On Gravity, Torsion and the Spectral Action Principle

We consider compact Riemannian spin manifolds without boundary equipped with orthogonal connections. We investigate the induced Dirac operators and the associated commutative spectral triples. In case of dimension four and totally anti-symmetric torsion we compute the Chamseddine-Connes spectral action, deduce the equations of motions and discuss critical points.Comment: minor modifications, some further typos fixe

An Insulin-Like Growth Factor-I Receptor Defect Associated with Short Stature and Impaired Carbohydrate Homeostasis in an Italian Pedigree

Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. Methods: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts. Results: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between –1.65 and –2.37 and birth length SDS between –1.78 and –3.08. Their postnatal growth was also impaired, with height SDS between –1.75 and –4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case’s sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity. Conclusion: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism

Passive strain distribution in the interosseous ligament of the forearm: Implications for injury reconstruction

Purpose: For severe forearm injuries such as an Essex-Lopresti fracture-dislocation, functional reconstruction necessitates repair of the interosseous ligament (IOL) to restore normal load sharing between the radius and ulna. Locating or tensioning such a reconstruction improperly can lead to abnormal load sharing and/or restriction of forearm rotation. The normal IOL strains should indicate the proper location of reconstruction grafts and the proper forearm rotation for tensioning the grafts. The objective of this study was to quantify the passive strain distribution of the IOL of the forearm with passive rotation of the forearm throughout the range of motion. Methods: The 3-dimensional motions of the radius with respect to the ulna were measured throughout forearm rotation in 10 cadaveric forearms by using an instrumented spatial linkage. From the bone motions and ligament insertion site geometry from dissection and computed tomographic scanning, insertion site motions were determined and used to calculate changes in ligament fiber lengths. Results: The measured strain distribution in the IOL was nonuniform and varied with forearm rotation. The overall magnitude of IOL strain was found to be greatest in supination and smallest in pronation. In supination the strains varied across fibers with strains being greatest in the distal fibers and lowest in the proximal fibers. Strains in neutral rotation were uniform across fibers. Although fibers were generally slack in pronation proximal fibers were less slack than distal fibers. Conclusions: The results of this study indicate that fiber strains in the IOL vary from proximal to distal and depend on forearm rotation. Our data suggest that to prevent restriction of forearm rotation all grafts should be tensioned in supination, where measured strains were generally highest. Our data also suggest that a 2-bundle IOL reconstruction may be necessary for proper load transfer between the radius and ulna in both supination and pronation. Copyright (C) 2004 by the American Society for Surgery of the Hand

A method for measuring joint kinematics designed for accurate registration of kinematic data to models constructed from CT data

A method for measuring three-dimensional kinematics that incorporates the direct cross-registration of experimental kinematics with anatomic geometry from Computed Tomography (CT) data has been developed. Plexiglas registration blocks were attached to the bones of interest and the specimen was CT scanned. Computer models of the bone surface were developed from the CT image data. Determination of discrete kinematics was accomplished by digitizing three pre-selected contiguous surfaces of each registration block using a three-dimensional point digitization system. Cross-registration of bone surface models from the CT data was accomplished by identifying the registration block surfaces within the CT images. Kinematics measured during a biomechanical experiment were applied to the computer models of the bone surface. The overall accuracy of the method was shown to be at or below the accuracy of the digitization system used. For this experimental application, the accuracy was better than +/-0.l mm for position and 0.1 degrees for orientation for linkage digitization and better than +/- 0.2 mm and +/- 0.2 degrees for CT digitization. Surface models of the radius and ulna were constructed from CT data, as an example application. Kinematics of the bones were measured for simulated forearm rotation. Screw-displacement axis analysis showed 0.1 mm (proximal) translation of the radius (with respect to the ulna) from supination to neutral (85.2 degrees rotation) and 1.4 mm (proximal) translation from neutral to pronation (65.3 degrees rotation). The motion of the radius with respect to the ulna was displayed using the surface models. This methodology is a useful tool for the measurement and application of rigid-body kinematics to computer models. (C) 2001 Elsevier Science Ltd. All rights reserved

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation

. This work was supported by funding from NIH NICHHD (R01HD078592 to V.H.), NIH NICHHD (1K23HD073351 to A.D.), and a Junior Research grant by the Medical Faculty of the University of Leipzig (to D.R.). M.T.D. receives funding from the Great Ormond Street Hospital Children’s Charity (GOSHCC)

A Naturally Occurring Polymorphism at Drosophila melanogaster Lim3 Locus, a Homolog of Human LHX3/4, Affects Lim3 Transcription and Fly Lifespan

Lim3 encodes an RNA polymerase II transcription factor with a key role in neuron specification. It was also identified as a candidate gene that affects lifespan. These pleiotropic effects indicate the fundamental significance of the potential interplay between neural development and lifespan control. The goal of this study was to analyze the causal relationships between Lim3 structural variations, and gene expression and lifespan changes, and to provide insights into regulatory pathways controlling lifespan. Fifty substitution lines containing second chromosomes from a Drosophila natural population were used to analyze the association between lifespan and sequence variation in the 5′-regulatory region, and first exon and intron of Lim3A, in which we discovered multiple transcription start sites (TSS). The core and proximal promoter organization for Lim3A and a previously unknown mRNA named Lim3C were described. A haplotype of two markers in the Lim3A regulatory region was significantly associated with variation in lifespan. We propose that polymorphisms in the regulatory region affect gene transcription, and consequently lifespan. Indeed, five polymorphic markers located within 380 to 680 bp of the Lim3A major TSS, including two markers associated with lifespan variation, were significantly associated with the level of Lim3A transcript, as evaluated by real time RT-PCR in embryos, adult heads, and testes. A naturally occurring polymorphism caused a six-fold change in gene transcription and a 25% change in lifespan. Markers associated with long lifespan and intermediate Lim3A transcription were present in the population at high frequencies. We hypothesize that polymorphic markers associated with Lim3A expression are located within the binding sites for proteins that regulate gene function, and provide general rather than tissue-specific regulation of transcription, and that intermediate levels of Lim3A expression confer a selective advantage and longer lifespan