First harmonic measurements of the spin Seebeck effect

We present measurements of the spin Seebeck effect (SSE) by a technique that combines alternating currents (AC) and direct currents (DC). The method is applied to a ferrimagnetic insulator/heavy metal bilayer, Y$_3$Fe$_5$O$_{12}$(YIG)/Pt. Typically, SSE measurements use an AC current to produce an alternating temperature gradient and measure the voltage generated by the inverse spin-Hall effect in the heavy metal at twice the AC frequency. Here we show that when Joule heating is associated with AC and DC bias currents, the SSE response occurs at the frequency of the AC current drive and can be larger than the second harmonic SSE response. We compare the first and second harmonic responses and show that they are consistent with the SSE. The field dependence of the voltage response is used to characterize the damping-like and field-like torques. This method can be used to explore nonlinear thermoelectric effects and spin dynamics induced by temperature gradients.Comment: 4 pages, 5 figure

Third Harmonic Characterization of Antiferromagnetic Heterostructures

Electrical switching of antiferromagnets is an exciting recent development in spintronics, which promises active antiferromagnetic devices with high speed and low energy cost. In this emerging field, there is an active debate about the mechanisms of current-driven switching of antiferromagnets. Harmonic characterization is a powerful tool to quantify current-induced spin-orbit torques and spin Seebeck effect in heavy-metal/ferromagnet systems. However, the harmonic measurement technique has never been verified in antiferromagnetic heterostructures. Here, we report for the first time harmonic measurements in Pt/$\alpha$-Fe$_2$O$_3$ bilayers, which are explained by our modeling of higher-order harmonic voltages. As compared with ferromagnetic heterostructures where all current-induced effects appear in the second harmonic signals, the damping-like torque and thermally-induced magnetoelastic effect contributions in Pt/$\alpha$-Fe$_2$O$_3$ emerge in the third harmonic voltage. Our results provide a new path to probe the current-induced magnetization dynamics in antiferromagnets, promoting the application of antiferromagnetic spintronic devices

Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis

Purpose We aimed to identify the underlying genetic cause for a novel form of distal arthrogryposis. Methods Rare variant family-based genomics, exome sequencing, and disease-specific panel sequencing were used to detect ADAMTS15 variants in affected individuals. Adamts15 expression was analyzed at the single-cell level during murine embryogenesis. Expression patterns were characterized using in situ hybridization and RNAscope. Results We identified homozygous rare variant alleles of ADAMTS15 in 5 affected individuals from 4 unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Radiographic investigations showed physiological interphalangeal joint morphology. Additional features included knee, Achilles tendon, and toe contractures, spinal stiffness, scoliosis, and orthodontic abnormalities. Analysis of mouse whole-embryo single-cell sequencing data revealed a tightly regulated Adamts15 expression in the limb mesenchyme between embryonic stages E11.5 and E15.0. A perimuscular and peritendinous expression was evident in in situ hybridization in the developing mouse limb. In accordance, RNAscope analysis detected a significant coexpression with Osr1, but not with markers for skeletal muscle or joint formation. Conclusion In aggregate, our findings provide evidence that rare biallelic recessive trait variants in ADAMTS15 cause a novel autosomal recessive connective tissue disorder, resulting in a distal arthrogryposis syndrome

Acute-onset axonal neuropathy following infection in children with biallelic RCC1 variants: a case series

\ua9 2025 This is an Open Access article under the CC BY 4.0 licenseBackground: The reasons why some individuals have severe neuropathy following an infection are not known. Through the agnostic screening of children with acute axonal neuropathy after an infection, we identified several families with biallelic variants in RCC1. We aimed to describe the clinical phenotype of these patients, and the molecular and cellular pathology associated with the genetic variants identified in these families. Methods: For this case series, we identified children affected by a severe, acute-onset axonal neuropathy following infection through an international research consortium of paediatric neurologists and clinical geneticists from nine countries (Canada, Cyprus, Czechia, Germany, Iran, Saudi Arabia, Slovakia, T\ufcrkiye, and the UK). Clinical assessments included nerve conduction studies and neuroimaging. We did exome or genome sequencing in DNA samples from all patients. We characterised the proteins encoded by the genetic variants by use of thermal stability and enzymatic assays, using recombinantly expressed proteins. We assessed cellular protein transport under heat or oxidative stress by use of immunofluorescence in primary fibroblasts, obtained from patients. We generated a humanised Drosophila knock-in model to assess the effects of stress on the in vivo function of RCC1. Findings: Between Nov 2, 2011, and July 10, 2024, we identified 24 individuals from 12 families who had severe, acute-onset axonal neuropathy following infection (13 female and 11 male patients, with a mean age at diagnosis of 1 year 10 months [SD 2\ub727]). Eight biallelic missense variants in RCC1 were identified in affected individuals with autosomal recessive inheritance. Patients had variable phenotypes, ranging from rapidly progressive fatal axonal neuropathy to mild motor neuropathy with impaired walking. Neurological presentation was often secondary to an infection, resulting in initial misdiagnoses of Guillain-Barr\ue9 syndrome in several patients. 15 children had disease recurrence. The disease was fatal in 15 patients. The RCC1 variants in these patients code for proteins that alter GDP-to-GTP exchange activity and have reduced thermal stability in vitro. In primary fibroblasts, heat shock or oxidative stress revealed defects in Ran nuclear localisation and impaired nucleocytoplasmic transport. A Drosophila model of the disease revealed a fatal intolerance to oxidative stress. Interpretation: We describe an autosomal recessive, acute-onset paediatric axonal neuropathy, seemingly triggered by infection, that affects individuals with biallelic RCC1 variants. In these children, the disease can mimic Guillain-Barr\ue9 syndrome. The pathological mechanisms underlying this novel axonal neuropathy might overlap with those of amyotrophic lateral sclerosis. Cellular studies indicate that RCC1 variants affect nucleocytoplasmic transport, which is crucial for healthy axonal function. Future studies should be directed at pre-symptomatic treatment by exploring ways to maintain nucleocytoplasmic transport. Funding: National Institute for Health and Care Research, LifeArc, and Wellcome Trust

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice