A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.     

Leptin receptor action and mechanisms of leptin resistance

The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004     

Giant spin Seebeck effect in a non-magnetic material

The spin Seebeck effect is observed when a thermal gradient applied to a spin-polarized material leads to a spatially varying transverse spin current in an adjacent non-spin-polarized material, where it gets converted into a measurable voltage. It has been previously observed with a magnitude of microvolts per kelvin in magnetically ordered materials, ferromagnetic metals, semiconductors and insulators. Here we describe a signal in a non-magnetic semiconductor (InSb) that has the hallmarks of being produced by the spin Seebeck effect, but is three orders of magnitude larger (millivolts per kelvin). We refer to the phenomenon that produces it as the giant spin Seebeck effect. Quantizing magnetic fields spin-polarize conduction electrons in semiconductors by means of Zeeman splitting, which spin-orbit coupling amplifies by a factor of ～25 in InSb. We propose that the giant spin Seebeck effect is mediated by phonon-electron drag, which changes the electrons' momentum and directly modifies the spin-splitting energy through spin-orbit interactions. Owing to the simultaneously strong phonon-electron drag and spin-orbit coupling in InSb, the magnitude of the giant spin Seebeck voltage is comparable to the largest known classical thermopower values.     

Silicon carbide resonant tuning fork for microsensing applications in high temperature and high G shock environments

We present the fabrication and testing of a silicon carbide(SiC)balanced mass double-ended tuning fork that survives harsh environments without compromising the device strain sensitivity and resolution bandwidth.The device features a material stack that survives corrosive environments and enables high-temperature operation.To perform high-temperature testing,a specialized setup was constructed that allows the tuning fork to be characterized using traditional silicon electronics.The tuning fork has been operated at 600 ℃ in the presence of dry steam for short durations.This tuning fork has also been tested to 64 000 G using a hard-launch,soft-catch shock implemented with a light gas gun.However,the device still has a strain sensitivity of 66 Hz/με and strain resolution of 0.045 με in a 10 kHz bandwidth.As such,this balanced-mass double-ended tuning fork can be used to create a variety of different sensors including strain gauges,accelerometers,gyroscopes,and pressure transducers.Given the adaptable fabrication process flow,this device could be useful to micro-electro-mechanical systems(MEMS) designers creating sensors for a variety of different applications.     

Coherent spin manipulation without magnetic fields in strained semiconductors

A consequence of relativity is that in the presence of an electric field, the spin and momentum states of an electron can be coupled; this is known as spin-orbit coupling. Such an interaction opens a pathway to the manipulation of electron spins within non-magnetic semiconductors, in the absence of applied magnetic fields. This interaction has implications for spin-based quantum information processing and spintronics, forming the basis of various device proposals. For example, the concept of spin field-effect transistors is based on spin precession due to the spin-orbit coupling. Most studies, however, focus on non-spin-selective electrical measurements in quantum structures. Here we report the direct measurement of coherent electron spin precession in zero magnetic field as the electrons drift in response to an applied electric field. We use ultrafast optical techniques to spatiotemporally resolve spin dynamics in strained gallium arsenide and indium gallium arsenide epitaxial layers. Unexpectedly, we observe spin splitting in these simple structures arising from strain in the semiconductor films. The observed effect provides a flexible approach for enabling electrical control over electron spins using strain engineering. Moreover, we exploit this strain-induced field to electrically drive spin resonance with Rabi frequencies of up to approximately 30 MHz.     

Detection of single base substitutions in total genomic DNA

Certain single base substitutions causing genetic diseases or resulting in polymorphisms linked to mutant alleles, alter a restriction enzyme cleavage site and can therefore be detected in total genomic DNA using DNA blots. Many base substitutions do not lead to an altered restriction site, but these can be detected using synthetic oligonucleotides as hybridization probes if the DNA sequence surrounding the base substitution is known. In the case of beta-thalassaemia, where 22 different single base mutations have been identified, a large number of probes would be required for diagnosis. An approach which was used to detect mutations in viral DNA involves the S1 nuclease treatment of heteroduplexes formed between wild-type and mutant DNA. Although certain single base mismatches are cleaved by S1 nuclease (ref. 11 and T. Shenk, personal communication), many other mismatches examined by this procedure are not cleaved (B. Seed, personal communication; R.M.M., unpublished data). Heteroduplexes between mutant and wild-type subgenomic fragments of double-stranded reovirus RNA migrate slower than the corresponding homoduplexes in polyacrylamide gels containing 7 M urea, but it is not known whether this method is applicable to DNA heteroduplexes containing single base mismatches. Here we describe a procedure that involves the electrophoretic separation of DNA heteroduplexes in a well-characterized gel system. We show that four different human beta-thalassaemia alleles with known single base mutations can be detected with as little as 5 micrograms of total genomic DNA. The method should be useful in the localization and diagnosis of mutations associated with genetic diseases.     

Perception of apparent motion by commissurotomy patients

When two spatially separated light spots are flashed in rapid succession, the spot will appear to move between the two locations--an illusion called apparent motion. We have presented this display to callosum-sectioned human patients and found that they could correctly report the temporal order of a simple apparent motion sequence presented across the vertical meridian. Hence, the forebrain commissures are not required for this function.     

Guest Editorial

Systemic Practice and Action Research -