98 research outputs found
Fighting a losing battle: Vigorous immune response countered by pathogen suppression of host defenses in the chytridiomycosis-susceptible frog Atelopus zeteki
The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist
at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly
understood: differences in host immune responses have been proposed, yet previous studies suggest a lack
of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutchmates
of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found
significant changes in expression of numerous genes involved in innate and inflammatory responses in
infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune
responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility
complex genes. In addition, fungal-killing genes had significantly greater expression in frogs
previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases.
However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated
by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings,suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus
More than skin deep: Functional genomic basis for resistance to Amphibian Chytridiomycosis
The amphibian-killing chytrid fungus Batrachochytriumdendrobatidis (Bd) is one of themost generalist pathogens known, capable of
infecting hundreds of species globally and causing widespread population declines and extinctions. However, some host species are
seemingly unaffected by Bd, tolerating or clearing infections without clinical signs of disease. Variation in host immune responses is
commonly evoked for these resistant or tolerant species, yet to date,we have nodirect comparisonof amphibian species responses to
infection at the level of gene expression. In this study,we challenged four CentralAmerican frog species that vary in Bd susceptibility,
with a sympatric virulent strain of the pathogen. We compared skin and spleen orthologous gene expression using differential
expression tests and coexpression gene network analyses.Wefound that resistant species have reduced skin inflammatory responses
andincreased expressionofgenes involved inskin integrity. Incontrast, onlyhighly susceptible species exhibited suppressionof splenic
T-cell genes. We conclude that resistance to chytridiomycosis may be related to a species’ ability to escape the immunosuppressive
activity of the fungus. Moreover, our results indicate that within-species differences in splenic proteolytic enzyme gene expression
may contribute to intraspecific variation in survival. This first comparison of amphibian functional immunogenomic architecture in
response to Bd provides insights into key genetic mechanisms underlying variation in disease outcomes among amphibian species
Non-perturbative Landau gauge and infrared critical exponents in QCD
We discuss Faddeev-Popov quantization at the non-perturbative level and show
that Gribov's prescription of cutting off the functional integral at the Gribov
horizon does not change the Schwinger-Dyson equations, but rather resolves an
ambiguity in the solution of these equations. We note that Gribov's
prescription is not exact, and we therefore turn to the method of stochastic
quantization in its time-independent formulation, and recall the proof that it
is correct at the non-perturbative level. The non-perturbative Landau gauge is
derived as a limiting case, and it is found that it yields the Faddeev-Popov
method in Landau gauge with a cut-off at the Gribov horizon, plus a novel term
that corrects for over-counting of Gribov copies inside the Gribov horizon.
Non-perturbative but truncated coupled Schwinger-Dyson equations for the gluon
and ghost propagators and in Landau gauge are solved
asymptotically in the infrared region. The infrared critical exponents or
anomalous dimensions, defined by and are obtained in space-time dimensions . Two
possible solutions are obtained with the values, in dimensions, , or .Comment: 26 pages. Modified 2.25.02 to update references and to clarify
Introduction and Conclusio
Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy
Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These include targeting the level of estrogen, blocking estrogen action at the ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is limited by either intrinsic or acquired resistance. Identifying the factors and pathways responsible for sensitivity and resistance remains a challenge in improving the treatment of breast cancer. With a better understanding of coordinated action of ER, its coregulatory factors, and the influence of other intracellular signaling cascades, improvements in breast cancer therapy are emerging
Edible Halophytes and Halo-Tolerant Species in Apulia Region (Southeastern Italy): Biogeography, Traditional Food Use and Potential Sustainable Crops
The Mediterranean basin is rich in wild edible species which have been used for food and medicinal purposes by humans throughout the centuries. Many of these species can be found near coastal areas and usually grow under saline conditions, while others can adapt in various harsh conditions including high salinity. Many of these species have a long history of gathering from the wild as a source of food. The aim of this contribution is an overview on the most important halophyte species (Salicornia sp. pl., Arthrocaulon macrostachyum (Moric.) Piirainen & G. Kadereit, Soda inermis Fourr., Cakile maritima Scop., Crithmum maritimum L., Reichardia picroides (L.) Roth., Silene vulgaris (Moench) Garcke subsp. tenoreana (Colla) Soldano & F. Conti, Allium commutatum Guss., Beta vulgaris L. subsp. maritima (L.) Arcang., Capparis spinosa L.) that traditionally have been gathered by rural communities in southern Italy, with special interest on their ecology and distribution, traditional uses, medicinal properties, marketing and early attempts of cultivation. It is worth noting that these species have an attractive new cash crop for marsh marginal lands
FOLFIRI with or without Celecoxib in avanced colorectal cancer: a randomized phase II study of the Gruppo Oncologico dell’ Italia Meridionale (GOIM)
Background: The aim of the study was to verify the efficacy and safety of the addition of celecoxib to FOLFIRI
combination therapy in patients affected by advanced colorectal cancer.
Patients and methods: Eighty-one chemotherapy-naı¨ve patients entered in this randomized phase II trial of the
GOIM (protocol no. 2301). Patients were randomized to receive FOLFIRI regimen (arm A): irinotecan 180 mg/m2
on day 1 with LV5FU2 regimen (LV at 100 mg/m2 administered as a 2-h infusion before FU at 400 mg/m2 as an
intravenous bolus injection, and FU at 600 mg/m2 as a 22-h infusion immediately after 5-FU bolus injection on
day 1 and 2); or FOLFIRI plus celecoxib 400 mg twice daily for 14 days (arm B). Both treatments were repeated
every 2 weeks.
Results: Seventy-seven patients (38 in arm A and 39 in arm B) were evaluable for response. The overall response rate
was 41% in arm A (95% CI 27% to 57%) and 35% in arm B (95% CI 20% to 50%). When only assessable patients
were analyzed, overall response rate was 45% in arm A (95% CI 29% to 61%) and 36% in arm B (95% CI 21%
to 51%). Median time to progression, median duration of response and survival were, respectively, 8 months,
9 months and 16 months in arm A, and 7 months, 9 months and 19 months in arm B. All patients were evaluable
for toxicity, which was globally mild in both arms; grade 3–4 toxicity was uncommon, and gastrointestinal
disturbances were the most common.
Conclusions: FOLFIRI regimen is effective and well-tolerated as a first-line treatment in patients with advanced
colorectal cancer. The addition of celecoxib to FOLFIRI regimen does not improve results
PLASMA PROLACTIN LEVELS IN THE INFERIOR PETROSAL SINUSES IN VARIOUS PITUITARY DISORDERS DURING PERIHYPOPHYSEAL PHLEBOGRAPHY
A rare case of multiple sclerosis and McArdle disease
McArdle disease is the most common metabolic myopathy with autosomal recessive inheritance due to mutations in the gene PYGM encoding myophosphorylase. In this report, we describe the first case of a patient affected by MS and McArdle diseas
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