University of Iowa

About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.

Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein

Abstract: Aeroallergy results frommaladaptiveimmuneresponses toubiquitous, otherwise innocuous environmental proteins 1 . Although the proteinstargetedbyaeroallergicresponses representa tinyfraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon—the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house-dust-mite allergen, Derp2, has structural homology with MD-2 (also known as LY96), the lipopolysaccharide (LPS)-binding component of the Toll-like receptor (TLR) 4 signalling complex 2–4 . HereweshowthatDerp2alsohasfunctionalhomology,facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS-driven TLR4 signalling in the absence of MD-2. Mirroring this, airway sensitization and challenge with Derp2 led to experimental allergic asthma in wild type and MD-2-deficient, butnotTLR4-deficient,mice.OurresultsindicatethatDerp2tends to be targeted by adaptive immune responses because of its autoadjuvant properties. The fact that other members of the MD-2-like lipid-binding family are allergens, and that most defined major allergens are thought to be lipid-binding proteins 5 ,s uggests that intrinsicadjuvantactivitybysuchproteinsandtheiraccompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity. Although the potential biological significance of several allergens having protease activity has received experimental attention 5,6 , cogent mechanistic hypotheses for why most aeroallergens have a propensitytogeneratemaladaptiveeffectorT-cellresponsesarelacking. TLRs, receptors for conserved microbial structures, have a critical role in the controlling initiation and class specification of adaptive immune responses by antigen-presenting cells (APCs) 7 . Exogenous antigen presentation by APCs in the absence of direct TLR stimulation generally leads to tolerance 8 . Moreover, efficient generation of effector T-cell responses by APCs is dependent on thepresence ofTLRligandsinthephagosomecontaining theantigen being presented 9 . House dust mites are a major source of aeroallergens for patients with allergic asthma 10 . Concentrated in mite faecal pellets 11 , the

Strength increases from the motor program: comparison of training with maximal voluntary and imagined muscle contractions.

Abstract: 1. This study addressed potential neural mechanisms of the strength increase that occur before muscle hypertrophy. In particular we examined whether such strength increases may result from training-induced changes in voluntary motor programs. We compared the maximal voluntary force production after a training program of repetitive maximal isometric muscle contractions with force output after a training program that did not involve repetitive activation of muscle; that is, after mental training. 2. Subjects trained their left hypothenar muscles for 4 wk, five sessions per week. One group produced repeated maximal isometric contractions of the abductor muscles of the fifth digit's metacarpophalangeal joint. A second group imagined producing these same, effortful isometric contractions. A third group did not train their fifth digit. Maximal abduction force, flexion/extension force and electrically evoked twitch force (abduction) of the fifth digit were measured along with maximal integrated electromyograms (EMG) of the hypothenar muscles from both hands before and after training. 3. Average abduction force of the left fifth digit increased 22% for the Imagining group and 30% for the Contraction group. The mean increase for the Control group was 3.7%. 4. The maximal abduction force of the right (untrained) fifth digit increased significantly in both the Imagining and Contraction groups after training (10 and 14%, respectively), but not in the Control group (2.3%). These results are consistent with previous studies of training effects on contralateral limbs. 5. The abduction twitch force evoked by supramaximal electrical stimulations of the ulnar nerve was unchanged in all three groups after training, consistent with an absence of muscle hypertrophy. The maximal force of the left great toe extensors for individual subjects remained unchanged after training, which argues against strength increases due to general increases in effort level. 6. Increases in abduction and flexion forces of the fifth digit were poorly correlated in subjects of both training groups. The fifth finger abduction force and the hypothenar integrated EMG increases were not well correlated in these subjects either. Together these results indicate that training-induced changes of synergist and antagonist muscle activation patterns may have contributed to force increases in some of the subjects. 7. Strength increases can be achieved without repeated muscle activation. These force gains appear to result from practice effects on central motor programming/planning. The results of these experiments add to existing evidence for the neural origin of strength increases that occur before muscle hypertrophy.

Functional annotation of a full-length mouse cDNA collection

Abstract: The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.