bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of maternal intermittent fasting during pregnancy on cardiovascular, metabolic and renal function in adult rat offspring
Authors: Alkhalefah Alaa , Eyre Heather J. , Hussain Rezwana , Glazier Jocelyn D. , Ashton Nick 
Published: September 2021

AbstractPregnant Muslim women are exempt from fasting during Ramadan; however a majority are reported to fast. The impact of this form of maternal intermittent fasting (IF) on fetal development and offspring health is not well defined. Using a rat model, we have shown previously that maternal IF results in fetal growth restriction accompanied by changes in placental nutrient transport function. The aim of this study was to assess cardiovascular, metabolic and renal function in adult offspring of IF-exposed dams. Food was withheld from Wistar rats from 17:00 to 09:00 daily throughout pregnancy; controls had ad libitum access to food. Birth weight was unaffected; however male IF pups grew more slowly up to 10 weeks of age (P < 0.01) whereas IF females matched their control counterparts. Systolic blood pressure (SBP), glucose tolerance and basal renal function at 14 weeks were not affected by IF exposure. When offered saline solutions (0.9-2.1%) to drink, females showed a greater salt preference than males (P < 0.01); however there were no differences between dietary groups. A separate group of pups was weaned onto a 4% NaCl diet. SBP increased in IF pups sooner, at 7 weeks (P < 0.01), than controls which became hypertensive from 10 weeks. Renal function did not appear to differ; however markers of renal injury were elevated in IF males (P < 0.05). Maternal IF does not affect resting cardiovascular, metabolic and renal function; but when challenged by dietary salt load male IF offspring are more prone to renal injury.
Fast resupply of synaptic vesicles requires Synaptotagmin-3
Authors: Weingarten Dennis J. , Shrestha Amita , Kissiwaa Sarah A. , Spruston Evan , Jackman Skyler L. 
Published: September 2021

AbstractSustained neuronal activity demands quick resupply of synaptic vesicles in order to maintain reliable synaptic transmission. Such vesicle replenishment is accelerated by sub-micromolar presynaptic Ca2+ signals by an as yet unidentified high-affinity Ca2+ sensor1-4. Here we identify a novel presynaptic role for the high-affinity Ca2+ sensor Synaptotagmin-3 (SYT3)5 in driving vesicle replenishment and short-term synaptic plasticity. Synapses in Syt3 knockout mice exhibit enhanced short-term depression, and recovery is slower and insensitive to presynaptic residual Ca2+. During sustained neuronal firing, SYT3 speeds vesicle replenishment and increases the size of the readily releasable pool of vesicles. SYT3 also mediates a second form of short-term enhancement called facilitation, under conditions of low vesicle release probability. Models of vesicle trafficking suggest that SYT3 could combat synaptic depression by accelerating vesicle docking at active zones. Our results reveal a critical role for presynaptic SYT3 in maintaining reliable high-frequency synaptic transmission in neural circuits.
The bacterial magnesium transporter MgtA reveals highly selective interaction with specific cardiolipin species
Authors: Weikum Julia , van Dyck Jeroen , Subramani Saranya , Klebl David P. , Storflor Merete , Muench Stephen P. , Abel Sören , Sobott Frank , Morth J. Preben 
Published: September 2021

AbstractA significant challenge today within protein lipidology is to understand the relationship between cell structure, lipid membrane integrity, ion homeostasis and the embedded membrane proteins. The bacterial magnesium transporter A (MgtA) is a specialized P-type ATPase important for Mg2+ import into the cytoplasm; disrupted magnesium homeostasis is linked to intrinsic ribosome instability and nitro-oxidative stress in Salmonella strains. MgtA’s function is highly dependent on anionic lipids, particularly cardiolipin, and further co-localization of cardiolipin with MgtA at the E. coli cell poles has been revealed. Here, we show that MgtA has functional specificity for cardiolipin 18:1, but it reaches maximum activity only in combination with cardiolipin 16:0, equivalent to the major components of native cardiolipin found in E. coli membranes. This is the first time it has been shown experimentally that two different lipid species from the same class, individually promoting low activity, can enhance activity in combination. Native mass spectrometry verifies the presence of two binding sites for cardiolipin and kinetic studies reveal that a cooperative relationship likely exists between the two different cardiolipin variants (cardiolipin 16:0 and cardiolipin 18:1). This is the first experimental evidence of cooperative effects between lipids of the same class, with only minor variations in their acyl chain composition, acting on a membrane protein. In summary, our results reveal that MgtA exhibits a highly complex interaction with one cardiolipin 18:1 and one cardiolipin 16:0, affecting protein activity and stability, and contributing to our understanding of the particular interactions between lipid environment and membrane proteins. Further, a better understanding of Mg2+ homeostasis in bacteria, due to its role as a virulence regulator, will provide further insights into the regulation and mechanism of bacterial infections.
Src-Family B Kinase Inhibition Promotes Lung Endothelial Dysfunction and Guides Drug Discovery
Authors: Andruska Adam M. , Tian Xuefei , Ali Md Khadem , Spiekerkoetter Edda 
Published: September 2021

AbstractProtein tyrosine kinase (PTK) inhibition is efficacious in treating conditions ranging from cancer to fibrosis but can be limited by endothelial cell dysfunction. In trials of protein tyrosine kinase inhibitors (TKIs) a broad range of vascular effects is observed, inducing clinically detrimental endothelial cell apoptosis, impaired barrier function, or improved pulmonary vascular resistance in pulmonary arterial hypertension (PAH). We hypothesize this range of effects is due to subsets of PTKs either impairing or promoting endothelial homeostasis by modulating Bone Morphogenetic Protein receptor 2 (BMPR2) signaling, a pathway essential for vascular development and dysfunctional in PAH. In a high-throughput siRNA screen we find SRC-Family B PTKs activate whereas SRC-Family A PTKs suppress BMPR2 signaling, measured by the transcription factor inhibitor of differentiation 1 (Id1). Induced loss of function of the strongest ID1 activating PTK LCK (a Src-B kinase) in human pulmonary artery endothelial cells suppresses BMPR2 signaling and induces multiple measures of endothelial dysfunction. However, loss of function of the strongest ID1 inhibitor PTK FYN (a Src- A kinase) does the opposite. Whole-genome transcriptional analysis identifies two multi-gene signatures inversely regulated by LCK and FYN we term “endothelial” and “inflammatory”. To find TKIs mimicking selective Src-A and Src-B inhibition, we use Connectivity map to identify drugs connecting to the endothelial and inflammatory signatures. We find several TKIs: a pro-inflammatory (Regorafanib), a BMPR2 potentiating (Brivanib), and a BMPR2 suppressing (Quizartinib). Here we show a dichotomy in pathway regulation by Src- A and -B kinases that may have utility in transcriptionally based drug discovery.
PIN-FORMED1 polarity in the shoot is insensitive to the polarity of neighbouring cells
Authors: Kareem Abdul , Bhatia Neha , Ohno Carolyn , Heisler Marcus G. 
Published: September 2021

AbstractIn plants, epidermal cells are planar-polarized along an axis marked by the asymmetric localization patterns of several proteins including PIN-FORMED1 (PIN1), which facilitates the directional efflux of the plant hormone auxin to pattern phyllotaxis (Heisler et al., 2010; Mansfield et al., 2018; Reinhardt et al., 2003). While PIN1 polarity is known to be regulated non-cell autonomously via the MONOPTEROS (MP) transcription factor, how this occurs has not been determined (Bhatia et al., 2016). Here we use mosaic expression of the serine threonine kinase PINOID (PID) to test whether PIN1 polarizes according to the polarity of neighbouring cells. Our findings reveal that PIN1 is insensitive to the polarity of PIN1 in neighbouring cells arguing against auxin flux or extracellular auxin concentrations acting as a polarity cue, in contrast to previous model proposals (Abley et al., 2016; Stoma et al., 2008).
Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex
Authors: Xia Tian , Chen Di , Liu Xiaolong , Qi Huan , Wang Wen , Chen Huan , Ling Ting , Otkur Wuxiyar , Zhang Chen-Song , Kim Jongchan , Lin Sheng-Cai , Piao Hai-long 
Published: September 2021

ABSTRACTMidkine (MDK), an extracellular growth factor, regulates signal transduction and cancer progression by interacting with receptors, and it can be internalized into the cytoplasm by endocytosis. However, its intracellular function and signaling regulation remain unclear. Here, we show that intracellular MDK interacts with LKB1 and STRAD to disrupt the LKB1-STRAD-Mo25 complex. Consequently, MDK decreases the activity of LKB1 to dampen both the basal and stress-induced activation of AMPK by glucose starvation or treatment of 2-DG. We also found that MDK accelerates cancer cell proliferation by inhibiting the activation of the LKB1-AMPK axis. In human cancers, compared to other well-known growth factors, MDK expression is most significantly upregulated in cancers, especially in liver, kidney and breast cancers, correlating with clinical outcomes and inversely correlating with PRKAA1 (encoding AMPKα1) expression and phosphorylated AMPK levels. Our study elucidates an inhibitory mechanism for AMPK activation, which is mediated by the intracellular MDK through disrupting the LKB1-STRAD-Mo25 complex.
PCSK9 affects expression of key surface proteins in human pancreatic beta cells through intra- and extracellular regulatory circuits
Authors: Saitoski Kevin , Ryaboshapkina Maria , Hamza Ghaith M. , Jarnuczak Andrew F. , Berthault Claire , Carlotti Françoise , Armanet Mathieu , Sengupta Kaushik , Underwood Christina Rye , Andersson Shalini , Guillas Isabelle , Le Goff Wilfried , Scharfmann Raphael 
Published: September 2021

AbstractAims/hypothesisProprotein convertase subtilisin/kexin 9 (PCSK9) is involved in the degradation of LDLR. However, PCSK9 can target other proteins in a cell-type specific manner. While PCSK9 has been detected in pancreatic islets, its expression in insulin-producing pancreatic beta cells is debated. Herein, we studied PCSK9 expression, regulation and function in the human pancreatic beta cell line EndoC-βH1.MethodsWe assessed PCSK9 expression in mouse and human pancreatic islets, and in the pancreatic beta cell line EndoC-βH1. We also studied PCSK9 regulation by cholesterol, lipoproteins, Mevastatin, and by SREBPs transcription factors. To evaluate PCSK9 function in pancreatic beta cells, we performed PCSK9 gain-and loss-of-function experiments in EndoC-βH1 using siPCSK9 or recombinant PCSK9 treatments, respectively.ResultsWe demonstrate that PCSK9 is expressed and secreted by pancreatic beta cells. In EndoC-βH1 cells, PCSK9 expression is regulated by cholesterol and by SREBPs transcription factors. Importantly, PCSK9 knockdown results in multiple transcriptome, proteome and secretome deregulations and impaired insulin secretion. By gain- and loss-of-function experiments, we observed that PCSK9 regulates the expression levels of LDLR and VLDLR through an extracellular mechanism while CD36, PD-L1 and HLA-ABC are regulated through an intracellular mechanism.Conclusions/interpretationCollectively, these results highlight PCSK9 as an important regulator of CD36, PD-L1 and HLA-ABC cell surface expression in pancreatic beta cells.Data availabilityRNA-seq data have been deposited to GEO database with accession number GSE182016. Mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the following identifiers: PXD027921, PXD027911 and PXD027913.
Seeing the unseen: A trifoliate (MYB117) mutant allele fortifies folate and carotenoids in tomato fruits
Authors: Tyagi Kamal , Sunkum Anusha , Rai Meenakshi , Sarma Supriya , Thakur Nidhi , Yadav Amita , Sircar Sanchari , Sreelakshmi Yellamaraju , Sharma Rameshwar 
Published: September 2021

SummaryMicronutrient deficiency also termed hidden hunger affects a large segment of the human population, particularly in developing and underdeveloped nations. Tomato the second most consumed vegetable crop in the world after potato can serve as a sustainable source to alleviate micronutrient deficiency. In tomato, the mutations in the R2R3-MYB117 transcription factor elicit trifoliate leaves and initiate axillary meristems; however, its effect on fruit metabolome remains unexplored. The fruits of a new trifoliate (tf) allele (tf-5) were firmer, had higher °Brix, folate, and carotenoids. The transcriptome, proteome, and metabolome profiling of tf-5 reflected a broad-spectrum change in homeostasis. The tf-5 allele enhanced the fruit firmness by suppressing cell wall softening-related proteins. The tf-5 fruit displayed a substantial increase in aminome, particularly γ-aminobutyric acid, with a parallel reduction in aminoacyl t-RNA synthases. The increased lipoxygenases proteins and transcripts seemingly elevated jasmonic acid. In addition, increased abscisic acid hydrolases transcripts coupled with reduced precursor supply lowered abscisic acid. The upregulation of carotenoids was mediated by modulation of methylerythreitol and plastoquinone pathways along with an increase in carotenoids isomerization proteins. The upregulation of folate in tf-5 was connoted by the increase in precursor p-aminobenzoic acid and transcripts of several folate biosynthesis pathway genes. The reduction in pterin-6-carboxylate and γ-glutamyl hydrolase activity indicated that the diminished folate degradation also enriched folate levels. Our study delineates that introgression of the tf-5 can be used for the γ-aminobutyric acid, carotenoids, and folate fortification of tomato.One-sentence summaryA tomato trifoliate allele encoding a truncated MYB117 transcription factor alters cellular homeostasis and fortifies γ-aminobutyric acid, folate, and carotenoids in tomato fruits.
A merger between compatible but divergent genomes supports allopolyploidization in the Brassicaceae family
Authors: Shin Hosub , Park Jeong Eun , Park Hye Rang , Choi Woo Lee , Yu Seung Hwa , Koh Wonjun , Kim Seungill , Soh Hye Yeon , Waminal Nomar Espinosa , Belandres Hadassah Roa , Lim Joo Young , Yi Gibum , Ahn Jong Hwa , Kim June-Sik , Kim Yong-Min , Koo Namjin , Kim Kyunghee , Perumal Sampath , Kang Taegu , Kim Junghyo , Jang Hosung , Kang Dong Hyun , Kim Ye Seul , Jeong Hyeon-Min , Yang Junwoo , Song Somin , Park Suhyoung , Kim Jin A , Lim Yong Pyo , Park Beom-Seok , Hsieh Tzung-Fu , Yang Tae-Jin , Choi Doil , Kim Hyun Hee , Lee Soo-Seong , Huh Jin Hoe 
Published: September 2021

AbstractHybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species rarely occur in nature mainly due to reproductive barriers but how such hurdles can be overcome is largely unknown. xBrassicoraphanus is a fertile intergeneric allopolyploid synthesized between Brassica rapa and Raphanus sativus in the Brassicaceae family. Genomes of B. rapa and R. sativus are diverged enough to suppress synapsis formation between non-homologous progenitor chromosomes during meiosis, and we found that both genomes reside in the single nucleus of xBrassicoraphanus without genome loss or rearrangement. Expressions of syntenic orthologs identified in B. rapa and R. sativus were adjusted to a hybrid nuclear environment of xBrassicoraphanus, which necessitates reconfiguration of transcription network by rewiring cis-trans interactions. B. rapa coding sequences have a higher level of gene-body methylation than R. sativus, and such methylation asymmetry is maintained in xBrassicoraphanus. B. rapa-originated transposable elements were transcriptionally silenced in xBrassicoraphanus, rendered by gain of CHG methylation in trans via small RNAs derived from the same sequences of R. sativus subgenome. Our work proposes that not only transcription compatibility but also a certain extent of genome divergence supports hybrid genome stabilization, which may explain great diversification and expansion of angiosperms during evolution.
Design of a small-scale and failure-resistant IaaS cloud using OpenStack
Authors: Heuchert Samuel , Rimal Bhaskar Prasad , Reisslein Martin , Wang Yong 
Published: September 2021

PurposeMajor public cloud providers, such as AWS, Azure or Google, offer seamless experiences for infrastructure as a service (IaaS), platform as a service (PaaS) and software as a service (SaaS). With the emergence of the public cloud's vast usage, administrators must be able to have a reliable method to provide the seamless experience that a public cloud offers on a smaller scale, such as a private cloud. When a smaller deployment or a private cloud is needed, OpenStack can meet the goals without increasing cost or sacrificing data control.Design/methodology/approachTo demonstrate these enablement goals of resiliency and elasticity in IaaS and PaaS, the authors design a private distributed system cloud platform using OpenStack and its core services of Nova, Swift, Cinder, Neutron, Keystone, Horizon and Glance on a five-node deployment.FindingsThrough the demonstration of dynamically adding an IaaS node, pushing the deployment to its physical and logical limits, and eventually crashing the deployment, this paper shows how the PackStack utility facilitates the provisioning of an elastic and resilient OpenStack-based IaaS platform that can be used in production if the deployment is kept within designated boundaries.Originality/valueThe authors adopt the multinode-capable PackStack utility in favor of an all-in-one OpenStack build for a true demonstration of resiliency, elasticity and scalability in a small-scale IaaS. An all-in-one deployment is generally used for proof-of-concept deployments and is not easily scaled in production across multiple nodes. The authors demonstrate that combining PackStack with the multi-node design is suitable for smaller-scale production IaaS and PaaS deployments.
Identification of specific metrics for sustainable lean manufacturing in the automobile industries
Authors: Kumar Naveen , Kaliyan Mathiyazhagan , Thilak M. , Acevedo-Duque Ángel 
Published: September 2021

PurposeThis study explains the importance of performance measures and identifies the specific performance measures of sustainable lean manufacturing (SLM) for automobile industries. Awareness towards sustainability and continuous improvement approaches demand monitoring of the sustainable lean impact on organization/industry, and hence, identifying the specific performance metrics is of peak importance.Design/methodology/approachIn this study, specific metrics for social, economic and environmental performance are identified from a systematic literature review of 82 significantly related journal articles. The importance of the identified metrics is assessed with the help of questionnaire responses from a group of industrial experts.FindingsPerformance indicators are statistically analyzed category wise and assessed. The key metrics are summarized based on the survey data followed by a discussion with industrial experts. From this study, performance measures have been identified and validated through hypothesis testing for Indian automobile industries. Certification of IATF16949 implementation found an important vertical for SLM implementation. In this study, SLM implementation initiatives are discussed, and reward scheme for outstanding performers are identified as important initiatives are followed by small improvement culture.Practical implicationsThe proposed discussion of this study is useful for industrialist and researchers, as SLM performance measures are well explained for Indian automobile industries. In this study, future research direction is also explained related to other industries. These summarized performance measures will help to maintain SLM in industries.Originality/valueThis paper presents the original literature review based on the study of SLM, as no extensive study is available where SLM performance measure explained for automobile industries. Key initiatives and vertical of SLM are well explained for Indian automobile industries. This study proposed a complete framework for SLM implementation considering competitive manufacturing targets.
Impact of mobile banking failure on bank customers' usage behaviour: the mediating role of user satisfaction
Authors: Kamboj Shampy , Sharma Manika , Sarmah Bijoylaxmi 
Published: September 2021

PurposeThis study seeks to observe the association between mobile banking failures, use of m-banking and customer engagement to determine the contribution of user satisfaction towards m-banking as mediator between the aforementioned relationship.Design/methodology/approachThis study proposes a Mobile Banking Failure Model (MBFM) by integrating four failure dimensions (functional, system, information and service) based on Tan's failure model and DeLone and Mclean's Information Success model. In this paper, data was gathered from 338 respondents, who were the customers of banks and regular users of m-banking services of their respective banks in India. A survey method was employed to collect data. Structure equation modelling (SEM) was used to analyse the collected data.FindingsThe results suggest that all m-banking failure dimensions (functional, system, information and service) affect the use of m-banking, which in turn affects user satisfaction towards m-banking and customer engagement. Additionally, this study found that user satisfaction towards m-banking acts as a partial mediator between the use of m-banking and customer engagement.Research limitations/implicationsThe banking failure and its use by customers have been examined in the context of mobile banking in India only and thereby limits the generalization of results to other industry and country contexts.Practical implicationsThe results of this paper will guide bank managers and policy planners in implementing MBFM in the Indian banking context, specifically for their m-banking apps.Originality/valueThe use of m-banking, user satisfaction towards m-banking and customer engagement have been added as three supportive variables to the basic Tan's failure model and DeLone and Mclean's Information Success model to examine the impact of m-banking failure on bank customers' usage behaviour. This is a novel addition to the extant literature, as most empirical works in this domain are from industries other than banking (specifically m-banking) and with differing contexts.