Developmental ocular malformations, including anophthalmia-microphthalmia (AM), are heterogeneous disorders with frequent sporadic or non-Mendelian inheritance. Recurrent interstitial deletions of 14q22-q23 have been associated with AM, sometimes with poly/syndactyly and hypopituitarism. We identify two further cases of AM (one with associated pituitary anomalies) with a 14q22-q23 deletion. Using a positional candidate gene approach, we analyzed the BMP4 (Bone Morphogenetic Protein-4) gene and identified a frameshift mutation (c.226del2, p.S76fs104X) that segregated with AM, retinal dystrophy, myopia, brain anomalies, and polydactyly in a family and a nonconservative missense mutation (c.278A-->G, p.E93G) in a highly conserved base in another family. MR imaging and tractography in the c.226del2 proband revealed a primary brain developmental disorder affecting thalamostriatal and callosal pathways, also present in the affected grandmother. Using in situ hybridization in human embryos, we demonstrate expression of BMP4 in optic vesicle, developing retina and lens, pituitary region, and digits strongly supporting BMP4 as a causative gene for AM, pituitary, and poly/syndactyly. Because BMP4 interacts with HH signaling genes in animals, we evaluated gene expression in human embryos and demonstrate cotemporal and cospatial expression of BMP4 and HH signaling genes. We also identified four cases, some of whom had retinal dystrophy, with "low-penetrant" mutations in both BMP4 and HH signaling genes: SHH (Sonic Hedgehog) or PTCH1 (Patched). We propose that BMP4 is a major gene for AM and/or retinal dystrophy and brain anomalies and may be a candidate gene for myopia and poly/syndactyly. Our finding of low-penetrant variants in BMP4 and HH signaling partners is suggestive of an interaction between the two pathways in humans.

Femtosecond photoelectron spectroscopy measurements of dissociation CH3I show complex dynamics in the high energy region of absorption band A.

Inversion-symmetric crystals are optically isotropic and thus naively not expected to show dichroism effects in optical absorption and photoemission processes. Here, we find a strong linear dichroism effect (up to 42.4%) in the conduction band of inversion-symmetric bilayer MoS2, when measuring energy-and momentum-resolved snapshots of excited electrons by time-and angle-resolved photoemission spectroscopy. We model the polarization-dependent photoemission intensity in the transiently-populated conduction band using the semiconductor Bloch equations and show that the observed dichroism emerges from intralayer single-particle effects within the isotropic part of the dispersion. This leads to optical excitations with an anisotropic momentum-dependence in an otherwise inversion symmetric material.Optical selection rules in absoprtion experiments are powerful tools that can be used to determine the symmetry of electronic states in solids [1]. Given the similarity of the processes underlying optical absorption and photoemission, selection rules have also been exploited in angle-resolved photoemission spectroscopy (ARPES) for decades [2]. More recently, optical dichroism has been used in ARPES to study orbital degrees of freedom [3][4][5], as well as the Berry curvature of the initial Bloch states [6, 7]. A particularly interesting opportunity for polarization-dependent excitations arises in single-layer (SL) transition metal dichalcogenides (TMDCs) such as MoS 2 , where the helicity of circularly polarized light strongly couples to the valley and spin degrees of freedom [8, 9], permitting the generation of a finite valley polarization [10, 11].Adding time-resolution (TR) to ARPES in a pumpprobe experiment leads to a process involving two optical excitations. This opens the possibility of exploiting not only the selection rules governing the photoemission process, but also those giving rise to the initial optical excitation into a transiently populated conduction band (CB) state [12][13][14][15][16][17][18]. Indeed, the creation of a finite valleypolarization in SL WS 2 has recently been followed in momentum space by TR-ARPES using circularly polarized pump pulses [19,20]. Here, we extend such an experiment to the case of bilayer (BL) MoS 2 in the 2H structure, which is inversion-symmetric and hence an optically isotropic material. Surprisingly, we observe a substantial linear dichroism effect. Our results can be reconciled with the momentum-dependent excited state population determined by solving the semiconductor Bloch equations within the framework of a low energy k · p model that ac-counts for intra-and interlayer interactions between the d orbitals forming the valence band maximum (VBM) and conduction band minimum (CBM) aroundK (K ). These findings underline the necessity of accounting for selection rules governing the optical excitation in addition to the photoemission matrix elements when interpreting the intensity in dichroic TR-ARPES.Our BL MoS 2 sample is grown on Ag(111) and has predominantly one domain orie...

Femtosecond pump-probe photoelectron spectroscopy measurements using an extreme ultravioletprobe have been made on the photodissociation dynamics of UV (269 nm) excited CH3I. TheUV excitation leads to population of the 3Q0...