bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric Evaluation of Periorbital Region and Facial Projection Using Three-Dimensional Photogrammetry
Authors: Jodeh Diana S. , Curtis Heather , Cray James J. , Ford Jonathan , Decker Summer , Rottgers S. Alex
Published: October 2018

Introduction:

Direct anthropometric and three-dimensional (3D) photogrammetry measurements have been used extensively in cleft/craniofacial surgery to assess morphological changes and surgical outcomes. Craniofacial procedures alter the sagittal projection of periorbital bony prominences. Mulliken described a method of measuring their projection relative to the corneal plane but is impractical in clinical practice. Three-dimensional photogrammetry may offer a solution; however, the cornea is not visualized on this. The authors propose to develop new normative measurements of facial projection relative to the pupil.

Methods:

Five 3D photographs were taken of 5 individuals using Vectra M5 camera. Facial projection measurements were taken of the sagittal projection of the bilateral periorbital landmarks and nasal radix relative to the pupil using Mirror 3D analysis. Standard deviations (SD) were determined for each subject and laterality. Chi-square tests confirmed all SD <1 mm. Intra and inter-rater reliability were confirmed with an intraclass correlation coefficient assessment.

Results:

Three male and 2 female subjects were photographed with 5 unique images. Standard deviations of repeat measures of all landmarks were <0.5 mm. Chi-square tests confirmed with statistical significance that SD for all values except for the radix was <1 mm (P<0.05). Intrarater reliability was high for all landmarks (intraclass correlation coefficient coefficients 0.93–0.99). Inter-rater reliability was good for the lateral canthi and excellent for all others.

Conclusion:

This technique demonstrates repeatability with high reliability on serial photographs and is applicable to measuring surgery effects and growth on facial projection. Establishment of age-specific normative values for landmark projection will refine usage applicability in operative planning.
Osteotomy in Genioplasty by Piezosurgery
Authors: Bertossi Dario , Albanese Massimo , Mortellaro Carmen , Malchiodi Luciano , Kumar Narendra , Nocini Riccardo , Nocini Pier Francesco
Published: October 2018

Background:

The chin is the most prominent and median sector of the lower third of the face giving harmony to nose and lips. The authors present the application of piezoelectric scalpel for the correction of different chin deformities. The distinctive characteristics of this device allow the authors to avoid or reduce the immediate genioplasty complications.

Methods:

Fifty-five patients of defective chin have been treated from January 2006 to April 2008. Intraoral genioplasty was performed during the correction of dentofacial dysmorphisms or associated with nasal surgery. The authors used a piezoelectric cutting device to perform different osteotomies and if necessary, interpositional graft was used to stabilize bony segments.

Results:

Piezosurgery has been associated with a fewer number of postoperative complications, especially as regard intraoperative bleeding, nerve injuries (immediate and late), hematomas and seromas, asymmetry (immediate and early). The mean time for completing the complete procedure of genioplasty with piezosurgery was almost the same compared with the saw and drill.

Conclusion:

Genioplasty represents one of the most common ancillary procedures and may be associated with corrective surgery of dentofacial dysmorphisms. Mental nerve injuries, asymmetries, intraoperative bleeding are the main immediate complications of genioplasty. Distinctive characteristics of ultrasonic piezoelectric osteotomy are selective cut of mineralized structure with less risk of vascular and nervous damage (microvibrations), intraoperative precision (thin cutting scalpel and no macrovibrations), blood free site (cavitation effect). In the authors’ experience, piezoelectric scalpel, compared with saw and drill, enables them to reduce or avoid immediate complications of chin surgery, helping the surgeon to reach patients’ satisfaction.
A New Technique for Sagittal Synostosis: A Plurality of Small Incisions Minimally Invasive Technique Used on Infants and Young Patients
Authors: Liu Tian-Jia , Wu Shui-Hua , Fan Shuang-Shi , Chen Zhao-Hui , Gu Shuo
Published: October 2018

Objectiv:

The authors devised a multiple small incisions minimally invasive technique for use in isolated nonsyndromic sagittal synostosis to achieve better esthetic effect and satisfactory reshaping of the calvarial vault. The purpose of this study is to provide clinicians with new and feasible solution.

Methods:

From April 2016 to January 2017, 5 male patients were successfully treated with minimally invasive surgery. The age ranges from 1.5 to 3.3 years. The authors designed 9 short skin linear incisions (2–3 cm long) strategically to disperse in the scalp. The patient was assessed in a series including sex, age of surgery, blood loss, blood transfusion, duration of surgery, postoperative complications, preoperative and postoperative cephalic index (CI), length of stay (LOS), esthetic outcomes, and intellectual developmental quotient (DQ).

Results:

The shortest operation time is 1.5 hours. The shortest hospital stay is 6 days. The blood loss ranged from 135 to 280 mL. No serious complications occurred during the follow-up time. Postoperative 3-dimensional CT scan showed that the extensive floating bone formed well. Preoperative CI ranged from 64.2 to 68 and postoperatively 69.4 to 74.3. Mental development was tested by children heath care practioners, significantly improving DQ from 67 to 81 preoperatively and 76 to 90 postoperatively. All children receive good esthetic results.

Conclusion:

The new technique is safe and effective. The advantages are satisfactory: calvarial fornix remodeling, less visible appearance of scars, shorter length of surgery, lower mental and financial stress, optimal age for surgery, no endoscopic adjuvant and postoperative helmet are needed.
Maxillary Alveolar Ridge Atrophy Reconstructed With Autogenous Bone Graft Harvested From the Proximal Ulna
Authors: Garcia-Júnior Idelmo Rangel , Souza Francisley Ávila , Figueiredo Antônio Alberto Scarabucci , Poli Pier Paolo , Benetti Francine , Ferreira Sabrina , de Melo Willian Morais , Rahal Sandra
Published: October 2018

Atrophy of the alveolar ridge requires bone grafting at the implant site for rehabilitation of the masticatory function with dental implants. Despite the advances in the development of bone substitutes, autogenous bone graft remains the “criterion standard” because of its osteogenic, osteoinductive, osteoconductive potential, and non-immunogenic properties. However, harvesting of autogenous bone is not exempt from donor site morbidity. In this context, the use of autogenous bone derived from the proximal ulna might be a viable resource to obtain corticocancellous bone graft, as the harvesting from this donor site is associated with low morbidity. Thus, this article aimed to describe a case in which a maxillary sinus floor augmentation was performed by means of autogenous bone graft harvested from the proximal ulna, as the donor site. An appositional bone block graft harvested from the same region was used to augment the residual alveolar ridge. Clinically, healing proceeded uneventfully with no major complications. After 8 months, a proper amount of bone was found at the implant site, allowing a prosthetically driven implant insertion and subsequent implant-supported rehabilitation. Results were clinically and radiographically stable after a 3-year follow-up. The present case report suggested that proximal ulna as a donor site should be considered as a safe and reliable alternative for alveolar ridge augmentation. Besides the case presentation, a comprehensive review of the literature was also provided.
Jug Handle Tributary of Internal Jugular Vein: A Potentially Dangerous Venous Variation
Authors: Nayak Satheesha B.
Published: October 2018

Variations of internal jugular vein (IJV) are rare and are surgically important. Here an unreported variation of IJV is presented. Right IJV had an unusual vein joining it in the form of a “jug handle.” This vein arose from the junction of IJV and common facial vein (CFV), coursed down for 3 cm and joined IJV again. The CFV was dilated. Knowledge of this rare case could be useful to craniofacial surgeons, radiologists, and anesthesiologists. It might decrease the chances of iatrogenic bleeding during head and neck surgeries and radiologic procedures.
Three Dimensional Printed Bone Implants in the Clinic
Authors: Tellisi Nazzar , Ashammakhi Nureddin A. , Billi Fabrizio , Kaarela Outi
Published: October 2018

Implants are being continuously developed to achieve personalized therapy. With the advent of 3-dimensional (3D) printing, it is becoming possible to produce customized precisely fitting implants that can be derived from 3D images fed into 3D printers. In addition, it is possible to combine various materials, such as ceramics, to render these constructs osteoconductive or growth factors to make them osteoinductive. Constructs can be seeded with cells to engineer bone tissue. Alternatively, it is possible to load cells into the biomaterial to form so called bioink and print them together to from 3D bioprinted constructs that are characterized by having more homogenous cell distribution in their matrix. To date, 3D printing was applied in the clinic mostly for surgical training and for planning of surgery, with limited use in producing 3D implants for clinical application. Few examples exist so far, which include mostly the 3D printed implants applied in maxillofacial surgery and in orthopedic surgery, which are discussed in this report. Wider clinical application of 3D printing will help the adoption of 3D printers as essential tools in the clinics in future and thus, contribute to realization of personalized medicine.
An update on the management of adult traumatic nerve injuries—replacing old paradigms: A review
Authors: Smith Brandon W. , Sakamuri Sarada , Spain David A. , Joseph Jacob R. , Yang Lynda J.-S. , Wilson Thomas J.
Published: October 2018

Acute nerve injuries are routinely encountered in multisystem trauma patients. Advances in surgical treatment of nerve injuries now mean that good outcomes can be achieved. Despite this, old mantras associated with management of nerve injuries, including “wait a year to see if recovery occurs” and “there's nothing we can do”, persist. Practicing by these mantras places these patients at a disadvantage. Changes begin to occur in the nerve, neuromuscular junction, and muscle from the moment a nerve injury occurs. These changes can become irreversible approximately 18 to 24 months following denervation. Thus, it is a race to reestablish a functional nerve-muscle connection before these irreversible changes. Good outcomes rely on appropriate acute management and avoiding delays in care. Primary nerve surgery options include direct primary repair, nerve graft repair, and nerve transfer. Acute management of nerve injuries proceeds according to the rule of 3's and requires early cooperation between trauma surgeons who recognize the nerve injury and consultant nerve surgeons. Care of patients with acute traumatic nerve injuries should not be delayed. Awareness of current management paradigms among trauma surgeons will help facilitate optimal upfront management. With the ever-expanding surgical options for management of these injuries and the associated improvement of outcomes, early multidisciplinary approaches to these injuries have never been more important. Old mantras must be replaced with new paradigms to continue to see improvements in outcomes for these patients. The importance of this review is to raise awareness among trauma surgeons of new paradigms for management of traumatic nerve injuries.
Endogenous BioID elucidates TCF7L1 interactome modulation upon GSK-3 inhibition in mouse ESCs
Authors: Moreira Steven , Seo Caleb , Gordon Victor , Xing Sansi , Wu Ruilin , Polena Enio , Fung Vincent , Ng Deborah , Wong Cassandra J , Larsen Brett , Raught Brian , Gingras Anne-Claude , Lu Yu , Doble✉ Bradley W.
Published: October 2018

Modulation of Wnt target gene expression via the TCF/LEFs remains poorly understood. We employ proximity-based biotin labeling (BioID) to examine GSK-3 inhibitor effects on the TCF7L1 interactome in mouse ESCs. We generated ESC lines with biotin ligase BirA* fused to TCF7L1 by knocking it into the endogenousTCF7L1locus or by inserting a doxinducible BirA*-TCF7L1 transgene into theRosa26locus. Induction yielded BirA*-TCF7L1 levels 3-fold higher than in the endogenous system, but substantial overlap in biotinylated proteins with high peptide counts were detected by each method. Known TCF7L1 interactors TLE3/4 and β-catenin, and numerous proteins not previously associated with TCF7L1, were identified in both systems. Despite reduced BirA*-TCF7L1 levels, the number of hits identified with both BioID approaches increased after GSK-3 inhibition. We elucidate the network of TCF7L1 proximal proteins regulated by GSK-3 inhibition, validate the utility of endogenous BioID, and provide mechanistic insights into TCF7L1 target gene regulation.

Highlights

BirA*-TCF7L1 at single-copy physiological levels generates robust BioID data

CHIR99021 reduces TCF7L1 levels but increases detectable TCF7L1-proximal proteins

The TCF7L1 interactome of largely epigenetic/transcription factors fluctuates with GSK-3 inhibition

JMJD1C, SALL4 and BRG1/SMARCA4 are validated as TCF7L-interacting proteins
The architecture of the endoplasmic reticulum is regulated by the reversible lipid modification of the shaping protein CLIMP-63
Authors: Sandoz Patrick A. , Denhardt-Eriksson Robin A. , Abrami Laurence , Abriata Luciano , Spreemann Gard , Maclachlan Catherine , Ho Sylvia , Kunz Béatrice , Hess Kathryn , Knott Graham , Hatzimanikatis Vassily , van der Goot F. Gisou
Published: October 2018

The endoplasmic reticulum (ER) has a complex morphology generated and maintained by membrane-shaping proteins and membrane energy minimization, though not much is known about how it is regulated. The architecture of this intracellular organelle is balanced between large, thin sheets that are densely packed in the perinuclear region and a connected network of branched, elongated tubules that extend throughout the cytoplasm. Sheet formation is known to involve the cytoskeleton-linking membrane protein 63 (CLIMP-63), though its regulation and the depth of its involvement remain unknown. Here we show that the post-translational modification of CLIMP-63 by the palmitoyltransferase ZDHHC6 controls the relative distribution of CLIMP-63 between the ER and the plasma membrane. By combining data-driven mathematical modeling, predictions, and experimental validation, we found that the attachment of a medium chain fatty acid, so-called S-palmitoylation, to the unique CLIMP-63 cytoplasmic cysteine residue drastically reduces its turnover rate, and thereby controls its abundance. Light microscopy and focused ion beam electron microcopy further revealed that enhanced CLIMP-63 palmitoylation leads to strong ER-sheet proliferation. Altogether, we show that ZDHHC6-mediated S-palmitoylation regulates the cellular localization of CLIMP-63, the morphology of the ER, and the interconversion of ER structural elements in mammalian cells through its action on the CLIMP-63 protein.

Significance Statement

Eukaryotic cells subcompartmentalize their various functions into organelles, the shape of each being specific and necessary for its proper role. However, how these shapes are generated and controlled is poorly understood. The endoplasmic reticulum is the largest membrane-bound intracellular compartment, accounting for more than 50% of all cellular membranes. We found that the shape and quantity of its sheet-like structures are controlled by a specific protein, cytoskeleton-linking membrane protein 63, through the acquisition of a lipid chain attached by an enzyme called ZDHHC6. Thus, by modifying the ZDHHC6 amounts, a cell can control the shape of its ER. The modeling and prediction technique used herein also provides a method for studying the interconnected function of other post-translational modifications in organelles.
hsp-16.2 chaperone biomarkers track physiological states of proteome dosage
Authors: Burnaevskiy Nikolay , Sands Bryan , Yun Soo , Tedesco Patricia M , Johnson Thomas E , Kaeberlein Matt , Brent Roger , Mendenhall Alexander
Published: October 2018

Phenotypic expression of many traits varies among isogenic individuals in homogeneous environments. Intrinsic variation in the protein chaperone system affects a wide variety of traits in diverse biological systems. In C. elegans, expression of hsp-16.2 chaperone biomarkers predicts the penetrance of mutations and lifespan after heat shock. But the physiological mechanisms by which cells express different amounts of the biomarker were unknown. Here, we used an in vivo microscopy approach to dissect the mechanisms of cell-to-cell variation in hsp-16.2 biomarker expression, focusing on the intestines, which generate most signal. We found both intrinsic noise and signaling noise are low. The major axis of cell-to-cell variation in gene expression is composed of general differences in protein dosage. Thus, hsp-16.2 biomarkers reveal states of high or low effective dosages for many genes. It is possible that natural variation in protein dosage or chaperone activity may account for missing heritability of some traits.
Temporal control of cortico-thalamic neuron specification by regulation of Neurogenin activity and Polycomb repressive complexes
Authors: Oishi Koji , van den Berg Debbie L. C. , Guillemot Franç
Published: October 2018

Neural progenitor cells (NPCs) in the embryonic mammalian neocortex generate different neuronal subtypes sequentially. A long-standing hypothesis to account for this temporal fate specification process is that NPCs change their differentiation potential over time. However, the molecular mechanisms underlying these temporal changes in NPC properties are poorly understood. Here we show that Neurogenin1 and Neurogenin2 (Neurog1/2), two proneural transcription factors expressed in NPCs throughout cortical neurogenesis, specify the identity of one of the first cortical neuron subtypes generated, layer 6 cortico-thalamic neurons (CTNs). We found that Neurog1/2 specify the CTN fate through regulation of the cortical fate determinants Fezf2 and Foxp2 and that this Neurog-induced programme becomes inactive after the period of CTN production. Two independent mechanisms contribute to the arrest of CTN neuron generation at the end of layer 6 neurogenesis, including a reduction in the transcriptional activity of Neurog1/2 and the deposition of epigenetic repressive modifications mediated by Polycomb repressive complexes at the Foxp2 gene. Therefore, the duration of production of a cortical neuron subtype is controlled by multiple locking mechanisms involving both transcriptional and epigenetic processes.
Using camouflage for conservation: colour change in juvenile European lobster
Authors: Mynott Sara , Daniels Carly , Widdicombe Stephen , Stevens Martin
Published: October 2018

Changes in coloration enable animals to refine their camouflage to match different visual environments. Such plasticity provides ecological benefits and could potentially be exploited to support conservation or stock enhancement efforts. One application could be ensuring that hatchery-reared animals, reared to stock wild populations, are appropriately matched to their environment on release. European lobster (Homarus gammarus) hatcheries aim to restock or enhance local lobster populations by rearing juveniles through their most vulnerable stages, then releasing them into the wild. However, little consideration has been given to their camouflage and the implications of matching individuals to their release site. This study assesses to what extent juvenile lobsters can change coloration to match their background and whether hatchery practices could be altered to enhance lobster camouflage. We test this by switching individuals between black or white backgrounds in the laboratory and monitoring their coloration over time. Our work demonstrates the capacity of juvenile lobsters to change lightness in response to their surroundings. We show that juvenile lobsters are capable of small changes in luminance (perceived lightness) to better match their background over 2-3 weeks. These changes potentially correspond to improved camouflage, based on a model of predator (European pollack,Pollachius pollachius) vision. However, over a longer period (5 weeks), lobsters maintained on either background converged on the same darker coloration, suggesting that lobsters also experience changes in appearance associated with ontogeny. By refining the approaches used here, there is potential for hatcheries to rear lobsters on backgrounds that better match their release site. However, such manipulations should be considered in the context of ontogenetic changes and release timing (which varies between stocking programmes). This study highlights the potential to use colour change in stocking and aquaculture, as well as gaps that could be addressed through further research in this area.
An Orthographic Prediction Error as the basis for efficient Visual Word Recognition
Authors: Gagl Benjamin , Sassenhagen Jona , Haan Sophia , Gregorova Klara , Richlan Fabio , Fiebach Christian J.
Published: October 2018

Most current models assume that the perceptual and cognitive processes of visual word recognition and reading operate upon neuronally coded domain-general low-level visual representations – typically oriented line representations. We here demonstrate, consistent with neurophysiological theories of Bayesian-like predictive neural computations, that prior visual knowledge of words may be utilized to ‘explain away’ redundant and highly expected parts of the visual percept. Subsequent processing stages, accordingly, operate upon an optimized representation of the visual input, the orthographic prediction error, highlighting only the visual information relevant for word identification. We show that this optimized representation is related to orthographic word characteristics, accounts for word recognition behavior, and is processed early in the visual processing stream, i.e., in V4 and before 200 ms after word-onset. Based on these findings, we propose that prior visual-orthographic knowledge is used to optimize the representation of visually presented words, which in turn allows for highly efficient reading processes.
There is no single functional atlas even for a single individual: Parcellation of the human brain is state dependent
Authors: Salehi Mehraveh , Greene Abigail S. , Karbasi Amin , Shen Xilin , Scheinost Dustin , Constable R.Todd
Published: October 2018

The goal of human brain mapping has long been to delineate the functional subunits in the brain and elucidate the functional role of each of these brain regions. Recent work has focused on whole-brain parcellation of functional Magnetic Resonance Imaging (fMRI) data to identify these subunits and create a functional atlas. Functional connectivity approaches to understand the brain at the network level require such an atlas to assess connections between parcels and extract network properties. While no single functional atlas has emerged as the dominant atlas to date, there remains an underlying assumption that such an atlas exists. Using fMRI data from a highly sampled subject as well as two independent replication data sets, we demonstrate that functional parcellations based on fMRI connectivity data reconfigure substantially and in a meaningful manner, according to brain state.
Hexameric helicase G40P unwinds DNA in single base pair steps
Authors: Schlierf Michael , Wang Ganggang , Chen Xiaojiang S. , Ha Taekjip
Published: October 2018

Most replicative helicases are hexameric, ring-shaped motor proteins that translocate on and unwind DNA. Despite extensive biochemical and structural investigations, how their translocation activity is utilized chemo-mechanically in DNA unwinding is poorly understood. We examined DNA unwinding by G40P, a DnaB-family helicase, using a single-molecule fluorescence assay with a single base pair resolution. The high-resolution assay revealed that G40P by itself is a very weak helicase that stalls at barriers as small as a single GC base pair and unwinds DNA with the step size of a single base pair. Single ATPγS binding could stall unwinding, demonstrating highly coordinated ATP hydrolysis between the six identical subunits. We observed frequent slippage of the helicase, which is fully suppressed by the primase DnaG. We anticipate that these findings allow a better understanding on the fine balance of thermal fluctuation activation and energy derived from hydrolysis.
PUMILIO hyperactivity drives premature aging ofNorad-deficient mice
Authors: Kopp Florian , Yalvac Mehmet E. , Chen Beibei , Zhang He , Lee Sungyul , Gillett Frank A. , Elguindy Mahmoud M. , Sivakumar Sushama , Yu Hongtao , Xie Yang , Mishra Prashant , Sahenk Zarife , Mendell Joshua T.
Published: October 2018

Although numerous long noncoding RNAs (lncRNAs) have been identified, our understanding of their roles in mammalian physiology remains limited. Here we investigated the physiologic function of the conserved lncRNANorad in vivo.Deletion ofNoradin mice results in genomic instability and mitochondrial dysfunction, leading to a dramatic multi-system degenerative phenotype resembling premature aging. Loss of tissue homeostasis in Norad-deficient animals is attributable to augmented activity of PUMILIO proteins, which act as post-transcriptional repressors of target mRNAs to which they bind.Noradis the preferred RNA target of PUMILIO2 (PUM2) in mouse tissues and, upon loss ofNorad,PUM2 hyperactively represses key genes required for mitosis and mitochondrial function. Remarkably, enforcedPum2expression fully phenocopiesNoraddeletion, resulting in rapid-onset aging-associated phenotypes. These findings provide new insights and open new lines of investigation into the roles of noncoding RNAs and RNA binding proteins in normal physiology and aging.
Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor
Authors: Yousefi O. Sascha , Günther Matthias , Hörner Maximilian , Chalupsky Julia , Wess Maximilian , Brandl Simon M. , Smith Robert W. , Fleck Christian , Kunkel Tim , Zurbriggen Matias D. , Höfer Thomas , Weber Wilfried , Schamel Wolfgang W.A.
Published: October 2018

The pivotal task of the immune system is to distinguish between self and foreign antigens. The kinetic proofreading model (KPR) proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the ligand-TCR interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B to selectively control the dynamics of ligand binding to the TCR by light. Combining experiments with mathematical modeling we find that the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating the KPR hypothesis.

One Sentence Summary

The half-life of the ligand-T cell receptor complex determines T cell activation.
Primary Cilium Disassembly in Mammalian Cells Occurs Predominantly by Whole-Cilium Shedding
Authors: Mirvis Mary , Siemers Kathleen , Nelson W. James , Stearns Tim
Published: October 2018

The primary cilium is a central signaling hub in cell proliferation and differentiation, and is built and disassembled every cell cycle in most animal cells. Disassembly is critically important: misregulation or delay of disassembly leads to cell cycle defects. The physical means by which cilia are disassembled are poorly understood, and thought to involve resorption of disassembled components into the cell body. To investigate cilium disassembly in mammalian cells, we used rapid live-cell imaging to comprehensively characterize individual disassembly events. The predominant mode of disassembly was rapid cilium loss via deciliation, in which the membrane and axoneme of the cilium was shed from the cell. Gradual resorption was also observed, as well as events in which a period of gradual resorption ended with rapid deciliation. Deciliation resulted in intact shed cilia that could be recovered from culture medium and contained both membrane and axoneme proteins. We modulated levels of katanin and intracellular calcium, two putative regulators of deciliation, and found that excess katanin promotes disassembly by deciliation, independently of calcium. Together, these results demonstrate that mammalian ciliary disassembly involves a tunable decision between deciliation and resorption.
Forensic STR profiling using Oxford Nanopore Technologies’ MinION sequencer
Authors: Cornelis Senne , Willems Sander , Van Neste Christophe , Tytgat Olivier , Weymaere Jana , Vander Plaetsen Ann-Sophie , Deforce Dieter , Van Nieuwerburgh Filip
Published: October 2018

Forensic STR profiling using massively parallel sequencing (MPS) has gained much attention as an alternative for the traditional capillary electrophoresis (CE) methods. Oxford Nanopore Technologies recently developed the ‘MinION’, a pocket-sized nanopore sequencer with promising features that could be useful in the field of forensic genetics. We applied this technology for forensic sequencing in a pilot study. Using standard STR primers, originally designed for multiplex PCR and CE, we developed a library preparation method suited for nanopore sequencing. Several analysis approaches were evaluated to explore the usefulness of the generated data: we developed and applied both a sequence-based and an amplicon length-based analysis on data originating from a 14-loci multiplex PCR on a single contributor DNA sample. Despite the high sequencing error rate, the analyses yielded partial forensic profiles with some useful evidential value.
Automatic local resolution-based sharpening of cryo-EM maps
Authors: Ramírez-Aportela Erney , Vilas Jose Luis , Melero Roberto , Conesa Pablo , Martínez Marta , Maluenda David , Mota Javier , Jiménez Amaya , Vargas Javier , Marabini Roberto , Carazo Jose Maria , Sorzano Carlos Oscar S.
Published: October 2018

Recent technological advances and computational developments, have allowed the reconstruction of cryo-EM maps at near-atomic resolution structures. Cryo-EM maps benefit significantly of a “postprocessing” step, normally referred to as “sharpening”, that tends to increase signal at medium/high resolution. Here, we propose a new method for local sharpening of volumes generated by cryo-EM. The algorithm (LocalDeblur) is based on a local resolution-guided Wiener restoration approach, does not need any prior atomic model and it avoids artificial structure 1 factor corrections. LocalDeblur is fully automatic and parameter free. We show that the new method significantly and quantitatively improving map quality and interpretability, especially in cases of broad local resolution changes (as is often the case of membrane proteins).
Revealing the Complexities of Metabarcoding with a Diverse Arthropod Mock Community
Authors: Braukmann Thomas W. A. , Ivanova Natalia V. , Prosser Sean W. J. , Elbrecht Vasco , Steinke Dirk , Ratnasingham Sujeevan , deWaard Jeremy R. , Sones Jayme E. , Zakharov Evgeny V. , Hebert Paul D. N.
Published: October 2018

DNA metabarcoding is an attractive approach for monitoring biodiversity. However, it is subject to biases that often impede detection of all species in a sample. In particular, the proportion of sequences recovered from each species depends on its biomass, mitome copy number, and primer set employed for PCR. To examine these variables, we constructed a mock community of terrestrial arthropods comprised of 374 BINs, a species proxy. We used this community to examine how species recovery was impacted when amplicon pools were constructed in four ways. The first two protocols involved the construction of bulk DNA extracts from different body partitions (Bulk Abdomen, Bulk Leg). The other protocols involved the production of DNA extracts from single legs which were then merged prior to PCR (Composite Leg) or PCR-amplified separately (Single Leg) and then pooled. The amplicon generated by these four treatments were then sequenced on three platforms (Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5). The choice of sequencing platform did not substantially influence species recovery, other variables did. As expected, the best recovery was obtained from the Single Leg treatment, but the Bulk Abdomen produced a more uniform read abundance than the Bulk Leg or Composite Leg samples. Primer choice also influenced species recovery. Our results reveal how variation in protocols can have substantive impacts on perceived diversity unless sequencing coverage is sufficient to reach an asymptote. Although metabarcoding is a powerful approach, further optimization of analytical protocols is crucial to obtain reproducible results and increase its cost-effectiveness.
Urgency reveals an attentional vortex during antisaccade performance
Authors: Salinas Emilio , Steinberg Benjamin R , Sussman Lauren A , Fry Sophia M , Hauser Christopher K , Anderson Denise D , Stanford Terrence R
Published: October 2018

In the antisaccade task, which is considered a sensitive assay of cognitive function, a salient visual cue appears and the participant must look away from it. This requires sensory, motor-planning, and cognitive neural mechanisms. But what are the unique contributions of these mechanisms to performance, and when exactly are they engaged? By introducing an urgency requirement into the antisaccade task, we track the evolution of the choice process with millisecond resolution and find a singular, nonlinear dependence on cue exposure: when viewed briefly (∼100–140 ms), the cue captures attention so powerfully that looking at it (erroneously) is virtually inevitable, but as the cue viewing time increases, the probability of success quickly rises and saturates. The psychophysical and modeling results reveal concerted interactions between reflexive and voluntary cognitive mechanisms that (1) unfold extremely rapidly, (2) are qualitatively consistent across participants, and (3) are nevertheless quantitatively distinctive of each individual’s perceptual capacities
GREB1 amplifies androgen receptor output in prostate cancer and contributes to antiandrogen resistance
Authors: Lee Eugine , Wongvipat John , Choi Danielle , Wang Ping , Zheng Deyou , Watson Philip A. , Gopalan Anuradha , Sawyers Charles L.
Published: October 2018

Genomic amplification of the androgen receptor (AR) is an established mechanism of antiandrogen resistance in prostate cancer. Here we show that the magnitude of AR signaling output, independent of AR genomic alteration or expression level, also contributes to antiandrogen resistance, through upregulation of the coactivator GREB1. We demonstrate 100-fold heterogeneity in AR output within cell lines and show that cells with high AR output have reduced sensitivity to enzalutamide. Through transcriptomic and shRNA knockdown studies, together with analysis of clinical datasets, we identify GREB1 as a gene responsible for high AR output. We show that GREB1 is an AR target gene that amplifies AR output by enhancing AR DNA binding and promoting p300 recruitment. GREB1 knockdown in high AR output cells restores enzalutamide sensitivity in vivo. Thus, GREB1 is a candidate driver of enzalutamide resistance through a novel feed forward mechanism.
Crystal structure of dichloridobis{μ-2-methoxy-6-[(methylimino)methyl]phenolato}{2-methoxy-6-[(methylimino)methyl]phenolato}cadmium(II)cobalt(III) monohydrate
Authors: Vassilyeva Olga Yu. , Kasyanova Katerina V. , Kokozay Vladimir N. , Skelton Brian W.
Published: October 2018

The title compound, [CoCd(C9H10NO2)3Cl2]·H2O, is a solvatomorph of the corresponding hemihydrate recently published by us [Nesterova et al. (2018). Appl. Cat. A, 560, 171–184]. The current structure reveals different cell parameters and space group compared with the published one while both are monoclinic with almost the same cell volume. The title compound is formed of discrete neutral dinuclear molecules with no crystallographically imposed symmetry and water molecules of crystallization. The overall geometry about the cobalt(III) ion is octahedral with an N3O3 environment; each ligand acts as a meridional ONO donor. The CdII coordination sphere approximates an irregular square pyramid with a chlorine atom at the apex. There is significant shortening of a Cd—O bond length to the oxygen atom of the methoxo group on one of the ligands [2.459 (3) Å] compared to the corresponding distance in the published structure [2.724 (7) Å], while other Cd—Cl/N/O bonds remain roughly the same. In the crystal lattice, the heterometallic molecules, which are related by the crystallographic n-glide plane and interlinked by weak hydrogen bonds to solvent water molecules, form columns along [101]. Adjacent columns lie antiparallel to each other.
Rational modification of vanillin derivatives to stereospecifically destabilize sickle hemoglobin polymer formation
Authors: Deshpande Tanvi M. , Pagare Piyusha P. , Ghatge Mohini S. , Chen Qiukan , Musayev Faik N. , Venitz Jurgen , Zhang Yan , Abdulmalik Osheiza , Safo Martin K.
Published: October 2018

Increasing the affinity of hemoglobin for oxygen represents a feasible and promising therapeutic approach for sickle cell disease by mitigating the primary pathophysiological event,i.e.the hypoxia-induced polymerization of sickle hemoglobin (Hb S) and the concomitant erythrocyte sickling. Investigations on a novel synthetic antisickling agent, SAJ-310, with improved and sustained antisickling activity have previously been reported. To further enhance the biological effects of SAJ-310, a structure-based approach was employed to modify this compound to specifically inhibit Hb S polymer formation through interactions which perturb the Hb S polymer-stabilizing αF-helix, in addition to primarily increasing the oxygen affinity of hemoglobin. Three compounds, TD-7, TD-8 and TD-9, were synthesized and studied for their interactions with hemoglobin at the atomic level, as well as their functional and antisickling activitiesin vitro. X-ray crystallographic studies with liganded hemoglobin in complex with TD-7 showed the predicted mode of binding, although the interaction with the αF-helix was not as strong as expected. These findings provide important insights and guidance towards the development of molecules that would be expected to bind and make stronger interactions with the αF-helix, resulting in more efficacious novel therapeutics for sickle cell disease.
Precipitant–ligand exchange technique reveals the ADP binding mode inMycobacterium tuberculosisdethiobiotin synthetase
Authors: Thompson Andrew P. , Wegener Kate L. , Booker Grant W. , Polyak Steven W. , Bruning John B.
Published: October 2018

Dethiobiotin synthetase fromMycobacterium tuberculosis(MtDTBS) is a promising antituberculosis drug target. Small-molecule inhibitors that targetMtDTBS provide a route towards new therapeutics for the treatment of antibiotic-resistant tuberculosis. Adenosine diphosphate (ADP) is an inhibitor ofMtDTBS; however, structural studies into its mechanism of inhibition have been unsuccessful owing to competitive binding to the enzyme by crystallographic precipitants such as citrate and sulfate. Here, a crystallographic technique termed precipitant–ligand exchange has been developed to exchange protein-bound precipitants with ligands of interest. Proof of concept for the exchange method was demonstrated using cytidine triphosphate (CTP), which adopted the same binding mechanism as that obtained with traditional crystal-soaking techniques. Precipitant–ligand exchange also yielded the previously intractable structure ofMtDTBS in complex with ADP solved to 2.4 Å resolution. This result demonstrates the utility of precipitant–ligand exchange, which may be widely applicable to protein crystallography.
Using sound pulses to solve the crystal-harvesting bottleneck
Authors: Samara Yasmin N. , Brennan Haley M. , McCarthy Liam , Bollard Mary T. , Laspina Denise , Wlodek Jakub M. , Campos Stefanie L. , Natarajan Ramya , Gofron Kazimierz , McSweeney Sean , Soares Alexei S. , Leroy Ludmila
Published: October 2018

Crystal harvesting has proven to be difficult to automate and remains the rate-limiting step for many structure-determination and high-throughput screening projects. This has resulted in crystals being prepared more rapidly than they can be harvested for X-ray data collection. Fourth-generation synchrotrons will support extraordinarily rapid rates of data acquisition, putting further pressure on the crystal-harvesting bottleneck. Here, a simple solution is reported in which crystals can be acoustically harvested from slightly modified MiTeGen In Situ-1 crystallization plates. This technique uses an acoustic pulse to eject each crystal out of its crystallization well, through a short air column and onto a micro-mesh (improving on previous work, which required separately grown crystals to be transferred before harvesting). Crystals can be individually harvested or can be serially combined with a chemical library such as a fragment library.
The X-ray structure of human calbindin-D28K: an improved model
Authors: Noble James W. , Almalki Rehab , Roe S. Mark , Wagner Armin , Duman Ramona , Atack John R.
Published: October 2018

Calbindin-D28K is a widely expressed calcium-buffering cytoplasmic protein that is involved in many physiological processes. It has been shown to interact with other proteins, suggesting a role as a calcium sensor. Many of the targets of calbindin-D28K are of therapeutic interest: for example, inositol monophosphatase, the putative target of lithium therapy in bipolar disorder. Presented here is the first crystal structure of human calbindin-D28K. There are significant deviations in the tertiary structure when compared with the NMR structure of rat calbindin-D28K (PDB entry 2g9b), despite 98% sequence identity. Small-angle X-ray scattering (SAXS) indicates that the crystal structure better predicts the properties of calbindin-D28K in solution compared with the NMR structure. Here, the first direct visualization of the calcium-binding properties of calbindin-D28K is presented. Four of the six EF-hands that make up the secondary structure of the protein contain a calcium-binding site. Two distinct conformations of the N-terminal EF-hand calcium-binding site were identified using long-wavelength calcium single-wavelength anomalous dispersion (SAD). This flexible region has previously been recognized as a protein–protein interaction interface. SAXS data collected in both the presence and absence of calcium indicate that there are no large structural differences in the globular structure of calbindin-D28K between the calcium-loaded and unloaded proteins.
High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design
Authors: Lountos George T. , Raran-Kurussi Sreejith , Zhao Bryan M. , Dyas Beverly K. , Burke Terrence R. , Ulrich Robert G. , Waugh David S.
Published: October 2018

Here, new crystal structures are presented of the isolated membrane-proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTP∊), a protein tyrosine phosphatase that has been shown to play a positive role in the survival of human breast cancer cells. A triple mutant of the PTP∊ D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTP∊ D1 catalytic domain that are important for phosphatase activity, resulting in only a slight increase in the phosphatase activity compared with the native D2 protein. The structures reported here are of sufficient resolution for structure-based drug design, and a microarray-based assay for high-throughput screening to identify small-molecule inhibitors of the PTP∊ D1 domain is also described.
Robot nonlinear control for Unmanned Aerial Vehicles’ multitasking
Authors: Andaluz Víctor H. , Gallardo Cristian M. , Chicaiza Fernando A. , Carvajal Christian P. , Morales José , Cuzco Giovanny , Morales Vicente , Vaca Byron E. , Samaniego Nicolay
Published: October 2018

Purpose

This paper aims to present a unified motion control scheme for quadcopters which not only solves the point stabilization and trajectory tracking problems but also the path following problem.

Design/methodology/approach

The control problem is solved based on the kinematic model of the unmanned aerial vehicles (UAV). Next, a dynamic compensation controller is considered through of a quadcopter-inner-loop system to independently track four velocity commands: forward, lateral, up/downward and heading rate. Stability and robustness of the whole control system are proved through the Lyapunov’s method. To evaluate the controller’s performance, a multi-user application which allows bilateral communication between a ground station and the Phantom 3 PRO quadrotor is developed.

Findings

The performance of the proposed unified controller is shown through real experiments for the different motion control objectives: point stabilization, trajectory tracking and path following. The experiments confirm the capability of the unified controller to solve different motion problems by an adequate selection of the control references.

Originality/value

This work proposes the design of three types of motion controllers, which can be switched to comply a task in outdoor. Based on the software development kit provided by the company DJI, an application to get and send data to the UAV is developed. By means of this application, the three tasks are tested and the robustness of the controllers is proved.
Analysing the accounting measurement of financial sustainability in local governments through political factors
Authors: Rodríguez Bolívar Manuel Pedro , Navarro Galera Andrés , López Subirés María Deseada , Alcaide Muñoz Laura
Published: October 2018

Purpose

The purpose of this paper is to obtain new knowledge about the accounting measurement of financial sustainability in local governments, by studying the influence of political factors on the evolution of income statements.

Design/methodology/approach

This paper analyses income statements of Spanish municipalities from 2006 to 2014, together with mayor profiles and political-institutional factors, using the generalised method of moments system.

Findings

The income statement represents a useful measure to assess financial sustainability, showing the effect of political factors on three dimensions proposed by IFAC (i.e. service, revenue and debt), such as ideological coincidence, political competition, political ideology, and absolute majority or political fragmentation.

Practical implications

The findings can be useful for policymakers and accountants responsible for accountability, supervisory bodies, fiscal authorities, voters, users of public services and other stakeholders interested in governmental income statements.

Social implications

In the Eurozone, the crisis of government finance has made the citizens and the policymakers question the size and volume of public services. Likewise, in countries such as Spain, politicians remain one of the main problems for citizens. These circumstances make it very interesting and timely to study the accounting measurement of financial sustainability and its political explanations.

Originality/value

The findings provide new empirical evidence about the accounting measurement of financial sustainability in local governments, and they identify political factors that influence the evolution of income statements.