296 research outputs found
Three Generations on the Quintic Quotient
A three-generation SU(5) GUT, that is 3x(10+5bar) and a single 5-5bar pair,
is constructed by compactification of the E_8 heterotic string. The base
manifold is the Z_5 x Z_5-quotient of the quintic, and the vector bundle is the
quotient of a positive monad. The group action on the monad and its
bundle-valued cohomology is discussed in detail, including topological
restrictions on the existence of equivariant structures. This model and a
single Z_5 quotient are the complete list of three generation quotients of
positive monads on the quintic.Comment: 19 pages, LaTeX. v2: section on anomaly cancellation adde
Diagnostic examination of the child with urolithiasis or nephrocalcinosis
Urolithiasis and nephrocalcinosis are more frequent in children then currently anticipated, but still remain under- or misdiagnosed in a significant proportion of patients, since symptoms and signs may be subtle or misleading. All children with colicky abdominal pain or macroscopic hematuria should be examined thoroughly for urolithiasis. Also, other, more general, abdominal manifestations can be the first symptoms of renal stones. The patients and their family histories, as well as physical examination, are important initial steps for diagnostic evaluation. Thereafter, diagnostic imaging should be aimed at the location of calculi but also at identification of urinary tract anomalies or acute obstruction due to stone disease. This can often be accomplished by ultrasound examination alone, but sometimes radiological methods such as plain abdominal films or more sensitive non-enhanced computed tomography are necessary. Since metabolic causes are frequent in children, diagnostic evaluation should be meticulous so that metabolic disorders that cause recurrent urolithiasis or even renal failure, such as the primary hyperoxalurias and others, can be ruled out. The stone is not the disease itself; it is only one serious sign! Therefore, thorough and early diagnostic examination is mandatory for every infant and child with the first stone event, or with nephrocalcinosis
Surfactant protein D modulates HIV infection of both T-cells and dendritic cells
Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo
Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes
Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress host defense functions, including generation of proinflammatory mediators, phagocytosis and killing. However, the spatial and kinetic characteristics of cAMP generation in phagocytosing macrophages have yet to be examined. Using a Förster resonance energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP in live macrophages. We detected no difference in bulk intracellular cAMP levels between resting cells and cells actively phagocytosing IgG-opsonized particles. However, analysis with the biosensor revealed a rapid decrease in FRET signal corresponding to a transient burst of cAMP production localized to the forming phagosome. cAMP levels returned to baseline after the particle was internalized. These studies indicate that localized increases in cAMP accompany phagosome formation and provide a framework for a more complete understanding of how cAMP regulates macrophage host defense functions
Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK
The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin
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Ubiquitin sets the timer: impacts on aging and longevity
Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals
Is there adaptation in the ozone mortality relationship: A multi-city case-crossover analysis
<p>Abstract</p> <p>Background</p> <p>Ozone has been associated with daily mortality, mainly in the summer period. Despite the ample literature on adaptation of inflammatory and pulmonary responses to ozone, and the link, in cohort studies, between lung function and mortality risk there has been little done to date to examine the question of adaptation in the acute mortality risk associated with ambient ozone.</p> <p>Methods</p> <p>We applied a case-crossover design in 48 US cities to examine the ozone effect by season, by month and by age groups, particularly focusing on whether there was an adaptation effect.</p> <p>Results</p> <p>We found that the same day ozone effect was highest in summer with a 0.5% (95% CI: 0.38, 0.62) increase in total mortality for 10 ppb increase in 8-hr ozone, whilst the effect decrease to null in autumn and winter. We found higher effects in the months May- July with a 0.46% (95% CI: 0.24, 0.68) increase in total mortality for 10 ppb increase in ozone in June, and a 0.65% (95% CI: 0.47, 0.82) increase in mortality during July. The effect decreased in August and became null in September. We found similar effects from the age group 51–60 up to age 80 and a lower effect in 80 years and older.</p> <p>Conclusion</p> <p>The mortality effects of ozone appear diminished later in the ozone season, reaching the null effect previously reported in winter by September. More work should address this issue and examine the biological mechanism of adaptation.</p
Medical treatment of pediatric urolithiasis
In recent years the incidence of pediatric stone disease has increased several fold, mostly due to hypercalciuria and hypocitraturia. The goal of medical treatment is to protect the patient from formation of new stones and expansion of existing ones. The non-pharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. The pharmacological treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. This review discusses the current options of medical treatment of pediatric urolithiasis
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