Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD

Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1

Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation

Attained energy densities and neutral pion spectra in nucleus-nucleus collisions at 200 GeV/nucleon

The main goal of the CERN heavy-ion experiments is the search for an indication that the predicted state of deconfined quarks and gluons, the quark-gluon plasma (QGP), has been produced. The quantity most crucial to the probability of QGP formation is the thermalized energy density attained during the heavy-ion reaction. The amount of energy radiated transverse to the beam direction is the experimental quantity which is believed to be a measure of the amount of energy deposition in the reaction, and hence to reflect the energy density attained. In this presentation we consider the systematics of transverse energy production at CERN SPS energies, and we use the results to make estimates, under various assumptions, of attained energy densities. 18 refs., 2 figs

Photons and neutral mesons from hot hadronic matter

Results from the experimental program with light ion beams and heavy target nuclei at the CERN SPS could demonstrate the occurrence of an unprecedented state of high density in hadronic matter. The thermal nature of the hadronic system has been investigated by analyzing spectra and production ratios of hadrons which reveal a large degree of rescattering of primary and secondary hadrons.Thermal photons from elementary quark-gluon interactions are considered a promising signal for the occurrence of a phase transition to the quark-gluon plasma. The predictions for thermal photons from elementary parton interactions are discussed and compared to the thermal emission rate of photons from a hot hadronic gas. Recent results from the photon spectrometers in heavy ion experiments are presented. Production cross sections of pi0 and eta mesons are determined and the projectile and target mass dependence is discussed. An upper limit for the single photon yield was determined for central O+Au reactions. Recent S+Au reactions exhibit an excess of photons over the yield expected from hadronic decays. The spectral shape of the expected single photon signal is discussed which might reveal the temperature of hot matter and indicate a phase transition.</p

Drivers of Cape Verde archipelagic endemism in keyhole limpets

Oceanic archipelagos are the ideal setting for investigating processes that shape species assemblages. Focusing on keyhole limpets, genera Fissurella and Diodora from Cape Verde Islands, we used an integrative approach combining molecular phylogenetics with ocean transport simulations to infer species distribution patterns and analyse connectivity. Dispersal simulations, using pelagic larval duration and ocean currents as proxies, showed a reduced level of connectivity despite short distances between some of the islands. It is suggested that dispersal and persistence driven by patterns of oceanic circulation favouring self-recruitment played a primary role in explaining contemporary species distributions. Mitochondrial and nuclear data revealed the existence of eight Cape Verde endemic lineages, seven within Fissurella, distributed across the archipelago, and one within Diodora restricted to Boavista. The estimated origins for endemic Fissurella and Diodora were 10.2 and 6.7 MY, respectively. Between 9.5 and 4.5 MY, an intense period of volcanism in Boavista might have affected Diodora, preventing its diversification. Having originated earlier, Fissurella might have had more opportunities to disperse to other islands and speciate before those events. Bayesian analyses showed increased diversification rates in Fissurella possibly promoted by low sea levels during Plio-Pleistocene, which further explain differences in species richness between both genera.FCT - Portuguese Science Foundation [SFRH/BPD/109685/2015, SFRH/BPD/111003/2015]; Norte Portugal Regional Operational Program (NORTE), under the PORTUGAL Partnership Agreement, through the European Regional Development Fund (ERDF) [MARINFO - NORTE-01-0145-FEDER-000031]info:eu-repo/semantics/publishedVersio

Limits on the production of direct photons in 200 A GeV32^{32}S + Au collisions

A search for the production of direct photons in S+Au collisions at 200\cdotA~GeV has been carried out in the CERN-WA80 experiment. For central collisions the measured photon excess at each p_T, averaged over the range 0.5~GeV/c~ \leq p_T \leq 2.5~GeV/c, corresponded to 5.0\% of the total inclusive photon yield with a statistical error of \sigma_{\rm stat}=0.8\% and a systematic error of \sigma_{\rm syst}=5.8\%. Upper limits on the invariant yield for direct photon production at the 90\%~C.L. are presented. Possible implications for the dynamics of high-energy heavy-ion collisions are discussed