bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation and histone H1 cooperatively repress transposable elements and aberrant intragenic transcripts
Authors: Choi Jaemyung , Lyons David B. , Yvonne Kim M. , Moore Jonathan D. , Zilberman Daniel 
Published: January 2019

SummaryDNA methylation and histone H1 mediate transcriptional silencing of genes and transposable elements, but how they interact is unclear. In plants and animals with mosaic genomic methylation, functionally mysterious methylation is also common within constitutively active housekeeping genes. Here we show that H1 is enriched in methylated sequences, including genes, ofArabidopsis thaliana, yet this enrichment is independent of DNA methylation. Loss of H1 disperses heterochromatin, globally alters nucleosome organization, and activates H1-bound genes, but only weakly de-represses transposable elements. However, H1 loss strongly activates transposable elements hypomethylated through mutation of DNA methyltransferaseMET1. Loss of H1 also activates antisense transcripts within demethylated genes. Our results demonstrate that H1 and DNA methylation cooperatively maintain transcriptional homeostasis by silencing transposable elements and aberrant intragenic transcripts. Such functionality plausibly explains why DNA methylation, a well-known mutagen, has been maintained within coding sequences of crucial plant and animal genes.HighlightsHistone H1 is enriched in methylated DNA independently of methylationLoss of H1 activates genes, alters nucleosome organization and disperses heterochromatinDNA methylation and H1 jointly silence transposonsDNA methylation and H1 cooperatively suppress intragenic antisense transcripts
Long-term potentiation in neurogliaform cells modulates excitation-inhibition balance in the temporoammonic pathway
Authors: Mercier Marion S. , Magloire Vincent , Cornford Jonathan H. , Kullmann Dimitri M. 
Published: January 2019

AbstractApical dendrites of pyramidal neurons integrate information from higher-order cortex and thalamus, and gate signaling and plasticity at proximal synapses. In the hippocampus, neurogliaform cells and other interneurons located within stratum lacunosum-moleculare mediate powerful inhibition of CA1 pyramidal neuron distal dendrites. Is the recruitment of such inhibition itself subject to use-dependent plasticity, and if so, what induction rules apply? Here we show that interneurons in mouse stratum lacunosum-moleculare exhibit Hebbian NMDA receptor-dependent long-term potentiation (LTP). Such plasticity can be induced by selective optogenetic stimulation of afferent fibers in the temporoammonic pathway from the entorhinal cortex, but not by equivalent stimulation of afferents from the thalamic nucleus reuniens. We further show that theta-burst patterns of afferent firing induces LTP in neurogliaform interneurons identified using neuron-derived neurotrophic factor (Ndnf)-Cre mice. Theta-burst activity of entorhinal cortex afferents led to an increase in disynaptic feed-forward inhibition, but not monosynaptic excitation, of CA1 pyramidal neurons. Activity-dependent synaptic plasticity of neurogliaform cells in stratum lacunosum-moleculare thus alters the excitation-inhibition balance at entorhinal cortex inputs to the apical dendrites of pyramidal neurons, implying a dynamic role for these interneurons in gating CA1 dendritic computations.Significance statementElectrogenic phenomena in distal dendrites of principal neurons in the hippocampus have a major role in gating synaptic plasticity at afferent synapses on proximal dendrites. Apical dendrites also receive powerful feed-forward inhibition mediated in large part by neurogliaform neurons. Here we show that theta-burst activity in afferents from the entorhinal cortex induces ‘Hebbian’ long-term potentiation at excitatory synapses recruiting these GABAergic cells. Such LTP increases disynaptic inhibition of principal neurons, thus shifting the excitation-inhibition balance in the temporoammonic pathway in favor of inhibition, with implications for computations and learning rules in proximal dendrites.
Selective inhibition of HDAC3 targets synthetic vulnerabilities and activates immune surveillance in lymphoma
Authors: Mondello Patrizia , Tadros Saber , Teater Matt , Fontan Lorena , Chang Aaron Y. , Jain Neeraj , Singh Shailbala , Ma Man Chun John , Yang Haopeng , Toska Eneda , Alig Stefan , Durant Matthew , Stanchina Elisa de , Mottok Anja , Nastoupil Loretta , Neelapu Sattva , Weigert Oliver , Inghirami Giorgio , Baselga Josè , Dhogan Ahmet , Younes Anas , Yee Cassian , Scheinberg David A. , Melnick Ari , Green Michael R. 
Published: January 2019

CREBBP mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by CREBBP mutation are direct targets of the BCL6/HDAC3 onco-repressor complex. Accordingly, we show that HDAC3 selective inhibitors fully reverse CREBBP mutant aberrant epigenetic programming resulting in: a) growth inhibition of lymphoma cells through induction of BCL6 target genes such as CDKN1A and b) restoration of immune surveillance due to induction of BCL6 repressed IFN pathway and antigen presentation genes. By reactivating these genes, exposure to HDAC3-i restored the ability of tumor infiltrating lymphocytes to kill DLBCL cells in an MHC II and MHC I dependent manner. Hence HDAC3-i represent a novel mechanism-based immune-epigenetic therapy for CREBBP mutant lymphomas.STATEMENT OF SIGNIFICANCEWe have leveraged the molecular characterization of different types of CREBBP mutations to define a rational approach for targeting these mutations through selective inhibition of HDAC3. This represents an attractive therapeutic avenue for targeting synthetic vulnerabilities in CREBBP mutant cells in tandem with promoting anti-tumor immunity.
Quality of Whole Genome Sequencing from Blood versus Saliva Derived DNA in Cardiac Patients
Authors: Yao Roderick A. , Akinrinade Oyediran , Chaix Marie , Mital Seema 
Published: January 2019

AbstractWhole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes. We compared the level of microbial contamination, sequencing coverage, as well as yield and concordance of single-nucleotide polymorphism (SNP) and copy number variant (CNV) calls in WGS from paired blood and saliva samples from 5 pediatric heart disease patients. We found that although saliva samples contained a higher proportion of sequence reads that map to the human oral microbiome, these reads were readily excluded by mapping the reads to the human reference genome. Sequencing coverage was low only in 1 of 5 saliva samples. Over 95% SNPs (including rare SNPs) but <80% CNVs called in blood genomes were detected in paired saliva genomes. These findings suggest that most good quality saliva samples can serve as an alternative to blood samples for detection of sequence variants from WGS in cardiovascular disease patients.
Redating of the To’aga site (Ofu Island, Manu’a) and a revised chronology for the Lapita to Polynesian Plainware transition in Tonga and Samoa
Authors: Petchey Fiona , Kirch Patrick V. 
Published: January 2019

AbstractRadiocarbon dating Pacific archaeological sites is fraught with difficulties. Often situated in coastal beach ridges or sand dunes, sites exhibit horizontal and vertical disturbances, while datable materials such as wood charcoal are typically highly degraded, or derived from old trees or drift wood and bone collagen rarely survives in the tropical conditions. Shell, therefore, is the most logical material for dating Pacific sites since it is resistant to alteration, can be sampled to ensure only the last few seasons of growth are represented and is often closely tied to human economic activities. However, shell radiocarbon (14C) dating has been plagued by interpretive problems largely due to our limited knowledge of the 14C cycle in near shore marine and estuarine environments. Consequently, shell dates are typically ignored in regional chronometric evaluations and often avoided for dating altogether. Recent advances in our understanding of the source of shell 14C content as well as the development of the first South Pacific Gyre model of changing marine 14C over time, combined with Bayesian statistical modelling, have now provided us with insight into the value of these shell radiocarbon dates, enabling a revision of the age of the To’aga site on Ofu Island, an early occupation site associated with the initial Polynesian Plainware period in Samoa, the earliest use of which is now dated to between 2782 and 2667 cal BP.
A glucose-dependent spatial patterning of exocytosis in human β-cells is disrupted in type 2 diabetes
Authors: Fu Jianyang , Githaka John Maringa , Dai Xiaoqing , Plummer Gregory , Suzuki Kunimasa , Spigelman Aliya F. , Bautista Austin , Kim Ryekjang , Greitzer-Antes Dafna , Fox Jocelyn E Manning , Gaisano Herbert Y. , MacDonald Patrick E 
Published: February 2019

SUMMARYImpaired insulin secretion in type 2 diabetes (T2D) is linked to reduced insulin granule docking, disorganization of the exocytotic site, and an impaired glucose-dependent facilitation of insulin exocytosis. We show in β-cells from 80 human donors that the glucose-dependent amplification of exocytosis is disrupted in T2D. Spatial analyses of granule fusion events, visualized by total internal reflection fluorescence (TIRF) microscopy, demonstrate that these are non-random across the surface of β-cells from donors with no diabetes (ND). The compartmentalization of events occurs within regions defined by concurrent or recent membrane-resident secretory granules. This organization, and the number of membrane-associated granules, is glucose-dependent and notably impaired in T2D β-cells. Mechanistically, multi-channel Kv2.1 clusters contribute to maintaining the density of membrane-resident granules and the number of fusion ‘hot spots’, while SUMOylation sites at the channel N-(K145) and C-terminus (K470) determine the relative proportion of fusion events occurring within these regions. Thus, a glucose-dependent compartmentalization of fusion, regulated in part by a structural role for Kv2.1, is disrupted in β-cells from donors with type 2 diabetes.HIGHLIGHTSExocytosis of secretory granules is non-random across the surface of human β-cells, and this organization is disrupted in type 2 diabetes.Increasing glucose facilitates the spatial compartmentalization of fusion, independent of an overall increase in event frequency.Compartmentalized ‘hot spots’ occur at sites marked by membrane-associated granules, the density of which is regulated in part by a clustered K+ channel (Kv2.1).SUMOylation status of the channel controls the proportion of events that occur within these local regions.
Modulating the human functional connectome using deep brain stimulation
Authors: Horn Andreas , Wenzel Gregor , Irmen Friederike , Hübl Julius , Li Ningfei , Neumann Wolf-Julian , Krause Patricia , Bohner Georg , Scheel Michael , Kühn Andrea A. 
Published: February 2019

AbstractNeuroimaging has seen a paradigm shift from a formal description of local activity patterns toward studying distributed brain networks. The recently defined framework of the ‘human connectome’ allows to globally analyse parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in twenty Parkinson’s disease (PD) patients with subthalamic DBS switched ON and OFF. An age-matched control cohort of fifteen subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus (STN) was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting ON and OFF DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the sensorimotor STN explained half the variance in global connectivity increases within the sensorimotor network (R = 0.711, p < 0.001). Moreover, local impact of DBS on the motor STN could explain the degree of how much voxel-wise average brain connectivity normalized toward healthy controls (R = 0.713, p < 0.001). Finally, a network based statistics analysis revealed that DBS attenuated specific couplings that are known to be pathological in PD. Namely, coupling between motor thalamus and sensorimotor cortex was increased and striatal coupling with cerebellum, external pallidum and STN was decreased by DBS.Our results show that rs-fMRI may be acquired in DBS ON and OFF conditions on clinical MRI hardware and that data is useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile toward healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.
Improving customer satisfaction of a healthcare facility: reading the customers’ needs
Authors: Gonzalez Marvin E. 
Published: January 2019

Purpose
Customer satisfaction refers to the extent to which customers are happy and satisfied with the products and services provided by a business. The purpose of this paper is twofold: first, to integrate lean tools in the analysis of customer satisfaction and, second, to examine its implications for research and practice.

Design/methodology/approach
The author proposes the combination of three lean tools in order to design a service quality system that has customer expectations (CEs) as the first input. These tools are quality function deployment (QFD), Hoshin Kanri planning process (HKPP) and benchmarking. The author uses a case study to show the functionality of these tools and the final design of a service quality system for a medical center.

Findings
Interaction between the service provider and the customer is the primary core activity for service-oriented businesses of different natures. A key relationship between trust in service quality and customer satisfaction cannot be ignored in interpersonal-based service encounters. However, there is a gap in the literature in terms of standardized lean-based procedures or methodologies that lead to improved customer satisfaction that are based directly on CEs.

Research limitations/implications
Given the variety of the population, the authors developed several methodologies to standardize the customer responses. Using several total quality management tools, the standardization allows the authors to separate the different CEs. The gathering of customers’ expectations (voice of the customers) allows the companies to focus on the real problems expressed by the users of the service, increasing their loyalty and, most importantly in the field under study, the customer’s satisfaction with the service received.

Practical implications
For practitioners, this study helps with the use of lean tools such as QFD, benchmarking and HKPP and attempts to bridge such a gap with an evidence-based real case.

Social implications
With the incorporation of all the customer needs, additional elements must be considered in the design of new services. Availability for all and sustainability play an important part of the CEs.

Originality/value
This paper presents a real application of QFD and Hoshin Kanri and how they may help the service organizations with future development.
Benchmarking the strategic roles of the project management office (PMO) when developing business ecosystems
Authors: Sandhu Maqsood Ahmad , Al Ameri Tareq Zayed , Wikström Kim 
Published: January 2019

PurposeProjects are an inherent part of implementing strategies. Still, the challenge is to connect a long-term strategy for larger ecosystem development to the individual projects being undertaken. The purpose of this paper is to test the ability of seven project management office (PMO) roles to achieve strategic planning in large society development public organisations in the United Arab Emirates (UAE).Design/methodology/approachThe questionnaire survey that was employed for data collected from 450 project members in 19 project-based public organisations having PMO unit had a response rate of 60 per cent. The received data analysed quantitatively by using multiple regression.FindingsThe survey data revealed that PMO enhanced the achievement of the strategic plan for better development of the business ecosystem. The analysis outputs, as expected, have indicated that 95 per cent of the targeted organisations established their own PMO for developing business ecosystem.Research limitations/implicationsDespite there are PMOs hosted by private organisations, the study is limited to the PMO within the context of the government and semi-government organisations in the UAE.Practical implicationsThese findings further utilised in developing the conceptual PMO model that would be flexible to be applied to similar project management methodology in various business settings, as well as pave the way for further scholarly investigations.Originality/valueThis work is both exploratory and causal study, which concentrates on investigating the effectiveness of seven proposed PMO roles (as independent variables) in carrying out the strategic plan (as the dependent variable) of the public-sector organisations in the UAE for the development of business ecosystem.
An empirical study on productivity analysis of Indian leather industry
Authors: Gupta Sandeep Kumar , Gupta Shivam , Dhamija Pavitra 
Published: January 2019

Purpose
It is essential to track the development of resource and pollution intensive industries such as textile, leather, pharmaceutical, etc., under burgeoning pressure of environmental compliance. Therefore, the purpose of this paper is to analyze the progress of Indian leather industry in terms of individual factors and total factor productivity.

Design/methodology/approach
This study applies and examines the various concepts of productivity such as labor productivity, capital productivity, material productivity and energy productivity. Further, it assesses and compares the performance of Indian leather industry in Tamil Nadu (TN), West Bengal (WB) and Uttar Pradesh (UP) based on productivity analysis, spatial variations determinants in productivity and technology closeness ratio.

Findings
The findings suggest that as per the productivity analysis, WB leather clusters have performed remarkably better in terms of partial factor productivity and technical efficiency (TE), followed by TN and UP. This can be attributed to shifting of leather cluster of WB to a state-of art leather complex with many avenues for resource conservation. Further, the findings reveal that the firm size and partial factor productivities have significant positive correlation with TE which supports technological theory of the firm.

Practical implications
The results of this study can be useful for the policy makers associated with the Indian leather industry especially to design interventions to support capacity building at individual firm level as well as cluster level to enhance the efficiency and productivity of overall industry.

Social implications
The findings also support the resource dependence theory of firm according to which the larger size firms should reflect on resource conservation practices, for instance the concept of prevention is better than cure based upon 3R (reduce, recycle and reuse) principles.

Originality/value
The paper gives an explanation of the productivity in the leather industry in terms of its factor productivity and TE.
An empirical investigation on lean production system framework in the Indian manufacturing industry
Authors: Jasti Naga Vamsi Krishna , Kodali Rambabu 
Published: January 2019

Purpose
The purpose of this paper is to verify the applicability of proposed lean production system (LPS) framework in the Indian manufacturing industry.

Design/methodology/approach
The authors conducted a cross-sectional study to collect responses from five major sectors, namely, automobile, process, machines and equipment, electronics and components and textile. They collected 200 responses to perform empirical validation from Indian manufacturing industry. They performed reliability analysis on the proposed framework of LPS in the Indian manufacturing industry.

Findings
The findings revealed that all the elements and sub-elements have a high value in reliability. Subsequently, the study performed principles component analysis on LPS framework. The empirical investigation revealed that the proposed LPS framework has a high level of reliability as well as validity in the Indian manufacturing industry. Hence, the study concluded that the LPS framework is helpful to implement lean principles in a structured manner in any Indian manufacturing industry to achieve excellence in organizational functions.

Originality/value
The authors conducted an empirical survey to verify the applicability of the proposed LPS framework in the Indian manufacturing industry. They observed that many researchers proposed various LPS frameworks, but none of the researchers focused on verifying the proposed frameworks. To overcome, the same limitations, the study verified the proposed framework with the larger sample size.
Which personal values matter most? Job performance and job satisfaction across job categories
Authors: Ismail Hussein N. , Karkoulian Silva , Kertechian Sevag K. 
Published: January 2019

PurposeAs one of the first studies in this field, the purpose of this paper is to explore the effect of personal values on job performance and job satisfaction across different jobs. Further, it aims to identify personal value types that are positively, or negatively, related to behavioural and attitudinal outcomes in different job categories.Design/methodology/approachBased on a sample of 270 participants across several job categories including finance, accounting, marketing, sales, HR (human resources), operations and information technology (IT), this research explores the relationship between personal values, job performance and job satisfaction across the listed job categories. Ordinary least square (OLS) stepwise-regression and partial least square (PLS) regression were used in analysing the results.FindingsFindings showed that for some of the jobs examined, different types of personal values were associated with different worker outcomes.Originality/valueThis research study identifies sets of personal values that are suited to some jobs more than others in terms of job performance and job satisfaction outcomes. Moreover, this research demonstrates the importance of controlling for job categories in future research models that investigate the links between values, performance and satisfaction.