsis. Based on the cross-talk evident from our results, they also suggest that reports of constitutive resistance phenotypes in Col-0 need to consider the possible involvement of SNC1

Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

<p>Abstract</p> <p>Background</p> <p>The inactivation of tumor suppressor genes (TSGs) by aberrant DNA methylation plays an important role in the development of malignancy. Since this epigenetic change is reversible, it is a potential target for chemotherapeutic intervention using an inhibitor of DNA methylation, such as 5-aza-2'-deoxycytidine (DAC). Although clinical studies show that DAC has activity against hematological malignancies, the optimal dose-schedule of this epigenetic agent still needs to be established.</p> <p>Methods</p> <p>Clonogenic assays were performed on leukemic and tumor cell lines to evaluate the <it>in vitro </it>antineoplastic activity of DAC. The reactivation of TSGs and inhibition of DNA methylation by DAC were investigated by reverse transcriptase-PCR and Line-1 assays. The <it>in vivo </it>antineoplastic activity of DAC administered as an i.v. infusion was evaluated in mice with murine L1210 leukemia by measurement of survival time, and in mice bearing murine EMT6 mammary tumor by excision of tumor after chemotherapy for an <it>in vitro </it>clonogenic assay.</p> <p>Results</p> <p>Increasing the DAC concentration and duration of exposure produced a greater loss of clonogenicity for both human leukemic and tumor cell lines. The reactivation of the TSGs (<it>p57KIP2 </it>in HL-60 leukemic cells and <it>p16CDKN2A </it>in Calu-6 lung carcinoma cells) and the inhibition of global DNA methylation in HL-60 leukemic cells increased with DAC concentration. In mice with L1210 leukemia and in mice bearing EMT6 tumors, the antineoplastic action of DAC also increased with the dose. The plasma level of DAC that produced a very potent antineoplastic effect in mice with leukemia or solid tumors was > 200 ng/ml (> 1 μM).</p> <p>Conclusion</p> <p>We have shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer. Our data also show that there is a good correlation between the concentrations of DAC that reduce <it>in vitro </it>clonogenicity, reactivate TSGs and inhibit DNA methylation. These results suggest that the antineoplastic action of DAC is related to its epigenetic action. Our observations provide a strong rationale to perform clinical trials using dose intensification of DAC to maximize the chemotherapeutic potential of this epigenetic agent in patients with cancer.</p