Born Free ? New Evidence for the Status of Sus scrofa at Neolithic Çayönü Tepesi (Southeastern Anatolia, Turkey)

A renewed analysis was undertaken of the Sus remains from all habitation phases at Neolithic Çayönü Tepesi, a site which spans more than two millennia and has been considered as among the oldest domestication sites of the pig in Western Asia. The research included age at death estimations, osteometrical analysis of both dental and postcranial material, and the recording of a dental defect (Linear Enamel Hypoplasia or LEH). The analysis revealed a diachronic trend towards younger ages at death, smaller body size, shorter dentition and an increasing frequency of LEH. The results, however, cannot easily be interpreted within the simple dichotomy of "domestic " versus "wild "populations, instead, they show gradual and slow changes and not sudden, dramatic events. This suggests a gradual intensification of the relationship between humans and Sus, a. process that started, early but developed only slowly. The data, support the hypothesis that the Sus population at and around Çayönü lived in a relationship with humans, that was intermediary between "wild" and "domestic ".Un réexamen des restes de Sus provenant, des différentes phases d 'occupation de Çayönü a. été entrepris. Le site néolithique, habité pendant plus de deux millénaires, est un des lieux où l 'on peut le mieux observer les premières traces de domestication du porc. L 'analyse repose sur l 'estimation de l 'âge de la mort, l 'analyse ostéométrique des éléments dentaires et crâniens et. le relevé d 'une anomalie dentaire (l'Hypoplasie linéaire de l'émail ou HLE). Cet examen montre des modifications au cours du temps qui s'expriment par un abattage des individus à un plus jeune âge, une diminution de la stature des animaux, une réduction, de la taille des dents et une augmentation de la fréquence de HLE. Les résultats obtenus ne doivent cependant pas être interprétés comme une simple dichotomie où les populations "domestiques " s 'opposeraient aux "sauvages ". En effet, on observe des changements lents et progressifs et non pas des événements soudains et dramatiques. Ceci suggère une intensification graduelle des relations entre humains et Sus, processus qui débuta, tôt et connut un lent développement. Les données étayent l 'hypothèse que la population de Sus à Çayönü et dans ses environs avait des rapports avec les humains qui n 'étaient pas ceux que l 'homme entretient soit avec le porc "sauvage " soit avec le porc "domestique " mais qui indiquent un état, intermédiaire.Ervynck Anton, Dobney Keith, Hongo Hitomi, Meadow R. Born Free ? New Evidence for the Status of Sus scrofa at Neolithic Çayönü Tepesi (Southeastern Anatolia, Turkey). In: Paléorient, 2001, vol. 27, n°2. pp. 47-73

An anti-gdnf family receptor alpha 1 (gfra1 antibody–drug conjugate for the treatment of hormone receptor–positive breast cancer

Luminal A (hormone receptor-positive) breast cancer constitutes 70% of total breast cancer patients. In an attempt to develop a targeted therapeutic for this cancer indication, we have identified and characterized Glial cell line–Derived Neurotrophic Factor (GDNF) Family Receptor Alpha 1 (GFRA1) antibody–drug conjugates (ADC) using a cleavable valine-citrulline-MMAE (vcMMAE) linker-payload. RNAseq and IHC analysis confirmed the abundant expression of GFRA1 in luminal A breast cancer tissues, whereas minimal or no expression was observed in most normal tissues. Anti–GFRA-vcMMAE ADC internalized to the lysosomes and exhibited target-dependent killing of GFRA1-expressing cells both in vitro and in vivo. The ADCs using humanized anti-GFRA1 antibodies displayed robust therapeutic activity in clinically relevant cell line–derived (MCF7 and KPL-1) tumor xenograft models. The lead anti-GFRA1 ADC cross-reacts with rodent and cynomolgus monkey GFRA1 antigen and showed optimal pharmacokinetic properties in both species. These properties subsequently enabled a target-dependent toxicity study in rats. Anti-GFRA1 ADC is well tolerated in rats, as seen with other vcMMAE linker–payload based ADCs. Overall, these data suggest that anti–GFRA1-vcMMAE ADC may provide a targeted therapeutic opportunity for luminal A breast cancer patients. Mol Cancer Ther; 17(3); 638–49. 2017 AACR