bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Ultrasound-Guided Erector Spinae Plane Block for Perioperative Pain Control and Short-Term Outcomes in Lumbar Laminoplasty
Authors: Jin Yanwu , Zhao Shanshan , Cai Jiahui , Blessing Marcelle , Sun Yongtao , Hu Shuai , Han Qi , Zhao Xin , Tan Haizhu , Li Jinlei
Published: February 2020

Background

Erector spinae plane (ESP) block has been reported to provide analgesia in spine surgery in case reports or case series, and there have been no controlled studies to date evaluating its efficacy. We aimed to exam the roles of ESP block in lumbar surgery in a single center randomized control trial by injecting local analgesic into the interfacial plane between the erector spinae muscles and the transverse process under ultrasound guidance.

Methods

Consecutive elective lumbar surgery patients were randomized into either a control group (general anesthesia only, Group G, N=32) or a treatment group (general anesthesia plus ESP block, Group E, N=30). Several parameters including visual analog scale (VAS, primary outcome), perioperative anesthetics and analgesics usage, indexes of hemodynamics variation, return of bowel function and overall benefit of analgesia score (OBAS) were measured.

Results

Significant differences in VAS scores over time were found between the two matched groups (P = 0.010). Group E patients had significantly lower pain scores than Group G patients in the early postoperative period within the first 6 hr. Group G and Group E VAS scores peaked at 1 hr and 12 hr, respectively, and the peak pain score in Group G is significantly higher than that of Group E (P = 0.002). In addition, patients who received ESP block had lower perioperative analgesic and sedative medication requirements, improved satisfaction with pain management, more stable hemodynamics, and earlier bowel function return than those using general anesthesia alone.

Conclusion

Pre-incision bilateral single injection ESP blocks provided effective analgesia perioperatively during lumbar laminoplasty, decreased perioperative anesthesia and analgesia requirement, and accelerated short-term recovery.
Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle fusion and replenishment in a dosage-dependent manner
Authors: Guan Zhuo , Quiñones-Frías Mónica C. , Akbergenova Yulia , Littleton J. Troy
Published: February 2020

Synchronous neurotransmitter release is triggered by Ca2+binding to the synaptic vesicle protein Synaptotagmin 1, while asynchronous fusion and short-term facilitation is hypothesized to be mediated by plasma membrane-localized Synaptotagmin 7 (SYT7). We generated mutations in DrosophilaSyt7to determine if it plays a conserved role as the Ca2+sensor for these processes. Electrophysiology and quantal imaging revealed evoked release was elevated 2-fold.Syt7mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and robust facilitation.Syt1/Syt7double mutants displayed more release thanSyt1mutants alone, indicating SYT7 does not mediate the residual asynchronous release remaining in the absence of SYT1. SYT7 localizes to an internal membrane tubular network within the peri-active zone, but does not enrich at release sites. These findings indicate the two Ca2+sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at Drosophila synapses.
ImmunoPET as Stoichiometric Sensor for Glypican-3 in Models of Hepatocellular Carcinoma
Authors: Kelada Olivia J. , Gutsche Nicholas T. , Bell Meghan , Berman Rose M. , Baidoo Kwamena E. , Warner Blake M. , Szajek Lawrence P. , Hong Jessica , Ho Mitchell , Choyke Peter L. , Escorcia Freddy E.
Published: February 2020

Background

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. While conventional imaging approaches like ultrasound, CT, and MRI play critical roles in the diagnosis and surveillance of HCC, improved methods for detection and assessment of treatment response are needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (immunoPET) imaging. Glypican-3 (GPC3) is a proteoglycan that is highly expressed in the majority of HCC tumors. GPC3-specific antibodies are used to diagnose HCC histopathologically, and have been proposed as a treatment of HCC. Here, we design, synthesize and demonstrate that our humanized immunoPET agent, [89Zr]Zr-DFO-TAB-H14, can stoichiometrically bind to models of human liver cancer with varied GPC3 expression. Methods: The GPC3-specific monoclonal humanized IgG1, TAB-H14, was used as a scaffold for engineering our immunoPET agent. Fluorescent and deferroxamine (DFO) chelate conjugates of TAB-H14 were characterized using mass spectrometry. Binding affinity of TAB-H14 and conjugates for GPC3 was determined in cell-free biolayer interferometry, and cell-based radioimmunoassays. GPC3-expression was assessed by flow cytometry and immunofluorescence using commercially available anti-GPC3 antibodies and TAB-H14 in GPC3−(A431) and GPC3+cell lines including an engineered line (A431-GPC3+, G1) and liver cancer lines (HepG2, Hep3B, and Huh7). DFO-TAB-H14, was radiolabeled with Zr-89. Mice were subcutaneously engrafted with the aforementioned cell lines and in vivo target engagement of the immunoPET agent [89Zr]Zr-DFO-TAB-H14 was determined using PET/CT, quantitative biodistribution, and autoradiography. Results: TAB-H14 demonstrated subnanomolar to nanomolar affinity for human GPC3. Fluorescently tagged TAB-H14 was able to bind to GPC3 on cell membranes of GPC3-expressing lines by flow cytometry. These results were confirmed by immunofluorescence staining of A431, G1 HepG2, Hep3B, and Huh7 tumor sections. ImmunoPET imaging with [89Zr]Zr-DFO-TAB-H14 showed stoichiometric tumor uptake corresponding to the cell surface expression levels. Autoradiography and immunostaining confirmed in vivo findings. Conclusion: We systematically demonstrate that the humanized immnoPET agent [89Zr]Zr-DFO-TAB-H14 specifically and stoichiometrically binds to GPC3 in several models of human liver cancer, serving as a promising in vivo GPC3 sensor. This agent may provide utility in HCC diagnosis and surveillance, and the selection of candidates for GPC3-directed therapies.
Segment-specific orientation of the dorsal and ventral roots for precise therapeutic targeting of human spinal cord
Authors: Mendez Alan , Islam Riazul , Latypov Timur , Basa Prathima , Joseph Ogeneitsega J. , Knudsen Bruce , Siddiqui Ahad M. , Summer Priska , Staehnke Luke J. , Grahn Peter J. , Lachman Nirusha , Windebank Anthony J. , Lavrov Igor A.
Published: February 2020

An understanding of spinal cord functional neuroanatomy is essential for diagnosis and treatment of multiple disorders including, chronic pain, movement disorders, and spinal cord injury. Till now, no information is available on segment-specific spinal roots orientation in humans. In this study we collected neuroanatomical measurements of the dorsal and ventral roots from C2-L5, as well as spinal cord and vertebral bone measurements from adult cadavers. Spatial orientation of dorsal and ventral roots were measured and correlated to the anatomical landmarks of the spinal cord and vertebral column. The results show less variability in rostral root angles compared to the caudal angles across all segments. Dorsal and ventral rootlets were oriented mostly perpendicular to the spinal cord at the cervical level and demonstrate more parallel orientation at the thoracic and lumbar segments. The number of rootlets was the highest in dorsal cervical and lumbar segments. Spinal cord transverse diameter and size of the dorsal columns were largest at cervical and lumbar segments. The strongest correlation was found between the length of intervertebral foramen to rostral rootlet and vertebral bone length. These results could be used to locate spinal roots and spinal cord landmarks based on bone marks on CT or X-rays. These results also provide background for future correlations between anatomy of spinal cord and spinal column structures that could improve stereotactic surgical procedures and electrode positioning for spinal cord neuromodulation.

One Sentence Summary

This is the first detailed analysis of the segment-specific dorsal and ventral spinal roots spatial orientation measured and correlated to the anatomical landmarks of the spinal cord and vertebral column for human.
Development of a high-throughput radial migration device
Authors: Oliver C. Ryan , Little Andrew C. , Westerhof Trisha M. , Pathanjeli Pragathi , Yates Joel A. , Merajver Sofia D.
Published: February 2020

By combining the radial migration assay with injection molded gaskets and a rigid fixture, we have developed a more reliable and sensitive method for measuring radial cell migration. This method is well adapted for use on high throughput automated imaging systems. The use of injection molded gaskets enables low cost replacement of cell-wetted components. Furthermore, the design enables secondary placement of attractants and co-cultures. This device and high-throughput application permit the use of therapeutic screening to evaluate phenotypic responses e.g. cancer cell migration. This approach is orthogonal to other 2D cell migration applications such as scratch wound assays, although here we offer a non-invasive, high-throughput device which is currently not commercially available. Collectively, we have designed a systematic, reliable, high-throughput application to monitor phenotypic responses to chemotherapeutic screens, genetic alterations (e.g. RNAi; CRISPR; others), supplemental regiments, and other approaches offering a reliable methodology to survey unbiased and non-invasive cell migration.
Widespread divergent transcription from prokaryotic promoters
Authors: Warman Emily , Forrest David , Wade Joseph T. , Grainger David C.
Published: February 2020

Promoters are DNA sequences that stimulate the initiation of transcription. In all prokaryotes, promoters are believed to drive transcription in a single direction. Here we show that prokaryotic promoters are frequently bidirectional and drive divergent transcription. Mechanistically, this occurs because key promoter elements have inherent symmetry and often coincide on opposite DNA strands. Reciprocal stimulation between divergent transcription start sites also contributes. Horizontally acquired DNA is enriched for bidirectional promoters suggesting that they represent an early step in prokaryotic promoter evolution.
Biofilm Formation byStaphylococcus aureusis Triggered by a Drop in the Levels of the Second Messenger cyclic-di-AMP
Authors: Syed Adnan K. , Vickery Christopher R. , Lenhart Taliesin , Llewellyn Eliza , Walker Suzanne , Losick Richard
Published: February 2020

The bacterial pathogenStaphylococcus aureusforms multicellular communities known as biofilms in which cells are held together by an extracellular matrix. The matrix consists of repurposed cytoplasmic proteins and extracellular DNA. These communities assemble during growth on medium containing glucose, but the intracellular signal for biofilm formation was unknown. Here we present evidence that biofilm formation is triggered by a drop in the levels of the second messenger cyclic-di-AMP. Previous work identified genes needed for the release of extracellular DNA, including genes for the cyclic-di-AMP phosphodiesterase GdpP, the transcriptional regulator XdrA, and the purine salvage enzyme Apt. Using a cyclic-di-AMP riboswitch biosensor and mass spectrometry, we show that the levels of the second messenger drop during biofilm formation in a glucose-dependent manner and that the drop is prevented in mutants of all three genes. Importantly, we also show that expression of the “accessory gene regulator” operonagris under the positive control of cyclic-di-AMP and that anagrmutation, which is known to promote biofilm formation, bypasses the block in biofilm formation and eDNA release caused by agdpPmutation. We conclude that the effect of the glucose-dependent drop in c-di-AMP levels is principally mediated by a reduction inagrexpression, which in turn promotes biofilm formation.
Kinematic analysis deconstructs the evolved loss of schooling behavior in cavefish
Authors: Patch Adam , Paz Alexandra , Holt Karla , Duboue Erik , Kowalko Johanna E. , Keene Alex C. , Fily Yaouen
Published: February 2020

Fish display a remarkable diversity of social behaviors, from highly social to largely solitary. While social behaviors are likely critical for survival, surprisingly little is known about how they evolve in response to changing environmental pressures. With its highly social surface form and multiple populations of a largely asocial, blind, cave-dwelling form, the Mexican tetra,Astyanax mexicanus, provides a powerful model to study the evolution of social behavior. Given numerous morphological and behavioral differences between the surface and cave forms, a primary impediment to understanding how this behavior evolved is a lack of computational and statistical approaches that can precisely identify independent aspects of social behavior. Here, we use motion tracking and kinematic analysis to quantify social swimming patterns and argue that the absence of schooling in cavefish is not merely a consequence of their inability to see but rather a genuine behavioral adaptation that impacts the way they explore their cave environment. Surface fish school, maintaining both close proximity and alignment with each other. In the dark, surface fish no longer school, but we show that they still attempt to align and maintain proximity when they find themselves near another fish. Conversely, cavefish exhibit little preference for proximity or alignment, instead actively avoiding each other. Cavefish also slow down when more fish are present in the tank, which neither surface fish in the light or in the dark do. Using data-driven computer simulations, we show that those two traits – active avoidance and collective slowdown – are sufficient to shift the exploration strategy of cavefish from mostly-following-the-walls to exploring-the-entire-tank. Finally, we find that those differences in collective swimming patterns are largely consistent across independently-evolved cave populations, revealing an evolutionary convergence on this emergent social behavior.

Author Summary

The Mexican tetra fish offers a fascinating window into the evolution of schooling behavior. Its ancestral-like surface form is found in the rivers and lakes of Mexico and Texas and is highly social. Over the last million years,A. mexicanusrepeatedly evolved a second, largely asocial cave form after colonizing a series of dark, underground caves. Here we use motion tracking technology to compare the collective displacement patterns of four populations and present evidence that the loss of schooling in cave populations (i) is a genuine example of parallel behavioral evolution rather than a mere consequence of not being able to see in the dark and (ii) could constitute a cave-specific exploration strategy.
Klp2 and Ase1 synergize to maintain meiotic spindle stability during metaphase I
Authors: Zheng Fan , Dong Fenfen , Yu Shuo , Li Tianpeng , Jian Yanze , Nie Lingyun , Fu Chuanhai
Published: February 2020

The spindle apparatus segregates bi-oriented sister chromatids during mitosis but mono-oriented homologous chromosomes during meiosis I. It has remained unclear if similar molecular mechanisms operate to regulate spindle dynamics during mitosis and meiosis I. Here, we employed live-cell microscopy to compare the spindle dynamics of mitosis and meiosis I in fission yeast cells and demonstrated that the conserved kinesin-14 motor Klp2 plays a specific role in maintaining metaphase spindle length during meiosis I, but not during mitosis. Moreover, the maintenance of metaphase spindle stability during meiosis I requires the synergism between Klp2 and the conserved microtubule crosslinker Ase1 as the absence of both proteins causes exacerbated defects in metaphase spindle stability. The synergism is not necessary for regulating mitotic spindle dynamics. Hence, our work reveals a new molecular mechanism underlying meiotic spindle dynamics and provides insights into understanding differential regulation of meiotic and mitotic events.
Cross-feeding betweenThauera aminoaromaticaandRhodococcus pyridinivoransdrove quinoline biodegradation in a denitrifying bioreactor
Authors: Wu Xinxin , Wu Xiaogang , Li Ji , Wu Qiaoyu , Ma Yiming , Sui Weikang , Zhao Liping , Zhang Xiaojun
Published: February 2020

The complex bacterial community is predominated by several taxa, such asThaueraandRhodococcus, in a quinoline-degrading denitrifying bioreactor. Yet it remains unclear about how the interactions between the different bacteria mediate the quinoline metabolism in denitrifying condition. In this study, we designed a sequence-specific amplification to guide the isolation of the most predominant bacteria and obtained four strains ofThauera aminoaromatica,the representative of one key member in the bioreactor. Test on these isolates demonstrated that all of them were unable to strive on quinoline but could efficiently degrade 2-hydroxyquinoline, the hypothesized primary intermediate of quinoline catabolism, under nitrate-reducing condition. However, another isolate,Rhodococcus pyridinivoransYF3, corresponding to the second abundant taxon in the same bioreactor, was found to degrade quinoline via 2-hydroxyquinoline. The end products and removal rate of quinoline by isolate YF3 were largely varied with the quantity of available oxygen. Specifically, quinoline could only be converted into 2-hydroxyquinoline without further transformation under the condition with insufficient oxygen, e.g. less than 0.5% initial oxygen in the vials. However, if were aerobically pre-cultured in the medium with quinoline the resting cells of YF3 could anaerobically convert quinoline into 2-hydroxyquinoline. A two-strain consortium constructed with isolates fromThauera(R2) andRhodococcus(YF3) demonstrated an efficient denitrifying degradation of quinoline. Thus, we experimentally proved that the metabolism interaction based on the 2-hydroxyquinoline cross-feeding between two predominant bacteria constituted the mainstream of quinoline degradation. This work sheds light on the understanding of mechanism of quinoline removal in the denitrifying bioreactor.

Importance

We experimentally verified the most predominantThauerasp. was indeed active degrader for the intermediate metabolites and the second abundant taxonRhodococcusexerted, however, key function for opening the food box for a complex quinoline-degrading community. An ecological guild composed of two isolates was assembled, revealing the different roles of keystone organisms in the microbial community. This study, to our best knowledge, is the first report on the cross feeding between the initial attacker with unprofitable catalysis of reluctant heterocyclic compounds and the second bacterium which then completely degrade the compound transformed by the first bacterium. These results could be a significant step forward towards elucidation of microbial mechanism for quinoline denitrifying degradation.
Carbohydrate complexity structures stable diversity in gut-derived microbial consortia under high dilution pressure
Authors: Yao Tianming , Chen Ming-Hsu , Lindemann Stephen R.
Published: February 2020

Dietary fibers are major substrates for the colonic microbiota, but the structural specificity of these fibers for the diversity, structure, and function of gut microbial communities are poorly understood. Here, we employed anin vitrosequential batch fecal culture approach to determine: 1) whether the chemical complexity of a carbohydrate structure influences its ability to maintain microbial diversity in the face of high dilution pressure and 2) whether substrate structuring or obligate microbe-microbe metabolic interactions (e.g. exchange of amino acids or vitamins) exert more influence on maintained diversity. Sorghum arabinoxylan (SAX, complex polysaccharide), inulin (low-complexity oligosaccharide) and their corresponding monosaccharide controls were selected as model carbohydrates. Our results demonstrate that complex carbohydrates stably sustain diverse microbial consortia. Further, very similar final consortia were enriched on SAX from the same individual’s fecal microbiota across a one-month interval, suggesting that polysaccharide structure is more influential than stochastic alterations in microbiome composition in governing the outcomes of sequential batch cultivation experiments. SAX-consuming consortia were anchored byBacteroides ovatusand retained diverse consortia of >12 OTUs; whereas final inulin-consuming consortia were dominated either byKlebsiella pneumoniaeorBifidobacteriumsp. andEscherichia coli. Furthermore, auxotrophic interactions were less influential in structuring microbial consortia consuming SAX than the less-complex inulin. These data suggest that carbohydrate structural complexity affords independent niches that structure fermenting microbial consortia, whereas other metabolic interactions govern the composition of communities fermenting simpler carbohydrates.

IMPORTANCE

The mechanisms by which gut microorganisms compete for and cooperate on human-indigestible carbohydrates of varying structural complexity remain unclear. Gaps in this understanding make it challenging to predict the effect of a particular dietary fiber’s structure on the diversity, composition, or function of gut microbiomes, especially with inter-individual variability in diets and microbiomes. Here, we demonstrate that carbohydrate structure governs the diversity of gut microbiota under high dilution pressure, suggesting that such structures may support microbial diversityin vivo. Further, we also demonstrate that carbohydrate polymers are not equivalent in the strength by which they influence community structure and function, and that metabolic interactions among members arising due to auxotrophy exert significant influence on the outcomes of these competitions for simpler polymers. Collectively, these data suggest that large, complex dietary fiber polysaccharides structure the human gut ecosystem in ways that smaller and simpler ones may not.
Entner–Doudoroff pathway and Non-OxPPP bypasses glycolysis and OxPPP inRalstonia solanacearum
Authors: Jyoti Poonam , Shree Manu , Joshi Chandrakant , Prakash Tulika , Ray Suvendra Kumar , Satapathy Siddhartha Sankar , Masakapalli Shyam Kumar
Published: February 2020

InRalstonia solanacearum, a devastating phytopathogen whose metabolism is poorly understood, we observed that Entner-Doudoroff (ED) pathway and NonOxidative pentose phosphate pathway (OxPPP) bypasses glycolysis and OxPPP under glucose oxidation. Evidences derived from13C stable isotopes feeding and genome annotation based comparative metabolic network analysis supported the observations. Comparative metabolic network analysis derived from the currently available53annotatedR. solanacearumstrains also including the recently reported strain (F1C1), representing the four phylotypes confirmed the lack of key genes coding for phosphofructokinase (pfk-1) and phosphogluconate dehydrogenase (gnd) enzymes that are relevant for glycolysis and OxPPP respectively.R. solanacearumF1C1 cells fed with13C Glucose (99%[1-13C]- or 99%[1,2-13C]- or 40%[13C6]-glucose) followed by GC-MS based labelling analysis of fragments from amino acids, glycerol and ribose provided clear evidence that rather than Glycolysis and OxPPP, ED pathway and NonOxPPP are the main routes sustaining metabolism inR. solanacearum. The13C incorporation in the mass ions of alanine (m/z 260, m/z 232); valine (m/z 288, m/z 260), glycine (m/z 218), serine (m/z 390, m/z 362), histidine (m/z 440, m/z 412), tyrosine (m/z 466, m/z 438), phenylalanine (m/z 336, m/z 308), glycerol (m/z 377) and ribose (m/z 160) mapped the pathways supporting the observations. The outcomes help better defining the central carbon metabolic network ofR. solanacearumthat can be integrated with13C metabolic flux analysis as well as flux balance analysis studies for defining the metabolic phenotypes.

Importance

Understanding the metabolic versatility ofRalstonia solanacearumis important as it regulates the tradeoff between virulence and metabolism (1, 2) in a wide range of plant hosts. Due to a lack of clear evidence until this work, several published research papers reported on potential roles of Glycolysis and Oxidative pentose phosphate pathways (OxPPP) inR. solanacearum(3, 4). This work provided evidence from13C stable isotopes feeding and genome annotation based comparative metabolic network analysis that Entner-Doudoroff pathway and Non-OxPPP bypasses glycolysis and OxPPP during the oxidation of Glucose, one of the host xylem pool that serves as a potential carbon source (5). The outcomes help better defining the central carbon metabolic network ofR. solanacearumthat can be integrated with13C metabolic flux analysis as well as flux balance analysis studies for defining the metabolic phenotypes. The study highlights the need to critically examine phytopathogens whose metabolism is poorly understood.
Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig
Authors: Lei Changhai , Fu Wenyan , Qian Kewen , Li Tian , Zhang Sheng , Ding Min , Hu Shi
Published: February 2020

2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoVin vitro.As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV.
Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
Authors: Govaere Olivier , Kragh Petersen Sine , Martinez-Lopez Nuria , Wouters Jasper , Van Haele Matthias , Mancina Rosellina M. , Jamialahmadi Oveis , Bilkei-Gorzo Orsolya , Bel Lassen Pierre , Darlay Rebecca , Peltier Julien , Palmer Jeremy M. , Younes Ramy , Tiniakos Dina , Aithal Guruprasad P. , Allison Michael , Vacca Michele , Göransson Melker , Drinnan Michael J , Yki-Järvinen Hannele , Dufour Jean-Francois , Ekstedt Mattias , Francque Sven , Petta Salvatore , Bugianesi Elisabetta , Schattenberg Jörn M , Day Christopher P. , Cordell Heather J. , Topal Baki , Clément Karine , Romeo Stefano , Ratziu Vlad , Roskams Tania , Daly Ann K. , Anstee Quentin M. , Trost Matthias , Härtlova Anetta
Published: February 2020

Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic lipid metabolism. We show that MSR1 induces a pro-inflammatory response via the JNK signaling pathway upon triggering by saturated fatty acids.In vitroblockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNFa. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model andex vivohuman liver slices resulted in the prevention of foamy macrophage formation and liver inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region ofMSR1,was associated with altered serum triglycerides and aspartate transaminase levels in a cohort of over 400,000 patients. Taken together, our data suggest a critical role for MSR1 in lipid homeostasis and a potential therapeutic target for the treatment of NAFLD.

One Sentence Summary

The immunometabolic role of MSR1 in human NAFLD.
Scleraxis-Lineage Cell Depletion Improves Tendon Healing and Disrupts Adult Tendon Homeostasis
Authors: Best Katherine T. , Korcari Antonion , Mora Keshia E. , Knapp Emma , Buckley Mark R. , Loiselle Alayna E.
Published: February 2020

Despite the requirement forScleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLincells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLincells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTRmice would exhibit functionally deficient healing compared to wildtype littermates. Surprisingly, depletion of ScxLincells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTRmice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLincell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.
FK506-binding protein FklB is involved in biofilm formation through its peptidyl-prolyl isomerase activity
Authors: Zografou Chrysoula , Dimou Maria , Katinakis Panagiotis
Published: February 2020

FklB is a member of the FK506-binding proteins (FKBPs), a family that consists of five genes inEscherichia coli. Little is known about the physiological and functional role of FklB in bacterial movement. In the present study, FklB knock-out mutant ΔfklBpresented an increased swarming and swimming motility and biofilm formation phenotype, suggesting that FklB is a negative regulator of these cellular processes. Complementation with Peptidyl-prolyl isomerase (PPIase)-deficientfklBgene(Y181A) revealed that the defects in biofilm formation were not restored byY181A, indicating that PPIase activity of FklB is modulating biofilm formation inE. coli. The mean cell length of ΔfklBswarming cells was significantly smaller as compared to the wild-type BW25113. Furthermore, the mean cell length of swarming and swimming wild-type and ΔfklBcells overexpressingfklBorY181Awas considerably larger, suggesting that PPIase activity of FklB plays a role in cell elongation and/or cell division. A multi-copy suppression assay demonstrated that defects in motility and biofilm phenotype were compensated by overexpressing sets of PPIase-encoding genes. Taken together, our data represent the first report demonstrating the involvement of FklB in cellular functions ofE. coli.
Sleep-like behavior is a fundamental property of the tripartite synapse
Authors: Joshi Shubhada N , Joshi Aditya N , Joshi Narendra D
Published: February 2020

The tripartite synapse, consisting of the presynaptic neuron, post-synaptic neuron, and an astrocyte, is considered to be the main locus of signaling between neurons in the brain.1,2Neurotransmission is energetically very expensive3,4, and the primary neurotransmitter utilized for signaling is glutamate. It has been found that glutamate is also used as a substrate for energy generation.5,6However, it is unclear what the relationship is between energy generation and availability of neurotransmitter during glutamatergic neurotransmission. Here we show that availability of energy, represented by adenosine triphosphate (ATP), and glutamate for neurotransmission are intimately related, and in fact determine the ability to signal at the tripartite synapse. Using a novel neurochemical mathematical model of the tripartite synapse, we found that glutamate concentrations for neurotransmission and ATP concentrations were interdependent, and their interplay controlled the firing pattern of the presynaptic terminal, as defined by synaptic vesicle release. Furthermore, we found that depending on the parameters chosen in the model, the tripartite synapse demonstrated behavior with limit cycles, alternating between high- and low-frequency firing rates. Our results show that complex behavior with high- and low-activity states, qualitatively meeting the characteristics of sleep7emerges directly from the nature of the tripartite synapse, with glutamate and ATP concentrations serving as the signals for state changes. We anticipate that our model will serve as a starting point to further elucidate the energetics of neuronal and brain functioning, and eventually shed light on the fundamental question of the nature and necessity of sleep.
Purification of Recombinant Adeno-Associated Viruses (rAAVs) by Iodixanol Gradient Centrifugation
Authors: Sena-Esteves Miguel , Gao Guangping
Published: February 2020

This is a simple method for rapid preparation of recombinant adeno-associated virus (rAAV) stocks, which can be used for in vivo gene delivery. The purity of these vectors is considerably lower than that obtained by either CsCl gradient centrifugation or by combination of iodixanol gradient ultracentrifugation followed by column chromatography.
Differential Detergent Lysis of Cellular Fractions for Immunoprecipitation
Authors: DeCaprio James , Kohl Thomas O.
Published: February 2020

Differential detergent fractionation of cells is a rapid method for extraction of cytoplasmic and nuclear proteins in preparation of an immunoprecipitation. This method can be applied for use of adherent or suspension cells and can significantly reduce nonspecific background in an immunoprecipitation by separation of cellular compartments into individual fractions. The lysis of cells by differential detergents permits the rapid extraction of proteins from the cytoplasm (digitonin), the cytoplasmic membranes, and organelles (Triton X-100), and nucleoplasm (Tween/DOC), facilitated through the use of distinct extraction buffers. Cytoplasmic and nuclear matrix proteins as well as DNA are left behind during the detergent-based extraction.
Staining Nucleic Acids
Authors: Green Michael R. , Sambrook Joseph
Published: February 2020

This introduction describes the features and uses of ethidium bromide, methylene blue, and SYBR dyes for staining nucleic acids.
For emancipation: a Marxist critique of structure within critical realism
Authors: Andrew Jane , Baker Max
Published: February 2020

Purpose

The authors critique Modell's proposition that critical realism is useful in elucidating and creating possibilities for emancipation.

Design/methodology/approach

The authors begin by outlining Modell's conception of enabling structures. If ‘activated’ by reflexive individuals, these are theorised to be a mechanism through which agents can begin to emancipate themselves. However, the authors argue that emancipation must be contextualised within the material realities of global capitalism, paying particular attention to the shape of inequality and the subjects of exploitation. In doing this, they draw on Marx to pose an alternative view of structure.

Findings

In offering a Marxist critique of critical realism, the authors show how capitalist superstructure and base work together to reinforce inequality. In doing this, they highlight the enduring importance of collective action as the engine of emancipation. It is for this reason that they advocate for an emancipatory politics, which is collectively informed outside of, and in conflict with, the logics of capitalism.

Research limitations/implications

The authors argue that explicit discussions of capitalism and its structures must be at the centre of critical accounting research, especially when it pertains to emancipation.

Originality/value

Given the importance of the conceptual framing of critical accounting research, this article suggests that critical realism has much to offer. That said, the authors draw on Marx to raise a number of important questions about both the nature of structure and the identity of reflexive agents within critical realism. They do this to encourage further debate about the emancipatory possibilities of the critical accounting project and the ideas proposed by Modell (2020).
An exploratory factor analysis of HONOS-LD scales
Authors: Turton Rai
Published: February 2020

Purpose

The purpose of this study is to identify clinically meaningful groups of Health of the Nation Scales Learning Disabilities (HONOS-LD) single-item scales that might be used as short scales that are more reliable than single-item scale scores and more focused than the sum of scale scores. The single-item scales are likely to be unreliable in many applications. The sum of scale scores is a heterogeneous measure that is not a good representative of any specific difficulties that people who have intellectual disabilities may have and the effects of interventions on any specific difficulties may be masked by fluctuations in the ratings of other scales.

Design/methodology/approach

A total of 2,109 pseudonymised complete HONOS-LD ratings were factor-analysed using principal factor extraction and oblimin rotation. Three-, four- and five-factor rotated patterns were examined.

Findings

Three factors that each have three or more strong loadings (≥|0.50|) were identified that jointly included 11 single-item scales: one representing problems with cognitive competencies, one representing depressive phenomena or other mood problems and one representing problems with social competencies. A weaker factor that represents behaviour that challenges services is indicated; it includes five single-item scales. Both the cognitive competencies and social competencies groups of items were also reported in a previous study by Skelly and D’Antonio (2008) and may be stable. The present study’s factor representing behavioural difficulty has some similarity to Skelly and D’Antonio’s “functional behaviour and attachment disturbance” group. In other respects, the present study and the previous study differ.

Research limitations/implications

The outcomes of these factor analyses indicate that some of the single-item scales can be combined into groups. However, the specific groups found in this study must be regarded as possibly unstable because of the likelihood of weak inter-rater reliability in HONOS-LD data and differences between this analysis and Skelly and D’Antonio’s. Further research is needed to support or modify them.

Practical implications

The cognitive competence and social competence groups of items may be used as subscales if they are convenient. The groups representing mood and behavioural problems should be supported by further research before being used.

Originality/value

This is the second published factor analysis of the HONOS-LD and includes a much larger data set than the first. It has some similarities to and differences from the first and is a further step in the process of identifying useful groupings of HONOS-LD single-item scales.
Cocreation of tourism experiences: are food-related activities being explored?
Authors: Rachão Susana , Breda Zélia , Fernandes Carlos , Joukes Veronique
Published: February 2020

Purpose

This study analyses the dimensions of cocreation in on-site food-related activities.

Design/methodology/approach

A systematic literature review was conducted in two databases (Scopus and Institute for Scientific Information (ISI) Web of Science), and 67 peer-reviewed articles were identified on cocreation in tourism experiences.

Findings

The study reveals that food-related activities involving active participation are more likely to be successfully performed in more informal environments, in which culinary experiences cocreated by both tourists and hosts are favoured. Moreover, tourists who learn something new appreciate the value of cocreation within food tourism experiences better.

Research limitations/implications

Although the researchers used two renowned databases to conduct the systematic literature review, there is the risk that some manuscripts related to the topic were excluded.

Practical implications

The transfer of new skills and knowledge through direct contact between tourists and hosts are prerequisites for the raise of the value of the cocreation process itself and of the final outcome of the cocreation experience. As a result, professional service providers should dedicate more attention to the inclusion of cocreative ‘learning’ elements in the food tourism experiences they create.

Social implications

Due to the changing structure of the tourism ecosystem (technological advances), the manner in which experiences are designed, distributed and consumed (cocreated) is being transformed. The present study highlights some aspects to be developed by tourism destination managers.

Originality/value

This study is the first to explore food-related tourism experiences through the lens of cocreation.
Proposed 3.5 µW CNTFET-MOSFET hybrid CSVCO for power-efficient gigahertz applications
Authors: Ghanbari Khorram Hamidreza , Kokabi Alireza
Published: February 2020

Purpose

Several ultra-low power and gigahertz current-starved voltage-controlled oscillator (CSVCO) circuits have been proposed and compared here. The presented structures are based on the three-stage hybrid circuit of the carbon nanotube field-effect transistors (CNTFETs) and low-power MOSFETs. The topologies exploit modified and compensated Schmitt trigger comparator parts to demonstrate better consumption power and frequency characteristics. The basic idea in the presented topologies is to compensate the Schmitt trigger comparator part of the basic CSVCO for achieving faster carrier mobility of the holes, reducing transistor leakage current and eliminating dummy transistors.

Design/methodology/approach

This study aims to propose and compare three different comparator-based VCOs that have been implemented using the CNTFETs. The considered circuits are shown to be capable of delivering the maximum 35 tuning frequency in the order of 1 GHz to 5 GHz. A major power thirsty part of the high-frequency ring VCOs is the Schmitt trigger stage. Here, several fast and low-power Schmitt trigger topologies are exploited to mitigate the dissipation power and enhance the oscillation frequency.

Findings

As a result of proposed modifications, more than one order of magnitude mitigation in the VCO power consumption with respect to the previously presented three-stage CSVCO is reported here. Thus, a VCO dissipation power of 3.5 µW at the frequency of 1.1 GHz and the tuning range of 26 per cent is observed for the well-established 32 nm technology and the supply voltage of 1 V. Such a low dissipation power is obtained around the operating frequency of the battery-powered cellular phones. In addition, using the p-carrier mobility compensation and enhancing the rise time of the Schmitt trigger part of the CSVCO, a maximum of 2.38 times higher oscillation frequency and 72 per cent wider tuning range with respect to Rahane and Kureshi (2017) are observed. Simultaneously, this topology exhibits an average of 20 per cent reduction in the power consumption.

Originality/value

Several new VCO topologies are presented here, and it is shown that they can significantly enhance the power dissipation of the GHz CSVCOs.
Ideal physical features of environmental design in children’s hospital
Authors: Nourmusavi Nasab Sara , Karimi Azeri Amir Reza , Mirbazel Seyedjalal
Published: February 2020

Purpose

During hospitalization, children are faced with physical disorders and many psychological challenges. One important factor affecting children is the environmental design of the hospital. The inappropriate design of hospitals may contribute to an increase in fear, anxiety and behavioral disorders. The purpose of this study is to use children’s perspectives to evaluate the importance and impact of effective environmental factors to generate children’s hospital design guidelines.

Design/methodology/approach

In this study, children’s desired atmosphere during treatment was examined via 16 drawings and 24 interviews from children at a children’s hospital in Iran.

Findings

The encoding of information extracted environmental components such as window view, color, hobby, playing, decorations, family presence, structure of hospital, presence of nurse, furniture, water features, light and green space. The results indicate that children prefer a hospital environment that provides entertainment facilities while also offering design features such as the presence of light, colorful decorations, the existence of green spaces and conditions suitable for their families to be present.

Research limitations/implications

Depending on the location and their living conditions, the children’s prioritization can be different in any society. In addition, the data of this research was descriptive; thus, the conclusions must be considered tentative.

Originality/value

A number of studies focus on the needs of populations in developed countries. This topic has not been investigated in a major way via professionals in non-western countries such as Iran. Thus, the context of this study and present findings can be deemed unique.
Design incubatees' perspectives and experiences in Hong Kong
Authors: FONG Tiffany W.M.
Published: February 2020

Purpose

This paper discusses the services and support from one of the government design-based business incubators in Hong Kong. The characteristics of a design business incubator are explained, and a multiple-case study indicates the perspectives of incubatees from different design disciplines after their graduation from the incubation programme.

Design/methodology/approach

The research under discussion in this paper was based on eight design incubatees in different design disciplines within two years of incubation period, all of whom had participated in one of the government-funded business incubation programmes for designers in Hong Kong. The programme is unique because there are no other government-based incubation programmes for designers in Hong Kong. Semi-structured interviews were conducted to collect feedback from incubatees in areas ranging from terms of service to support of the incubation programme.

Findings

The services of training, mentorship and finance were found to be the most important to design start-ups. Financial support and flexible funding allocation were another important issue for design incubatees, but training in these subject areas was not included in the incubation programme. However, it was confirmed that funding provided may have helped a number of the incubatees in developing their start-up businesses as a result of the reduced financial burden and office allocation.

Research limitations/implications

The research focused on one incubation programme because of the lack of incubation programmes for designers in Hong Kong, therefore future research which compares different types of business incubation programmes is suggested.

Practical implications

The outcomes of the research not only identified the possible areas of development and improvement of business incubation in entrepreneurship but they will also be useful for the government, universities, institutions, designers, policy makers, entrepreneurs and practitioners. These, in addition to industry stakeholders who want to evaluate their entrepreneurship programmes and develop their plans for potential development in incubation- or entrepreneurial-related programmes or training, especially in the area of design, will find the results useful.