bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a Sample of Patients With Unilateral Cleft Lip and Palate Treated With a Two-Stage Protocol
Authors: Brusati Roberto , Meazzini Maria Costanza , Rezzonico Angela , Biglioli Federico , Garattini Giovanna , Battista Valeria Marinella Augusta , Autelitano Luca
Published: October 2018

The aim of this paper was to assess growth, speech, and aesthetic results at the completion of growth in patients with unilateral cleft lip and palate treated with the 2 stages Milan surgical protocol.

Craniofacial growth was evaluated with cephalometric analysis and a theoretical need for orthognathic surgery.

Nasolabial appearance was qualitatively assessed using the Asher McDade Aesthetic Index.

Speech was assessed using the Gos.Sp.Ass ’98 modified for Italian language scoring system.

Burden of care was recorded in terms of number of secondary surgical procedures. All of the patients were treated and evaluated at San Paolo Hospital, Smile House, Milan.

Fifty-two consecutive patients treated by the same surgeon were recalled, 12 patients did not come for assessment.

The first surgical step (average age of 6 months) was cheilorhinoplasty (Millard modified Delaire technique) and soft palate rapair (Pigott). The second step (average age of 35 months) was hard palate and alveolar repair performed simultaneously with an early secondary gengivo alveolo plasty. Fifty-six percent of the patients did not need further surgery after the 2-stage surgery protocol.

The 2-stage surgical protocol of Milano, Smile House, seems to be effective for treatment of unilateral cleft lip and palate, with good results in terms of speech, labial appearance, and alveolar cleft management. Nevertheless, maxillary growth was moderately impaired by the protocol.
Can Volumetric and Morphological Variants of Sphenoid Sinuses Influence Sinuses Opacification?
Authors: Gibelli Daniele Maria , Cellina Michaela , Gibelli Stefano , Schiavo Paolo , Oliva Antonio Giancarlo , Termine Giovanni , Ferrario Virgilio F. , Dolci Claudia , Sforza Chiarella
Published: October 2018

Improvements in computed tomography and in functional endoscopic sinus surgery have recently increased interest toward paranasal sinus anatomy and anatomic variations that can be observed in patients affected by sinusitis. Isolated sphenoid sinusitis is a relatively rare pathology, often related to nonspecific symptoms, therefore making diagnosis difficult. The correlation between this type of sinusitis and anatomical variants remains unclear.

The authors’ aim was to retrospectively revise paranasal sinuses computed tomography scans of patients affected by sphenoid sinusitis, compared with a control group, analyzing the types of sphenoid sinus and the presence of aberrant pneumatization, and performing a segmentation of the sphenoid sinuses to calculate the volumes.

Sphenoid sinuses of 60 patients affected by sinus opacification, compared with a control group, were segmented. Type of sinus (sellar, presellar, postsellar) and presence of aberrant pneumatization were assessed as well. Possible statistically significant differences in volumes according to sex and group were assessed through 2-way ANOVA test (P < 0.05). Post-hoc test was assessed through Student t test. χ
2 test was applied in order to verify the statistically significance of differences in frequency of different types of sinus pneumatization variants (P < 0.05).

Average volume of sphenoid sinuses in males was of 7.672 cm3 and of 7.751 cm3 in females within the group of patients; statistically significant differences in volume were found according to sex (P: 0.342), but not between the patients and control group (P: 0.0929). Post-hoc test verified that males affected by sinus opacification showed smaller volumes in comparison with the control males (P < 0.05). In addition, patients by affected sinus opacification showed more frequently the postsellar type and were less affected by pneumatization variants of the sphenoid bone than the control group (P < 0.05).

This study first suggests the possible protective role of variants of pneumatization in the development of sphenoid sinus opacification.
Novel Application of Platelet-Rich Fibrin as a Wound Healing Enhancement in Extraction Sockets of Patients Who Smoke
Authors: Asmael Huda Moutaz , Jamil Firas A. , Hasan Ali Mohammed
Published: October 2018

The objectives of this study were to assess the potential of platelet-rich fibrin (PRF) on acceleration of soft tissue healing after tooth extraction and to evaluate its effectiveness in reducing the prevalence of dry socket among smoker patients. Twenty smoker male patients aged (18–72) years with multiple teeth extraction were participated in this clinical research. They underwent trans-alveolar extraction of 40 teeth. The extraction sockets were divided in each patient into 2 groups: the study group in which extraction sockets were treated with PRF and the control group: in which extraction sockets left to heal naturally without PRF. Platelet-rich fibrin enhanced soft tissue healing and reduced inflammatory process within the study group compared with control group as the 2-tailed P value equaled 0.0035 which was very statistically significant. Pain level according to visual analog scale in control group had average of (1.8), while in the study group had average of (0.65) and the P value equaled 0.1511 which was not statistically significant. Degree of epithelization was recorded by dental caliper for both groups and the 2-tailed P value equaled 0.7134 which was insignificant. The results from this study showed that PRF enhanced the quality of soft tissue healing of extraction socket among smoker patients but it did not show significant difference regarding pain reduction, dry socket prevention, and socket closure. Future clinical trials are required to clearly identify the effectiveness of PRF regarding this subject.
Huge Extra Cranial Arteriovenous Malformation Presenting as Fluctuant Mass in Scalp
Authors: Ogul Hayri , Keskin Emine
Published: October 2018

Arteriovenous malformation (AVM) of the scalp is an uncommon condition. Clinical manifestations usually include local pain, pulsatile mass, headache, numbness, tinnitus; and less frequently, necrosis and hemorrhage. This study discusses and illustrates an unusual case of AVM in scalp with its radiologic appearance and clinical features.
Intra- and Postoperative Complications of Le Fort I Maxillary Osteotomy
Authors: Eshghpour Majid , Mianbandi Vajiheh , Samieirad Sahand
Published: October 2018

Background:

The Le Fort I maxillary osteotomy is a versatile and simple procedure, which has gained popularity nowadays, to correct a wide range of malocclusion and maxillofacial deformities. This procedure is often associated with significant but rare postoperative complications. The aim of this study was to evaluate the types and frequencies of intra- and perioperative complications related to Le Fort I osteotomies in noncleft Iranian patients.

Materials and Methods:

In this prospective study, all the healthy systemic patients, (ASA I, II) with the age range of 18 to 30 years from both genders, who had the skeletal class II or III deformities and required only isolated 1-piece maxillary Le Fort I osteotomy, were included in this study. These patients had no craniofacial cleft history and were candidates for orthognathic surgery in Maxillofacial Surgery Department of Qaem Hospital of Mashhad (Iran), 2015 to 2017. All of the operations were carried out or supervised by a single surgeon and anesthesiologist using the same protocol. The patients were monitored for occurrence of intra- or postoperative complications till 6 months. The t-test, Chi-squared test, and Fisher exact test were performed for data analysis using SPSS version 16 (SPSS Inc, Chicago, IL).

Results:

In the present study, a total of 114 consecutive patients with the average age of 22 ± 5 years from October 2015 to November 2017 were recruited. About 77 (67.54%) patients were presented skeletal class III deformity and 37 (32.46%) were class II. The most prevalent maxillary movement after Le Fort I osteotomy was identified to be isolated maxillary advancement in 51 (44.75%) patients. Only 10 (8.77%) of all 114 patients confronted surgical complications. Hemorrhagic complication (arterial bleeding from descending palatine artery and epistaxis) and anatomic complications (septal deviation and bad fracture) would be the most prevalent complications with the frequency of 5.25% and 3.5% in total. Maxillary setback with impaction presented the highest rate (36.4%) of complications compared to other maxillary movement types. On balance, there was a significant association between Le Fort I surgery complications and maxillary movement types in our research (P = 0.002).

Conclusion:

The rate of intra- and postoperative complications following Le Fort I osteotomy for healthy noncleft adults in our center was low. Therefore, it can be concluded that this technique is safe and reliable. The maxillofacial surgeon should pay more attention for prevention or even management of the risk of intra- and perioperative complications in patients with anatomic irregularities (previous craniofacial cleft or trauma history) and those who required maxillary setback concomitant with impaction movements.
Does the incidence of thoracic aortic injury warrant the routine use of chest computed tomography in children?
Authors: Arbuthnot Mary , Onwubiko Chinwendu , Osborne Michele , Mooney David P.
Published: October 2018

BACKGROUND

Thoracic aortic injury is a potentially life-threatening injury associated with rapid deceleration mechanisms. Diagnosis is made by chest computed tomography (CT), which is associated with a risk of radiation-induced malignancy. We sought to determine the incidence of aortic injuries in the pediatric population to weigh against the risk of CT imaging.

METHODS

The Pediatric Health Information Systems was queried for children ≤18 years with discharge diagnosis code of thoracic aortic injury (901.0) between December 2004 and 2014. Data abstracted included patient age, gender, diagnosis and procedure codes, and discharge disposition, where available. We also queried for imaging codes to determine what type of chest imaging the child received.

RESULTS

Between December 2004 and 2014, 311,850 children were admitted to Pediatric Health Information Systems hospitals with traumatic injury. Of these patients, 46 (0.015%) were coded with a thoracic aortic injury and an accompanying E-code. Twenty-seven patients (58.7%) were male, and the median age was 13 years. The most common mechanism of injury was motor vehicle collision (63%, n = 29). Eighteen hospitals (41.9%) had no patients with a thoracic aortic injury in the 10-year period. In children with a thoracic aortic injury, the mortality rate was 11% (n = 5) and 22 (47.8%) underwent a chest CT during their hospitalization. Forty percent (124,909) of all trauma patients underwent chest CT, with a positive rate for aortic injury of 1.8/10,000. The reported estimated cancer risk from a chest CT scan is 25/10,000 for girls and 7.5/10, 000 in boys, greater than the positive CT rate.

CONCLUSION

Thoracic aortic injuries are rare in children in the United States. The risk of cancer associated with screening chest CT is greater than the likelihood of identifying an aortic injury. Therefore, screening chest CT scans are unwarranted in injured children.

LEVEL OF EVIDENCE

Therapeutic/Care Management, level IV.
Label-free Identification of Antibody-mediated Rejection in Cardiac Allograft Biopsies Using Infrared Spectroscopic Imaging
Authors: Uraizee Imran , Varma Vishal K. , Sreedhar Hari , Gambacorta Francesca , Nazeer Shaiju S. , Husain Aliya , Walsh Michael J.
Published: October 2018

Background.

Antibody-mediated rejection (AMR) in cardiac allograft recipients remains less well-understood than acute cellular rejection, is associated with worse outcomes, and portends a greater risk of developing chronic allograft vasculopathy. Diffuse immunohistochemical C4d staining of capillary endothelia in formalin-fixed, paraffin-embedded right ventricular endomyocardial biopsies is diagnostic of immunopathologic AMR but serves more as a late-stage marker. Infrared (IR) spectroscopy may be a useful tool in earlier detection of rejection. We performed mid-IR spectroscopy to identify a unique biochemical signature for AMR.

Methods.

A total of 30 posttransplant formalin-fixed paraffin-embedded right ventricular tissue biopsies (14 positive for C4d and 16 negative for C4d) and 14 native heart biopsies were sectioned for IR analysis. Infrared images of entire sections were acquired and regions of interest from cardiomyocytes were identified. Extracted spectra were averaged across many pixels within each region of interest. Principal component analysis coupled with linear discriminant analysis and predictive classifiers were applied to the data.

Results.

Comparison of averaged mid-IR spectra revealed unique features among C4d-positive, C4d-negative, and native heart biopsies. Principal component analysis coupled with linear discriminant analysis and classification models demonstrated that spectral features from the mid-IR fingerprint region of these 3 groups permitted accurate automated classification into each group.

Conclusions.

In cardiac allograft biopsies with immunopathologic AMR, IR spectroscopy reveals a biochemical signature unique to AMR compared with that of nonrejecting cardiac allografts and native hearts. Future study will focus on the predictive capabilities of this IR signature.
CyanoGate: A Golden Gate modular cloning suite for engineering cyanobacteria based on the plant MoClo syntax
Authors: Vasudevan Ravendran , Gale Grant A.R. , Schiavon Alejandra A. , Puzorjov Anton , Malm John , Gillespie Michael D. , Vavitsas Konstantinos , Zulkower Valentin , Wang Baojun , Howe Christopher J. , Lea-Smith David , McCormick Alistair J.
Published: October 2018

Recent advances in synthetic biology research have been underpinned by an exponential increase in available genomic information and a proliferation of advanced DNA assembly tools. The adoption of plasmid vector assembly standards and parts libraries has greatly enhanced the reproducibility of research and exchange of parts between different labs and biological systems. However, a standardised Modular Cloning (MoClo) system is not yet available for cyanobacteria, which lag behind other prokaryotes in synthetic biology despite their huge potential in biotechnological applications. By building on the assembly library and syntax of the Plant Golden Gate MoClo kit, we have developed a versatile system called CyanoGate that unites cyanobacteria with plant and algal systems. We have generated a suite of parts and acceptor vectors for making i) marked/unmarked knock-outs or integrations using an integrative acceptor vector, and ii) transient multigene expression and repression systems using known and novel replicative vectors. We have tested and compared the CyanoGate system in the established model cyanobacteriumSynechocystissp. PCC 6803 and the more recently described fast-growing strainSynechococcus elongatusUTEX 2973. The system is publicly available and can be readily expanded to accommodate other standardised MoClo parts.
Coverage and timeliness of vaccination and the validity of routine estimates: Insights from a Vaccine Registry in Kenya
Authors: Adetifa Ifedayo M.O. , Karia Boniface , Mutuku Alex , Bwanaali Tahreni , Makumi Anne , Wafula Jackline , Chome Martina , Mwatsuma Pauline , Bauni Evasius , Hammitt Laura L , Mataza Christine , Tabu Collins , Kamau Tatu , William Thomas N. , G. Scott J. Anthony
Published: October 2018

The benefits of childhood vaccines are critically dependent on vaccination coverage. We used a vaccine registry (as gold standard) in Kenya to quantify errors in routine coverage methods (surveys and administrative reports), to estimate the magnitude of survivor bias, contrast coverage with timeliness and use both measures to estimate population immunity.

We found coverage surveys in the 2nd year of life overestimate coverage by 2%. Compared to mean coverage in infants, static coverage at 12 months was exaggerated by 7–8% for third doses of oral polio, pentavalent (Penta3) and pneumococcal conjugate vaccines, and by 24% for the measles vaccine. Surveys and administrative coverage also underestimated the proportion of the fully immunised child by 10–14%. For BCG, Penta3 and measles, timeliness was 23–44% higher in children born in a health facility but 20–37% lower in those who first attended during vaccine stock outs.

Coverage surveys in 12–23 month old children overestimate protection by ignoring timeliness, and survivor and recall biases.
Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm
Authors: Gladstein Scott , Almassalha Luay M. , Cherkezyan Lusik , Chandler John E. , Eshein Adam , Eid Aya , Zhang Di , Wu Wenli , Bauer Greta M. , Stephens Andrew D. , Morochnik Simona , Subramanian Hariharan , Marko John F. , Ameer Guillermo A. , Szleifer Igal , Backman Vadim
Published: October 2018

We present a multimodal label-free interferometric imaging platform for measuring intracellular nanoscale structure and macromolecular dynamics in living cells with a sensitivity to macromolecules as small as 20nm and millisecond temporal resolution. We validate this system by pairing experimental measurements of nanosphere phantoms with a novel interferometric theory. Applying this system in vitro, we explore changes in higher-order chromatin structure and dynamics that occur due to cellular fixation, stem cell differentiation, and ultraviolet (UV) light irradiation. Finally, we discover a new phenomenon, cellular paroxysm, a near-instantaneous, synchronous burst of motion that occurs early in the process of UV induced cell death. Given this platform’s ability to obtain nanoscale sensitive, millisecond resolved information within live cells without concerns of photobleaching, it has the potential to answer a broad range of critical biological questions about macromolecular behavior in live cells, particularly about the relationship between cellular structure and function.
Bridging the spatiotemporal scales of macromolecular transport in crowded biomimetic systems
Authors: Regan Kathryn , Wulstein Devynn , Rasmussen Hannah , McGorty Ryan , Robertson-Anderson Rae M.
Published: October 2018

Crowding plays a key role in the transport and conformations of biological macromolecules. Gene therapy, viral infection and transfection require DNA to traverse the crowded cytoplasm, including a heterogeneous cytoskeleton of filamentous proteins. Given the complexity of cellular crowding, the dynamics of biological molecules can be highly dependent on the spatiotemporal scale probed. We present a powerful platform that spans molecular and cellular scales by coupling single-molecule conformational tracking (SMCT) and selective-plane illumination differential dynamic microscopy (SPIDDM). We elucidate the transport and conformational properties of large DNA, crowded by custom-designed networks of actin and microtubules, to link single-molecule conformations with ensemble DNA transport and cytoskeleton structure. We show that actin crowding leads to DNA compaction and suppression of fluctuations, combined with anomalous subdiffusion and heterogeneous transport, whereas microtubules have much more subdued impact across all scales. Interestingly, in composite networks of both filaments, microtubules primarily govern single-molecule DNA dynamics whereas actin governs ensemble transport.
Straightjacket/α2δ3deregulation is associated with cardiac conduction defects in Myotonic Dystrophy type 1
Authors: Plantié Emilie , Nakamori Masayuki , Renaud Yoan , Huguet Aline , Choquet Caroline , Dondi Cristiana , Miquerol Lucile , Takahashi Masanori , Gourdon Geneviève , Junion Guillaume , Jagla Teresa , Zmojdzian Monika , Jagla Krzysztof
Published: October 2018

Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a complex toxic CTG repeat disorder involving misbalance between two RNA- binding factors, MBNL1 and CELF1. How this pathogenic DM1 condition translates into cardiac conduction disorders remains poorly understood. Here, we simulated MBNL1 and CELF1 misbalance in theDrosophilaheart and identified associated gene deregulations using TU-tagging based transcriptional profiling of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels and among them increased expression ofstraightjacket/α2δ3that encodes a regulatory subunit of a voltage-gated calcium channel.Straightjacketoverexpression in the fly heart leads to asynchronous heart beating, a hallmark of affected conduction, whereas cardiacstraightjacketknockdown improves these symptoms in DM1 fly models. We also show that ventricularα2δ3expression is low in healthy mice and humans but significantly elevated in ventricular muscles from DM1 patients with conduction defects. Taken together, this suggests that reducing thestraightjacket/α2δ3transcript levels in ventricular cardiomyocytes could represent a strategy to prevent conduction defects and in particular intraventricular conduction delay associated with DM1 pathology.
Redistribution of a glucuronoxylomannan epitope towards the capsule surface coincides with Titanisation in the human fungal pathogenCryptococcus neoformans
Authors: Probert Mark , Zhou Xin , Goodall Margaret , Johnston Simon A. , Bielska Ewa , Ballou Elizabeth R. , May Robin C.
Published: October 2018

Disseminated infections with the fungal speciesCryptococcus neoformansor, less frequently,C. gattii,are a leading cause of mortality in immunocompromised individuals. Central to the virulence of both species is an elaborate polysaccharide capsule that consists predominantly of glucuronoxylomannan (GXM). Due to its abundance, GXM is an ideal target for host antibodies, and several monoclonal antibodies (mAbs) have previously been derived using purified GXM or whole capsular preparations as antigen. In addition to their application in the diagnosis of cryptococcosis, anti-GXM mAbs are invaluable tools for studying capsule structure. In this study, we report the production and characterisation of a novel anti-GXM mAb, Crp127, that unexpectedly reveals a role for GXM remodelling during the process of fungal Titanisation. We show that Crp127 recognises a GXM epitope in anO-acetylation dependent, but xylosylation-independent, manner. The epitope is differentially expressed by the four main serotypes ofCryptococcus neoformansandgattii,is heterogeneously expressed within clonal populations ofC. gattiiserotype B strains and is typically confined to the central region of the enlarged capsule. Uniquely, however, this epitope redistributes to the capsular surface in Titan cells, a recently recognised subset of giant fungal cells that are produced in the host lung and are critical for successful infection. Crp127 therefore highlights hitherto unexpected features of cryptococcal morphological change and may hold significant therapeutic potential in differentially identifying cryptococcal strains and subtypes.

Importance

Cryptococcus neoformansandCryptococcus gattiiare the etiological agents of cryptococcosis, an invasive fungal infection responsible for approximately 200,000 deaths each year and 15% of AIDS-related deaths annually. Whilst the main virulence factor for both species is a highly variable polysaccharide capsule, formation of Titan cells also underlies the pathogenesis ofC. neoformans.Previous studies have shown that capsule composition differs between yeast and Titan cells, however no clear distinctions in the expression or localisation of specific capsular epitopes have been made. In this study, we characterise a novel monoclonal antibody (mAb) specific to a capsular epitope that is differentially distributed throughout the capsules produced by yeast and Titan cells. Whilst this epitope is found within the midzone of yeast capsules, the presentation of this epitope on the surface of Titan cell capsules may represent a way in which these cell types are perceived differently by the immune system.
Immune regeneration in irradiated mice is not impaired by the absence of DPP9 enzymatic activity
Authors: Gall Margaret G. , Zhang Hui Emma , Cook Adam , Jolly Christopher J. , McCaughan Geoffrey W. , Roediger Ben , Gorrell Mark D.
Published: October 2018

The ubiquitous intracellular protease dipeptidyl peptidase 9 (DPP9) has roles in antigen presentation and B cell signaling. To investigate the importance of DPP9 in immune regeneration, primary and secondary chimeric mice were created in irradiated recipients using fetal liver cells and adult bone marrow cells, respectively, using wild-type (WT) and DPP9 gene-knockin (DPP9S729A) enzyme-inactive mice. Immune cell reconstitution was assessed at 6 and 16 weeks post-transplant. Primary chimeric mice successfully regenerated neutrophils, natural killer, T and B cells, irrespective of donor cell genotype. There were no significant differences in total myeloid cell or neutrophil numbers between DPP9-WT and DPP9S729A-reconstituted mice. There were fewer B cells in the DPP9S729A-origin compared to DPP9 WT-origin mice in primary chimeric mice. In secondary chimeric mice, cells of DPP9S729A-origin cells displayed enhanced engraftment compared to WT. However, we observed no differences in myeloid or lymphoid lineage reconstitution between WT and DPP9S729A donors, indicating that hematopoietic stem cell (HSC) engraftment and self-renewal is not diminished by the absence of DPP9 enzymatic activity. This is the first report on transplantation of bone marrow cells that lack DPP9 enzymatic activity.
Proteomic Profile of TGF-β1 treated Lung Fibroblasts identifies Novel Markers of Activated Fibroblasts in the Silica Exposed Rat Lung
Authors: Na Mao , Hong Xu , Fuyu Jin , Dingjie Xu , Sales Dominic , Hui Zhang , Zhongqiu Wei , Shifeng Li , Xuemin Gao , Wenchen Cai , Dan Li , Guizhen Zhang , Bonan Zhang , Lijuan Zhang , Shumin Li , Ying Zhu , Jin Wang , Mingwang Rui , Summer Ross , Fang Yang
Published: October 2018

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-β1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-β1 treatment and 196 proteins were expressed at ≥ 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-β1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-β1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-β1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.

Highlights

We identified 196 proteins differentially expressed between control and TGF-β1 treated fibroblastsby LC-MS/MS.

Several proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2

Knockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.
In vivo characterisation of fluorescent proteins in budding yeast
Authors: Botman Dennis , de Groot Daan Hugo , Schmidt Phillipp , Goedhart Joachim , Teusink Bas
Published: October 2018

Fluorescent proteins (FPs) are widely used in many organisms, but are commonly characterised in vitro. However, the in vitro properties may poorly reflect in vivo performance. Therefore, we characterised 27 FPs in vivo using Saccharomyces cerevisiae as model organism. We linked the FPs via a T2A peptide to a control FP, producing equimolar expression of the 2 FPs from 1 plasmid. Using this strategy, we characterised the FPs for brightness, photostability, photochromicity and pH-sensitivity, achieving a comprehensive in vivo characterisation. Many FPs showed different in vivo properties compared to existing in vitro data. Additionally, various FPs were photochromic, which affects readouts due to complex bleaching kinetics. Finally, we codon optimized the best performing FPs for optimal expression in yeast, and found that codon-optimization alters FP characteristics. These FPs improve experimental signal readout, opening new experimental possibilities. Our results may guide future studies in yeast that employ fluorescent proteins.
Motor context dominates output from Purkinje cell functional regions during reflexive visuomotor behaviours
Authors: Knogler Laura D. , Kist Andreas M. , Portugues Ruben
Published: October 2018

The cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum.
Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships
Authors: Howden Sara E , Vanslambrouck Jessica M , Wilson Sean B , Tan Ker Sin , Little Melissa H
Published: October 2018

While mammalian kidney morphogenesis has been well documented, human kidney development is poorly understood. Here we combine reprogramming, CRISPR/Cas9 gene-editing and organoid technologies to study human nephron lineage relationships in vitro. Early kidney organoids contained a SIX2+ population with a transcriptional profile akin to human nephron progenitors. Lineage-tracing using gene-edited induced pluripotent stem cell (iPSC) lines revealed that SIX2-expressing cells contribute to nephron formation but not to the putative collecting duct epithelium. However, Cre-mediated temporal induction of the SIX2+ lineage revealed a declining capacity for these cells to contribute to nephron formation over time. This suggests human kidney organoids, unlike the developing kidney in vivo, lack a nephron progenitor niche capable of both self-renewal and ongoing nephrogenesis. Nonetheless, human iPSC-derived kidney tissue maintains previously identified lineage relationships supporting the utility of pluripotent stem cell-derived kidney organoids for interrogating the molecular and cellular basis of early human development.
IRE1α is critical for kaempferol induced neuroblastoma differentiation
Authors: Abdullah Ahmad , Talwar Priti , Ravanan Palaniyandi
Published: October 2018

Neuroblastoma is an embryonic malignancy arises out of the neural crest cells of the sympathetic nervous system. It is the most common childhood tumor and well known for its spontaneous regression via the process of differentiation. The induction of differentiation using small molecule modulators such as all trans retinoic acid is one of the treatment strategies to treat the residual disease. In this study, we have reported the effect of kaempferol, a phytoestrogen in inducing differentiation of neuroblastoma cellsin vitro. Treatment of neuroblastoma cells with kaempferol reduced the proliferation and enhanced apoptosis along with the induction of neuritogenesis. Analysis of the expression of neuron specific markers such as β III tubulin, neuron specific enolase and NRDG1 (N-myc down regulated gene 1) revealed the process of differentiation accompanying kaempferol induced apoptosis. Further analysis on understanding the molecular mechanism of action showed that the activity of kaempferol happened through the activation of the endoribonuclease activity of IRE1α (Inositol requiring enzyme 1 alpha), an endoplasmic reticulum (ER) resident transmembrane protein. Thein silicodocking analysis and biochemical assays using recombinant human IRE1α confirms the binding of kaempferol to the ATP binding site of IRE1α and thereby activating ribonuclease activity. Treatment of cells with the small molecule inhibitor STF083010 which specifically targets and inhibits the endoribonuclease activity of IRE1α showed reduced expression of neuron specific markers and curtailed neuritogenesis. The knock down of IRE1α using plasmid based shRNA lentiviral particles also showed diminished changes in the change in morphology of the cells upon kaempferol treatment. Thus our study suggests that kaempferol induces differentiation of neuroblastoma cells via the IRE1α-XBP1 pathway.
Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia
Authors: Popa Traian , Morris Laurel S. , Hunt Rachel , Deng Zhi-De , Horovitz Silvina , Mente Karin , Shitara Hitoshi , Baek Kwangyeol , Hallett Mark , Voon Valerie
Published: October 2018

The mesial prefrontal cortex, cingulate cortex and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity. In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre-and post-TMS functional connectivity using seed-based and independent components analysis. In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum. These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesioprefrontal–cingulo–striatal circuit.
Quiescent cells actively replenish CENP-A nucleosomes to maintain centromere identity and proliferative potential
Authors: Swartz S. Zachary , McKay Liliana S. , Su Kuan-Chung , Padeganeh Abbas , Maddox Paul S. , Knouse Kristin A. , Cheeseman Iain M.
Published: October 2018

Centromeres provide a robust model for epigenetic inheritance as they are specified by sequence-independent mechanisms involving the histone H3-variant CENP-A. Prevailing models indicate that the high intrinsic stability of CENP-A nucleosomes maintains centromere identity indefinitely. Here, we demonstrate that CENP-A is not stable at centromeres, but is instead gradually and continuously incorporated in quiescent cells including G0-arrested tissue culture cells and prophase I-arrested oocytes. Quiescent CENP-A incorporation involves the canonical CENP-A deposition machinery, but displays distinct requirements from cell cycle-dependent deposition. We demonstrate that Plk1 is required specifically for G1 CENP-A deposition, whereas transcription promotes CENP-A incorporation in quiescent oocytes. Preventing CENP-A deposition during quiescence results in significantly reduced CENP-A levels and perturbs chromosome segregation following the resumption of cell division. In contrast to quiescent cells, terminally differentiated cells fail to maintain CENP-A levels. Our work reveals that quiescent cells actively maintain centromere identity providing an indicator of proliferative potential.
Cloning and functional characterization of Komagataella phaffii centromeres by a color-based plasmid stability assay
Authors: Piva Luiza Cesca , De Marco Janice Lisboa , de Moraes Lidia Maria Pepe , Branco Reis Viviane Castelo , Gonçalves Torres Fernando Araripe
Published: October 2018

The yeast Komagataella phaffii is widely used as a microbial host for heterologous protein production. However, molecular tools for this yeast are basically restricted to a few integrative and replicative plasmids. Four sequences that have recently been proposed as the K. phaffii centromeres could be used to develop a new class of mitotically stable vectors. In this work we designed a color-based genetic assay to investigate genetic stability in K. phaffii. Plasmids bearing K. phaffii centromeres and the ADE3 marker were evaluated in terms of mitotic stability in an ade2/ade3 auxotrophic strain which allows plasmid screening through colony color. Plasmid copy number was verified through qPCR. Our results confirmed that the centromeric plasmids were maintained at low copy number as a result of typical chromosome-like segregation during cell division. These features, combined with high transformation efficiency and in vivo assembly possibilities, prompt these plasmids as a new addition to the K. phaffii genetic toolbox.
Rubsicolins are naturally occurring G-protein-biased delta opioid receptor peptides
Authors: Cassell Robert J. , Mores Kendall L. , Zerfas Breanna L. , H. Mahmoud Amr , Lill Markus A. , Trader Darci J. , van Rijn Richard M.
Published: October 2018

The impact that β-arrestin proteins have on G-protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. These findings have led to the development of biased opioid small molecule agonists that do not recruit β-arrestin, activating only the canonical G-protein pathway. Similar G-protein biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G-protein-biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G-protein signaling pathways with minimal β-arrestin recruitment. We find that rubiscolin peptides, which are produced as cleavage products of the plant protein rubisco, bind to and activate G-protein signaling at δ opioid receptors. However, unlike the naturally occurring δ opioid peptides leu-enkephalin and deltorphin II, the rubiscolin peptides only very weakly recruit β-arrestin 2 and have undectable recruitment of β-arrestin 1 at the δ opioid receptor.
A multiple rule-based genetic algorithm for cost-oriented stochastic assembly line balancing problem
Authors: Foroughi Ahad , Gökçen Hadi
Published: October 2018

Purpose

This research aims to address the cost-oriented stochastic assembly line balancing problem (ALBP) and propose a chance-constrained programming model.

Design/methodology/approach

The cost-oriented stochastic ALBP is solved for small- to medium-sized problems. Owing to the non-deterministic polynomial-time (NP)-hardness problem, a multiple rule-based genetic algorithm (GA) is proposed for large-scale problems.

Findings

The experimental results show that the proposed GA has superior performance and efficiency compared to the global optimum solutions obtained by the IBM ILOG CPLEX optimization software.

Originality/value

To the best of the authors’ knowledge, only one study has discussed the cost-oriented stochastic ALBP using the new concept of cost. Owing to the NP-hard nature of the problem, it was necessary to develop a heuristic or meta-heuristic algorithm for large data sets; this research paper contributes to filling this gap.
Dynamic modeling and controller design for SEA joints
Authors: Ni Fenglei , Li Tianhui , Liu Yiwei , Liu Hong , Li Yang , Zhao Liangliang , Chen Zhaopeng
Published: October 2018

Purpose

The purpose of this paper is to study the dynamic modeling and controller design for the series element actuator (SEA) joints. The robot equipped with SEA joints is a strong coupling, nonlinear, highly flexible system, which can prevent itself from damaging by the accidental impact and the people to be injured by the robot.

Design/methodology/approach

Based on the torque source model, the authors built a dynamic model for the SEA joint. To improve the accuracy of this model, the authors designed an elastic element into the joint and implemented the vector control for the joint motor. A control method of combined PD controller and back-stepping was proposed. Moreover, the torque control could be transformed into position control by stiffness transformation.

Findings

The established model and the proposed method are verified by the position and torque control experiments. The experimental results show that the dynamic model of the SEA joint is accurate and the proposed control strategies for the SEA joint are reasonable and feasible.

Originality/value

The main contribution of the paper is as follows: designing an elastic element with high linearity to improve the model accuracy of the SEA joint. The control strategy-based back-stepping method for the SEA joint is proposed to increase the robustness of the controller.
Effective corrosion inhibition of mild steel in acidic medium using inexpensive kermes natural dye: experimental and quantum chemical study
Authors: El Boraei Nobl F. , Halim Shimaa Abdel , Ibrahim Magdy A.M.
Published: October 2018

Purpose

The purpose of this paper is to test the Natural Kermes dye (NKD) as a cheap and stable corrosion inhibitor for mild steel in 1.0 M HCl and its adsorption mechanism on the steel surface.

Design/methodology/approach

The inhibition action of NKD was studied using AC impedance, potentiodynamic polarization, scanning electron microscope (SEM) and UV-visible spectra techniques complemented with quantum study.

Findings

Here, the authors show that addition of NKD inhibits effectively the corrosion of steel in HCl solution via its adsorption on the steel surface. The inhibition efficiency of NKD increases with increase in its concentration and decreases with temperature. Potentiodynamic results revealed that NKD acts as a mixed–type inhibitor. Thermodynamic parameters for corrosion and adsorption process were obtained from the experimental data. Moreover, the experimental inhibition efficiencies were correlated with the electronic properties of NKD using density functional theory.

Originality/value

To the best of the authors’ knowledge, this is the first report showing the effect of NKD on the corrosion inhibition of steel.
Comparing fluid ring and CMG servomechanisms for active control of rigid satellites
Authors: Akbaritabar Saleh , Esmaelzadeh Reza , Zardashti Reza
Published: October 2018

Purpose

This paper aims to describe a novel type of attitude control system (ACS) in different configurations. This servomechanism is compared with control moment gyro (CMG) in significant parameters of performance for ACS of rigid satellite.

Design/methodology/approach

This new actuator is the fluid containing one or more rings and fluid flow is supplied by pump. The required torque control is obtained by managing fluid angular velocity. The cube-shaped satellite with three rings of fluid in the principle axes is considered for modeling. The satellite is considered rigid and nonlinear dynamics equation is used for it. In addition, the failure of the pyramid-shaped satellite with an additional ring fluid is discussed.

Findings

The controller model for four fluid rings has more complexity than for three fluid rings. The simulation results illustrated that four fluid rings need less energy for stabilization than three fluid rings. The performance of this type of actuator is compared with CMG. At last, it is demonstrated that performance parameters are improved with fluid ring actuator.

Research limitations/implications

Fluid ring actuator can be affected by environmental pressure and temperature. Therefore, freezing and boiling temperature of the fluid should be considered in system designation.

Practical implications

Fluid ring servomechanism can be used as ACS in rigid satellites. This actuator is compared by CMG, the prevalent actuator. It has less displacement attitude maneuver.

Originality/value

The results provide the feasibility and advantages of using fluid rings as satellite ACS. The quaternion error controller is used for this model to enhance its performance.