Palaeohistology and palaeopathology of an Aeolosaurini (Sauropoda: Titanosauria) from Morro do Cambambe (Upper Cretaceous, Brazil)

Altres ajuts: CAISEP (Comisión de Ayudas a la Investigación de la Sociedad Española de Paleontología) project #2018-07153A recent publication of fossil bones of titanosaurs assigned to Aeolosaurini from the Morro do Cambambe site (Mato Grosso state, Brazil, Upper Cretaceous) reported anomalous growth in some of them. Here, we present osteohistological sections of elements to understand not only the microstructure and growth of such bones, but also the nature of those anomalies. The primary bone of all specimens consisted of a variation of the fibrolamellar complex, with the inner cortex being rich in woven bone with dispersed longitudinal canals, while the outer cortex was parallel-fibred with rows of longitudinal canals, interlayered by Lines of Arrested Growth (LAGs). We identified a maximum of two LAGs in the cervical rib and haemal arch, and four in the dorsal rib. The haemal arch shows an External Fundamental System (EFS) in most sections. The advanced remodelling and variation of the fibrolamellar bone in the cortex suggests that all the specimens represent individuals that reached sexual maturity. However, the haemal arch was distinct due to the wide distribution of EFS. The dorsal rib exhibited periosteal and endosteal outgrowth. Such microstructure was assigned to a reactive bone due to an intra-thoracic infection (a pneumonia, probably related to a tuberculosis), which is the first report in a non-avian dinosaur. The microstructure resembles the medullary bone recovered in dinosaurs, which suggests that further studies of medullary bone in thoracic bones should also regard the pathological cases.En una reciente publicación de los huesos fósiles de titanosaurios asignados al clado Aeolosaurini provenientes del yacimiento de Morro do Cambambe (estado de Mato Grosso, Brasil, Cretácico Superior), se reconocieron anormalidades en el crecimiento de algunos de ellos. En el presente trabajo presentamos cortes osteohistológicos de elementos para entender no sólo la microestructura y crecimiento de los mismos, sino también la naturaleza de aquellas anomalías. Entre ellos, seleccionamos una costilla cervical y una costilla dorsal media posterior, así como un arco hemal. El hueso primario de todos los especímenes comprendía una variación del complejo fibrolamelar, siendo la corteza interna rica en tejido reticular óseo con canales longitudinales dispersos, mientras que la corteza externa tenía fibras paralelas con hileras de canales longitudinales, intercaladas por líneas de crecimiento detenido. Identificamos un máximo de dos líneas de crecimiento detenido tanto en la costilla cervical como en el arco hemal, y cuatro en la costilla dorsal. El arco hemal muestra un Sistema Externo Fundamental en la mayoría de las secciones. La remodelación avanzada y la variación del hueso fibrolamelar en la corteza, se sugiere que todas los especímenes alcanzaron la madurez sexual. Sin embargo, el arco hemal fue distinto debido a la amplia distribución de Sistema Externo Fundamental. Con base en la microestructura, identificamos un semaforonte subadulto, y probablemente a un adulto. La costilla dorsal mostró una excrecencia perióstica y endosteal. Dicha microestructura se ha identificado con un hueso reactivo a una infección intratorácica (una neumonía, probablemente relacionada con una tuberculosis), que es el primer informe de un dinosaurio no aviano. La microestructura se asemeja al hueso medular recuperado en los dinosaurios, lo que sugiere que los estudios posteriores del hueso medular en los huesos torácicos también deberían considerar los casos patológicos

Integration of miRNA and mRNA expression profles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron transport. We further identified 11 miRNAs, including miR-29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins related to ECM organization. Integrative miRNA and mRNA global expression data allowed us to identify miRNA target genes involved in skeletal muscle wasting in CC. Our functional experiments in C2C12 cells confirmed that miR-29b down-regulates collagen genes and contributes to muscle cell atrophy. Collectively, our results suggest that key ECM-associated miRNAs and their target genes may contribute to CC in HF

Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. alpha(2A)/alpha(2C)-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease

New insights about host response to smallpox using microarray data

<p>Abstract</p> <p>Background</p> <p>Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease.</p> <p>Results</p> <p>We used KEGG pathways annotations to define groups of genes (or modules), and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox.</p> <p>Conclusion</p> <p>Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.</p

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu