bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral DIEP Flap Breast Reconstruction to a Single Set of Internal Mammary Vessels: Technique, Safety, and Outcomes after 250 Flaps
Authors: Opsomer Dries , D’Arpa Salvatore , Benmeridja Lara , Stillaert Filip , Noel Warren , Van Landuyt Koenraad
Published: October 2019

Background:

The deep inferior epigastric artery perforator (DIEP) flap is considered the gold standard in autologous breast reconstruction. In bilateral cases, both flaps are often anastomosed to the internal mammary vessels on either side of the sternum. The authors propose a method in which both flaps are anastomosed to only the right side internal mammary artery and vein.

Methods:

Between November of 2009 and March of 2018, 125 patients underwent bilateral DIEP flap breast reconstruction with this technique. One flap is perfused by the anterograde proximal internal mammary artery and the second one by the retrograde distal internal mammary artery after presternal tunneling. Patient demographics and operative details were reviewed retrospectively.

Results:

Two hundred fifty flaps were performed. One hundred fifty-two flaps were prophylactic or primary reconstructions (60.8 percent), 70 were secondary reconstructions (28 percent), and 28 were tertiary reconstructions (11.2 percent). Mean patient age was 46 years, and the mean body mass index was 25 kg/m2. Sixty patients underwent radiation therapy or chemotherapy (48 percent). The authors encountered one significant partial failure (0.4 percent) and nine complete flap failures (3.6 percent). The authors did not see a statistically significant predisposition for failure comparing the retrograde with the anterograde flow flaps, nor when comparing the tunneled with the nontunneled flaps.

Conclusions:

The authors’ results show that anastomosing both DIEP flaps to a single set of mammary vessels is safe and reliable. The authors conclude that the retrograde flow through the distal internal mammary artery is sufficient for free flap perfusion and that subcutaneous tunneling of a free flap pedicle does not predispose to flap failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Safety of Postoperative Opioid Alternatives in Plastic Surgery: A Systematic Review
Authors: O’Neill Rebecca C. , Hayes Kylie D. , Davison Steven P.
Published: October 2019

With the growing opioid epidemic, plastic surgeons are being encouraged to transition away from reliance on postoperative opioids. However, many plastic surgeons hesitate to use nonopioid analgesics such as nonsteroidal antiinflammatory drugs and local anesthetic blocks because of concerns about their safety, particularly bleeding. The goal of this systematic review is to assess the validity of risks associated with nonopioid analgesic alternatives. A comprehensive literature search of the PubMed and MEDLINE databases was conducted regarding the safety of opioid alternatives in plastic surgery. Inclusion and exclusion criteria yielded 34 relevant articles. A systematic review was performed because of the variation between study indications, interventions, and complications. Thirty-four articles were reviewed that analyzed the safety of ibuprofen, ketorolac, celecoxib, intravenous acetaminophen, ketamine, gabapentin, liposomal bupivacaine, and local and continuous nerve blocks after plastic surgery procedures. There were no articles that showed statistically significant bleeding associated with ibuprofen, celecoxib, or ketorolac. Similarly, acetaminophen administered intravenously, ketamine, gabapentin, and liposomal bupivacaine did not have any significant increased risk of adverse events. Nerve and infusion blocks have a low risk of pneumothorax. Limitations of this study include small sample sizes, different dosing and control groups, and more than one medication being studied. Larger studies of nonopioid analgesics would therefore be valuable and may strengthen the conclusions of this review. As a preliminary investigation, this review showed that several opioid alternatives have a potential role in postoperative analgesia. Plastic surgeons have the responsibility to lead the reduction of postoperative opioid use by further developing multimodal analgesia.
18F-FDG PET/CT of Multiorgan Sarcoid-Like Reaction During Anti–PD-1 Treatment for Melanoma
Authors: van Willigen Wouter W. , Gerritsen Winald R. , Aarntzen Erik H.J.G.
Published: October 2019

We report a case of a 50-year-old woman treated with anti–PD-1 inhibition for metastatic melanoma. During treatment, extensive and transient histopathologically confirmed sarcoid-like reaction was detected in multiple organ systems and at different time points using 18F-FDG PET/CT imaging. Immune-related adverse events during anti-PD-1/PD-L1 antibody treatment are increasingly being reported. This case report emphasizes the broad spectrum of possible presentations of sarcoid-like reaction detected by 18F-FDG PET/CT and its evolution in time. For the clinician, awareness of these immune-related adverse events helps to accurately interpret findings on imaging.
Polyarteritis Nodosa With Reversible FDG Accumulation in Vessels and Kidneys
Authors: Mino Nanami , Yamashita Hiroyuki , Takahashi Yuko , Kaneko Hiroshi
Published: October 2019

A 59-year-old man presented with fever and lower extremity myalgia. Laboratory studies revealed elevated C-reactive protein.18F-FDG PET/CT demonstrated FDG uptake not only in the brachial arteries, femoral arteries, and their main ramifications, which were equivalent to small- to medium-sized arteries but also in the kidneys. Angiography revealed a renal aneurysm, confirming the diagnosis of polyarteritis nodosa. The increased FDG uptake in the vessels and kidneys resolved after 6 months of glucocorticoid treatment.
Identification of Distant Metastases From Recurrent Gliosarcoma Using Whole-Body 18F-FDG PET/CT
Authors: Unterrainer Marcus , Ruf Viktoria , Cyran Clemens C. , Brendel Matthias , Thon Niklas , Herms Jochen , Schüller Ulrich , Tonn Joerg-Christian , Bartenstein Peter , Albert Nathalie Lisa
Published: October 2019

A 51-year-old man presented with recurrent gliosarcoma and increasing cough over the last months. On 18F-FDG PET/CT, solid lung masses with high 18F-FDG uptake were present. A biopsy taken from a lung lesion indicated distant metastases from gliosarcoma. Gliosarcoma, a rare malignant central nervous system tumor, presents with extracranial metastases in only less than 10%. As highlighted by this case, 18F-FDG PET/CT can be used for whole-body staging in patients with metastatic brain tumor. Vice versa, highly 18F-FDG–avid lung lesions in patients with brain tumors should lead to distant metastases as differential diagnosis despite their rare occurrence.
Co-existence of multiple distinct lineages in Vibrio parahaemolyticus serotype O4:K12
Authors: Zhao Lin , Chen Hongyou , Didelot Xavier , Li Zhenpeng , Li Yinghui , Chen Meiling , Du Yu , Zhao Hongqun , Li Jie , Hu Qinghua , Kan Biao , Chen Min , Pang Bo
Published: October 2019

Vibrio parahaemolyticus

is an important cause of foodborne gastroenteritis globally. Thermostable direct haemolysin (TDH) and the TDH-related haemolysin are the two key virulence factors in V. parahaemolyticus. Vibrio pathogenicity islands harbour the genes encoding these two haemolysins. The serotyping of

V. parahaemolyticus

is based on the combination of O and K antigens. Frequent recombination has been observed in

V. parahaemolyticus

, including in the genomic regions encoding the O and K antigens.

V. parahaemolyticus

serotype O4:K12 has caused gastroenteritis outbreaks in the USA and Spain. Recently, outbreaks caused by this serotype of

V. parahaemolyticus

have been reported in China. However, the relationships among this serotype of

V. parahaemolyticus

strains isolated in different regions have not been addressed. Here, we investigated the genome variation of the

V. parahaemolyticus

serotype O4:K12 using the whole-genome sequences of 29 isolates. We determined five distinct lineages in this strain collection. We observed frequent recombination among different lineages. In contrast, little recombination was observed within each individual lineage. We showed that the lineage of this serotype of

V. parahaemolyticus

isolated in America was different from those isolated in Asia and identified genes that exclusively existed in the strains isolated in America. Pan-genome analysis showed that strain-specific and cluster-specific genes were mostly located in the genomic islands. Pan-genome analysis also showed that the vast majority of the accessory genes in the O4:K12 serotype of

V. parahaemolyticus

were acquired from within the genus

Vibrio

. Hence, we have shown that multiple distinct lineages exist in

V. parahaemolyticus

serotype O4:K12 and have provided more evidence about the gene segregation found in

V. parahaemolyticus

isolated in different continents.
A sorghum Practical Haplotype Graph facilitates genome-wide imputation and cost-effective genomic prediction
Authors: Jensen Sarah E. , Charles Jean Rigaud , Muleta Kebede , Bradbury Peter , Casstevens Terry , Deshpande Santosh P. , Gore Michael A. , Gupta Rajeev , Ilut Daniel C. , Johnson Lynn , Lozano Roberto , Miller Zachary , Ramu Punna , Rathore Abhishek , Romay M. Cinta , Upadhyaya Hari D. , Varshney Rajeev , Morris Geoffrey P. , Pressoir Gael , Buckler Edward S. , Ramstein Guillaume P.
Published: October 2019

Successful management and utilization of increasingly large genomic datasets is essential for breeding programs to increase genetic gain and accelerate cultivar development. To help with data management and storage, we developed a sorghum Practical Haplotype Graph (PHG) pangenome database that stores all identified haplotypes and variant information for a given set of individuals. We developed two PHGs in sorghum, one with 24 individuals and another with 398 individuals, that reflect the diversity across genic regions of the sorghum genome. 24 founders of the Chibas sorghum breeding program were sequenced at low coverage (0.01x) and processed through the PHG to identify genome-wide variants. The PHG called SNPs with only 5.9% error at 0.01x coverage - only 3% lower than its accuracy when calling SNPs from 8x coverage sequence. Additionally, 207 progeny from the Chibas genomic selection (GS) training population were sequenced and processed through the PHG. Missing genotypes in the progeny were imputed from the parental haplotypes available in the PHG and used for genomic prediction. Mean prediction accuracies with PHG SNP calls range from 0.57-0.73 for different traits, and are similar to prediction accuracies obtained with genotyping-by-sequencing (GBS) or markers from sequencing targeted amplicons (rhAmpSeq). This study provides a proof of concept for using a sorghum PHG to call and impute SNPs from low-coverage sequence data and also shows that the PHG can unify genotype calls from different sequencing platforms. By reducing the amount of input sequence needed, the PHG has the potential to decrease the cost of genotyping for genomic selection, making GS more feasible and facilitating larger breeding populations that can capture maximum recombination. Our results demonstrate that the PHG is a useful research and breeding tool that can maintain variant information from a diverse group of taxa, store sequence data in a condensed but readily accessible format, unify genotypes from different genotyping methods, and provide a cost-effective option for genomic selection for any species.
Low E2F2 activity is associated with high genomic instability and PARPi resistance
Authors: Rennhack Jonathan P , Andrechek Eran R.
Published: October 2019

The E2F family, classically known for a central role in cell cycle, has a number of emerging roles in cancer including angiogenesis, metabolic reprogramming, metastasis and DNA repair. E2F1 specifically has been shown to be a critical mediator of DNA repair; however, little is known about DNA repair and other E2F family members. Here we present an integrative bioinformatic and high throughput drug screening study to define the role of E2F2 in maintaining genomic integrity in breast cancer. We utilizedin vitroE2F2 ChIP-chip and over expression data to identify transcriptional targets of E2F2. This data was integrated with gene expression from E2F2 knockout tumors in an MMTV-Neu background. Finally, this data was compared to human datasets to identify conserved roles of E2F2 in human breast cancer through the TCGA breast cancer, Cancer Cell Line Encyclopedia, and CancerRx datasets. Here we have computationally predicted that E2F2 transcriptionally regulates key mediators of DNA repair. Our gene expression data supports this hypothesis and low E2F2 activity is associated with a highly unstable tumor. In human breast cancer E2F2, status was also correlated with a patient’s response to PARP inhibition therapy. Taken together this manuscript defines a novel role of E2F2 in cancer progression beyond cell cycle and could be therapeutically relevant.

Author Summary

The E2F family of proteins have been known to regulate cell cycle and have recently been shown to have a number of roles in tumor progression. Here we use a combination of computational techniques and high-throughput drug screening data to establish a novel role of E2F2 in maintaining genomic integrity. We have shown that a number of direct and indirect target genes of E2F2 are involved in multiple classical DNA repair pathways. Importantly, this was shown to be unique to E2F2 and not present with other activator E2Fs like E2F1. We have also shown that E2F2 activity is positively correlated with PARP inhibitor sensitivity regardless of BRCA1/2 status. This is important due to the recent approval of PARP inhibitor therapy in the clinic. Based on our work E2F2 activity could serve as a novel biomarker of response and may identify a new cohort of patients which could benefit from PARPi therapy.
Virtual reality as a tool for environmental conservation and fundraising
Authors: Nelson Katherine M. , Anggraini Eva , Schlüter Achim
Published: October 2019

Anecdotal evidence from philanthropic fundraisers shows that virtual reality (VR) technology increases empathy and can influence people toward pro-environmental behavior. Non-profit organizations are increasingly marketing their causes using virtual reality and they report increased donations when VR technology is employed. In VR, users are immersed in situations intended to feel more like the real world through technology, such as 360° video screened through 3D headsets that block out visual and auditory distractions. The framing of the message as either positive or negative has long shown to have an effect on behavior, although consensus on the impact of framing has not been reached in relation to encouraging contributions to public goods. This paper focuses on field experiments used to investigate the effects of varying degrees of visual immersion and positive versus negative message framing on respondents’ contributions to a conservation charity. Participants were exposed to a five-minute underwater film about coral reefs and the importance of protecting them. We employed a 2×2 experimental design using 3D head-mounted displays comparing 360° film footage vs. unidirectional film and a positive message vs. a negative message. After watching the film, each participant completed a short questionnaire and had the opportunity to donate to a marine conservation charity. In addition, we tested a control treatment where no video was observed. The video was filmed in Indonesia which is host to some of the world’s most biodiverse reefs that are under great threat from human activity. We also conducted the study in Indonesia, sampling a total of 1006 participants from the Bogor city area and tourists on the island of Gili Trawangan - which is popular for scuba diving and snorkeling. We find significant differences in observed behavior and reported emotions between all treatments compared to the control condition. Among the tourist sample, we find significant differences between the 360° film with a negative message which garnered significantly larger average donation amounts compared to the unidirectional film with both positive and negative framing. Overall, we can infer from these studies that virtual reality is an effective way to raise awareness of environmental threats and encourage behavioral action, especially when tailored to target groups. New technology, such as the VR head-mounted display, is highly effective at attracting interest which is an important point to encourage organizations to invest in new technologies.
Target-responsive vasoactive probes for ultrasensitive molecular imaging
Authors: Ohlendorf Robert , Wiśniowska Agata , Desai Mitul , Barandov Ali , Slusarczyk Adrian L. , Jasanoff Alan
Published: October 2019

The ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly-caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.
Membrane stiffness is a key determinant of E coli MscS channel mechanosensitivity
Authors: Xue Feng , Cox Charles D. , Bavi Navid , Rohde Paul R , Nakayama Yoshitaka , Martinac Boris
Published: October 2019

Prokaryotic mechanosensitive (MS) channels have an intimate relationship with membrane lipids. Membrane lipids may influence channel activity by directly interacting with bacterial MS channels or by influencing the global properties of the membrane such as area stretch and bending moduli. Previous work has implicated membrane stiffness as a key determinant of the mechanosensitivity of E. coli (Ec)MscS. Here we systematically tested this hypothesis using patch fluorometry of azolectin liposomes doped with lipids of increasing area stretch moduli. Increasing DOPE content of azolectin liposomes causes a rightward shift in the tension response curve of EcMscS. These rightward shifts are further magnified by the addition of stiffer forms of PE such as the branched chain lipid DPhPE and the fully saturated lipid DSPE. Furthermore, a comparison of the branched chain lipid DPhPC to the stiffer DPhPE showed a rightward shift in the tension response curve in the presence of the stiffer DPhPE. We show that these changes are not due to changes in membrane bending rigidity as the tension threshold of EcMscS in membranes doped with PC18:1 and PC18:3 are the same, despite a two-fold difference in their bending rigidity. We also show that after prolonged pressure application sudden removal of force in softer membranes causes a rebound reactivation of EcMscS and we discuss the relevance of this phenomenon to bacterial osmoregulation. Collectively, our data demonstrate that membrane stiffness is a key determinant of the mechanosensitivity of EcMscS.
A physics-based energy function allows the computational redesign of a PDZ domain
Authors: Opuu Vaitea , Sun Young Joo , Hou Titus , Panel Nicolas , Fuentes Ernesto J. , Simonson Thomas
Published: October 2019

A powerful approach to understand protein structure and evolution is to perform computer simulations that mimic aspects of evolution. In particular, structure-based computational protein design (CPD) can address the inverse folding problem, exploring a large space of amino acid sequences and selecting ones predicted to adopt a given fold. Previously, CPD has been used to entirely redesign several proteins: all or most of the protein sequence was allowed to mutate freely; among sampled sequences, those with low computed folding energy were selected, and a few percent of them did indeed adopt the correct fold. Those studies used an energy function that was partly or largely knowledge-based, with several empirical terms. Here, we show that a PDZ domain can be entirely redesigned using a "physics-based" energy function that combines standard molecular mechanics and a recent, continuum electrostatic solvent model. Many thousands of sequences were generated by Monte Carlo simulation. Among the lowest-energy sequences, three were chosen for experimental testing. All three could be overexpressed and had native-like circular dichroism and 1D NMR spectra. Two exhibited an upshift of their thermal denaturation curves when a peptide ligand was present, indicating they were able to bind and were most likely correctly folded. Evidently, the physical principles that govern molecular mechanics and continuum electrostatics are sufficient to perform whole-protein redesign. This is encouraging, since these methods provide physical insights, can be systematically improved, and are transferable to other biopolymers and ligands of medical or technological interest.
Assembly of novel, nuclear dimers of the PI3-Kinase regulatory subunits underpins the pro-proliferative activity of the Cdc42-activated tyrosine kinase, ACK
Authors: Clayton Natasha S. , Fox Millie , Vicenté-Garcia Jose J. , Schroeder Courtney M. , Littlewood Trevor D. , Wilde Jonathan I. , Corry Jessica , Krishnan Kadalmani , Zhang Qifeng , Wakelam Michael J. O. , Brown Murray J. B. , Crafter Claire , Mott Helen R. , Owen Darerca
Published: October 2019

The tyrosine kinase ACK is an oncogene associated with poor prognosis in human cancers. ACK promotes proliferation, in part, by contributing to the activation of Akt, the major PI3-Kinase effector. We show that ACK also regulates PI3-Kinase directly, via interactions with the PI3-Kinase regulatory subunits. ACK interacts with all five regulatory subunit isoforms and directly phosphorylates p85α, p85β, p55α and p50α on Tyr607 (or equivalent). Phosphorylation of p85β at this residue promotes cell proliferation but, counterintuitively, ACK does not stimulate PI3-Kinase catalytic activity. We show that ACK stabilizes p85α levels by promoting an interaction between the p85 nSH2 domain and pTyr607, protecting p85 from ubiquitination. We demonstrate that ACK interacts with p85α exclusively in nuclear-enriched cell fractions where the increased levels of the regulatory subunits, together with the nSH2-pTyr607 interaction, promote formation of dimeric p85. We postulate that these novel dimers undertake nuclear functions that contribute to Cdc42-ACK driven oncogenesis. We propose that ACK shapes PI3-Kinase signalling by dampening the PIP3response, whilst continuing to drive cell proliferation through Akt activation and hereto unexplored but crucial functions of nuclear dimeric p85. These new regulatory subunit dimers represent a previously undescribed mode of regulation for PI3-Kinase and potentially reveal additional avenues for therapeutic intervention.
White matter hyperintensities and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment
Authors: Misquitta Karen , Dadar Mahsa , Collins D. Louis , Tartaglia Maria Carmela ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

Background and Purpose: Neuropsychiatric symptoms (NPS) are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease can cause focal lesions and is common among AD patients. As cerebrovascular disease can be detected on MRI as white matter hyperintensities (WMH), this study evaluated WMH burden in mild cognitive impairment (MCI), AD and normal controls and determined their relationship with NPS. Methods: NPS were assessed using the Neuropsychiatric Inventory and grouped into subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry was used to measure atrophy of grey matter regions. Results: WMHs and grey matter atrophy both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. Conclusions: This study could provide a better understanding of the pathophysiology of NPS in AD.
Widespread dysregulation of long non-coding genes associated with fatty acid metabolism, cell division, and immune response gene networks in xenobiotic-exposed rat liver
Authors: Karri Kritika , Waxman David J.
Published: October 2019

Xenobiotic exposure activates or inhibits transcription of hundreds of protein-coding genes in mammalian liver, impacting many physiological processes and inducing diverse toxicological responses. Little is known about the effects of xenobiotic exposure on long noncoding RNAs (lncRNAs), many of which play critical roles in regulating gene expression. Objective: to develop a computational framework to discover liver-expressed, xenobiotic-responsive lncRNAs (xeno-lncs) with strong functional, gene regulatory potential and elucidate the impact of xenobiotic exposure on their gene regulatory networks. We analyzed 115 liver RNA-seq data sets from male rats treated with 27 individual chemicals representing seven mechanisms of action (MOAs) to assemble the long non-coding transcriptome of xenobiotic-exposed rat liver. Ortholog analysis was combined with co-expression data and causal inference methods to infer lncRNA function and deduce gene regulatory networks, including causal effects of lncRNAs on protein-coding gene expression and biological pathways. We discovered >1,400 liver-expressed xeno-lncs, many with human and/or mouse orthologs. Xenobiotics representing different MOAs were often regulated common xeno-lnc targets: 123 xeno-lncs were dysregulated by at least 10 chemicals, and 5 xeno-lncs responded to at least 20 of the 27 chemicals investigated. 81 other xeno-lncs served as MOA-selective markers of xenobiotic exposure. Xeno-lnc–protein-coding gene co-expression regulatory network analysis identified xeno-lncs closely associated with exposure-induced perturbations of hepatic fatty acid metabolism, cell division, and immune response pathways. We also identified hub and bottleneck lncRNAs, which are expected to be key regulators of gene expression incisor intrans. This work elucidates extensive networks of xeno-lnc–protein-coding gene interactions and provides a framework for understanding the extensive transcriptome-altering actions of diverse foreign chemicals in a key responsive mammalian tissue.
CircFOXK2 Promotes Tumor Growth and Metastasis of Pancreatic Ductal Adenocarcinoma via Complexing with RNA Binding Proteins and Sponging MiR-942
Authors: Wong Chi Hin , Lou Ut Kei , Li Youjia , Chan Stephen Lam , Tong Joanna Hung-Man , To Ka-Fai , Chen Yangchao
Published: October 2019

Objective

Circular RNA (circRNA) is a novel class of non-coding RNAs that regulate gene expression. However, the role of circRNAs in pancreatic ductal adenocarcinoma (PDAC) is largely unknown.

Design

We performed circRNA sequencing of non-tumor HPDE and PDAC cells. We investigated the functions of circFOXK2 in PDAC by gain-of-function and loss-of-function assays. Bioinformatics analysis, luciferase assay and microRNA pulldown assays were performed to identify circFOXK2 interacting-miRNAs. To further investigate the mechanism, we performed circRNA-pulldown and mass spectrometry to identify circFOXK2-interacting proteins in PDAC.

Results

We identified 169 differentially expressed circRNAs in PDAC cells. We validated that one of the circRNAs circFOXK2 was significantly up-regulated in PDAC cells and in 63 % of primary tumor (53 out of 84). Gain-of-function and loss-of-function assays demonstrated that circFOXK2 promoted PDAC cell growth, migration and invasion. CircFOXK2 was also involved in cell cycle progression and apoptosis. circFOXK2 functioned as sponge for miR-942, and in turn promoted the expression of miR-942 targets ANK1, GDNF and PAX6. Furthermore, circFOXK2 interacted with 94 proteins, which were involved in cell adhesion and mRNA splicing. Among these circFOXK2-interacting proteins, YBX1 and hnRNPK were validated by RNA immunoprecipitation. Importantly, circFOKX2 interacted with YBX1 and hnRNPK targets NUF2 and PDXK in PDAC cells. Knockdown of circFOXK2 reduced the binding of YBX1 and hnRNPK to NUF2 and PDXK, and in turn decreased their expressions in PDAC cells.

Conclusion

We identified that circFOXK2 promoted PDAC cells growth and metastasis. Also, circFOXK2 complexed with YBX1 and hnRNPK to promote the expressions of oncogenic proteins.

Significance of this study

What is already known on this subject?

Differentially expressed circRNAs are involved in carcinogenesis of many cancers.

CircRNAs function as microRNA sponges to regulate gene expression.

The roles of circRNAs in PDAC progression is largely unknown.

What are the new findings?

circFOXK2 is upregulated in PDAC primary tumors.

circFOXK2 promotes PDAC tumor growth and liver metastasis.

circFOXK2 functions as sponges for miR-942 to promote the expressions of oncogenic ANK1, GDNF and PAX6.

circFOXK2 complexes with YBX1 and hnRNPK to promote the expressions of oncogenic proteins in PDAC.

How might it impact on clinical practice in the foreseeable future?

circFOXK2 upregulation in PDAC may function as a novel biomarker for diagnosis.

circFOXK2 may be a novel therapeutic target in treating PDAC.
GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control
Authors: Hickey Kelsey L. , Dickson Kimberley , Cogan J. Zachery , Replogle Joseph M. , Schoof Michael , D’Orazio Karole N. , Sinha Niladri K. , Frost Adam , Green Rachel , Weissman Jonathan S. , Kostova Kamena K.
Published: October 2019

Ribosome-associated Quality Control (RQC) pathways protect cells from toxicity caused by incomplete protein products resulting from translation of damaged or problematic mRNAs. Extensive work in yeast has identified highly conserved mechanisms that lead to the degradation of the faulty mRNA and partially synthesized polypeptide. Here, we used CRISPR-Cas9-based screening to search for additional RQC strategies in mammals. We found that failed translation leads to specific silencing of translation initiation on that message. This negative feedback loop is mediated by two translation inhibitors, GIGYF2 and 4EHP. Their recruitment to defective messages can be mediated by different factors, including potentially the collision sensor ZNF598. Both model substrates and growth-based assays established that inhibition of additional rounds of translation acts in concert with known RQC pathways to prevent buildup of toxic proteins. Inability to block translation of faulty mRNAs, and subsequent accumulation of partially synthesized polypeptides, could explain the neurodevelopmental and neuropsychiatric disorders observed in mice and humans with compromised GIGYF2 function.
Strain-Dependent Kinetic Properties of KIF3A and KIF3C Tune the Mechanochemistry of the KIF3AC Heterodimer
Authors: Bensel Brandon M. , Woody Michael S. , Pyrpassopoulos Serapion , Goldman Yale E. , Gilbert Susan P. , Ostap E. Michael
Published: October 2019

KIF3AC is a mammalian neuron-specific kinesin-2 implicated in intracellular cargo transport. It is a heterodimer of KIF3A and KIF3C motor polypeptides which have distinct biochemical and motile properties as engineered homodimers. Single-molecule motility assays show that KIF3AC moves processively along microtubules at a rate faster than expected given the motility rates of the KIF3AA and much slower KIF3CC homodimers. To resolve the stepping kinetics of KIF3A and KIF3C motors in homo-and heterodimeric constructs, and to determine their transport potential under mechanical load, we assayed motor activity using interferometric scattering (iSCAT) microscopy and optical trapping. The distribution of stepping durations of KIF3AC molecules is described by a rate (k1 = 11 s−1) without apparent kinetic asymmetry in stepping. Asymmetry was also not apparent under hindering or assisting mechanical loads of 1 pN in the optical trap. KIF3AC shows increased force sensitivity relative to KIF3AA, yet is more capable of stepping against mechanical load than KIF3CC. Microtubule gliding assays containing 1:1 mixtures of KIF3AA and KIF3CC result in speeds similar to KIF3AC, indicating the homodimers mechanically impact each other’s motility to reproduce the behavior of the heterodimer. We conclude that the stepping of KIF3C can be activated by KIF3A in a strain-dependent manner which is similar to application of an assisting load, and the behavior of KIF3C mirrors prior studies of kinesins with increased interhead compliance. These results suggest that KIF3AC-based cargo transport likely requires multiple motors, and its mechanochemical properties arise due to the strain-dependences of KIF3A and KIF3C.

Significance Statement

Kinesins are important long-range intracellular transporters in neurons required by the extended length of the axon and dendrites and selective cargo transport to each. The mammalian kinesin-2, KIF3AC, is a neuronal heterodimer of fast and slow motor polypeptides. Our results show that KIF3AC has a single observed stepping rate in the presence and absence of load and detaches from the microtubule rapidly under load. Interestingly, both KIF3A and assisting loads accelerate the kinetics of KIF3C. These results suggest that KIF3AC is an unconventional cargo transporter and its motile properties do not represent a combination of alternating fast and slow step kinetics. We demonstrate that the motile properties of KIF3AC represent a mechanochemistry that is specific to KIF3AC and may provide functional advantages in neurons.
RCy3: Network Biology using Cytoscape from within R
Authors: Gustavsen Julia A. , Pai Shraddha , Isserlin Ruth , Demchak Barry , Pico Alexander R.
Published: October 2019

RCy3 is an R package in Bioconductor that communicates with Cytoscape via its REST API, providing access to the full feature set of Cytoscape from within the R programming environment. RCy3 has been redesigned to streamline its usage and future development as part of a broader Cytoscape Automation effort. Over 100 new functions have been added, including dozens of helper functions specifically for intuitive data overlay operations. Over 40 Cytoscape apps have implemented automation support so far, making hundreds of additional operations accessible via RCy3. Two-way conversion with networks from igraph and graph ensures interoperability with existing network biology workflows and dozens of other Bioconductor packages. These capabilities are demonstrated in a series of use cases involving public databases, enrichment analysis pipelines, shortest path algorithms and more. With RCy3, bioinformaticians will be able to quickly deliver reproducible network biology workflows as integrations of Cytoscape functions, complex custom analyses and other R packages.
Optimal bang–bang feedback for bursty gene expression
Authors: Zabaikina Iryna , Bokes Pavol , Singh Abhyudai
Published: October 2019

Stochasticity in gene expression poses a critical challenge to the precise control of cellular function. In this paper we examine how precisely can a stochastically expressed protein attain a given target expression level. We consider a protein which is produced in bursts and which is able to control its expression via a negative feedback loop; we specifically focus on feedback of a bang–bang type which turns off the production of the protein whenever its concentration exceeds a given threshold. Using a piecewise deterministic mathematical formalism, we derive explicit expressions for the probabilistic distribution of the protein concentration, and for the mean square deviation from the target level. Employing a combination of analytic and numerical optimization, we identify the optimal value of the bang–bang threshold, in terms of minimising the deviation, and examine the dependence of the optimal value on the target level and the sub-threshold burst frequency. The systematic analysis allows us to formulate a number of quantitative and qualitative conclusions about the controllability of burst like gene expression. Finally, we outline directions for future research into the topic.
Unusual structure of a biphenyl fragment: the important role of weak interactions
Authors: Vashchenko Alexander , Smirnov Vladimir , Semenova Nadezhda , Schmidt Elena
Published: October 2019

1,5-Bis([1,1′-biphenyl]-4-yl)-5-hydroxy-3-methylheptane-1,6-dione, C32H30O3, was investigated by X-ray analysis, quantum chemical calculations and AIM (atoms in molecules) analysis. It was shown that four intramolecular C—H...π forces are established between the two biphenyl fragments. C—H...π interactions lead to a bending of the biphenyl part. The energy of the intramolecular interactions was estimated and the exclusive role of the moment of force was established.
A new polymorph of phenylselenium trichloride
Authors: Bloomfield Hannah R. , Ritch Jamie S.
Published: October 2019

A second polymorph of phenylselenium trichloride, PhSeCl3 or C6H5Cl3Se, is disclosed, which is comprised of asymmetric chlorine-bridged noncovalent dimer units rather than polymeric chains. These dimers are each weakly bound to an adjacent dimer through noncovalent Se...Cl bonding interactions. Phenyl rings within each dimer are oriented in a syn fashion. Density functional theory (DFT) calculations reveal that the putative anti isomer is within 5 kJ mol−1 of the experimentally observed form. This structure represents the first additional polymorph discovered for an organoselenium trihalide compound.
Crystal structure and pale-yellow emitting properties of K3Gd1–xDyxB6O12solid solutions
Authors: Zhang Rui-Juan , Shi Jian-Chao , Zhao Dan-Dan , Han Xiao-Yang , Deng Ling , Cui Xiao-Qi , Zhao Dan
Published: October 2019

A new potassium dysprosium polyborate, K3DyB6O12, has been preparedviathe high-temperature molten salt method and structurally characterized by single-crystal X-ray diffraction analysis. The structure can be described as a three-dimensional framework composed of isolated bicyclic [B5O10]5−groups and Dy3+and K+ions. The Fourier transform IR (FT–IR) and ultraviolet–visible (UV–Vis) spectra were investigated. A series of K3Gd1–xDyxB6O12phosphors was prepared and their photoluminescence properties were studied. The K3Gd1–xDyxB6O12phosphors exhibit a strong yellow emission band at 577 nm (the4F9/2→6H13/2transition of Dy3+) under UV excitation of 275 nm (the8S7/2→6IJtransition of Gd3+), suggesting the occurrence of the energy transfer Gd3+→Dy3+. The optimized doping concentration of the Dy3+ion was 8 mol%. We may expect that K3Gd1–xDyxB6O12is a promising pale-yellow emission phosphor for visual displays or solid-state lighting.
Fractal characteristics of AC corrosion morphology of X80 pipeline steel in coastal soil solution
Authors: Fu Yu , Kou Jie , Du Cuiwei
Published: October 2019

Purpose

Pipelines are seriously corroded due to the close distance between pipelines and high voltage transmission lines. The purpose of this paper is to study the influence of alternating current (AC) on corrosion behavior of X80 pipeline steel in coastal soil solution.

Design/methodology/approach

The corrosion behavior of X80 steel under different AC densities in coastal soil solution was investigated by electrochemical measurements and image processing technology. Furthermore, a quantitative description model of AC corrosion through fractal dimension of corrosion image was established.

Findings

The results show that under low AC density the X80 steel is mainly uniform corrosion, and once AC density reaches 150 A/m2, the corrosion morphology gradually turns to pitting corrosion with irregular circle. For another aspect, the fractal dimension of corrosion images shows that the two/three-dimensional fractal dimension increase with the increase of AC density, presenting a linear and an exponential relationship respectively. In addition, the variation of the three-dimensional fractal dimension is the same as that of average corrosion rate. The threshold of the increasing trend of fractal dimension as well as corrosion type is 150 A/m2.

Originality/value

The investigation provides a quantitative method to describe AC corrosion morphology through fractal dimension. Furthermore, the method is of benefit to process corrosion images automatically.
Do “high-performance” human resource practices work in public universities? Mediation of organizational and supervisors’ supports
Authors: Tabiu Abubakar
Published: October 2019

Purpose

The purpose of this paper is to explore the relationship between “high-performance” human resource practices (HPHRP) and organizational performance, using organizational and supervisors’ supports as mediating variables.

Design/methodology/approach

Using cross-sectional design, the data were obtained from 311 public university lecturers in Nigeria. The study employed partial least square structural equation modeling (PLS-SEM) in the analysis.

Findings

The results suggested that the application of HPHRP in the public universities has direct and indirect effects on organizational performance. Also, HPHRP are linked with both organizational support and supervisory support. In turn, the organizational support and supervisory support are strongly linked with organizational performance. Furthermore, both organizational support and supervisory support fully mediate the positive relationships between HPHRP and organizational performance. The mediating role of both organizational support and supervisory support revealed their significance in HPHRP-performance link particularly within the context of public universities.

Research limitations/implications

The study employed self-report in collecting data for all the major constructs.

Practical implications

The study demonstrated the importance of HPHR practices (rigorous selection processes; training and development opportunities; information and communication practices; employee involvement in decision making; job security; fair reward system; team working and career management) and how they are directly related to organizational support, supervisory support and performance of organization. Second, for the management to enhance organizational performance (particularly in public universities), the need to emphasize on appropriate and effective HRM practices capable of promoting organizational and supervisory supports is required. This will enable the creation of supportive work environment that will promote better organizational performance.

Originality/value

The study adds value by providing additional understanding of the significant role of organizational support and supervisors support in HPHRP-organizational performance link.
The making of information nations
Authors: Stone Merlin , Machtynger Jon , Machtynger Liz , Aravopoulou Eleni
Published: October 2019

Purpose

The purpose of this paper is to identify the main characteristics of what have come to be called information nations and to identify some of the determinants of success in becoming an information nation.

Design/methodology/approach

The paper is based on a critical review of the literature and of secondary data on information technology and services from studies of the innovativeness of nations.

Findings

Success in becoming an information nation is not necessarily closely connected with investments in information technology and services by firms and policies supporting these investments by governments, or with education policies designed to support the development of science, technology, engineering and mathematics. Other factors, such as the vibrancy of capitalism, particularly the funding of new ventures, the culture of the nation and its focus on non-scientific determinants of innovation, such as design, are also important. Governments should be careful not to take credit for achievements when their policies are merely coincident with those achievements.

Research limitations/implications

The main limitations relate to the focus of this article on two sets of nations, South East/East Asia and two Western nations. The review of their performance is relatively high level and needs to be deepened, while the number of nations included in the research needs to be increased.

Practical implications

This paper has substantial practical implications for government policymakers, in terms of whether and how they should make policy at all in this area, and for companies trying to establish a long-term position in the global economy, in terms of being careful not to go against the very strong economic forces which favour certain kinds of activities in certain countries.

Social implications

This paper has significant social implications, because much of the thinking about developing information societies relies on generalisations about the creation of information nations that may not hold. Governments and social commentators are encouraged to approach the idea of making “big policies” in this area with some scepticism.

Originality/value

The content of this paper is not original, but the challenge to policymakers is relatively original, as too often the work of academics is sponsored by governments that are trying to legitimate the value of their own efforts.
Continued use intention of lifestyle mobile applications: the Starbucks app in Taiwan
Authors: Hsiao Kuo-Lun , Lin Kuan-Yu , Wang Yi-Ting , Lee Chun-Hsiung , Zhang Zhe-Ming
Published: October 2019

Purpose

In recent years, the ongoing development and rapid popularization of mobile devices, not only has brought new forms of lifestyle but also has boomed a wide array of service contents, allowing users to engage in entertainment, study and other daily activities, in addition to business transactions. To explore the factors that affect users' continued use of mobile app software, this paper aims to take into account the utilitarian value and privacy, as well as security factors and intends to propose an integrated research model based on the information systems success (ISS) model.

Design/methodology/approach

The data for this study were collected via an online survey questionnaire. A total of 190 valid responses were used to examine the hypotheses in the research model. The casual model was assessed using partial least squares techniques.

Findings

The results indicated that the three quality factors (information quality, system quality and service quality) in the ISS model significantly affected satisfaction and utilitarian value. Private and security have significant negative association with utilitarian value. The results also showed that private and security did not significantly affect satisfaction. The findings also provide some directions for further research.

Practical implications

The results show that user's continued use of mobile app software depends upon the perceived utilitarian value and satisfaction. The quality characteristics are the three critical factors that would affect the perceived utilitarian value and satisfaction. Compared to information quality and service quality, system quality has a higher degree of positive impact, which indicates that users are more concerned about the immediate download ability and ease-of-use provided by the system. Furthermore, the research also finds that privacy and security concerns have a negative influence on the utilitarian value, showing that in the context of task-oriented IS, the perceived risk of privacy and security during the process of using mobile app software services, will negatively affect users’ perception of utilitarian value. The insights provided by this study can help mobile app developers optimize design and marketing strategies.

Originality/value

This study provides a better understanding of how the factors in the theories influence the continuance usage intention of life style mobile applications.