Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol\u27s anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol\u27s effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs

Molecular Characterization of Borrelia persica, the Agent of Tick Borne Relapsing Fever in Israel and the Palestinian Authority

The identification of the Tick Borne Relapsing Fever (TBRF) agent in Israel and the Palestinian Authority relies on the morphology and the association of Borrelia persica with its vector Ornithodoros tholozani. Molecular based data on B. persica are very scarce as the organism is still non-cultivable. In this study, we were able to sequence three complete 16S rRNA genes, 12 partial flaB genes, 18 partial glpQ genes, 16 rrs-ileT intergenic spacers (IGS) from nine ticks and ten human blood samples originating from the West Bank and Israel. In one sample we sequenced 7231 contiguous base pairs that covered completely the region from the 5′end of the 16S rRNA gene to the 5′end of the 23S rRNA gene comprising the whole 16S rRNA (rrs), and the following genes: Ala tRNA (alaT), Ile tRNA (ileT), adenylosuccinate lyase (purB), adenylosuccinate synthetase (purA), methylpurine-DNA glycosylase (mag), hypoxanthine-guanine phosphoribosyltransferase (hpt), an hydrolase (HAD superfamily) and a 135 bp 5′ fragment of the 23S rRNA (rrlA) genes. Phylogenic sequence analysis defined all the Borrelia isolates from O. tholozani and from human TBRF cases in Israel and the West Bank as B. persica that clustered between the African and the New World TBRF species. Gene organization of the intergenic spacer between the 16S rRNA and the 23S rRNA was similar to that of other TBRF Borrelia species and different from the Lyme disease Borrelia species. Variants of B. persica were found among the different genes of the different isolates even in the same sampling area

Defining multiple inhabitations of a cave environment using interdisciplinary archaeometry: the ‘Christmas Cave’ of the Wadi en-Nar/Nahal Qidron, west of the Dead Sea

The present study reports a series of interdisciplinary archaeometrical analyses of objects found in the Christmas Cave, which was discovered by John Allegro and his team in 1960 on the West Bank of the Dead Sea and assumed to be inhabited only in the Chalcolithic era and by Jewish refugees of the second century CE, at the end of the Bar Kokhba Revolt. Like many other Judaean desert caves, there was an abundance of organic material, especially textiles, surviving in the dry environment. In the absence of clear stratigraphy and even a proper publication of the finds, the present study shows how archaeometry can provide important insights. We analysed food crusts on ceramics by gas chromatography with mass spectrometric detection (GC–MS), made petrographic descriptions to estimated provenance of the ceramics, produced new radiocarbon dates from organic material and thermoluminescence (TL) dates from the pottery. It appears from the data that the Christmas Cave has been briefly inhabited or visited intermittently over a very long time, starting ca. 4000 BCE (the Chalcolithic period), and extending all the way to the Medieval period, even though there is also a concentration of dates near the period of the Bar Kokhba Revolt (132–136 CE). We argue, through a detailed analysis of the radiometric and TL-datings and by the artefactual evidence, that there was likely another refuge episode connected with the First Jewish Revolt during which people fled to this cave. However, we see no material connection to Qumran and nearby caves. Overall, our study demonstrates the importance of archaeometric studies in cave environments where stratigraphy is veritably absent

The Earliest Lead Object in the Levant.

In the deepest section of a large complex cave in the northern Negev desert, Israel, a bi-conical lead object was found logged onto a wooden shaft. Associated material remains and radiocarbon dating of the shaft place the object within the Late Chalcolithic period, at the late 5th millennium BCE. Based on chemical and lead isotope analysis, we show that this unique object was made of almost pure metallic lead, likely smelted from lead ores originating in the Taurus range in Anatolia. Either the finished object, or the raw material, was brought to the southern Levant, adding another major component to the already-rich Late Chalcolithic metallurgical corpus known to-date. The paper also discusses possible uses of the object, suggesting that it may have been used as a spindle whorl, at least towards its deposition

Results of lead isotope analysis.

<p>Lead isotope ratios of the Ashalim Cave lead object plotted against ores from selected regions. Details and references are provided in the text.</p

Normalized trace element concentrations (ppm) measured by WDS.

<p>Normalized trace element concentrations (ppm) measured by WDS.</p

View of Ashalim Cave in its desert environment.

<p>The vertical entrance to the cave is located in front of the standing figure.</p

The Lead object.

<p>The lead object with shaft <i>insitu</i> at Ashalim Cave.</p

The Ashalim Cave lead object.

<p>The Ashalim Cave lead object.</p