bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cholinergic system and treatment response in subtypes of Alzheimer’s disease
Authors: Machado Alejandra , Ferreira Daniel , Grothe Michel J. , Eyjolfsdottir Helga , Almqvist Per M. , Cavallin Lena , Lind Göran , Linderoth Bengt , Seiger Åke , Teipel Stefan , Wahlberg Lars U. , Wahlund Lars-Olof , Westman Eric , Eriksdotter Maria ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2020

AbstractBACKGROUNDThe heterogeneity within Alzheimer’s disease (AD) seriously challenges the development of disease modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subtypes of AD, and explored the relevance of subtype stratification in a clinical trial on encapsulated cell biodelivery (ECB) of nerve growth factor (NGF) to the basal forebrain.METHODSStructural MRI data was collected for 90 amyloid-positive patients and 69 amyloid-negative healthy controls at baseline, 6-, 12-, and 24-month follow-up. The effect of the NGF treatment was investigated in 10 biopsy verified AD patients with structural MRI data at baseline and at 6- or 12-months follow-up. Patients were classified as typical, limbic-predominant, hippocampal-sparing, or minimal atrophy AD, using a validated visual assessment method. Volumetric analyses were performed using a region-of-interest approach.RESULTSAll AD subtypes showed reduced basal forebrain volume as compared with controls. Limbic-predominant subtype showed fastest basal forebrain atrophy rate, whereas minimal atrophy subtype did not show significant volume decline over time. Atrophy rates of hippocampus and precuneus also differed across subtypes. The NGF treatment seemed to slow the rate of atrophy in precuneus and hippocampus, particularly in the hippocampal-sparing AD subtype.CONCLUSIONSThe cholinergic system is differentially affected in distinct atrophy subtypes of AD, possibly contributing to their differential response to cholinergic treatment. Our findings suggest that future clinical trials should target specific subtypes of AD, or at least report treatment effects stratifying by subtype.Trial registrationClinicalTrials.gov identifier: NCT01163825. Registered 14 July 2010 - https://clinicaltrials.gov/ct2/show/NCT01163825
Effects of Metformin compared to Thiazolidinediones on vascular endothelial function in Polycystic Ovary syndrome: A systematic review
Authors: Mazumder Hoimonty , Faizah Farah , Hossain Md. Mahbub 
Published: January 2020

AbstractMetformin and Thiazolidinediones are insulin sensitizers used as the first-line treatment of PCOS, which are recently being examined for their extensive beneficial impacts at biochemical and molecular level of body function in Polycystic ovary syndrome. Therefore, purpose of this review is to compare the effectiveness of Metformin and Thiazolidinediones on vascular endothelial function in PCOS. MEDLINE (1966- October 2018), CINAHL (1982 to October 2018), Cochrane Central Register of Controlled Trials and Cochrane Menstrual Disorders and Subfertility Group trials register (October 2018) and Google Scholar were searched electronically without language restriction. Three Randomized controlled trials (RCTs) were selected with a total of 90 participants comparing effect of Metformin (Intervention) to Thiazolidinediones (Comparator) with an outcome on endothelial function among women with PCOS. In results, Meta-analysis shows no statistically significant difference on endothelial-dependent vasodilation between Metformin and Thiazolidinedione (p value= 0.59 at 95% CI - 1.31, 0.74).
Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A-NK cells
Authors: Bennstein Sabrina Bianca , Weinhold Sandra , Manser Angela Ricarda , Scherenschlich Nadine , Noll Angela , Raba Katharina , Kögler Gesine , Walter Lutz , Uhrberg Markus 
Published: January 2020

AbstractDespite their identification several years ago, molecular identity and developmental relation between human ILC1 and NK cells, comprising group 1 ILCs, is still elusive. To unravel their connection, thorough transcriptional, epigenetic, and functional characterization was performed from umbilical cord blood (CB). Unexpectedly, ILC1-like cells lacked Tbet expression and failed to produce IFNg. Moreover, in contrast to previously described ILC1 subsets they could be efficiently differentiated into NK cells. These were characterized by highly diversified KIR repertoires including late stage NKG2A-KIR+ effector cells that are commonly not generated from previously known NK cell progenitor sources. This property was dependent on stroma cell-derived Notch ligands. The frequency of the novel ILC1-like NK cell progenitor (NKP) significantly declined in CB from early to late gestational age. The study supports a model in which circulating fetal ILC1-like NKPs travel to secondary lymphoid tissues to initiate the formation of diversified NK cell repertoires after birth.
TMEM184b is necessary for IL-31 induced itch
Authors: Larsen Erik G. , Cho Tiffany S. , McBride Matthew L. , Feng Jing , Manivannan Bhagyashree , Madura Cynthia , Klein Nathaniel E. , Wright Elizabeth B. , Garcia-Verdugo Hector D. , Jarvis Chelsea , Khanna Rajesh , Hu Hongzhen , Largent-Milnes Tally M. , Bhattacharya Martha R.C. 
Published: January 2020

AbstractNociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. One subtype of mature DRG neurons, comprising about 5% of neurons in the ganglia, is responsible for sensing mediators of acute itch and atopic dermatitis, including the cytokine IL-31. How itch-sensitive (pruriceptive) neurons are specified is unclear. Here we show thatTmem184b, a gene with roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors, including those for IL-31, Leukotriene C4, and Histamine. Male and female mice lackingTmem184bshow reduced responses to IL-31, but maintain normal responses to pain and mechanical force, indicating a specific behavioral defect in pruriception. Calcium imaging experiments indicate that a reduction in IL-31 induced calcium entry is a likely contributor to this phenotype. We identify an early failure of proper Wnt-dependent transcriptional signatures and signaling components in Tmem184b mutant mice that may explain the improper DRG neuronal subtype specification. Accordingly, lentiviral re-expression of Tmem184b in mutant embryonic neurons restores Wnt signatures. Together, these data demonstrate that Tmem184b promotes adult somatosensation through developmental Wnt signaling and promotion of proper pruriceptive gene expression. Our data illuminate a new key regulatory step in the processes controlling the establishment of diversity in the somatosensory system.
Giant magnetoresistive biosensors for real-time quantitative detection of protease activity
Authors: Adem Sandeep , Jain Sonal , Sveiven Michael , Zhou Xiahan , O’Donoghue Anthony J. , Hall Drew A. 
Published: January 2020

ABSTRACTProteases are enzymes that cleave proteins and are crucial to physiological processes such as digestion, blood clotting, and wound healing. Unregulated protease activity is a biomarker of several human diseases. Synthetic peptides that are selectively hydrolyzed by a protease of interest can be used as reporter substrates of unregulated protease activity. We developed an activity-based protease sensor by immobilizing magnetic nanoparticles (MNP) to the surface of a giant magnetoresistive spin-valve (GMR SV) sensor using peptides. Cleavage of these peptides by a protease, releases the magnetic nanoparticles resulting in a time-dependent change in the local magnetic field. Using this approach, we detected a significant release of MNPs after 3.5 minutes incubation using just 4 nM of the cysteine protease, papain. In addition, we show that proteases in healthy human urine do not release the MNPs, however addition of 20 nM of papain to the urine samples resulted in a time-dependent change in magnetoresistance. This study lays the foundation for using GMR SV sensors as a platform for real-time quantitative detection of protease activity in biological fluids.
Computationally-guided technology platform for on-demand production of diversified therapeutic phage cocktails
Authors: Mageeney Catherine M. , Sinha Anupama , Mosesso Richard A. , Medlin Douglas L. , Lau Britney Y. , Rokes Alecia B. , Lane Todd W. , Branda Steven S. , Williams Kelly P. 
Published: January 2020

ABSTRACTNew therapies are necessary to combat increasingly antibiotic-resistant bacterial pathogens. We have developed a technology platform of computational, molecular biology, and microbiology tools which together enable on-demand production of phages that target virtually any given bacterial isolate. Two complementary computational tools that identify and precisely map prophages and other integrative genetic elements (IGEs) in bacterial genomes are used to identify prophage-laden bacteria that are close relatives of the target strain. Phage genomes are engineered to disable lysogeny, through use of long amplicon PCR and Gibson assembly. Finally, the engineered phage genomes are introduced into host bacteria for phage production. As an initial demonstration, we used this approach to produce a phage cocktail against the opportunistic pathogenPseudomonas aeruginosaPAO1. Two prophage-ladenP. aeruginosastrains closely related to PAO1 were identified, ATCC 39324 and ATCC 27853. Deep sequencing revealed that mitomycin C treatment of these strains induced seven phages that grow onP. aeruginosaPAO1. The most diverse five of these were engineered for non-lysogeny by deleting the integrase gene (int), which is readily identifiable and typically conveniently located at one end of the prophage. The Δintphages, individually and in cocktails, showed killing ofP. aeruginosaPAO1in vitroas well as in a waxworm (Galleria mellonella) model of infection.SIGNIFICANCE STATEMENTThe antibiotic-resistance crisis in medicine and agriculture has led to renewed interest in phage therapy as an alternative means of treating infection. However, conventional methods for isolating pathogen-specific phage are slow, labor-intensive, and frequently unsuccessful. We have demonstrated that prophages carried by near-neighbor bacteria can serve as starting material for production of engineered phages that kill the target pathogen. Our approach and technology platform offer new opportunity for rapid development of phage therapies against most, if not all, bacterial pathogens, a foundational advance for use of phage in treating infectious disease.
Investigating resting brain perfusion abnormalities and target-engagement by intranasal oxytocin in women with bulimia nervosa and binge-eating disorder and healthy controls
Authors: Martins Daniel , Leslie Monica , Rodan Sarah , Zelaya Fernando , Treasure Janet , Paloyelis Yannis 
Published: January 2020

ABSTRACTAdvances in the treatment of bulimia nervosa and binge eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared to healthy controls and investigate if intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomised, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40IU) or placebo over 18-26 minutes post-dosing, as we have previously shown robust OT-induced changes in resting rCBF in men 15-36min post-dosing. We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in key neural circuits previously implicated in BN/BED pathophysiology, namely the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of 40IU intranasal OT on perfusion abnormalities in these patients 18-26 minutes post-dosing. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring.
The Power of Citizen Science to Quantify Ecological Risks in Cities
Authors: Putman Breanna J. , Williams Riley , Li Enjie , Pauly Gregory B. 
Published: January 2020

AbstractUrbanization is an extreme form of habitat modification that can alter ecological relationships among organisms, but these can be hard to study because much of the urban landscape is inaccessible private property. We show that citizen science can be a powerful tool to overcome this challenge. We used photo-vouchered observations submitted to the citizen science platform iNaturalist to assess predation and parasitism across urbanization gradients in a secretive yet widespread species, the Southern Alligator Lizard (Elgaria multicarinata), in Southern California, USA. From photographs, we quantified predation risk by assessing tail injuries and quantified parasitism rates by counting tick loads on lizards. We estimated urbanization intensity by determining percent impervious surface around each lizard observation. We found that tail injuries increased with age of the lizard and with urbanization, suggesting that urban areas are riskier habitats, likely because of elevated populations of predators such as outdoor cats. Conversely, parasitism decreased with urbanization likely due to a loss of mammalian hosts and anti-tick medications used on companion animals. Moreover, our citizen science approach allowed us to generate a large dataset on a secretive species extremely rapidly and at an immense spatial scale that facilitated quantitative measures of urbanization (e.g. percent impervious surface cover) as opposed to qualitative measures (e.g. urban vs rural). This study demonstrates that citizen science is allowing researchers to answer ecological questions that otherwise would go unanswered.
High fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imagingin vivo
Authors: Xie Michael E. , Adam Yoav , Fan Linlin Z. , Böhm Urs L. , Kinsella Ian , Zhou Ding , Paninski Liam , Cohen Adam E. 
Published: January 2020

AbstractThe ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved high signal to noise ratioin vivowith 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise that present analysis challenges, namely light scattering, out-of-focus sources, motion, and blood flow. We present a novel signal extraction methodology, Spike-Guided Penalized Matrix Decomposition-Nonnegative Matrix Factorization (SGPMD-NMF), which resolves supra- and sub-threshold voltages with high fidelity, even in the presence of correlated noise. The method incorporates biophysical constraints (shared soma profiles for spiking and subthreshold dynamics) and optical constraints (smoother spatial profiles from defocused vs. in-focus sources) to cleave signal from background. We validated the pipeline using simulated and composite datasets with realistic noise properties. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon, mouse cortex expressing SomArchon or Voltron, and zebrafish spine expressing zArchon1.
Robustness testing and scalability of phosphate regulated promoters useful for two-stage autoinduction inE. coli
Authors: Moreb Eirik A. , Ye Zhixia , Efromson John P. , Hennigan Jennifer N. , Menacho-Melgar Romel , Lynch Michael D. 
Published: January 2020

AbstractA key challenge in synthetic biology is the successful utilization of characterized parts, such as promoters, in different biological contexts. We report the robustness testing of a small library ofE. coliPhoB regulated promoters that enable heterologous protein production in two-stage cultures. Expression levels were measured both in a rich Autoinduction Broth as well as a minimal mineral salts media. Media dependent differences were promoter dependent. 4 out of 16 promoters tested were identified to have tightly controlled expression which was also robust to media formulation. Improved promoter robustness led to more predictable scale up and consistent expression in instrumented bioreactors. This subset of PhoB activated promoters, useful for two-stage autoinduction, highlight the impact of the environment on the performance of biological parts, and the importance of robustness testing in synthetic biology.HighlightsCharacterization of the impact of media on promoter activityIdentification of promoters robust to environmental variablesIdentification of promoters whose expression scale from microtiter plates to bioreactorsAbstract FigureGraphical Abstract
Opposing neural signals of CaV1-encoded peptides are tuned by C-terminus mediated inhibition
Authors: Yang Yaxiong , Liu Min , Liu Nan , Li Wenxiang , Yu Zhen , Hong Weili , Li Ping , Jiang He , Ge Haiyan , Wang Ping , Song Sen , Li Xiaomei , Fan Yubo , Liu Xiaodong 
Published: January 2020

AbstractL-type calcium (CaV1) channels regulate gene expressions via the cascade of excitation-transcription coupling, or directly as standalone CCAT (Calcium Channel Associated Transcriptional-regulator) peptides encoding distal carboxyl-terminus (DCT) of CaV1, both evidenced in dendritogenesis signaling in neurons. We here discover that DCT peptides opposedly mediate these two sets of transcription signals, all tunable in accordance to C-terminus mediated inhibition (CMI) of Ca2+/CaV1 influx. By electrophysiology, neurite morphology, and FRET 2-hybrid binding analyses, we systematically examined native and derived DCT peptides across CaV1, unveiling that the overall balance between cytosolic inhibitionversusnuclear facilitation is spatially and temporally tuned by CMI of each DCT variant. Our findings not only resolve several controversies existing to DCT variants, but also propose ade novoscheme of CaV1-centric gene regulation: two concurrent routes of transcription signals initiated from either membrane CaV1 channels or nuclear CaV1-encoded peptides are subject to autonomous feedback tuning by peptide/channel interactions.
Challenges in auditing fair value measurement and accounting estimates
Authors: Oyewo Babajide , Emebinah Ebuka , Savage Romeo 
Published: January 2020

PurposeFollowing the issuance of International Financial Reporting Standard 13 on fair value measurement (which became operational from January 2013), this study aims to investigate post-implementation challenges in the audit of fair value measurement and accounting estimates in the Nigerian context.Design/methodology/approachData-collection was through a structured-questionnaire administered on 400 auditors from diverse backgrounds in terms of audit firm size, international affiliation and global presence.FindingsEmpirical data obtained from 277 auditors were analysed using descriptive statistics, factor analysis, one-way ANOVA, cluster analysis, independent samplet-test and one-way multivariate analysis of co-variance. It was observed that the two highest-ranking and most-prevalent challenges of auditing fair value measurement and accounting estimates are the tendency for managers to manipulate earnings owing to the inability of auditor to effectively test fair value estimates; and the difficulty in testing unobservable inputs due to the application of assumptions and judgement in arriving at estimates by preparers of financial reports.Originality/valueWhile there is no significant difference in the perception of auditors on the audit challenges associated with fair value measurement and accounting estimates, there is a significant difference in the magnitude of audit challenges faced in verifying fair value measurements and accounting estimates across industry sectors. Concerned stakeholders (including but not limited to accounting regulators, auditing standard setters, audit firms, researchers) are importuned to come up with robust and pragmatic measures to curtain these challenges, as the inability of auditors to rigorously verify fair value estimates may jeopardize the very essence of fair value measurement which is to elevate financial reporting quality.
Money laundering through banks in Dubai
Authors: Teichmann Fabian Maximilian , Falker Marie-Christin 
Published: January 2020

PurposeThe purpose of this paper is to illustrate how illegally obtained funds from Austria, Germany, Liechtenstein and Switzerland are laundered through the banking system in Dubai.Design/methodology/approachThe study is conducted using a qualitative content analysis of 60 semi-structured expert interviews with both criminals and money laundering prevention experts, and a quantitative survey of 200 financial sector compliance officers.FindingsSome banks in Dubai are highly suitable for all stages of the money laundering process. However, although certain banks have weak compliance mechanisms, others act in an exemplary manner.Research limitations/implicationsThe qualitative findings are based on semi-structured interviews and are limited to the 60 interviewees’ perspectives.Practical implicationsIdentification of gaps in anti-money laundering mechanisms provides compliance officers, law enforcement agencies and legislators with valuable insights into how money laundering criminals operate.Originality/valueThe existing literature focuses mainly on organizations and the methods they use to combat money laundering. This paper outlines how money launderers operate to avoid detection. Authentic experiences are illustrated. The reader is provided with valuable insights into the minds of money launderers. Both lawful and criminal perspectives are taken into account.
Consumer engagement in social media: scale comparison analysis
Authors: Ferreira Mateus , Zambaldi Felipe , Guerra Diego de Sousa 
Published: January 2020

Purpose
Engagement is a construct that varies according to the subject, object and context; this has been used to justify the coexistence of a variety of construct definitions and scales. Instead of proposing a new scale, this paper aims to create a procedure for comparing scales and to use it to evaluate brand engagement measures in social media.

Design/methodology/approach
This study first defines a procedure for the selection, standardization and comparison of scales; this procedure considers both the classical test theory (CTT) and item response theory (IRT). The authors apply the procedure in a survey of 233 respondents to compare three scales for measuring consumer engagement with brands in social media.

Findings
The establishment of a procedure for scale comparison is useful in assisting researchers to choose specific measures. Results showed that the three scales have similar characteristics, but Vivek et al.’s (2014) scale is recommended when better discrimination between construct dimensions is required, Hollebeek et al.’s (2014) scale could be used as a one-dimensional scale and Dessart et al.’s (2016) reduced scale has better ability to capture information for the affective and cognitive dimensions. None of the scales were very efficient in discriminating weakly and strongly engaged individuals.

Originality/value
This study makes a substantive contribution by proposing a procedure for scale comparison that considers CTT and IRT and shows the advantages, limitations and recommendations for using three different scales of consumer engagement.