bluuebunny/crossref_metadata_2025 huggingface dataset:
The class II histone deacetylases as therapeutic targets for Parkinson’s disease
Authors: Mazzocchi Martina , Collins Louise M , Sullivan Aideen M. , O'Keeffe Gerard W.
Published: May 2020

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by specific motor impairments. The neuropathological hallmarks of PD include progressive degeneration of midbrain dopaminergic neurons, and loss of their axonal projections to the striatum. Additionally, there is progressive accumulation and spread of intracellular aggregates of α-synuclein. Although dopamine-replacement pharmacotherapy can treat PD symptoms in the short-term, there is a critical need for the development of disease-modifying therapies based on an understanding of the underlying disease mechanisms. One such mechanism is histone acetylation, which is a common epigenetic modification that alters gene transcription. A number of studies have described alterations in histone acetylation in the brains of PD patients. Moreover, α-synuclein accumulation has been linked to alterations in histone acetylation and pharmacological strategies aimed at modulating histone acetylation are under investigation as novel approaches to disease modification in PD. Currently, such strategies are focused predominantly on pan-inhibition of histone deacetylase (HDAC) enzymes. Inhibition of specific individual HDAC enzymes is a more targeted strategy that may allow for future clinical translation. However, the most appropriate class of HDACs that should be targeted for neuroprotection in PD is still unclear. Recent work has shed new light on the role of class-II HDACs in dopaminergic degeneration. For this reason, here we describe the regulation of histone acetylation, outline the evidence for alterations in histone acetylation in the PD brain, and focus on the roles of class II HDACs and the potential of class-II HDAC inhibition as a therapeutic approach for neuroprotection in PD.
Distances to the supernova remnants in the inner disk
Authors: Wang Shu , Zhang Chengyu , Jiang Biwei , Zhao He , Chen Bingqiu , Chen Xiaodian , Gao Jian , Liu Jifeng
Published: May 2020

Context. Distance measurements of supernova remnants (SNRs) are essential as accurate estimates of physical size, dust masses, and some other properties of SNRs depend critically on accurate distance measurements. However, the determination of SNR distances is still a tough task.

Aims. Red clump stars (RCs) have a long history of being used as standard candles. In this work, we take RCs as tracers to determine the distances to a large group of SNRs in the inner disk.

Methods. We first selected RC stars based on the near-infrared (IR) color-magnitude diagram. Then the distance to and extinction of RC stars were calculated. To extend the measurable range of distance, we combined near-IR photometric data from the 2MASS survey with the deeper UKIDSS and VVV surveys. With the help of the Gaia parallaxes, we also removed contaminants, including dwarfs and giants. Because an SN explosion compresses the surrounding interstellar medium, the SNR region would become denser and exhibit higher extinction than the surroundings. The distance of an SNR is then recognized by the position where the extinction and its gradient is higher than that of the ambient medium.

Results. A total of 63 SNRs distances in the Galactic inner disk were determined and divided into three Levels A, B, and C with decreasing reliability. The distances to 43 SNRs are well determined with reliability A or B. The diameters and dust masses of SNRs were estimated with the obtained distance and extinction.
Binary evolution along the red giant branch with BINSTAR: The barium star perspective
Authors: Escorza A. , Siess L. , Van Winckel H. , Jorissen A.
Published: May 2020

Barium (Ba), CH, and extrinsic or Tc-poor S-type stars are evolved low- and intermediate-mass stars that show enhancement of slow-neutron-capture-process elements on their surface, an indication of mass accretion from a former asymptotic giant branch companion, which is now a white dwarf (WD). Ba and CH stars can be found in the main-sequence (MS), the sub-giant, and the giant phase, while extrinsic S-type stars populate the giant branches only. As these polluted stars evolve, they might be involved in a second phase of interaction with their now white dwarf companion. In this paper, we consider systems composed of a main-sequence Ba star and a WD companion when the former evolves along the red giant branch (RGB). We want to determine if the orbital properties of the known population of Ba, CH, and S giants can be inferred from the evolution of their suspected dwarf progenitors. For this purpose, we used the BINSTAR binary evolution code and model MS+WD binary systems, considering different binary interaction mechanisms, such as a tidally enhanced wind mass loss, and a reduced circularisation efficiency. To explore their impact on the second RGB ascent, we compared the modelled orbits with the observed period and eccentricity distributions of Ba and related giants. We show that, independently of the considered mechanism, there is a strong period cut-off below which core-He burning stars should not be found in binary systems with a WD companion. This limit is shorter for more massive RGB stars and for more metal-poor systems. However, we still find a few low-mass short-period giant systems that are difficult to explain with our models, as well as two systems with very high eccentricities.
C18O,13CO, and12CO abundances and excitation temperatures in the Orion B molecular cloud
Authors: Roueff Antoine , Gerin Maryvonne , Gratier Pierre , Levrier François , Pety Jérôme , Gaudel Mathilde , Goicoechea Javier R. , Orkisz Jan H. , de Souza Magalhaes Victor , Vono Maxime , Bardeau Sébastien , Bron Emeric , Chanussot Jocelyn , Chainais Pierre , Guzman Viviana V. , Hughes Annie , Kainulainen Jouni , Languignon David , Le Bourlot Jacques , Le Petit Franck , Liszt Harvey S. , Marchal Antoine , Miville-Deschênes Marc-Antoine , Peretto Nicolas , Roueff Evelyne , Sievers Albrecht
Published: May 2020

Context.CO isotopologue transitions are routinely observed in molecular clouds for the purpose of probing the column density of the gas and the elemental ratios of carbon and oxygen, in addition to tracing the kinematics of the environment.

Aims.Our study is aimed at estimating the abundances, excitation temperatures, velocity field, and velocity dispersions of the three main CO isotopologues towards a subset of the Orion B molecular cloud, which includes IC 434, NGC 2023, and the Horsehead pillar.

Methods.We used the Cramer Rao bound (CRB) technique to analyze and estimate the precision of the physical parameters in the framework of local-thermodynamic-equilibrium (LTE) excitation and radiative transfer with added white Gaussian noise. We propose a maximum likelihood estimator to infer the physical conditions from the 1–0 and 2–1 transitions of CO isotopologues. Simulations show that this estimator is unbiased and proves efficient for a common range of excitation temperatures and column densities (Tex> 6 K,N> 1014−1015  cm−2).

Results.Contrary to general assumptions, the various CO isotopologues have distinct excitation temperatures and the line intensity ratios between different isotopologues do not accurately reflect the column density ratios. We find mean fractional abundances that are consistent with previous determinations towards other molecular clouds. However, significant local deviations are inferred, not only in regions exposed to the UV radiation field, but also in shielded regions. These deviations result from the competition between selective photodissociation, chemical fractionation, and depletion on grain surfaces. We observe that the velocity dispersion of the C18O emission is 10% smaller than that of13CO. The substantial gain resulting from the simultaneous analysis of two different rotational transitions of the same species is rigorously quantified.

Conclusions.The CRB technique is a promising avenue for analyzing the estimation of physical parameters from the fit of spectral lines. Future works will generalize its application to non-LTE excitation and radiative transfer methods.
The variation of carbon abundance in galaxies and its implications
Authors: Romano D. , Franchini M. , Grisoni V. , Spitoni E. , Matteucci F. , Morossi C.
Published: May 2020

The trends of chemical abundances and abundance ratios observed in stars of different ages, kinematics, and metallicities bear the imprints of several physical processes which concur, thus shaping the host galaxy properties. By inspecting these trends, we obtain precious information on stellar nucleosynthesis, the stellar mass spectrum, the timescale of structure formation, the efficiency of star formation, as well as any inward or outward flows of gas. In this paper, we analyse recent determinations of carbon-to-iron and carbon-to-oxygen abundance ratios in different environments (the Milky Way and elliptical galaxies), using our latest chemical evolution models that implement up-to-date stellar yields and rely on the tight constraints provided by asteroseismic stellar ages, whenever available. A scenario where most carbon is produced by rotating massive stars, with yields largely dependent on the metallicity of the parent proto-star clouds, allowed us to simultaneously fit the high-quality data available for the local Galactic components (thick and thin discs) and for microlensed dwarf stars in the Galactic bulge, as well as the abundance ratios inferred for massive elliptical galaxies. Nevertheless, more efforts are needed from both observers and theoreticians in order to base these conclusions on firmer ground.
Analysis of control problems of nonmontone semilinear elliptic equations
Authors: Casas Eduardo , Mateos Mariano , Rösch Arnd
Published: May 2020

In this paper we study optimal control problems governed by a semilinear elliptic equation. The equation is nonmonotone due to the presence of a convection term, despite the monotonocity of the nonlinear term. The resulting operator is neither monotone nor coervive. However, by using conveniently a comparison principle we prove existence and uniqueness of solution for the state equation. In addition, we prove some regularity of the solution and differentiability of the relation control-to-state. This allows us to derive first and second order conditions for local optimality.
Design and development of pressure sensor based on Fiber Bragg Grating (FBG) for ocean applications
Authors: Vaddadi Venkata Satya Chidambara Swamy , Parne Saidi Reddy , Afzulpurkar Sanjeev , Prabhu Desai Shivanand , Vadakke Parambil Vijeesh
Published: May 2020

A Fiber Bragg Grating (FBG) based sensors has been designed, fabricated and is being prototyped to measure the ocean water column pressure. To measure the pressure variation, a compact design is made by using stainless steel disks and rubber “O” rings in a closed air cavity setup. The pressure in static freshwater column ranging from 0 to 0.04 MPa was gauged, using closed air cavity setup. Also, another “T” shaped design, for testing, has been made of solid stainless-steel tube with the open-air cavity for an extended range of pressure sensing. By using an oil pressure pump and open-air cavity setup, pressure values from 0 to 0.5 MPa have been measured. In both setups same thickness of copper, stainless steel diaphragms are used to measure the pressure. Range of measurements has been carried out to test both the setups. Results indicate that the pressure sensitivity in closed air cavity setup is 24.95 nm/MPa with linearity 99.72%. In the open-air cavity, setup is 16.22 nm/MPa with linearity 99.34% is achieved. Simulation and experimental studies are performed to validate the efficacy of the designed FBG pressure sensor.
Analysis of a stabilized finite element approximation for a linearized logarithmic reformulation of the viscoelastic flow problem
Authors: Codina Ramon , Moreno Laura
Published: May 2020

In this paper we present the numerical analysis of a finite element method for a linearized viscoelastic flow problem. In particular, we analyze a linearization of the logarithmic reformulation of the problem, which in particular should be able to produce results for Weissenberg numbers higher than the standard one. In order to be able to use the same interpolation for all the unknowns (velocity, pressure and logarithm of the conformation tensor), we employ a stabilized finite element formulation based on the Variational Multi-Scale concept. The study of the linearized problem already serves to show why the logarithmic reformulation performs better than the standard one for high Weissenberg numbers; this is reflected in the stability and error estimates that we provide in this paper.
Des tests génétiques pour prédire des maladies communes
Authors: Turrini Mauro , Connault Jérôme , Bourgain Catherine
Published: May 2020

Introduit au lendemain de l’identification des « thrombophilies non rares » (TNR), au milieu des années 1990 afin de prédire et de prévenir la maladie thromboembolique veineuse (MTEV), le bilan génétique pour ces thrombophilies est un exemple assez rare de test génétique de susceptibilité pour une maladie complexe, à avoir franchi le pas d’un véritable usage de routine en clinique. Bien que ce test soit le plus répandu des tests de génétique post-natale en France, son usage (À qui proposer le test ? Que faire des résultats?) fait encore l’objet de débats. Cet article analyse la trajectoire de régulation clinique de ce test et illustre l’importance du contexte spécifique d’usage pour comprendre sa diffusion. Cette analyse vise à nourrir une réflexion plus générale sur les enjeux que pose l’intégration clinique des tests génétiques pour les maladies communes, en considérant notamment les modalités de définition de l’utilité clinique d’un test (statistiqueversusbiologique), des sujets du test (le cas indexversusses apparentés), et des critères en sous-tendant l’accès (modalités des calculs médico-économiques).
Scores polygéniques et risque de cancer
Authors: Jordan Bertrand
Published: May 2020

Risk assessment for a cancer type with moderate heritability can be accurately performed using a relatively small number of SNPs detected by GWAS analyses to calculate a polygenic risk score (PRS) that has definite clinical utility.
Prevention of Pregnancy Complications in Antiphospholipid Syndrome
Authors: Czwalinna Andreas , Bergmann Frauke
Published: May 2020

Despite a lot of research on antiphospholipid antibodies (aPL), standardization of test systems, and better definition of its clinical symptoms, the pathomechanism of this acquired autoimmune disease is not yet fully explained. Progress in treatment increased the live birth rate in 70 to 80% of women suffering from obstetric antiphospholipid syndrome (OAPS). However, still 20 to 30% will develop adverse pregnancy outcome. Lack of awareness of this disorder as the cause for pregnancy complications is very harmful to mothers and to their newborns. Complications can be avoided or minimized by proper treatment. The aim of this article is to increase the awareness of gynecologists and medical personal for OAPS.
Augenärztliches Screening für Menschen mit geistiger und Mehrfachbehinderung
Authors: Grundel Bastian , Stech Milena , Bründer Marie-Christine , Böhringer Daniel , Haug Thomas , Ness Thomas , Reinhard Thomas
Published: May 2020

Einführung Special Olympics Deutschland (SOD) ist die deutsche Organisation der weltweit größten Sportbewegung für Menschen mit geistiger und mehrfacher Behinderung: Viele Landesverbände von SOD bieten mittlerweile alle 4 Jahre Sommerspiele für diese Klientel an, an denen Kinder und Erwachsene aus dem jeweiligen Bundesland teilnehmen. Während der Landessommerspiele von SO Baden-Württemberg in Offenburg im Jahr 2017 konnten die Athletinnen und Athleten im Rahmen des Gesundheitsprogramms „Opening Eyes – Besser Sehen“ an einem augenärztlichen Screening teilnehmen.

Methoden Optiker und Optometristen erhoben die Anamnese und Refraktion, prüften auf Farbfehlsichtigkeiten, Sehschärfe (Ferne und Nähe) sowie den orthoptischen Status. Insgesamt 4 erfahrene Ärzte in Weiterbildung und Fachärzte der Klinik für Augenheilkunde des Universitätsklinikums Freiburg führten Spaltlampenuntersuchungen, Funduskopie und Augendruckmessungen durch. Bei Bedarf wurde eine Funduskopie in Mydriase bzw. eine OCT-Untersuchung angeschlossen.

Ergebnisse Insgesamt wurden 166 Personen untersucht (48% weiblich = 80; 52% männlich = 86). Der Abdecktest war in etwa 45% der Fälle in der Ferne und in 47% der Fälle in der Nähe auffällig. Sechs bzw. 11% der Patienten gaben Doppelbilder an (9/156; 17/156; jeweils Ferne und Nähe). Eine auffällige Farbsehprüfung mit weniger als 9 von 9 erkannten CVTM-Testtafeln (Color Vision Testing Made Easy nach Waggoner) wurde bei 8% (11/143) dokumentiert. Fundusauffälligkeiten sahen wir in 13% der Fälle (16/125). 41% (48/118) benötigten eine neue Brillenverschreibung. 29% (45/157) gaben eine Überempfindlichkeit gegenüber Licht an. Jeder 2. Teilnehmer hatte in den letzten 3 Jahren einen Augenarzttermin wahrgenommen; dennoch ergab die Erhebung in 10% (16/160), dass noch kein Augenarztbesuch stattgefunden hatte. In 4% der Fälle wurde eine notfallmäßige Vorstellung beim niedergelassenen Augenarzt empfohlen (z. B. im Falle eines akuten Keratokonus oder aufgrund eines erhöhten
Augeninnendrucks). Eine optionale Behandlung (z. B. wegen eines Trockenen Auges) wurde in 40% der Fälle (66/166) empfohlen.

Diskussion Menschen mit geistiger Behinderung beklagen allgemeine Probleme mit den Augen oder neu aufgetretene Sehprobleme nicht zwangsläufig und unmittelbar. Zusätzlich besteht möglicherweise ein eingeschränkter Zugang zur augenärztlichen Versorgung im Vergleich zu Menschen ohne geistige Behinderung. Aufgrund der 4% behandlungsbedürftiger Diagnosen sowie der 53% der Teilnehmer mit nicht optimalem Refraktionsausgleich erscheint eine augenärztliche Begleitung von Special Olympics sinnvoll, sollte verstetigt und mit öffentlichen Mitteln unterstützt werden.
Bempedoinsäure – Wirkmechanismus und klinische Studien
Authors: Katzmann Julius L. , Laufs Ulrich
Published: May 2020

Bempedoinsäure (ETC-1002) ist ein neuartiger Wirkstoff zur Behandlung der LDL-Hypercholesterinämie. Bempedoinsäure inhibiert das Enzym ATP-Citrat-Lyase, das im selben Stoffwechselweg liegt wie das Schlüsselenzym der Cholesterinbiosynthese und Angriffsort der Statine, die HMG-CoA-Reduktase. Bempedoinsäure wird als Prodrug appliziert und durch ein spezifisches Enzym in der Leber aktiviert, welches im Skelettmuskel nicht exprimiert wird. Randomisierte Studien zeigen eine Senkung des LDL-Cholesterins durch Bempedoinsäure; diese ist ausgeprägter bei statinnaiven Patienten und synergistisch mit Ezetimib. Die Verträglichkeit ist auch bei Patienten mit statinassoziierten Muskelschmerzen gut. Es gibt Hinweise auf eine geringe Erhöhung der Harnsäure und eine mögliche Verbesserung der Glukosetoleranz. C-reaktives Protein wird um ca. 25% gesenkt. Eine Endpunktstudie mit 12 600 Patienten mit manifester Atherosklerose und Unverträglichkeit von Statinen läuft, Ergebnisse werden 2022
erwartet. Bempedoinsäure stellt eine zukünftige Therapieoption für Patienten mit nicht erreichten LDL-Cholesterin-Zielwerten insbesondere aufgrund von statinassoziierten Muskelschmerzen dar.
Diagnosis and Treatment of Postthrombotic Syndrome
Authors: Bruning Guido , Woitalla-Bruning Jasmin , Queisser Anne-Caroline , Buhr Johanna Katharina
Published: May 2020

After acute treatment of deep vein thrombosis, not only the risk but also associated side effects of postthrombotic syndrome (PTS) are often underestimated.

There are essentially two main types of PTS.

1. Obstructive type—no sufficient recanalization of the deep vein.

2. Refluctive type—sufficient recanalization of the deep vein, but insufficient venous valves in conjunction with venous reflux.

A statement regarding deep vein recanalization and venous valve function can be made at the earliest after 6 months.

PTS is often diagnosed without appropriate medical history. However, the assessment of the degree of recanalization and venous reflux is paramount to the medical prognosis. In our opinion, beside proximal thrombosis, sufficient recanalization combined with a strong venous reflux, especially in the popliteal vein, works as a powerful predictor for an unfavorable and fast progression of PTS and chronic venous insufficiency. Thus, the obstructive type is prognostically more favorable. For PTS in general, consistent compression therapy represents the first-line treatment option.

With concomitant varicosis, one should assess whether the varicose veins represent primary varicosis with reflux or secondary varicosis without reflux. Especially in the presence of venous ulcers, the elimination of concomitant primary varicosis leads to an improved prognosis. Moist wound treatment is considered to be the standard treatment for all wounds undergoing secondary healing. A standardized set of topical therapeutic agents also facilitates the treatment. In individual cases “ulcershaving” and mesh graft transplantation proved to be successful.
Role of Basal Hormones on Sweat Rate and Sweat
Na+  Loss in Elite Women Soccer
Players
Authors: Castro-Sepulveda Mauricio , Cancino Jorge , Jannas-Vela Sebastian , Jesam Francisca , Lobos Casandra , Del Coso Juan , Zbinden-Foncea Hermann
Published: May 2020

We aimed to determine whether basal concentrations of testosterone, cortisol or
the ratio testosterone/cortisol were related to sweat
Na+ loss, sweat Na+ concentration
([Na+]) and sweat rate during exercise. Twenty-two female
elite soccer players participated in the study. Testosterone and cortisol were
measured in blood samples before exercise. Sweat samples were collected during a
training session (~20°C, ~30% RH, and
~0.55 m/s of wind speed) to measure sweat
[Na+]. Sweat rate was determined by considering the
difference between post-and pre-body weight, along with the amount of liquid
consumed. During exercise, sweat Na+ loss
(0.33[0.19] g/h) and sweat rate (0.49[0.20] L/h)
were related to basal testosterone concentration
(1.4[0.4] pg/mL) (r=0.54; r=0.55, respectively;
p<0.05), but not with basal cortisol concentration
(119.2[24.2] ng/mL) nor testosterone/cortisol ratio
(0.012[0.003]) (p>0.05). However, when Na+ loss was
adjusted to sweat rate, no association was found between Na+
loss and testosterone (p>0.05). In addition, no differences were found
between players with high vs. low Na+ loss adjusted to sweat
loss in menstrual phase or intensity during exercise (p>0.05). In
conclusion, these results suggest that in these specific environmental
conditions, basal levels of testosterone might increase sweat rate and
therefore, the amount of Na+ lost during exercise in elite
women soccer players.
Akutes Abdomen mit galligem Erbrechen – Ein Leinsamen-Bezoar als
ungewöhnliche Ursache eines obstruktiven Ileus bei einer Adoleszenten mit
Anorexie
Authors: Schlag Stephanie , Liese Johannes , Veldhoen Simon
Published: May 2020

Akute Bauchschmerzen im Kindes- und Jugendalter sind ein häufiger Grund ärztlicher
Konsultation. Die Ätiologien der Beschwerden sind vielfältig und oft eine
diagnostische Herausforderung für den Kliniker. Komplizierend führen auch
extraabdominelle Erkrankungen zum Leitsymptom „Bauchschmerzen“. Wichtig ist die
Unterscheidung zwischen akuten Krankheitsbildern, die einer sofortigen
diagnostischen oder therapeutischen, ggf. auch chirurgischen Intervention bedürfen
und denen, die zunächst beobachtet werden können. Auch müssen lebensbedrohliche
Zustände erkannt und rasch behandelt werden. Die Schmerzursachen unterscheiden sich
je nach Alter und Vorgeschichte der Patienten erheblich, so kann bspw. ein
mechanischer Ileus auf dem Boden unterschiedlichster Erkrankungen entstehen (Yang
WC, Chen CY, Wu HP. Etiology of non-traumatic acute abdomen in pediatric emergency
departments. World J Clin Cases 2013; 1(9): 276–284). Im vorgestellten Fall soll die
Schwierigkeit der ätiologischen Zuordnung eines mechanischen Ileus aufgezeigt
werden.
Abnormal coalition of navicular and cuboid - a case report
Authors: Gindha Gurbachan Singh , Sharma Maneesha , Singh Manjit
Published: May 2020

The flat foot may result from a number of causes, out of which fusion between the adjoining tarsals can be one of the causes. An orthopedic surgeon should be aware of such coalitions. The present case study is a report of abnormal fusion of tarsal bones and the effects of such fusion on the adjoining structures and thereby resulting in difficulty during walking. The case presented here was observed while examining tarsal bones during routine undergraduate teaching. A right sided navicular had on its plantar aspect an abnormal wedge shaped accessory ossified part with a facet on its proximal aspect and a cut edge on its anterolateral aspect, corresponding cut edge was observed in proximo-medial aspect of the cuboid belonging to the same body, proving it to be a bar of bone between Navicular and cuboid. This naviculo- cuboid bar of bone might have resulted from lack of differentiation of mesenchyme.
Establishing a Data-Sharing Environment for a 21st-Century Academic Health Center
Authors: Khurshid Anjum , Rousseau Justin F. , Andrews Steven B. , Tierney William M.
Published: May 2020

Objective The main purpose of this study was to establish a seamless clinical data sharing system in a new medical school in partnership with community health systems.

Methods We developed a Data Request Management System (DRMS) and a data request process to streamline access to and management of data for quality improvement, population health, and research. We utilized a four-pronged methodology in implementing our clinical data sharing system: data governance, data extraction, external relationships, and internal engagement.

Results The Data Core team of honest data brokers through the established relationships, data use agreements, data request processes, and the DRMS processed more than 50 data requests from all the departments during its first year of operation. The DRMS application and the supporting governance and relationships provided a platform for improved process and accuracy of data sharing environment by facilitating trust, transparency, standardization, and service provisioning.

Conclusion Developing a seamless data ecosystem that forms the basis of a learning health system between an academic health center and community health systems requires a combination of people (the Data Core team), processes (common data request process policies and procedures), and technology (an effective online DRMS). Future work is needed to measure the impact of the clinical data sharing system on efficiency and accuracy of data sharing.
Infantile Onset Encephalomyopathy, Heart Block, and Sensorineural Hearing Loss: RMND1-Associated Mitochondrial Disease
Authors: Nagappa Madhu , Vandana V.P. , Chiplunkar Shwetha , Govindaraj Periyasamy , Ponmalar J.N. Jessiena , Gayathri Narayanappa , Sinha Sanjib , Taly Arun B. , Sankaran Bindu Parayil
Published: May 2020

Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mitochondrial disease and combined oxidation phosphorylation deficiency. This report describes a girl child of Indian origin with RMND1-associated mitochondrial disease. This 13-month-old girl, born to consanguineous parents presented with gradual loss of acquired milestones and recurrent vomiting from 5 months of age. She experienced failure to thrive, profound hypotonia, areflexia, and sensorineural deafness. Evaluation showed elevated serum lactate and complete heart block. Audiological evaluation done at 6 and 13 months of age revealed bilateral A type tympanogram, bilateral absent stapedial reflexes, absent otoacoustic emissions (OAE), and absent brainstem auditory evoked responses suggestive of bilateral profound sensorineural hearing loss. Muscle biopsy revealed evidence of ragged red fibers, ragged blue fibers, and Cytochrome coxidase (COX) deficient fibers on histochemistry and multiple complex deficiency on spectrophotometry. Exome sequencing revealed homozygous stop-loss variation, c.1349G > C, in exon 12 of RMDN1 resulting in substitution of amino acid serine for stop codon at position 450 and subsequent elongation of the protein by 31 amino acids (p.Ter450SerextTer31) which was verified by Sanger's sequencing. This report further strengthens the phenotype genotype correlations in RMND1-associated mitochondrial disease, especially the occurrence of the reported variation in South Asian patients. In addition, familiarity with the phenotype might help the physician to do targeted metabolic testing and facilitate appropriate early interventions.
2D large-scale EWOD devices with honeycomb electrodes for multiplexed multidirectional driving of micro-droplets
Authors: Zhang Kaidi , Wang Wei , Li Chunqiao , Riaud Antoine , Zhou Jia
Published: May 2020

Chemical and biological applications could strongly benefit from large-scale droplet manipulation of electrowetting-on-dielectric (EWOD). However, the large number of driving electrodes of EWOD chips has been one of the most significant obstacles for these applications. This paper unveils a compact printed circuit board based EWOD chip with a hexagonal electrode array, which uses only seven signals to control an unlimited number of driving electrodes (169 in this paper). Simulation and experimental results illustrate the device’s ability to transport multiple droplets synchronously with a reconfigurable driving route and a velocity of up to 10.0 mm/s, which is beneficial for complex or high-throughput EWOD applications.
Stability of flow in a deformable channel with an unrestrained boundary
Authors: Mandloi Shraddha , Shankar V.
Published: May 2020

We report results from a linear stability analysis of Newtonian plane Poiseuille flow through a deformable linear elastic channel with an unrestrained boundary wherein the deformable wall is not rigidly bonded to a substrate and is free to undergo motion. The objective of this study is to address the experimental observations of instabilities for this configuration [S. S. Srinivas and V. Kumaran, “Transitions to different kinds of turbulence in a channel with soft walls,” J. Fluid Mech. 822, 267–306 (2017)]. We analyze the role of an unrestrained deformable boundary on the stability of channel flow using both asymptotic and numerical methods. Our results show that when the solid to fluid layer thickness ratio is O(1), both wall modes (whose critical Reynolds number Rec ∝ G3/4, with G being the shear modulus of the solid) and inviscid modes (whose Rec ∝ G1/2) are significantly destabilized by the presence of an unrestrained boundary when compared to channels with completely bonded deformable boundaries. In agreement with experimental observations, the eigenfunctions corresponding to both these unstable modes exhibit a pronounced asymmetric behavior, thereby highlighting the influence of the unrestrained deformable boundary on the stability of the flow. The asymptotic predictions for the wall mode instability are shown to be in excellent agreement with our numerical results. However, for the solid to fluid thickness ratio ∼7.7 (used in the aforementioned experiments), our results show that the reduction in the critical Reynolds number due to the unrestrained boundary is only moderate; we provide possible reasons for the same.
Stability analysis of a rotor system with fluid applying wave resonance theory
Authors: Wang Haifei , Chen Chen
Published: May 2020

There is a great influence of the stability of a rotor system filled with fluid on the performance of the rotor. Wave resonance theory and the model established by Wolf are applied to study the stability boundaries. First, the resonant frequencies of the radial–circular waves on the nonviscous, incompressible fluid are obtained in a rotor with radial baffles. Based on the Navier–Stokes equations of the fluid, a simple form of the Bessel equation is derived by the perturbation method. Then, the relationship of the radial–circular wave frequencies and the rotation frequencies is obtained. Furthermore, the unstable regions under varying modes are predicted, and the effects of the fluid-fill ratio on the unstable regions are analyzed. In order to verify the accuracy of this model, a comparison is made with the model by Wolf. The results show that two lower boundaries of the unstable regions are in good agreement, while the upper boundaries do not coincide with the internal resonance when the baffle is equal to 2. The mechanism of the stability of a rotor filled with fluid is revealed in the case of the chamber without baffles.
Neural representations of perceptual color experience in the human ventral visual pathway
Authors: Kim Insub , Hong Sang Wook , Shevell Steven K. , Shim Won Mok
Published: May 2020

Color is a perceptual construct that arises from neural processing in hierarchically organized cortical visual areas. Previous research, however, often failed to distinguish between neural responses driven by stimulus chromaticity versus perceptual color experience. An unsolved question is whether the neural responses at each stage of cortical processing represent a physical stimulus or a color we see. The present study dissociated the perceptual domain of color experience from the physical domain of chromatic stimulation at each stage of cortical processing by using a switch rivalry paradigm that caused the color percept to vary over time without changing the retinal stimulation. Using functional MRI (fMRI) and a model-based encoding approach, we found that neural representations in higher visual areas, such as V4 and VO1, corresponded to the perceived color, whereas responses in early visual areas V1 and V2 were modulated by the chromatic light stimulus rather than color perception. Our findings support a transition in the ascending human ventral visual pathway, from a representation of the chromatic stimulus at the retina in early visual areas to responses that correspond to perceptually experienced colors in higher visual areas.
Putative regulators for the continuum of erythroid differentiation revealed by single-cell transcriptome of human BM and UCB cells
Authors: Huang Peng , Zhao Yongzhong , Zhong Jianmei , Zhang Xinhua , Liu Qifa , Qiu Xiaoxia , Chen Shaoke , Yan Hongxia , Hillyer Christopher , Mohandas Narla , Pan Xinghua , Xu Xiangmin
Published: May 2020

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34
−
CD235a
+
) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes,
AKAP8L
,
TERF2IP
, and
RNF10
, by monitoring cell differentiation and apoptosis. We documented that knockdown of
AKAP8L
suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of
TERF2IP
and
RNF10
delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.
Ancient genomes from present-day France unveil 7,000 years of its demographic history
Authors: Brunel Samantha , Bennett E. Andrew , Cardin Laurent , Garraud Damien , Barrand Emam Hélène , Beylier Alexandre , Boulestin Bruno , Chenal Fanny , Ciesielski Elsa , Convertini Fabien , Dedet Bernard , Desbrosse-Degobertiere Stéphanie , Desenne Sophie , Dubouloz Jerôme , Duday Henri , Escalon Gilles , Fabre Véronique , Gailledrat Eric , Gandelin Muriel , Gleize Yves , Goepfert Sébastien , Guilaine Jean , Hachem Lamys , Ilett Michael , Lambach François , Maziere Florent , Perrin Bertrand , Plouin Suzanne , Pinard Estelle , Praud Ivan , Richard Isabelle , Riquier Vincent , Roure Réjane , Sendra Benoit , Thevenet Corinne , Thiol Sandrine , Vauquelin Elisabeth , Vergnaud Luc , Grange Thierry , Geigl Eva-Maria , Pruvost Melanie
Published: May 2020

Genomic studies conducted on ancient individuals across Europe have revealed how migrations have contributed to its present genetic landscape, but the territory of present-day France has yet to be connected to the broader European picture. We generated a large dataset comprising the complete mitochondrial genomes, Y-chromosome markers, and genotypes of a number of nuclear loci of interest of 243 individuals sampled across present-day France over a period spanning 7,000 y, complemented with a partially overlapping dataset of 58 low-coverage genomes. This panel provides a high-resolution transect of the dynamics of maternal and paternal lineages in France as well as of autosomal genotypes. Parental lineages and genomic data both revealed demographic patterns in France for the Neolithic and Bronze Age transitions consistent with neighboring regions, first with a migration wave of Anatolian farmers followed by varying degrees of admixture with autochthonous hunter-gatherers, and then substantial gene flow from individuals deriving part of their ancestry from the Pontic steppe at the onset of the Bronze Age. Our data have also highlighted the persistence of Magdalenian-associated ancestry in hunter-gatherer populations outside of Spain and thus provide arguments for an expansion of these populations at the end of the Paleolithic Period more northerly than what has been described so far. Finally, no major demographic changes were detected during the transition between the Bronze and Iron Ages.
Competition and hybridization drive interspecific territoriality in birds
Authors: Drury Jonathan P. , Cowen Madeline C. , Grether Gregory F.
Published: May 2020

Costly interactions between species that arise as a by-product of ancestral similarities in communication signals are expected to persist only under specific evolutionary circumstances. Territorial aggression between species, for instance, is widely assumed to persist only when extrinsic barriers prevent niche divergence or selection in sympatry is too weak to overcome gene flow from allopatry. However, recent theoretical and comparative studies have challenged this view. Here we present a large-scale, phylogenetic analysis of the distribution and determinants of interspecific territoriality. We find that interspecific territoriality is widespread in birds and strongly associated with hybridization and resource overlap during the breeding season. Contrary to the view that territoriality only persists between species that rarely breed in the same areas or where niche divergence is constrained by habitat structure, we find that interspecific territoriality is positively associated with breeding habitat overlap and unrelated to habitat structure. Furthermore, our results provide compelling evidence that ancestral similarities in territorial signals are maintained and reinforced by selection when interspecific territoriality is adaptive. The territorial signals linked to interspecific territoriality in birds depend on the evolutionary age of interacting species, plumage at shallow (within-family) timescales, and song at deeper (between-family) timescales. Evidently, territorial interactions between species have persisted and shaped phenotypic diversity on a macroevolutionary timescale.
Spatial frequency tuning of motor responses reveals differential contribution of dorsal and ventral systems to action comprehension
Authors: Amoruso Lucia , Finisguerra Alessandra , Urgesi Cosimo
Published: May 2020

Understanding object-directed actions performed by others is central to everyday life. This ability is thought to rely on the interaction between the dorsal action observation network (AON) and a ventral object recognition pathway. On this view, the AON would encode action kinematics, and the ventral pathway, the most likely intention afforded by the objects. However, experimental evidence supporting this model is still scarce. Here, we aimed to disentangle the contribution of dorsal vs. ventral pathways to action comprehension by exploiting their differential tuning to low-spatial frequencies (LSFs) and high-spatial frequencies (HSFs). We filtered naturalistic action images to contain only LSF or HSF and measured behavioral performance and corticospinal excitability (CSE) using transcranial magnetic stimulation (TMS). Actions were embedded in congruent or incongruent scenarios as defined by the compatibility between grips and intentions afforded by the contextual objects. Behaviorally, participants were better at discriminating congruent actions in intact than LSF images. This effect was reversed for incongruent actions, with better performance for LSF than intact and HSF. These modulations were mirrored at the neurophysiological level, with greater CSE facilitation for congruent than incongruent actions for HSF and the opposite pattern for LSF images. Finally, only for LSF did we observe CSE modulations according to grip kinematics. While results point to differential dorsal (LSF) and ventral (HSF) contributions to action comprehension for grip and context encoding, respectively, the negative congruency effect for LSF images suggests that object processing may influence action perception not only through ventral-to-dorsal connections, but also through a dorsal-to-dorsal route involved in predictive processing.
Collective effects of XMAP215, EB1, CLASP2, and MCAK lead to robust microtubule treadmilling
Authors: Arpağ Göker , Lawrence Elizabeth J. , Farmer Veronica J. , Hall Sarah L. , Zanic Marija
Published: May 2020

Microtubule network remodeling is essential for fundamental cellular processes including cell division, differentiation, and motility. Microtubules are active biological polymers whose ends stochastically and independently switch between phases of growth and shrinkage. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is observed in cells; however, the underlying mechanisms are not known. Here, we use a combination of computational and in vitro reconstitution approaches to determine the conditions leading to robust microtubule treadmilling. We find that microtubules polymerized from tubulin alone can treadmill, albeit with opposite directionality and order-of-magnitude slower rates than observed in cells. We then employ computational simulations to predict that the combinatory effects of four microtubule-associated proteins (MAPs), namely EB1, XMAP215, CLASP2, and MCAK, can promote fast and sustained plus-end-leading treadmilling. Finally, we experimentally confirm the predictions of our computational model using a multi-MAP, in vitro microtubule dynamics assay to reconstitute robust plus-end-leading treadmilling, consistent with observations in cells. Our results demonstrate how microtubule dynamics can be modulated to achieve a dynamic balance between assembly and disassembly at opposite polymer ends, resulting in treadmilling over long periods of time. Overall, we show how the collective effects of multiple components give rise to complex microtubule behavior that may be used for global network remodeling in cells.
Y‐RNA subtype ratios in plasma extracellular vesicles are cell type‐ specific and are candidate biomarkers for inflammatory diseases
Authors: Driedonks Tom A.P. , Mol Sanne , de Bruin Sanne , Peters Anna‐Linda , Zhang Xiaogang , Lindenbergh Marthe F.S. , Beuger Boukje M. , van Stalborch Anne‐Marieke D. , Spaan Thom , de Jong Esther C. , van der Vries Erhard , Margadant Coert , van Bruggen Robin , Vlaar Alexander P.J. , Groot Kormelink Tom , Nolte‐‘T Hoen Esther N.M.
Published: May 2020

Major efforts are made to characterize the presence of microRNA (miRNA) and messenger RNA in blood plasma to discover novel disease‐associated biomarkers. MiRNAs in plasma are associated to several types of macromolecular structures, including extracellular vesicles (EV), lipoprotein particles (LPP) and ribonucleoprotein particles (RNP). RNAs in these complexes are recovered at variable efficiency by commonly used EV‐ and RNA isolation methods, which causes biases and inconsistencies in miRNA quantitation. Besides miRNAs, various other non‐coding RNA species are contained in EV and present within the pool of plasma extracellular RNA. Members of the Y‐RNA family have been detected in EV from various cell types and are among the most abundant non‐coding RNA types in plasma. We previously showed that shuttling of full‐length Y‐RNA into EV released by immune cells is modulated by microbial stimulation. This indicated that Y‐RNAs could contribute to the functional properties of EV in immune cell communication and that EV‐associated Y‐RNAs could have biomarker potential in immune‐related diseases. Here, we investigated which macromolecular structures in plasma contain full length Y‐RNA and whether the levels of three Y‐RNA subtypes in plasma (Y1, Y3 and Y4) change during systemic inflammation. Our data indicate that the majority of full length Y‐RNA in plasma is stably associated to EV. Moreover, we discovered that EV from different blood‐related cell types contain cell‐type‐specific Y‐RNA subtype ratios. Using a human model for systemic inflammation, we show that the neutrophil‐specific Y4/Y3 ratios and PBMC‐specific Y3/Y1 ratios were significantly altered after induction of inflammation. The plasma Y‐RNA ratios strongly correlated with the number and type of immune cells during systemic inflammation. Cell‐type‐specific “Y‐RNA signatures” in plasma EV can be determined without prior enrichment for EV, and may be further explored as simple and fast test for diagnosis of inflammatory responses or other immune‐related diseases.
Multi-wavelength focusing based on nanoholes
Authors: Han Yuansheng , Lu Xiaoqing , Lv Haoran , Mou Zhen , Zhou Changda , Wang Shuyun , Teng Shuyun
Published: May 2020

A kind of controllable multi-wavelength focusing metalenses is proposed. The proposed metalenses consist of identical nanometer holes etched in silver film and the beam focusing at three primary wavelengths is controlled without additional phase compensation. Transmission field of metalens satisfies the in-phase interference condition at different wavelength and the fixed focal effect for three primary wavelengths and the color separation along the transverse or longitudinal direction are realized respectively. Simulation and experimental results verify the controllable focusing performance of the proposed metalenses. Simple design, convenient manufacture and effective color controllable focusing of these proposed metalenses are helpful for the applications of metalenses in lightweight chromatically-corrected displaying and imaging systems.