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Background: Percutaneous, transverse distal metatarsal osteotomy with K-wire fixation (the Bösch technique) is an established technique for hallux valgus correction. Nevertheless, the risk of damaging the anatomical structures during the operation is unknown., Methods: Forty fresh-frozen anatomical foot specimens with hallux valgus deformity underwent a percutaneous corrective procedure. Specimens of group A (n = 20) were operated by an experienced surgeon while specimens of group B (n = 20) were done by untrained residents., Results: The dorsal cutaneous nerve was injured in 1 of 20 cases in group A and 6 of 20 cases in group B ( P = .037). There was a significant difference in overall complication rate between specimens of group A and group B ( P = .043)., Conclusions: The results show an increased risk of perioperative injury of the dorsal cutaneous branch of the deep peroneal nerve as well as a significant effect of the surgeon's experience on the overall complication rate., Clinical Relevance: Results of this study are highly relevant for all surgeons who perform percutaneous, minimally invasive hallux valgus surgery to avoid damage to the peripheral nerves. In addition, the data suggest an intensive training for surgeons before minimally invasive hallux valgus surgery is performed without supervision.

Purpose: Corneal anesthesia leads to chronic corneal injury. This anatomical study characterizes the donor nerve branches of the supratrochlear and supraorbital nerves used for corneal neurotization., Methods: In 13 non-embalmed cadavers, the supratrochlear and supraorbital nerves were dissected and distances to anatomical landmarks measured. Cross-sections of supratrochlear and supraorbital donor nerves were harvested and histomorphometrically analyzed to assess the number of myelinated axons., Results: The donor axon counts were 3146 ± 1069.9 for the supratrochlear and 1882 ± 903 for the supraorbital nerve distal to the supraorbital notch. The supratrochlear nerve was dissected on the medial upper eyelid 2 cm lateral to the facial midline and the branch of the supraorbital nerve 1 cm medial to the mid-pupillary line., Conclusion: The supraorbital and supratrochlear branches of the trigeminal nerve are potent donor nerves for corneal neurotization in the treatment of neuropathic keratopathy and can be reliably dissected using anatomical landmarks., Competing Interests: The authors have declared that no competing interests exist.

Organic photodetectors offer distinct advantages over their inorganic analogues, most notably through optical transparency and flexibility, yet their figures-of-merit still lag behind those of inorganic devices, and optimization strategies generally encounter a trade-off between device responsivity and bandwidth. Here we propose a novel photodetector architecture in which an organic photoactive semiconductor layer (S) is sandwiched between two thick insulating layers (I) that separate the semiconductor from the metallic contacts (M). In this architecture a differential photocurrent response is generated purely from the polarization of the active layer under illumination. Especially for an asymmetric MISIM design, where one insulating layer is a high-k ionic liquid I IL and the other a low-k polymer dielectric I p , the responsivity/bandwidth trade-off is broken, since the role of the I IL in efficient charge separation is maintained, while the total device capacitance is reduced according to I p . Thus the benefits of single insulating layer differential photodetectors (MISM) using either I IL or I p are combined in a single device. Further improvements in device performance are also demonstrated by decreasing the series resistance of the photoactive layer through semiconductor:metal blending and by operation under strong background light.

Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub-stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal null mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage-specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging., (© 2017 The Authors Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The structure and electronic properties of a novel cobalt half sandwich complex of cyclopentadiene (Cp) and diaminonaphthalene (DAnap) [CpCo(DAnap)] are described and compared to the previously reported diaminobenzene derivative [CpCo(DAbnz)] in view of their potential for (opto)electronic device application. Both complexes show stable redox processes, tunable through the diaminoacene ligand, and show strong absorption in the visible region, with additional transitions stretching into the near infrared (NIR). CpCo(DAnap) crystallises with a particularly large unit cell (9301 Å 3 ), comprising 32 molecules, with a gradual rotation over 8 molecules along the long c-axis. In the solid state the balance of the optical transitions in both complexes is reversed, with a suppression of the visible band and an enhancement of the NIR band, attributed to extensive intermolecular electronic interaction. In the case of CpCo(DAnap), highly crystalline thin films could be formed under physical vapor deposition, which show a photocurrent response stretching into the NIR, and p-type semiconductor behavior in field effect transistors with mobility values of the order 1 × 10 -4 cm 2 V -1 s -1 . The device performance is understood through investigation of the morphology of the grown films.

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates., Competing Interests: No competing interests were disclosed.

Background: Harvesting the submental flap for vascularized lymph node transfer (VLNT) presents a challenging procedure because of, the topographic variation of the submental artery (SA) and the marginal mandible nerve (MMN) and the limited pedicle length for a free tissue transfer. The aim of this study was to evaluate surgical anatomical landmarks and variations of the submental lymph node flap (SLNF)., Methods and Materials: The authors examined the characteristics and landmarks of 18 SLNF in nine fresh cadavers. The diameter, length, and caliber of the SA and its relation to bony anatomic landmarks were measured. In addition, the number of lymph nodes (LNN) was evaluated through dissection and ultrasound., Results: Within the designated SLNF (10 × 5 cm 2 ), the number of LNN was on average 3 ± 0.6, with an average size of 4.5 ± 1.8 mm × 2.9 ± 1.2 mm. Projection of the LNN on the mandible, measured from the gnathion (GT, median-sagittal-plane) toward the gonion (GN, mandibular angle), was at 63.4 ± 5.8 mm (e.g., 65%) of the mandible for the first lymph node (LN), and for the following LNN was at 50.4 ± 7.7 mm (e.g., 52%), 44.0 ± 8.6 mm (e.g., 45%), and 40.50  ±  2.1 mm (e.g., 42%). The MMN consistently crossed the mandible body and the facial artery (FA) from dorso-caudal to ventro-cranial at 72 ± 5.2 mm, e.g., 75% of the mandible's length. Here, the nerve always lay superficial to the FA and was on average 0.96 ± 0.14 mm in diameter. Submental artery was located on average at 64 mm (e.g., 66%) of the mandible, with an average diameter of 1.34 ± 0.2 mm., Conclusion: The submental lymph node flap has a constant vascular supply by the submental artery. Lymph node count is on average three. Lymph nodes are close to the submental artery and its perforators. Marginal mandibular nerve lies superficial to the facial artery and crosses the artery at 75% of the mandible body length (gnathion to gonion = 100%). J. Surg. Oncol. 2017;115:54-59. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The addition of an insulating layer (I) between one of the metal electrodes (M) and the photoactive semiconducting layer (S) in a standard organic MSM solar cell architecture changes the DC photocurrent response into a strong transient signal. Such a device can, in simple terms, be thought of as a charging voltage source (S) in contact with a charging capacitor (I). The magnitude of the photocurrent signal can be strongly enhanced through the intimate contact of the active layer with the insulating layer, if the various pre-polarizations within the device act synergically. In this study, the effect of the built-in potentials within the device on the polarity and magnitude of the photocurrent response is studied using the well-characterized bulk heterojunction blend system of poly(3-hexylthiophenone):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) as the semiconductor layer, and an ionic liquid as the insulating layer. This study shows that the polarity of the response is not simply determined by the energy level difference of the outer electrodes, but through a delicate interplay of all the energy levels in the device. Furthermore, these observations could be reproduced for devices with a solid-state insulator layer, where possible side-effects of the ionic liquid, such as swelling and doping, could be considered absent.

A novel platform for transient photodetector component screening has been developed whereby an optical fiber tip serves as the counter electrode when placed in a variety of dielectric media, connected to a photoresponsive working electrode. The soft processing conditions allow for ubiquitous photodetection for organic and biological systems.

Channelrhodopsins have become a focus of interest because of their ability to control neural activity by light, used in a technology called optogenetics. The channelrhodopsin in the eukaryote Chlamydomonas reinhardtii (CrChR-1) is a light-gated cation channel responsible for motility changes upon photo-illumination and a member of the membrane-embedded retinal protein family. Recent crystal structure analysis revealed that CrChR-1 has unique extended modules both at its N- and C-termini compared to other microbial retinal proteins. This study reports the first successful expression of a ChR-1 variant in Escherichia coli as a holoprotein: the ChR-1 variant lacking both the N- and C-termini (CrChR-1_82-308). However, compared to ChR-1 having the extended modules (CrChR-1_1-357), truncation of the termini greatly altered the absorption maximum and photochemical properties, including the pKa values of its charged residues around the chromophore, the reaction rates in the photocycle and the photo-induced ion channeling activity. The results of some experiments regarding ion transport activity suggest that CrChR-1_82-308 has a proton channeling activity even in the dark. On the basis of these results, we discuss the structural and functional roles of the N- and C-terminal extended modules in CrChR-1.

A novel planar architecture has been developed for the study of photodetectors utilizing the transient photocurrent response induced by a metal/insulator/semiconductor/metal (MISM) structured device, where the insulator is an ionic liquid (IL-MISM). Using vanadyl 2,3-naphthalocyanine, which absorbs in the communications-relevant near-infrared wavelength region (λ(max,film) ≈ 850 nm), in conjunction with C60 as a bulk heterojunction, the high capacitance of the formed electric double layers at the ionic liquid interfaces yields high charge separation efficiency within the semiconductor layer, and the minimal potential drop in the bulk ionic liquid allows the electrodes to be offset by distances of over 7 mm. Furthermore, the decrease in operational speed with increased electrode separation is beneficial for a clear modeling of the waveform of the photocurrent signal, free from the influence of measurement circuitry. Despite the use of a molecular semiconductor as the active layer in conjunction with a liquid insulating layer, devices with a stability of several days could be achieved, and the operational stability of such devices was shown to be dependent solely on the solubility of the active layer in the ionic liquid, even under atmospheric conditions. Furthermore, the greatly simplified device construction process, which does not rely on transparent electrode materials or direct electrode deposition, provides a highly reproducible platform for the study of the electronic processes within IL-MISM detectors that is largely free from architectural constraints.

We evaluate the usefulness of digital volume data produced with the high-resolution episcopic microscopy (HREM) method for visualizing the three-dimensional (3D) arrangement of components of human skin, and present protocols designed for processing skin biopsies for HREM data generation. A total of 328 biopsies collected from normally appearing skin and from a melanocytic nevus were processed. Cuboidal data volumes with side lengths of ~2×3×6 mm3 and voxel sizes of 1.07×1.07×1.5 µm3 were produced. HREM data fit ideally for visualizing the epidermis at large, and for producing highly detailed volume and surface-rendered 3D representations of the dermal and hypodermal components at a structural level. The architecture of the collagen fiber bundles and the spatial distribution of nevus cells can be easily visualized with volume-rendering algorithms. We conclude that HREM has great potential to serve as a routine tool for researching and diagnosing skin pathologies.

Ion-transporting rhodopsins are widely utilized as optogenetic tools both for light-induced neural activation and silencing. The most studied representative is Bacteriorhodopsin (BR), which absorbs green/red light (∼570 nm) and functions as a proton pump. Upon photoexcitation, BR induces a hyperpolarization across the membrane, which, if incorporated into a nerve cell, results in its neural silencing. In this study, we show that several residues around the retinal chromophore, which are completely conserved among BR homologs from the archaea, are involved in the spectral tuning in a BR homolog (HwBR) and that the combination mutation causes a large spectral blue shift (λmax = 498 nm) while preserving the robust pumping activity. Quantum mechanics/molecular mechanics calculations revealed that, compared with the wild type, the β-ionone ring of the chromophore in the mutant is rotated ∼130° because of the lack of steric hindrance between the methyl groups of the retinal and the mutated residues, resulting in the breakage of the π conjugation system on the polyene chain of the retinal. By the same mutations, similar spectral blue shifts are also observed in another BR homolog, archearhodopsin-3 (also called Arch). The color variant of archearhodopsin-3 could be successfully expressed in the neural cells of Caenorhabditis elegans, and illumination with blue light (500 nm) led to the effective locomotory paralysis of the worms. Thus, we successfully produced a blue-shifted proton pump for neural silencing.

Rhodopsin contains retinal as the chromophore within seven transmembrane helices. Recently, we found a unique rhodopsin (middle rhodopsin, MR), which is evolutionarily located between the well-studied bacteriorhodopsin and sensory rhodopsin II, and which accommodates three retinal isomers in its ground state (the all-trans, the 13-cis, and, uniquely, the 11-cis isomers). In this study, we investigated structural changes of both the protein moiety and the retinal chromophore during photocycles of MR by time-resolved Fourier-transform infrared spectroscopy. Three photointermediates with decay time constants of 95 μs, 0.9 ms, and >~10 ms were identified by the global exponential fitting analysis. The first and third intermediates were attributed to the all-trans photocycle, in accordance with recently published results, whereas the second intermediate was likely one that was spectroscopically silent in the visible region and that was formed between the first and third states or resulted from the activation of the 13-cis isomer. By comparing light-induced difference spectra with various isotope labels in either the retinal or the protein moiety, we concluded that a β-sheet structure in the hydrophilic part was significantly altered during the all-trans photocycle of MR, which may involve an active state of the protein. This feature is characteristic of MR among microbial (type-1) rhodopsins.

In nature, organisms are subjected to a variety of environmental stimuli to which they respond and adapt. They can show avoidance or attractive behaviors away from or toward such stimuli in order to survive in the various environments in which they live. One such stimuli is light, to which, for example, the receptor sensory rhodopsin I (SRI) has been found to respond by regulating both negative and positive phototaxis in, e.g., the archaeon Halobacterium salinarum. Interestingly, to date, all organisms having SRI-like proteins live in highly halophilic environments, suggesting that salt significantly influences the properties of SRIs. Taking advantage of the discovery of the highly stable SRI homologue from Salinibacter ruber (SrSRI), which maintains its color even in the absence of salt, the importance of the chloride ion for the color tuning and for the slow M-decay, which is thought to be essential for the phototaxis function of SRIs, has been reported previously [Suzuki, D., et al. (2009) J. Mol. Biol.392, 48-62]. Here the effects of the anion binding on the structure and structural changes of SRI during its photocycle are investigated by means of Fourier transform infrared (FTIR) spectroscopy and electrochemical experiments. Our results reveal that, among other things, the structural change and proton movement of a characteristic amino acid residue, Asp102 in SrSRI, is suppressed by the binding of an anion in its vicinity, both in the K- and M-intermediate. The presence of this anion also effects the extent of chromophore distrotion, and tentative results indicate an influence on the number and/or properties of internal water molecules. In addition, a photoinduced proton transfer could only be observed in the absence of the bound anion. Possible proton movement pathways, including the residues Asp102 and the putative Cl binding site His131, are discussed. In conclusion, the results show that the anion binding to SRI is not only important for the color tuning, and for controlling the photocycle kinetics, but also induces some structural changes which facilitate the observed properties.

Photoactive proteins with cognate chromophores are widespread in organisms, and function as light-energy converters or receptors for light-signal transduction. Rhodopsins, which have retinal (vitamin A aldehyde) as their chromophore within their seven transmembrane α-helices, are classified into two groups, microbial (type-1) and animal (type-2) rhodopsins. In general, light absorption by type-1 or type-2 rhodopsins triggers a trans-cis or cis-trans isomerization of the retinal, respectively, initiating their photochemical reactions. Recently, we found a new microbial rhodopsin (middle rhodopsin, MR), binding three types of retinal isomers in its original state: all-trans, 13-cis, and 11-cis. Here, we identified the absolute absorption spectra of MR by a combination of high performance liquid chromatography (HPLC) and UV-vis spectroscopy under varying light conditions. The absorption maxima of MR with all-trans, 13-cis, or 11-cis retinal are located at 485, 479, and 495 nm, respectively. Their photocycles were analyzed by time-resolved laser spectroscopy using various laser wavelengths. In conclusion, we propose that the photocycles of MR are MR(trans) → MR(K):lifetime = 93 μs → MR(M):lifetime = 12 ms → MR, MR(13-cis) → MR(O-like):lifetime = 5.1 ms → MR, and MR(11-cis) → MR(K-like):lifetime = 8.2 μs → MR, respectively. Thus, we demonstrate that a single photoactive protein drives three independent photochemical reactions.

Organisms sense and respond to environmental stimuli through membrane-embedded receptors and transducers. Sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII) are the photoreceptors for the positive and negative phototaxis in microorganisms, respectively. They form signaling complexes in the membrane with their cognate transducer proteins, HtrI and HtrII, and these SRI-HtrI and SRII-HtrII complexes transmit a light signal through their cytoplasmic sensory signaling system, inducing opposite effects (i.e., the inactivation or activation of the kinase CheA). Here we found, by using Fourier transformed infrared spectroscopy, that a conserved residue, Asp102 in Salinibacter SRI (SrSRI), which is located close to the β-ionone ring of the retinal chromophore, is deprotonated upon formation of the active M-intermediate. Furthermore, the D102E mutant of SrSRI affects the structure and/or structural changes of Cys130. This mutant shows a large spectral shift and is comparably unstable, especially in the absence of Cl(-). These phenomena have not been observed in the wild-type, or the N105Q and N105D mutants of Natronomonas pharaonis SRII (NpSRII), indicating differences in the structure and structural changes between SrSRI and NpSRII around the β-ionone ring. These differences could also be supported by the measurements of the reactivity with the water-soluble reagent azide. On the basis of these results, we discuss the structure and structural changes around the retinal chromophore in SrSRI.

After contact with water, surfactant lamellar phases (L(α)) can show spectacular interface instabilities: multibilayer tubules, so-called myelins, grow from the L(α)/water interface into the water. We have studied the shape, size, and growth of myelins in aqueous solutions of the nonionic surfactant C(12)E(3) (triethylene glycol monododecyl ether) during dissolution. We used a combination of different imaging techniques: optical microscopy providing 2-D projections of the sample and confocal microscopy offering a complete 3-D reconstruction. These techniques provide quantitative information on the shape and growth of myelins, such as their width, length, and depth profile as a function of time. The growth rate of myelins, characterized by a swelling or diffusion coefficient, was found to increase with surfactant mass fraction and, seemingly, with sample thickness. We demonstrate that myelin creaming due to buoyancy can explain the apparent dependence on sample thickness. Our experiments furthermore suggest that myelin growth is controlled by an interplay between the water mobility in the lamellar phase and the osmotic pressure difference between the lamellar phase and the contacting water.