Archaeobotanical data and crop storage evidence from an early Bronze Age 2 burnt house at Arslantepe, Malatya, Turkey

Excavations on the southwest area at Arslantepe, Malatya, Turkey, by far the largest tell on the Malatya plain from the 5th millennium to the Neo-Hittite age, revealed an important change in the settlement patterns during the two main levels of the VI C Period of the site (Early Bronze Age 2, 2750–2500 cal b.c.). The latter level corresponds to a village founded on neatly shaped terraces in a layout which lasted for centuries, well into the following Early Bronze Age 3. This continuity was not broken even by violent fires that at times destroyed some houses, producing a huge quantity of charred plant remains, which comprised fruits, seeds and wood charcoal. The archaeobotanical data so far obtained from the EB2 house A607, the richest one in macro-remains, on which efforts have been concentrated first, provides much data about the use of the surrounding land. Charcoal of Quercus (deciduous oaks) (85%) followed by Populus (poplar) (9%) are dominant among wood remains, while Hordeum (barley) (70%) is the dominant crop found, followed by Cicer (chickpea) (17%). The crop storage methods were investigated by mapping the positions of charred fruits and seeds both according to the grid system and in comparison to the layout of facilities (grinding stone, hearths, oven) and the distribution of pottery (jars, bowls, pots) in order to detect where the crops were kept and the ways in which they were stored, processed, and used. The house facilities and furniture suggest that the house was a multifunctional place, which included storage space, but which was limited to household needs. The new archaeobotanical investigation so far carried out on the burnt house A607 suggests some implications on the degree of agriculture, on crop storage and on food processing practises and also gives information on the natural landscape surrounding the site.     

The kinetic deuterium isotope effect as applied to metabolic deactivation of imatinib to the des-methyl metabolite,CGP74588

There has recently been a burgeoning interest in impeding drug metabolism by replacing hydrogen atoms with deuterium to invoke a kinetic isotope effect. Imatinib, a front-line therapy for both chronic myeloid leukemia and of gastrointestinal stromal tumours, is often substantially metabolised via N-demethylation to the significantly less active CGP74588. Since deuterium–carbon bonds are stronger than hydrogen–carbon bonds, we hypothesised that the N-trideuteromethyl analogue of imatinib might be subject to a reduced metabolic turnover as compared to imatinib and lead to different pharmacokinetic properties, and hence improved efficacy, in vivo. Consequently, we investigated whether the N-trideuteromethyl analogue would maintain target inhibition and show a reduced propensity for N-demethylation in in vitro assays with liver microsomes and following oral administration to rats. The N-trideuteromethyl compound exhibited similar activity as a tyrosine kinase inhibitor as imatinib and similar efficacy as an antiproliferative in cellular assays. In comparison to imatinib, the trideuterated analogue also showed reduced N-demethylation upon incubation with both rat and human liver microsomes, consistent with a deuterium isotope effect. However, the reduced in vitro metabolism did not translate into increased exposure of the N-trideuteromethyl analogue following intravenous administration of the compound to rats and no significant difference was observed for the formation of the N-desmethyl metabolite from either parent drug.     

Detection and Genotyping of Campylobacter jejuni and Campylobacter coli by Use of DNA Oligonucleotide Arrays

Campylobacter have emerged as the most common bacterial food-borne illness in the developed world. The ability to reduce Campylobacter infections in humans is linked to the full comprehension of the principal key aspects of its infection cycle. A microbial diagnostic microarray detecting Campylobacter housekeeping, structural, and virulence associated genes was designed and validated using genomic DNA from reference and field strains of Campylobacter jejuni and coli isolated from human, chicken, and raw milk. This microarray was confirmed to be a powerful diagnostic tool for monitoring emerging Campylobacter pathotypes as well as for epidemiological, environmental, and phylogenetic studies including the evaluation of genome plasticity.     

A hierarchical Na?ve Bayes Model for handling sample heterogeneity in classification problems: an application to tissue microarrays

Background  

Uncertainty often affects molecular biology experiments and data for different reasons. Heterogeneity of gene or protein expression within the same tumor tissue is an example of biological uncertainty which should be taken into account when molecular markers are used in decision making. Tissue Microarray (TMA) experiments allow for large scale profiling of tissue biopsies, investigating protein patterns characterizing specific disease states. TMA studies deal with multiple sampling of the same patient, and therefore with multiple measurements of same protein target, to account for possible biological heterogeneity. The aim of this paper is to provide and validate a classification model taking into consideration the uncertainty associated with measuring replicate samples.     

Multiple endocrine neoplasia type 1

Solitary median maxillary central incisor syndrome (SMMCI) is a complex disorder consisting of multiple, mainly midline defects of development resulting from unknown factor(s) operating in utero about the 35th–38th day(s) from conception. It is estimated to occur in 1:50,000 live births. Aetiology is uncertain. Missense mutation in the SHH gene (I111F) at 7q36 may be associated with SMMCI. The SMMCI tooth differs from the normal central incisor, in that the crown form is symmetric; it develops and erupts precisely in the midline of the maxillary dental arch in both primary and permanent dentitions. Congenital nasal malformation (choanal atresia, midnasal stenosis or congenital pyriform aperture stenosis) is positively associated with SMMCI. The presence of an SMMCI tooth can predict associated anomalies and in particular the serious anomaly holoprosencephaly. Common congenital anomalies associated with SMMCI are: severe to mild intellectual disability, congenital heart disease, cleft lip and/or palate and less frequently, microcephaly, hypopituitarism, hypotelorism, convergent strabismus, oesophageal and duodenal atresia, cervical hemivertebrae, cervical dermoid, hypothyroidism, scoliosis, absent kidney, micropenis and ambiguous genitalia. Short stature is present in half the children. Diagnosis should be made by eight months of age, but can be made at birth and even prenatally at 18–22 weeks from the routine mid-trimester ultrasound scan. Management depends upon the individual anomalies present. Choanal stenosis requires emergency surgical treatment. Short stature may require growth hormone therapy. SMMCI tooth itself is mainly an aesthetic problem, which is ideally managed by combined orthodontic, prosthodontic and oral surgical treatment; alternatively, it can be left untreated.