bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrategias de manejo de plantas leñosas en ambientes de altura: Área Natural Protegida Laguna del Diamante (Mendoza, Argentina)
Authors: Andreoni Diego , Durán Víctor
Published: October 2021

Los sitios arqueológicos de altura en el Centro Oeste Argentino y Chile Central se caracterizan por estar localizados en ambientes altoandinos, presentar recintos pircados, cerámica afín a complejos culturales de la cuenca Maipo-Mapocho de Chile Central, evidencias de caza de camélidos y procesamiento de plantas silvestres y cultivadas. En este trabajo se presenta el estudio antracológico de dos sitios ubicados en el Área Natural Protegida Laguna del Diamante (3.200 m snm), con evidencias de ocupación humana entre 2.100 años aP y tiempos históricos. Para caracterizar cuali-cuantitativamente el registro antracológico de LD-S2 y LD-S4 se utilizaron métodos estándar. Se identificaron siete taxa vegetales. Las estrategias de manejo de plantas leñosas detectadas estuvieron orientadas a la recolección de maderas locales (familia Asteraceae yAdesmiasp.), junto con otras de pisos altitudinales inferiores, tanto de Chile Central (Acaciaaff.caven,Persea lingueyQuillaja saponaria) como de Argentina (Prosopisaff.alpataco), así como de un taxón que crece en ambos flancos cordilleranos (Ochetophilasp.). Los resultados obtenidos se integraron con estudios previos sobre fuentes y artefactos de obsidiana y análisis isotópicos y cerámicos. Todos muestran un acceso predominante de sociedades de la cuenca cordillerana del río Maipo a Laguna del Diamante.
Tilting pairs in extriangulated categories
Authors: Zhao Tiwei , Zhu Bin , Zhuang Xiao
Published: October 2021

Extriangulated categories were introduced by Nakaoka and Palu to give a unification of properties in exact categories and extension-closed subcategories of triangulated categories. A notion of tilting pairs in an extriangulated category is introduced in this paper. We give a Bazzoni characterization of tilting pairs in this setting. We also obtain the Auslander–Reiten correspondence of tilting pairs which classifies finite $\mathcal {C}$-tilting subcategories for a certain self-orthogonal subcategory $\mathcal {C}$ with some assumptions. This generalizes the known results given by Wei and Xi for the categories of finitely generated modules over Artin algebras, thereby providing new insights in exact and triangulated categories.
Middle Miocene climate transition in the Tibetan Plateau: identification and significance
Authors: Song Shijun , Huang Lei , Zhang Yongshu , Zhang Qi , Zhou Fei , Liu Chiyang , Chen Yan , Wu Yingxiong , Zhang Yiming
Published: October 2021

The Middle Miocene Climatic Optimum is known for abrupt events during the global cooling trend of the past 20 Ma. Its identification in the Tibetan Plateau can help explain the cause of the critical Middle Miocene climate transition in Central Asia. In this study, fine-grained mixed sediments widely distributed in the Miocene Qaidam Lake in the northern Tibetan Plateau were used as a sensitive indicator for palaeoclimate. Their geochemical characteristics were investigated, together with an analysis of 2600 m long successive gamma-ray logging data from the whole JS2 drillcore, to understand the mid-Miocene climate transition in the Tibetan Plateau. By comparing the gamma-ray curve of the mixed sediments with global temperature, the Middle Miocene Climatic Optimum event can be easily identified. Further, the detailed petrological features and geochemical data of lacustrine fine-grained mixed sediments from a 400 m drillcore show oxidizing, high-sedimentation rate and brackish-saline water conditions in a semi-arid climate during the Middle Miocene period, demonstrating a dryer climate in the Qaidam Basin than in the monsoon-sensitive regions in Central Asia. These fine-grained mixed sediments have recorded climate drying before 15.3 Ma that represents a climatic transition within the Middle Miocene Climatic Optimum; increasing carbonate-rich mixed sediments, decreasing algal limestone layers and decreasing lacustrine organic matter are indicators of this transition. Regional tectonic events include the retreat of the Paratethys from Central Asia at ∼15 Ma and the synchronous tectonic reorganization of the Altyn-Tagh fault system and the northeastern Tibetan Plateau. We find that global climate change is the primary factor affecting the overall characteristics and changes of the Neogene climate in the Qaidam Basin, including the occurrence of the Middle Miocene Climatic Optimum and the cooling and drying tendency, while the regional events are a secondary factor.
Paediatric otogenic cerebral venous sinus thrombosis: a multidisciplinary approach
Authors: Constable J D , Hajioff D
Published: October 2021

Background

Paediatric otogenic cerebral venous sinus thrombosis is a rare, heterogeneous and life-threatening condition, with possible otological, neurological and ophthalmological sequelae. Its course and outcomes can be widely variable. The publications available often consider individual aspects of paediatric otogenic cerebral venous sinus thrombosis management. The condition itself and the nature of the currently available guidance can lead to uncertainties when holistically managing patients with paediatric otogenic cerebral venous sinus thrombosis.

Objectives

Clear recommendations for the comprehensive assessment and management of paediatric otogenic cerebral venous sinus thrombosis are presented, along with the literature review upon which they are based. Its clinical and radiological assessment are discussed.

Conclusion

A multidisciplinary approach to assessment and management is recommended, inclusive of infectious diseases, ENT surgery, neurology, ophthalmology and haematology. On balance, anticoagulation is recommended for three months. Follow-up imaging is not recommended in the absence of clinical concern. Follow up by ENT surgery, neurology and ophthalmology departments is recommended.
Reciprocal circulation pattern of SARS-CoV-2 and influenza viruses during the influenza seasons 2019/2020 and 2020/2021 in the Bavarian Influenza Sentinel (Germany)
Authors: Heinzinger Susanne , Eberle Ute , Angermeier Hildegard , Flechsler Jennifer , Konrad Regina , Dangel Alexandra , Berger Carola , Sprenger Annika , Hepner Sabrina , Biere Barbara , Liebl Bernhard , Ackermann Nikolaus , Sing Andreas
Published: October 2021

The corona virus disease-2019 (COVID-19) pandemic began in Wuhan, China, and quickly spread around the world. The pandemic overlapped with two consecutive influenza seasons (2019/2020 and 2020/2021). This provided the opportunity to study community circulation of influenza viruses and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in outpatients with acute respiratory infections during these two seasons within the Bavarian Influenza Sentinel (BIS) in Bavaria, Germany. From September to March, oropharyngeal swabs collected at BIS were analysed for influenza viruses and SARS-CoV-2 by real-time polymerase chain reaction. In BIS 2019/2020, 1376 swabs were tested for influenza viruses. The average positive rate was 37.6%, with a maximum of over 60% (in January). The predominant influenza viruses were Influenza A(H1N1)pdm09 (n = 202), Influenza A(H3N2) (n = 144) and Influenza B Victoria lineage (n = 129). In all, 610 of these BIS swabs contained sufficient material to retrospectively test for SARS-CoV-2. SARS-CoV-2 RNA was not detectable in any of these swabs. In BIS 2020/2021, 470 swabs were tested for influenza viruses and 457 for SARS-CoV-2. Only three swabs (0.6%) were positive for Influenza, while SARS-CoV-2 was found in 30 swabs (6.6%). We showed that no circulation of SARS-CoV-2 was detectable in BIS during the 2019/2020 influenza season, while virtually no influenza viruses were found in BIS 2020/2021 during the COVID-19 pandemic.
Closing lower secondary schools had no impact on COVID-19 incidence in 13–15-year-olds in Finland
Authors: Juutinen Aapo , Sarvikivi Emmi , Laukkanen-Nevala Päivi , Helve Otto
Published: October 2021

School lockdowns have been widely used to control the COVID-19 pandemic. However, these lockdowns may have a significant negative impact on the lives of young people. In this study, we have evaluated the impact of closing lower secondary schools for COVID-19 incidence in 13–15-year-olds in Finland, in a situation where restrictions and recommendation of social distancing were implemented uniformly in the entire country. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, in which clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner. The NIDR is linked to population data registry, enabling calculation of incidences. We estimated the differences in trends between areas with both restaurant and lower secondary school closures and areas with only restaurant closures in different age groups by using joinpoint regression. We also estimated the differences in trends between age groups. Based on our analysis, closing lower secondary schools had no impact on COVID-19 incidence among 13–15-year-olds. No significant changes on COVID-19 incidence were observed in other age groups either.
The phenotypic associations and gene–environment underpinnings of socioeconomic status and diurnal cortisol secretion in adolescence
Authors: Cantave Christina Y. , Brendgen Mara , Paquin Stéphane , Lupien Sonia , Dionne Ginette , Vitaro Frank , Boivin Michel , Ouellet-Morin Isabelle
Published: October 2021

While converging evidence suggests that both environmental and genetic factors underlie variations in diurnal cortisol, the extent to which these sources of influence vary according to socioeconomic status (SES) has seldom been investigated, particularly in adolescence. To investigate whether a distinct genetic and environmental contribution to youth’s diurnal cortisol secretion emerges according to family SES and whether the timing of these experiences matters. Participants were 592 twin pairs, who mostly came from middle-income and intact families and for whom SES was measured in childhood and adolescence. Diurnal cortisol was assessed at age 14 at awakening, 30 min later, in the afternoon and evening over four nonconsecutive days. SES–cortisol phenotypic associations were specific to the adolescence period. Specifically, higher awakening cortisol levels were detected in wealthier backgrounds, whereas higher cortisol awakening response (CAR) and diurnal changes were present at both ends of the SES continuum. Moreover, smaller genetic contributions emerged for awakening cortisol in youth from poorer compared to wealthier backgrounds. The results suggest that the relative contribution of inherited factors to awakening cortisol secretion may be enhanced or suppressed depending on the socio-family context, which may help to decipher the mechanisms underlying later adjustment.
Das Potenzial kooperativen Lernens ausschöpfen: Die Bedeutung der transaktiven Kommunikation für eine lernwirksame Zusammenarbeit
Authors: Hänze Martin , Jurkowski Susanne
Published: October 2021

Zusammenfassung. Kooperatives Lernen eröffnet Chancen und birgt gleichzeitig Risiken für den Wissenserwerb. Der Beitrag arbeitet die Bedeutung der transaktiven Kommunikation als zentralen Wirkmechanismus für den genuinen Mehrwert kooperativen Lernens heraus. Unter transaktiver Kommunikation wird die fachinhaltliche Bezugnahme auf den Lernpartner verstanden, wobei niedrig-transaktive (z.B. paraphrasierende) von hoch-transaktiven (z.B. integrierenden) Äußerungen unterschieden werden. Es werden Bedingungen, unter denen sich transaktive Kommunikation positiv auf Lernprozesse auswirken kann, in den Bereichen individuelle Kommunikationsfähigkeiten, Gruppenzusammensetzung, Aufgabenstellung und methodisch-didaktische Umsetzung analysiert. Es wird deutlich, dass die Bedingungen eine transaktive Kommunikation sowohl zulassen als auch erfordern müssen, damit kooperatives Lernen effektiv sein kann. Daraus ergeben sich Ansatzpunkte für die Förderung transaktiver Kommunikation und somit für die Steigerung der Wirksamkeit kooperativen Lernens. Abschließend werden Forschungsdesiderata aufgezeigt.
Measuring Self-Control in International Large-Scale	Surveys
Authors: Partsch Melanie V. , Danner Daniel
Published: October 2021

Abstract. Self-control – that is, the ability to control impulses, emotions, or actions in order to achieve goals – is associated with a broad range of positive life outcomes, such as educational attainment and health. The present study describes the development and validation of a four-item self-control scale in English, French, German, Japanese, Polish, and Spanish. We used a sample comprising 973 survey respondents from the United States to select the scale items, and a sample comprising 5,557 respondents from six countries to validate the short scale. Results suggest that with just four items, self-control can be measured in a valid, partially scalar invariant, and time-efficient way, and can be adjusted for acquiescence.
How Will Baseflow Respond to Climate Change in the Upper Colorado River Basin?
Authors: Miller Olivia L. , Miller Matthew P. , Longley Patrick C. , Alder Jay R. , Bearup Lindsay A. , Pruitt Tom , Jones Daniel K. , Putman Annie L. , Rumsey Christine A. , McKinney Tim
Published: October 2021

Baseflow is critical to sustaining streamflow in the Upper Colorado River Basin. Therefore, effective water resources management requires estimates of baseflow response to climatic changes. This study provides the first estimates of projected baseflow changes from historical (1984–2012) to thirty‐year periods centered around 2030, 2050, and 2080 under warm/wet, median, and hot/dry climatic conditions using a hybrid statistical‐deterministic baseflow model. Total baseflow supplied to the Lower Colorado River Basin may decline by up to 33%, although this value may increase in the near future by 6% under warm/wet conditions. The percentage of baseflow lost during in‐stream transport is projected to increase by 1%–5% relative to historical conditions. Results highlight that climate‐driven changes in high‐elevation hydrology have impacts on basinwide water availability. Study results have implications for human and ecological water availability in one of the most heavily managed watersheds in the world.
Seasonal Variability of the Daytime and Nighttime Atmospheric Turbulence Experienced by InSight on Mars
Authors: Chatain A. , Spiga A. , Banfield D. , Forget F. , Murdoch N.
Published: October 2021

The InSight mission, featuring continuous high‐frequency high‐sensitivity pressure measurements, is in ideal position to study the active atmospheric turbulence of Mars. Data acquired during 1.25 Martian year allows us to study the seasonal evolution of turbulence and its diurnal cycle. We investigate vortices (abrupt pressure drops), local turbulence (frequency range Hz) and non‐local turbulence often caused by convection cells and plumes (frequency range Hz). Contrary to non‐local turbulence, local turbulence is strongly sensitive at all local times and seasons to the ambient wind. We report many remarkable events with the arrival of northern autumn at the InSight landing site: a spectacular burst of daytime vortices, the appearance of nighttime vortices, and the development of nighttime local turbulence as intense as its daytime counterpart. Nighttime turbulence at this dusty season appears as a result of the combination of a stronger low‐level jet, producing shear‐driven turbulence, and a weaker stability.
Contribution of Recycled Moisture to Precipitation: A Modified D‐Excess‐Based Model
Authors: Zhang Fen , Huang Tianming , Man Wenmin , Hu Hongchang , Long Yin , Li Zhenbin , Pang Zhonghe
Published: October 2021

Defining moisture sources and evolution of precipitation is of significance for further exploration of complex hydro‐climatic interactions, especially under global warming with alternations of evapotranspiration capacity and precipitation moisture source structure. As a sensitive indicator, d‐excess has been widely used to quantify the proportion of recycled vapor to precipitation (fre). However, existing d‐excess‐based models ignore to take transpiration vapor into account and the calculated fre tends to be lower than the true value, thus underestimating the importance of recycled vapor in precipitation. Herein, the existing model was modified with transpiration vapor considered and applied in Guyuan, China located in a monsoon marginal zone with complex precipitation moisture sources. After modification, the estimated annual average fre was increased from 7.5% to 14.8%, well calibrating the existing model. This study highlights the contribution of transpiration vapor to precipitation and provides more information on the formation and evolution of precipitation to better serve future hydro‐climatic research.
Geoscientists, Who Have Documented the Rapid and Accelerating Climate Crisis for Decades, Are Now Pleading for Immediate Collective Action
Authors: Filippelli Gabriel , Beal Lisa , Rajaram Harihar , AghaKouchak Amir , Balikhin Michael A. , Destouni Georgia , East Amy , Faccenna Claudio , Florindo Fabio , Frost Carol , Griffies Stephen , Huber Matthew , Lugaz Noé , Manighetti Isabelle , Montesi Laurent , Pirenne Benoit , Raymond Peter , Salous Sana , Schildgen Taylor , Trumbore Susan , Wysession Michael , Xenopoulos Marguerite , Zhang Minghua
Published: October 2021

Key Points

Editors‐in‐chief of AGU journals stress urgent need for greening economy

Cross‐sector solutions‐based science must supplement basic research

AGU is adding solutions‐based community science journal to portfolio
Upregulating sirtuin 6 ameliorates glycolysis, EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency
Authors: Tsai Yi-Chih , Chen Su-Liang , Peng Shu-Ling , Tsai Ya-Li , Chang Zuong-Ming , Chang Vincent Hung-Shu , Ch’ang Hui-Ju
Published: October 2021

Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC.

Clinical Trial Registration:ClinicalTrials.gov. identifier: NCT01666184.
The current status of risk-stratified breast screening
Authors: Clift Ash Kieran , Dodwell David , Lord Simon , Petrou Stavros , Brady Sir Michael , Collins Gary S. , Hippisley-Cox Julia
Published: October 2021

Apart from high-risk scenarios such as the presence of highly penetrant genetic mutations, breast screening typically comprises mammography or tomosynthesis strategies defined by age. However, age-based screening ignores the range of breast cancer risks that individual women may possess and is antithetical to the ambitions of personalised early detection. Whilst screening mammography reduces breast cancer mortality, this is at the risk of potentially significant harms including overdiagnosis with overtreatment, and psychological morbidity associated with false positives. In risk-stratified screening, individualised risk assessment may inform screening intensity/interval, starting age, imaging modality used, or even decisions not to screen. However, clear evidence for its benefits and harms needs to be established. In this scoping review, the authors summarise the established and emerging evidence regarding several critical dependencies for successful risk-stratified breast screening: risk prediction model performance, epidemiological studies, retrospective clinical evaluations, health economic evaluations and qualitative research on feasibility and acceptability. Family history, breast density or reproductive factors are not on their own suitable for precisely estimating risk and risk prediction models increasingly incorporate combinations of demographic, clinical, genetic and imaging-related parameters. Clinical evaluations of risk-stratified screening are currently limited. Epidemiological evidence is sparse, and randomised trials only began in recent years.
Cardiac-specific CGI-58 deficiency activates the ER stress pathway to promote heart failure in mice
Authors: Xie Xin , Tie Yi-Fan , Lai Song , Zhang Yun-Long , Li Hui-Hua , Liu Ying
Published: October 2021

Excess myocardial triacylglycerol accumulation (i.e., cardiac steatosis) impairs heart function, suggesting that enzymes promoting triacylglycerol metabolism exert essential regulatory effects on heart function. Comparative gene identification 58 (CGI-58) is a key enzyme that promotes the hydrolysis of triglycerides by activating adipose triglyceride lipase and plays a protective role in maintaining heart function. In this study, the effects of CGI-58 on heart function and the underlying mechanism were investigated using cardiac-specific CGI58-knockout mice (CGI-58cko mice). Echocardiography and pathological staining were performed to detect changes in the structure and function of the heart. Proteomic profiling, immunofluorescent staining, western blotting, and real-time PCR were used to evaluate molecular changes. In CGI-58cko mice, we detected cardiac hypertrophic remodeling and heart failure associated with excessive cardiac lipid accumulation, ROS production, and decreased expression of regulators of fatty acid metabolism. These changes were markedly attenuated in CGI-58cko mice injected with rAAV9-CGI58. A quantitative proteomics analysis revealed significant increases in the expression of ER stress-related proteins and decreases in proteins related to fatty acid and amino acid metabolism in the hearts of CGI-58cko mice. Furthermore, the inhibition of ER stress by the inhibitor 4-PBA improved mitochondrial dysfunction, reduced oxidative stress, and reversed cardiac remodeling and dysfunction in cultured cardiomyocytes or in CGI-58cko mice. Our results suggested that CGI-58 is essential for the maintenance of heart function by reducing lipid accumulation and ER stress in cardiomyocytes, providing a new therapeutic target for cardiac steatosis and dysfunction.
Obesity in pregnant women: a 20-year analysis of the German experience
Authors: Strauss Alexander , Rochow Niels , Kunze Mirjam , Hesse Volker , Dudenhausen Joachim W. , Voigt Manfred
Published: October 2021

Background/objective

To investigate the longitudinal development of maternal body weight and analyze the influence of obesity on obstetrics during more than two decades in Germany.

Subjects/methods

Data collected from the Federal state of Schleswig-Holstein (German Perinatal Survey) were analyzed with regard to the dynamics of maternal anthropometric variables (body weight, BMI) between 1995–7 and 2004–17. In total 335,511 mothers substantiated the presented study-collective. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY.

Results

Maternal BMI advanced significantly over the study period. Among a rise in mean periconceptional body weight (67.6–72.0 kg), the segment of obese women increased disproportionately (in average 9.4–19.2%). Despite the observed trend to late giving birth (mean maternal age 1995: 29.3 vs. 30.7 years in 2017), it was not advanced maternal age but parity that influenced the continuous increase in maternal weight (mean maternal body weight 1995–7: primi- bi-, multiparae 67.4, 68.3 and 69.0 kg vs. 2004–17: primi- bi-, multiparae 70.0, 71.5 and 73.2 kg respectively).

Conclusion

Obesity is a major problem on health issues in obstetrics. Advancing maternal BMI, increasing mother’s age and derived prenatal risks considerably complicate pregnancy and delivery. It has to be emphasized that its consequences do not end with delivery or childbed, but represent a livelong burden to the mother and their offspring. Hence, multimodal strategies to reduce/control periconceptional body weight are mandatory.
The geography of intergenerational social mobility in Britain
Authors: Longley Paul A. , van Dijk Justin , Lan Tian
Published: October 2021

Empirical analysis of social mobility is typically framed by outcomes recorded for only a single, recent generation, ignoring intergenerational preconditions and historical conferment of opportunity. We use the detailed geography of relative deprivation (hardship) to demonstrate that different family groups today experience different intergenerational outcomes and that there is a distinct Great Britain-wide geography to these inequalities. We trace the evolution of these inequalities back in time by coupling family group level data for the entire Victorian population with a present day population-wide consumer register. Further geographical linkage to neighbourhood deprivation data allows us to chart the different social mobility outcomes experienced by every one of the 13,378 long-established family groups. We identify clear and enduring regional divides in England and Scotland. In substantive terms, use of family names and new historical digital census resources are central to recognising that geography is pivotal to understanding intergenerational inequalities.
Increasing large wildfires over the western United States linked to diminishing sea ice in the Arctic
Authors: Zou Yufei , Rasch Philip J. , Wang Hailong , Xie Zuowei , Zhang Rudong
Published: October 2021

The compound nature of large wildfires in combination with complex physical and biophysical processes affecting variations in hydroclimate and fuel conditions makes it difficult to directly connect wildfire changes over fire-prone regions like the western United States (U.S.) with anthropogenic climate change. Here we show that increasing large wildfires during autumn over the western U.S. are fueled by more fire-favorable weather associated with declines in Arctic sea ice during preceding months on both interannual and interdecadal time scales. Our analysis (based on observations, climate model sensitivity experiments, and a multi-model ensemble of climate simulations) demonstrates and explains the Arctic-driven teleconnection through regional circulation changes with the poleward-shifted polar jet stream and enhanced fire-favorable surface weather conditions. The fire weather changes driven by declining Arctic sea ice during the past four decades are of similar magnitude to other leading modes of climate variability such as the El Niño-Southern Oscillation that also influence fire weather in the western U.S.
CDH2 mutation affecting N-cadherin function causes attention-deficit hyperactivity disorder in humans and mice
Authors: Halperin D. , Stavsky A. , Kadir R. , Drabkin M. , Wormser O. , Yogev Y. , Dolgin V. , Proskorovski-Ohayon R. , Perez Y. , Nudelman H. , Stoler O. , Rotblat B. , Lifschytz T. , Lotan A. , Meiri G. , Gitler D. , Birk O. S.
Published: October 2021

Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder characterized by inattention, impulsivity and hyperactivity. ADHD exhibits substantial heritability, with rare monogenic variants contributing to its pathogenesis. Here we demonstrate familial ADHD caused by a missense mutation in CDH2, which encodes the adhesion protein N-cadherin, known to play a significant role in synaptogenesis; the mutation affects maturation of the protein. In line with the human phenotype, CRISPR/Cas9-mutated knock-in mice harboring the human mutation in the mouse ortholog recapitulated core behavioral features of hyperactivity. Symptoms were modified by methylphenidate, the most commonly prescribed therapeutic for ADHD. The mutated mice exhibited impaired presynaptic vesicle clustering, attenuated evoked transmitter release and decreased spontaneous release. Specific downstream molecular pathways were affected in both the ventral midbrain and prefrontal cortex, with reduced tyrosine hydroxylase expression and dopamine levels. We thus delineate roles for CDH2-related pathways in the pathophysiology of ADHD.
A macroscopic object passively cooled into its quantum ground state of motion beyond single-mode cooling
Authors: Cattiaux D. , Golokolenov I. , Kumar S. , Sillanpää M. , Mercier de Lépinay L. , Gazizulin R. R. , Zhou X. , Armour A. D. , Bourgeois O. , Fefferman A. , Collin E.
Published: October 2021

The nature of the quantum-to-classical crossover remains one of the most challenging open question of Science to date. In this respect, moving objects play a specific role. Pioneering experiments over the last few years have begun exploring quantum behaviour of micron-sized mechanical systems, either by passively cooling single GHz modes, or by adapting laser cooling techniques developed in atomic physics to cool specific low-frequency modes far below the temperature of their surroundings. Here instead we describe a very different approach, passive cooling of a whole micromechanical system down to 500 μK, reducing the average number of quanta in the fundamental vibrational mode at 15 MHz to just 0.3 (with even lower values expected for higher harmonics); the challenge being to be still able to detect the motion without disturbing the system noticeably. With such an approach higher harmonics and the surrounding environment are also cooled, leading to potentially much longer mechanical coherence times, and enabling experiments questioning mechanical wave-function collapse, potentially from the gravitational background, and quantum thermodynamics. Beyond the average behaviour, here we also report on the fluctuations of the fundamental vibrational mode of the device in-equilibrium with the cryostat. These reveal a surprisingly complex interplay with the local environment and allow characteristics of two distinct thermodynamic baths to be probed.
Miniature type V-F CRISPR-Cas nucleases enable targeted DNA modification in cells
Authors: Bigelyte Greta , Young Joshua K. , Karvelis Tautvydas , Budre Karolina , Zedaveinyte Rimante , Djukanovic Vesna , Van Ginkel Elizabeth , Paulraj Sushmitha , Gasior Stephen , Jones Spencer , Feigenbutz Lanie , Clair Grace St. , Barone Pierluigi , Bohn Jennifer , Acharya Ananta , Zastrow-Hayes Gina , Henkel-Heinecke Selgar , Silanskas Arunas , Seidel Ralf , Siksnys Virginijus
Published: October 2021

Class 2 CRISPR systems are exceptionally diverse, nevertheless, all share a single effector protein that contains a conserved RuvC-like nuclease domain. Interestingly, the size of these CRISPR-associated (Cas) nucleases ranges from >1000 amino acids (aa) for Cas9/Cas12a to as small as 400-600 aa for Cas12f. For in vivo genome editing applications, compact RNA-guided nucleases are desirable and would streamline cellular delivery approaches. Although miniature Cas12f effectors have been shown to cleave double-stranded DNA, targeted DNA modification in eukaryotic cells has yet to be demonstrated. Here, we biochemically characterize two miniature type V-F Cas nucleases, SpCas12f1 (497 aa) and AsCas12f1 (422 aa), and show that SpCas12f1 functions in both plant and human cells to produce targeted modifications with outcomes in plants being enhanced with short heat pulses. Our findings pave the way for the development of miniature Cas12f1-based genome editing tools.
The spatial configuration of biotic interactions shapes coexistence-area relationships in an annual plant community
Authors: García-Callejas David , Bartomeus Ignasi , Godoy Oscar
Published: October 2021

The increase of species richness with area is a universal phenomenon on Earth. However, this observation contrasts with our poor understanding of how these species-area relationships (SARs) emerge from the collective effects of area, spatial heterogeneity, and local interactions. By combining a structuralist approach with five years of empirical observations in a highly-diverse Mediterranean grassland, we show that spatial heterogeneity plays a little role in the accumulation of species richness with area in our system. Instead, as we increase the sampled area more species combinations are realized, and they coexist mainly due to direct pairwise interactions rather than by changes in single-species dominance or by indirect interactions. We also identify a small set of transient species with small population sizes that are consistently found across spatial scales. These findings empirically support the importance of the architecture of species interactions together with stochastic events for driving coexistence- and species-area relationships.
Macrophages in heterotopic ossification: from mechanisms to therapy
Authors: Huang Yifei , Wang Xinyi , Zhou Daixuan , Zhou Wenwen , Dai Fengyi , Lin Hui
Published: October 2021

Heterotopic ossification (HO) is the formation of extraskeletal bone in non-osseous tissues. It is caused by an injury that stimulates abnormal tissue healing and regeneration, and inflammation is involved in this process. It is worth noting that macrophages are crucial mediators of inflammation. In this regard, abundant macrophages are recruited to the HO site and contribute to HO progression. Macrophages can acquire different functional phenotypes and promote mesenchymal stem cell (MSC) osteogenic differentiation, chondrogenic differentiation, and angiogenesis by expressing cytokines and other factors such as the transforming growth factor-β1 (TGF-β1), bone morphogenetic protein (BMP), activin A (Act A), oncostatin M (OSM), substance P (SP), neurotrophin-3 (NT-3), and vascular endothelial growth factor (VEGF). In addition, macrophages significantly contribute to the hypoxic microenvironment, which primarily drives HO progression. Thus, these have led to an interest in the role of macrophages in HO by exploring whether HO is a “butterfly effect” event. Heterogeneous macrophages are regarded as the “butterflies” that drive a sequence of events and ultimately promote HO. In this review, we discuss how the recruitment of macrophages contributes to HO progression. In particular, we review the molecular mechanisms through which macrophages participate in MSC osteogenic differentiation, angiogenesis, and the hypoxic microenvironment. Understanding the diverse role of macrophages may unveil potential targets for the prevention and treatment of HO.
Vertebrate host phylogeny influences gut archaeal diversity
Authors: Youngblut Nicholas D. , Reischer Georg H. , Dauser Silke , Maisch Sophie , Walzer Chris , Stalder Gabrielle , Farnleitner Andreas H. , Ley Ruth E.
Published: October 2021

Commonly used 16S rRNA gene primers do not detect the full range of archaeal diversity present in the vertebrate gut. As a result, several questions regarding the archaeal component of the gut microbiota remain, including which Archaea are host-associated, the specificities of such associations and the major factors influencing archaeal diversity. Using 16S rRNA gene amplicon sequencing with primers that specifically target Archaea, we obtained sufficient sequence data from 185 gastrointestinal samples collected from 110 vertebrate species that span five taxonomic classes (Mammalia, Aves, Reptilia, Amphibia and Actinopterygii), of which the majority were wild. We provide evidence for previously undescribed Archaea–host associations, including Bathyarchaeia andMethanothermobacter, the latter of which was prevalent among Aves and relatively abundant in species with higher body temperatures, although this association could not be decoupled from host phylogeny. Host phylogeny explained archaeal diversity more strongly than diet, while specific taxa were associated with both factors, and cophylogeny was significant and strongest for mammalian herbivores. Methanobacteria was the only class predicted to be present in the last common ancestors of mammals and all host species. Further analysis indicated that Archaea–Bacteria interactions have a limited effect on archaeal diversity. These findings expand our current understanding of Archaea–vertebrate associations.
Liver and brain differential expression of one-carbon metabolism genes during ontogenesis
Authors: Imbard Apolline , Schwendimann Leslie , Lebon Sophie , Gressens Pierre , Blom Henk J. , Benoist Jean-François
Published: October 2021

One-carbon metabolism (1C metabolism) is of paramount importance for cell metabolism and mammalian development. It is involved in the synthesis or modification of a wide variety of compounds such as proteins, lipids, purines, nucleic acids and neurotransmitters. We describe here the evolution of expression of genes related to 1C metabolism during liver and brain ontogeny in mouse. The level of expression of 30 genes involved in 1C metabolism was quantified by RT-qPCR in liver and brain tissues of OF1 mice at E9, E11, E13, E15, E17, P0, P3, P5, P10, P15 developmental stages and in adults. In the liver, hierarchical clustering of the gene expression patterns revealed five distinct clades of genes with a first bifurcating hierarchy distinguishing two main developmental stages before and after E15. In the brain most of the 1C metabolism genes are expressed but at a lower levels. The gene expression of enzymes involved in 1C metabolism show dramatic changes during development that are tissue specific. mRNA expression patterns of all major genes involved in 1C metabolism in liver and brain provide clues about the methylation demand and methylation pathways during embryonic development.
Catechol thwarts virulent dimorphism in Candida albicans and potentiates the antifungal efficacy of azoles and polyenes
Authors: Jothi Ravi , Sangavi Ravichellam , Kumar Ponnuchamy , Pandian Shunmugiah Karutha , Gowrishankar Shanmugaraj
Published: October 2021

The present study was deliberately focused to explore the antivirulence efficacy of a plant allelochemical—catechol against Candida albicans, and attempts were made to elucidate the underlying mechanisms as well. Catechol at its sub-MIC concentrations (2–256 μg/mL) exhibited a dose dependent biofilm as well as hyphal inhibitory efficacies, which were ascertained through both light and fluorescence microscopic analyses. Further, sub-MICs of catechol displayed remarkable antivirulence efficacy, as it substantially inhibited C. albicans’ virulence enzymes i.e. secreted hydrolases. Notably, FTIR analysis divulged the potency of catechol in effective loosening of C. albicans’ exopolymeric matrix, which was further reinforced using EPS quantification assay. Although, catechol at BIC (256 μg/mL) did not disrupt the mature biofilms of C. albicans, their initial adherence was significantly impeded by reducing their hydrophobic nature. Besides, FTIR analysis also unveiled the ability of catechol in enhancing the production of farnesol—a metabolite of C. albicans, whose accumulation naturally blocks yeast-hyphal transition. The qPCR data showed significant down-regulation of candidate genes viz., RAS1, HWP1 and ALS3 which are the key targets of Ras-cAMP-PKA pathway -the pathway that contribute for C. albicans’ pathogenesis. Interestingly, the up-regulation of TUP1 (a gene responsible for farnesol-mediated hyphal inhibition) during catechol exposure strengthen the speculation of catechol triggered farnesol-mediated hyphal inhibition. Furthermore, catechol profusely enhanced the fungicidal efficacy of certain known antifungal agent’s viz., azoles (ketoconazole and miconazole) and polyenes (amphotericin-B and nystatin).
Unraveling the complexity of faba bean (Vicia faba L.) transcriptome to reveal cold-stress-responsive genes using long-read isoform sequencing technology
Authors: Lyu Jae Il , Ramekar Rahul , Kim Jung Min , Hung Nguyen Ngoc , Seo Ji Su , Kim Jin-Baek , Choi Ik-Young , Park Kyong-Cheul , Kwon Soon-Jae
Published: October 2021

Faba bean (Vicia faba L.), a globally important grain legume providing a stable source of dietary protein, was one of the earliest plant cytogenetic models. However, the lack of draft genome annotations and unclear structural information on mRNA transcripts have impeded its genetic improvement. To address this, we sequenced faba bean leaf transcriptome using the PacBio single-molecule long-read isoform sequencing platform. We identified 28,569 nonredundant unigenes, ranging from 108 to 9669 bp, with a total length of 94.5 Mb. Many unigenes (3597, 12.5%) had 2–20 isoforms, indicating a highly complex transcriptome. Approximately 96.5% of the unigenes matched sequences in public databases. The predicted proteins and transcription factors included NB-ARC, Myb_domain, C3H, bHLH, and heat shock proteins, implying that this genome has an abundance of stress resistance genes. To validate our results, we selected WCOR413-15785, DHN2-12403, DHN2-14197, DHN2-14797, COR15-14478, and HVA22-15 unigenes from the ICE-CBF-COR pathway to analyze their expression patterns in cold-treated samples via qRT-PCR. The expression of dehydrin-related genes was induced by cold stress. The assembled data provide the first insights into the deep sequencing of full-length RNA from faba bean at the single-molecule level. This study provides an important foundation to improve gene modeling and protein prediction.
Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291–1329 CE) indicates the first known case of late-onset Pompe disease
Authors: Iadarola Barbara , Lavezzari Denise , Modi Alessandra , Degli Esposti Chiara , Beltrami Cristina , Rossato Marzia , Zaro Valentina , Napione Ettore , Latella Leonardo , Lari Martina , Caramelli David , Salviati Alessandro , Delledonne Massimo
Published: October 2021

Mummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic heritage. Using the strictest criteria currently available for the validation of ancient DNA sequences, whole-genome and whole-exome sequencing were generated from the mummy remains of an Italian nobleman died almost 700 years ago, Cangrande della Scala. While its genome sequencing could not yield sufficient coverage for in depth investigation, exome sequencing could overcome the limitations of this approach to achieve significantly high coverage on coding regions, thus allowing to perform the first extensive exome analysis of a mummy genome. Similar to a standard “clinical exome analysis” conducted on modern DNA, an in-depth variant annotation, high-quality filtering and interpretation was performed, leading to the identification of a genotype associated with late-onset Pompe disease (glycogen storage disease type II). This genetic diagnosis was concordant with the limited clinical history available for Cangrande della Scala, who likely represents the earliest known case of this autosomal recessive metabolic disorder.
Multiparametric analysis of geometric features of fibrotic textures leading to cardiac arrhythmias
Authors: Nezlobinsky T. , Okenov A. , Panfilov A. V.
Published: October 2021

One of the important questions in cardiac electrophysiology is to characterise the arrhythmogenic substrate; for example, from the texture of the cardiac fibrosis, which is considered one of the major arrhythmogenic conditions. In this paper, we perform an extensive in silico study of the relationships between various local geometric characteristics of fibrosis on the onset of cardiac arrhythmias. In order to define which texture characteristics have better predictive value, we induce arrhythmias by external stimulation, selecting 4363 textures in which arrhythmia can be induced and also selecting 4363 non-arrhythmogenic textures. For each texture, we determine such characteristics as cluster area, solidity, mean distance, local density and zig-zag propagation path, and compare them in arrhythmogenic and non-arrhythmogenic cases. Our study shows that geometrical characteristics, such as cluster area or solidity, turn out to be the most important for prediction of the arrhythmogenic textures. Overall, we were able to achieve an accuracy of 67% for the arrhythmogenic texture-classification problem. However, the accuracy of predictions depends on the size of the region chosen for the analysis. The optimal size for the local areas of the tissue was of the order of 0.28 of the wavelength of the arrhythmia. We discuss further developments and possible applications of this method for characterising the substrate of arrhythmias in fibrotic textures.
Epidemiology of mutant Plasmodium falciparum parasites lacking histidine-rich protein 2/3 genes in Eritrea 2 years after switching from HRP2-based RDTs
Authors: Mihreteab Selam , Anderson Karen , Pasay Cielo , Smith David , Gatton Michelle L. , Cunningham Jane , Berhane Araia , Cheng Qin
Published: October 2021

Eritrea was the first African country to complete a nationwide switch in 2016 away from HRP2-based RDTs due to high rates of false-negative RDT results caused by Plasmodium falciparum parasites lacking hrp2/hrp3 genes. A cross-sectional survey was conducted during 2019 enrolling symptomatic malaria patients from nine health facilities across three zones consecutively to investigate the epidemiology of P. falciparum lacking hrp2/3 after the RDT switch. Molecular analyses of 715 samples revealed the overall prevalence of hrp2-, hrp3-, and dual hrp2/3-deleted parasites as 9.4% (95%CI 7.4–11.7%), 41.7% (95% CI 38.1–45.3%) and 7.6% (95% CI 5.8–9.7%), respectively. The prevalence of hrp2- and hrp3-deletion is heterogeneous within and between zones: highest in Anseba (27.1% and 57.9%), followed by Gash Barka (6.4% and 37.9%) and Debub zone (5.2% and 43.8%). hrp2/3-deleted parasites have multiple diverse haplotypes, with many shared or connected among parasites of different hrp2/3 status, indicating mutant parasites have likely evolved from multiple and local parasite genetic backgrounds. The findings show although prevalence of hrp2/3-deleted parasites is lower 2 years after RDT switching, HRP2-based RDTs remain unsuitable for malaria diagnosis in Eritrea. Continued surveillance of hrp2/3-deleted parasites in Eritrea and neighbouring countries is required to monitor the trend.