353 research outputs found
Techniques for the study of singularities with applications to resolution of 2-dimensional schemes
We give an overview of invariants of algebraic singularities over perfect
fields. We then show how they lead to a synthetic proof of embedded resolution
of singularities of 2-dimensional schemes.Comment: 26 pages; minor changes have been adde
Log canonical thresholds of Del Pezzo Surfaces in characteristic p
The global log canonical threshold of each non-singular complex del Pezzo
surface was computed by Cheltsov. The proof used Koll\'ar-Shokurov's
connectedness principle and other results relying on vanishing theorems of
Kodaira type, not known to be true in finite characteristic.
We compute the global log canonical threshold of non-singular del Pezzo
surfaces over an algebraically closed field. We give algebraic proofs of
results previously known only in characteristic . Instead of using of the
connectedness principle we introduce a new technique based on a classification
of curves of low degree. As an application we conclude that non-singular del
Pezzo surfaces in finite characteristic of degree lower or equal than are
K-semistable.Comment: 21 pages. Thorough rewrite following referee's suggestions. To be
published in Manuscripta Mathematic
Evidence of CO2-induced progressive cooling of the middle atmosphere derived from radio observations
Reflection heights of low frequency radio waves in midlatitude summer, which are closely associated with the neutral atmosphere isobaric level of 0.0052 hPa, exhibit a statistically significant downgoing trend from 1962 to 1987. This indicates a systematic decrease of air pressure at 80 km height by 10.3 plus or minus 4.9 percent over this period, to be regarded as a sufficient evidence of a true signal of progressive cooling of the middle atmosphere, expected with the growing content of CO2 and other greenhouse bases in the atmosphere. It is quantitatively consistent with a temperature decrease at the stratopause by about 4 K, as predicted by the recent model of interactive greenhouse and ozone processes of Brasseur and de Rudder (1987)
Sequence learning in Associative Neuronal-Astrocytic Network
The neuronal paradigm of studying the brain has left us with limitations in
both our understanding of how neurons process information to achieve biological
intelligence and how such knowledge may be translated into artificial
intelligence and its most brain-derived branch, neuromorphic computing.
Overturning our fundamental assumptions of how the brain works, the recent
exploration of astrocytes is revealing that these long-neglected brain cells
dynamically regulate learning by interacting with neuronal activity at the
synaptic level. Following recent experimental evidence, we designed an
associative, Hopfield-type, neuronal-astrocytic network and analyzed the
dynamics of the interaction between neurons and astrocytes. We show that
astrocytes were sufficient to trigger transitions between learned memories in
the neuronal component of the network. Further, we mathematically derived the
timing of the transitions that was governed by the dynamics of the
calcium-dependent slow-currents in the astrocytic processes. Overall, we
provide a brain-morphic mechanism for sequence learning that is inspired by,
and aligns with, recent experimental findings. To evaluate our model, we
emulated astrocytic atrophy and showed that memory recall becomes significantly
impaired after a critical point of affected astrocytes was reached. This
brain-inspired and brain-validated approach supports our ongoing efforts to
incorporate non-neuronal computing elements in neuromorphic information
processing.Comment: 8 pages, 5 figure
Theory of Interaction of Memory Patterns in Layered Associative Networks
A synfire chain is a network that can generate repeated spike patterns with
millisecond precision. Although synfire chains with only one activity
propagation mode have been intensively analyzed with several neuron models,
those with several stable propagation modes have not been thoroughly
investigated. By using the leaky integrate-and-fire neuron model, we
constructed a layered associative network embedded with memory patterns. We
analyzed the network dynamics with the Fokker-Planck equation. First, we
addressed the stability of one memory pattern as a propagating spike volley. We
showed that memory patterns propagate as pulse packets. Second, we investigated
the activity when we activated two different memory patterns. Simultaneous
activation of two memory patterns with the same strength led the propagating
pattern to a mixed state. In contrast, when the activations had different
strengths, the pulse packet converged to a two-peak state. Finally, we studied
the effect of the preceding pulse packet on the following pulse packet. The
following pulse packet was modified from its original activated memory pattern,
and it converged to a two-peak state, mixed state or non-spike state depending
on the time interval
NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy
Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity.
Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low.
Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes
Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport
Pyocin S5 (PyoS5) is a potent protein bacteriocin that eradicates the human pathogen Pseudomonas aeruginosa in animal infection models, but its import mechanism is poorly understood. Here, using crystallography, biophysical and biochemical analyses, and live-cell imaging, we define the entry process of PyoS5 and reveal links to the transport mechanisms of other bacteriocins. In addition to its C-terminal pore-forming domain, elongated PyoS5 comprises two novel tandemly repeated kinked 3-helix bundle domains that structure-based alignments identify as key import domains in other pyocins. The central domain binds the lipid-bound common polysaccharide antigen, allowing the pyocin to accumulate on the cell surface. The N-terminal domain binds the ferric pyochelin transporter FptA while its associated disordered region binds the inner membrane protein TonB1, which together drive import of the bacteriocin across the outer membrane. Finally, we identify the minimal requirements for sensitizing Escherichia coli toward PyoS5, as well as other pyocins, and suggest that a generic pathway likely underpins the import of all TonB-dependent bacteriocins across the outer membrane of Gram-negative bacteria
The Spectrin Cytoskeleton Is Crucial for Adherent and Invasive Bacterial Pathogenesis
Various enteric bacterial pathogens target the host cell cytoskeletal machinery as a crucial event in their pathogenesis. Despite thorough studies detailing strategies microbes use to exploit these components of the host cell, the role of the spectrin-based cytoskeleton has been largely overlooked. Here we show that the spectrin cytoskeleton is a host system that is hijacked by adherent (Entropathogenic Escherichia coli [EPEC]), invasive triggering (Salmonella enterica serovar Typhimurium [S. Typhimurium]) and invasive zippering (Listeria monocytogenes) bacteria. We demonstrate that spectrin cytoskeletal proteins are recruited to EPEC pedestals, S. Typhimurium membrane ruffles and Salmonella containing vacuoles (SCVs), as well as sites of invasion and comet tail initiation by L. monocytogenes. Spectrin was often seen co-localizing with actin filaments at the cell periphery, however a disconnect between the actin and spectrin cytoskeletons was also observed. During infections with S. Typhimurium ΔsipA, actin-rich membrane ruffles at characteristic sites of bacterial invasion often occurred in the absence of spectrin cytoskeletal proteins. Additionally, early in the formation of L. monocytogenes comet tails, spectrin cytoskeletal elements were recruited to the surface of the internalized bacteria independent of actin filaments. Further studies revealed the presence of the spectrin cytoskeleton during SCV and Listeria comet tail formation, highlighting novel cytoplasmic roles for the spectrin cytoskeleton. SiRNA targeted against spectrin and the spectrin-associated proteins severely diminished EPEC pedestal formation as well as S. Typhimurium and L. monocytogenes invasion. Ultimately, these findings identify the spectrin cytoskeleton as a ubiquitous target of enteric bacterial pathogens and indicate that this cytoskeletal system is critical for these infections to progress
Septins Regulate Bacterial Entry into Host Cells
Background: Septins are conserved GTPases that form filaments and are required in many organisms for several processes including cytokinesis. We previously identified SEPT9 associated with phagosomes containing latex beads coated with the Listeria surface protein InlB. Methodology/Principal Findings: Here, we investigated septin function during entry of invasive bacteria in non-phagocytic mammalian cells. We found that SEPT9, and its interacting partners SEPT2 and SEPT11, are recruited as collars next to actin at the site of entry of Listeria and Shigella. SEPT2-depletion by siRNA decreased bacterial invasion, suggesting that septins have roles during particle entry. Incubating cells with InlB-coated beads confirmed an essential role for SEPT2. Moreover, SEPT2-depletion impaired InlB-mediated stimulation of Met-dependent signaling as shown by FRET. Conclusions/Significance: Together these findings highlight novel roles for SEPT2, and distinguish the roles of septin an
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 CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, JesĂşs Sebastián. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂa y EmbriologĂa de Mendoza Dr. Mario H. Burgos; Argentin
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