bluuebunny/crossref_metadata_2025 huggingface dataset:
Music as a coevolved system for social bonding
Authors: Savage Patrick E. , Loui Psyche , Tarr Bronwyn , Schachner Adena , Glowacki Luke , Mithen Steven , Fitch W. Tecumseh
Published: August 2020

Why do humans make music? Theories of the evolution of musicality have focused mainly on the value of music for specific adaptive contexts such as mate selection, parental care, coalition signaling, and group cohesion. Synthesizing and extending previous proposals, we argue that social bonding is an overarching function that unifies all of these theories, and that musicality enabled social bonding at larger scales than grooming and other bonding mechanisms available in ancestral primate societies. We combine cross-disciplinary evidence from archeology, anthropology, biology, musicology, psychology, and neuroscience into a unified framework that accounts for the biological and cultural evolution of music. We argue that the evolution of musicality involves gene–culture coevolution, through which proto-musical behaviors that initially arose and spread as cultural inventions had feedback effects on biological evolution because of their impact on social bonding. We emphasize the deep links between production, perception, prediction, and social reward arising from repetition, synchronization, and harmonization of rhythms and pitches, and summarize empirical evidence for these links at the levels of brain networks, physiological mechanisms, and behaviors across cultures and across species. Finally, we address potential criticisms and make testable predictions for future research, including neurobiological bases of musicality and relationships between human music, language, animal song, and other domains. The music and social bonding hypothesis provides the most comprehensive theory to date of the biological and cultural evolution of music.
Frequency and level of self-efficacy predict the effectiveness of therapist- and self-guided exposure in obsessive compulsive disorder
Authors: Voderholzer Ulrich , Hilbert Sven , Fischer Anne , Neumüller Jakob , Schwartz Caroline , Hessler-Kaufmann Johannes Baltasar
Published: August 2020

Background:

While exposure and response prevention (ERP) is the most effective treatment for obsessive compulsive disorder (OCD), less is known about the specific mechanisms underlying symptom change after ERP.

Aims:

We tested the hypothesis that the frequency of self- and therapist-guided ERP related to the extent of symptom reduction and that this link is mediated by increased self-efficacy.

Method:

In a sample of 377 in-patients with a primary diagnosis of OCD receiving in-patient CBT, we assessed symptoms (YBOCS-SR) and self-efficacy (General Self-Efficacy Scale), before and after treatment, as well as the frequency of therapist- and self-guided ERP sessions.

Results:

Patients with more therapist-guided ERP sessions during treatment showed more symptom reduction and the association of self-guided ERP on outcome was mediated by enhanced self-efficacy.

Conclusions:

These findings highlight the importance of both therapist- and self-guided ERP sessions and suggest that therapists should conduct a sufficient number of ERP sessions to optimise treatment.
Rate of gestational weight gain trajectory is associated with adverse pregnancy outcomes
Authors: Yong Heng Yaw , Mohd Shariff Zalilah , Appannah Geeta , Rejali Zulida , Mohd Yusof Barakatun Nisak , Bindels Jacques , Tee Yvonne Yee Siang , van der Beek Eline M
Published: August 2020

Objective:

To examine the gestational weight gain (GWG) trajectory and its possible association with pregnancy outcomes.

Design:

GWG trajectories were identified using the latent class growth model. Binary logistic regression was performed to examine the associations between adverse pregnancy outcomes and these trajectories.

Setting:

Negeri Sembilan, Malaysia.

Participants:

Two thousand one hundred ninety-three pregnant women.

Results:

Three GWG trajectories were identified: ‘Group 1 – slow initial GWG but followed by drastic GWG’, ‘Group 2 – maintaining rate of GWG at 0·58 kg/week’ and ‘Group 3 – maintaining rate of GWG at 0·38 kg/week’. Group 1 had higher risk of postpartum weight retention (PWR) (adjusted OR (AOR) 1·02, 95 % CI 1·01, 1·04), caesarean delivery (AOR 1·03, 95 % CI 1·01, 1·04) and having low birth weight (AOR 1·04, 95 % CI 1·02, 1·05) compared with group 3. Group 2 was at higher risk of PWR (AOR 1·18, 95 % CI 1·16, 1·21), preterm delivery (AOR 1·03, 95 % CI 1·01, 1·05) and caesarean delivery (AOR 1·02, 95 % CI 1·01, 1·03), but at lower risk of having small-for-gestational-age infants (AOR 0·97, 95 % CI 0·96, 0·99) compared with group 3. The significant associations between group 1 and PWR were observed among non-overweight/obese women; between group 1 and caesarean delivery among overweight/obese women; group 2 with preterm delivery and caesarean delivery were only found among overweight/obese women.

Conclusions:

Higher GWG as well as increasing GWG trajectories was associated with higher risk of adverse pregnancy outcomes. Promoting GWG within the recommended range should be emphasised in antenatal care to prevent the risk of adverse pregnancy outcomes.
Reliability and validity of Arabic version of revised general nutrition knowledge questionnaire on university students
Authors: Bataineh Mo’ath F , Attlee Amita
Published: August 2020

Objective:

The current study evaluated the reliability and validity of the Arabic version of the revised general nutrition knowledge questionnaire (GNKQ-R) for adults.

Design:

The eighty-eight-item English GNKQ-R was adapted into an eighty-six-item Arabic version. Four validation studies were conducted for internal (n 805) and external (n 106) reliability, construct validity between participants with (n 84) and without (n 88) nutrition background, convergent validity for associations between nutrition knowledge and demographic characteristics (n 750) and responsiveness to online nutrition information (n 55).

Setting:

United Arab Emirates University in United Arab Emirates and Hashemite University in Jordan.

Participants:

Undergraduate students aged 18 years and above, enrolled in any programme at the two universities, were recruited.

Results:

Overall, internal reliability (Cronbach’s α = 0·91) and external reliability (P = 0·350; intra-class correlation coefficient = 0·84) were high. Significantly higher GNKQ-R scores of students with (66·0 (10·6)) v. without (38·0 (10·7), P < 0·001; d = 2·6) nutrition background indicated high construct validity. Significantly higher GNKQ-R scores among females v. males, older and senior students v. younger and junior students and students in health discipline v. non-health discipline reflected good convergent validity. Significant differences in GNKQ-R scores with nutrition information (time 1 = 37·8 (10·5) and time 2 = 47·7 (9·1), P < 0·001; d = 1·0) indicated high responsiveness to nutrition intervention.

Conclusions:

The Arabic GNKQ-R showed high reliability and validity in the young adult Arab population. Besides the reliability of the overall questionnaire, each section demonstrated adequate reliability. Further studies are warranted to establish the generalisability and applicability of the Arabic GNKQ-R in older adults and in different middle-eastern Arab countries.
Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients’ outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery – a prospective observational study
Authors: Gombert Alexander , Kotelis Drosos , Rückbeil Marcia V. , Barbati Mohammad , Martin Lukas , Marx Gernot , Grommes Jochen , Jacobs Michael J. , Schälte Gereon
Published: August 2020

Summary: Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients’ outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older ( p <0.0001). 40.4% ( n = 21) developed AKI, and 21.2% ( n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% ( n = 4) and 9.6% ( n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1–72.1%], specificity: 90.91% [58.7–99.8%] with an area under the curve [AUC]: 0.694 [0.543–0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4–99.5%], specificity: 52.38% [36.4–68%], and AUC: 0.607 [0.454–0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6–12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients’ outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.
Decrease in amygdala activity during repeated exposure to spider images predicts avoidance behavior in spider fearful individuals
Authors: Björkstrand Johannes , Agren Thomas , Frick Andreas , Hjorth Olof , Furmark Tomas , Fredrikson Mats , Åhs Fredrik
Published: August 2020

Spider phobia is characterized by exaggerated fear of situations where spiders could be present, resulting in avoidance of such situations and compromised quality of life. An important component in psychological treatment of spider phobia is exposure to phobic situations that reduces avoidance behaviors. At the neural level, amygdala responses to phobic material are elevated, but normalizes following exposure treatment. To what extent amygdala activity decreases during a session of repeated phobic stimulation, and whether activity decrease is related to subsequent avoidance is not well studied. We hypothesized reduced amygdala activity during the course of repeated exposure to spider pictures, and that the degree of reduction would predict subsequent avoidance of spider pictures. To test our hypothesis, functional magnetic resonance imaging was performed in 45 individuals with spider fear during repeated exposure to spider pictures. Results showed that repeated exposure to spider stimuli attenuated amygdala reactivity and individual differences in activity reductions predicted subsequent avoidance behavior to spider pictures in an incentive-conflict task, with larger attenuations predicting less avoidance. At 6-month follow up, initial reductions in amygdala activation still predicted avoidance. This result demonstrates that reduction in amygdala responses is related to clinically meaningful outcomes in human anxiety, and suggests that within-session reductions in amygdala responses could be an important mechanism explaining the clinical effects of exposure therapy.
Shedding of cancer susceptibility candidate 4 by the convertases PC7/furin unravels a novel secretory protein implicated in cancer progression
Authors: Duval Stéphanie , Abu-Thuraia Afnan , Elkholi Islam E. , Chen Rui , Seebun Deeptee , Mayne Janice , Côté Jean-François , Figeys Daniel , Seidah Nabil G.
Published: August 2020

The proprotein convertases (PCs) are responsible for the maturation of precursor proteins, and are involved in multiple and critical biological processes. Over the past 30 years, the PCs have had great translational applications, but the physiological roles of PC7, the seventh member of the family, are still obscure. Searching for new substrates of PC7, a quantitative proteomics screen for selective enrichment of N-glycosylated polypeptides secreted from hepatic HuH7 cells identified two human type-II transmembrane proteins of unknown function(s): Cancer Susceptibility Candidate 4 (CASC4) and Golgi Phosphoprotein of 130 kDa (GPP130/GOLIM4). Concentrating on CASC4, its mutagenesis characterized the PC7/Furin-shedding site to occur at KR66↓NS, in HEK293 cells. We defined PC7 and Furin trafficking and activity, and demonstrated that CASC4 shedding occurs in acidic endosomes and/or in the trans-Golgi Network. Our data unraveled a cancer-protective role for CASC4, because siRNA silencing of endogenous CASC4 expression in the invasive triple-negative breast cancer human cell line MDA-MB-231 resulted in a significantly increased cellular migration and invasion. Conversely, MDA-MB-231 cells stably expressing CASC4 exhibited reduced migration and invasion, which can be explained by an increased number of paxillin-positive focal adhesions. This phenotypic cancer-protective role of CASC4 is reversed in cells overexpressing an optimally PC7/Furin-cleaved CASC4 mutant, or upon overexpression of the N-terminally convertase-generated membrane-bound segment. This phenotype was associated with increased formation of podosome-like structures, especially evident in cells overexpressing the N-terminal fragment. In accord, breast cancer patients’ data sets show that high CASC4 and PCSK7 expression levels predict a significantly worse prognosis compared to high CASC4 but low PCSK7 levels. In conclusion, CASC4 shedding not only disrupts its anti-migratory/invasive role, but also generates a membrane-bound fragment that drastically modifies the actin cytoskeleton, resulting in an enhanced cellular migration and invasion. This phenotype might be clinically relevant in the prognosis of breast cancer patients.
Typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis
Authors: Xu Fang , Ma Yuxiang , Huang Wei , Gao Jian , Guo Mengmeng , Li Jianxin , Kong Lingdong , Liang Guang , Du Ronghui , Xu Qiang , Wu Xudong
Published: August 2020

Macrophages, with diverse functions and variable phenotypes, are considered as an important executor of inflammatory diseases. And it has been proved that autophagy is deeply connected with the development of inflammation, while the exact regulatory mechanism still remains unclear, and the application of autophagy regulators in anti-inflammation needs to be further confirmed. Here, we firstly verified that neochromine S5 (hereinafter referred to as S5) significantly inhibited M1-like macrophage polarization with decrease of the proinflammatory cytokines and downregulation of NF-κB and STAT1 signals. Then, in vivo experiments demonstrated S5 improved cecal ligation and puncture (CLP)-induced sepsis specially based on the regulation of M1-like macrophages. Mechanistic studies indicated that S5 treatment dramatically upregulated cellular autophagy in M1-like macrophage. Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization. Animal experiments also confirmed the protection of S5 in CLP mice was dependent on activation of macrophage autophagy. What’s more, as a novel USP14 inhibitor, S5 exhibited higher efficiency and safety than IU1, the known USP14 inhibitor. Therefore, this study has demonstrated that typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis. Moreover, we provide a new candidate compound, S5, for sensitizing autophagy to interfere with the macrophage inflammation.
Systems level profiling of arginine starvation reveals MYC and ERK adaptive metabolic reprogramming
Authors: Brashears Caitlyn B. , Barlin Meltem , Ehrhardt William R. , Rathore Richa , Schultze Matthew , Tzeng Shin-Chen , Van Tine Brian A. , Held Jason M.
Published: August 2020

Arginine auxotrophy due to the silencing of argininosuccinate synthetase 1 (ASS1) occurs in many carcinomas and in the majority of sarcomas. Arginine deiminase (ADI-PEG20) therapy exploits this metabolic vulnerability by depleting extracellular arginine, causing arginine starvation. ASS1-negative cells develop resistance to ADI-PEG20 through a metabolic adaptation that includes re-expressing ASS1. As arginine-based multiagent therapies are being developed, further characterization of the changes induced by arginine starvation is needed. In order to develop a systems-level understanding of these changes, activity-based proteomic profiling (ABPP) and phosphoproteomic profiling were performed before and after ADI-PEG20 treatment in ADI-PEG20-sensitive and resistant sarcoma cells. When integrated with metabolomic profiling, this multi-omic analysis reveals that cellular response to arginine starvation is mediated by adaptive ERK signaling and activation of the Myc–Max transcriptional network. Concomitantly, these data elucidate proteomic changes that facilitate oxaloacetate production by enhancing glutamine and pyruvate anaplerosis and altering lipid metabolism to recycle citrate for oxidative glutaminolysis. Based on the complexity of metabolic and cellular signaling interactions, these multi-omic approaches could provide valuable tools for evaluating response to metabolically targeted therapies.
Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury
Authors: Blanc Roméo S. , Kallenbach Jacob G. , Bachman John F. , Mitchell Amanda , Paris Nicole D. , Chakkalakal Joe V.
Published: August 2020

Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is a feature of age-related regenerative deficits, yet the underlying mechanisms are poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, the expression of Ccr2 in MPs corresponds to the levels of its ligands, the chemokines Ccl2, 7, and 8. We find stimulation of Ccr2-activity inhibits MP fusion and contribution to myofibers. This occurs in association with increases in MAPKp38δ/γ signaling, MyoD phosphorylation, and repression of the terminal myogenic commitment factor Myogenin. High levels of Ccr2-chemokines are a feature of regenerating aged muscle. Correspondingly, deletion of Ccr2 in MPs is necessary for proper fusion into regenerating aged muscle. Finally, opportune Ccr2 inhibition after injury enhances aged regeneration and functional recovery. These results demonstrate that inflammatory-induced activation of Ccr2 signaling in myogenic cells contributes to aged muscle regenerative decline.
Genes with spiralian-specific protein motifs are expressed in spiralian ciliary bands
Authors: Wu Longjun , Hiebert Laurel S. , Klann Marleen , Passamaneck Yale , Bastin Benjamin R. , Schneider Stephan Q. , Martindale Mark Q. , Seaver Elaine C. , Maslakova Svetlana A. , Lambert J. David
Published: August 2020

Spiralia is a large, ancient and diverse clade of animals, with a conserved early developmental program but diverse larval and adult morphologies. One trait shared by many spiralians is the presence of ciliary bands used for locomotion and feeding. To learn more about spiralian-specific traits we have examined the expression of 20 genes with protein motifs that are strongly conserved within the Spiralia, but not detectable outside of it. Here, we show that two of these are specifically expressed in the main ciliary band of the mollusc Tritia (also known as Ilyanassa). Their expression patterns in representative species from five more spiralian phyla—the annelids, nemerteans, phoronids, brachiopods and rotifers—show that at least one of these, lophotrochin, has a conserved and specific role in particular ciliated structures, most consistently in ciliary bands. These results highlight the potential importance of lineage-specific genes or protein motifs for understanding traits shared across ancient lineages.
How machine learning can help select capping layers to suppress perovskite degradation
Authors: Hartono Noor Titan Putri , Thapa Janak , Tiihonen Armi , Oviedo Felipe , Batali Clio , Yoo Jason J. , Liu Zhe , Li Ruipeng , Marrón David Fuertes , Bawendi Moungi G. , Buonassisi Tonio , Sun Shijing
Published: August 2020

Environmental stability of perovskite solar cells (PSCs) has been improved by trial-and-error exploration of thin low-dimensional (LD) perovskite deposited on top of the perovskite absorber, called the capping layer. In this study, a machine-learning framework is presented to optimize this layer. We featurize 21 organic halide salts, apply them as capping layers onto methylammonium lead iodide (MAPbI3) films, age them under accelerated conditions, and determine features governing stability using supervised machine learning and Shapley values. We find that organic molecules’ low number of hydrogen-bonding donors and small topological polar surface area correlate with increased MAPbI3film stability. The top performing organic halide, phenyltriethylammonium iodide (PTEAI), successfully extends the MAPbI3stability lifetime by 4 ± 2 times over bare MAPbI3and 1.3 ± 0.3 times over state-of-the-art octylammonium bromide (OABr). Through characterization, we find that this capping layer stabilizes the photoactive layer by changing the surface chemistry and suppressing methylammonium loss.
Automatic design of mechanical metamaterial actuators
Authors: Bonfanti Silvia , Guerra Roberto , Font-Clos Francesc , Rayneau-Kirkhope Daniel , Zapperi Stefano
Published: August 2020

Mechanical metamaterial actuators achieve pre-determined input–output operations exploiting architectural features encoded within a single 3D printed element, thus removing the need for assembling different structural components. Despite the rapid progress in the field, there is still a need for efficient strategies to optimize metamaterial design for a variety of functions. We present a computational method for the automatic design of mechanical metamaterial actuators that combines a reinforced Monte Carlo method with discrete element simulations. 3D printing of selected mechanical metamaterial actuators shows that the machine-generated structures can reach high efficiency, exceeding human-designed structures. We also show that it is possible to design efficient actuators by training a deep neural network which is then able to predict the efficiency from the image of a structure and to identify its functional regions. The elementary actuators devised here can be combined to produce metamaterial machines of arbitrary complexity for countless engineering applications.
Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function
Authors: Salzer Benjamin , Schueller Christina M. , Zajc Charlotte U. , Peters Timo , Schoeber Michael A. , Kovacic Boris , Buri Michelle C. , Lobner Elisabeth , Dushek Omer , Huppa Johannes B. , Obinger Christian , Putz Eva M. , Holter Wolfgang , Traxlmayr Michael W. , Lehner Manfred
Published: August 2020

T cells engineered to express chimeric antigen receptors (CAR-T cells) have shown impressive clinical efficacy in the treatment of B cell malignancies. However, the development of CAR-T cell therapies for solid tumors is hampered by the lack of truly tumor-specific antigens and poor control over T cell activity. Here we present an avidity-controlled CAR (AvidCAR) platform with inducible and logic control functions. The key is the combination of (i) an improved CAR design which enables controlled CAR dimerization and (ii) a significant reduction of antigen-binding affinities to introduce dependence on bivalent interaction, i.e. avidity. The potential and versatility of the AvidCAR platform is exemplified by designing ON-switch CARs, which can be regulated with a clinically applied drug, and AND-gate CARs specifically recognizing combinations of two antigens. Thus, we expect that AvidCARs will be a highly valuable platform for the development of controllable CAR therapies with improved tumor specificity.
Author Correction: Engineering monocyte/macrophage−specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing
Authors: Scharenberg Samantha G. , Poletto Edina , Lucot Katherine L. , Colella Pasqualina , Sheikali Adam , Montine Thomas J. , Porteus Matthew H. , Gomez-Ospina Natalia
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Iron phthalocyanine with coordination induced electronic localization to boost oxygen reduction reaction
Authors: Chen Kejun , Liu Kang , An Pengda , Li Huangjingwei , Lin Yiyang , Hu Junhua , Jia Chuankun , Fu Junwei , Li Hongmei , Liu Hui , Lin Zhang , Li Wenzhang , Li Jiahang , Lu Ying-Rui , Chan Ting-Shan , Zhang Ning , Liu Min
Published: August 2020

Iron phthalocyanine (FePc) is a promising non-precious catalyst for the oxygen reduction reaction (ORR). Unfortunately, FePc with plane-symmetric FeN4 site usually exhibits an unsatisfactory ORR activity due to its poor O2 adsorption and activation. Here, we report an axial Fe–O coordination induced electronic localization strategy to improve its O2 adsorption, activation and thus the ORR performance. Theoretical calculations indicate that the Fe–O coordination evokes the electronic localization among the axial direction of O–FeN4 sites to enhance O2 adsorption and activation. To realize this speculation, FePc is coordinated with an oxidized carbon. Synchrotron X-ray absorption and Mössbauer spectra validate Fe–O coordination between FePc and carbon. The obtained catalyst exhibits fast kinetics for O2 adsorption and activation with an ultralow Tafel slope of 27.5 mV dec−1 and a remarkable half-wave potential of 0.90 V. This work offers a new strategy to regulate catalytic sites for better performance.
COVID-19 and possible links with Parkinson’s disease and parkinsonism: from bench to bedside
Authors: Sulzer David , Antonini Angelo , Leta Valentina , Nordvig Anna , Smeyne Richard J. , Goldman James E. , Al-Dalahmah Osama , Zecca Luigi , Sette Alessandro , Bubacco Luigi , Meucci Olimpia , Moro Elena , Harms Ashley S. , Xu Yaqian , Fahn Stanley , Ray Chaudhuri K.
Published: August 2020

This Viewpoint discusses insights from basic science and clinical perspectives on coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the brain, with a particular focus on Parkinson’s disease. Major points include that neuropathology studies have not answered the central issue of whether the virus enters central nervous system neurons, astrocytes or microglia, and the brain vascular cell types that express virus have not yet been identified. Currently, there is no clear evidence for human neuronal or astrocyte expression of angiotensin-converting enzyme 2 (ACE2), the major receptor for viral entry, but ACE2 expression may be activated by inflammation, and a comparison of healthy and infected brains is important. In contrast to the 1918 influenza pandemic and avian flu, reports of encephalopathy in COVID-19 have been slow to emerge, and there are so far no documented reports of parkinsonism apart from a single case report. We recommend consensus guidelines for the clinical treatment of Parkinson’s patients with COVID-19. While a role for the virus in causing or exacerbating Parkinson’s disease appears unlikely at this time, aggravation of specific motor and non-motor symptoms has been reported, and it will be important to monitor subjects after recovery, particularly for those with persisting hyposmia.
Morphological and immunohistochemical phenotype of TCs in the intestinal bulb of Grass carp and their potential role in intestinal immunity
Authors: Abd-Elhafeez Hanan H. , Abou-Elhamd Alaa S. , Soliman Soha A.
Published: August 2020

The current study investigated telocytes (TCs) in the intestinal bulb of Grass carp using light microscopy (LM), Transmission electron microscopy (TEM), scanning electron microscopy, and immunohistochemistry (IHC). By LM, TCs were distinguished by the typical morphological features that had a cell body and telopodes using HE, toluidine blue, methylene blue, Marsland silver stain, Grimelius’s silver nitrate, Giemsa, PAS, combined AB pH2,5/PAS, Crossmon’s and Mallory triple trichrome, Van Gieson stains, Verhoeff’s stain, Sudan black, osmic acid, performic acid with methylene blue and bromophenol blue. TCs were identified under the epithelium as an individual cell or formed a TCs sheath. They detected in the lamina propria, between muscle fibers, around the myenteric plexus and fibrous tissue. TCs acquired immunological features of endocrine cells that exhibited high affinity for silver stain, performic acid with methylene blue, Marsland stain, and immunohistochemical staining using chromogranin A. Sub epithelial TCs were closely related to the endocrine cells. TCs and their secretory activities were recognized using acridine orange. TCs were identified by IHC using CD34, CD117, S100-protein, desmin. TCs formed a3D network that established contact with macrophage, mast cells, dendritic cells, lymphocytes, smooth muscle fibers, fibroblast, Schwann cells and nerve fibers. In conclusion, the localization of TCs in relation to different types of immune cells indicated their potential role in the maintenance of intestinal immunity.
Brain-scale cortico-cortical functional connectivity in the delta-theta band is a robust signature of conscious states: an intracranial and scalp EEG study
Authors: Bourdillon Pierre , Hermann Bertrand , Guénot Marc , Bastuji Hélène , Isnard Jean , King Jean-Rémi , Sitt Jacobo , Naccache Lionel
Published: August 2020

Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. In the present work, we estimate long-range cortical connectivity in a series of intracranial and scalp EEG recordings experiments. In the two first experiments intracranial-EEG (iEEG) was recorded during four distinct states within the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We estimated functional connectivity using the following two methods: weighted Symbolic-Mutual-Information (wSMI) and phase-locked value (PLV). Our results showed that long-range functional connectivity in the delta-theta frequency band specifically discriminated CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients. FC in the delta-theta band was significantly higher in patients being in a minimally conscious state (MCS) than in those being in a vegetative state (or unresponsive wakefulness syndrome). Taken together the present results suggest that FC of cortical activity in this slow frequency band is a new and robust signature of conscious states.
Generation of interconnected vesicles in a liposomal cell model
Authors: Ali Doosti Baharan , Fjällborg Daniel , Kustanovich Kiryl , Jesorka Aldo , Cans Ann-Sofie , Lobovkina Tatsiana
Published: August 2020

We introduce an experimental method based upon a glass micropipette microinjection technique for generating a multitude of interconnected vesicles (IVs) in the interior of a single giant unilamellar phospholipid vesicle (GUV) serving as a cell model system. The GUV membrane, consisting of a mixture of soybean polar lipid extract and anionic phosphatidylserine, is adhered to a multilamellar lipid vesicle that functions as a lipid reservoir. Continuous IV formation was achieved by bringing a micropipette in direct contact with the outer GUV surface and subjecting it to a localized stream of a Ca2+ solution from the micropipette tip. IVs are rapidly and sequentially generated and inserted into the GUV interior and encapsulate portions of the micropipette fluid content. The IVs remain connected to the GUV membrane and are interlinked by short lipid nanotubes and resemble beads on a string. The vesicle chain-growth from the GUV membrane is maintained for as long as there is the supply of membrane material and Ca2+ solution, and the size of the individual IVs is controlled by the diameter of the micropipette tip. We also demonstrate that the IVs can be co-loaded with high concentrations of neurotransmitter and protein molecules and displaying a steep calcium ion concentration gradient across the membrane. These characteristics are analogous to native secretory vesicles and could, therefore, serve as a model system for studying secretory mechanisms in biological systems.
Peripheral serum metabolomic profiles inform central cognitive impairment
Authors: Wang Jingye , Wei Runmin , Xie Guoxiang , Arnold Matthias , Kueider-Paisley Alexandra , Louie Gregory , Mahmoudian Dehkordi Siamak , Blach Colette , Baillie Rebecca , Han Xianlin , De Jager Philip L. , Bennett David A. , Kaddurah-Daouk Rima , Jia Wei
Published: August 2020

The incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profiling in both brain (n = 109) and matching serum samples (n = 566) to identify differentially expressed metabolites and metabolic pathways associated with neuropathology and cognitive performance and to identify individuals at high risk of developing cognitive impairment. The abundances of 6 metabolites, glycolithocholate (GLCA), petroselinic acid, linoleic acid, myristic acid, palmitic acid, palmitoleic acid and the deoxycholate/cholate (DCA/CA) ratio, along with the dysregulation scores of 3 metabolic pathways, primary bile acid biosynthesis, fatty acid biosynthesis, and biosynthesis of unsaturated fatty acids showed significant differences across both brain and serum diagnostic groups (P-value < 0.05). Significant associations were observed between the levels of differential metabolites/pathways and cognitive performance, neurofibrillary tangles, and neuritic plaque burden. Metabolites abundances and personalized metabolic pathways scores were used to derive machine learning models, respectively, that could be used to differentiate cognitively impaired persons from those without cognitive impairment (median area under the receiver operating characteristic curve (AUC) = 0.772 for the metabolite level model; median AUC = 0.731 for the pathway level model). Utilizing these two models on the entire baseline control group, we identified those who experienced cognitive decline in the later years (AUC = 0.804, sensitivity = 0.722, specificity = 0.749 for the metabolite level model; AUC = 0.778, sensitivity = 0.633, specificity = 0.825 for the pathway level model) and demonstrated their pre-AD onset prediction potentials. Our study provides a proof-of-concept that it is possible to discriminate antecedent cognitive impairment in older adults before the onset of overt clinical symptoms using metabolomics. Our findings, if validated in future studies, could enable the earlier detection and intervention of cognitive impairment that may halt its progression.
Effects of empagliflozin and target-organ damage in a novel rodent model of heart failure induced by combined hypertension and diabetes
Authors: Kräker Kristin , Herse Florian , Golic Michaela , Reichhart Nadine , Crespo-Garcia Sergio , Strauß Olaf , Grune Jana , Kintscher Ulrich , Ebrahim Manal , Bader Michael , Alenina Natalia , Heuser Arnd , Luft Friedrich C. , Müller Dominik N. , Dechend Ralf , Haase Nadine
Published: August 2020

Type 2 diabetes mellitus and hypertension are two major risk factors leading to heart failure and cardiovascular damage. Lowering blood sugar by the sodium-glucose co-transporter 2 inhibitor empagliflozin provides cardiac protection. We established a new rat model that develops both inducible diabetes and genetic hypertension and investigated the effect of empagliflozin treatment to test the hypothesis if empagliflozin will be protective in a heart failure model which is not based on a primary vascular event. The transgenic Tet29 rat model for inducible diabetes was crossed with the mRen27 hypertensive rat to create a novel model for heart failure with two stressors. The diabetic, hypertensive heart failure rat (mRen27/tetO-shIR) were treated with empagliflozin (10 mg/kg/d) or vehicle for 4 weeks. Cardiovascular alterations were monitored by advanced speckle tracking echocardiography, gene expression analysis and immunohistological staining. The novel model with increased blood pressure und higher blood sugar levels had a reduced survival compared to controls. The rats develop heart failure with reduced ejection fraction. Empagliflozin lowered blood sugar levels compared to vehicle treated animals (182.3 ± 10.4 mg/dl vs. 359.4 ± 35.8 mg/dl) but not blood pressure (135.7 ± 10.3 mmHg vs. 128.2 ± 3.8 mmHg). The cardiac function was improved in all three global strains (global longitudinal strain − 8.5 ± 0.5% vs. − 5.5 ± 0.6%, global radial strain 20.4 ± 2.7% vs. 8.8 ± 1.1%, global circumferential strain − 11.0 ± 0.7% vs. − 7.6 ± 0.8%) and by increased ejection fraction (42.8 ± 4.0% vs. 28.2 ± 3.0%). In addition, infiltration of macrophages was decreased by treatment (22.4 ± 1.7 vs. 32.3 ± 2.3 per field of view), despite mortality was not improved. Empagliflozin showed beneficial effects on cardiovascular dysfunction. In this novel rat model of combined hypertension and diabetes, the improvement in systolic and diastolic function was not secondary to a reduction in left ventricular mass or through modulation of the afterload, since blood pressure was not changed. The mRen27/tetO-shIR strain should provide utility in separating blood sugar from blood pressure-related treatment effects.
Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide
Authors: Isabel Sandra , Graña-Miraglia Lucía , Gutierrez Jahir M. , Bundalovic-Torma Cedoljub , Groves Helen E. , Isabel Marc R. , Eshaghi AliReza , Patel Samir N. , Gubbay Jonathan B. , Poutanen Tomi , Guttman David S. , Poutanen Susan M.
Published: August 2020

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10–25 January) 2020. We also applied structural bioinformatics to assess the potential impact of D614G on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.
Interfacial rheology for the assessment of potential health effects of inhaled carbon nanomaterials at variable breathing conditions
Authors: Kondej Dorota , Sosnowski Tomasz R.
Published: August 2020

Lung surface is the first line of contact between inhaled carbon nanomaterials, CNMs, and the organism, so this is the place where pulmonary health effects begin. The paper analyzes the influence of several CNMs (single- and multi-walled nanotubes with various surface area: 90–1,280 m2/g and aspect ratio: 8–3,750) on the surface-active properties of the lung surfactant, LS, model (Survanta). Effects of CNM concentration (0.1–1 mg/ml) and surface oscillation rate were determined using the oscillating drop method at simulated breathing conditions (2–10 s per cycle, 37 °C). Based on the values of apparent elasticity and viscosity of the interfacial region, new parameters: Sε and Sμ were proposed to evaluate potential effect of particles on the LS at various breathing rates. Some of tested CNMs (e.g., COOH- functionalized short nanotubes) significantly influenced the surfactant dynamics, while the other had weaker effects even at high particle concentration. Analysis of changes in Sε and Sμ provides a new way to evaluate of a possible disturbance of the basic functions of LS. The results show that the expected pulmonary effects caused by inhaled CNMs at variable breathing rate depend not only on particle concentration (inhaled dose) but also on their size, structure and surface properties.
Autophagy regulates trophoblast invasion by targeting NF-κB activity
Authors: Oh Soo-young , Hwang Jae Ryoung , Choi Minji , Kim Yoo-Min , Kim Jung-Sun , Suh Yeon-Lim , Choi Suk-Joo , Roh Cheong-Rae
Published: August 2020

Preeclampsia is one of the most serious complications of pregnancy, affecting 5–10% of parturients worldwide. Recent studies have suggested that autophagy is involved in trophoblast invasion and may be associated with defective placentation underlying preeclampsia. We thus aimed to understand the mechanistic link between autophagy and trophoblast invasion. Using the two most commonly used trophoblast cell lines, JEG-3 and HTR-8/SVneo, we inhibited autophagy by ATG5 and beclin-1 shRNA. Conversion of LC3-II was evaluated in ATG5 and beclin-1 knock-down cells in the presence of the lysosomal protease inhibitors E-64d and pepstatin A, to detect the efficiency of autophagy inhibition. Upon autophagy inhibition, we measured cell invasion, activity of NF-κB and related signaling pathways, MMP-2, MMP-9, sFlt-1, and TNF-α levels. Autophagy inhibition increased the invasiveness of these trophoblastic cell lines and increased Akt and NF-κB activity as well as p65 expression. Of note, an NF-κB inhibitor significantly attenuated the trophoblast invasion induced by autophagy inhibition. Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-α. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-κB pathway and MMP-2, MMP-9, sFlt-1 and TNF-α levels are affected.
Non-linear changes in modelled terrestrial ecosystems subjected to perturbations
Authors: Newbold Tim , Tittensor Derek P. , Harfoot Michael B. J. , Scharlemann Jörn P. W. , Purves Drew W.
Published: August 2020

Perturbed ecosystems may undergo rapid and non-linear changes, resulting in ‘regime shifts’ to an entirely different ecological state. The need to understand the extent, nature, magnitude and reversibility of these changes is urgent given the profound effects that humans are having on the natural world. General ecosystem models, which simulate the dynamics of ecosystems based on a mechanistic representation of ecological processes, provide one novel way to project ecosystem changes across all scales and trophic levels, and to forecast impact thresholds beyond which irreversible changes may occur. We model ecosystem changes in four terrestrial biomes subjected to human removal of plant biomass, such as occurs through agricultural land-use change. We find that irreversible, non-linear responses commonly occur where removal of vegetation exceeds 80% (a level that occurs across nearly 10% of the Earth’s land surface), especially for organisms at higher trophic levels and in less productive ecosystems. Very large, irreversible changes to ecosystem structure are expected at levels of vegetation removal akin to those in the most intensively used real-world ecosystems. Our results suggest that the projected twenty-first century rapid increases in agricultural land conversion may lead to widespread trophic cascades and in some cases irreversible changes to ecosystem structure.
Impact of aerobic exercise type on blood flow, muscle energy metabolism, and mitochondrial biogenesis in experimental lower extremity artery disease
Authors: Pellegrin Maxime , Bouzourène Karima , Aubert Jean-François , Bielmann Christelle , Gruetter Rolf , Rosenblatt-Velin Nathalie , Poitry-Yamate Carole , Mazzolai Lucia
Published: August 2020

Exercise training (ET) is recommended for lower extremity artery disease (LEAD) management. However, there is still little information on the hemodynamic and metabolic adaptations by skeletal muscle with ET. We examined whether hindlimb perfusion/vascularization and muscle energy metabolism are altered differently by three types of aerobic ET. ApoE−/− mice with LEAD were assigned to one of four groups for 4 weeks: sedentary (SED), forced treadmill running (FTR), voluntary wheel running (VWR), or forced swimming (FS). Voluntary exercise capacity was improved and equally as efficient with FTR and VWR, but remained unchanged with FS. Neither ischemic hindlimb perfusion and oxygenation, nor arteriolar density and mRNA expression of arteriogenic-related genes differed between groups. 18FDG PET imaging revealed no difference in the steady-state levels of phosphorylated 18FDG in ischemic and non-ischemic hindlimb muscle between groups, nor was glycogen content or mRNA and protein expression of glucose metabolism-related genes in ischemic muscle modified. mRNA (but not protein) expression of lipid metabolism-related genes was upregulated across all exercise groups, particularly by non-ischemic muscle. Markers of mitochondrial content (mitochondrial DNA content and citrate synthase activity) as well as mRNA expression of mitochondrial biogenesis-related genes in muscle were not increased with ET. Contrary to FTR and VWR, swimming was ineffective in improving voluntary exercise capacity. The underlying hindlimb hemodynamics or muscle energy metabolism are unable to explain the benefits of running exercise.
Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM
Authors: Kashirina Alena S. , López-Duarte Ismael , Kubánková Markéta , Gulin Alexander A. , Dudenkova Varvara V. , Rodimova Svetlana A. , Torgomyan Hayk G. , Zagaynova Elena V. , Meleshina Aleksandra V. , Kuimova Marina K.
Published: August 2020

Membrane fluidity plays an important role in many cell functions such as cell adhesion, and migration. In stem cell lines membrane fluidity may play a role in differentiation. Here we report the use of viscosity-sensitive fluorophores based on a BODIPY core, termed “molecular rotors”, in combination with Fluorescence Lifetime Imaging Microscopy, for monitoring of plasma membrane viscosity changes in mesenchymal stem cells (MSCs) during osteogenic and chondrogenic differentiation. In order to correlate the viscosity values with membrane lipid composition, the detailed analysis of the corresponding membrane lipid composition of differentiated cells was performed by time-of-flight secondary ion mass spectrometry. Our results directly demonstrate for the first time that differentiation of MSCs results in distinct membrane viscosities, that reflect the change in lipidome of the cells following differentiation.