bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Herbal Medicines Against CNS Disorders from Bangladesh
Authors: Uddin Md. Josim , Zidorn Christian
Published: October 2020

The majority of the population in Bangladesh uses traditional plant-based medicines to manage various ailments, including central nervous system (CNS) disorders. This review presents ethnobotanical information and relevant scientific studies on plants used in traditional healthcare for the management of various CNS disorders in Bangladesh. The information on the medicinal plants of Bangladesh effective against CNS disorders published in scientific journals, books, and reports was compiled from different electronic databases using specific key words. The present article provides comprehensive information on a total of 224 medicinal plant species belonging to 81 families used for the treatment of CNS disorders by the various peoples of Bangladesh. In total, we reviewed more than 290 relevant papers. In this study, leaves were found as the most often used plant organ, followed by roots, fruits, whole plants, barks, seeds, stems, rhizomes, and flowers. The Fabaceae family contributes the highest number of used species, followed by Rubiaceae, Lamiaceae, Cucurbitaceae, Vitaceae, Euphorbiaceae, Malvaceae, and Zingiberaceae. The most frequently used species (in decreasing order) areAsparagus racemosus, Centella asiatica, Stephania japonica,Aegle marmelos, Coccinia grandis, Tabernaemontana divaricata,Bacopa monnieri,Abroma augusta,andScoparia dulcis. This review may serve as a starting point for a rational search for neuroactive natural products against CNS disorders within the Flora of Bangladesh.

Graphic Abstract
Liver Transplantation for Colorectal Liver Metastasis
Authors: Lanari Jacopo , Dueland Svein , Line Pål-Dag
Published: October 2020

Purpose of Review

Accumulating evidence suggest that selected patients with nonresectable liver only metastases from colorectal cancer can be offered liver transplantation with acceptable outcome. This review provides an update on the scientific literature.

Recent Findings

The SECA-I study showed an estimated 5-year survival of 60% in a heterogenous patient population and guided the development of the first clinical selection criteria. In the sequel SECA-II trial, an estimated 5-year survival of 83% was obtained. A recent study shows that an Oslo score of 0–2, a metabolic tumor volume below 70 cm3 on PET-CT or Fong score of 0–2 at time of listing, can stratify patients with superior survival. Recurrence is common, but about 70% are slow-growing lung metastases, whereof the majority are resectable.

Liver transplantation for colorectal liver metastasis is an option in highly selected patients. Futile use of grafts can be avoided by applying stringent selection criteria.
TSH lowering effects of metformin: a possible mechanism of action
Authors: Cannarella R. , Condorelli R. A. , Barbagallo F. , Aversa A. , Calogero A. E. , La Vignera S.
Published: October 2020

Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.
Is There a Relation Between Caregiver Burden and Cognitive Dysfunction in Huntington’s Disease?
Authors: Schumacher-Kuiper M. M. , van Loon A. M. , Peeters C. F. W. , Ekkel M. R. , Hertogh C. M. P. M. , Veenhuizen R. B.
Published: October 2020

Caring for a family member with Huntington’s disease (HD) can be seriously burdensome. Cognitive and neuropsychiatric symptoms that are part of HD can impact the quality of life of caregivers. Therefore, we investigated the relationship between caregiver burden, cognitive impairment and patient characteristics. A retrospective cross-sectional study was performed on 33 adult HD-outpatient-caregiver dyads. We assessed caregiver burden and cognitive functioning of the included patient on the same day with the MCSI and MoCA respectively. For statistical analysis, we performed a network analysis and used descriptive statistics to describe our study sample. Caregivers scored on average 13.5 out of 26 points on the MCSI. The scores on the MoCA of the HD patients varied from 9 to 30 and was on average 22. Our network analysis demonstrated an indirect relationship between cognitive functioning and caregiver burden, in which CAG repeat length and the time since HD has been diagnosed are the primary mediators. We found a negative association between CAG repeat length and cognitive functioning. Furthermore, a relationship was found between higher caregiver burden and psychotropic drug use. We observed an indirect relationship between cognitive functioning and caregiver burden using network analysis. This analysis produces comprehensible results with the variables of interest. This study sheds new light on the components that make up caregiver burden in HD.
Motive und Rationalität des Protektionismus. Einige einfache spieltheoretische Überlegungen
Authors: Jerger Jürgen
Published: October 2020

Dieser Beitrag nutzt einen einfachen spieltheoretischen Rahmen, um die protektionistischen Tendenzen der jüngeren Vergangenheit als Ergebnis der Interaktion von politischen Entscheidungsträgern in zwei Ländern zu verstehen. Die (in diesem Rahmen: binäre) Politikentscheidung zwischen Protektionismus und Freihandel hängt natürlich von den erwarteten wahrgenommenen Ergebnissen dieser Politikoptionen ab. Die Wahrnehmung dieser Ergebnisse steht dabei im Fokus dieses Papiers. Es werden die Bedingungen untersucht, unter denen Freihandel das Ergebnis der beiden Politikentscheidungen bleibt bzw. wann sich dieses Ergebnis in ein protektionistisches Gleichgewicht ändert.
Augmented bricklaying
Authors: Mitterberger Daniela , Dörfler Kathrin , Sandy Timothy , Salveridou Foteini , Hutter Marco , Gramazio Fabio , Kohler Matthias
Published: October 2020

Augmented bricklaying explores the manual construction of intricate brickwork through visual augmentation, and applies and validates the concept in a real-scale building project—a fair-faced brickwork facade for a winery in Greece. As shown in previous research, robotic systems have proven to be very suitable to achieve various differentiated brickwork designs with high efficiency but show certain limitations, for example, in regard to spatial freedom or the usage of mortar on site. Hence, this research aims to show that through the use of a craft-specific augmented reality system, the same geometric complexity and precision seen in robotic fabrication can be achieved with an augmented manual process. Towards this aim, a custom-built augmented reality system for in situ construction was established. This process allows bricklayers to not depend on physical templates, and it enables enhanced spatial freedom, preserving and capitalizing on the bricklayer’s craft of mortar handling. In extension to conventional holographic representations seen in current augmented reality fabrication processes that have limited context-awareness and insufficient geometric feedback capabilities, this system is based on an object-based visual–inertial tracking method to achieve dynamic optical guidance for bricklayers with real-time tracking and highly precise 3D registration features in on-site conditions. By integrating findings from the field of human–computer interfaces and human–machine communication, this research establishes, explores, and validates a human–computer interactive fabrication system, in which explicit machine operations and implicit craftsmanship knowledge are combined. In addition to the overall concept, the method of implementation, and the description of the project application, this paper also quantifies process parameters of the applied augmented reality assembly method concerning building accuracy and assembly speed. In the outlook, this paper aims to outline future directions and potential application areas of object-aware augmented reality systems and their implications for architecture and digital fabrication.
3D Model for Active Vibration Control of Rotating Machines Mounted on Active Machine Foot Mounts Using Vibration Mode Coupling by Asymmetry
Authors: Werner Ulrich
Published: October 2020

Purpose

In this work, active vibration control of rotating machines mounted on active machine foot mounts is investigated.

Methods

Therefore, a simplified 3D model is derived and the mathematical coherences are described. Different mathematical solutions are presented for special boundary conditions and a method called “vibration mode coupling by asymmetry” is derived.

Results

It could be shown that a symmetrical system with a machine design, where the center of gravity lies symmetrically between the machine feet with a vertical distance, and where all actuators are identical, represents a system, where all vibration shapes but one can be influenced by the controllers, when the gyroscopic effect can be neglected. In this case, a special vibration shape occurs—where the machine is only rotating at its vertical axis—which cannot be influenced by the controllers. When the stiffness and/or damping in axial and/or horizontal direction of only one actuator will be changed—which will lead to an asymmetrical system—the vibration shape with pure rotation at the vertical axis will not exist anymore. Now, the vibration shapes will become more coupled and they all can be influenced by the controllers, which is here called “vibration mode coupling by asymmetry”.

Conclusions

With the here presented method of “vibration mode coupling by asymmetry”, all vibrations mode shapes can now be active controlled.
Relation of Birthweight and Ovarian and Uterine Size Prior to Menarche
Authors: Parisi Nadia , Tassi Alice , Capodicasa Valentina , Xholli Anjeza , Cagnacci Angelo
Published: October 2020

During pregnancy, supply of nutrients and exposure of the mother to environmental factors can influence fetus phenotype, possibly modifying growth of fetal tissues and organs. Few studies inconsistently reported that fetuses exposed to an insufficient energy supply, as those born small for gestational age, may have a reduced volume of uterus and ovaries. A retrospective analysis was performed on ultrasound data performed between 2012 and 2018 in 69 young premenarchal girls, 5 to 9 years of age, attending our endocrine–gynecologic clinic for a suspect of early puberty. Length of pregnancy and birthweight was also retrieved. When corrected for age, and presence of ovarian follicles, ovarian volume was positively (R2 = 0.210; p = 0.001) related to percentiles of birthweight (beta coefficient 0.012; 95% CI, 0.002–0.021). Similarly, uterine volume was positively (R2 = 0.237; p = 0.005) related to percentiles of birthweight (beta coefficient 0.067; 95% CI, 0.021–0.114). Ovarian (p = 0.034) and uterine (p = 0.014) volume was higher in the upper 3rd distribution of birthweight percentiles. In conclusion, development of ovarian and uterine volume increases progressively with the increase of birthweight percentiles. The data indicate an association between birthweight and the volume of uterus and ovary at 5–9 years of age.
The Music of Leos Janácek
Authors: Skoumal Zdeněk
Published: October 2020

The first thorough theoretical study of Janácek's compositions, focusing on motivic and rhythmic structure and identifying elements that give the music coherence, character, and interest.
The effects of treatment and management history on the control of Old World climbing fern (Lygodium microphyllum), Brazilian pepper (Schinus terebinthifolia), and punktree (Melaleuca quinquenervia)
Authors: Dietz Samantha L. , Anderson Chad T. , Sowell Dexter R. , Gundy Robert L. , King Linda E.
Published: October 2020

To successfully reduce overall invasive plant cover over time, an effective treatment plan must be established such that mortality exceeds new colonization and resprouting growth rates. However, few evaluations of the effects of long-term, consistent treatment at different intervals exist. We report the effects of treatment intensity on Old World climbing fern [Lygodium microphyllum(Cav.) R. Br.], Brazilian pepper (Schinus terebinthifoliaRaddi), and punktree [Melaleuca quinquenervia(Cav.) S. F. Blake] as part of a large restoration project that has been underway for 6 yr in Telegraph Swamp at Babcock Ranch Preserve, a 27,520-hectare (68,000-acre) conservation area in Florida, USA. We found that at the end of the 6-yr period, for all three species, average live cover did not exceed 5% across all transects. In addition, dead foliar cover was higher than live cover for all three invasive plants, indicating progress toward restoration goals. We also found that percent live cover ofL. microphyllumwas significantly reduced only after four or more treatments were applied during the 6-yr period, as opposed to when three or fewer treatments were applied. Reductions in percent cover of live foliage were apparent only when the treatments were applied more often than biennially, as opposed to less often than biennially. Additionally, we found higherL. microphyllumcover in clear-cut and replanted cypress stands than in natural stands. Based on these findings, we conclude that treatments applied four or more times, or more often than biennially, were more effective at significantly reducing advanced invasions ofL. microphyllum,S. terebinthifolia, andM. quinquenervia, especially where previous management activities or their effects may have increased the cover of invasive plants.
Direct numerical simulation of subsonic, transonic and supersonic flow over an isolated sphere up to a Reynolds number of 1000
Authors: Nagata T. , Nonomura T. , Takahashi S. , Fukuda K.
Published: October 2020

In the present study, compressible low-Reynolds-number flow past a stationary isolated sphere was investigated by direct numerical simulations of the Navier–Stokes equations using a body-fitted grid with high-order schemes. The Reynolds number based on free-stream quantities and the diameter of the sphere was set to be between 250 and 1000, and the free-stream Mach number was set to be between 0.3 and 2.0. As a result, it was clarified that the wake of the sphere is significantly stabilized as the Mach number increases, particularly at the Mach number greater than or equal to 0.95, but turbulent kinetic energy at the higher Mach numbers conditions is higher than that at the lower Mach numbers conditions of similar flow regimes. A rapid extension of the length of the recirculation region was observed under the transitional condition between the steady and unsteady flows. The drag coefficient increases as the Mach number increases mainly in the transonic regime and its increment is almost due to the increment in the pressure component. In addition, the increment in the drag coefficient is approximately a function of the Mach number and independent of the Reynolds number in the continuum regime. Moreover, the effect of the Mach and Reynolds numbers on the flow properties such as the drag coefficient and flow regime can approximately be characterized by the position of the separation point.
An Accurate Performance Prediction of Solid Fuel Ramjets Using Coupled Intake-Combustor-Nozzle Simulation
Authors: Tahsini A. M.
Published: October 2020

The performance of the solid fuel ramjet is accurately predicted using full part simulation of this propulsion system, where the flow fields of the intake, combustion chamber, and the nozzle are numerically studied all together. The conjugate heat transfer is considered between the solid phase and the gas phase to directly compute the regression rate of the fuel. The finite volume solver of the compressible turbulent reacting flow is utilized to study the axisymmetric three dimensional flow fields, and two blocks are used to discretize the computational domain. It is shown that the combustion chamber's pressure is changed due to the fuel flow rate's increment which must be taken into account in predictions. The results demonstrate that omitting the pressure dependence of the regression rate and also the effect of the combustor's inlet profile on the regression rate, which specially exists when simulating the combustion chamber individually, under-predicts the solid fuel burning rate when the regression rate augmentation technique is applied to improve the performance of the solid fuel ramjets. It is also illustrated that using the inlet swirl to increase the regression rate of the solid fuel augments considerably the thrust level of the considered SFRJ, while the predictions without considering all parts of the ramjet is not accurate.
Teleseismic earthquake wavefields observed on the Ross Ice Shelf
Authors: Baker Michael G. , Aster Richard C. , Wiens Douglas A. , Nyblade Andrew , Bromirski Peter D. , Gerstoft Peter , Stephen Ralph A.
Published: October 2020

Observations of teleseismic earthquakes using broadband seismometers on the Ross Ice Shelf (RIS) must contend with environmental and structural processes that do not exist for land-sited seismometers. Important considerations are: (1) a broadband, multi-mode ambient wavefield excited by ocean gravity wave interactions with the ice shelf; (2) body wave reverberations produced by seismic impedance contrasts at the ice/water and water/seafloor interfaces and (3) decoupling of the solid Earth horizontal wavefield by the sub-shelf water column. We analyze seasonal and geographic variations in signal-to-noise ratios for teleseismic P-wave (0.5–2.0 s), S-wave (10–15 s) and surface wave (13–25 s) arrivals relative to the RIS noise field. We use ice and water layer reverberations generated by teleseismic P-waves to accurately estimate the sub-station thicknesses of these layers. We present observations consistent with the theoretically predicted transition of the water column from compressible to incompressible mechanics, relevant for vertically incident solid Earth waves with periods longer than 3 s. Finally, we observe symmetric-mode Lamb waves generated by teleseismic S-waves incident on the grounding zones. Despite their complexity, we conclude that teleseismic coda can be utilized for passive imaging of sub-shelf Earth structure, although longer deployments relative to conventional land-sited seismometers will be necessary to acquire adequate data.
The stellar rotation–activity relation for a sample of SuperWASP and ASAS-SN field stars
Authors: Thiemann Heidi B. , Norton Andrew J. , Kolb Ulrich C.
Published: October 2020

It is well established that late-type main-sequence (MS) stars display a relationship between X-ray activity and the Rossby number,Ro, the ratio of rotation period to the convective turnover time. This manifests itself as a saturated regime (where X-ray activity is constant) and an unsaturated regime (where X-ray activity anti-correlates with Rossby number). However, this relationship breaks down for the fastest rotators. We cross-correlated SuperWASP visually classified photometric light curves and All-Sky Automated Survey for Supernovae automatically classified photometric light curves with XMM-Newton X-ray observations to identify 3 178 stars displaying a photometrically defined rotational modulation in their light curve and corresponding X-ray observations. We fitted a power-law to characterise the rotation–activity relation of 900 MS stars. We identified that automatically classified rotationally modulated light curves are not as reliable as visually classified light curves for this work. We found a power-law index in the unsaturated regime of G- to M-type stars of$\beta=-1.84\,\pm\,0.18$for the SuperWASP catalogue, in line with the canonical value of$\beta=-2$. We find evidence of supersaturation in the fastest rotating K-type stars, with a power-law index of$\beta_{s}=1.42\pm0.26$.
Viewpoint: do antipsychotics protect against early death? A critical view
Authors: Whitaker Robert
Published: October 2020

In the past 15 years, researchers utilizing prescription databases to assess medication usage have concluded that antipsychotics reduce mortality in patients diagnosed with schizophrenia and other psychotic disorders. These findings stand in contrast to studies in non-psychiatric patients that have found that antipsychotics, because of their adverse effects on physical health, increase the risk of early death. A critical review of the evidence reveals that the worry remains. There is reason to conclude that antipsychotics contribute to the ‘mortality gap’ between the seriously mentally ill and the general population and that the database studies are plagued with methodological and reporting issues. Most importantly, the database studies tell of mortality rates within a drug-centered paradigm of care, which confounds any comparison of mortality risks when patients are on or off antipsychotics.
What distinguishes positive deviance (PD) health professionals from their peers and what impact does a PD intervention have on behaviour change: a cross-sectional study of infection control and prevention in three Israeli hospitals
Authors: Cohen R. , Gesser-Edelsburg A. , Singhal A. , Benenson S. , Moses A.E.
Published: October 2020

Past studies using the positive deviance (PD) approach in the field of infection prevention and control (IPC) have primarily focused on impacts on healthcare-associated infection rates. This research aimed to determine if health professionals who exhibit PD behaviours have distinctive socio-cognitive profiles compared to non-PD professionals, and to examine the impact of a PD intervention on healthcare professionals’ (HPs) behavioural changes in maintaining IPC guidelines. In a cross-sectional study among 135 HPs, respondents first filled out a socio-cognitive characteristics questionnaire, and after 5 months were requested to complete a self-reported behavioural change questionnaire. The main findings indicate that socio-cognitive variables such as external locus of control, perceived threat and social learning were significant predictors of a person exhibiting PD behaviours. Almost 70% of HPs reported behavioural change and creating social networks as a result of the PD intervention in maintaining IPC guidelines, 16.9% of them are a ‘PD boosters’ (a new group of HPs who have adopted the positive practices of PDs that were originally identified, and also added additional practices of their own). Social networks can contribute to internalizing and raising personal accountability even among non-PD professionals, by creating a mind map that makes each person believe they are an important node in the network, regardless of their status and role. Health intervention programmes should purposely make visible and prominent social network connections in the hospital system.
How does supervision aid cognitive behaviour therapy skill development? Perspectives of CBT trainees: a thematic analysis
Authors: Murr Stephanie , Nicklas Leeanne , Harper Sean
Published: October 2020

Eleven cognitive behaviour therapy (CBT) trainees in Scotland were interviewed regarding their experiences of clinical supervision and its impact on their skill development. Using thematic analysis, the authors developed four main themes: Linking Theory to Practice, Mirroring CBT in Supervision, The Expert Supervisor, and Trainees’ Reluctance to Give Negative Feedback. Clinical supervision was essential in helping trainees to link theory to practice; particularly through audio recordings, discussing formulations, and modelling and role-play. A CBT-specific approach to supervision and a CBT expert supervisor were also identified as valuable to learning. Trainees were reluctant to give negative feedback to supervisors, fearing negative consequences. The findings inform supervision practice.

Key learning aims

Readers of this paper will be able to:

(1)

Describe trainees’ most valued elements of CBT supervision.

(2)

Determine key learning methods in CBT supervision.

(3)

Explain the value of modality specific CBT supervision.

(4)

Articulate the context of supervision in CBT training and consider mutual feedback as a method to address identified challenges.
Mentorship During a Pandemic: Transitions from Lab and Sea to Virtual
Authors: Sima Richard
Published: October 2020

With mentorship having gone virtual this past summer, three geosciences programs offer case studies about how to form meaningful connections during a time of social distancing.
Capturing Heat-Driven Atmospheric Tides on Mars
Authors: Stanley Sarah
Published: October 2020

Spacecraft observations and model simulations provide new insights into tidal patterns that transport momentum and energy into the planet’s upper atmosphere.
Detection of the Chandler Wobble of Mars From Orbiting Spacecraft
Authors: Konopliv Alex S. , Park Ryan S. , Rivoldini Attilio , Baland Rose‐Marie , Le Maistre Sebastien , Van Hoolst Tim , Yseboodt Marie , Dehant Veronique
Published: October 2020

For the first time for any planetary body other than the Earth, the free wobble of the pole called the Chandler wobble has been detected for Mars with a period of 206.9 ± 0.5 days and amplitude of 10 cm from radio tracking observations of Mars Odyssey, Mars Reconnaissance Orbiter (MRO), and Mars Global Surveyor (MGS), in order of decreasing sensitivity. The motion of the rotation pole location on the surface of Mars, or polar motion, is observed using two different approaches: (1) joint global estimates of Mars' orientation and its gravity field and (2) time series solutions of C21 and S21. For Mars interior models, the Chandler wobble period is combined with other measurements including the moments of inertia from our estimated precession rate
and tidal Love number k2 = 0.169 ± 0.006. The Chandler wobble period constrains the rheology of the Martian mantle and in particular its long‐term frequency dependence.
Cross‐Scale Quantification of Storm‐Time Dayside Magnetospheric Magnetic Flux Content
Authors: Akhavan‐Tafti M. , Fontaine D. , Slavin J. A. , Le Contel O. , Turner D.
Published: October 2020

A clear understanding of storm‐time magnetospheric dynamics is essential for a reliable storm forecasting capability. The dayside magnetospheric response to an interplanetary coronal mass ejection (ICME; dynamic pressure Pdyn > 20 nPa and storm‐time index SYM‐H < −150 nT) is investigated using in situ OMNI, Geotail, Cluster, MMS, GOES, Van Allen Probes, and THEMIS measurements. The dayside magnetic flux content is directly quantified from in situ magnetic field measurements at different radial distances. The arrival of the ICME, consisting of shock and sheath regions preceding a magnetic cloud, initiated a storm sudden commencement (SSC) phase (SYM‐H ~ +50 nT). At SSC, the magnetopause standoff distance was compressed earthward at ICME shock encounter at an average rate ~−10.8 Earth radii per hour for ~10 min, resulting in a rapid 40% reduction in the magnetospheric volume. The “closed” magnetic flux content remained constant at 170 ± 30 kWb inside the compressed dayside magnetosphere, even in the presence of dayside reconnection, as evident by an outsized flux transfer event containing 160 MWb. During the storm main and recovery phases, the magnetosphere expanded. The dayside magnetic flux did not remain constant within the expanding magnetosphere (110 ± 30 kWb), resulting in a 35% reduction in pre‐storm flux content during the magnetic cloud encounter. At that stage, the magnetospheric magnetic flux was eroded resulting in a weakened dayside magnetospheric field strength at radial distances R ≥ 5 RE. It is concluded that the inadequate replenishment of the eroded dayside magnetospheric flux during the magnetosphere expansion phase is due to a time lag in storm‐time Dungey cycle.
Proline-rich transmembrane protein 2 (PRRT2) regulates the actin cytoskeleton during synaptogenesis
Authors: Savino Elisa , Cervigni Romina Inès , Povolo Miriana , Stefanetti Alessandra , Ferrante Daniele , Valente Pierluigi , Corradi Anna , Benfenati Fabio , Guarnieri Fabrizia Claudia , Valtorta Flavia
Published: October 2020

Mutations in proline-rich transmembrane protein 2 (PRRT2) have been recently identified as the leading cause of a clinically heterogeneous group of neurological disorders sharing a paroxysmal nature, including paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. To date, studies aimed at understanding its physiological functions in neurons have mainly focused on its ability to regulate neurotransmitter release and neuronal excitability. Here, we show that PRRT2 expression in non-neuronal cell lines inhibits cell motility and focal adhesion turnover, increases cell aggregation propensity, and promotes the protrusion of filopodia, all processes impinging on the actin cytoskeleton. In primary hippocampal neurons, PRRT2 silencing affects the synaptic content of filamentous actin and perturbs actin dynamics. This is accompanied by defects in the density and maturation of dendritic spines. We identified cofilin, an actin-binding protein abundantly expressed at the synaptic level, as the ultimate effector of PRRT2. Indeed, PRRT2 silencing unbalances cofilin activity leading to the formation of cofilin-actin rods along neurites. The expression of a cofilin phospho-mimetic mutant (cof-S3E) is able to rescue PRRT2-dependent defects in synapse density, spine number and morphology, but not the alterations observed in neurotransmitter release. Our data support a novel function of PRRT2 in the regulation of the synaptic actin cytoskeleton and in the formation of synaptic contacts.
Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche
Authors: Peng Xiaohong , Wu Yi , Brouwer Uilke , van Vliet Thijmen , Wang Boshi , Demaria Marco , Barazzuol Lara , Coppes Rob P.
Published: October 2020

Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent state of cell cycle arrest accompanied by a secretory phenotype which contributes to inflammation and tissue deterioration. Genotoxic stresses, including radiation-induced DNA damage, are known to induce a senescence response. Here, we show that radiation induces cellular senescence preferentially in the salivary gland stem/progenitor cell niche of mouse models and patients. Similarly, salivary gland-derived organoids show increased expression of senescence markers and pro-inflammatory senescence-associated secretory phenotype (SASP) factors after radiation exposure. Clearance of senescent cells by selective removal of p16Ink4a-positive cells by the drug ganciclovir or the senolytic drug ABT263 lead to increased stem cell self-renewal capacity as measured by organoid formation efficiency. Additionally, pharmacological treatment with ABT263 in mice irradiated to the salivary glands mitigates tissue degeneration, thus preserving salivation. Our data suggest that senescence in the salivary gland stem/progenitor cell niche contributes to radiation-induced hyposalivation. Pharmacological targeting of senescent cells may represent a therapeutic strategy to prevent radiotherapy-induced xerostomia.
Photobase effect for just-in-time delivery in photocatalytic hydrogen generation
Authors: Fang Jiawen , Debnath Tushar , Bhattacharyya Santanu , Döblinger Markus , Feldmann Jochen , Stolarczyk Jacek K.
Published: October 2020

Carbon dots (CDs) are a promising nanomaterial for photocatalytic applications. However, the mechanism of the photocatalytic processes remains the subject of a debate due to the complex internal structure of the CDs, comprising crystalline and molecular units embedded in an amorphous matrix, rendering the analysis of the charge and energy transfer pathways between the constituent parts very challenging. Here we propose that the photobasic effect, that is the abstraction of a proton from water upon excitation by light, facilitates the photoexcited electron transfer to the proton. We show that the controlled inclusion in CDs of a model photobase, acridine, resembling the molecular moieties found in photocatalytically active CDs, strongly increases hydrogen generation. Ultrafast spectroscopy measurements reveal proton transfer within 30 ps of the excitation. This way, we use a model system to show that the photobasic effect may be contributing to the photocatalytic H2 generation of carbon nanomaterials and suggest that it may be tuned to achieve further improvements. The study demonstrates the critical role of the understanding the dynamics of the CDs in the design of next generation photocatalysts.
A strategy to incorporate prior knowledge into correlation network cutoff selection
Authors: Benedetti Elisa , Pučić-Baković Maja , Keser Toma , Gerstner Nathalie , Büyüközkan Mustafa , Štambuk Tamara , Selman Maurice H. J. , Rudan Igor , Polašek Ozren , Hayward Caroline , Al-Amin Hassen , Suhre Karsten , Kastenmüller Gabi , Lauc Gordan , Krumsiek Jan
Published: October 2020

Correlation networks are frequently used to statistically extract biological interactions between omics markers. Network edge selection is typically based on the statistical significance of the correlation coefficients. This procedure, however, is not guaranteed to capture biological mechanisms. We here propose an alternative approach for network reconstruction: a cutoff selection algorithm that maximizes the overlap of the inferred network with available prior knowledge. We first evaluate the approach on IgG glycomics data, for which the biochemical pathway is known and well-characterized. Importantly, even in the case of incomplete or incorrect prior knowledge, the optimal network is close to the true optimum. We then demonstrate the generalizability of the approach with applications to untargeted metabolomics and transcriptomics data. For the transcriptomics case, we demonstrate that the optimized network is superior to statistical networks in systematically retrieving interactions that were not included in the biological reference used for optimization.
Plant species determine tidal wetland methane response to sea level rise
Authors: Mueller Peter , Mozdzer Thomas J. , Langley J. Adam , Aoki Lillian R. , Noyce Genevieve L. , Megonigal J. Patrick
Published: October 2020

Blue carbon (C) ecosystems are among the most effective C sinks of the biosphere, but methane (CH4) emissions can offset their climate cooling effect. Drivers of CH4 emissions from blue C ecosystems and effects of global change are poorly understood. Here we test for the effects of sea level rise (SLR) and its interactions with elevated atmospheric CO2, eutrophication, and plant community composition on CH4 emissions from an estuarine tidal wetland. Changes in CH4 emissions with SLR are primarily mediated by shifts in plant community composition and associated plant traits that determine both the direction and magnitude of SLR effects on CH4 emissions. We furthermore show strong stimulation of CH4 emissions by elevated atmospheric CO2, whereas effects of eutrophication are not significant. Overall, our findings demonstrate a high sensitivity of CH4 emissions to global change with important implications for modeling greenhouse-gas dynamics of blue C ecosystems.
Self-reliance crowds out group cooperation and increases wealth inequality
Authors: Gross Jörg , Veistola Sonja , De Dreu Carsten K. W. , Van Dijk Eric
Published: October 2020

Humans establish public goods to provide for shared needs like safety or healthcare. Yet, public goods rely on cooperation which can break down because of free-riding incentives. Previous research extensively investigated how groups solve this free-rider problem but ignored another challenge to public goods provision. Namely, some individuals do not need public goods to solve the problems they share with others. We investigate how such self-reliance influences cooperation by confronting groups in a laboratory experiment with a safety problem that could be solved either cooperatively or individually. We show that self-reliance leads to a decline in cooperation. Moreover, asymmetries in self-reliance undermine social welfare and increase wealth inequality between group members. Less dependent group members often choose to solve the shared problem individually, while more dependent members frequently fail to solve the problem, leaving them increasingly poor. While self-reliance circumvents the free-rider problem, it complicates the governing of the commons.
Rationally designed transition metal hydroxide nanosheet arrays on graphene for artificial CO2 reduction
Authors: Lu Kang-Qiang , Li Yue-Hua , Zhang Fan , Qi Ming-Yu , Chen Xue , Tang Zi-Rong , Yamada Yoichi M. A. , Anpo Masakazu , Conte Marco , Xu Yi-Jun
Published: October 2020

The performance of transition metal hydroxides, as cocatalysts for CO2 photoreduction, is significantly limited by their inherent weaknesses of poor conductivity and stacked structure. Herein, we report the rational assembly of a series of transition metal hydroxides on graphene to act as a cocatalyst ensemble for efficient CO2 photoreduction. In particular, with the Ru-dye as visible light photosensitizer, hierarchical Ni(OH)2 nanosheet arrays-graphene (Ni(OH)2-GR) composites exhibit superior photoactivity and selectivity, which remarkably surpass other counterparts and most of analogous hybrid photocatalyst system. The origin of such superior performance of Ni(OH)2-GR is attributed to its appropriate synergy on the enhanced adsorption of CO2, increased active sites for CO2 reduction and improved charge carriers separation/transfer. This work is anticipated to spur rationally designing efficient earth-abundant transition metal hydroxides-based cocatalysts on graphene and other two-dimension platforms for artificial reduction of CO2 to solar chemicals and fuels.
Fermentative production of Vitamin E tocotrienols in Saccharomyces cerevisiae under cold-shock-triggered temperature control
Authors: Shen Bin , Zhou Pingping , Jiao Xue , Yao Zhen , Ye Lidan , Yu Hongwei
Published: October 2020

The diverse physiological functions of tocotrienols have listed them as valuable supplementations to α-tocopherol-dominated Vitamin E products. To make tocotrienols more readily available, tocotrienols-producing S. cerevisiae has been constructed by combining the heterologous genes from photosynthetic organisms with the endogenous shikimate pathway and mevalonate pathway. After identification and elimination of metabolic bottlenecks and enhancement of precursors supply, the engineered yeast can produce tocotrienols at yield of up to 7.6 mg/g dry cell weight (DCW). In particular, proper truncation of the N-terminal transit peptide from the plant-sourced enzymes is crucial. To further solve the conflict between cell growth and tocotrienols accumulation so as to enable high-density fermentation, a cold-shock-triggered temperature control system is designed for efficient control of two-stage fermentation, leading to production of 320 mg/L tocotrienols. The success in high-density fermentation of tocotrienols by engineered yeast sheds light on the potential of fermentative production of vitamin E tocochromanols.
Fungal oxylipins direct programmed developmental switches in filamentous fungi
Authors: Niu Mengyao , Steffan Breanne N. , Fischer Gregory J. , Venkatesh Nandhitha , Raffa Nicholas L. , Wettstein Molly A. , Bok Jin Woo , Greco Claudio , Zhao Can , Berthier Erwin , Oliw Ernst , Beebe David , Bromley Michael , Keller Nancy P.
Published: October 2020

Filamentous fungi differentiate along complex developmental programs directed by abiotic and biotic signals. Currently, intrinsic signals that govern fungal development remain largely unknown. Here we show that an endogenously produced and secreted fungal oxylipin, 5,8-diHODE, induces fungal cellular differentiation, including lateral branching in pathogenic Aspergillus fumigatus and Aspergillus flavus, and appressorium formation in the rice blast pathogen Magnaporthe grisea. The Aspergillus branching response is specific to a subset of oxylipins and is signaled through G-protein coupled receptors. RNA-Seq profiling shows differential expression of many transcription factors in response to 5,8-diHODE. Screening of null mutants of 33 of those transcription factors identifies three transcriptional regulators that appear to mediate the Aspergillus branching response; one of the mutants is locked in a hypo-branching phenotype, while the other two mutants display a hyper-branching phenotype. Our work reveals an endogenous signal that triggers crucial developmental processes in filamentous fungi, and opens new avenues for research on the morphogenesis of filamentous fungi.
Topological analysis reveals state transitions in human gut and marine bacterial communities
Authors: Chang William K. , VanInsberghe David , Kelly Libusha
Published: October 2020

Microbiome dynamics influence the health and functioning of human physiology and the environment and are driven in part by interactions between large numbers of microbial taxa, making large-scale prediction and modeling a challenge. Here, using topological data analysis, we identify states and dynamical features relevant to macroscopic processes. We show that gut disease processes and marine geochemical events are associated with transitions between community states, defined as topological features of the data density. We find a reproducible two-state succession during recovery from cholera in the gut microbiomes of multiple patients, evidence of dynamic stability in the gut microbiome of a healthy human after experiencing diarrhea during travel, and periodic state transitions in a marine Prochlorococcus community driven by water column cycling. Our approach bridges small-scale fluctuations in microbiome composition and large-scale changes in phenotype without details of underlying mechanisms, and provides an assessment of microbiome stability and its relation to human and environmental health.
Dynamic disorder phonon scattering mediated by Cu atomic hopping and diffusion in Cu3SbSe3
Authors: Wang Chen , Wu Yixuan , Pei Yanzhong , Chen Yue
Published: October 2020

Cu3SbSe3 that exhibits distinct liquid-like sublattice due to the heterogeneous bonding environment has emerged as a promising low cost superionic semiconductor with intrinsic ultralow thermal conductivity. However, the relationship between atomic dynamics resulting in liquid-like diffusion and anomalous phonon transport properties remains poorly understood. Herein, combing ab initio molecular dynamics with temperature-dependent Raman measurements, we have performed a thorough investigation on the lattice dynamics of Cu3SbSe3. Superionic transition is unveiled for both structurally inequivalent Cu atoms at elevated temperatures, while the Se-formed tetrahedral framework can simultaneously maintain. An intermediate state of Cu3SbSe3 through the mixture of quasi-1D/2D Cu nearest-neighbor vacancy hopping is discovered below the superionic transition temperature. Our results also manifest that phonons predominately involved with Cu contributions along diffusion channels have been strongly scattered during the superionic transition, whereas the liquid-like diffusion of Cu is too slow to completely breakdown the propagation of all transverse phonon modes. The insight provided by this work into the atomic dynamics and phonon scattering relationship may pave the way for further phonon engineering of Cu3SbSe3 and related superionic materials.
Subthalamic deep brain stimulation improves sleep and excessive sweating in Parkinson’s disease
Authors: Bjerknes Silje , Skogseid Inger Marie , Hauge Tuva Jin , Dietrichs Espen , Toft Mathias
Published: October 2020

Parkinson’s disease (PD) is a complex multisystem disorder with motor and non-motor symptoms (NMS). NMS may have an even greater impact on quality of life than motor symptoms. Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor fluctuations and quality of life, whereas the effects on different NMS have been less examined. Sleep disturbances and autonomic dysfunction are among the most prevalent NMS. We here report the efficacy of STN-DBS on sleep disturbances and autonomic dysfunction. In the parent trial, 60 patients were included in a single-center randomized prospective study, with MDS-UPDRS III and PDQ-39 as primary endpoints at 12 months of STN-DBS. Preplanned assessments at baseline and postoperatively at 3 and 12 months also included Parkinson’s Disease Sleep Scale (PDSS); Scopa-Aut; and MDS-UPDRS I, II, and IV. We found that STN-DBS had a significant and lasting positive effect on overall sleep quality, nocturnal motor symptoms and restlessness, and daytime dozing. Several aspects of autonomic dysfunction were also improved at 3 months postoperatively, although at 12 months only thermoregulation (sudomotor symptoms) remained significantly improved. We could not identify preoperative factors that predicted improvement in PDSS or Scopa-Aut. There was a close relationship between improved autonomic symptoms and improved quality of life after 1 year. NMS and especially sleep and autonomic dysfunction deserve more focus to improve patient outcomes further.
Engineering a fidelity-variant live-attenuated vaccine for chikungunya virus
Authors: Weiss Christopher M. , Liu Hongwei , Riemersma Kasen K. , Ball Erin E. , Coffey Lark L.
Published: October 2020

Chikungunya virus (CHIKV), which causes a febrile illness characterized by severe and prolonged polyarthralgia/polyarthritis, is responsible for a global disease burden of millions of cases each year with autochthonous transmission in over 100 countries and territories worldwide. There is currently no approved treatment or vaccine for CHIKV. One live-attenuated vaccine (LAV) developed by the United States Army progressed to Phase II human clinical trials but was withdrawn when 8% of volunteers developed joint pain associated with vaccination. Attenuation of the Army’s CHIKV LAV strain 181 clone 25 (CHIKV-181/25) relies on two mutations in the envelope 2 (E2) glycoprotein responsible for cell binding and entry, making it particularly prone to reversion, a common concern for replication-competent vaccines. High error rates associated with RNA virus replication have posed a challenge for LAV development where stable incorporation of attenuating elements is necessary for establishing safety in pre-clinical models. Herein, we incorporate two replicase mutations into CHIKV-181/25 which modulate CHIKV replication fidelity combined with additional attenuating features that cannot be eliminated by point mutation. The mutations were stably incorporated in the LAV and did not increase virulence in mice. Two fidelity-variant CHIKV LAVs generated neutralizing antibodies and were protective from CHIKV disease in adult mice. Unexpectedly, our fidelity-variant candidates were more mutable than CHIKV-181/25 and exhibited restricted replication in mice and Aedes mosquitoes, a possible consequence of hypermutation. Our data demonstrate safety and efficacy but highlight a further need to evaluate fidelity-altering phenotypes before use as a LAV given the potential for virulent reversion.