bluuebunny/crossref_metadata_2025 huggingface dataset:
The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with a hypermutant, hypermethylated state
Authors: Hallam Sally , Stockton Joanne , Bryer Claire , Whalley Celina , Pestinger Valerie , Youssef Haney , Beggs Andrew D
Published: February 2020

Coloretcal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and poor prognosis CPM, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome, epigenome and genome of CPM and matched primary CRC was performed.

CPM were characterised by frequent Wnt/ β catenin negative regulator mutations, mismatch repair mutations and resulting high tumour mutational burden and dysregulation of methylation suggested by frequent TET2 mutations and mutations suggesting an immune evasive phenotype. Several novel therapies could be targeted to these frequent mutations including porcupine inhibitors, immune checkpoint inhibitors and methylation inhibitors. Here we show the molecular features associated with CPM development and with poor prognosis. Potential applications include improving patient selection for treatment and in the development of novel and personalised treatments.

NOVELTY AND IMPACT

Colorectal peritoneal metastasis (CPM) are associated with limited and variable survival despite patient selection using known prognostic factors and optimal currently available treatments. There is a paucity of research concerning the biology of CPM. This study describes the biological landscape of CPM and the molecular features associated with CPM development, conferring poor prognosis and has identified that the majority of CPM develop a hypermutant phenotype that may be suitable for treatment with anti-PD1/CTLA4 immunotherapy.
The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists
Authors: Fang Zijian , Chen Shiqian , Pickford Philip , Broichhagen Johannes , Hodson David J , Corrêa Ivan R , Kumar Sunil , Görlitz Frederik , Dunsby Christopher , French Paul , Rutter Guy A , Tan Tricia , Bloom Stephen R , Tomas Alejandra , Jones Ben
Published: February 2020

Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying sequence homology between native GLP-1 and exendin-4, the archetypal ligands on which approved GLP-1R agonists are based. We find notable differences in agonist-mediated signalling, endocytosis and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific mid-peptide helical regions and C-termini of the two agonists. These observations were linked to insulin secretion in a beta cell model and provide insights into how ligand factors influence GLP-1R function at the cellular level.

Graphical abstract
Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis
Authors: Jang Jin Sung , Juran Brian , Cunningham Kevin Y. , Gupta Vinod K. , Son YoungMin , Yang Ju Dong , Ali Ahmad H. , Enninga Elizabeth Ann L. , Sung Jaeyun , Lazaridis Konstantinos N.
Published: February 2020

The relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3-CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3-CD19+CD20+CD24-CD27-) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8+CD161+T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.
Projections of non-invasive human recordings into state space show unfolding of spontaneous and over-trained choice
Authors: Takagi Yu , Hunt Laurence , Woolrich Mark W , Behrens Timothy EJ , Klein-Flügge Miriam C
Published: February 2020

Choices rely on a transformation of sensory inputs into motor responses. Using invasive single neuron recordings, the evolution of a choice process has been tracked by projecting population neural responses into state spaces. Here we develop an approach that allows us to recover state space trajectories on a millisecond timescale in non-invasive human recordings. We selectively suppress activity related to relevant and irrelevant sensory inputs and response direction in magnetoencephalography data acquired during context-dependent choices. Recordings from premotor cortex show a smooth progression from sensory input encoding to response encoding. In contrast to previous macaque recordings, information related to choice-irrelevant features is represented more weakly than choice-relevant sensory information. To test whether this mechanistic difference between species is caused by extensive overtraining common in non-human primate studies, we trained humans on >20,000 trials of the task. Choice-irrelevant features were still weaker than relevant features in premotor cortex after overtraining.
Duchenne Muscular Dystrophy Cell Culture Models Created By CRISPR/Cas 9 Gene Editing And Their Application To Drug Screening
Authors: Soblechero-Martín P. , Albiasu-Arteta E. , Anton-Martinez A. , de la Puente-Ovejero L. , Garcia-Jimenez I. , González-Iglesias G. , Larrañaga-Aiestaran I. , López-Martinez A. , Poyatos-García J. , Ruiz-Del-Yerro E. , Gonzalez F. , Arechavala-Gomeza V.
Published: February 2020

Gene edition methods are an attractive putative therapeutic option for Duchenne muscular dystrophy and they have an immediate application in the generation of research models. To generate two new edited myoblast cultures that could be usefulin vitrodrug screening, we have optimised a CRISPR/Cas9 gene edition protocol. We have successfully used it in wild type immortalised myoblasts to delete exon 52 of the dystrophin gene: DMDΔ52-Model, modelling a common Duchenne muscular dystrophy mutation; and in patient’s immortalised cultures we have deleted an inhibitory microRNA target region of the utrophin UTR, leading to utrophin upregulation. We have characterised these cultures and, to show their use in the assessment of DMD treatments, we have performed exon skipping in the DMDΔ52-Model and have used the unedited cultures/ DMD-UTRN-Model combo to assess utrophin overexpression after drug treatment. While the practical use of DMDΔ52-Model is limited to the validation to our gene edition protocol, DMD-UTRN-Model offers a possible therapeutic gene edition target as well as a useful positive control in the screening of utrophin overexpression drugs.
Intra-abdominal resection of the umbilical vein and urachus of bovine fetuses using videolaparoscopy and celiotomy: surgical time and feasibility (cadaveric study)
Authors: Monteiro Francisco Décio de Oliveira , Gurgel Heytor Jales , de Sousa Simon Silva , Barroso João Pedro Monteiro , Vasconcelos Gabrielle Patrizi Braga , dos Santos Daniele Lira , Araújo Luiz Henrique Vilela , de Sousa Loise Araújo , dos Santos Gabriela Melo Alves , Rossy Kayan da Cunha , da Silva Verena Siqueira , Fernandes Camila do Espirito Santo , Guilherme Barbara da Conceição , Miranda Helaine Freitas , Silva Carla Rozilene Guimarães , Albuquerque Rodrigo dos Santos , Borges Luisa Pucci Bueno , de Araújo Gilson Ferreira , Teixeira Pedro Paulo Maia
Published: February 2020

Surgical intervention for umbilical diseases in calves, when indicated, is a complementary and indispensable therapeutic resource for the treatment of umbilical conditions and is commonly performed using celiotomy. However, videolaparoscopy has demonstrated feasibility in many diagnostic and therapeutic procedures. The aim of this study was to assess the feasibility of the techniques and the surgical time of videolaparoscopy and celiotomy used in intra-abdominal resection of the umbilical vein and urachus of bovine fetuses (cadavers). Resection of the umbilical vein and urachus using videolaparoscopy and celiotomy was performed in 26 anatomical specimens (bovine fetuses obtained from an official slaughterhouse). Resection of umbilical structures was feasible with both techniques, but shorter surgical time and minimal tissue damage were achieved using videolaparoscopy. Laparoscopy requires specialized training and appropriate instruments and is an important tool for diagnostic and therapeutic exploration of the umbilical structures, liver, bladder, and associated/adjacent structures.
Coevolution of retroviruses withSERINCs following whole-genome duplication divergence
Authors: Ramdas Pavitra , Bhardwaj Vipin , Singh Aman , Vijay Nagarjun , Chande Ajit
Published: February 2020

TheSERINCgene family comprises of five paralogs in humans of whichSERINC3andSERINC5inhibit HIV-1 infectivity and are counteracted by Nef. The origin of this anti-retroviral activity, its prevalence among the remaining paralogs, and its ability to target retroviruses remain largely unknown. Here we show that despite their early divergence, the anti-retroviral activity is functionally conserved among four humanSERINCparalogs withSERINC2 being an exception. The lack of activity in humanSERINC2 is associated with its post-whole genome duplication (WGD) divergence, as evidenced by the ability of pre-WGD orthologs from yeast, fly, and a post-WGD-proximateSERINC2 from coelacanth to inhibit nef-defective HIV-1. Intriguingly, potent retroviral factors from HIV-1 and MLV are not able to relieve theSERINC2-mediated particle infectivity inhibition, indicating that such activity was directed towards other retroviruses that are found in coelacanth (like foamy viruses). However, foamy-derived vectors are intrinsically resistant to the action ofSERINC2, and we show that a foamy virus envelope confers this resistance. Despite the presence of weak arms-race signatures, the functional reciprocal adaptation amongSERINC2 andSERINC5 and, in response, the emergence of antagonizing ability in foamy virus appears to have resulted from a long-term conflict with the host.
Correlation of pathogenic factors with antimicrobial resistance of clinicalProteus mirabilisstrains
Authors: Filipiak Aneta , Chrapek Magdalena , Literacka Elżbieta , Wawszczak Monika , Głuszek Stanisław , Majchrzak Michał , Wróbel Grzegorz , Gniadkowski Marek , Adamus-Białek Wioletta
Published: February 2020

Proteus mirabilisis the third most common etiological factor of the urinary tract infection (UTI). It produces urease, which contributes to the formation of crystalline biofilm, considered to be one of the most important virulence factors ofP. mirabilisstrains, along with their ability to swarm on a solid surface. The aim of this study was to analyze the pathogenic properties of two selected groups of clinicalP. mirabilisisolates, antimicrobial-susceptible and multidrug-resistant (MDR), collected from hospitals in different regions in Poland. The strains were examined based on virulence gene profiles, urease and hemolysin production, biofilm formation, and swarming properties. Additionally, the strains were differentiated based on the Dienes test and antibiotic susceptibility patterns. It turned out that the MDR strains exhibited kinship more often than susceptible ones. The strains which were able to form stronger biofilm had broader antimicrobial resistance profiles. It was also found that the strongest swarming motility correlated with susceptibility to most antibiotics. The correlations described in this work encourage further investigation of the mechanisms of pathogenicity ofP. mirabilis.

Author summary

Proteus mirabilisis widely widespread in environment but also it is responsible for mostProteusinfections, especially in human urinary tracts. They cause complicated, persistent infections especially due to the ability to form urinary stones. The clinical importance ofP. mirabilishave been described in the literature many times. However, the role of pathogenic features with correlation to drug resistance require further investigation. In this research we analyzed thee virulence factors in relation to drug resistance of clinicalP. mirabilisstrains isolated from urine. The virulence genes, ureolytic and hemolytic activity, biofilm formation, swarming growth and strains kindship were analyzed. The most important observation was that the strains exhibited a stronger territorialism were kindred to a lower number of other strains, formed weaker biofilm and exhibited a lower resistance to antibiotics. Furthermore, we proved that the strains which were more likely to mutual growth, they were also less similar in the drug resistance profile but exhibited a higher resistance to antibiotics, which can be beneficial for different bacteria living together. We believe thatP. mirabiliswith strong territorialism can represent a wild group of strains with poor experience of antibiotic pressure. The environmental influence (toxins, antibiotics, bacterial neighbors) stimulates the development of a less dispersed community with stronger biofilm, exchange of genes and increase of resistance to antibiotics.
Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function
Authors: Oppong Abel K. , Diallo Kadidia , Frayne Isabelle Robillard , Rosiers Christine Des , Lim Gareth E.
Published: February 2020

One of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Hormone-sensitive lipase (HSL) is a critical lipolytic enzyme, and its phosphorylation and subsequent activation by PKA generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. While we previously identified essential roles of the 14-3-3ζ isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on HSL suggests that 14-3-3ζ could also influence mature adipocyte processes like lipolysis. Herein, we demonstrate that 14-3-3ζ is necessary for lipolysis in male mice and fully differentiated 3T3-L1 adipocytes, as depletion of 14-3-3ζ significantly impaired glycerol and FFA release. Unexpectedly, this was not due to impairments in signaling events underlying lipolysis; instead, reducing 14-3-3ζ expression was found to significantly impact adipocyte maturity, as observed by reduced abundance of PPARγ2 protein and expression of mature adipocytes genes and those associated withde novotriglyceride synthesis and lipolysis. The impact of 14-3-3ζ depletion on adipocyte maturity was further examined with untargeted lipidomics, which revealed that reductions in 14-3-3ζ abundance promoted the acquisition of a lipidomic signature that resembled undifferentiated, pre-adipocytes. Collectively, these findings reveal a novel aspect of 14-3-3ζ in adipocytes, as reducing 14-3-3ζ was found to have a negative effect on adipocyte maturity and adipocyte-specific processes like lipolysis.
The metabolite receptor SUCNR1 in oxidative stress-induced age-related macular degeneration
Authors: Louer Elja M.M. , Deen Peter M.T. , den Hollander Anneke I.
Published: February 2020

Age-related macular degeneration (AMD) is the leading cause of vision impairment in elderly people. AMD is a multifactorial disease which is characterised by complex interactions between metabolic and environmental factors as well as multiple genetic susceptibility factors. The exact mechanism of the most prominent environmental factors, age and smoking, in combination with genetic susceptibility factors is little studied. Here, we set out to study the influence of age, smoking induced oxidative stress and the role of succinate receptor 1 (SUCNR1) in AMD development in mice.

Sucnr1wild-type (WT), heterozygous (HT) and knock-out (KO) mice were exposed to smoking related oxidative stress by the addition of hydroquinone (HQ), the most abundant oxidant in cigarette smoke, to the drinking water of the mice. Using immunohistochemical staining, accumulation of oxidized LDL (oxLDL) in the mouse retina was assessed at 40 and 48 weeks of age.

At 40 weeks of age, a significant increase in oxLDL in theSucnr1KO mice treated with HQ was observed when compared to the WT and HT mice treated with HQ (p<0.01). However, at 48 weeks, no significant difference was observed between any of the groups. A second experiment analyzing the mice at 40 weeks of age was unable to confirm the observed results of the first experiment.

We identified oxLDL accumulations inSucnr1KO retinas exposed to HQ, but were unable to repeat this finding. Therefore, under the present conditions, theSucnr1KO mouse model is not a suitable model to study AMD development.
Structure and conformational cycle of a bacteriophage-encoded chaperonin
Authors: Bracher Andreas , Paul Simanta S. , Wang Huping , Wischnewski Nadine , Hartl F. Ulrich , Hayer-Hartl Manajit
Published: February 2020

Chaperonins are ubiquitous molecular chaperones found in all domains of life. They form ring-shaped complexes that assist in the folding of substrate proteins in an ATP-dependent reaction cycle. Key to the folding cycle is the transient encapsulation of substrate proteins by the chaperonin. Here we present a structural and functional characterization of the chaperonin gp146 (ɸEL) from the phage EL ofPseudomonas aeruginosa. ɸEL, an evolutionary distant homolog of bacterial GroEL, is active in ATP hydrolysis and prevents the aggregation of denatured protein in a nucleotide-dependent manner. However, ɸEL failed to refold the encapsulation-dependent model substrate rhodanese and did not interact withE. coliGroES, the lid-shaped co-chaperone of GroEL. ɸEL forms tetradecameric double-ring complexes, which dissociate into single rings in the presence of ATP. Crystal structures of ɸEL (at 3.54 and 4.03 Å) in presence of ATP•BeFxrevealed two distinct single-ring conformational states, both with open access to the ring cavity. One state showed uniform ATP-bound subunit conformations (symmetric state), whereas the second combined distinct ATP- and ADP-bound subunit conformations (asymmetric state). Cryo-electron microscopy of apo-ɸEL revealed a double-ring structure composed of rings in the asymmetric state (3.45 Å resolution). We propose that the phage chaperonin undergoes nucleotide-dependent conformational switching between double- and single rings and functions in aggregation prevention without substrate protein encapsulation. Thus, ɸEL may represent an evolutionary more ancient chaperonin prior to acquisition of the encapsulation mechanism.
RNF40-dependent epigenetic regulation of actin cytoskeletal dynamics is required for HER2-driven mammary tumorigenesis
Authors: Wegwitz Florian , Prokakis Evangelos , Pejkovska Anastasija , Kosinsky Robyn Laura , Glatzel Markus , Pantel Klaus , Wikman Harriet , Johnsen Steven A.
Published: February 2020

The HER2-driven breast cancer subtype displays a particularly aggressive behavior. Alterations of the epigenome are common in cancers and represent attractive novel molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by its obligate heterodimeric E3 ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specificRnf40deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-positive breast cancer. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-positive breast cancer, revealing the RNF20/RNF40/H2Bub1 axis as a possible tumor context-dependent therapeutic target in breast cancer.

Statement of significance

HER2-positive breast cancer patients frequently develop resistance to anti-HER2 therapies. Here we demonstrate that RNF20/RNF40-mediated H2B monoubiquitination supports the oncogenic properties of cancer cells of this subtype by regulating actin dynamics. The RNF20/RNF40/H2Bub1 axis may therefore represent an attractive drug target for novel therapies.
Alterations of specific inhibitory circuits of the prefrontal cortex underlie abnormal network activity in a mouse model of Down syndrome
Authors: de San Martin Javier Zorrilla , Donato Cristina , Peixoto Jérémy , Aguirre Andrea , Choudhary Vikash , De Stasi Angela Michela , Lourenço Joana , Potier Marie-Claude , Bacci Alberto
Published: February 2020

Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether this is due to specific alterations of distinct GABAergic circuits is unknown. In the prefrontal cortex of Ts65Dn mice (a well-established DS model), we found that the dendritic synaptic inhibitory loop formed by somatostatin-positive Martinotti cells (MCs) and pyramidal neurons (PNs) was strongly enhanced, with no alteration of their excitability. Conversely, perisomatic inhibition from parvalbumin-positive (PV) interneurons was unaltered, but PV cells of DS mice lost their classical fast-spiking phenotype and exhibited increased excitability. These microcircuit alterations resulted in reduced pyramidal-neuron firing and increased phase locking to cognitive-relevant network oscillationsin vivo. These results define important synaptic and circuit mechanisms underlying of cognitive dysfunctions in DS.
Ultrasound Mediated Delivery of Quantum Dots from a Capsule Endoscope to the Gastrointestinal Wall
Authors: Stewart Fraser , Cummins Gerard , Turcanu Mihnea V. , Cox Benjamin F. , Prescott Alan , Clutton Eddie , Newton Ian P. , Desmulliez Marc P.Y. , Thanou M. , Mulvana H. , Cochran Sandy , Näthke Inke
Published: February 2020

Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in-vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focussed ultrasound. These findings suggest that the use of focused ultrasound together with microbubbles could play a role in the oral delivery of biologic therapeutics.
Prostaglandin receptor EP2 is a novel molecular target for high-risk neuroblastoma
Authors: Hou Ruida , Yu Ying , Nguyen Davis T. , Sluter Madison N. , Li Lexiao , Yang Jun , Jiang Jianxiong
Published: February 2020

As the third-most common type of cancers in infants and young children, neuroblastoma accounts for nearly 10% of all childhood cancers. Despite remarkable advances in tumor diagnosis and management during the past decades, the five-year survival rates for patients with high-risk neuroblastoma remain below 50%. Developing new therapies for this devastating type of childhood cancer is an urgent unmet need. Cyclooxygenase (COX) via synthesizing prostaglandin E2 (PGE2) promotes tumor cell proliferation, survival, migration and invasion, and fosters an inflammation-enriched microenvironment that can facilitate angiogenesis, immune evasion and treatment resistance. However, which downstream PGE2receptor subtype – namely EP1, EP2, EP3 and EP4 – is directly involved in COX activity-promoted neuroblastoma growth remains elusive. Analyzing five major neuroblastoma patient datasets: Versteeg-88, Kocak-649, SEQC-498, Primary NRC-283, and Oberthuer-251, we show that COX-1/PGE2/EP2 signaling axis is highly associated with the aggressiveness of human neuroblastoma. A time-resolved fluorescence resonance energy transfer (TR-FRET) method reveals EP2 as the key Gαs-coupled receptor that mediates PGE2-initiated cAMP signaling in neuroblastoma cells with various risk factors. Taking advantage of novel, selective and bioavailable small-molecule antagonists that we recently developed to target the PGE2/EP2 signalingin vivo, we have demonstrated that pharmacological inhibition of the peripheral EP2 receptor substantially impairs the growth of human neuroblastoma xenografts and the associated angiogenesis in mice. Collectively, our results suggest that the PGE2/EP2 pathway contributes to the growth and malignant potential of human neuroblastoma cells; pharmacological inhibition on EP2 receptor by our drug-like compounds might provide a novel therapeutic strategy for this deadly pediatric cancer.
Phytochemical Screening and Antimicrobial Activity ofZiziphus spina-christiStem Barks
Authors: Makhawi Abdelrafie M. , Mustafa Mujahed I. , Uagoub Hajer A.
Published: February 2020

This study was carried out in Khartoum State, during December 2017 The plant of Ziziphusspina-christibelong to family Rhamnaceae and locally known as Cedar, it was chosen for this study because of its using traditionally in treatment of many diseases. Microwave-assisted extraction (MAE) approach had been used to the dried sample at 170°C to reduce both time and extraction solvent volume, and to decrease the damage of bioactive compounds without extending the period of extraction. 20 g of sample was soaked with Petroleum ether, Ethyl-acetate, ethanol, methanol and distilled water for 72 hour. The extracts were concentrated using rotary evaporator at 40°C and were stored at 4°C. The phytochemical screening were carried out on different extracts ofZiziphus spina-christistem bark and they showed to contain high amount of Tannins (4+ in all extracts), moderate amount of flavonoids and Triterpenes, trace amount of coumarins and Alkaloids and high amount of Saponins, Anthraquinones and Cardiac glycosides. The antimicrobial activity of extracts were evaluated against four standard bacteria species (gram positive;Bacillus subtilis, Staphylococcus aureus) and (gram negative;Escherichia coli, Pseudomonas aeruginosa; in addition of one standard fungi (Candida albicans). The results of antimicrobial tests indicated that the methanolic extract inhibited the growth of all microorganisms and most extracts showed several points of antimicrobial activity. These findings act as platform to assist in cure of bacterial and fungal infections.
miR169 andPmRGL2synergistically regulate NF-Y complex to active dormancy release in Japanese apricot (Prunus mumeSieb. et Zucc.)
Authors: Jie Gao , Xiaopeng Ni , Hantao Li , Make Faisal Hayat , Ting Shi , Zhihong Gao
Published: February 2020

Insufficient chilling requirements affect the floral bud quality and fruit yield in fruit crop production. Endodormancy is a process to meet the chilling requirement. To understand the mechanism of dormancy release in woody plants, we compared the miRNA database during the transition stage from endodormancy to dormancy release in Japanese apricot and found that the miR169 family showed significant differentially up-regulated expression during dormancy and down-regulated during dormancy release periods. The 5’ RACE assay and RT-qPCR validated its target gene NUCLEAR FACTOR-Y subunit A (NF-YA) exhibited the opposite expression pattern. Further study showed that exogenous GA4could inhibit the expression ofPmRGL2and promote the expression ofNF-Y. Moreover, the interaction between NF-Y family and GA inhibitorPmRGL2was verified by yeast-two-hybrid system and Bimolecular fluorescence complementarity (BiFC) experiment. These results suggested that synergistic regulation of NF-Y andPmRGL2complex to active dormancy release induced by GA4.These will help to elucidate the functional and regulatory roles of miR169 and its target gene of the seasonal bud dormancy induced by GA4in Japanese apricot woody plants and to provide new sights for the discovery of dormancy release mechanism.
Light microscopy based approach for mapping connectivity with molecular specificity
Authors: Shen Fred Y. , Harrington Margaret M. , Walker Logan A. , Jimmy Cheng Hon Pong , Boyden Edward S. , Cai Dawen
Published: February 2020

Mapping neuroanatomy is a foundational goal towards understanding brain function. Electron microscopy (EM) has been the gold standard for connectivity analysis because nanoscale resolution is necessary to unambiguously resolve chemical and electrical synapses. However, molecular information that specifies cell types is often lost in EM reconstructions. To address this, we devised a light microscopy approach for connectivity analysis of defined cell types called spectral connectomics. We combined multicolor genetic labeling (Brainbow) of neurons with amulti-roundimmunostainingExpansion Microscopy (miriEx) strategy to simultaneously interrogate morphology, molecular markers, and connectivity in the same brain section. We applied our multimodal profiling strategy to directly link inhibitory neuron cell types with their network morphologies. Furthermore, we showed that correlative Brainbow and endogenous synaptic machinery immunostaining can be used to define putative synaptic connections between spectrally unique neurons, as well as map putative inhibitory and excitatory inputs. We envision that spectral connectomics can be applied routinely in neurobiology labs to gain insights into normal and pathophysiological neuroanatomy across multiple animals and time points.
ALIXE: a phase-combination tool for fragment-based molecular replacement
Authors: Millán Claudia , Jiménez Elisabet , Schuster Antonia , Diederichs Kay , Usón Isabel
Published: February 2020

Fragment-based molecular replacement exploits the use of very accurate yet incomplete search models. In the case of theARCIMBOLDOprograms, consistent phase sets produced from the placement and refinement of fragments withPhasercan be combined in order to increase their signal before proceeding to the step of density modification and autotracing withSHELXE. The programALIXEcompares multiple phase sets, evaluating mean phase differences to determine their common origin, and subsequently produces sets of combined phases that group consistent solutions. In this work, its use on different scenarios of very partial molecular-replacement solutions and its performance after the development of a much-optimized set of algorithms are described. The program is available both standalone and integrated within theARCIMBOLDOprograms.ALIXEhas been analysed to identify its rate-limiting steps while exploring the best parameterization to improve its performance and make this software efficient enough to work on modest hardware. The algorithm has been parallelized and redesigned to meet the typical landscape of solutions. Analysis of pairwise correlation between the phase sets has also been explored to test whether this would provide additional insight.ALIXEcan be used to exhaustively analyse all partial solutions produced or to complement those already selected for expansion, and also to reduce the number of redundant solutions, which is particularly relevant to the case of coiled coils, or to combine partial solutions from different programs. In each case parallelization and optimization to provide speedup makes its use amenable to typical hardware found in crystallography.ARCIMBOLDO_BORGESandARCIMBOLDO_SHREDDERnow call onALIXEby default.
Structural evidence for a latch mechanism regulating access to the active site of SufS-family cysteine desulfurases
Authors: Dunkle Jack A. , Bruno Michael R. , Frantom Patrick A.
Published: February 2020

Cysteine serves as the sulfur source for the biosynthesis of Fe–S clusters and thio-cofactors, molecules that are required for core metabolic processes in all organisms. Therefore, cysteine desulfurases, which mobilize sulfur for its incorporation into thio-cofactors by cleaving the Cα—S bond of cysteine, are ubiquitous in nature. SufS, a type 2 cysteine desulfurase that is present in plants and microorganisms, mobilizes sulfur from cysteine to the transpersulfurase SufE to initiate Fe–S biosynthesis. Here, a 1.5 Å resolution X-ray crystal structure of the Escherichia coli SufS homodimer is reported which adopts a state in which the two monomers are rotated relative to their resting state, displacing a β-hairpin from its typical position blocking transpersulfurase access to the SufS active site. A global structure and sequence analysis of SufS family members indicates that the active-site β-hairpin is likely to require adjacent structural elements to function as a β-latch regulating access to the SufS active site.
Food choice in the e-commerce era
Authors: Wang Ou , Somogyi Simon , Charlebois Sylvain
Published: February 2020

Purpose

This study associated consumers' food choice motives and socio-demographic characteristics with their attitudes and consumptions towards food shopping with four e-commerce modes: business-to-consumer (B2C), online-to-offline delivery (O2O Delivery), online-to-offline in-store (O2O In-store) and New Retail. It also explored consumer preferences for specific food categories within the four e-commerce modes.

Design/methodology/approach

An online survey was administered to 954 participants from three Chinese cities: Beijing, Shanghai and Shenzhen. Descriptive analysis and linear regression were used in the data analysis.

Findings

The following food choice motives (FCMs) and socio-demographic characteristics had a significant effect on food e-commerce attitudes and/or consumption, with some or all of the four e-commerce modes: Taste Appeal, Value for Money, Safety Concerns, Quality Concerns, Processed Convenience, Purchase Convenience, Others' Reviews, City, Gender, Household Size, Age, Income, Occupation and Marital Status. Consumers also have different consumption preferences for food categories in the four e-commerce modes.

Originality/value

This is the first study to associate consumer FCMs and socio-demographics with their e-commerce attitudes and consumption regarding food in four e-commerce modes: B2C, O2O Delivery, O2O In-store and New Retail.
Indonesian Millennials’ Halal food purchasing: merely a habit?
Authors: Amalia Fatya Alty , Sosianika Adila , Suhartanto Dwi
Published: February 2020

Purpose

To investigate the determinants of Muslim Millennials’ purchasing behavior of Halal food in a Muslim-majority country under the reflective and reflexive systems.

Design/methodology/approach

Through 339 responds collected from the survey, this study uses 319 responds from Muslim Millennial consumers in Indonesia for further analysis. Data analysis is conducted using a partial least square (PLS) to verify the relationships between the variables herein.

Findings

Though purchasing Halal food is familiar to Muslim Millennial consumers in a religious society, this study demonstrated that purchase intention and habit can independently affect their purchasing behavior. In forming the purchase intention, attitude, subjective norms, perceived behavioral control, and religiosity are all necessary determinants on this phenomenon.

Practical implications

This study enlightens the food providers to continuously intervene in the purchase intention of Muslim Millennials as a consumer group as purchasing of Halal food is also a matter of habit for such consumers in the religious community. To strengthen Muslim Millennials’ purchase intention of Halal food, governments should harmonize their actions with the various stakeholders involved in this purchase intention.

Originality/value

This study focuses on the Muslim Millennial consumer group regarding their Halal food purchasing behavior by integrating two behavioral theories (theory of planned behavior and theory of interpersonal behavior) to obtain a more comprehensive explanation of their purchasing behavior.
Identification and analysis of handovers in organisations using process model repositories
Authors: Leyer Michael , Iren Deniz , Aysolmaz Banu
Published: February 2020

Purpose

Identifying handovers is an important but difficult to achieve goal for companies as handovers have advantages allowing for specialisation in processes as well as disadvantages by creating erroneous interfaces.

Design/methodology/approach

Conceptualisation of a method based on theory and evaluation with company data using a process model repository.

Findings

The method allows to evaluate handovers from the perspective of roles in processes and grouping of employees in organisational units. It uses existing process model repositories connected with organisational chart information in companies to determine the density of handovers. The method is successfully evaluated using the example of a major telecommunications company with 1,010 process models in its repository.

Practical implications

Companies can determine on various levels, up to the overall organisational level, in which parts of the company efforts are best spent to manage handovers in an optimal way.

Originality/value

This paper is first in showing how handovers can be conceptualised and identified with a large-scale method.
What factors affect Chinese consumers’ online grocery shopping? Product attributes, e-vendor characteristics and consumer perceptions
Authors: Zheng Qiujie , Chen Junhong , Zhang Robin , Wang H. Holly
Published: February 2020

Purpose

In this paper, we provide a simple conceptual framework with empirical analysis to investigate the effect of product attributes and e-vendor characteristics that are potentially included in the online shopper’s information search on their online shopping behavior in China.

Design/methodology/approach

This paper examines consumers’ online shopping frequency for food/grocery using an ordered logit model and for fresh food (a subcategory of food/grocery) using a two-part model, considering product attributes, e-vendor characteristics, and consumer perceptions and characteristics.

Findings

The results show that product origin is an influencing factor in shopping for fresh food online, reflecting consumers’ growing interests in imported food or specialty food from other areas. Consumers are more likely to shop online for fresh food if they perceive online shopping as having a price advantage. But consumers who view price as a top factor are less likely to buy fresh food online frequently. Thus competitive prices might be a motive for online fresh food shopping, but consumers concerned about price do not necessarily shop frequently. Negative perceptions of product freshness reduce consumers’ likelihood and frequency of shopping for fresh food online. Concerns on food quality and e-vendors’ credibility prevent consumers from frequently shopping for fresh food online. Social and demographic characteristics also influence consumers’ decisions.

Originality/value

This paper provides a better understanding of consumer’s online grocery shopping preferences and sheds light on policy and regulation design and implementation in the e-commerce industry, which will ultimately protect and benefit consumers.
Making sense of text: artificial intelligence-enabled content analysis
Authors: Lee Linda W. , Dabirian Amir , McCarthy Ian P. , Kietzmann Jan
Published: February 2020

Purpose

The purpose of this paper is to introduce, apply and compare how artificial intelligence (AI), and specifically the IBM Watson system, can be used for content analysis in marketing research relative to manual and computer-aided (non-AI) approaches to content analysis.

Design/methodology/approach

To illustrate the use of AI-enabled content analysis, this paper examines the text of leadership speeches, content related to organizational brand. The process and results of using AI are compared to manual and computer-aided approaches by using three performance factors for content analysis: reliability, validity and efficiency.

Findings

Relative to manual and computer-aided approaches, AI-enabled content analysis provides clear advantages with high reliability, high validity and moderate efficiency.

Research limitations/implications

This paper offers three contributions. First, it highlights the continued importance of the content analysis research method, particularly with the explosive growth of natural language-based user-generated content. Second, it provides a road map of how to use AI-enabled content analysis. Third, it applies and compares AI-enabled content analysis to manual and computer-aided, using leadership speeches.

Practical implications

For each of the three approaches, nine steps are outlined and described to allow for replicability of this study. The advantages and disadvantages of using AI for content analysis are discussed. Together these are intended to motivate and guide researchers to apply and develop AI-enabled content analysis for research in marketing and other disciplines.

Originality/value

To the best of the authors’ knowledge, this paper is among the first to introduce, apply and compare how AI can be used for content analysis.
Factors in the acquisition of ethical training
Authors: Rodriguez Gomez Sara , Lopez Perez María Victoria , Garde Sánchez Raquel , Rodríguez Ariza Lázaro
Published: February 2020

Purpose

Society in general demands ethical behaviour in the business world. The research aim of the paper is to analyse whether higher education institutions of business contribute to ethical decision-making in students through a specific training approach based on practical methodologies that take into account students' personal characteristics, which may affect ethical decision-making. The acquisition of knowledge should be more effective when it is based on personal characteristics.

Design/methodology/approach

Case method, discussion and self-learning methodology were used, and at the end of the term, the students were evaluated and asked to complete a 48 closed-question questionnaire. A linear regression model is performed to analyse to what extent the results are associated to the variables proposed.

Findings

The results show that knowledge is an explanatory variable, but personal characteristics such as gender or empathy reinforce the learning. Gender difference affects the ethical decisions made and empathy, showing that training based on emotions is effective. Besides, the results show that students integrate family influence in their training process.

Research limitations/implications

In this paper, the authors have selected empathy, gender and instruction. They have taken into account the incidence of age and family education. In addition, other contextual factors can have an incidence on training and the model could be improved.

Practical implications

The results show that it is necessary to take into account the students' personal characteristics and select an appropriate training methodology to teach ethics and obtain success.

Social implications

The students graduating from these courses will be future managers and entrepreneurs and will make decisions in which ethical questions must be taken into account, hence the need for training in this respect.

Originality/value

The teaching of business ethics in business faculties is not an easy subject. It is necessary to select the approach of ethic and an effective methodology to achieve the learning objective. This learning methodology must take into account students' characteristics to be effective. The business students are future managers and entrepreneurs who will make decisions in which ethical questions must be considered, hence the need for training in this respect.
Enrolment scenario of LIS education in India through distance mode: a study
Authors: Gupta Jyotsna , Singh Shivendra , Pandita Ramesh , Bhat Suneel Kumar
Published: February 2020

Purpose

This study aims to assess the enrolment scenario of Library and Information Science (LIS) education in India offered through distance mode.

Design/methodology/approach

The scope of the study is limited to India, reflecting the trend of distance education in LIS in India. The study is based on the secondary data collected by the Ministry of Human Resource and Development, Government of India (GOI) under All India Survey on Higher Education (AISHE). It is to mention that Ministry of Human Resource and Development, GOI, is regularly collecting data from higher education institutions all across the country under AISHE project. The data in the study have been analysed for the period 2011 to 2018.

Findings

The findings of the study reveal that, of the total enrolments made in LIS education in India during the period 2011 to 2018, nearly one-fourth of students were enrolled through regular mode and three-fourth were enrolled through distance mode, signifying distance mode of education as the largest medium of LIS education in India. The enrolment figures through distance mode showed slight inconsistency with the result, a negative (−0.49%) average annual corresponding growth was recorded in the enrolment of LIS students through distance mode. Of the total students enrolled in different LIS programmes through distance mode during the period of study, the majority (67.78%) of students were enrolled in the Under Graduate programme (B.Lib.I.Sc.). Similarly, of the total students enrolled in LIS through distance mode during the period of study, 51.36% were female students and 48.63% male students. In terms of caste category, of the total students enrolled during the period of study, 10.12% belonged to the Scheduled Caste category, 4.7% to Scheduled Tribes category, 28.77% Other Backward Class and 56.08% to others, which include general category students as well.

Research limitations/implications

Learning through distance education is a welcome step as long as the idea is to improve the society and to reach out to those who hitherto remained unreached. Sustainable means of enrolment and employability has to be the order of the day, mostly based on demand and supply principle.

Originality/value

This study is original and first of its kind covering enrolment of the students in LIS courses.