Ana Ortega

Neandertal roots: Cranial and chronological evidence from Sima de los Huesos

Neandertal ancestors from Pleistocene Spain The Sima de los Huesos site in Atapuerca, northern Spain, is a rich source of fossil hominin specimens. The site has now yielded further skull specimens that illuminate patterns of human evolution in Europe nearly half a million years ago. Arsuaga et al. studied 17 crania, including 7 that are new specimens and 6 that are more complete than before (see the Perspective by Hublin). This assemblage of specimens reveals the cranial, facial, and dental features of the Atapuerca hominins, which allows more precise evolutionary positioning of these Neandertal ancestors. Science, this issue p. 1358; see also p. 1338 Seventeen skulls from at least 430 thousand years ago illuminate hominin evolutionary patterns in Pleistocene Europe. [Also see Perspective by Hublin] Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.

Primary Angioplasty Reduces the Risk of Left Ventricular Free Wall Rupture Compared With Thrombolysis in Patients With Acute Myocardial Infarction

OBJECTIVESnThis study aimed to evaluate the effect of primary angioplasty (PA) over the risk of free wall rupture (FWR) in reperfused acute myocardial infarction (AMI).nnnBACKGROUNDnIt has been suggested that PA reduces the risk of FWR compared with thrombolysis. However, few studies have evaluated this issue, and there are no data demonstrating this hypothesis.nnnMETHODSnA total of 1,375 patients with AMI treated with PA (n = 762, 55.4%) or thrombolysis (n = 613, 44.6%) within 12 h after symptoms onset were included. The diagnosis of FWR was made either in the presence of sudden death due to electromechanical dissociation with large pericardial effusion on an echocardiogram or when demonstrated post mortem or at surgery. A multivariable analysis was performed including type of reperfusion strategy.nnnRESULTSnThe overall incidence of FWR was 2.5% (n = 34): 1.8% and 3.3% in patients treated with PA and with thrombolysis, respectively (p = 0.686). The following characteristics were associated with a higher rate of FWR in the univariable analysis: age >70 (5.2% vs. 1.2%, p < 0.001), female gender (5.1% vs. 1.8%, p = 0.006), anterior location (3.3% vs. 1.4%, p = 0.020) and treatment >2 h after symptoms onset (3.6% vs. 1.7%, p = 0.043). In the multivariable analysis, age >70 (odds ratio [OR]: 4.12, 95% confidence interval [CI]: 2.04 to 8.62, p < 0.001) and anterior location (OR: 2.91, 95% CI: 1.36 to 6.63, p = 0.008) were independent risk factors of FWR, whereas treatment with PA was an independent protective factor (OR: 0.46, 95% CI: 0.22 to 0.96, p = 0.0371).nnnCONCLUSIONSnIn patients with AMI, PA reduces the risk of FWR in comparison with thrombolysis.

Géologie de la Sierra de Atapuerca et stratigraphie des remplissages karstiques de Galería et Dolina (Burgos, Espagne)

Resume Lanticlinal inverse de materiels mesozoiques de la Sierra de Atapuerca, de direction Iberique NW-SE, represente geomorphologiquement un mont mis en place par des mouvements verticaux durant le Miocene et le Pliocene (?). Cest un systeme karstique de galeries, de 3000 m lineaires, qui sest developpe dans les calcaires, dolomites et marnes du Cretace superieur (Turonien-Santonien). Sur le flanc sud, une tranchee de chemim de fer abandonnee, a permis la decouverte dun nombre eleve de cavites comblees de depots dinterieur de grottes et dautres provenant de lexterieur. Dans ce present travail sont analyses les remplissages des gisements de Galeria (TG) et de Dolina (TD), avec les faunes, flores et restes humains du Pleistocene moyen a Galeria, et du Pleistocene inferieur ( Homo antecessor ) a Dolina, dans lunite lithostratigraphique de TD6 (780 ka). Les donnees magnetostratigraphiques, les chronologies par les series de lUranium-ESR et dautres caracteristiques du remplissage indiquent que la sedimentation allochtone (TD3–4) a commence il y a environ 1 million dannees.

Combined ESR/U-series chronology of Acheulian hominid-bearing layers at Trinchera Galería site, Atapuerca, Spain

The Sierra de Atapuerca, northern Spain, is known from many prehistoric and palaeontological sites documenting human prehistory in Europe. Three major sites, Gran Dolina, Galería and Sima del Elefante, range in age from the oldest hominin of Western Europe dated to 1.1 to 1.3xa0Ma (millions of years ago) at Sima del Elefante to c.a. 0.2xa0Ma on the top of the Galería archaeological sequence. Recently, a chronology based on luminescence methods (Thermoluminescence [TL] and Infrared Stimulated Luminescence [IRSL]) applied to cave sediments was published for the Gran Dolina and Galería sites. The authors proposed for Galería an age of 450xa0ka (thousands of years ago) for the units lower GIII and GII, suggesting that the human occupation there is younger than the hominid remains of Sima de los Huesos (>530xa0ka) around 1xa0km away. In this paper, we present new results obtained by combined Electron Spin Resonance/Uranium-series (ESR/U-series) dating on 20 herbivorous teeth from different levels at the Galería site. They are in agreement with the TL results for the upper part of the stratigraphic sequence (GIV and GIIIb), in the range of between 200 and 250xa0ka. But for the GIIIa to GIIb levels, the TL ages become abruptly older by 200 ka while ESR ages remain relatively constant. Finally, the TL and ESR data agree in the lowest part of the section (GIIa); both fall in the range of around 350-450xa0ka. Our results suggest a different interpretation for the GII, GIII and GIV units of Galería and the upper part of Gran Dolina (TD10 and TD11) than obtained by TL. The ESR/U-series results are supported by a Bayesian analysis, which allows a better integration between stratigraphic information and radiometric data.

New luminescence ages for the Galería Complex archaeological site: resolving chronological uncertainties on the acheulean record of the Sierra de Atapuerca, northern Spain.

The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean ageu200a=u200a313±14 ka; nu200a=u200a4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT-OSL dating are suitable for resolving Middle Pleistocene chronologies for the Sierra de Atapuerca karstic infill sequences.

The Atapuerca sites and the ibeas hominids

The Atapuerca railway Trench and Ibeas sites near Burgos, Spain, are cave fillings that include a series of deposits ranging from below the Matuyama/Bruhnes reversal up to the end of Middle Pleistocene. The lowest fossil-bearing bed in the Trench contains an assemblage of large and small Mammals includingMimomys savini, Pitymys gregaloides, Pliomys episcopalis, Crocuta crocuta, Dama sp. and Megacerini; the uppermost assemblage includesCanis lupus, Lynx spelaea, Panthera (Leo) fossilis, Felis sylvestris, Equus caballus steinbeimensis, E.c. germanicus, Pitymys subterraneus, Microtus arvalis agrestis, Pliomys lenki, and alsoPanthera toscana, Dicerorbinus hemitoechus, Bison schoetensacki, which are equally present in the lowest level. The biostratigraphic correlation and dates of the sites are briefly discussed, as are the paleoclimatic interpretation of the Trench sequences. Stone artifacts are found in several layers; the earliest occurrences correspond to the upper beds containingMimomys savini. A set of preserved human occupation floors has been excavated in the top fossil-bearing beds. The stone-tool assemblages of the upper levels are of upper-medial Acheulean to Charentian tradition. The rich bone breccia SH, in the Cueva Mayor-Cueva del Silo, Ibeas de Juarros, is a derived deposit, due to a mud flow that dispersed and carried the skeletons of many carnivores and humans. The taxa represented are:Ursus deningeri (largely dominant),Panthera (Leo) fossilis, Vulpes vulpes, Homo sapiens var. Several traits of both mandibular and cranial remains are summarized. Preliminary attempts at dating suggest that the Ibeas fossil man is older than the Last Interglacial, or oxygen-isotope stage 5.

Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.

Background The endoplasmic reticulum (ER) is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF). To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM) and ischemic (ICM) cardiomyopathies, and its relationship with patients functional status. Methods and Results We examined 52 explanted human hearts from DCM (nu200a=u200a21) and ICM (nu200a=u200a21) subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05) and structural (Reticulon 1, p<0.01) protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function. Conclusions In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.

Prognosis of medically stabilized unstable angina pectoris with a negative exercise test

Three hundred twenty seven patients with medically stabilized unstable angina and a negative exercise test were followed-up during a mean of 39 months. Male gender, diabetes mellitus, and previous myocardial infarction, but not exercise parameters, were predictors of death or acute myocardial infarction.

RNA Sequencing Analysis and Atrial Natriuretic Peptide Production in Patients with Dilated and Ischemic Cardiomyopathy

Background The atrium is the major site of ANP synthesis, which has been said to increase in heart failure as a result of increased production in the left ventricular (LV) myocardium. This is a key issue related to its diagnostic and prognostic capabilities. We aimed to evaluate protein levels of proANP and ANP and the enzymes that cleave the natriuretic peptides, corin and furin, in the LV tissue of heart transplant patients with dilated (DCM) and ischemic (ICM) cardiomyopathy compared with control donors (CNT). We also evaluate mRNA levels of ANP gene (NPPA) by RNA sequencing in the same tissue. Methods and Results Seventy-three human LV tissue samples from ICM (nu200a=u200a30) and DCM (nu200a=u200a33) patients and CNT (nu200a=u200a10) were analyzed by Western blot and RNA sequencing. Comparing protein levels according to etiology, neither DCM nor ICM showed levels of proANP or ANP different from those of CNT. However, NPPA was increased in both groups compared to CNT (DCM 32 fold, p<0.0001; ICM 10 fold, p<0.0001). Corin (but not furin) was elevated in the ICM group compared to CNT (112±24 vs. 100±7, p<0.05), and its level was inversely related with LV ejection fraction (LVEF) (ru200a=u200a−0.399, p<0.05). Conclusions Patients present with elevated levels of NPPA but not of proANP or ANP proteins in LV tissue, which may be due to posttranscripcional regulation of NPPA or different pathways for ANP secretion between the atrium and ventricle. Moreover, there are differences between DCM and ICM in corin levels, indicating that a different molecular mechanism may exist that converge in this syndrome. Further, LV concentration of corin is inversely related to LVEF in ICM.

Heart failure entails significant changes in human nucleocytoplasmic transport gene expression

BACKGROUNDnHeart failure (HF) induces alterations in nucleocytoplasmic transport, which is essential to the cardiomyocyte biology. The objective of this study was to analyze the changes in gene expression in human HF, particularly focusing on nucleocytoplasmic transport-related genes.nnnMETHODS AND RESULTSn29 RNA heart samples from dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) patients undergoing heart transplantation and control donors (CNT, n = 5) were extracted to perform a microarray profiling using Affymetrix Human Gene® 1.0 ST arrays. We focused on the study of 5 nucleocytoplasmic transport-related genes, since this functional category has not previously been studied in HF. XPO1, GABPB2, and RANBP17 were upregulated, while KALRN was downregulated in both DCM and ICM, and XPO5 only in DCM. Validation of the results by RT-qPCR increasing the total heart samples up to 41 showed a high degree of consistency with microarray results. Moreover, we observed a strong relationship between the XPO1 mRNA and robust left ventricular function parameters in ICM: left ventricular end-systolic (r = 0.81, p<0.0001) and end-diastolic diameters (r = 0.80, p<0.0001), and ejection fraction (r = -0.57, p<0.05).nnnCONCLUSIONSnWe show that the expression of nucleocytoplasmic transport-related genes is altered in HF. Furthermore, XPO1 mRNA level is closely related with robust left ventricular function parameters in ICM patients. These changes may help to distinguish DCM and ICM in HF at the level of the transcriptome and provide a base for novel therapeutic approaches.