bluuebunny/crossref_metadata_2025_split huggingface dataset:
The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches
Authors: Yde Ohki Cristine Marie , Grossmann Leoni , Alber Emma , Dwivedi Tanushree , Berger Gregor , Werling Anna Maria , Walitza Susanne , Grünblatt Edna 
Published: September 2020

AbstractAttention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.
Protein kinase D1 phosphorylation of KAT7 enhances its protein stability and promotes replication licensing and cell proliferation
Authors: Liang Yao , Su Yuanyuan , Xu Chenzhong , Zhang Na , Liu Doudou , Li Guodong , Tong Tanjun , Chen Jun 
Published: September 2020

AbstractThe histone acetyltransferase (HAT) KAT7/HBO1/MYST2 plays a crucial role in the pre-replication complex (pre-RC) formation, DNA replication and cell proliferation via acetylation of histone H4 and H3. In a search for protein kinase D1 (PKD1)-interacting proteins, we have identified KAT7 as a potential PKD1 substrate. We show that PKD1 directly interacts and phosphorylates KAT7 at Thr97 and Thr331 in vitro and in vivo. PKD1-mediated phosphorylation of KAT7 enhances its expression levels and stability by reducing its ubiquitination-mediated degradation. Significantly, the phospho-defective mutant KAT7-Thr97/331A attenuates histone H4 acetylation levels, MCM2/6 loading on the chromatin, DNA replication and cell proliferation. Similarly, PKD1 knockdown decreases, whereas the constitutive active mutant PKD1-CA increases histone H4 acetylation levels and MCM2/6 loading on the chromatin. Overall, these results suggest that PKD1-mediated phosphorylation of KAT7 may be required for pre-RC formation and DNA replication.
Prevalence of the mitochondrial 1555 A>G and 1494 C>T mutations in a community-dwelling population in Japan
Authors: Maeda Yasunori , Sasaki Akira , Kasai Shuya , Goto Shinichi , Nishio Shin-ya , Sawada Kaori , Tokuda Itoyo , Itoh Ken , Usami Shin-ichi , Matsubara Atsushi 
Published: September 2020

AbstractSingle nucleotide polymorphisms in mitochondrial DNA, such as mitochondrial 1555 A>G (m.1555 A>G) and mitochondrial 1494 C>T (m.1494 C>T), are known to be causative mutations of nonsyndromic hearing loss following exposure to aminoglycoside antibiotics. The prevalence of the m.1555 A>G and m.1494 C>T mutations has not been reported for the general population in Japan. The purpose of this study was to investigate the prevalence of m.1555 A>G and m.1494 C>T mutations in a community-dwelling population in Japan in order to prevent aminoglycoside-induced hearing loss. We recruited participants older than 20 years of age to the Iwaki Health Promotion Project in 2014, 2015, and 2016, resulting in the recruitment of 1,683 participants. For each participant, we performed a hearing test and a genetic test for the m.1555 A>G and m.1494 C>T mutations using the TaqMan genotyping method. The m.1555 A>G mutation was detected in only 1 of the 1,683 participants (0.06%). This carrier of the m.1555 A>G mutation was a 69-year-old male with bilateral, symmetric, and high-frequency hearing loss. We provided genetic counseling and distributed a drug card advising him to avoid the administration of aminoglycoside antibiotics. In contrast, the m.1494 C>T mutation was not detected in this study population.
Progress toward a capacitively mediated CNOT between two charge qubits in Si/SiGe
Authors: MacQuarrie E. R. , Neyens Samuel F. , Dodson J. P. , Corrigan J. , Thorgrimsson Brandur , Holman Nathan , Palma M. , Edge L. F. , Friesen Mark , Coppersmith S. N. , Eriksson M. A. 
Published: September 2020

AbstractFast operations, an easily tunable Hamiltonian, and a straightforward two-qubit interaction make charge qubits a useful tool for benchmarking device performance and exploring two-qubit dynamics. Here, we tune a linear chain of four Si/SiGe quantum dots to host two double dot charge qubits. Using the capacitance between the double dots to mediate a strong two-qubit interaction, we simultaneously drive coherent transitions to generate correlations between the qubits. We then sequentially pulse the qubits to drive one qubit conditionally on the state of the other. We find that a conditional π-rotation can be driven in just 74 ps with a modest fidelity demonstrating the possibility of two-qubit operations with a 13.5 GHz clockspeed.
Emerging contaminants affect the microbiome of water systems—strategies for their mitigation
Authors: Gomes Inês B. , Maillard Jean-Yves , Simões Lúcia C. , Simões Manuel 
Published: September 2020

AbstractThe presence of emerging contaminants (ECs) in the environment has been consistently recognized as a worldwide concern. ECs may be defined as chemicals or materials found in the environment at trace concentrations with potential, perceived, or real risk to the “One Health” trilogy (environment, human, and animal health). The main concern regarding pharmaceuticals and in particular antibiotics is the widespread dissemination of antimicrobial resistance. Nevertheless, non-antimicrobials also interact with microorganisms in both bulk phase and in biofilms. In fact, drugs not developed for antimicrobial chemotherapy can exert an antimicrobial action and, therefore, a selective pressure on microorganisms. This review aims to provide answers to questions typically ignored in epidemiological and environmental monitoring studies with a focus on water systems, particularly drinking water (DW): Do ECs exposure changes the behavior of environmental microorganisms? May non-antibiotic ECs affect tolerance to antimicrobials? Do ECs interfere with biofilm function? Are ECs-induced changes in microbial behavior of public health concern? Nowadays, the answers to these questions are still very limited. However, this study demonstrates that some ECs have significant effects in microbial behavior. The most studied ECs are pharmaceuticals, particularly antibiotics, carbamazepine and diclofenac. The pressure caused by antibiotic and other antimicrobial agents on the acquisition and spread of antibiotic resistance seems to be unquestionable. However, regarding the effects of ECs on the development and behavior of biofilms, the conclusions of different studies are still controversial. The dissimilar findings propose that standardized tests are needed for an accurate assessment on the effects of ECs in the microbiome of water systems. The variability of experimental conditions, combined with the presence of mixtures of ECs as well as the lack of information about the effects of non-pharmaceutical ECs constitute the main challenge to be overcome in order to improve ECs prioritization.
Decoding mitochondrial heterogeneity in single muscle fibres by imaging mass cytometry
Authors: Warren Charlotte , McDonald David , Capaldi Roderick , Deehan David , Taylor Robert W. , Filby Andrew , Turnbull Doug M. , Lawless Conor , Vincent Amy E. 
Published: September 2020

AbstractThe study of skeletal muscle continues to support the accurate diagnosis of mitochondrial disease and remains important in delineating molecular disease mechanisms. The heterogeneous expression of oxidative phosphorylation proteins and resulting respiratory deficiency are both characteristic findings in mitochondrial disease, hence the rigorous assessment of these at a single cell level is incredibly powerful. Currently, the number of proteins that can be assessed in individual fibres from a single section by immunohistochemistry is limited but imaging mass cytometry (IMC) enables the quantification of further, discrete proteins in individual cells. We have developed a novel workflow and bespoke analysis for applying IMC in skeletal muscle biopsies from patients with genetically-characterised mitochondrial disease, investigating the distribution of nine mitochondrial proteins in thousands of single muscle fibres. Using a semi-automated analysis pipeline, we demonstrate the accurate quantification of protein levels using IMC, providing an accurate measure of oxidative phosphorylation deficiency for complexes I–V at the single cell level. We demonstrate signatures of oxidative phosphorylation deficiency for common mtDNA variants and nuclear-encoded complex I variants and a compensatory upregulation of unaffected oxidative phosphorylation components. This technique can now be universally applied to evaluate a wide range of skeletal muscle disorders and protein targets.
Structure and mechanism of a dehydratase/decarboxylase enzyme couple involved in polyketide β-methyl branch incorporation
Authors: Nair Asha V. , Robson Alice , Ackrill Thomas D. , Till Marisa , Byrne Matthew J. , Back Catherine R. , Tiwari Kavita , Davies Jonathan A. , Willis Christine L. , Race Paul R. 
Published: September 2020

AbstractComplex polyketides of bacterial origin are biosynthesised by giant assembly-line like megaenzymes of the type 1 modular polyketide synthase (PKS) class. The trans-AT family of modular PKSs, whose biosynthetic frameworks diverge significantly from those of the archetypal cis-AT type systems represent a new paradigm in natural product enzymology. One of the most distinctive enzymatic features common to trans-AT PKSs is their ability to introduce methyl groups at positions β to the thiol ester in the growing polyketide chain. This activity is achieved through the action of a five protein HCS cassette, comprising a ketosynthase, a 3-hydroxy-3-methylglutaryl-CoA synthase, a dehydratase, a decarboxylase and a dedicated acyl carrier protein. Here we report a molecular level description, achieved using a combination of X-ray crystallography, in vitro enzyme assays and site-directed mutagenesis, of the bacillaene synthase dehydratase/decarboxylase enzyme couple PksH/PksI, responsible for the final two steps in β-methyl branch installation in this trans-AT PKS. Our work provides detailed mechanistic insight into this biosynthetic peculiarity and establishes a molecular framework for HCS cassette enzyme exploitation and manipulation, which has future potential value in guiding efforts in the targeted synthesis of functionally optimised ‘non-natural’ natural products.
Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis
Authors: Mollenhauer Martin , Mehrkens Dennis , Klinke Anna , Lange Max , Remane Lisa , Friedrichs Kai , Braumann Simon , Geißen Simon , Simsekyilmaz Sakine , Nettersheim Felix S. , Lee Samuel , Peinkofer Gabriel , Geisler Anne C. , Geis Bianca , Schwoerer Alexander P. , Carrier Lucie , Freeman Bruce A. , Dewenter Matthias , Luo Xiaojing , El-Armouche Ali , Wagner Michael , Adam Matti , Baldus Stephan , Rudolph Volker 
Published: September 2020

AbstractNitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.
Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
Authors: Wahlund Casper J. E. , Gucluler Akpinar Gozde , Steiner Loïc , Ibrahim Ahmed , Bandeira Elga , Lepzien Rico , Lukic Ana , Smed-Sörensen Anna , Kullberg Susanna , Eklund Anders , Grunewald Johan , Gabrielsson Susanne 
Published: September 2020

AbstractPulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.
A novel method for achieving an optimal classification of the proteinogenic amino acids
Authors: Then Andre , Mácha Karel , Ibrahim Bashar , Schuster Stefan 
Published: September 2020

AbstractThe classification of proteinogenic amino acids is crucial for understanding their commonalities as well as their differences to provide a hint for why life settled on the usage of precisely those amino acids. It is also crucial for predicting electrostatic, hydrophobic, stacking and other interactions, for assessing conservation in multiple alignments and many other applications. While several methods have been proposed to find “the” optimal classification, they have several shortcomings, such as the lack of efficiency and interpretability or an unnecessarily high number of discriminating features. In this study, we propose a novel method involving a repeated binary separation via a minimum amount of five features (such as hydrophobicity or volume) expressed by numerical values for amino acid characteristics. The features are extracted from the AAindex database. By simple separation at the medians, we successfully derive the five properties volume, electron–ion-interaction potential, hydrophobicity, α-helix propensity, and π-helix propensity. We extend our analysis to separations other than by the median. We further score our combinations based on how natural the separations are.
Analysis of temporal correlation in heart rate variability through maximum entropy principle in a minimal pairwise glassy model
Authors: Agliari Elena , Alemanno Francesco , Barra Adriano , Barra Orazio Antonio , Fachechi Alberto , Vento Lorenzo Franceschi , Moretti Luciano 
Published: September 2020

AbstractIn this work we apply statistical mechanics tools to infer cardiac pathologies over a sample of M patients whose heart rate variability has been recorded via 24 h Holter device and that are divided in different classes according to their clinical status (providing a repository of labelled data). Considering the set of inter-beat interval sequences $$\{\mathbf {r}(i) \} = \{ r_1(i), r_2(i), \ldots , \}$$

{
r

(
i
)

}

=

{

r
1

(
i
)

,

r
2

(
i
)

,
…
,
}

, with $$i=1,\ldots ,M$$

i
=
1
,
…
,
M

, we estimate their probability distribution $$P(\mathbf {r})$$

P
(
r
)

exploiting the maximum entropy principle. By setting constraints on the first and on the second moment we obtain an effective pairwise $$(r_n,r_m)$$

(

r
n

,

r
m

)

model, whose parameters are shown to depend on the clinical status of the patient. In order to check this framework, we generate synthetic data from our model and we show that their distribution is in excellent agreement with the one obtained from experimental data. Further, our model can be related to a one-dimensional spin-glass with quenched long-range couplings decaying with the spin–spin distance as a power-law. This allows us to speculate that the 1/f noise typical of heart-rate variability may stem from the interplay between the parasympathetic and orthosympathetic systems.
Dynamic regulation of the cholinergic system in the spinal central nervous system
Authors: Rima Mohamad , Lattouf Yara , Abi Younes Maroun , Bullier Erika , Legendre Pascal , Mangin Jean-Marie , Hong Elim 
Published: September 2020

AbstractWhile the role of cholinergic neurotransmission from motoneurons is well established during neuromuscular development, whether it regulates central nervous system development in the spinal cord is unclear. Zebrafish presents a powerful model to investigate how the cholinergic system is set up and evolves during neural circuit formation. In this study, we carried out a detailed spatiotemporal analysis of the cholinergic system in embryonic and larval zebrafish. In 1-day-old embryos, we show that spinal motoneurons express presynaptic cholinergic genes including choline acetyltransferase (chata), vesicular acetylcholine transporters (vachta, vachtb), high-affinity choline transporter (hacta) and acetylcholinesterase (ache), while nicotinic acetylcholine receptor (nAChR) subunits are mainly expressed in interneurons. However, in 3-day-old embryos, we found an unexpected decrease in presynaptic cholinergic transcript expression in a rostral to caudal gradient in the spinal cord, which continued during development. On the contrary, nAChR subunits remained highly expressed throughout the spinal cord. We found that protein and enzymatic activities of presynaptic cholinergic genes were also reduced in the rostral spinal cord. Our work demonstrating that cholinergic genes are initially expressed in the embryonic spinal cord, which is dynamically downregulated during development suggests that cholinergic signaling may play a pivotal role during the formation of intra-spinal locomotor circuit.
Sentence-Based Experience Logging in New Hearing Aid Users
Authors: Lund Katja , Ordoñez Rodrigo , Nielsen Jens Bo , Hammershøi Dorte 
Published: September 2020

Purpose
The aim of this study was to develop a tool to gain insight into the daily experiences of new hearing aid users and to shed light on aspects of aided performance that may not be unveiled through standard questionnaires.

Method
The tool is developed based on clinical observations, patient experiences, expert involvement, and existing validated hearing rehabilitation questionnaires.

Results
An online tool for collecting data related to hearing aid use was developed. The tool is based on 453 prefabricated sentences representing experiences within 13 categories related to hearing aid use.

Conclusions
The tool has the potential to reflect a wide range of individual experiences with hearing aid use, including auditory and nonauditory aspects. These experiences may hold important knowledge for both the patient and the professional in the hearing rehabilitation process.
Potential for Cognitive Communication Impairment in COVID-19 Survivors: A Call to Action for Speech-Language Pathologists
Authors: Ramage Amy E. 
Published: September 2020

Purpose

Severe acute respiratory syndrome coronavirus 2 is the virus resulting in COVID-19 infections in nearly 4.3 million Americans with COVID-19 in the United States as of July 29, 2020, with nearly 150,000 deaths and hundreds of thousands of survivors (
https://www.coronavirus.jhu.edu/map.html
). This tutorial reviews (a) what has been reported about neurological insults in cases of COVID-19 infection, (b) what is known from similar conditions in other disorders, and (c) how that combined information can inform clinical decision making.

Method
PubMed and the Cochrane Central Register of Controlled Trials were searched for COVID-19 or other coronavirus infections, cognitive impairment observed following critical care, and disorders for which intermittent or chronic hypoxia is characteristic. These were combined with searches relating to cognition, brain, and communication. All searches were conducted between April 8 and May 23, 2020. Meta-analyses and randomized clinical trials addressing other critical illnesses were also included to extend findings to potential cognitive communication outcomes following COVID-19.

Results
COVID-19 infection results in a combination of (a) respiratory infection with mechanical ventilation secondary to inadequate oxygenation, (b) inflammatory system reactivity, and (c) increased blood clotting factors. These affect central nervous system function incurring long-term cognitive communication impairment in a proportion of survivors. Diagnostic and intervention approaches for such impairments are discussed.

Conclusions
The existing literature on cognitive sequela of COVID-19 infection is small to date, but much can be learned from similar viral infections and disorders. Although COVID-19 is novel, the speech-language pathology approaches to evaluation and intervention of other populations of critical care patients are applicable. However, speech-language pathologists have not routinely been involved in these patients' acute care. As such, this is a call to action to speech-language pathologists to address the unprecedented numbers of patients who will need their services early in the disease process and throughout recovery.
Perceptual Dimensions Underlying Tinnitus-Like Sounds
Authors: Lentz Jennifer J. , He Yuan 
Published: September 2020

Purpose
The goal of this study was to establish the perceptual underpinnings of the terms that are commonly used by patients when describing the quality of their tinnitus.

Method
Using a free-classification method, 15 subjects with normal hearing placed 60 different tinnitus-like sounds into similarity clusters on a grid. Multidimensional scaling, hierarchical clustering, and acoustic analyses were used to determine the acoustic underpinnings of the perceptual dimensions and perceptual similarity.

Results
Multidimensional scaling revealed three different perceptual dimensions (pitch, modulation depth + spectral elements, and envelope rate). Hierarchical clustering revealed five explicit similarity clusters: tonal, steady noise, pulsatile, low-frequency fluctuating noise, and high-frequency fluctuating.

Conclusions
Results are consistent with tinnitus perceptions falling into a small set of categories that can be characterized by their acoustics. As a result, there is the potential to develop different tools to assess tinnitus using a variety of different sounds.