bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrasting Impacts of Cultivated Exotics on the Functional Diversity of Domestic Gardens in Three Regions with Different Aridity
Authors: Padullés Cubino Josep , Borowy Dorothy , Knapp Sonja , Lososová Zdeňka , Ricotta Carlo , Siebert Stefan , Cavender-Bares Jeannine , Sol Daniel , Jeliazkov Alienor , Swan Christopher
Published: September 2020

Cultivated exotic plants are often introduced for their aesthetic value and today comprise a substantial fraction of the flora of urban domestic gardens. Yet, their relative contribution to the functional diversity of domestic gardens and how it changes across different climate zones is insufficiently understood. Here, we investigated whether the effects of cultivated exotics on functional diversity of three plant traits related to plant aesthetics (that is, plant showiness, plant height, and leaf area) varied in suburban domestic gardens in three regions (Minnesota, USA; Alt Empordà, Spain; and central South Africa) that differ in aridity. For each garden, we calculated the mean and variance of each plant trait considering all co-occurring species and also splitting them into co-occurring cultivated exotics and natives. Our results revealed that mean plant showiness increased linearly with the proportion of cultivated exotics both across and within studied regions. Moreover, co-occurring cultivated exotics were, on average, showier than natives in all regions, but differences in their trait variances were context-dependent. The interaction between cultivated exotics and aridity explained variation in mean plant height and leaf area better than either predictor alone, with the effect of cultivated exotics being stronger in more arid regions. Accordingly, co-occurring cultivated exotics were taller and had larger leaves than natives in warmer and drier regions, while the opposite was true in cooler and wetter regions. Our study highlights the need to consider the combined effects of exotic species and climate in future studies of urban ecology.
Epidemiology, bacteriology, and clinical characteristics of HACEK bacteremia and endocarditis: a population-based retrospective study
Authors: Berge Andreas , Morenius Christian , Petropoulos Alexandros , Nilson Bo , Rasmussen Magnus
Published: September 2020

The objective was to describe the epidemiology, bacteriology, clinical presentation, risk factors for endocarditis (IE), diagnostic workup, and outcome of patients with bacteremia caused by the non-influenzae Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella genera (HACEK). A retrospective population-based cohort of patients with bacteremia collected from 2012 to 2017 was identified. Clinical data from identified patients were collected from medical records to classify patients, calculate incidences, analyze risk factors of IE, and describe the management and outcome of the cohort. A total of 118 episodes of HACEK bacteremia were identified, of which 27 were definite IE. The incidence of HACEK bacteremia was 5.2 and of HACEK IE 1.2 episodes per 1,000,000 inhabitants per year. Other focal infections were identified in 55 of 118 of the episodes, most commonly within the abdomen (26 episodes). The propensity to cause IE ranged from 62 in Aggregatibacter actinomycetemcomitans to 6% in Eikenella. Risk factors for IE were cardiac implantable electronical device, predisposing cardiac conditions, community acquisition, long duration of symptoms, multiple positive blood cultures, fever, heart murmur, embolization, and unknown origin of infection. The scoring system DENOVA developed to predict IE in bacteremia with Enterococcus faecalis also had a high sensitivity and specificity for predicting IE in HACEK bacteremia. The 30-day mortality was 4% in IE and 15% in non-IE bacteremia, and only one case of relapse was found. IE is common in bacteremia with Aggregatibacter, Cardiobacterium, and Kingella but relatively rare in Haemophilus and Eikenella. Treatment failures are very rare, and DENOVA can be used to evaluate the need for transesophageal echocardiography.
Efficient Genome Editing in Multiple Salmonid Cell Lines Using Ribonucleoprotein Complexes
Authors: Gratacap Remi L. , Jin Ye Hwa , Mantsopoulou Marina , Houston Ross D.
Published: September 2020

Infectious and parasitic diseases have major negative economic and animal welfare impacts on aquaculture of salmonid species. Improved knowledge of the functional basis of host response and genetic resistance to these diseases is key to developing preventative and treatment options. Cell lines provide valuable models to study infectious diseases in salmonids, and genome editing using CRISPR/Cas systems provides an exciting avenue to evaluate the function of specific genes in those systems. While CRISPR/Cas editing has been successfully performed in a Chinook salmon cell line (CHSE-214), there are no reports to date of editing of cell lines derived from the most commercially relevant salmonid species Atlantic salmon and rainbow trout, which are difficult to transduce and therefore edit using lentivirus-mediated methods. In the current study, a method of genome editing of salmonid cell lines using ribonucleoprotein (RNP) complexes was optimised and tested in the most commonly used salmonid fish cell lines: Atlantic salmon (SHK-1 and ASK cell lines), rainbow trout (RTG-2) and Chinook salmon (CHSE-214). Electroporation of RNP based on either Cas9 or Cas12a was efficient at targeted editing of all the tested lines (typically > 90% cells edited), and the choice of enzyme expands the number of potential target sites for editing within the genomes of these species. These optimised protocols will facilitate functional genetic studies in salmonid cell lines, which are widely used as model systems for infectious diseases in aquaculture.
Simulation for skills training in neurosurgery: a systematic review, meta-analysis, and analysis of progressive scholarly acceptance
Authors: Davids Joseph , Manivannan Susruta , Darzi Ara , Giannarou Stamatia , Ashrafian Hutan , Marcus Hani J
Published: September 2020

At a time of significant global unrest and uncertainty surrounding how the delivery of clinical training will unfold over the coming years, we offer a systematic review, meta-analysis, and bibliometric analysis of global studies showing the crucial role simulation will play in training. Our aim was to determine the types of simulators in use, their effectiveness in improving clinical skills, and whether we have reached a point of global acceptance. A PRISMA-guided global systematic review of the neurosurgical simulators available, a meta-analysis of their effectiveness, and an extended analysis of their progressive scholarly acceptance on studies meeting our inclusion criteria of simulation in neurosurgical education were performed. Improvement in procedural knowledge and technical skills was evaluated. Of the identified 7405 studies, 56 studies met the inclusion criteria, collectively reporting 50 simulator types ranging from cadaveric, low-fidelity, and part-task to virtual reality (VR) simulators. In all, 32 studies were included in the meta-analysis, including 7 randomised controlled trials. A random effects, ratio of means effects measure quantified statistically significant improvement in procedural knowledge by 50.2% (ES 0.502; CI 0.355; 0.649,p< 0.001), technical skill including accuracy by 32.5% (ES 0.325; CI − 0.482; − 0.167,p< 0.001), and speed by 25% (ES − 0.25, CI − 0.399; − 0.107,p< 0.001). The initial number of VR studies (n= 91) was approximately double the number of refining studies (n= 45) indicating it is yet to reach progressive scholarly acceptance. There is strong evidence for a beneficial impact of adopting simulation in the improvement of procedural knowledge and technical skill. We show a growing trend towards the adoption of neurosurgical simulators, although we have not fully gained progressive scholarly acceptance for VR-based simulation technologies in neurosurgical education.
Chiral Symmetry Breaking in Large Peptide Systems
Authors: Konstantinov Konstantin K , Konstantinova Alisa F
Published: September 2020

Chiral symmetry breaking in far from equilibrium systems with large number of amino acids and peptides, like a prebiotic Earth, was considered. It was shown that if organic catalysts were abundant, then effective averaging of enantioselectivity would prohibit any symmetry breaking in such systems. It was further argued that non-linear (catalytic) reactions must be very scarce (called the abundance parameter) and catalysts should work on small groups of similar reactions (called the similarity parameter) in order to chiral symmetry breaking have a chance to occur. Models with 20 amino acids and peptide lengths up to three were considered. It was shown that there are preferred ranges of abundance and similarity parameters where the symmetry breaking can occur in the models with catalytic synthesis / catalytic destruction / both catalytic synthesis and catalytic destruction. It was further shown that models with catalytic synthesis and catalytic destruction statistically result in a substantially higher percentage of the models where the symmetry breaking can occur in comparison to the models with just catalytic synthesis or catalytic destruction. It was also shown that when chiral symmetry breaking occurs, then concentrations of some amino acids, which collectively have some mutually beneficial properties, go up, whereas the concentrations of the ones, which don’t have such properties, go down. An open source code of the whole system was provided to ensure that the results can be checked, repeated, and extended further if needed.
Environmental exposure to persistent organic pollutants measured in breast milk of lactating women from an urban area in central Poland
Authors: Grešner Peter , Zieliński Marek , Ligocka Danuta , Polańska Kinga , Wąsowicz Wojciech , Gromadzińska Jolanta
Published: September 2020

Mothers’ milk is considered a channel by means of which new-borns are exposed to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs), environmental pollutants entering food chain and accumulating in fat-rich tissues. In this study, the concentrations of selected PCDDs, PCDFs, and dl-PCBs (a total of 29 substances) in milk samples of 110 breast-feeding women from an urban area were analyzed using the high-resolution gas chromatography/high-resolution mass spectrometry method. Environmental exposure to these substances was expressed by means of the World Health Organization Toxicity Equivalent (WHO-TEQ2005) using the Toxicity Equivalent Factor values from van der Berg et al. (Toxicol. Sci. 93: 223-241, 2006). Concentrations and WHO-TEQ2005 values were then searched for plausible relationships with selected demographic and diet-related factors. The total WHO-TEQ2005 toxicity equivalent for all 29 substances was (mean ± SD) 10.57 ± 4.57 pg/g fat, while the WHO-TEQ2005 levels of PCDDs/PCDFs and dl-PCBs were 7.90 ± 4.17 pg/g fat and 2.67 ± 1.36 pg/g fat, respectively. The concentration and WHO-TEQ2005 toxicity equivalent of dl-PCBs correlated significantly with the mothers’ age (rP = 0.3814, p < 0.00005; rP = 0.2817, p < 0.005, respectively). The total WHO-TEQ2005 toxicity equivalent for all analyzed substances was found to be positively associated with the frequency of consumption of fish and dairy products (p < 0.05 for both associations). These outcomes must, however, be interpreted cautiously due to limited size of the study. The results of this paper may provide a basis for further studies on the exposure to PCDDs, PCDFs, and dl-PCBs, and mechanisms underlying their action.
Annuloplasty for mitral valve repair in degenerative disease: to be flexible or to be rigid? That’s still the question
Authors: Bruno Vito Domenico , Di Tommaso Ettorino , Ascione Raimondo
Published: September 2020

The choice of ring for mitral valve repair is still largely left to the surgeon's preferences and there are no specific guidelines regulating this decision. Despite this previous researches have described important features appertaining to each of the different types of rings currently available. Particularly, the debate is still open in regards to the flexibility that these devices should or should not have. Later in this issue of the Journal, Panicker and colleagues have reported their results with flexible and rigid rings in mitral valve repair. The results are very interesting and once again are highlighting the importance of using the right ring for the right disease.
Do we still need CRS and HIPEC in colorectal cancer in times of modern chemotherapy and immunotherapy?
Authors: Gasser Elisabeth , Kogler Pamela , Lorenz Andreas , Kafka-Ritsch Reinhold , Öfner Dietmar , Perathoner Alexander
Published: September 2020

Peritoneal carcinomatosis from colorectal cancer is associated with a poor prognosis and is usually treated with systemic chemotherapy and immunotherapy alone. In patients with isolated peritoneal carcinomatosis (PC) without nonperitoneal metastases, however, cytoreductive surgery (CRS) has been shown to significantly improve outcome and to achieve even cure in selected patients in combination with systemic therapy. The additional use of a hyperthermic intraperitoneal chemotherapy (HIPEC) is primarily indicated to control microscopical residual tumor tissue in the peritoneal cavity after successful CRS. Another more recent option is the application of an adjuvant HIPEC to prevent peritoneal carcinomatosis in high risk patients with pT4 cancer or perforated cancer at the time of or after primary surgery. The aim of this short review is to highlight the corresponding available literature and assess the role of CRS and HIPEC in the context of modern chemotherapy and immunotherapy.
Zukunft der Arbeit – Implikationen und Herausforderungen durch autonome Informationssysteme
Authors: Neuburger Rahild , Fiedler Marina
Published: September 2020

Autonome Informationssysteme (AIS), die lernen, schlussfolgern und entscheiden und damit eigenständig Programme zur Handlung entwickeln, stellen ein zusätzliches Element im Arbeitskontext dar. Je nach Anwendung führen sie dazu, dass sich die Arbeitsteilung zwischen Mensch und Technologie weiter verschiebt. Zwischen den beiden Extrema – Übernahme der Aufgaben alleine durch das AIS bzw. nur durch den Menschen – eröffnet sich ein breites Spektrum an Aufgaben, die in einer neuartigen Form der Arbeitsteilung durchgeführt werden können. Wir beleuchten diese veränderten Arbeitsbedingungen anhand der drei Felder Unternehmensführung, Human-Ressourcen-Management und Organisation und zeigen auf, welche Anforderungen sich hierdurch an die Kompetenzentwicklung des Menschen stellen.
Exploring childhood temperament as a moderator of the association between adolescent sexual minority status and internalizing and externalizing behavior problems
Authors: Martin‐Storey Alexa , Lemelin Jean‐Pascal , Temcheff Caroline , Déry Michèle
Published: September 2020

Introduction

Sexual minority youth experience worse mental health compared to their heterosexual peers, reflecting the consequences of sexual minority‐based stigma. Previous research has focused on contextual variation to understand variability within this vulnerability. Childhood temperament factors such as negative affect, effortful control and surgency/extraversion are important for understanding differential susceptibility to environmental stressors. The objective of the current study was to understand how childhood temperament factors, measured prior to the most difficult developmental period for sexual minority youth, moderated the association between sexual minority status and internalizing and externalizing behavior problems.

Methods

Youth reporting same‐sex attraction in an ongoing longitudinal project on the development of conduct problems in Quebec, Canada were matched with heterosexual peers, for an analytic sample of 280 youth (62% girls). Structural equation models were used to examine (1) the association between youth‐reported same‐sex attraction (ages 13–16) and parent and youth‐reported internalizing and externalizing problems a year later at ages 14–17, and (2) the moderating role of temperament (ages 6–9) in this association between sexual minority status and internalizing and externalizing problems.

Results

Same‐sex attraction was associated with higher levels of youth‐reported internalizing and externalizing behavior problems. Surgency/extraversion moderated the association between sexual minority status and youth‐reported internalizing and externalizing problems.

Conclusions

These findings suggest that temperament linked to individual visibility may be important for understanding variation in self‐reported mental health among sexual minority youth, and supports the use of developmental constructs like temperament to better understand vulnerability to psychosocial difficulties within this population.
Response of macrobenthic communities to changes in water quality in a subtropical, microtidal estuary (Oso Bay, Texas)
Authors: de Santiago Kevin , Palmer Terence A. , Wetz Michael S. , Beseres Pollack Jennifer
Published: September 2020

The influence of nutrient loading and other anthropogenic stressors is thought to be greater in low inflow, microtidal estuaries, where there is limited water exchange. This 11-month study compared spatial changes in macrofaunal communities adjacent to regions that varied in land cover in Oso Bay, Texas, an estuarine secondary bay with inflow dominated by hypersaline discharge, in addition to discharge from multiple municipal wastewater treatment plants. Macrofauna communities changed in composition with distance away from a wastewater treatment plant in Oso Bay, with the western region of the bay containing different communities than the head and the inlet of the bay. Ostracods were numerically dominant close to the wastewater discharge point. Macrobenthic community composition is most highly correlated with silicate concentrations in the water column. Silicate is negatively correlated with salinity and dissolved oxygen, and positively correlated with nutrients within the bay. Results are relevant for environmental management purposes by demonstrating that point-source discharges can still have ecological effects in hydrologically altered estuaries.
… but what about the Aboriginal and/or Torres Strait Islander Health Worker academic? Transcending the role of ‘unknowing assistant’ in health care and research through higher education: a personal journey
Authors: Stajic Janet
Published: September 2020

Abstract
The Aboriginal and Torres Strait Islander Health Worker/Practitioner (A&TSIHW) workforce provides not only clinical skills but also responds to specific social and cultural needs of the communities they serve bringing knowledge derived from lived and embodied knowledges. The A&TSIHW is a recognised health professional within the Australian health system; however, this workforce continues to be under-supported, under-recognised and under-utilised. A common discourse in literature written about A&TSIHWs focused on the need to empower and enhance the A&TSIHW capabilities, or rendered the A&TSIHW as part of the problem in improving the health of Indigenous peoples. In contrast, articles written by A&TSIHWs, published in the Aboriginal and Islander Health Worker Journal, tell a different story, one about the limitations of the health system in its ability to care for Indigenous peoples, recognising A&TSIHW leadership. This paper deals with two interrelated tensions—the undervaluing of the A&TSIHW as a clinician and the undervaluing of the A&TSIHW as an academic—both of which the author has had to navigate. It explores the specific challenges of the A&TSIHW academic who too seeks recognition beyond that of ‘assistant’ within the research enterprise, drawing upon personal experiences and engagement with educational institutions, including higher education.
Plant- and animal-based diet quality and mortality among US adults: a cohort study
Authors: Keaver Laura , Ruan Mengyuan , Chen Fan , Du Mengxi , Ding Chenyueyi , Wang Jiaqi , Shan Zhilei , Liu Junxiu , Zhang Fang Fang
Published: September 2020

Not all plant-based and animal foods exert the same health effects due to their various nutrient compositions. We aimed to assess the quality of plant-based v. animal foods in relation to mortality in a prospective cohort study. Using data collected from a nationally representative sample of 36 825 adults in the National Health and Nutrition Examination Survey 1999–2014, we developed a de novo Comprehensive Diet Quality Index (cDQI) that assesses the quality of seventeen foods based on the healthfulness and separately scored the quality of eleven plant-based foods in a plant-based Diet Quality Index (pDQI) and six animal foods in an animal-based Diet Quality Index (aDQI). Mortality from all causes, heart disease and cancer were obtained from linkage to the National Death Index up to 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI after multivariable adjustments. During a median follow-up of 8·3 years, 4669 all-cause deaths occurred, including 798 deaths due to heart disease and 1021 due to cancer. Compared with individuals in the lowest quartile, those in the highest quartile of cDQI had a lower risk of all-cause mortality (HR 0·75, 95 % CI 0·65, 0·86; Ptrend < 0·001), which largely reflected the inverse relationship between quality of plant-based foods (pDQI) and all-cause mortality (HR 0·66, 95 % CI 0·58, 0·74; Ptrend < 0·001). No independent association was found for the quality of animal foods (aDQI) and mortality. Our results suggest that consuming healthy plant-based foods is associated with lower all-cause mortality among US adults.
Afterword: Newsprint Worlds and Reading Publics in Colonial Contexts
Authors: Newell Stephanie
Published: September 2020

This article discusses the ways in which newsprint allowed local contributors and readers in colonial settings to think across gender, race, and other core colonial subject-positions. It also asks about the extent to which the central role of men in controlling local print networks has implications for how we conceptualise “publics” and “public spheres” in the colonial era.
Deep‐Time Paleoclimate Proxies
Authors: Macdonald Francis A.
Published: September 2020

Pre‐Cenozoic climate (>66 million years ago) has been reconstructed with climate sensitive sedimentary deposits. However, sedimentary records are inherently local and can be affected by topography and oceanic and atmospheric currents. Additionally, in tectonically active environments, the interpretation of glacigenic rocks can be ambiguous. Temperature and CO2 proxies complement the record of climate sensitive sedimentary rocks. With samples that have been carefully screened for post‐depositional alteration, carbonate clumped isotope thermometry has produced ocean temperature estimates that are consistent with the sedimentary record and CO2 proxy data. Although there are many challenges for quantitative temperature reconstructions through Earth history, maximum temperature estimates are now being extracted across the onset of Cryogenian (720–635 million years ago) snowball Earth glaciations that follow the expected cooling trend.
Divergent Estimates of Forest Photosynthetic Phenology Using Structural and Physiological Vegetation Indices
Authors: Yin Gaofei , Verger Aleixandre , Filella Iolanda , Descals Adrià , Peñuelas Josep
Published: September 2020

The accurate estimation of photosynthetic phenology using vegetation indices (VIs) is important for measuring the interannual variation of atmospheric CO2 concentrations, but the relative performances of structural and physiological VIs remain unclear. We found that structural VIs (normalized difference VI, enhanced VI, and near‐infrared reflectance of vegetation) were suitable for estimating the start of the photosynthetically active season in deciduous broadleaf forests using gross primary production measured by FLUXNET as a benchmark, and a physiological VI (chlorophyll/carotenoid index) was better at identifying the end of the photosynthetically active season for deciduous broadleaf forests and both the start and end of season for evergreen needleleaf forests. The divergent performances were rooted in the combined control of structural and physiological regulations of carbon uptake by plants. Most existing studies of photosynthetic phenology have been based on structural VIs, so we suggest revisiting the dynamics of photosynthetic phenology using physiological VIs, which has significant implications on global plant phenology and carbon uptake studies.
On Energy Cascades in General Flows: A Lagrangian Application
Authors: Jamet Q. , Ajayi A. , Le Sommer J. , Penduff T. , Hogg A. , Dewar W. K.
Published: September 2020

An important characteristic of geophysically turbulent flows is the transfer of energy between scales. Balanced flows pass energy from smaller to larger scales as part of the well‐known upscale cascade, while submesoscale and smaller scale flows can transfer energy eventually to smaller, dissipative scales. Much effort has been put into quantifying these transfers, but a complicating factor in realistic settings is that the underlying flows are often strongly spatially heterogeneous and anisotropic. Furthermore, the flows may be embedded in irregularly shaped domains that can be multiply connected. As a result, straightforward approaches like computing Fourier spatial spectra of nonlinear terms suffer from a number of conceptual issues. In this paper, we develop a method to compute cross‐scale energy transfers in general settings, allowing for arbitrary flow structure, anisotropy, and inhomogeneity. We employ Green's function approach to the kinetic energy equation to relate kinetic energy at a point to its Lagrangian history. A spatial filtering of the resulting equation naturally decomposes kinetic energy into length‐scale‐dependent contributions and describes how the transfer of energy between those scalestakes place. The method is applied to a doubly periodic simulation of vortex merger, resulting in the demonstration of the expected upscale energy cascade. Somewhat novel results are that the energy transfers are dominated by pressure work, rather than kinetic energy exchange, and dissipation is a noticeable influence on the larger scale energy budgets. We also describe, but do not employ here, a technique for developing filters to use in complex domains.
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

Attention-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

The 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

Single 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

Fast 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

The 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

The 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

Complex 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

Nitro-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

Pulmonary 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

The 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

In 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

While 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.
Structured Catalysts and Non-conventional Reactor Designs for Energy Applications
Authors: Ambrosetti Matteo , Balzarotti Riccardo , Fratalocchi Laura , Bracconi Mauro , Groppi Gianpiero , Tronconi Enrico
Published: September 2020

Process intensification is now considered to be the solution for the efficient scaling down of energy-intensive chemical processes to enable the exploitation of small, remote and associated natural gas reservoirs. However, the approach is not trivial and requires the design of innovative catalytic reactor concepts. Structured catalysts are strong candidates for promoting the development of such processes thanks to their superior heat and mass transfer properties. Different types of substrates have been proposed, including honeycomb monoliths, open-cell foams and periodic open cellular structures. Among these, thermally conductive metallic cellular substrates have attracted attention in view of de-bottlenecking heat transfer-limited exo- or endo-thermic processes in tubular reactors. The catalytic activation of these geometries is critical. These structures can be washcoated with a thin layer of catalytic active phase, but the resulting catalyst inventory is limited. A possible way to exploit the advantage provided by conductive structures while increasing catalyst load relies on packing the cavities of the metallic matrix with catalyst pellets. Recently, this new reactor concept has been successfully demonstrated at the lab scale. As an example, we will review herein its application to the intensification of two key processes for the energy scenario: (1) endothermic small-scale methane steam reforming for distributed hydrogen generation; and (2) the production of clean liquid fuels from synthesis gas via exothermic Fischer–Tropsch synthesis.