bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Transverse Ultrasound Images on the Classification and Treatment of Pediatric Lateral Humeral Condyle Fractures
Authors: Li Xiong-tao , Shen Xian-tao , Wu Xing , Li Jun , Xia Jing-dong
Published: December 2019

Background:

Pediatric lateral humeral condyle fractures (LHCFs) are sometimes misdiagnosed and inappropriately treated on the basis of x-ray radiographs because cartilage cannot be seen on radiographs. However, as a useful technique, transverse ultrasonography can accurately and readily determine the integrity of the cartilage hinge in pediatric LHCFs. The purpose of this study was to assess the reliability of the Jakob classification, the treatment plan, and the necessity for further examination of pediatric LHCFs with the use of x-ray with and without transverse ultrasound images.

Methods:

Five pediatric orthopaedic surgeons with different levels of experience evaluated 62 cases on the basis of the use of x-ray alone and x-ray combined with transverse ultrasound images. These 2 types of evaluations were repeated after an interval of 4 to 6 weeks. At the time of each evaluation, all observers were asked to classify the fractures according to the Jakob classification, to formulate treatment plans, and to determine whether further examinations were required.

Results:

After the training of transverse ultrasound image interpretation, the interobserver reliability of the Jakob classification significantly improved from fair (a kappa of 0.54) to moderate (a kappa of 0.71) with the addition of transverse ultrasound images. The treatment plan was changed from conservative treatment to surgical treatment in 7% of the ratings but from surgical treatment to conservative treatment in 15% of the ratings after reviewing the ultrasound images, and the difference was statistically significant (P=0.003).

Conclusions:

The use of the Jakob classification and a treatment plan for pediatric LHCFs can be optimized by the addition of transverse ultrasound images, especially after training for transverse ultrasound image interpretation.

Level of Evidence:

Level III—diagnostic study.
Sternal Wound Reconstruction Made Simple
Authors: Levy Adam S. , Ascherman Jeffrey A.
Published: December 2019

Sternal wounds and associated infections represent a complex reconstructive problem in a highly morbid patient population. Through strict adherence to excellent plastic surgical principles, this process can be simplified, allowing safe and effective wound closure. Emphasis is placed on thorough debridement, hardware removal, obtaining adequate tissue cultures, and finally, appropriate flap closure. In most cases, pectoralis major myocutaneous advancement flaps provide excellent coverage while eliminating dead space and providing sternal compression. Secondary flap options, such as the omental flap or rectus abdominis muscle, may occasionally be necessary. This article will provide an overview and simplified approach to sternal wound reconstruction.
Effect of Physical Therapy Dosage on Functional Recovery Following TBI
Authors: Tolland Joseph , Miccile Lauren A. , Burke Katherine
Published: December 2019

Background/Purpose:

Evidence supporting neurorehabilitation dosage after traumatic brain injury is limited. High-dose, high-intensity intervention, involving maximal frequency, time, and patient participation, facilitates neuroplasticity and optimizes outcomes. This patient made significant functional progress with the dosage of therapy provided, warranting investigation into the optimal dosage of therapy in this patient population.

Case Description:

A 27-year-old man with severe, traumatic brain injury defined by the Glasgow Coma Scale received physical therapy in an acute care hospital within a large academic medical center. Due to insurance complications, he was unable to be discharged to an inpatient rehabilitation facility. He remained in the hospital receiving physical therapy until he was safe to be discharged home.

Intervention:

The patient received an average of 16 minutes of physical therapy, 4 times/week, totaling 320 minutes over 35 additional days spent in the acute hospital setting. Treatment focused on progressing functional mobility, preventing complications, and task-specific functional training.

Outcomes:

The patient received a 79% lower dosage of physical therapy than expected based on standard requirements at an acute rehabilitation facility. The patient progressed from actively performing less than 25% of functional tasks to performing 100% of functional tasks with supervision for safety. He ambulated with supervision and negotiated stairs with contact guard assistance at time of discharge.

Discussion:

The patient made significant functional gains. This raises the question of optimal dosage of rehabilitation following traumatic brain injury. We challenge therapists to consider that the optimal dose of rehabilitation in the acute care setting remains unknown and further investigation is needed.
Hearing Recovery After Ejection of Air in a Case of Traumatic Pneumolabyrinth: Mechanism and Management Options
Authors: Oda Kiyoshi , Yamamoto Hiroki , Kobayashi Toshimitsu , Hidaka Hiroshi , Ikeda Ryoukichi , Yoshida Naohiro
Published: December 2019

Objective:

To describe a case of traumatic pneumolabyrinth and subsequent hearing recovery after ejection of air with transcanal endoscopic surgical exploration.

Patients:

A 38-year-old man was struck by his child while cleaning his ear with an ear pick made of bamboo, which penetrated deep into the left ear canal. Severe vertigo with vomiting and left hearing impairment ensued. In addition, high-resolution computed tomography demonstrated an air density within the vestibule.

Interventions:

Exploratory tympanotomy was performed endoscopically a day after the injury and air was ejected from the oval window surgically.

Main Outcome Measures:

High-resolution computed tomography, audiologic testing.

Results:

Several hours after surgery, the patient's subjective vestibular symptoms lessened and 7 days after surgery, the patient felt slight dizziness when moving his head and no apparent spontaneous nystagmus was observed with an infrared charge-coupled device camera and was discharged from the hospital. Two years later, there are no subjective vestibular symptoms at all and the pure-tone average of his left ear improved to 16.7 dB.

Conclusion:

We presented a case of traumatic pneumolabyrinth and the subsequent hearing recovery after ejection of air following endoscopic exploratory tympanotomy. We propose that initial management for traumatic pneumolabyrinth should be ejection of the air bubble if it is located solely in the vestibule and sparing the cochlea.
Latest developments in living kidney donation
Authors: Hilbrands Luuk B.
Published: December 2019

Purpose of review

Although the first successful kidney transplantation 65 years ago was performed with a living donor kidney, the number of living donor kidney transplantations has increased especially during the last 2 decades. The enlargement of living donor programs was made possible by new modes of living donation and by expansion of the living donor pool. At the same time, the long-term risks of kidney donation have been better delineated. In this review, the latest developments on these topics are summarized.

Recent findings

While the results of ABO-incompatible living kidney transplantation are superior to those of deceased donor transplantation, recent meta-analyses show a reduced patient and graft survival as compared with ABO compatible transplantation as well as increased risk of severe infection and bleeding. Kidney paired donation programs can be extended by including compatible couples and by advanced donation, although the latter raises ethical concerns. Living donors appear to have a higher risk of end-stage renal disease and this is especially true for obese donors and probably also for black donors with an APOL1 high-risk genotype. The importance of psychosocial outcomes after living kidney donation is increasingly recognized.

Living donor kidney transplantation remains the optimal treatment option for patients with end-stage renal disease. To increase the donor pool, a well developed paired kidney donation program and sufficient reimbursement of costs associated with donation are essential ingredients. Other ways of expanding the donor pool, such as ABO-incompatible transplantation, use of higher risk donors, providing donors with financial incentives and advanced donation are associated with medical, ethical and logistical complications. There should be a careful selection and follow-up of living kidney donors with attention for medical consequences as well as for psychosocial outcomes.
Evaluation of a Multimodal Resuscitation Program and Comparison of Mouth-to-Mouth and Bag-Mask Ventilation by Relatives of Children With Chronic Diseases*
Authors: Michel Jörg , Hofbeck Michael , Neunhoeffer Felix , Müller Manuel , Heimberg Ellen
Published: December 2019

Objectives:

Children with chronic critical illness are at higher risk for cardiopulmonary arrests. Before chronically ill children are discharged from hospital, family members receive training in basic life support at many institutions. We evaluated whether a multimodal training program is able to teach adherence to current resuscitation guidelines and whether laypersons can be trained to perform both bag-mask ventilation and mouth-to-mouth ventilation equally effective in infants.

Design:

Prospective observational study.

Setting:

Pediatric critical care unit of a tertiary referral center.

Subjects:

Relatives of children with chronic illness prior to discharge from hospital.

Interventions:

Multimodal emergency and cardiopulmonary resuscitation training program.

Measurements and Main Results:

Following participation in our cardiopulmonary resuscitation training program 56 participants performed 112 simulated cardiopulmonary resuscitations (56 with mouth-to-mouth ventilation, 56 with bag-mask ventilation). Nearly all participants checked for consciousness and breathing. Shouting for help and activation of the emergency response system was only performed in half of the cases. There was almost full adherence to the resuscitation guidelines regarding number of chest compressions, chest compression rate, compression depth, full chest recoil, and duration of interruption of chest compression for rescue breaths. The comparison of mouth-to-mouth ventilation and bag-mask ventilation revealed no significant differences regarding the rate of successful ventilation (mouth-to-mouth ventilation: 77.1% ± 39.6%, bag-mask ventilation: 80.4% ± 38.0%; p = 0.39) and the cardiopulmonary resuscitation performance.

Conclusions:

A standardized multimodal cardiopulmonary resuscitation training program for family members of chronically ill children is effective to teach good cardiopulmonary resuscitation performance and adherence to resuscitation guidelines. Laypersons could be successfully trained to equally perform mouth-to-mouth and bag-mask ventilation technique.
Microtubule-associated protein 2 knockdown sensitizes glioma cells to vincristine treatment
Authors: Yang Liusong , Xu Xiaoen , Zheng Jiajun
Published: December 2019

Gliomas are the most common and lethal tumor of the central nervous system (CNS). At present, standard treatment involves chemotherapy and radiotherapy after surgery, but the prognosis for most gliomas remains poor due to tumor heterogeneity and drug resistance. Microtubule-associated protein 2 (MAP2), a microtubule-stabilizing protein, plays a critical role in many cellular processes and may correlate with the proliferation, apoptosis, and drug sensitivity of tumor cells, especially their sensitivity to microtubule-targeting drugs (MTDs). In this study, we investigated the role of MAP2 in gliomas and its relationship to the chemosensitivity of vincristine (VCR), an MTD commonly used in glioma chemotherapy. We downregulated MAP2 expression in glioma cells using RNA interference, observed the resultant changes in the biological characteristics of the cells, and tested their drug sensitivity to VCR by MTT assay. The results show downregulation of MAP2 in glioma cells significantly inhibited cell viability and migration, induced apoptosis, and increased sensitivity to VCR in vitro. Our findings suggest that MAP2 may be a useful molecular marker in MTD chemotherapy and a potential therapeutic target in gliomas.
Microbacterium wangchenii sp. nov., isolated from faeces of Tibetan gazelles (Procapra picticaudata) on the Qinghai-Tibet Plateau
Authors: Dong Kui , Yang Jing , Lu Shan , Pu Ji , Lai Xin-He , Jin Dong , Li Junqin , Zhang Gui , Wang Xiaoxia , Zhang Sihui , Lei Wenjing , Ren Zhihong , Wu Xiaomin , Huang Ying , Wang Suping , Xu Jianguo
Published: December 2019

Two strains of Gram-stain-positive, aerobic, non-spore-forming, non-motile, rod-shaped bacteria (designated dk512T and dk508) were isolated from the faeces of Tibetan gazelle (Procapra picticaudata) collected from the Qinghai-Tibet Plateau, PR China. The 16S rRNA gene sequences of the strains showed the highest identity to

Microbacterium saccharophilum

K-1T (98.0 and 97.9 % similarity, respectively). The phylogenetic analysis based on 16S rRNA gene sequences revealed that dk512T and dk508 were members of the genus

Microbacterium

, and most closely related to strains

Microbacterium mitrae

M4-8T and

Microbacterium hatanonis

FCC-01T. The strains grew optimally on brain-heart infusion (BHI) agar with 5.0 % (v/v) sheep blood at 30 °C, pH 7.0 and with 1.0 % (w/v) NaCl. The genome of type strain dk512T was 3.8 Mb with a G+C content of 70.6 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain dk512T and previously characterized

Microbacterium

species were <95 and <70 %, respectively. In strain dk512T, the detected primary cellular fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0, the main respiratory quinones were MK-9 (37.9 %) and MK-10 (35.7 %), and the polar lipids included diphosphatidylglycerol, phosphatidylglycerol and three unidentified glycolipids. The major cell-wall sugars were rhamnose, ribose and galactose. Alanine, glutamic acid, glycine and ornithine were in the cell-wall peptidoglycan. Based on phenotypic data and phylogenetic inference, these two strains represent a novel species of the genus

Microbacterium

, named here as Microbacterium wangchenii sp. nov, where dk512T is designated the type strain (=CGMCC 1.16590T=JCM 33494T=KCTC 49313T).
Microglia Clear Neuron-released α-Synuclein via Selective Autophagy and Prevent Neurodegeneration
Authors: Choi Insup , Zhang Yuanxi , Seegobin Steven P. , Pruvost Mathilde , Wang Qian , Purtell Kerry , Zhang Bin , Yue Zhenyu
Published: December 2019

Microglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing, however, the precise mechanisms remain poorly understood. Herein we report a neuroprotective role for microglia in the clearance of neuron-released α-synuclein. Neuronal α-synuclein activates microglia, which in turn engulf α-synuclein into autophagosomes for degradation via selective autophagy (termed Synucleinphagy). Synucleinphagy is initiated by the interaction of α-synuclein with Toll-like receptor 4 (TLR4), which induces transcriptional upregulation ofp62/SQSTM1through the NF-κB signaling pathway without causing TLR4 endocytosis. Induction of p62, an autophagy receptor, is necessary for the formation of α-synuclein/ubiquitin-positive puncta that are degraded by autophagy. Finally, disruption of microglial autophagy in mice expressing human α-synuclein promotes the accumulation of misfolded α-synuclein and causes midbrain dopaminergic neuron degeneration. Our study thus identifies a novel neuroprotective function of microglia in the clearance of α-synuclein via TLR4-NF-κB-p62 mediated Synucleinphagy.
REPIC: A database for exploringN6-methyladenosine methylome
Authors: Liu Shun , He Chuan , Chen Mengjie
Published: December 2019

The REPIC (RNAEpitranscriptomeCollection) database records about 10 million peaks called from publicly available m6A-seq and MeRIP-seq data using our unified pipeline. These data were collected from 672 samples of 49 studies, covering 61 cell lines or tissues in 11 organisms. REPIC allows users to queryN6-methyladenosine (m6A) modification sites by specific cell lines or tissue types. In addition, it integrates m6A/MeRIP-seq data with 1,418 histone ChIP-seq and 118 DNase-seq data tracks from the ENCODE project in a modern genome browser to present a comprehensive atlas of m6A, histone modification sites and chromatin accessibility regions. REPIC is accessible athttp://epicmod.uchicago.edu/repic.
Robust nucleation control via crisscross polymerization of DNA slats
Authors: Minev Dionis , Wintersinger Christopher M. , Ershova Anastasia , Shih William M.
Published: December 2019

Natural biomolecular assemblies such as actin filaments or microtubules polymerize in a nucleation-limited fashion1,2. The barrier to nucleation arises in part from chelate cooperativity, where stable capture of incoming monomers requires straddling multiple subunits on a filament end3. For programmable self-assembly from building blocks such as synthetic DNA4–23, it is likewise desirable to be able to suppress spontaneous nucleation24–31. However, existing approaches that exploit just a low level of cooperativity can limit spontaneous nucleation only for slow growth, near-equilibrium conditions32. Here we introduce ultracooperative assembly of ribbons densely woven from single-stranded DNA slats. An inbound “crisscross” slat snakes over and under six or more previously captured slats on a growing ribbon end, forming weak but specific half-duplex interactions with each. We demonstrate growth of crisscross ribbons with distinct widths and twists to lengths representing many thousands of slat additions. Strictly seed-initiated extension is attainable over a broad range of temperatures, divalent-cation concentrations, and free-slat concentrations, without unseeded ribbons arising even after a hundred hours to the limit of agarose-gel detection. We envision that crisscross assembly will be broadly enabling for all-or-nothing formation of microstructures with nanoscale features, algorithmic self-assembly, and signal amplification in diagnostic applications requiring extreme sensitivity.
Bioremediation of chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) by a paddy field bacterial isolate: Insights from genome analysis for possible biodegradation pathway
Authors: Nayak Tanmaya , Adhya Tapan Kumar , Panda Ananta N , Das Bhaskar , Raina Vishakha
Published: December 2019

Chlorpyrifos (CP) is one of the world’s most widely used organophosphorous pesticides (OPs) in agriculture, has led to contaminate soil and water ecosystems along with human species. Here, we report a newly isolated strain,Ochrobactrumsp. CPD-03 form a paddy field which could degrade CP and its metabolite TCP (3,5,6-trichloro-2-pyridinol) in 48 hours with an efficiency of 85-88% in minimal salt medium. GC-MS analysis revealed possible metabolites during CP degradation. Whole genome analysis indicated the presence of arylesterase and existence of other genes accountable for xenobiotic compounds degradation. CPD-03 exhibited chemotactic features towards CP along with other OPs suggesting its versatile role for possible mineralization of these toxicants. Further screening of CPD-03 also displayed plant growth promoting activities. Taken altogether, our results highlight the potentials of this new isolateOchrobactrumsp. CPD-03 in bioremediation and application in OP-contaminated ecosystem.
Differences in Activation of Intracellular Signalling in Primary Human Retinal Endothelial Cells Between Isoforms of VEGFA-165
Authors: Dailey Wendelin , Shunemann Roberto , Yang Fang , Moore Megan , Knapp Austen , Chen Peter , Deshpande Mrinalini , Metcalf Brandon , Tompkins Quentin , Guzman Alvaro E. , Felisky Jennifer , Mitton Kenneth P.
Published: December 2019

Purpose

There are reports that a b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of some diseased eyes. While these isoforms appear to have a different ability to activate the VEGF-Receptor-2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signalling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signalling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA165target genes in primary human retinal microvascular endothelial cells (HRMECs).

Methods

To determine full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2, direct in-cell western assays were developed using primary Human Retinal Microvascular Endothelial Cells (HRMECs). Potential differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1andSELE) and tight-junctions (CLDN5andOCLN) were tested by quantitative-PCR.

Results

Activation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. MAPK activation in primary HRMECs displayed a sigmoidal dose-response to a range of VEGFA165a concentrations spanning 10-250 pM, which shifted higher into the 100-5,000 pM range with VEGFA165b. Similar maximum activation of MAPK was achieved by both isoforms at high concentration. Maximum activation of AKT by VEGFA165b was only half of the maximum activation from VEGFA165a. At a lower intermediate dose, where VEGFA165a activated intracellular signalling stronger than VEGFA165b, the changes to VEGFA target gene expression was generally greater with VEGFA165a.

Conclusions

In primary HRMECs, VEGFA165a could maximally activate MAPK and AKT at lower concentrations where VEGFA165b had relatively little effect. The timing for maximal activation of MAPK was similar for both isoforms, which is different than reprorted for non-retinal endothelial cells. While VEGFA165a and VEGFA165b are limited to the sequence of their six C-terminal six amino acids, this results in a large difference in their ablility to activate at least two key intracellular signalling pathways and potentially VEGF target gene expression in primary human retinal endothelial cells.
Tubular STAT3 limits renal inflammation in autosomal dominant polycystic kidney disease
Authors: Viau Amandine , Baziz Maroua , Aka Amandine , Nguyen Clément , Kuehn E. Wolfgang , Terzi Fabiola , Bienaimé Frank
Published: December 2019

The inactivation of the ciliary proteins polycystin 1 or 2 leads to autosomal dominant polycystic kidney disease (ADPKD), the leading genetic cause of chronic kidney disease. Both cilia signaling and interstitial inflammation play a critical role in the disease. Yet, the reciprocal interactions between immune and tubular cells are not well characterized. The transcription factor STAT3, which is suspected to fuel ADPKD progression, is involved in crosstalks between immune and non-immune cells in various tissues and is a component of the cilia proteome. Here, we explore how STAT3 intersects with cilia signaling, renal inflammation and cyst growth using conditional murine models of post-developmentalPkd1,Stat3and cilia ablation. Our results indicate that, although primary cilia directly modulate STAT3 activationin vitro, the bulk of STAT3 activation in polycystic kidneys occurs through an indirect mechanism in which primary cilia trigger macrophage recruitment to the kidney, which in turn promotes STAT3 activation. Surprisingly, while disruptingStat3inPkd1deficient tubules slightly reduced cyst burden, it resulted in a massive infiltration of the cystic kidneys by macrophages and T cells, precluding any improvement of kidney function. Mechanistically, STAT3 represses the expression of the inflammatory chemokines CCL5 and CXCL10 in polycystic kidneys and cultured tubular cells. These results demonstrate that STAT3 is not a critical driver of cyst growth in ADPKD but plays a major role in the crosstalk between immune and tubular cells that shapes disease expression.
Local adaptation fuels cryptic speciation in terrestrial annelids
Authors: Marchán Daniel Fernández , Novo Marta , Sánchez Nuria , Domínguez Jorge , Díaz Cosín Darío J. , Fernández Rosa
Published: December 2019

Uncovering the genetic and evolutionary basis of cryptic speciation is a major focus of evolutionary biology. Next Generation Sequencing (NGS) allows the identification of genome-wide local adaptation signatures, but has rarely been applied to cryptic complexes - particularly in the soil milieu - as is the case with integrative taxonomy. The earthworm genus Carpetania, comprising six previously suggested putative cryptic lineages, is a promising model to study the evolutionary phenomena shaping cryptic speciation in soil-dwelling lineages. Genotyping-By-Sequencing (GBS) was used to provide genome-wide information about genetic variability between seventeen populations, and geometric morphometrics analyses of genital chaetae were performed to investigate unexplored cryptic morphological evolution. Genomic analyses revealed the existence of three cryptic species, with half of the previously-identified potential cryptic lineages clustering within them. Local adaptation was detected in more than 800 genes putatively involved in a plethora of biological functions (most notably reproduction, metabolism, immunological response and morphogenesis). Several genes with selection signatures showed shared mutations for each of the cryptic species, and genes under selection were enriched in functions related to regulation of transcription, including SNPs located in UTR regions. Finally, geometric morphometrics approaches partially confirmed the phylogenetic signal of relevant morphological characters such as genital chaetae. Our study therefore unveils that local adaptation and regulatory divergence are key evolutionary forces orchestrating genome evolution in soil fauna.
Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes
Authors: Mahadevan Iyer Aditya , Kumar Sanjeev , Satyanarayana Rao Manchanahalli R.
Published: December 2019

Background

H1t is the major linker histone variant in pachytene spermatocytes, where it constitutes 50-60% of total H1. This linker histone variant was previously reported to localize in the nucleolar rDNA element in mouse spermatocytes. Our main aim was to determine the extra-nucleolar localization of this linker histone variant in pachytene spermatocytes.

Results

We generated H1t-specific antibodies in rabbits and validated its specificity by multiple assays like ELISA, western blot, etc. Genome-wide occupancy studies, as determined by ChIP-sequencing in P20 mouse testicular cells revealed that H1t did not closely associate with active gene promoters and open chromatin regions. Annotation of H1t bound genomic regions revealed that H1t is depleted from DSB hotspots and TSS, but are predominantly associated with retrotransposable repeat elements like LINE and LTR in pachytene spermatocytes. These chromatin domains are repressed based on co-association of H1t observed with methylated CpGs and repressive histone marks like H3K9me3 and H4K20me3 in vivo. Mass spectrometric analysis of proteins associated with H1t-containing oligonucleosomes identified piRNA-PIWI pathway proteins, repeat-repression associated proteins and heterochromatin proteins confirming the association with repressed repeat-element genomic regions. We validated the interaction of key proteins with H1t-containing oligonucleosomes by use of ChIP-western blot assays. On the other hand, we observe majority of H1t peaks to be associated with the intergenic spacer of the rDNA element, also in association with SINE elements of the rDNA element. Thus, we have identified the genomic and chromatin features of both nucleolar and extranucleolar localization patterns of linker histone H1t in the context of pachytene spermatocytes.

Conclusions

H1t-containing repeat-element LINE and LTR chromatin domains are associated with repressive marks like methylated CpGs, histone modifications H3K9me3 and H4K20me3, and heterochromatin proteins like HP1β, Trim28, PIWIL1 etc. Apart from localisation of H1t at the rDNA element, we demonstrate the extranucleolar association of this linker histone variant at repeat-associated chromatin domains in pachytene spermatocytes. We hypothesize that H1t might induce local chromatin relaxation to recruit heterochromatin and repeat repression-associated protein factors necessary for TE (transposable element) repression, the final biological effect being formation of closed chromatin repressed structures.
Mesoscale Dynamics of Spectrin and Acto-Myosin shape Membrane Territories during Mechanoresponse
Authors: Ghisleni Andrea , Galli Camilla , Monzo Pascale , Ascione Flora , Fardin Marc-Antoine , Scita Giorgio , Li Qingsen , Maiuri Paolo , Gauthier Nils
Published: December 2019

The spectrin cytoskeleton is a major component of the cell cortex. While ubiquitously expressed, its dynamic interaction with the other cortex components, including the plasma membrane or the acto-myosin cytoskeleton, is poorly understood. Here, we investigated how the spectrin cytoskeleton re-organizes spatially and dynamically under the membrane during changes in cell mechanics. We found spectrin and acto-myosin cytoskeletons to be spatially distinct but cooperating during mechanical challenges, such as cell adhesion and contraction, or compression, stretch and osmolarity fluctuations, creating a cohesive cortex supporting the plasma membrane. Actin territories control protrusions and contractile structures while spectrin territories concentrate in retractile zones and low-actin density/inter-contractile regions, acting as a fence to organize membrane trafficking events. We unveil here the existence of a dynamic interplay between acto-myosin and spectrin cytoskeletons necessary to support a mesoscale organization of the lipid bilayer into spatially-confined cortical territories during cell mechanoresponse.
Participation of the rostral anterior cingulate cortex in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray and contextual fear conditioning
Authors: de Oliveira Galvão Bruno , Filgueiras Alberto , Maisonnette Silvia , Krahe Thomas E. , Landeira-Fernandez J.
Published: December 2019

The rostral anterior cingulate cortex (rACC) is a critical brain structure related to defensive behavior. However, still unclear is whether the rACC also plays a role in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into the dPAG to determine freezing and escape response thresholds after sham or bilateral electrolytic lesions of the rACC. The duration of freezing behavior that outlasted electrical stimulation of the dPAG was also measured. The next day, these animals were subjected to contextual fear conditioning using footshock as an unconditioned stimulus. Lesions of the rACC did not change aversive freezing and escape response thresholds but disrupted post-dPAG stimulation freezing. The lesions also disrupted defensive freezing behavior and analgesia in the formalin test in response to contextual cues previously associated with footshock. These results indicate that the rACC is involved in some but not all aspects of defensive behavior generated at the level of the dPAG. The rACC also appears to play an important role in contextual fear conditioning.
A key regulatory protein for flagellum length control in stable flagella
Authors: Atkins Madison , Týč Jiří , Shafiq Shahaan , Ahmed Manu , Bertiaux Eloïse , De Castro Neto Artur Leonel , Sunter Jack , Bastin Philippe , Dean Samuel , Vaughan Sue
Published: December 2019

Cilia and flagella are highly conserved microtubule-based organelles that have important roles in cell motility and sensing [1]. They can be highly dynamic and short lived such as primary cilia or Chlamydomonas [2] or very stable and long lived such as those in spermatozoa [3] photoreceptors [4] or the flagella of many protist cells [3,4]. Although there is a wide variation in length between cell types, there is generally a defined length for a given cell type [1]. Many unicellular flagellated and ciliated organisms have an additional challenge as they must maintain flagella/cilia at a defined length whilst also growing new flagella/cilia in the same cell. It is not currently understood how this is achieved. A grow-and-lock model was proposed for the maintenance of stable flagella where a molecular lock is applied to prevent flagellum length change after assembly [5]. The molecular mechanisms of how this lock operates are unknown, but could be important in cells where an existing flagellum must be maintained whilst a new flagellum assembles. Here we show that Cep164C contributes to the locking mechanism at the base of the flagellum in Trypanosoma brucei. It is only localised on the transition fibres of basal bodies of fully assembled flagella and missing from assembling flagella. In fact, basal bodies only acquire Cep164C in the third cell cycle after they assemble in trypanosomes. Depletion leads to dysregulation of flagellum growth with both longer and shorter flagella; consistent with defects in a flagellum locking mechanism. By controlling delivery of components into the old assembled flagellum, maintenance of stable flagella can occur but limits further growth. This offers an important explanation for how many eukaryotic unicellular cells maintain their existing flagella whilst growing new ones before these cells divide. This work also reveals additional regulatory roles for Cep164 in eukaryotic organisms.
Muscle-derived Dpp regulates feeding initiation via endocrine modulation of brain dopamine biosynthesis
Authors: Robles-Murguia Maricela , Rao Deepti , Finkelstein David , Xu Beisi , Fan Yiping , Demontis Fabio
Published: December 2019

In animals, the brain regulates feeding behavior in response to local energy demands of peripheral tissues, which secrete orexigenic and anorexigenic hormones. Although skeletal muscle is a key peripheral tissue, it remains unknown whether muscle-secreted hormones regulate feeding. In Drosophila, we found that decapentaplegic (dpp), the homolog of human bone morphogenetic proteins BMP2 and BMP4, is a muscle-secreted factor (a myokine) that is induced by nutrient sensing and that circulates and signals to the brain. Muscle-restricted dpp RNAi promotes foraging and feeding initiation, whereas dpp overexpression reduces it. This regulation of feeding by muscle-derived Dpp stems from modulation of brain tyrosine hydroxylase (TH) expression and dopamine biosynthesis. Consistently, Dpp receptor signaling in dopaminergic neurons regulates TH expression and feeding initiation via the downstream transcriptional repressor Schnurri. Moreover, pharmacologic modulation of TH activity rescues the changes in feeding initiation due to modulation of dpp expression in muscle. These findings indicate that muscle-to-brain endocrine signaling mediated by the myokine Dpp regulates feeding behavior.
Induction of AP-1 by YAP/TAZ contributes to cell proliferation and organ growth
Authors: Koo Ja Hyun , Plouffe Steven W. , Meng Zhipeng , Lee Da-Hye , Yang Di , Lim Dae-Sik , Wang Cun-Yu , Guan Kun-Liang
Published: December 2019

Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway to control cell growth and organ size, of which dysregulation yields to tumorigenesis or hypertrophy. Upon activation, YAP/TAZ translocate into the nucleus and bind to TEAD transcription factors to promote transcriptional programs for proliferation or cell specification. Immediate early genes, represented by AP-1 complex, are rapidly induced and control later-phase transcriptional program to play key roles in tumorigenesis and organ maintenance. Here, we report that YAP/TAZ directly promote FOS transcription that in turn contributes to the biological function of YAP/TAZ. YAP/TAZ bind to the promoter region of FOS to stimulate its transcription. Deletion of YAP/TAZ blocks the induction of immediate early genes in response to mitogenic stimuli. FOS induction contributes to expression of YAP/TAZ downstream target genes. Genetic deletion or chemical inhibition of AP-1 suppresses growth of YAP-driven cancer cells, such as Lats1/2-deficient cancer cells as well as Gαq/11 mutated uveal melanoma. Furthermore, AP-1 inhibition almost completely abrogates the hepatomegaly induced by YAP overexpression. Our findings reveal a feed-forward interplay between immediate early transcription of AP-1 and Hippo pathway function.
Phosphoproteomic profiling reveals a defined genetic program for osteoblastic lineage commitment of human bone marrow–derived stromal stem cells
Authors: Barrio-Hernandez Inigo , Jafari Abbas , Rigbolt Kristoffer T.G. , Hallenborg Philip , Sanchez-Quiles Virginia , Skovrind Ida , Akimov Vyacheslav , Kratchmarova Irina , Dengjel Joern , Kassem Moustapha , Blagoev Blagoy
Published: December 2019

Bone marrow–derived mesenchymal stem cells (MSCs) differentiate into osteoblasts upon stimulation by signals present in their niche. Because the global signaling cascades involved in the early phases of MSCs osteoblast (OB) differentiation are not well-defined, we used quantitative mass spectrometry to delineate changes in human MSCs proteome and phosphoproteome during the first 24 h of their OB lineage commitment. The temporal profiles of 6252 proteins and 15,059 phosphorylation sites suggested at least two distinct signaling waves: one peaking within 30 to 60 min after stimulation and a second upsurge after 24 h. In addition to providing a comprehensive view of the proteome and phosphoproteome dynamics during early MSCs differentiation, our analyses identified a key role of serine/threonine protein kinase D1 (PRKD1) in OB commitment. At the onset of OB differentiation, PRKD1 initiates activation of the pro-osteogenic transcription factor RUNX2 by triggering phosphorylation and nuclear exclusion of the histone deacetylase HDAC7.
Precise correlative method of Cryo-SXT and Cryo-FM for organelle identification
Authors: Bai Haobo , Guan Yong , Liu Jianhong , Chen Liang , Wei Wenbin , Liu Gang , Tian Yangchao
Published: December 2019

Cryogenic soft X-ray tomography (Cryo-SXT) is ideally suitable to image the 3D sub-cellular architecture and organization of cells with high resolution in the near-native preservation state. Cryogenic fluorescence microscopy (Cryo-FM) can determine the location of a molecule of interest that has been labeled with a fluorescent tag, thus revealing the function of the cells. To understand the relations between the sub-cellular architecture and the function of cells, correlative Cryo-SXT and Cryo-FM was applied. This method required the matching of images of different modalities, and the accuracy of the matching is important. Here, a precise correlative method of Cryo-SXT and Cryo-FM is introduced. The capability of matching images of different modalities with high resolution was verified by simulations and practical experiments, and the method was used to identify vacuoles and mitochondria.
Airbnb impact and regulation issues through destination life cycle concept
Authors: Avdimiotis Spyros , Poulaki Ioulia
Published: December 2019

Purpose

The purpose of this paper is to re-establish the role of Airbnb platform in the contemporary tourism destination management. Given the fact that sharing economy is mega-trend with various impacts at any destination, the paper’s purpose is to underline that sharing economy platforms, such as Airbnb, has a different impact on each stage of destination’s life cycle. Given this, a more effective strategy and policies plan should be deployed and implemented, expanding the benefits of multiplying and accelerating effects on local economy.

Design/methodology/approach

The neologisms of “Over-tourism” and “Tourism-phobia” and the growing conflicts between locals and tourist, along with various collateral implications in local economy, were the initial incentive to focus on the subject. The methodology was based on the critical approach of regulatory measures taken in destinations with different characteristics.

Findings

Findings indicate that general and nationwide restrictions on Airbnb are often unfounded, mainly based on bias against its impact on traditional hotels and local lifestyle preservation, rather than concrete and objective impact measurements.

Research limitations/implications

A primary qualitative and quantitative research should follow the concept of association between destination’s life cycle and sharing economy applications, for authorities to form the appropriate regulatory framework.

Originality/value

The paper associates the implications of sharing economy with the stages of destinations life cycle, underlying that measures need to be customized to the specific characteristics of each destination.
Where are Islamic finance indices pointing towards?
Authors: El Maknouzi Mohammed El Hadi , Jadalhaq Iyad Mohammad
Published: December 2019

Purpose

This paper aims to survey the screening practices and regulatory arrangements that can be gleaned from the experience of Islamic financial indices on international stock markets. Such indices can be regarded as experiments in the demarcation of “pockets” of Sharī‘ah-compliant securities exchange, in the context of non-Sharī‘ah-compliant stock markets. They offer valuable regulatory precedent, with a view to the development of a transnational domain of Islamic financial transactions.

Design/methodology/approach

The paper leverages the experience of Islamic financial indices for charting the fault lines between the foundational principles of Islamic finance, and those of interest-based investment commonly accepted on international financial markets. It subsequently reviews the most salient regulatory arrangements in place for discriminating between permissible and forbidden securities and modes of trading, as implemented on Islamic financial indices. These include selection criteria for index inclusion, and Sharī‘ah committees with ex ante and ex post supervisory duties.

Findings

The paper makes a case for viewing Islamic finance indices on international capital markets as capacity-building experiments for the regulation of transnational Islamic financial flows.

Originality/value

The study rejuvenates the pragmatic approach towards the development of Islamic capital markets, by suggesting that incremental organisational innovations, as developed in connection with Islamic financial indices, can build institutional capacity towards an economy that abides by Islamic values.
Evaluation of brand relationship quality using formative index: a novel measurement approach
Authors: Adhikari Kishalay , Panda Rajeev Kumar
Published: December 2019

Purpose

This paper aims to develop a parsimonious and robust formative index for evaluating and measuring the brand relationship quality of automobile brands.

Design/methodology/approach

Survey questionnaires were used to collect empirical data from 395 car owners, out of which 362 samples were included in the final analysis. Partial least squares technique was used for index construction.

Findings

The empirical findings exhibit that the automobile brand relationship quality (ABRQ) index based on the final set of six indicators effectively captures the conceptual domain of brand relationship quality. In addition, the external validity check affirms positive and significant influence of ABRQ index toward enhancing customer loyalty.

Practical implications

ABRQ index can assist the brand managers and academicians for benchmarking and market strategy formulation while contributing to the limited literature on brand relationship quality. Also, this index having six-indicators can considerably reduce the time and effort of respondents for filling the questionnaires, in turn, improving response rates.

Originality/value

This study represents a novel attempt to formulate a brand relationship quality index using formative measurement indicators, and as per the authors’ knowledge, has not been attempted by prior researchers in this domain.
Coles and Woolworths have installed public access defibrillators in all their stores: It is time other Australian businesses followed their lead
Authors: Haskins Brian , Nehme Ziad , Cameron Peter , Bernard Stephen , Parker‐Stebbing Laura , Smith Karen
Published: December 2019

We welcome the recent announcement by Coles and Woolworths that public access defibrillators (PADs) are now available in their stores, as early defibrillation with PADs is associated with significantly increased survival from out‐of‐hospital cardiac arrests (OHCAs). From 2008 to 2018 there were 120 OHCAs in Victorian supermarkets, overall 26.6% survived; however, when defibrillated by a PAD 66.6% survived. For all OHCA in Victoria, survival for defibrillation by a PAD was also higher at 55.5%, compared to 28.8% for paramedic defibrillation. Using this state‐wide PAD survival rate, we estimate an additional 12 patients could have survived had PADs been available in all supermarkets. In Victoria last year there were 421 potentially viable OHCAs in public locations, of these 132 patients survived; however, had PADs been available an additional 101 patients could have survived. We therefore strongly encourage local businesses to install PADs, to safeguard the well‐being of their employees, customers and local communities.
Immunohistochemistry in screening for heritable colorectal cancer: what to do with an abnormal result
Authors: Paredes Steven R. , Chan Charles , Rickard Matthew J. F. X.
Published: December 2019

Recent developments in our understanding of molecular genetics have transformed screening and diagnostic practices for Lynch syndrome. The current standard involves universal tumour analysis of resected colorectal cancer (and ideally polypectomy) specimens using immunohistochemistry and molecular techniques. Patients with abnormal immunohistochemical findings are subsequently referred for definitive mutational testing. This review relates the molecular pathogenesis of Lynch syndrome to current immunohistochemistry‐based screening strategies and discusses the interpretation and clinical implications of screening results.
Does he sound cooperative? Acoustic correlates of cooperativeness
Authors: Tognetti Arnaud , Durand Valerie , Barkat‐Defradas Melissa , Hopfensitz Astrid
Published: December 2019

The sound of the voice has several acoustic features that influence the perception of how cooperative the speaker is. It remains unknown, however, whether these acoustic features are associated with actual cooperative behaviour. This issue is crucial to disentangle whether inferences of traits from voices are based on stereotypes, or facilitate the detection of cooperative partners. The latter is likely due to the pleiotropic effect that testosterone has on both cooperative behaviours and acoustic features. In the present study, we quantified the cooperativeness of native French‐speaking men in a one‐shot public good game. We also measured mean fundamental frequency, pitch variations, roughness, and breathiness from spontaneous speech recordings of the same men and collected saliva samples to measure their testosterone levels. Our results showed that men with lower‐pitched voices and greater pitch variations were more cooperative. However, testosterone did not influence cooperative behaviours or acoustic features. Our finding provides the first evidence of the acoustic correlates of cooperative behaviour. When considered in combination with the literature on the detection of cooperativeness from faces, the results imply that assessment of cooperative behaviour would be improved by simultaneous consideration of visual and auditory cues.