Vibronic Coupling Drives the Ultrafast Internal Conversion in a Functionalized Free-Base Porphyrin.

Internal conversion (IC) is a common radiationless transition in polyatomic molecules. Theory predicts that molecular vibrations assist IC between excited states, and ultrafast experiments can provide insight into their structure-function relationship. Here we elucidate the dynamics of the vibrational modes driving the IC process within the Q band of a functionalized porphyrin molecule.

Distinguishing Different Stackings in Layered Materials via Luminescence Spectroscopy.

Despite its simple crystal structure, layered boron nitride features a surprisingly complex variety of phonon-assisted luminescence peaks. We present a combined experimental and theoretical study on ultraviolet-light emission in hexagonal and rhombohedral bulk boron nitride crystals. Emission spectra of high-quality samples are measured via cathodoluminescence spectroscopy, displaying characteristic differences between the two polytypes.

Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome.

Ciliopathies may be classed as primary or motile depending on the underlying ciliary defect and are usually considered distinct clinical entities. Primary ciliopathies are associated with multisystem syndromes typically affecting the brain, kidney, and eye, as well as other organ systems such as the liver, skeleton, auditory system, and metabolism. Motile ciliopathies are a heterogenous group of disorders with defects in specialised motile ciliated tissues found within the lung, brain, and reproductive system, and are associated with primary ciliary dyskinesia, bronchiectasis, infertility and rarely hydrocephalus.

Anomalous non-equilibrium response in black phosphorus to sub-gap mid-infrared excitation.

The competition between the electron-hole Coulomb attraction and the 3D dielectric screening dictates the optical properties of layered semiconductors. In low-dimensional materials, the equilibrium dielectric environment can be significantly altered by the ultrafast excitation of photo-carriers, leading to renormalized band gap and exciton binding energies. Recently, black phosphorus emerged as a 2D material with strongly layer-dependent electronic properties.

Gap Opening in Double-Sided Highly Hydrogenated Free-Standing Graphene.

Conversion of free-standing graphene into pure graphane─where each C atom is sp bound to a hydrogen atom─has not been achieved so far, in spite of numerous experimental attempts. Here, we obtain an unprecedented level of hydrogenation (≈90% of sp bonds) by exposing fully free-standing nanoporous samples─constituted by a single to a few veils of smoothly rippled graphene─to atomic hydrogen in ultrahigh vacuum. Such a controlled hydrogenation of high-quality and high-specific-area samples converts the original conductive graphene into a wide gap semiconductor, with the valence band maximum (VBM) ∼ 3.

A discarded synonymous variant in NPHP3 explains nephronophthisis and congenital hepatic fibrosis in several families.

Half of patients with a ciliopathy syndrome remain unsolved after initial analysis of whole exome sequencing (WES) data, highlighting the need for improved variant filtering and annotation. By candidate gene curation of WES data, combined with homozygosity mapping, we detected a homozygous predicted synonymous allele in NPHP3 in two children with hepatorenal fibrocystic disease from a consanguineous family. Analyses on patient-derived RNA shows activation of a cryptic mid-exon splice donor leading to frameshift.

Gene and epigenetic editing in the treatment of primary ciliopathies.

Primary ciliopathies are inherited human disorders that arise from mutations in ciliary genes. They represent a spectrum of severe, incurable phenotypes, differentially involving several organs, including the kidney and the eye. The development of gene-based therapies is opening up new avenues for the treatment of ciliopathies.

Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases.

Mutations in CEP290 (also known as NPHP6), a large multidomain coiled coil protein, are associated with multiple cilia-associated syndromes. Over 130 CEP290 mutations have been linked to a wide spectrum of human ciliopathies, raising the question of how mutations in a single gene cause different disease syndromes. In zebrafish, the expressivity of cep290 deficiencies were linked to the type of genetic ablation: acute cep290 morpholino knockdown caused severe cilia-related phenotypes, whereas deficiencies in a CRISPR/Cas9 genetic mutant were restricted to photoreceptor defects.

Evidence of ideal excitonic insulator in bulk MoS under pressure.

Spontaneous condensation of excitons is a long-sought phenomenon analogous to the condensation of Cooper pairs in a superconductor. It is expected to occur in a semiconductor at thermodynamic equilibrium if the binding energy of the excitons-electron (e) and hole (h) pairs interacting by Coulomb force-overcomes the band gap, giving rise to a new phase: the "excitonic insulator" (EI). Transition metal dichalcogenides are excellent candidates for the EI realization because of reduced Coulomb screening, and indeed a structural phase transition was observed in few-layer systems.

Update of genetic variants in CEP120 and CC2D2A-With an emphasis on genotype-phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies.

Background: Mutations in ciliary genes cause a spectrum of both overlapping and distinct clinical syndromes (ciliopathies). CEP120 and CC2D2A are paradigmatic examples for this genetic heterogeneity and pleiotropy as mutations in both cause Joubert syndrome but are also associated with skeletal ciliopathies and Meckel syndrome, respectively. The molecular basis for this phenotypical variability is not understood but basal exon skipping likely contributes to tolerance for deleterious mutations via tissue-specific preservation of the amount of expressed functional protein.

Cell preservation methods and its application to studying rare disease.

The ability to preserve and transport human cells in a stable medium over long distances is critical to collaborative efforts and the advancement of knowledge in the study of human disease. This is particularly important in the study of rare diseases. Recently, advancements in the understanding of renal ciliopathies has been achieved via the use of patient urine-derived cells (UDCs).

Intermolecular conical intersections in molecular aggregates.

Conical intersections (CoIns) of multidimensional potential energy surfaces are ubiquitous in nature and control pathways and yields of many photo-initiated intramolecular processes. Such topologies can be potentially involved in the energy transport in aggregated molecules or polymers but are yet to be uncovered. Here, using ultrafast two-dimensional electronic spectroscopy (2DES), we reveal the existence of intermolecular CoIns in molecular aggregates relevant for photovoltaics.

Use of patient derived urine renal epithelial cells to confirm pathogenicity of PKHD1 alleles.

Background: PKHD1 is the main genetic cause of autosomal recessive polycystic kidney disease (ARPKD), a hereditary hepato-renal fibrocystic disorder which is the most important cause of end-stage renal disease during early childhood. ARPKD can also present in adulthood with milder phenotypes. In this study, we describe a 24-year-old woman with atypical polycystic kidney, no family history of renal disease and no obvious extra-renal manifestations who was referred for genetic investigation.

Vibrational signature of the graphene nanoribbon edge structure from high-resolution electron energy-loss spectroscopy.

Bottom-up approaches exploiting on-surface synthesis reactions allow atomic-scale precision in the fabrication of graphene nanoribbons (GNRs); this is essential for their technological applications since their unique electronic and optical properties are largely controlled by the specific edge structure. By means of a combined experimental-theoretical investigation of some prototype GNRs, we show here that high-resolution electron energy-loss spectroscopy (HREELS) can be successfully employed to fingerprint the details of the GNR edge structure. In particular, we demonstrate how the features of HREEL vibrational spectra - mainly dictated by edge CH out-of-plane modes - are unambiguously related to the GNR edge structure.

Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman.

Background: There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.

Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney Disorders.

The class of human genetic kidney diseases is extremely broad and heterogeneous. Accordingly, the range of associated disease phenotypes is highly variable. Many children and adults affected by inherited kidney disease will progress to ESKD at some point in life.

A monolayer transition-metal dichalcogenide as a topological excitonic insulator.

Monolayer transition-metal dichalcogenides in the T' phase could enable the realization of the quantum spin Hall effect at room temperature, because they exhibit a prominent spin-orbit gap between inverted bands in the bulk. Here we show that the binding energy of electron-hole pairs excited through this gap is larger than the gap itself in the paradigmatic case of monolayer T' MoS, which we investigate from first principles using many-body perturbation theory. This paradoxical result hints at the instability of the T' phase in the presence of spontaneous generation of excitons, and we predict that it will give rise to a reconstructed 'excitonic insulator' ground state.

Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome.

Genetic and phenotypic heterogeneity and the lack of sufficiently large patient cohorts pose a significant challenge to understanding genetic associations in rare disease. Here we identify (alias ) as a genetic modifier of cystic kidney disease in Joubert syndrome, using a -deficient mouse model to recapitulate the phenotypic variability observed in patients by mixing genetic backgrounds in a controlled manner and performing genome-wide analysis of these mice. Experimental down-regulation of in the parental mouse strain phenocopied the severe cystic kidney phenotype.

A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.

CEP104 is an evolutionarily conserved centrosomal and ciliary tip protein. CEP104 loss-of-function mutations are reported in patients with Joubert syndrome, but their function in the etiology of ciliopathies is poorly understood. Here, we show that cep104 silencing in zebrafish causes cilia-related manifestations: shortened cilia in Kupffer's vesicle, heart laterality, and cranial nerve development defects.

Targeted exon skipping rescues ciliary protein composition defects in Joubert syndrome patient fibroblasts.

Joubert syndrome (JBTS) is an incurable multisystem ciliopathy syndrome. The most commonly mutated gene in JBTS patients with a cerebello-retinal-renal phenotype is CEP290 (alias JBTS5). The encoded CEP290 protein localises to the proximal end of the primary cilium, in the transition zone, where it controls ciliary protein composition and signalling.

Tailoring optical properties and stimulated emission in nanostructured polythiophene.

Polythiophenes are the most widely utilized semiconducting polymers in organic electronics, but they are scarcely exploited in photonics due to their high photo-induced absorption caused by interchain polaron pairs, which prevents the establishment of a window of net optical gain. Here we study the photophysics of poly(3-hexylthiophene) configured with different degrees of supramolecular ordering, spin-coated thin films and templated nanowires, and find marked differences in their optical properties. Transient absorption measurements evidence a partially-polarized stimulated emission band in the nanowire samples, in contrast with the photo-induced absorption band observed in spin-coated thin films.

A case of ocular cystinosis associated with two potentially severe CTNS mutations.

Background: Ocular cystinosis is a rare autosomal recessive disorder caused by one severe and one mild mutation in the CTNS gene. It is characterised by cystine deposition within the cornea and conjunctiva however, the kidneys are not affected. We report a case of ocular cystinosis caused by two potentially severe CTNS mutations and discuss the possible mechanism of renal sparing.

Using zebrafish to study the function of nephronophthisis and related ciliopathy genes.

Zebrafish are a valuable vertebrate model in which to study development and characterize genes involved in cystic kidney disease. Zebrafish embryos and larvae are transparent, allowing non-invasive imaging during their rapid development, which takes place over the first 72 hours post fertilisation. Gene-specific knockdown of nephronophthisis-associated genes leads to ciliary phenotypes which can be assessed in various developmental structures.

Targeted exon skipping of a mutation rescues Joubert syndrome phenotypes in vitro and in a murine model.

Genetic treatments of renal ciliopathies leading to cystic kidney disease would provide a real advance in current therapies. Mutations in underlie a ciliopathy called Joubert syndrome (JBTS). Human disease phenotypes include cerebral, retinal, and renal disease, which typically progresses to end stage renal failure (ESRF) within the first two decades of life.