Cutaneous Basophilic Hypersensitivity Response to Fungal Antigens in Guinea Pigs

Guinea pigs infected with Trichophyton mentagrophytes developed a cutaneous fungal lesion and became skin test positive to fungal antigen (trichophytin). The cutaneous fungal lesion, while thought to be a cell-mediated response, differed histologically from the skin test site. Basophils were not demonstrated in biopsies of cutaneous fungal lesions, whereas basophils were numerous in biopsies of trichophytin skin test sites. When sensitization to trichophytin was accomplished by injection of hypha in complete Freund's adjuvant instead of infecting with live fungus, basophils could not be demonstrated in skin test sites. This report demonstrated that guinea pigs could be primed for cutaneous basophilic hypersensitivity (CBH) responses by infection with live fungus

Proto-Linguistic Variation: A Link between Historical Linguistics and Sociolinguistics

Proceedings of the Fifteenth Annual Meeting of the Berkeley Linguistics Society (1989), pp. 91-10

Calcium Regulation of Myosin-I Tension Sensing

AbstractMyo1b is a myosin that is exquisitely sensitive to tension. Its actin-attachment lifetime increases > 50-fold when its working stroke is opposed by 1 pN of force. The long attachment lifetime of myo1b under load raises the question: how are actin attachments that last >50 s in the presence of force regulated? Like most myosins, forces are transmitted to the myo1b motor through a light-chain binding domain that is structurally stabilized by calmodulin, a calcium-binding protein. Thus, we examined the effect of calcium on myo1b motility using ensemble and single-molecule techniques. Calcium accelerates key biochemical transitions on the ATPase pathway, decreases the working-stroke displacement, and greatly reduces the ability of myo1b to sense tension. Thus, calcium provides an effective mechanism for inhibiting motility and terminating long-duration attachments

A double law of comparative judgment for the analysis of preferential choice and similarities data

By virtue of certain modifications in the Law of Comparative Judgment, equations are developed which ( i ) permit the construction of a joint scale of individuals and items, as in the case of attitude measurement, directly from their pair-comparison preferences, and ( ii ) take into account the variable of laterality which is significant for the construction of group preference scales.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45709/1/11336_2005_Article_BF02289712.pd

Single Versus Multi-Center Surgeons\u27 Risk-Adjusted Mitral Valve Repair Procedural Outcomes

The purpose of this study is to explore strategies to improve mitral valve repair (MVr) outcomes. This research explores postoperative outcomes of patients undergoing MVr surgery by single center surgeons versus patients of multicenter surgeons. Specific outcomes of interest include 30-day operative mortality, major operative complications (e.g., deep sternal wound infection, permanent stroke, renal dysfunction requiring dialysis, reoperation, and prolonged ventilation), length of stay, and 30-day readmissions. In brief, the serisk-adjusted outcome rates for surgeons that perform mitral valve repair procedures will be compared for surgeons that operate at a single center [i.e. SC surgeons] versus multiple centers [i.e. MC surgeons]. The overarching study hypothesis is: H(0) There will be no difference in the risk-adjusted outcome rates between surgeons that operate at a single center [i.e. SC surgeons] versus multiple centers [i.e. MC surgeons]. Based on prior research, however, it is anticipated that single center surgeons may have superior outcomes compared to multi-center surgeons

Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum

A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.Chemistry and Chemical Biolog

Tacrolimus for the treatment of fistulas in patients with crohn’s disease: a randomized, placebo-controlled trial

AbstractBackground & Aims:This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas.Methods:The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg · kg−1 · day−1 or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of ≥50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks.Results:Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction.Conclusions:Oral tacrolimus 0.2 mg · kg−1 · day−1 is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated

N-Acetylcholinesterase-Induced Apoptosis in Alzheimer's Disease

Background: Alzheimer’s disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended ‘‘synaptic’ ’ acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena. Methodology and Principal Findings: In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation. Rapid internalization of fluorescently labeled fasciculin-2 to N-AChE-S transfected cells indicated membranal localization. In cultured cell lines, N-AChE-S transfection activated the Tau kinase GSK3, induced Tau hyper-phosphorylation and caused apoptosis. N-AChE-S-induced cell death was suppressible by inhibiting GSK3 or caspases, by enforced overexpression of the anti-apoptotic Bcl2 proteins, or by AChE inhibition or silencing. Moreover, inherent N-AChE-S was upregulated by stressors inducing protein misfolding and calcium imbalances, both characteristic of AD; and in cortical tissues from AD patients, N-AChE-S overexpression coincides with Tau hyper-phosphorylation. Conclusions: Together, these findings attribute an apoptogenic role to N-AChE-S and outline a potential value to ACh

The Arabidopsis Resistance-Like Gene SNC1 Is Activated by Mutations in SRFR1 and Contributes to Resistance to the Bacterial Effector AvrRps4

The SUPPRESSOR OF rps4-RLD1 (SRFR1) gene was identified based on enhanced AvrRps4-triggered resistance in the naturally susceptible Arabidopsis accession RLD. No other phenotypic effects were recorded, and the extent of SRFR1 involvement in regulating effector-triggered immunity was unknown. Here we show that mutations in SRFR1 in the accession Columbia-0 (Col-0) lead to severe stunting and constitutive expression of the defense gene PR1. These phenotypes were temperature-dependent. A cross between srfr1-1 (RLD background) and srfr1-4 (Col-0) showed that stunting was caused by a recessive locus in Col-0. Mapping and targeted crosses identified the Col-0-specific resistance gene SNC1 as the locus that causes stunting. SRFR1 was proposed to function as a transcriptional repressor, and SNC1 is indeed overexpressed in srfr1-4. Interestingly, co-regulated genes in the SNC1 cluster are also upregulated in the srfr1-4 snc1-11 double mutant, indicating that the overexpression of SNC1 is not a secondary effect of constitutive defense activation. In addition, a Col-0 RPS4 mutant showed full susceptibility to bacteria expressing avrRps4 at 24°C but not at 22°C, while RLD susceptibility was not temperature-dependent. The rps4-2 snc1-11 double mutant showed increased, but not full, susceptibility at 22°C, indicating that additional cross-talk between resistance pathways may exist. Intriguingly, when transiently expressed in Nicotiana benthamiana, SRFR1, RPS4 and SNC1 are in a common protein complex in a cytoplasmic microsomal compartment. Our results highlight SRFR1 as a convergence point in at least a subset of TIR-NBS-LRR protein-mediated immunity in Arabidopsis. Based on the cross-talk evident from our results, they also suggest that reports of constitutive resistance phenotypes in Col-0 need to consider the possible involvement of SNC1