Planar manipulation of magneto-tactic bacteria using unidirectional magnetic fields

We show for the first time that an alternating unidirectional magnetic field generated by a magnetic erase head allows planar manipulation of magneto-tactic bacteria (MTB), and is not restricted to parallel directions only. We used squared-shaped magnetic fields of approximately 4 mT while sweeping from 0.25 to 10 Hz, and found that at frequencies of over 3 Hz the mean orthogonal velocity becomes constant. The erase head offers a significant reduction in size and complexity over conventional manipulators

Co-Evolution of quasispecies: B-cell mutation rates maximize viral error catastrophes

Co-evolution of two coupled quasispecies is studied, motivated by the competition between viral evolution and adapting immune response. In this co-adaptive model, besides the classical error catastrophe for high virus mutation rates, a second ``adaptation-'' catastrophe occurs, when virus mutation rates are too small to escape immune attack. Maximizing both regimes of viral error catastrophes is a possible strategy for an optimal immune response, reducing the range of allowed viral mutation rates to a minimum. From this requirement one obtains constraints on B-cell mutation rates and receptor lengths, yielding an estimate of somatic hypermutation rates in the germinal center in accordance with observation.Comment: 4 pages RevTeX including 2 figure

The Error and Repair Catastrophes: A Two-Dimensional Phase Diagram in the Quasispecies Model

This paper develops a two gene, single fitness peak model for determining the equilibrium distribution of genotypes in a unicellular population which is capable of genetic damage repair. The first gene, denoted by $\sigma_{via}$, yields a viable organism with first order growth rate constant $k > 1$ if it is equal to some target ``master'' sequence $\sigma_{via, 0}$. The second gene, denoted by $\sigma_{rep}$, yields an organism capable of genetic repair if it is equal to some target ``master'' sequence $\sigma_{rep, 0}$. This model is analytically solvable in the limit of infinite sequence length, and gives an equilibrium distribution which depends on \mu \equiv L\eps , the product of sequence length and per base pair replication error probability, and \eps_r , the probability of repair failure per base pair. The equilibrium distribution is shown to exist in one of three possible ``phases.'' In the first phase, the population is localized about the viability and repairing master sequences. As \eps_r exceeds the fraction of deleterious mutations, the population undergoes a ``repair'' catastrophe, in which the equilibrium distribution is still localized about the viability master sequence, but is spread ergodically over the sequence subspace defined by the repair gene. Below the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds \ln k/\eps_r , while above the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds $\ln k/f_{del}$, where $f_{del}$ denotes the fraction of deleterious mutations.Comment: 14 pages, 3 figures. Submitted to Physical Review

Meson screening masses from lattice QCD with two light and the strange quark

We present results for screening masses of mesons built from light and strange quarks in the temperature range of approximately between 140 MeV to 800 MeV. The lattice computations were performed with 2+1 dynamical light and strange flavors of improved (p4) staggered fermions along a line of constant physics defined by a pion mass of about 220 MeV and a kaon mass of 500 MeV. The lattices had temporal extents Nt = 4, 6 and 8 and aspect ratios of Ns / Nt \geq 4. At least up to a temperature of 140 MeV the pseudo-scalar screening mass remains almost equal to the corresponding zero temperature pseudo-scalar (pole) mass. At temperatures around 3Tc (Tc being the transition temperature) the continuum extrapolated pseudo-scalar screening mass approaches very close to the free continuum result of 2 \pi T from below. On the other hand, at high temperatures the vector screening mass turns out to be larger than the free continuum value of 2 \pi T. The pseudo-scalar and the vector screening masses do not become degenerate even for a temperature as high as 4Tc. Using these mesonic spatial correlation functions we have also investigated the restoration of chiral symmetry and the effective restoration of the axial symmetry. We have found that the vector and the axial-vector screening correlators become degenerate, indicating chiral symmetry restoration, at a temperature which is consistent with the QCD transition temperature obtained in previous studies. On the other hand, the pseudo-scalar and the scalar screening correlators become degenerate only at temperatures larger than 1.3Tc, indicating that the effective restoration of the axial symmetry takes place at a temperature larger than the QCD transition temperature.Comment: Published versio

The BRCT Domain of PARP-1 Is Required for Immunoglobulin Gene Conversion

During affinity maturation, genomic integrity is maintained through specific targeting of DNA mutations. The DNA damage sensor PARP-1 helps determine whether a DNA lesion results in faithful or mutagenic repair

The Schnitzler syndrome

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections

Lipoxygenases and Poly(ADP-Ribose) Polymerase in Amyloid Beta Cytotoxicity

The 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the amyloid β (Aβ) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human Aβ precursor protein. Different levels of Aβ secretion and free radicals formation characterize these cells. The results demonstrated a relationship between the Aβ levels and LOX protein expression and activity. High Aβ concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-κB into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. We suggested that AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70–80% of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding non-treated cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in Aβ toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies

Salmonella-Induced Mucosal Lectin RegIIIβ Kills Competing Gut Microbiota

Intestinal inflammation induces alterations of the gut microbiota and promotes overgrowth of the enteric pathogen Salmonella enterica by largely unknown mechanisms. Here, we identified a host factor involved in this process. Specifically, the C-type lectin RegIIIβ is strongly upregulated during mucosal infection and released into the gut lumen. In vitro, RegIIIβ kills diverse commensal gut bacteria but not Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium). Protection of the pathogen was attributable to its specific cell envelope structure. Co-infection experiments with an avirulent S. Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease. These data suggest that RegIIIβ production by the host can promote S. Typhimurium infection by eliminating inhibitory gut microbiota

Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis

Cutaneous lesions of the external ear

Skin diseases on the external aspect of the ear are seen in a variety of medical disciplines. Dermatologists, othorhinolaryngologists, general practitioners, general and plastic surgeons are regularly consulted regarding cutaneous lesions on the ear