750 research outputs found
GERMAN BIBLICAL ARCHAEOLOGY: RETROSPECTIVE OF A NEGLECTED LEGACY; A Study of the German contribution to the Archaeology of Palestine in its longue durée, from 1871 to 1945
The history of biblical archaeology and of the archaeology of the Near East has been the subject of many publications until now. Those histories usually offer the reader a detailed account of progressive facts on a long and linear chronology, in which England stares as the main character, later losing its role to the United States. Besides those totalising explanations, there are other ways to interpret the history of Western archaeological interest in the Near East. In this thesis, the emphasis lays upon Germany, which is traditionally attributed a secondary role. Germanâs peculiar relation to the Orient, as the only western country to settle in Palestine even in the 19th century, or as the only western country to adopt a friendly position towards the Ottoman rulers, allowed German scientific exploration to develop under unique conditions. While studying the development of German archeological interest in Palestine from 1871 to 1945, I intend to present a different perspective on this scenario of western competition for the Holy Land
Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.
Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus
Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicentre, randomised trial (SUMIT)
Purpose:
Uveal melanoma is the most common primary intraocular malignancy in adults with no effective
systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an
oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent
activity in patients with metastatic uveal melanoma in a randomized phase II trial.
Methods:
The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT)
study was a phase III, double-blind trial (ClinicalTrial.gov identifier: NCT01974752) in which patients
with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to
selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m2 intravenously on day 1 of every 21-
day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by
blinded independent central radiologic review. Secondary end points included overall survival and
objective response rate.
Results:
A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or
placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%)
experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median,
2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The
objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus
dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave
a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse
events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash
(57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%).
Conclusion:
In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had
a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris)
The oxytocin system has a crucial role in human sociality;
several results prove that polymorphisms of the oxytocin
receptor gene are related to complex social behaviors in humans.
Dogs' parallel evolution with humans and their adaptation to the
human environment has made them a useful species to model human
social interactions. Previous research indicates that dogs are
eligible models for behavioral genetic research, as well. Based
on these previous findings, our research investigated
associations between human directed social behaviors and two
newly described (â212AG, 19131AG) and one known (rs8679684)
single nucleotide polymorphisms (SNPs) in the regulatory regions
(5âČ and 3âČ UTR) of the oxytocin receptor gene in German Shepherd
(N = 104) and Border Collie (N = 103) dogs. Dogs' behavior
traits have been estimated in a newly developed test series
consisting of five episodes: Greeting by a stranger, Separation
from the owner, Problem solving, Threatening approach, Hiding of
the owner. Buccal samples were collected and DNA was isolated
using standard protocols. SNPs in the 3âČ and 5âČ UTR regions were
analyzed by polymerase chain reaction based techniques followed
by subsequent electrophoresis analysis. The geneâbehavior
association analysis suggests that oxytocin receptor gene
polymorphisms have an impact in both breeds on (i) proximity
seeking towards an unfamiliar person, as well as their owner,
and on (ii) how friendly dogs behave towards strangers, although
the mediating molecular regulatory mechanisms are yet unknown.
Based on these results, we conclude that similarly to humans,
the social behavior of dogs towards humans is influenced by the
oxytocin system
Antibacterial and antiviral properties of Chenopodin-derived synthetic peptides
Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an An-dean plant with high nutritional and therapeutic properties. Here, we used computer- and physico-chemical-based strategies and designed four peptides derived from the primary structure of Che-nopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2 and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by ar-ginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 ”M against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. Fluorescence mi-croscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are as-sembled in the membrane. Whereas some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides
Hyperscanning of interactive juggling: expertise influence on source level functional connectivity
Hyperscanning studies, wherein brain activity is recorded from multiple participants simultaneously, offer an opportunity to
investigate interpersonal dynamics during interactive tasks at the neurophysiological level. In this study, we employed a dyadic juggling paradigm and EEG hyperscanning to evaluate functional connectivity between EEG sources within and between jugglersâ brains during individual and interactive juggling. We applied graph theoretical measures to identify significant differences in functional connectivity between the individual and interactive juggling conditions. Connectivity was measured in multiple juggler pairs with various skill levels where dyads were either skill-level matched or skill-level unmatched. We observed that global efficiency was reduced during paired juggling for less skilled jugglers and increased for more skilled jugglers. When jugglers were skill-level matched, additional reductions were found in the mean clustering coefficient and small-world topology during interactive juggling. A significant difference in hemispheric brain lateralization was detected between skill-level matched and skill-level unmatched jugglers during interactive juggling: matched jugglers had an increased right hemisphere lateralization while unmatched jugglers had an increased left hemisphere lateralization. These results reveal multiple differences in functional brain networks during individual and interactive juggling and suggest that similarities and disparities in individual skills can impact inter-brain dynamics in the performance and learning of motor tasks
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