Not the End of the World? Post-Classical Decline and Recovery in Rural Anatolia

Between the foundation of Constantinople as capital of the eastern half of the Roman Empire in 330 CE and its sack by the Fourth Crusade in 1204 CE, the Byzantine Empire underwent a full cycle from political-economic stability, through rural insecurity and agrarian decline, and back to renewed prosperity. These stages plausibly correspond to the phases of over-extension (K), subsequent release (Ω) and recovery (α) of the Adaptive Cycle in Socio-Ecological Systems. Here we track and partly quantify the consequences of those changes in different regions of Anatolia, firstly for rural settlement (via regional archaeological surveys) and secondly for land cover (via pollen analysis). We also examine the impact of climate changes on the agrarian system. While individual histories vary, the archaeological record shows a major demographic decline between ca .650 and ca. 900 CE in central and southwestern Anatolia, which was then a frontier zone between Byzantine and Arab armies. In these regions, and also in northwest Anatolia, century-scale trends in pollen indicate a substantial decline in the production of cereal and tree crops, and a smaller decline in pastoral activity. During the subsequent recovery (α) phase after 900 CE there was strong regional differentiation, with central Anatolia moving to a new economic system based on agro-pastoralism, while lowland areas of northern and western Anatolia returned to the cultivation of commercial crops such as olive trees. The extent of recovery in the agrarian economy was broadly predictable by the magnitude of its preceding decline, but the trajectories of recovery varied between different regions

A novel procedure to measure the antioxidant capacity of Yerba maté extracts

Yerba maté extracts have in vitro antioxidant capacity attributed to the presence of polyphenolic compounds, mainly chlorogenic acids and dicaffeoylquinic acid derivatives. DPPH is one of the most used assays to measure the antioxidant capacity of pure compounds and plant extracts. It is difficult to compare the results between studies because this assay is applied in too many different conditions by the different research groups. Thus, in order to assess the antioxidant capacity of yerba maté extracts, the following procedure is proposed: 100 µL of an aqueous dilution of the extracts is mixed in duplicate with 3.0 mL of a DPPH 'work solution in absolute methanol (100 µM.L-1), with an incubation time of 120 minutes in darkness at 37 ± 1 °C, and then absorbance is read at 517 nm against absolute methanol. The results should be expressed as ascorbic acid equivalents or Trolox equivalents in mass percentage (g% dm, dry matter) in order to facilitate comparisons. The AOC of the ethanolic extracts ranged between 12.8 and 23.1 g TE % dm and from 9.1 to 16.4 g AAE % dm. The AOC determined by the DPPH assay proposed in the present study can be related to the total polyphenolic content determined by the Folin-Ciocalteu assay

Modelling climate and societal resilience in the Eastern Mediterranean in the last Millennium

This article analyses high-quality hydroclimate proxy records and spatial reconstructions from the Central and Eastern Mediterranean and compares them with two Earth System Model simulations (CCSM4, MPI-ESM-P) for the Crusader period in the Levant (1095–1290 CE), the Mamluk regime in Transjordan (1260–1516 CE) and the Ottoman crisis and Celâlî Rebellion(1580–1610 CE). During the three time intervals, environmental and climatic stress tested the resilience of complex societies.We find that the multidecadal precipitation and drought variations in the Central and Eastern Mediterranean cannot be explained by external forcings (solar variations, tropical volcanism); rather they were driven by internal climate dynamics. Our research emphasises the challenges, opportunities and limitations of linking proxy records, palaeoreconstructions and model simulations to better understand how climate can affect human history

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors

Climate on the Southern Black Sea coast during the Holocene: implications from the Sofular Cave record

We present the updated Holocene section of the Sofular Cave record from the southernBlackSeacoast (northern Turkey); an area with considerably different present-day climate compared to that of the neighboring Eastern Mediterranean region. Stalagmite δ13C, growth rates and initial (234U/238U) ratios provide information about hydrological changes above the cave; and prove to be more useful than δ18O for deciphering Holocene climatic variations. Between ∼9.6 and 5.4 ka BP (despite a pause from ∼8.4 to 7.8 ka BP), the Sofular record indicates a remarkable increase in rainfall amount and intensity, in line with other paleoclimate studies in the Eastern Mediterranean. During that period, enhanced summertime insolation either produced much stronger storms in the following fall and winter through high sea surface temperatures, or it invoked a regional summer monsoon circulation and rainfall. We suggest that one or both of these climatic mechanisms led to a coupling of the BlackSea and the Mediterranean rainfall regimes at that time, which can explain the observed proxy signals. However, there are discrepancies among the Eastern Mediterranean records in terms of the timing of this wet period; implying that changes were probably not always occurring through the same mechanism. Nevertheless, the Sofular Cave record does provide hints and bring about new questions about the connection between regional and large scale climates, highlighting the need for a more extensive network of high quality paleoclimate records to better understand Holoceneclimate

Effect of intracanal medicament on bond strength of fibre posts

The aim of this study was to evaluate the effect of calcium hydroxide (CH), triple antibiotic paste (TAP) and double antibiotic paste (DAP) on the push-out bond strengths of three different self-adhesive resin cements. Forty-eight single-rooted human maxillary central incisors were selected. The crowns were removed and the root canals were performed. After the irrigation protocols, the post space was prepared. The teeth were then randomly divided into a control group (no intracanal medicament) and three medicament groups (n = 12 for each group). After three weeks, the medicaments were removed using 17% ethylenediaminetetraacetic acid, 2.5% sodium hypochlorite and EndoActivator agitation. The teeth were divided into three subgroups according to the fibre-post luting cement: Maxcem Elite, RelyX Unicem and BisCem. The specimens were sectioned and the push-out test was performed. One-way analysis of variance and Tukey's post hoc tests were used for statistical analyses. Regarding the type of cement, BisCem had significantly lower bond strength values than Maxcem and RelyX. There was no significant difference between the bond strength values of Maxcem and RelyX (p > 0.05). The TAP-RelyX group had the highest bond strength value and the DAP-BisCem group had the lowest bond strength value. RelyX and Maxcem had higher bond strength to root canal dentin than BisCem. The bond strength of BisCem, RelyX and Maxcem was not negatively affected by the use of DAP, CH and TAP as intracanal medicaments