bluuebunny/crossref_metadata_2025 huggingface dataset:
The “terra firma” anecdote: On the attempt to deceive Roald Amundsen during the meeting between the Fram and Terra Nova expeditions in 1911
Authors: Lantz Björn
Published: September 2020

This paper discusses an unsourced anecdote in Roland Huntford’s dual biography of Scott and Amundsen and their race for the South Pole; the first edition of the book was published in 1979. During a meeting between the Fram and Terra Nova in the Bay of Whales on 4 February 1911, Lieutenant Victor Campbell allegedly told Roald Amundsen—in order to deceive him—that one of the British motor sledges was “already on terra firma”. In a recent article in Polar Record, Huntford received criticism for (seemingly) having imagined the episode. However, a description of this incident, though with a slight variation compared to Huntford’s version, can be found in Tryggve Gran’s book, Kampen om Sydpolen [The Battle for the South Pole], published in 1961. Hence, one must conclude that Campbell really did try to mislead Amundsen regarding the motor sledges. Nevertheless, it is unlikely that the attempted deception had an impact on Amundsen’s plan for his south polar journey.
A Pilot Study using the Compensatory Reserve Index to evaluate individuals with Postural Orthostatic Tachycardia syndrome
Authors: Shahi Niti , Shirek Gabrielle , Pickett Kaci , Schwartz Alexandra , Shoop Jamie , Phillips Ryan , Workman Rachel , Kaplan David , Pitula Clio , Moulton Steven
Published: September 2020

Purpose:

The diagnosis of Postural Orthostatic Tachycardia syndrome traditionally involves orthostatic vitals evaluation. The Compensatory Reserve Index is a non-invasive, FDA-cleared algorithm that analyses photoplethysmogram waveforms in real time to trend subtle waveform features associated with varying degrees of central volume loss, from normovolemia to decompensation. We hypothesised that patients who met physiologic criteria for Postural Orthostatic Tachycardia syndrome would have greater changes in Compensatory Reserve Index with orthostatic vitals.

Methods:

Orthostatic vitals and Compensatory Reserve Index values were assessed in individuals previously diagnosed with Postural Orthostatic Tachycardia syndrome and healthy controls aged 12–21 years. Adolescents were grouped for comparison based on whether they met heart rate criteria for Postural Orthostatic Tachycardia syndrome (physiologic Postural Orthostatic Tachycardia syndrome).

Results:

Sixty-one patients were included. Eighteen percent of patients with an existing Postural Orthostatic Tachycardia syndrome diagnosis met heart rate criteria, and these patients had significantly greater supine to standing change in Compensatory Reserve Index (0.67 vs. 0.51; p<0.001). The optimal change in Compensatory Reserve Index for physiologic Postural Orthostatic Tachycardia syndrome was 0.60. Patients with physiologic Postural Orthostatic Tachycardia syndrome were more likely to report previous diagnoses of anxiety or depression (p = 0.054, 0.042).

Conclusion:

An accurate diagnosis of Postural Orthostatic Tachycardia syndrome may be confounded by related comorbidities. Only 18% (8/44) of previously diagnosed Postural Orthostatic Tachycardia syndrome patients met heart rate criteria. Findings support the utility of objective physiologic measures, such as the Compensatory Reserve Index, to more accurately identify patients with true autonomic dysfunction.
Feasibility and diagnostic performance of including point-of-care ultrasound (POCUS) in preparticipation screening of young competitive athletes
Authors: Fabregat-Andrés Óscar , Pina-Buded Santiago , Valverde-Navarro Alfonso Amador
Published: September 2020

Optimal pre-participative screening in young athletes is still controversial. We sought to evaluate the strategy of including point-of-care ultrasound to electrocardiogram. In total, 1188 young competitive athletes were screened in different sports institutions. This proved to be a useful strategy by improving diagnostic performance primarily with respect to detect structural abnormalities and also by minimising positive false cases of electrocardiogram alone.
Die Entdeckung des Insulins
Authors: Diem Peter
Published: September 2020

Zusammenfassung. Die Initiative für die Arbeiten, welche in Toronto 1921 zur Entdeckung des Insulins führten, ging von Frederik G. Banting aus. Er arbeitete unter der Leitung von John J. R. Macleod im Institut für Physiologie der Universität Toronto. In seinem Versuchsprogramm unterstützte ihn der Student Charles H. Best. An Hunden mit experimentellem Diabetes demonstrierten sie den blutzuckersenkenden Effekt von Pankreasextrakten. Dank Zusammenarbeit mit Macleod und James B. Collip, einem Biochemiker der Universität Alberta, der in Toronto ein Sabbatical absolvierte, waren die Arbeiten rasch von Erfolg gekrönt und erste klinische Anwendungen der Extrakte wurden anfangs 1922 möglich. Bereits 1923 erhielten Banting und Macleod den Nobelpreis für Physiologie oder Medizin. Banting teilte seine Hälfte des Preises mit Best, während Macleod seine Hälfte mit Collip teilte. Dass gerade ihre Untersuchungen von Erfolgt gekrönt waren, dürfte zu einem grossen Teil auf Bantings Fähigkeiten als Chirurg, Bests Enthusiasmus als Student, Collips Fähigkeiten als Biochemiker und Macleods Umsicht, die Gruppe zusammenzubringen und mit den notwendigen Ressourcen auszustatten, zurückzuführen sein. In den nächsten zwei Jahrzehnten wurden erste Depotinsulinpräparate verfügbar. In den 1950er Jahren gelangen in der Insulinforschung wichtige Fortschritte, welche die weitere Forschung in der Diabetologie beflügeln sollten. Dies betraf zum einen die Klärung der Insulinstruktur und zum andern die Möglichkeit der Insulinmessung im Blut. Diese beiden Entdeckungen wurden mit dem Nobelpreis für Chemie ausgezeichnet (siehe Kasten 1). In den 1960er und 70er Jahren entwickelten die Insulinhersteller immer bessere Reinigungsmethoden, die schliesslich zu Präparaten mit sehr guter Verträglichkeit und nur sehr seltenen Allergien führten. Später, in den 1980er Jahren, führte die Möglichkeit der biotechnologischen Herstellung von Insulin zu einer immer stärkeren Verbreitung des Humaninsulins. Auf der Grundlage derselben Technologie wurden in den 1990er Jahren und dann im neuen Jahrtausend Insulinanaloga hergestellt, die sozusagen als «Designer-Insuline» neue, klinisch interessante Wirkprofile ermöglichten. Die heutige Vielfalt der verfügbaren Insuline, moderne Formen der Insulinapplikation (Insulinpens, Insulinpumpen) sowie die Blutzuckerselbstkontrolle beziehungsweisen das kontinuierliche Glukosemonitoring bilden heute die Grundlage der modernen intensivierten Insulintherapie.
Diabetes mellitus: Hypoglykämien und Strassenverkehr
Authors: Arici Birsen
Published: September 2020

Zusammenfassung. Viele Diabetiker nehmen aktiv und sicher am Strassenverkehr teil. Hypoglykämien stellen ein besonderes Risiko für Unfälle dar. Daher muss bei Therapie-Formen mit potenziellem Hypoglykämie-Risiko der Fahrer über die geltenden Richtlinien vor und während der Autofahrt informiert werden und sich an diese halten. Diese Übersichtsarbeit zeigt die aktuell geltenden Richtlinien bezüglich Fahreignung und Fahrfähigkeit bei Diabetes mellitus.
Der diabetische Fuss
Authors: Slahor Lea , Iselin Lukas
Published: September 2020

Zusammenfassung. Der diabetische Fuss stellt eine häufige Diabetes-Komplikation dar, wird aber leider weiterhin zu oft vernachlässigt. So wie das Screening auf eine diabetische Retinopathie oder Nephropathie seit Jahren eine Selbstverständlichkeit darstellt, darf bei Patienten mit Diabetes mellitus das diabetische Fuss-Syndrom als relevante Komplikation nicht vergessen werden. Eine periphere Polyneuropathie wie auch die eingeschränkte arterielle Perfusion definieren das diabetische Fuss-Syndrom und stellen eine Risikosituation dar. Entsprechende internationale und schweizerische Guidelines helfen bei der Risikostratifizierung und regeln die Betreuung auf der adäquaten Versorgungsstufe. Durch eine multidisziplinäre Beurteilung und Therapie wird der multifaktoriellen Ätiologie Rechnung getragen. Das interdisziplinäre Konzept verfolgt das Ziel, die Morbidität und Mortalität zu senken, insbesondere Amputationen zu verhindern, und nicht zuletzt die Lebensqualität zu erhalten.
Unmittelbare Reaktionen von Menschen mit Demenz auf individualisierte Musik
Authors: Weise Lisette , Frithjof Töpfer Nils , Wilz Gabriele
Published: September 2020

Zusammenfassung. Hintergrund: Aufgrund steigender Prävalenzraten von Demenzerkrankungen besteht ein dringender Bedarf an effektiven, nicht-pharmakologischen Interventionen zur Verbesserung der Lebensqualität Betroffener und Entlastung ihrer Pflegepersonen. Erste Studien weisen auf die Wirksamkeit individualisierter Musik hin. Bisher sind jedoch die unmittelbar beobachtbaren Reaktionen der Menschen mit Demenz (MmD) auf individualisierte Musik unzureichend untersucht. Ziel: Ziel der Studie war die Erfassung und Auswertung unmittelbarer Auswirkungen einer individualisierten Musikintervention im Pflegeheim mit einem neu entwickelten Beobachtungsbogen zur systematischen Verhaltensbeobachtung. Methode: Bei 20 MmD wurden in 153 Verhaltensbeobachtungen jeweils 32 verschiedene Erlebens- und Verhaltensweisen in 11 Kategorien betrachtet, wie emotionale und motorische Veränderungen als direkte Reaktionen auf das Musikhören. Ergebnisse: Die Teilnehmenden zeigten direkt nach dem Musikhören im Vergleich zu vorher signifikant mehr positive Reaktionen (z. B. Freude, Entspannung) und weniger negative Reaktionen. Auch während des Musikhörens wurden signifikant mehr positive Reaktionen gezeigt, am häufigsten Lächeln, Bewegungen zur Musik, aufmerksames Zuhören, Entspannung und Allgemeine Wachheit / Interesse / Sozialer Kontakt. Schlussfolgerungen: Der Bogen zur systematischen Verhaltensbeobachtung erwies sich als geeignete Methode zur Erfassung der Erlebens- und Verhaltensweisen von MmD. Das Hören individualisierter Musik scheint eine hilfreiche Intervention für MmD im Pflegeheim zu sein.
Arbeitsengagement und Belastungserleben von Health Professionals in Zeiten der Corona-Pandemie
Authors: Wildgruber Domenika , Frey Jana , Seer Max , Pinther Kristina , Koob Clemens , Reuschenbach Bernd
Published: September 2020

Zusammenfassung. Hintergrund: Die Corona-Pandemie führte zu einer starken Beanspruchung von Health Professionals, deren allgemeine berufliche Situation mit einem hohem Belastungserleben verbunden ist. Quantitative Daten zum Belastungserleben der im Gesundheitswesen Tätigen in der Corona-Pandemie und mögliche Auswirkungen auf das Arbeitsengagement fehlen bis dato für Deutschland. Methode: Mittels einer Querschnittsbefragung wurden das Stresserleben, die Sorge um die Gesundheit und das Arbeitsengagement von Health Professionals deutschlandweit erhoben. Das „snapshot survey“ nutzte neben selbst entwickelten Fragen Items eines validierten Instrumentes zur Erfassung des Arbeitsengagements. Über soziale Medien wurden in Form einer Gelegenheitsstichprobe Health Professionals zur Teilnahme eingeladen. Es konnten 1168 gültige Fälle ausgewertet werden. Die Teilnehmenden waren mehrheitlich Pflegende (80 %, n = 855). Ergebnisse: Es zeigt sich, dass Health Professionals mit Direktkontakt zu COVID-19-Erkrankten im Gegensatz zu Befragten ohne Kontakt ein höheres Stresslevel angeben (MW = 3,81, SD = 1,09 vs. MW = 3,44, SD = 1,12, t(1062) = 5,40, p < 0,001; ε = 0,33), sich am meisten Sorgen um die Gesundheit ihrer Angehörigen sowie von Freundinnen und Freunden machen und dass diese Sorgen größer als bei Health Professionals ohne Kontakt sind (MW = 4,45, SD = 0,84 vs. MW = 4,19, SD = 0,94, t(1062) = 4,74, p < 0,001; ε = 0,29). Die Korrelationsanalysen (r = –0,182, p < 0,001) und die multiple Regressionsanalyse (β = –0,182, p < 0,001) ergaben, dass das Arbeitsengagement mit steigendem, pandemiebedingtem Stress abnimmt. Diskussion: Es zeigen sich theoriekonforme Zusammenhänge zwischen Anforderungen, Stresserleben und Arbeitsengagement. Im Vergleich zu früheren Studien ist das Arbeitsengagement in der Stichprobe gering. Zur Reduktion psychischer Belastungsfaktoren in einer Pandemie liegen vielfältige Empfehlungen vor, die nun auch in der Breite für Deutschland zur Anwendung kommen sollten. Hierzu zählen beispielsweise pandemiespezifische Präventionspläne oder die Schaffung eines sanktionsfreien Arbeitsumfeldes.
Pflege in Zeiten von Corona: Zentrale Ergebnisse einer deutschlandweiten Querschnittsbefragung vollstationärer Pflegeheime
Authors: Rothgang Heinz , Domhoff Dominik , Friedrich Anna-Carina , Heinze Franziska , Preuss Benedikt , Schmidt Annika , Seibert Kathrin , Stolle Claudia , Wolf-Ostermann Karin
Published: September 2020

Zusammenfassung. Hintergrund: Pflegebedürftige sind als hoch vulnerable Gruppe von der COVID-19-Pandemie besonders betroffen. Aufgrund ihrer Abhängigkeit von körpernahen Unterstützungsleistungen können Maßnahmen sozialer Distanzierung für sie aber nur sehr eingeschränkt durchgeführt werden. Zudem sind die sozialen und gesundheitlichen Folgen von Kontaktreduktionen für Pflegeheimbewohner_innen besonders hoch. Ziele: Die Studie erhebt die Verbreitung von COVID-19 in Pflegeheimen, die personellen und materiellen Ressourcen der Pflegeheime, den organisatorischen Umgang mit der Situation und die Unterstützungswünsche der Pflegeheime an die Pflegepolitik. Methode: Mehr als 7000 Pflegeheime wurden zur Teilnahme an einer Online-Befragung mit quantitativen und qualitativen Elementen eingeladen (Gelegenheitsstichprobe). Bei einem Rücklauf von 11,4 % liegen Fragebögen von 824 Heimen vor. Diese Daten wurden deskriptiv ausgewertet. Ergebnisse: 824 Pflegeheime nahmen an der Befragung teil. Jedes fünfte Heim hat mindestens einen laborbestätigten Fall von SARS-CoV-2 unter seinen Bewohner_innen und / oder Beschäftigten. Der anfänglich deutliche Mangel an Schutzausrüstung ist inzwischen zurückgegangen, allerdings müssen die Einrichtungen mit verringerten Personalressourcen einen Corona-bedingten Mehraufwand bewältigen. Pflegeheime haben Außenkontakte in einem Maße reduziert, das nun wieder zurückgefahren werden muss. Unterstützungswünsche der Pflegeheime richten sich auf die Bereitstellung und zusätzliche Finanzierung von Schutzausrüstung und Sachmitteln sowie die systematische und regelmäßige Testung der Pflegekräfte und die Bereitstellung bundeseinheitlicher Handlungsanweisungen. Schlussfolgerung: Pflegeheime bedürfen besonderer Aufmerksamkeit, da etwa die Hälfte aller mit COVID-19 Verstorbenen zuvor in Pflegeheimen gelebt haben. Notwendig ist insbesondere die Sicherstellung einer ausreichenden Versorgung mit Schutzausrüstung, die Schulung der Mitarbeitenden und die Durchführung von regelmäßigen Reihentests.
Leaded Soil Endangers Residents in New York Neighborhoods
Authors: Stonecash Matthew
Published: September 2020

New research documents dangerously high levels of lead in the soils of New York City parks and growing communities.
Bifurcations at the Stability Transition of Earthquake Faulting
Authors: Mele Veedu Deepa , Giorgetti Carolina , Scuderi Marco , Barbot Sylvain , Marone Chris , Collettini Cristiano
Published: September 2020

Tectonic faults typically break in a single rupture mode within the range of styles from slow slip to dynamic earthquake failure. However, in increasingly well‐documented instances, the same fault segment fails in both slow and fast modes within a short period, as in the sequences that culminated in the 2011 Mw = 9.0 Tohoku‐Oki, Japan, and 2014 Mw = 8.2 Iquique, Chile, earthquakes. Why slow slip alternates with dynamic rupture in certain regions but not in others is not well understood. Here, we integrate laboratory experiments and numerical simulations to investigate the physical conditions leading to cycles where the two rupture styles alternate. We show that a bifurcation takes place near the stability transition with sequences encompassing various rupture modes under constant loading rate. The range of frictional instabilities and slip cycles identified in this study represents important end‐members to understand the interaction of slow and fast slip on the same fault segment.
Temporal Modulation of the Local Microseism in the North Sea
Authors: Becker D. , Cristiano L. , Peikert J. , Kruse T. , Dethof F. , Hadziioannou C. , Meier T.
Published: September 2020

Primary and secondary microseism originating in the world oceans and peaking at around 14 and 7 s, respectively, characterize the Earth's background noise in that frequency range. Microseism generated in marginal seas with partly shorter periods and higher spatial and temporal variability is less studied and requires stations in immediate proximity to the source to be observed. Such studies can help to elucidate the exact microseism generation areas and mechanisms in a constrained area. We analyze 15 years of broadband data recorded at the seismic station on Helgoland island in the marginal North Sea. In addition to remote primary (RPM) and secondary microseism (RSM) originating in the North Atlantic, we observe strong and dominant local secondary microseism (LSM) with on average higher frequencies above 0.2 Hz, in accordance with shorter wave periods of about 4–8 s in the shallow North Sea. During times with low RSM activity we observe local primary microseism (LPM) at frequencies in agreement with local ocean wave periods. The higher horizontal to vertical (H/V) ratio of LPM with respect to LSM indicates a major non‐Rayleigh wave contribution. LSM and LPM show a strong modulation with local semidiurnal ocean tides and microseism energy maxima preceding the water level maximum by 2.5 and 1.5 hr, respectively. This time shift might be influenced by stronger currents during rising than falling tides. Active sources of tide‐modulated microseism migrate along the North Sea coast in sync with the ocean tidal signal as evidenced by comparison of LSM maxima at stations distributed along the coast.
Non‐Local Triggering in Rock Fracture
Authors: Xiong Qiquan , Hampton Jesse C.
Published: September 2020

Combining multiphysics observations in the laboratory, we present novel phenomena for the analogue between rock fracture and seismicity. We show, for the first time in a laboratory setting, how a large‐scale flaw in rock can facilitate “non‐local triggering”—remotely triggered damage in rock mass. Results prove analogues of rock fracture evolution to natural seismicity including several lab‐analogues on seismicity model predictions beyond power law. We observe under specimen‐scale criticality a relatively small AE perturbation occurring at a seemingly random location can trigger cascading events whose spatial span can traverse the entire rock fracture system. The inclination angle of the non‐local triggering pairs shows dependence on the large‐scale flaw, and the subsequent generations of triggered AEs by these non‐local triggers decline significantly slower than that of the general triggers. The rock fracture system evolves to a state where the resistance to non‐local triggering continuously reduces, bridging the gap between an idealized lab setting and a natural fault. The non‐locally triggered events can also be reactivated as the rock fracture system evolves towards increased complexity. These lab‐observations as well as the understanding on the analogue relationship between rock fracture and seismicity may shed new light on the insight of the periodical, dynamic, and unpredictable nature of the multiscale rock fracture process.
Characterization of Surface Heterogeneity‐Induced Convection Using Cluster Analysis
Authors: Chen Jingyi , Hagos Samson , Xiao Heng , Fast Jerome D. , Feng Zhe
Published: September 2020

Land‐atmosphere interactions and boundary layer processes often control the formation of shallow clouds and subsequently deep convective precipitation over the U.S. Southern Great Plains. In this study, we examine the impacts of large‐scale advection on the cloud populations and land‐atmospheric coupling observed during the Holistic Interactions of Shallow Clouds, Aerosols, and Land‐Ecosystems field campaign in 2016. We performed two large eddy simulations using the Weather Research and Forecasting Model for a day in which the transition from clear‐sky to shallow precipitating clouds and isolated deep convection was observed. The control simulation reproduced the overall distribution of cloud populations by using realistic soil conditions with an interactive land model. In the sensitivity simulation where large‐scale advection is removed, a strong relationship between the land and boundary layer is found. To study the timing, location, and intensity of convective initiation and the relationship of clouds with land surface properties, a cluster analysis of equivalent potential temperature is performed for the simulation without large‐scale advection. That analysis shows that convective clouds first form over regions with higher surface sensible heat flux. Precipitation from those convective clouds likely triggers new updrafts nearby about 2 hr later through the lifting associated with cold pools. The cluster analysis also shows that in addition to the spatial pattern of soil moisture, land use and soil texture in western Oklahoma also influence the location of convective initiation.
The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties
Authors: Liu Na , Yang Rui , Shi Ying , Chen Ling , Liu Yating , Wang Zuli , Liu Shouping , Ouyang Lianlian , Wang Haiyan , Lai Weiwei , Mao Chao , Wang Min , Cheng Yan , Liu Shuang , Wang Xiang , Zhou Hu , Cao Ya , Xiao Desheng , Tao Yongguang
Published: September 2020

Posttranslational modifications (PTMs) of proteins, including chromatin modifiers, play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties. However, the roles of Lymphoid-specific helicase (LSH), a DNA methylation modifier, in modulating stem-like properties in cancer are still not clearly clarified. Therefore, exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH. Here, we demonstrate that LSH is capable to undergo PTMs, including methylation and phosphorylation. The arginine methyltransferase PRMT5 can methylate LSH at R309 residue, meanwhile, LSH could as well be phosphorylated by MAPK1 kinase at S503 residue. We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue, which eventually promoting stem-like properties in lung cancer. Whereas, phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties, indicating the critical roles of LSH PTMs in modulating stem-like properties. Thus, our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.
Direct interactions with commensal streptococci modify intercellular communication behaviors of Streptococcus mutans
Authors: Kaspar Justin R , Lee Kyulim , Richard Brook , Walker Alejandro R , Burne Robert A
Published: September 2020

The formation of dental caries is a complex process that ultimately leads to damage of the tooth enamel from acids produced by microbes in attached biofilms. The bacterial interactions occurring within these biofilms between cariogenic bacteria, such as the mutans streptococci, and health-associated commensal streptococci, are thought to be critical determinants of health and disease. To better understand these interactions, a Streptococcus mutans reporter strain that actively monitors cell–cell communication via peptide signaling was cocultured with different commensal streptococci. Signaling by S. mutans, normally highly active in monoculture, was completely inhibited by several species of commensals, but only when the bacteria were in direct contact with S. mutans. We identified a novel gene expression pattern that occurred in S. mutans when cultured directly with these commensals. Finally, mutant derivatives of commensals lacking previously shown antagonistic gene products displayed wild-type levels of signal inhibition in cocultures. Collectively, these results reveal a novel pathway(s) in multiple health-associated commensal streptococci that blocks peptide signaling and induces a common contact-dependent pattern of differential gene expression in S. mutans. Understanding the molecular basis for this inhibition will assist in the rational design of new risk assessments, diagnostics, and treatments for the most pervasive oral infectious diseases.
Gene loss through pseudogenization contributes to the ecological diversification of a generalist Roseobacter lineage
Authors: Chu Xiao , Li Siyao , Wang Sishuo , Luo Danli , Luo Haiwei
Published: September 2020

Ecologically relevant genes generally show patchy distributions among related bacterial genomes. This is commonly attributed to lateral gene transfer, whereas the opposite mechanism—gene loss—has rarely been explored. Pseudogenization is a major mechanism underlying gene loss, and pseudogenes are best characterized by comparing closely related genomes because of their short life spans. To explore the role of pseudogenization in microbial ecological diversification, we apply rigorous methods to characterize pseudogenes in the 279 newly sequenced Ruegeria isolates of the globally abundant Roseobacter group collected from two typical coastal habitats in Hong Kong, the coral Platygyra acuta and the macroalga Sargassum hemiphyllum. Pseudogenes contribute to ~16% of the accessory genomes of these strains. Ancestral state reconstruction reveals that many pseudogenization events are correlated with ancestral niche shifts. Specifically, genes related to resource scavenging and energy acquisition were often pseudogenized when roseobacters inhabiting carbon-limited and energy-poor coral skeleton switched to other resource-richer niches. For roseobacters inhabiting the macroalgal niches, genes for nitrogen regulation and carbohydrate utilization were important but became dispensable upon shift to coral skeleton where nitrate is abundant but carbohydrates are less available. Whereas low-energy-demanding secondary transporters are more favorable in coral skeleton, ATP-driven primary transporters are preferentially kept in the energy-replete macroalgal niches. Moreover, a large proportion of these families mediate organismal interactions, suggesting their rapid losses by pseudogenization as a potential response to host and niche shift. These findings illustrate an important role of pseudogenization in shaping genome content and driving ecological diversification of marine roseobacters.
Fluoxetine-induced recovery of serotonin and norepinephrine projections in a mouse model of post-stroke depression
Authors: Zahrai Amin , Vahid-Ansari Faranak , Daigle Mireille , Albert Paul R.
Published: September 2020

Chronic treatment with fluoxetine (FLX) is required for its antidepressant effects, but the role of serotonin (5-HT) axonal plasticity in FLX action is unknown. To address this, we examined mice with a stroke in the left medial prefrontal cortex (mPFC) resulting in persistent anxiety-like and depression-like behaviors and memory deficits as a model of post-stroke depression. Chronic treatment with FLX (but not exercise) completely reversed the behavioral phenotype and partially reversed changes in FosB-labeled cells in the mPFC, nucleus accumbens, septum, hippocampus, basolateral amygdala (BLA), and dorsal raphe. In these regions, 5-HT or norepinephrine (NE) innervation was quantified by staining for 5-HT or NE transporters, respectively. 5-HT synapses and synaptic triads were identified as synaptophysin-stained sites on 5-HT axons located proximal to gephyrin-stained or PSD95-stained spines. A week after stroke, 5-HT innervation was greatly reduced at the stroke site (left cingulate gyrus (CG) of the mPFC) and the left BLA. Chronically, 5-HT and NE innervation was reduced at the left CG, nucleus accumbens, and BLA, with no changes in other regions. In these areas, pre-synaptic and post-synaptic 5-HT synapses and triads to inhibitory (gephyrin+) sites were reduced, while 5-HT contacts at excitatory (PSD95+) sites were reduced in the CG and prelimbic mPFC. Chronic FLX, but not exercise, reversed these reductions in 5-HT innervation but incompletely restored NE projections. Changes in 5-HT innervation were verified using YFP staining in mice expressing YFP-tagged channelrhodopsin in 5-HT neurons. Thus, FLX-induced 5-HT axonal neuroplasticity of forebrain projections may help mediate recovery from brain injury.
STING regulates BCR signaling in normal and malignant B cells
Authors: Tang Chih-Hang Anthony , Lee Avery C. , Chang Shiun , Xu Qin , Shao Andong , Lo Yun , Spalek Walker T. , Pinilla-Ibarz Javier A. , Del Valle Juan R. , Hu Chih-Chi Andrew
Published: September 2020

STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM, Igα, and Igβ via SEL1L/HRD1-mediated ER-associated degradation (ERAD). B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated STING. When immunized with T-independent antigens, STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type (WT) mice. We further generated B cell-specific STINGKO mice and showed that STINGKO B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient counterparts. When B cell-specific STINGKO mice were T-independently immunized, they produced significantly more antigen-specific plasma cells and antibodies than immunized STINGWT mice. Since both human and mouse IGHV-unmutated malignant chronic lymphocytic leukemia (CLL) cells downregulated the expression of STING, we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL cells. We generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient counterparts. These results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells.
Clinical development of CAR T cell therapy in China: 2020 update
Authors: Wei Jianshu , Guo Yelei , Wang Yao , Wu Zhiqiang , Bo Jian , Zhang Bin , Zhu Jun , Han Weidong
Published: September 2020

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to the data from the clinicaltrials.gov website, China became the country with the most registered CAR T trials in September 2017. As of June 30, 2020, the number of registered CAR T trials in China has reached 357. In addition, as many as 150 other CAR T trials have been registered on ChiCTR. Although CAR T therapy is flourishing in China, there are still some problems that cannot be ignored. In this review, we aim to systematically summarize the clinical practice of CAR T-cell therapy in China. This review will provide an informative reference for colleagues in the field, and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.
The use of mobile phone data to inform analysis of COVID-19 pandemic epidemiology
Authors: Grantz Kyra H. , Meredith Hannah R. , Cummings Derek A. T. , Metcalf C. Jessica E. , Grenfell Bryan T. , Giles John R. , Mehta Shruti , Solomon Sunil , Labrique Alain , Kishore Nishant , Buckee Caroline O. , Wesolowski Amy
Published: September 2020

The ongoing coronavirus disease 2019 (COVID-19) pandemic has heightened discussion of the use of mobile phone data in outbreak response. Mobile phone data have been proposed to monitor effectiveness of non-pharmaceutical interventions, to assess potential drivers of spatiotemporal spread, and to support contact tracing efforts. While these data may be an important part of COVID-19 response, their use must be considered alongside a careful understanding of the behaviors and populations they capture. Here, we review the different applications for mobile phone data in guiding and evaluating COVID-19 response, the relevance of these applications for infectious disease transmission and control, and potential sources and implications of selection bias in mobile phone data. We also discuss best practices and potential pitfalls for directly integrating the collection, analysis, and interpretation of these data into public health decision making.
Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D
Authors: Viñuela Ana , Varshney Arushi , van de Bunt Martijn , Prasad Rashmi B. , Asplund Olof , Bennett Amanda , Boehnke Michael , Brown Andrew A. , Erdos Michael R. , Fadista João , Hansson Ola , Hatem Gad , Howald Cédric , Iyengar Apoorva K. , Johnson Paul , Krus Ulrika , MacDonald Patrick E. , Mahajan Anubha , Manning Fox Jocelyn E. , Narisu Narisu , Nylander Vibe , Orchard Peter , Oskolkov Nikolay , Panousis Nikolaos I. , Payne Anthony , Stitzel Michael L. , Vadlamudi Swarooparani , Welch Ryan , Collins Francis S. , Mohlke Karen L. , Gloyn Anna L. , Scott Laura J. , Dermitzakis Emmanouil T. , Groop Leif , Parker Stephen C. J. , McCarthy Mark I.
Published: September 2020

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.
Evidence corroborates identity of isolated fossil feather as a wing covert of Archaeopteryx
Authors: Carney Ryan M. , Tischlinger Helmut , Shawkey Matthew D.
Published: September 2020

The historic fossil feather from the Jurassic Solnhofen has played a pivotal but controversial role in our evolutionary understanding of dinosaurs and birds. Recently, a study confirmed the diagnostic morphology of the feather’s original calamus, but nonetheless challenged the proposed identity as an Archaeopteryx covert. However, there are errors in the results and interpretations presented. Here we show that the feather is most likely an upper major primary covert, based on its long calamus (23.3% total length) and eight other anatomical attributes. Critically, this hypothesis is independently supported by evidence of similar primary coverts in multiple specimens of Archaeopteryx–including from the same fossil site and horizon as the isolated feather. We also provide additional insights, such as an updated colour reconstruction of the entire feather as matte black, with 90% probability. Given the isolated nature of the fossil feather, we can never know the anatomical and taxonomic provenance with 100% certainty. However, based on all available evidence, the most empirical and parsimonious conclusion is that this feather represents a primary covert from the ancient wing of Archaeopteryx.
Contact lenses, the reverse Pulfrich effect, and anti-Pulfrich monovision corrections
Authors: Rodriguez-Lopez Victor , Dorronsoro Carlos , Burge Johannes
Published: September 2020

Interocular differences in image blur can cause processing speed differences that lead to dramatic misperceptions of the distance and three-dimensional direction of moving objects. This recently discovered illusion—the reverse Pulfrich effect—is caused by optical conditions induced by monovision, a common correction for presbyopia. Fortunately, anti-Pulfrich monovision corrections, which darken the blurring lens, can eliminate the illusion for many viewing conditions. However, the reverse Pulfrich effect and the efficacy of anti-Pulfrich corrections have been demonstrated only with trial lenses. This situation should be addressed, for clinical and scientific reasons. First, it is important to replicate these effects with contact lenses, the most common method for delivering monovision. Second, trial lenses of different powers, unlike contacts, can cause large magnification differences between the eyes. To confidently attribute the reverse Pulfrich effect to interocular optical blur differences, and to ensure that previously reported effect sizes are reliable, one must control for magnification. Here, in a within-observer study with five separate experiments, we demonstrate that (1) contact lenses and trial lenses induce indistinguishable reverse Pulfrich effects, (2) anti-Pulfrich corrections are equally effective when induced by contact and trial lenses, and (3) magnification differences do not cause or impact the Pulfrich effect.
A non-lethal method for detection of Bonamia ostreae in flat oyster (Ostrea edulis) using environmental DNA
Authors: Jørgensen Louise von Gersdorff , Nielsen Johan Wedel , Villadsen Mikkel Kehler , Vismann Bent , Dalvin Sussie , Mathiessen Heidi , Madsen Lone , Kania Per Walter , Buchmann Kurt
Published: September 2020

Surveillance and diagnosis of parasitic Bonamia ostreae infections in flat oysters (Ostrea edulis) are prerequisites for protection and management of wild populations. In addition, reliable and non-lethal detection methods are required for selection of healthy brood oysters in aquaculture productions. Here we present a non-lethal diagnostic technique based on environmental DNA (eDNA) from water samples and demonstrate applications in laboratory trials. Forty oysters originating from Limfjorden, Denmark were kept in 30 ppt sea water in individual tanks. Water was sampled 6 days later, after which all oysters were euthanized and examined for infection, applying PCR. Four oysters (10%) were found to be infected with B. ostreae in gill and mantle tissue. eDNA purified from the water surrounding these oysters contained parasite DNA. A subsequent sampling from the field encompassed 20 oysters and 15 water samples from 5 different locations. Only one oyster turned out positive and all water samples proved negative for B. ostreae eDNA. With this new method B. ostreae may be detected by only sampling water from the environment of isolated oysters or isolated oyster populations. This non-lethal diagnostic eDNA method could have potential for future surveys and oyster breeding programs aiming at producing disease-free oysters.
Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
Authors: Hamamura-Yasuno Eri , Iguchi Takuma , Kumagai Kazuyoshi , Tsuchiya Yoshimi , Mori Kazuhiko
Published: September 2020

MAS-related G protein coupled receptor-X2 (MRGPRX2), expressed in human mast cells, is associated with drug-induced pseudo-allergic reactions. Dogs are highly susceptible to drug-induced anaphylactoid reactions caused by various drugs; however, the distribution and physiological function of canine MRGPR family genes, including MRGPRX2, remain largely unknown. In the present study, we clarified the distribution of dog MRGPR family genes by real-time quantitative PCR and in situ hybridisation. We also investigated the stimulatory effects of various histamine-releasing agents, including fluoroquinolones, on HEK293 cells transiently transfected with dog MRGPR family genes to identify their physiological function. Dog MRGPRX2 and MRGPRG were distributed in a limited number of tissues, including the skin (from the eyelid, abdomen, and cheek), whereas MRGPRD and MRGPRF were extensively expressed in almost all tissues examined. Histochemical and in situ hybridisation analyses revealed that MRGPRX2 was expressed in dog connective tissue-type mast cells in the skin. Intracellular Ca2+ mobilisation assay revealed that HEK293 cells, expressing dog MRGPRX2 or human MRGPRX2, but not dog MRGPRD, MRGPRF, and MRGPRG, responded to histamine-releasing agents. Our results suggest that dog MRGPRX2 is the functional orthologue of human MRGPRX2 and plays an essential role in drug-induced anaphylactoid reactions in dogs.
Cross-sectional and prospective relationship between physical activity and depression symptoms
Authors: Marques Adilson , Bordado Joana , Peralta Miguel , Gouveia Elvio R. , Tesler Riki , Demetriou Yolanda , Gomez Baya Diego
Published: September 2020

This study aimed to analyse the cross-sectional and prospective relationship between moderate and vigorous physical activity (PA) and depression symptoms. This study analysed 32,392 European late middle-aged to older adults, from 14 European countries across a 4-year follow-up. Data was collected in the fourth (in 2011) and sixth (in 2015) wave, from the Survey of Health, Ageing and Retirement in Europe (SHARE). For the present analysis, participants were considered who responded to the EURO-D 12-item scale of depression symptoms and reported the intensity and frequency of PA. ANCOVAs were conducted to assess the cross-sectional and prospective associations. For both men and women, engaging in moderate or vigorous PA in 2011 was associated with a lower score of depression in 2011 and 2015. From the prospective analysis, moderate and vigorous PA in 2011 was inversely associated with the score of depression. This association remains significant in the fully adjusted for self-rated health, sociodemographic characteristics, and the presence of chronic diseases. Moderate and vigorous PA at least once a week is negatively related to the score of depression, both in men and women. PA is negatively associated with depression symptoms, and from prospective analysis PA predicts lower depression scores 4 years later.
Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study
Authors: Albert Vega Chloé , Oriol Guy , Bartolo François , Lopez Jonathan , Pachot Alexandre , Rimmelé Thomas , Venet Fabienne , Leray Véronique , Monneret Guillaume , Delwarde Benjamin , Brengel-Pesce Karen , Textoris Julien , Mallet François , Trouillet-Assant Sophie
Published: September 2020

The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.
An association study of C9orf3, a novel component of the renin-angiotensin system, and hypertension in diabetes
Authors: Ichikawa Mai , Konoshita Tadashi , Makino Yasukazu , Suzuki Jinya , Ishizuka Tamotsu , Nakamura Hiroyuki
Published: September 2020

The renin-angiotensin system (RAS) is important in the onset and course of cardiovascular, kidney, and metabolic disorders. Previous reports showed that the RAS blockade protects organs and suppress the development of type 2 diabetes mellitus. A novel component of the RAS, namely, chromosome 9 open reading frame 3 (C9orf3), was recently identified, however, its effects are unclear. We evaluated whether the genetic variant of C9orf3 is associated with morbidity of hypertension among subjects with type 2 diabetes. We enrolled 382 subjects with type 2 diabetes, 222 of whom were diagnosed with hypertension. Human leukocyte genomic DNA was isolated and a genetic variant was analyzed for a C/T variant of C9orf3 (rs4385527) via PCR analysis. The relationship between the genotype and hypertension morbidity among subjects with diabetes was examined. The proportion of the respective C9orf3 genetic variants were as follows 247 CC, 119 CT, and 16 TT. The risk of hypertension was determined to be 1.58, with a 95% confidence interval of 1.11–2.27. Moreover, the p value was 0.012 for allelic comparison and for Armitage’s trend test, with the C allele identified as the risk factor. Consequently, hypertension was markedly associated with type 2 diabetes in subjects with the C9orf3 variant, exhibiting a nearly 1.6-fold increased risk. The C variant of a new component of the RAS, C9orf3 (rs4385527) might have a considerable impact on the pathogenesis of hypertension in diabetes.
Aenigmachannidae, a new family of snakehead fishes (Teleostei: Channoidei) from subterranean waters of South India
Authors: Britz Ralf , Dahanukar Neelesh , Anoop V. K. , Philip Siby , Clark Brett , Raghavan Rajeev , Rüber Lukas
Published: September 2020

Pronounced organism-wide morphological stasis in evolution has resulted in taxa with unusually high numbers of primitive characters. These ‘living fossils’ hold a prominent role for our understanding of the diversification of the group in question. Here we provide the first detailed osteological analysis ofAenigmachanna gollumbased on high-resolution nano-CT scans and one cleared and stained specimen of this recently described snakehead fish from subterranean waters of Kerala in South India. In addition to a number of derived and unique features,Aenigmachannahas several characters that exhibit putatively primitive conditions not encountered in the family Channidae. Our morphological analysis provides evidence for the phylogenetic position ofAenigmachannaas the sister group to Channidae. Molecular analyses further emphasize the uniqueness ofAenigmachannaand indicate that it is a separate lineage of snakeheads, estimated to have split from its sister group at least 34 or 109 million years ago depending on the fossil calibration employed. This may indicate thatAenigmachannais a Gondwanan lineage, which has survived break-up of the supercontinent, with India separating from Africa at around 120 mya. The surprising morphological disparity ofAenigmachannafrom members of the Channidae lead us to erect a new family of snakehead fishes, Aenigmachannidae, sister group to Channidae, to accommodate these unique snakehead fishes.