78 research outputs found
Critical dimensions for random walks on random-walk chains
The probability distribution of random walks on linear structures generated
by random walks in -dimensional space, , is analytically studied
for the case . It is shown to obey the scaling form
, where is
the density of the chain. Expanding in powers of , we find that
there exists an infinite hierarchy of critical dimensions, ,
each one characterized by a logarithmic correction in . Namely, for
, ; for ,
; for , ; for , ; for , , {\it etc.\/} In particular, for
, this implies that the temporal dependence of the probability density of
being close to the origin .Comment: LATeX, 10 pages, no figures submitted for publication in PR
Bottom pressure signals at the TAG deep-sea hydrothermal field : evidence for short-period, flow-induced ground deformation
Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 36 (2009): L19301, doi:10.1029/2009GL040006.Bottom pressure measurements acquired from the TAG hydrothermal field on the Mid-Atlantic Ridge (26°N) contain clusters of narrowband spectral peaks centered at periods from 22 to 53.2 minutes. The strongest signal at 53.2 min corresponds to 13 mm of water depth variation. Smaller, but statistically significant, signals were also observed at periods of 22, 26.5, 33.4, and 37.7 min (1â4 mm amplitude). These kinds of signals have not previously been observed in the ocean, and they appear to represent vertical motion of the seafloor in response to hydrothermal flow - similar in many ways to periodic terrestrial geysers. We demonstrate that displacements of 13 mm can be produced by relatively small flow-induced pressures (several kPa) if the source region is less than âŒ100 m below the seafloor. We suggest that the periodic nature of the signals results from a non-linear relationship between fluid pore pressure and crustal permeability
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Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery
Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumor cells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and composition and structure of the lytic granules. Here, using a proteomic approach we identified a panel of putative cytotoxic granule proteins, including some already known granule constituents and novel proteins that contribute to regulate the CTL lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous immune regulatory lectin, as an integral component of the secretory granule machinery and unveil the unexpected function of this lectin in regulating CTL killing activity. Mechanistic studies revealed the ability of Gal1 to control the non-secretory lytic pathway by influencing FasâFas ligand interactions. This study offers new insights on the composition of the cytotoxic granule machinery, highlighting the dynamic cross talk between secretory and non-secretory pathways in controlling CTL lytic function
Strong Host-Feeding Preferences of the Vector Triatoma infestans Modified by Vector Density: Implications for the Epidemiology of Chagas Disease
Chagas disease is a complex zoonosis with more than 150 mammalian host species, nearly a dozen blood-sucking triatomine species as main vectors, and 9â11 million people infected with Trypanosoma cruzi (its causal agent) in the Americas. Triatoma infestans, a highly domesticated species and one of the main vectors, feeds more often on domestic animals than on humans in northern Argentina. The question of whether there are host-feeding preferences among dogs, cats, and chickens is crucial to estimating transmission risks and predicting the effects of control tactics targeting them. This article reports the first host choice experiments of triatomine bugs conducted in small huts under natural conditions. The results demonstrate that T. infestans consistently preferred dogs to chickens or cats, with host shifts occurring more frequently at higher vector densities. Combined with earlier findings showing that dogs have high infection rates, are highly infectious, and have high contact rates with humans and domestic bugs, our results reinforce the role of dogs as the key reservoirs of T. cruzi. The strong bug preference for dogs can be exploited to target dogs with topical lotions or insecticide-impregnated collars to turn them into baited lethal traps or use them as transmission or infestation sentinels
Exploiting antitumor immunity to overcome relapse and improve remission duration
Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patientâs lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patientâs own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinibâs effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-Îł-producing-CD8+, -CD4+, -NK cell, and IFN-Îł-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types
Caenorhabditis elegans N-glycan Core ÎČ-galactoside Confers Sensitivity towards Nematotoxic Fungal Galectin CGL2
The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a GalÎČ1,4Fucα1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the GalÎČ1,4Fucα1,6GlcNAc trisaccharide at 1.5 Ă
resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms
Canalization of Gene Expression and Domain Shifts in the Drosophila Blastoderm by Dynamical Attractors
The variation in the expression patterns of the gap genes in the blastoderm of
the fruit fly Drosophila melanogaster reduces over time as a
result of cross regulation between these genes, a fact that we have demonstrated
in an accompanying article in PLoS Biology (see Manu et al.,
doi:10.1371/journal.pbio.1000049). This biologically essential process is an
example of the phenomenon known as canalization. It has been suggested that the
developmental trajectory of a wild-type organism is inherently stable, and that
canalization is a manifestation of this property. Although the role of gap genes
in the canalization process was established by correctly predicting the response
of the system to particular perturbations, the stability of the developmental
trajectory remains to be investigated. For many years, it has been speculated
that stability against perturbations during development can be described by
dynamical systems having attracting sets that drive reductions of volume in
phase space. In this paper, we show that both the reduction in variability of
gap gene expression as well as shifts in the position of posterior gap gene
domains are the result of the actions of attractors in the gap gene dynamical
system. Two biologically distinct dynamical regions exist in the early embryo,
separated by a bifurcation at 53% egg length. In the anterior region,
reduction in variation occurs because of stability induced by point attractors,
while in the posterior, the stability of the developmental trajectory arises
from a one-dimensional attracting manifold. This manifold also controls a
previously characterized anterior shift of posterior region gap domains. Our
analysis shows that the complex phenomena of canalization and pattern formation
in the Drosophila blastoderm can be understood in terms of the
qualitative features of the dynamical system. The result confirms the idea that
attractors are important for developmental stability and shows a richer variety
of dynamical attractors in developmental systems than has been previously
recognized
Classification of current anticancer immunotherapies
During the past decades, anticancer immunotherapy has evolved from a promising
therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are
now approved by the US Food and Drug Administration and the European Medicines
Agency for use in cancer patients, and many others are being investigated as standalone
therapeutic interventions or combined with conventional treatments in clinical
studies. Immunotherapies may be subdivided into âpassiveâ and âactiveâ based on
their ability to engage the host immune system against cancer. Since the anticancer
activity of most passive immunotherapeutics (including tumor-targeting monoclonal
antibodies) also relies on the host immune system, this classification does not properly
reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer
immunotherapeutics can be classified according to their antigen specificity. While some
immunotherapies specifically target one (or a few) defined tumor-associated antigen(s),
others operate in a relatively non-specific manner and boost natural or therapy-elicited
anticancer immune responses of unknown and often broad specificity. Here, we propose
a critical, integrated classification of anticancer immunotherapies and discuss the clinical
relevance of these approaches
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15â20 July 2017
This work was produced as part of the activities of FAPESP Research,\ud
Disseminations and Innovation Center for Neuromathematics (grant\ud
2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud
FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud
supported by a CNPq fellowship (grant 306251/2014-0)
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