Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m² intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m² and cyclophosphamide, 600 mg/m², plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

Higher plants possess two different types of ATX1-like copper chaperones

Copper (Cu) chaperones constitute a family of small Cu+-binding proteins required for Cu homeostasis in eukaryotes. The ATX1 family of Cu chaperones specifically delivers Cu to heavy metal P-type ATPases. The plant Arabidopsis thaliana expresses the ATX1-like Cu chaperone CCH, which exhibits a plant-specific carboxy-terminal domain (CTD) with unique structural properties. We show that CCH homologues from other higher plants contain CTDs with structural properties similar to Arabidopsis CCH. Furthermore, we identify a new ATX1-like Cu chaperone in Arabidopsis, AtATX1, which functionally complements yeast atx1Delta and sod1Delta associated phenotypes, and localizes to the cytosol of Arabidopsis cells. Interestingly, AtATX1, but not full-length CCH, interacts in vivo with the Arabidopsis RAN1 Cu-transporting P-type ATPase by yeast two-hybrid. We propose that higher plants express two types of ATX1-like Cu chaperones: the ATX1-type with a predominant function in Cu delivery to P-type ATPases, and the CCH-type with additional CTD-mediated plant-specific functions.     

Genetic study of the population of Tenerife (Canary Islands,Spain): Protein markers and review of classical polymorphisms

Data on six protein polymorphisms (19 alleles) from the human population of Tenerife are presented and discussed along with other classical markers in relation to the origin of the Canarians. Genetic influences from three population groups were considered: the Iberians, and the Berbers and non-Berbers (Arabs) from north Africa. The systems examined show the Tenerife population lies within the limits of variation described for various Iberian groups, with a slight tendency towards the characteristics of north African populations. When blood groups, red cell enzymes and serum protein data were considered, the similarity of the Canary population to Iberians seems strengthened (70% estimated contribution of Iberian peninsula genes to the present-day Canarian pool), while some relation with north African groups is shown. Genetic distances between Canarians and Arabs and Canarians and Berbers are lower than those between the two north African groups, indicating a relative and comparable contribution of each to the present-day gene pool of the Canarian population. The Arab contribution could be attributable to the slaves who were introduced to these islands after the conquest in the 15th century, while the Berber contribution could be the remnants of the extinct aboriginal peoples of the islands (Guanches) or a more recent immigration due to slavery. Genetic data do not allow us to distinguish between these two possibilities. Am. J. Phys. Anthropol. 102:337–349, 1997. © 1997 Wiley-Liss, Inc.     

Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

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Drought stress memory in the photosynthetic mechanisms of an invasive CAM species, <Emphasis Type="Italic">Aptenia cordifolia</Emphasis>

Plants are known for their high capacity to acclimatise to fluctuating environmental conditions. A wide range of environmental conditions can lead to suboptimal physiological efficiency. However, recent studies have shown that plants can withstand repeated periods of stress. To find out how they do it, we studied photosynthetic adjustments to repeated water stress in Aptenia cordifolia: a facultative, invasive CAM species. Plants were subjected to three cycles of water deficit, and photosynthetic parameters and chloroplast antioxidants were quantified to gain an understanding of the mechanisms by which they cope with repeated stress periods. Significant modification of the photosystems’ antenna and reaction centres was observed in plants subjected to previous water stress cycles, and this led to higher PSII efficiency than in plants challenged with drought for the first time. These findings underline the biological significance of stress memory and show how plants can adjust their photosynthetic apparatus to fluctuating environmental conditions and thus optimise photosynthesis and photoprotection under drought conditions.     

Colonization of dynamic Mediterranean landscapes: where do birds come from after fire?

Aim Two main mechanisms may explain post‐disturbance species colonization patterns of early successional habitats such as those originated by wildfires. First, post‐disturbance colonization is not limited by the dispersal ability of the species to reach the newly created open areas and, secondly, colonization is limited by dispersal. Under the first hypothesis, we expect, at a regional scale, to find similar post‐disturbance communities to develop on recently burned sites. However, colonization limited by dispersal will lead to strong between‐site variations in species composition. Location To test these hypotheses, we studied the post‐fire colonization patterns of nine open‐habitat bird species in eight distantly located wildfires in the north‐eastern Iberian Peninsula. Methods We censused post‐fire bird composition by means of field transects and identified potential colonization sources from species–habitat suitability maps derived from atlas data. Results Our results showed strong significant differences in post‐fire species composition between burnt areas. Burnt areas located in areas with low probability of species presence before the fire event showed lower species occurrence and richness after the fire. Main conclusions These results do not support the idea that early successional stages and open habitats have a homogeneous community structure at regional scales and suggest that dispersal is a key constraint determining bird colonization of post‐fire habitats. Further attention should be paid to landscape heterogeneity as a key factor in determining population dynamics of open‐habitat species in the light of current and future land‐use changes in Mediterranean regions.     

How calmodulin interacts with the adenosine A(2A) and the dopamine D(2) receptors

Receptor heteromerization is a mechanism used by G protein-coupled receptors to diversify their properties and function. We previously demonstrated that these interactions occur through salt bridge formation between epitopes of the involved receptors. Recent studies claim that calmodulin (CaM) binds to an Arg-rich epitope located in the amino-terminus of the dopamine D(2) receptor third intracellular loop. This is the same epitope involved in adenosine A(2A)-D(2) receptor heteromerization, through Coulombic interaction between the Arg residues and a phosphorylated serine (pS) located in the medial segment of the C-terminus of the A(2A) receptor. Mass spectrometric analysis indicates that an electrostatic interaction involving the D(2) receptor Arg-rich epitope and several CaM acidic epitopes are mainly responsible for the D(2) receptor-CaM binding. CaM could also form multiple noncovalent complexes by means of electrostatic interactions with an epitope localized in the proximal segment of the C-terminus of the A(2A) receptor. Ca(2+) disrupted the binding of CaM to the D(2) but not to the A(2A) receptor epitope, and CaM disrupted the electrostatic interactions between the D(2) receptor epitope and the more distal A(2A) receptor epitope. A model is introduced with the possible functional implications of A(2A)-D(2)-CaM interactions. These in vitro findings imply a possible regulatory role for CaM in receptor heteromers formation.     

Diurnal changes in photosystem II photochemistry, photoprotective compounds and stress-related phytohormones in the CAM plant, Aptenia cordifolia

Acclimation of photosynthetic light reactions to daily changes in solar radiation requires adjustments in photosystem II photochemistry and may be affected by environmental stresses, such as drought. In this study, we examined the effects of a short-term, severe water deficit on diurnal variations in photosystem II photochemistry, photoprotective compounds (tocopherols and carotenoids, including the xanthophyll cycle) and stress-related phytohormones (abscisic acid and salicylic acid) in the CAM plant, Aptenia cordifolia L. f. Schwantes. Violaxanthin was rapidly converted to zeaxanthin under high light, the de-epoxidation state of the xanthophyll cycle reaching maximum levels of 0.95 at midday in irrigated plants. Under a higher photoprotective demand caused by water deficit, plants showed significant increases in abscisic acid and γ-tocopherol levels, which were followed by decreases in β-carotene and the F_v/F_m ratio at later stages of stress. Decreases in this ratio below 0.70 correlated with sustained increases in the de-epoxidation state of the xanthophyll cycle, which kept above 0.90 at night after 15 days of water deficit. In contrast to abscisic acid, salicylic acid levels kept constant under water deficit and showed a sharp decrease during the day both under irrigated and water stress conditions. We conclude that the CAM plant, A. cordifolia showed several strategies of acclimation to short-term water deficit, including abscisic acid and γ-tocopherol accumulation, as well as sustained increases in the de-epoxidation state of the xanthophyll cycle, which was tightly coupled to daily variations in photosystem II photochemistry. The differential accumulation of tocopherol homologues under water deficit and the diurnal fluctuations of salicylic acid levels in this CAM plant will also be discussed.