Archaeobotanical investigations at the earliest horse herder site of Botai in Kazakhstan

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this recordThis paper presents new radiocarbon dates and the results of the first archaeobotanical investigations at Eneolithic Botai site, for the first time aiming to explore the plant food component in the diet of Botai population and if the inhabitants of the Botai were a part of an early crop food exchange network. Our excavation of a hut circle and associated radiocarbon dating placed its occupation within a date range commencing around 3550 and 3030 cal BC and ending between 3080 and 2670 cal BC. A separate feature (likely a stove or kiln), excavated in test trench E would seem to be younger, around 2000 cal BC. The dating of the site thus also indicates a previously unknown later occupation at Botai, opening further discussions on human subsistence and interaction as well as horse management in northern Eurasia from the Eneolithic to the Bronze Age. The archaeobotanical results, derived from systematic sampling and analysis of macrobotanical remains, plant phytoliths and molecular biomarker analysis show that the Botai populations were not part of any wider crop network. The relatively small seed count would indicate that plant foods did not constitute a substantial component of economic life. On the other hand, the presence of miliacin could suggest possible millet cultivation or consumption in this region at some point in the past, possibly after the main occupation period of Botai.European Research Council (ERC)National Science FoundationEuropean Union Horizon 202

Effects of quantum gravity on the inflationary parameters and thermodynamics of the early universe

The effects of generalized uncertainty principle (GUP) on the inflationary dynamics and the thermodynamics of the early universe are studied. Using the GUP approach, the tensorial and scalar density fluctuations in the inflation era are evaluated and compared with the standard case. We find a good agreement with the Wilkinson Microwave Anisotropy Probe data. Assuming that a quantum gas of scalar particles is confined within a thin layer near the apparent horizon of the Friedmann-Lemaitre-Robertson-Walker universe which satisfies the boundary condition, the number and entropy densities and the free energy arising form the quantum states are calculated using the GUP approach. A qualitative estimation for effects of the quantum gravity on all these thermodynamic quantities is introduced.Comment: 15 graghes, 7 figures with 17 eps graph

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Multifield Dynamics in Higgs-otic Inflation

In Higgs-otic inflation a complex neutral scalar combination of the $h^0$ and $H^0$ MSSM Higgs fields plays the role of inflaton in a chaotic fashion. The potential is protected from large trans-Planckian corrections at large inflaton if the system is embedded in string theory so that the Higgs fields parametrize a D-brane position. The inflaton potential is then given by a DBI+CS D-brane action yielding an approximate linear behaviour at large field. The inflaton scalar potential is a 2-field model with specific non-canonical kinetic terms. Previous computations of the cosmological parameters (i.e. scalar and tensor perturbations) did not take into account the full 2-field character of the model, ignoring in particular the presence of isocurvature perturbations and their coupling to the adiabatic modes. It is well known that for generic 2-field potentials such effects may significantly alter the observational signatures of a given model. We perform a full analysis of adiabatic and isocurvature perturbations in the Higgs-otic 2-field model. We show that the predictivity of the model is increased compared to the adiabatic approximation. Isocurvature perturbations moderately feed back into adiabatic fluctuations. However, the isocurvature component is exponentially damped by the end of inflation. The tensor to scalar ratio varies in a region $r=0.08-0.12$, consistent with combined Planck/BICEP results.Comment: 35 pages, 11 figure

The association of cardioprotective medications with pneumonia-related outcomes

Introduction: Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes. Materials and Methods: We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events. Results: Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63-0.77), ACE inhibitors (OR 0.82, 95% CI 0.74-0.91), and ARBs (OR 0.58, 95% CI 0.44-0.77). However, none of the medications were significantly associated with decreased cardiovascular events. Discussion: While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects

Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)

Knowledge, perceived stigma, and care-seeking experiences for sexually transmitted infections: a qualitative study from the perspective of public clinic attendees in Rio de Janeiro, Brazil

BACKGROUND: An estimated 12 million sexually transmitted infections (STIs) are documented in Brazil per year. Given the scope of this public health challenge and the importance of prompt treatment and follow-up counseling to reduce future STI/HIV-related risk behavior, we sought to qualitatively explore STI clinic experiences among individuals diagnosed with STIs via public clinics in Rio de Janeiro, Brazil. The study focused on eliciting the perspective of clinic users with regard to those factors influencing their STI care-seeking decisions and the health education and counseling which they received during their clinic visit. METHODS: Thirty semi-structured interviews were conducted with heterosexual men and women and men who have sex with men presenting with STIs at two public clinics. Content analysis was conducted by coding transcripts of audio-taped interviews for key domains of interest and comparing and synthesizing code output across participants and sub-groups. Thematic narratives were then developed per each of the study sub-groups. RESULTS: Salient themes that emerged from participant narratives included the importance of low STI-related knowledge and high perceived stigma, both STI-related and other types of social stigma, on STI care-seeking delays. However, there are indications in the data that the level of STI-related knowledge and the amount and types of stigma experienced vary across the study sub-groups suggesting the need for further research on the significance and program relevance of these potential differences. Interview findings also suggest that such barriers to care seeking are not adequately addressed through ongoing health education and counseling efforts at public STI clinics and in turn critical opportunities for STI/HIV prevention are currently being missed. CONCLUSION: Information, communication and education regarding early recognition and prompt care-seeking for STIs should be developed, with consideration given to the possibility of tailoring messages tailored to specific sub-groups. To promote prompt treatment-seeking, interventions must also address both STI-specific and other forms of social stigma which may limit access to care. Efforts to further assess and respond to barriers related to the delivery of quality health education and counseling within the context of public STI clinics are also needed

Examination of the effects of a new compression garment on skin tissue oxygenation in healthy volunteers

Objective: Compression devices have been shown to reduce venous stasis, increase blood flow and skin tissue oxygenation (StO2), promoting healthy tissue. This study aimed to explore the efficacy of a new compression garment in three different positions in healthy adults. Methods: In this quantitative study, potential participants were screened and recruited using the Physical Activity Readiness Questionnaire (PAR-Q, Canada). Participants attended three separate, one-hour sessions to evaluate StO2 in supine-lying, chair-sitting and long-sitting positions. StO2 was recorded for 20 minutes pre-, during and post- a 20-minute intervention using a compression garment, TributeWrap (Lohmann-Rauscher, Germany). A repeated-measures analysis of variance (ANOVA) was followed by post-hoc pairwise comparisons. Results: A total of 28 healthy volunteers took part (aged 24.6 ±8.4years; 13 males, 15 females). A significant difference was seen between the three positions (p<0.001). Chair-sitting had the lowest StO2 pre-intervention, increasing StO2 significantly (32.25%, p<0.001) during wear of the compression garment (24.8% higher than baseline post-intervention). No significant difference was seen between long sitting and supine-lying (p=1.000). In contrast, long-sitting and supine-lying StO2 was higher pre-intervention compared with chair-sitting and only increased post-intervention (11% and 16.8% respectively, p<0.001) compared with baseline. Conclusion: The compression garment significantly increased StO2 levels in both seating positions. Further studies are required to determine if increasing StO2 through short intervention sessions with this device has the potential to improve self-management of tissue health in individuals with reduced mobility, oedema or venous insufficiency

Repression of Floral Meristem Fate Is Crucial in Shaping Tomato Inflorescence

Tomato is an important crop and hence there is a great interest in understanding the genetic basis of its flowering. Several genes have been identified by mutations and we constructed a set of novel double mutants to understand how these genes interact to shape the inflorescence. It was previously suggested that the branching of the tomato inflorescence depends on the gradual transition from inflorescence meristem (IM) to flower meristem (FM): the extension of this time window allows IM to branch, as seen in the compound inflorescence (s) and falsiflora (fa) mutants that are impaired in FM maturation. We report here that JOINTLESS (J), which encodes a MADS-box protein of the same clade than SHORT VEGETATIVE PHASE (SVP) and AGAMOUS LIKE 24 (AGL24) in Arabidopsis, interferes with this timing and delays FM maturation, therefore promoting IM fate. This was inferred from the fact that j mutation suppresses the high branching inflorescence phenotype of s and fa mutants and was further supported by the expression pattern of J, which is expressed more strongly in IM than in FM. Most interestingly, FA - the orthologue of the Arabidopsis LEAFY (LFY) gene - shows the complementary expression pattern and is more active in FM than in IM. Loss of J function causes premature termination of flower formation in the inflorescence and its reversion to a vegetative program. This phenotype is enhanced in the absence of systemic florigenic protein, encoded by the SINGLE FLOWER TRUSS (SFT) gene, the tomato orthologue of FLOWERING LOCUS T (FT). These results suggest that the formation of an inflorescence in tomato requires the interaction of J and a target of SFT in the meristem, for repressing FA activity and FM fate in the IM