bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation der Implementation konzeptuell unterschiedlicher Maßnahmen zur Leseförderung in der Sekundarstufe I
Authors: Souvignier Elmar , Zeuch Nina , Jost Jörg , Karstens Fabiana , Meudt Sarah-Ines , Schmitz Anke
Published: July 2021

Im vorliegenden Beitrag werden basierend auf einem Evaluationsprojekt im Rahmen des von Bund und Ländern geförderten Programms „Bildung durch Sprache und Schrift“ (BiSS) Analysen zu Bedingungen einer wirksamen Implementation von evidenzbasierten Lesefördermaßnahmen in den schulischen Alltag am Beispiel zweier BiSS-Verbünde und einer Kontrollgruppe vorgestellt. Sowohl hinsichtlich der Implementationsstrategie (top-down vs. bottom-up) als auch im Hinblick auf das Fördermaterial (einfach vs. komplex) unterschieden sich die beiden Fördermaßnahmen deutlich voneinander. Zur Evaluation der Implementation kamen Lehrkräftebefragungen und Kompetenztestungen von Schüler*innen zum Einsatz. Zwei Stichproben von 100 bzw. 98 Lehrkräften wurden zu Begleitfaktoren der Leseförderung (Einstellungen, Selbstwirksamkeit, Wissen, Akzeptanz) und gewünschten Effekten (Wiedergabetreue, Nutzung) befragt. Im Rahmen einer Längsschnittuntersuchung an einer Stichprobe vonN = 1054 Schüler*innen wurden Entwicklungen wesentlicher Facetten der Lesekompetenz (Leseverständnis, Leseflüssigkeit, Lesestrategien, Lesemotivation) betrachtet. Die Ergebnisse zeigen zunächst, dass eine breite Nutzung und positive Effekte in den beteiligten Verbünden nicht in dem gewünschten Maße resultieren. Dabei liegen zwischen den beiden Verbünden – trotz der unterschiedlichen Fördermaßnahmen – nur marginale Unterschiede vor. Analysen der Interkorrelationsmuster zu den Implementationsmerkmalen weisen darauf hin, dass eine erfolgreiche Implementation letztlich von einer hohen Passung zwischen Merkmalen auf Seiten der Maßnahme, der Lehrkraft und der schulischen Rahmenbedingungen abhängt. Implikationen für Forschung und Praxis werden abgeleitet.
Wirkungen von Fortbildungen zur Sprachförderung für pädagogische Fach- und Lehrkräfte
Authors: Kämpfe Karin , Betz Tanja , Kucharz Diemut
Published: July 2021

In Kindertageseinrichtungen und Schulen wird dem pädagogischen Personal in Bezug auf Sprachförderung ein hoher Qualifizierungsbedarf attestiert; zugleich gibt es wenig gesichertes empirisches Wissen über die Wirkungen entsprechender Fortbildungen. Das Fortbildungsangebot und die Teilnehmenden sind heterogen. Um die Heterogenität der Teilnehmenden zu entschlüsseln, wurden im BiSS-Evaluationsprojekt „SPRÜNGE“ (Sprachförderung im Übergang Kindergarten – Grundschule evaluieren) auf Grundlage einer Typenbildung vonN = 27 Fach- und Lehrkräften Unterschiede in ihren Sprachförderkompetenzen und im Fortbildungsbesuch empirisch-quantitativ mittels des Online-Tests SprachKoPF überprüft und für zwei Sprachfördertypen ihre handlungsleitenden Orientierungen in Bezug auf die Wirkungen von Fortbildungen rekonstruiert. Bei diesen beiden, stark fortgebildeten Sprachfördertypen konnten differenzierbare Deutungen zu den Wirkungen von Fortbildungen herausgearbeitet werden, wobei einerseits eine stärkere Kita-Orientierung und andererseits eine stärkere Schulorientierung als (implizite) Referenz deutlich wird. Zudem ließen sich Gelingensbedingungen von Fortbildungen wie „Praxisrelevanz“, die als allgemeingültig angenommen werden, typenspezifisch ausdifferenzieren. Mit der multiperspektivischen Untersuchung der differentiellen Wirkungen von Fortbildungen leistet das Projekt einen explorativen Beitrag zu einer quantitativ und qualitativ ausgerichteten Wirkungsforschung am Übergang Kita-Grundschule.
Amyloidogenic, neuroinflammatory and memory dysfunction effects of HIV-1 gp120
Authors: Lee Young-Jung , Yeo In Jun , Choi Dong Young , Yun Jaesuk , Son Dong Ju , Han Sang-Bae , Hong Jin Tae
Published: July 2021

Human immunodeficiency virus 1 (HIV-1) infection can cause several HIV-associated neurocognitive disorders a variety of neurological impairments characterized by the loss of cortical and subcortical neurons and decreased cognitive and motor function. HIV-1 gp120, the major envelope glycoprotein on viral particles, acts as a binding protein for viral entry and is known to be an agent of neuronal cell death. To determine the mechanism of HIV-1 gp120-induced memory dysfunction, we performed mouse intracerebroventricular (i.c.v.) infusion with HIV-1 gp120 protein (300 ng per mouse) and investigated memory impairment and amyloidogenesis. Infusion of the HIV-1 gp120 protein induced memory dysfunction, which was evaluated using passive avoidance and water maze tests. Infusion of HIV-1 gp120 induced neuroinflammation, such as the release of iNOS and COX-2 and the activation of astrocytes and microglia and increased the mRNA and protein levels of IL-6, ICAM-1, M-CSF, TIM, and IL-2. In particular, we found that the infusion of HIV-1 gp120 induced the accumulation of amyloid plaques and signs of elevated amyloidogenesis, such as increased expression of amyloid precursor protein and BACE1 and increased β-secretase activity. Therefore, these studies suggest that HIV-1 gp120 may induce memory impairment through Aβ accumulation and neuroinflammation.
Current hurdles to the translation of nanomedicines from bench to the clinic
Authors: Đorđević Snežana , Gonzalez María Medel , Conejos-Sánchez Inmaculada , Carreira Barbara , Pozzi Sabina , Acúrcio Rita C. , Satchi-Fainaro Ronit , Florindo Helena F. , Vicent María J.
Published: July 2021

The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.

Graphical abstract
p-Groups of automorphisms of compact non-orientable Riemann surfaces
Authors: Bujalance E. , Cirre F. J. , Gamboa J. M.
Published: July 2021

We study p-groups of automorphisms of compact non-orientable Riemann surfaces of topological genus $$g\ge 3$$

g
≥
3

. We obtain upper bounds of the order of such groups in terms of p,  g and the minimal number of generators of the group. We also determine those values of g for which these bounds are sharp. Furthermore, the same kind of results are obtained when the p-group acts as the full automorphism group of the surface.
How supervisor trust affects early residents’ learning and patient care: A qualitative study
Authors: Gin Brian C. , Tsoi Stephanie , Sheu Leslie , Hauer Karen E.
Published: July 2021

Introduction Trust between supervisors and trainees mediates trainee participation and learning. A resident (postgraduate) trainee’s understanding of their supervisor’s trust can affect their perceptions of their patient care responsibilities, opportunities for and overall growth as physicians. While the supervisor perspective of trust has been well studied, less is known about how resident trainees recognize supervisor trust and how it affects them.
Methods In this qualitative study, 21 pediatric residents were interviewed at a single institution. Questions addressed their experiences during their first post-graduate year (PGY-1) on inpatient wards. Each interviewee was asked to describe three different patient care scenarios in which they perceived optimal, under-, and over-trust from their resident supervisor. Data were analyzed using thematic analysis.
Results Residents recognized and interpreted their supervisor’s trust through four factors: supervisor, task, relationship, and context. Optimal trust was associated with supervision balancing supervisor availability and resident independence, tasks affording participation in decision-making, trusting relationships with supervisors, and a workplace fostering appropriate autonomy and team inclusivity. The effects of supervisor trust on residents fell into three themes: learning experiences, attitudes and self-confidence, and identities and roles. Optimal trust supported learning via tailored guidance, confidence and lessened vulnerability, and a sense of patient ownership and team belonging.
Discussion Understanding how trainees recognize supervisor trust can enhance interventions for improving the dialogue of trust between supervisors and trainees.
Investigating feasibility of interlayers in Resistance Spot Welding of low-carbon steel sheets
Authors: Dharaiya Vishesh , Panchal Avinash , Acharya G. D.
Published: July 2021

In this study, experiments without interlayers and with interlayers of copper and stainless-steel sheets were performed. Design of Experiments based Full-Factorial Method was employed to generate experimental combinations. A total 81 samples were welded and tested in Universal Testing Machine to determine their Breaking Load. To investigate feasibility considering vehicle lightweightness, a novel LTW (Load-to-Weight) ratio has been proposed. Calculated LTW ratio for each experiment clearly showed that samples with stainless-steel interlayer outperformed over samples with copper interlayer and samples without interlayer. For feasibility in terms of machine durability, electrode corrosion has been found as the most auspicious parameter among all. Spot welding electrodes attain air oxidation above 700 °C. An FEA solver has been employed to determine time for electrodes to remain above air oxidation temperature during a single welding cycle through numerical simulation. A novel LTT (Load-to- Time) ratio has been proposed to find experimental combinations considering feasibility regarding electrode corrosion. LTT ratio, applied to experimental combinations with SS interlayer helped in selection of suitable process parameter combinations. Selected combinations through LTW and LTT ratio can be further proposed to industries. Study advocates method to calculate LTW ratio initially, following calculation of LTT ratio and eventually selecting process parameters contemplating feasibility in lightweightness and electrode corrosion.

Article Highlights

Study helps to decide feasibility of interlayer in RSW in terms of weight and electrode corrosion.

Load-to-Weight (LTW) ratio is proposed to decide feasibility of interlayer in terms of weight.

Load-to-Time (LTT) ratio is proposed to determine feasibility of interlayer against electrode corrosion.
Gaming the system: suboptimal compliance with loot box probability disclosure regulations in China
Authors: Xiao Leon Y. , Henderson Laura L. , Yang Yuhan , Newall Philip W. S.
Published: July 2021

Loot boxes provide randomized rewards in video games; their purchase is linked to disordered gambling and they are present in approximately half of UK video games. The relative novelty of loot boxes means that regulators and policymakers in various jurisdictions are still deciding how to regulate them. The People's Republic of China (PRC) is the first, and presently only, jurisdiction to legally require companies to disclose the probabilities of obtaining randomized loot box rewards – an approach that is also favored by the industry as self-regulation. This study is the first to assess paid loot box prevalence in the PRC and companies’ discretionary interpretations of probability disclosure regulations. Loot boxes were found in 91 of the 100 highest-grossing PRC iPhone games. Of games deemed suitable for children aged 12+, 90.5% contained loot boxes. Probability disclosures could not be found for 4.4% of games containing loot boxes. Disclosures were implemented through various methods both in-game and on the games’ official websites; however, consistent with the concept of ‘sludge,’ only 5.5% used the most prominent format of automatically displaying the probabilities on the in-game loot box purchase page. Loot box probability disclosures should be uniform and visually prominent to best help inform consumers.
Return to the Scene of the Crime: Revisiting Process Tracing, Bayesianism, and Murder
Authors: Zaks Sherry
Published: July 2021

In a recent article, I argued that the Bayesian process tracing literature exhibits a persistent disconnect between principle and practice. In their response, Bennett, Fairfield, and Charman raise important points and interesting questions about the method and its merits. This letter breaks from the ongoing point-by-point format of the debate by asking one question: In the most straightforward case, does the literature equip a reasonable scholar with the tools to conduct a rigorous analysis? I answer this question by walking through a qualitative Bayesian analysis of the simplest example: analyzing evidence of a murder. Along the way, I catalogue every question, complication, and pitfall I run into. Notwithstanding some important clarifications, I demonstrate that aspiring practitioners are still facing a method without guidelines or guardrails.
Legal Civic Orders and Equitable Lived Citizenships
Authors: SMITH ROGERS M.
Published: July 2021

Most modern Western political theories embrace equal citizenship as a normative ideal. Many scholars, however, focus on “legal citizenship” and conceive of equal citizenship as uniformity of legal rights and duties. Others focus on experiences of “lived citizenship” and conceive of equal citizenship as achieving sufficient economic, political, and social standing for persons to be seen as civic equals. Using the United States as its example, this article offers a unifying framework for mapping the relationship of legal citizenship to lived citizenship. It illustrates the value of this framework by using it show why realistic efforts to achieve equal citizenship must aim for not uniform legal rights and duties but instead equity in the possession of economic resources, political representation, and social recognition among different categories of citizens.
Maternal dietary intake, nutritional status and macronutrient composition of human breast milk: systematic review
Authors: Adhikari Shiksha , Kudla Urszula , Nyakayiru Jean , Brouwer-Brolsma Elske M.
Published: July 2021

Human breast milk (BM) is the best source of nutrition in early life, particularly during the first 6 months. Nevertheless, human BM composition is variable, and more insight in the exact factors contributing to this variability is warranted. In this review, we explored the impact of maternal dietary intake and nutritional status (e.g. anthropometric measures, BMI, bioimpedance) on human milk macronutrient composition. PubMed, Scopus and Cochrane were systematically searched till November 2019. In total, 4946 publications underwent title–abstract screening; 101 publications underwent full-text screening. Eventually, fifty publications were included in this review, investigating either associations between maternal dietary intake (n29) and/or maternal nutritional status (n29), and macronutrient composition of human BM. Reported energy composition ranged from 213 to 301 kJ/100 ml, and 67 % and 54 % of the studies reported associations between with maternal nutritional intake and status, respectively. Protein content ranged from 0·8 to 3·3 g/100 ml, and four studies suggested a negative association with nutritional status. Fat content ranged from 2·1 to 9·8 g/100 ml, and 68 % of the studies reported positive associations with nutritional status. Carbohydrate content ranged from 5·8 to 7·5 g/100 ml, and 67 % of the included studies did not report an association between intake and status. Literature investigating associations of maternal dietary intake and nutrition status with BM composition of macronutrients and energy content is diversified, both in terms of used methodology and results. Further studies using well-defined and standard parameters are essential to aid the formulation of scientific recommendations.
Geology and palaeontology of the Codos anticline, eastern Iberian Chains, NE Spain: age constraints for the Ediacaran–Cambrian boundary in the Iberian Chains
Authors: Streng Michael
Published: July 2021

The two major structural elements of the Iberian Chains, the Datos and Jarque thrust faults, have been described as occurring in proximity in the area around the village of Codos. The purported Jarque fault corresponds to the axial plane of an anticline known as the Codos anticline, which exposes the oldest stratigraphic unit in this area, i.e. the Codos Bed, a limestone bed bearing skeletal fossils of putative Ediacaran or earliest Cambrian age. Details of the geology of the area and the age of the known fossils are poorly understood or not universally agreed upon. New investigations in the anticline revealed the presence of a normal fault, introduced as the Codos fault, which cross-cuts the course of the alleged Jarque fault. The vertical displacement along the axial plane of the anticline appears to be insignificant, challenging the traditional interpretation of the plane as an equivalent of the Jarque thrust fault. Reinvestigation of the Codos Bed revealed previously unknown skeletal fossils of early Cambrian age, confirming notions that the bed is younger than traditionally assumed. In particular, two helcionelloid molluscs, Anabarella cf. plana and Igorella? sp., allow correlations with Terreneuvian strata of central Spain (Pusa and Fuentepizzara formations) and support previously suggested connections with the Heraultia Limestone of southern France. Former identification of the terminal Ediacaran index-fossil Cloudina in the bed is erroneous. Consequently, the Ediacaran–Cambrian boundary in the Iberian Chains, which has been placed at the top of the formation overlying the Codos Bed, is stratigraphically distinctly lower.
A review of telephone consultations for head and neck cancer follow up: a patient satisfaction survey
Authors: Stewart R , Collins L , Kerr B , Gray G , Devlin B , Black M , Ullah R
Published: July 2021

Objective

To review patient satisfaction with the change in practice towards telephone consultations during and after the coronavirus disease 2019 pandemic for head and neck cancer follow up.

Method

A retrospective analysis was conducted of head and neck cancer telephone appointments during a six-month period in a tertiary referral centre.

Results

Patients found the telephone consultations beneficial (98 per cent), with 30 per cent stating they were relieved to not have to attend hospital. Patients who travelled further, those with lower stage disease and patients with a greater interval from initial treatment were most satisfied with the telephone consultations. Sixty-eight per cent of patients stated they would be happy to have telephone consultations as part of their regular follow up after the pandemic.

Conclusion

Patients found the telephone consultations beneficial and 30 per cent considered them preferable to face-to-face appointments. This study demonstrates that telephone consultations can be used as an adjunct to face-to-face appointments in an effort to reduce hospital attendances whilst maintaining close follow up.
Recurrence of anxiety disorders and its predictors in the general population
Authors: Scholten Willemijn , ten Have Margreet , van Geel Carmen , van Balkom Anton , de Graaf Ron , Batelaan Neeltje
Published: July 2021

Background

Anxiety disorders frequently recur in clinical populations, but the risk of recurrence of anxiety disorders is largely unknown in the general population. In this study, recurrence of anxiety and its predictors were studied in a large cohort of the adult general population.

Methods

Baseline, 3-year and 6-year follow-up data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Respondents (N = 468) who had been in remission for at least a year prior to baseline were included. Recurrence was assessed at 3 and 6 years after baseline, using the Composite International Diagnostic Interview version 3.0. Cumulative recurrence rates were estimated using the number of years since remission of the last anxiety disorder. Furthermore, Cox regression analyses were conducted to investigate predictors of recurrence, using a broad range of putative predictors.

Results

The estimated cumulative recurrence rate was 2.1% at 1 year, 6.6% at 5 years, 10.6% at 10 years, and 16.2% at 20 years. Univariate regression analyses predicted a shorter time to recurrence for several variables, of which younger age at interview, parental psychopathology, neuroticism and a current depressive disorder remained significant in the, age and gender-adjusted, multivariable regression analysis.

Conclusions

Recurrence of anxiety disorders in the general population is common and the risk of recurrence extends over a lengthy period of time. In clinical practice, alertness to recurrence, monitoring of symptoms, and quick access to health care in case of recurrence are needed.
International rituals: An analytical framework and its theoretical repertoires
Authors: Baele Stephane J. , Balzacq Thierry
Published: July 2021

The performance of ritual and the ritualisation of performance are the two main theoretical repertoires of ritual study in international politics and beyond. However, they also escalate tensions between those who insist on ritual's ability to operate by virtue of participants’ presence and those who believe that global networks of media call for a representational turn, which must tie participants and audiences across borders. Should we fail to understand how these distinct theoretical repertoires interact, it would be difficult to study international ritual, identify its functions, and trace its effects. Anchored in the sociology of ‘social occasions’, this article weaves ritual's patterns, properties, and resources into a coherent analytical framework. The framework enables us to better to grasp how actors move between/within different worlds (ritual and performance) and to what effects. The comparative study of two post-terrorism ritual occasions (the 2011 Rose March in Oslo and the 2015 Republican Marches in France) illustrates the usefulness of this theoretical proposition and its related framework.
Partial anomalous pulmonary venous connection and pulmonary venous varix coexist in Turner syndrome: a case report
Authors: Li Qiao , Li Xiang , Li Xiao , Feng Yuan
Published: July 2021

Turner syndrome is a clinical syndrome caused by autosomal abnormalities in women. It is often accompanied by congenital cardiovascular malformations commonly including a bicuspid aortic valve malformation and aortic coarctation, but the presence of multiple pulmonary venous abnormalities is extremely rare. We present a 27-year-old woman who was diagnosed with Turner syndrome. She was revealed an anomalous right upper pulmonary venous connection, left upper pulmonary vein obstruction, and varicose vein malformations of the left pulmonary veins by a series of examination. Cardiac catheterisation and selective pulmonary angiography can further confirm the diagnosis, morphological characteristics, haemodynamic significance and provide a reference for the next step of treatment.
Sensory-Motor and Affective-Fatigue Factors are Associated with Symbol Digit Performance in Multiple Sclerosis
Authors: Arnett Peter A. , Cadden Margaret , Roman Cristina A.F. , Guty Erin , Riegler Kaitlin , Thomas Garrett
Published: July 2021

Objectives:

The oral Symbol Digit Modalities Test (SDMT) has become the standard for the brief screening of cognitive impairment in persons with multiple sclerosis (PwMS). It has been shown to be sensitive to sensory-motor factors involving rudimentary oral motor speed and visual acuity, as well as multiple sclerosis (MS) affective-fatigue factors including depression, fatigue, and anxiety. The present study was designed to provide a greater understanding of these noncognitive factors that might contribute to the oral SDMT by examining all these variables in the same sample.

Methods:

We examined 50 PwMS and 49 healthy controls (HCs). All participants were administered the oral SDMT, two sensory-motor tasks (visual acuity and oral motor speed), and three affective-fatigue measures (depression, fatigue, and anxiety).

Results:

Partially consistent with hypotheses, we found that sensory-motor skills, but not affective-fatigue factors, accounted for some of the group differences between the MS and HC groups on the oral SDMT, reducing the MS/HC group variance predicted from 10% to 4%. Also, PwMS with below average sensory-motor abilities had oral SDMT scores that were lower than PwMS with intact sensory-motor skills (p < .05). Finally, 71% of PwMS in the below-average sensory-motor group were impaired on the oral SDMT compared with 14% of the intact group (p = .006).

Conclusions:

When the oral SDMT is used as the sole screening tool for cognitive impairment in MS, clinicians should know that limitations in visual acuity and rudimentary oral motor speed should be considered as possibly being associated with performance on it in MS.
The association between low-carbohydrate diet score and metabolic syndrome among Iranian adults
Authors: Sangsefidi Zohreh Sadat , Lorzadeh Elnaz , Nadjarzadeh Azadeh , Mirzaei Masoud , Hosseinzadeh Mahdieh
Published: July 2021

Objective:

Assessing the relationship between low-carbohydrate diet (LCD) score and metabolic syndrome (Mets) in Iranian adults.

Design:

Cross-sectional study

Setting:

Yazd Health Study and Taghzieh Mardom-e-Yazd study.

Participants:

Data of 2074 participants were used. Dietary intakes were assessed by a validated semi-quantitative FFQ. LCD score was calculated for each person by summing up the assigned scores to deciles of energy percentages from macronutrients. Mets was evaluated using National Cholesterol Education Program Adult Treatment Panel III. Eventually, association between LCD score and Mets was examined using logistic regression.

Results:

Total Mets prevalence was approximately 40·5 %. After adjustment for confounders, subjects in the higher quartile of LCD score had a significant lower chance of Mets than lower quartile among all participants (Q4 v. Q1: OR: 0·68, 95 % CI (0·50, 0·92)) and separately in men (Q4 v. Q1: OR: 0·54, 95 % CI (0·34, 0·86)) and women (Q2 v. Q1: OR: 0·53, 95 % CI (0·34, 0·82)). Furthermore, more LCD adherence in men reduced abdominal obesity by 47 % (Q3 v. Q1: OR: 0·53, 95 % CI (0·28, 0·99)). A significant inverse relation was also observed between low HDL cholesterol and LCD score in all participants (Q4 versus Q1 OR: 0·74, 95% CI: 0·56–0·99) and separately in men (Q4 versus Q1 OR: 0·63, 95% CI: 0·40–0·98).

Conclusions:

More adherence to LCD might be related to lower chance of Mets and some of its components such as low HDL-cholesterol and abdominal obesity specially in men. Further studies are required to confirm the findings.
Microscopic Analysis Applied to the Quality Control ofHancornia speciosaGomes
Authors: Campos Edca Priscila Cardoso Ferreira , Santos Deysielle Maria dos , Sá Rafaela Damasceno , Randau Karina Perrelli
Published: July 2021

Hancornia speciosaGomes is popularly known as mangabeira and occurs throughout Brazil. It belongs to the Apocynaceae family and is very important for its food and medicinal uses. The objective of this study was to perform the anatomical and histochemical characterization of the leaves ofH. speciosa. Microscope slides were made containing cross sections of petiole and leaf blade, as well as paradermic sections of the leaf blade. The analyses were performed under light and polarized microscopy. For the histochemical analysis, different reagents were used, according to the targeted metabolite. Through microscopic analysis, it was possible to identify the anatomical structures that provide the detailed diagnosis of the studied species. Through histochemistry, the presence of phenolic compounds, tannins, alkaloids, triterpenes and steroids, lipophilic compounds, lignin, starch, and calcium oxalate crystals was evidenced in the leaf blade. Thus, the results presented contribute to the quality control ofH. speciosa, as well as to bring unpublished data about the species and to increase knowledge about the Apocynaceae family.
Morphological Changes in the Motor Endplate and in the Belly Muscle Induced by Previous Static Stretching to the Climbing Protocol
Authors: Barbosa Gabriela K. , Jacob Carolina dos S. , Rodrigues Mariana P. , Rocha Lara C. , Pimentel Neto Jurandyr , Ciena Adriano P.
Published: July 2021

Static stretching provides benefits to the range of motion, modulates intramuscular connective tissue, and is incorporated into warm-up exercises. In this study, we present the effects in the motor endplate and belly muscle resulting from previous static stretching to climbing training. Twenty-four adult maleWistarrats were divided into four groups (n= 6 each): Sedentary (Sed), Climbing (Clb), Static stretching (Ss), and Static stretching prior to climbing (Ssc). The animals (Clb, Ss, and Ssc groups) were subjected to a training protocol 3×/week for 8 weeks, and the Ssc group was subjected to the Ss and Clb protocols in the same session. Samples from the animals were processed for immunostaining, histochemistry, and light microscopy. The Clb group presented a higher motor endplate; the Ss group presented no changes in the motor endplate; and the Ssc group demonstrated a higher compactness. We concluded that static stretching prior to the climbing protocol maintained the density of the motor endplate and increased the compactness of the neuromuscular junction structure. Also, there was a reduction in the myofibers’ diameter (Type I and IIa), an increase in myofibrillar densities (Type I and IIx, and total), and the reorganization of the myonuclei and the interstitium.
Contextualising Radhabinod Pal's Dissenting Opinion in Contemporary International Criminal Law
Authors: CHOUDHURY Sumedha
Published: July 2021

Radhabinod Pal, a judge at the Tokyo Tribunal, wrote a dissenting opinion absolving all the accused Japanese of the alleged crimes. In so doing, he advanced several conceptual and theoretical arguments to support his opinion. This paper focuses on the opinion of Pal concerning non-retroactivity of law, global democracy, imperialism, and victor's justice. The paper analyses his opinion in the light of contemporary developments and argues that his criticisms of the international criminal law regime and global justice are still relevant.
Isoscape of Surface Runoff in High Mountain Catchments: An Alternate Model for Meteoric Water Characterization and Its Implications
Authors: Dasgupta Bibhasvata , Ajay Ajay , Kumar Anurag , Thamban Meloth , Sanyal Prasanta
Published: July 2021

Water isotope‐based hydrological and paleoaltimetry studies in high mountain areas are generally done using the isotopic composition of river discharge. However, rivers capture a basin averaged signal of regional precipitation and are less likely to register the meteorological processes intrinsic to distinct hydrological fractions at different altitudes. This has been observed in the Khumbu (Mt. Everest) Himalayan watersheds of Dudh Kosi Basin (DKB), where the δ18O values of snowpack and stream water vary non‐uniformly with altitude while the δ18O values of river water show a uniform relationship. Snow exhibits the highest (+0.9 to −4.4‰/100 m) isotopic lapse rate (ILR), followed by streams (+0.2 to −0.4‰/100 m) and rivers (−0.05‰/100 m). Sublimation, catchment vegetation, diurnal temperature, cloud type, and insolation play a significant role in controlling the isotopic composition of snowpack and stream water. Similarly, the isotopic composition of small streams disproportionately represents the meteoric water composition of an area, as rainfall immediately joins the stream‐runoff while the snow melts gradually around the year. To map the isotopic heterogeneity in DKB surface waters, we have modeled the isoscape for surface runoff using the isotopic composition of snow and stream water, and remotely sensed parameters. Accordingly, we simulate the isoscapes for snow and stream‐runoff via multi‐regression models which extrapolate the observed data as a function of the controlling factors. The amount‐weighted summation of both the isoscapes (relative contribution (%) *δ18O value) constitutes the hydropool. The hydropool model incorporates spatiotemporal variation in ILR computed from the δ18O values of surface runoff.
ULF‐Modulation of Whistler‐Mode Waves in the Inner Magnetosphere During Solar Wind Compression
Authors: Shang Xiongjun , Liu Si , Chen Lunjin , Gao Zhonglei , Wang Geng , He Qian , Li Tong , Xiao Fuliang
Published: July 2021

The solar wind plays important roles in terrestrial magnetosphere dynamics, including the particle population and plasma wave generation. Here, we report an interesting event that ultralow frequency (ULF) waves are enhanced right after solar wind compression and the compressional mode ULF wave subsequently modulates both the intensity and energy flux direction of whistler‐mode waves. Quasi‐periodic whistler‐mode wave packets are observed around  = 5.6 at noon sector by Van Allen Probes. Growth rate calculation demonstrates that the compressional mode ULF wave can modulate the whistler‐mode wave intensity by modulating the energetic electron anisotropy. Moreover, the direction of wave energy flux is observed to alternate between northward and southward at equator, which is probably because the intense ULF waves periodically alter the relative direction of the wave source region with respect to the spacecraft. The current results provide a chain of observational evidences to illustrate how the generation and propagation of whistler‐mode waves in the inner magnetosphere are affected by ULF waves during the solar wind dynamic pressure enhancement.
RETRACTED ARTICLE: GRP78 determines glioblastoma sensitivity to UBA1 inhibition-induced UPR signaling and cell death
Authors: Liu Guanzheng , Yu Jiefeng , Wu Runqiu , Shi Lin , Zhang Xu , Zhang Wanhong , Zhong Xiaomin , Wang Yifeng , Li Huan , Shen Yang , Wu Changyong , Yu Rutong , Niu Mingshan , Liu Xuejiao
Published: July 2021

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor for which new therapeutic approaches are urgently required. Unfolded protein response (UPR) plays an important role in the progression of GBM and is a promising target for developing novel therapeutic interventions. We identified ubiquitin-activating enzyme 1 (UBA1) inhibitor TAK-243 that can strongly induce UPR in GBM cells. In this study, we evaluated the functional activity and mechanism of TAK-243 in preclinical models of GBM. TAK-243 significantly inhibited the survival, proliferation, and colony formation of GBM cell lines and primary GBM cells. It also revealed a significant anti-tumor effect on a GBM PDX animal model and prolonged the survival time of tumor-bearing mice. Notably, TAK-243 more effectively inhibited the survival and self-renewal ability of glioblastoma stem cells (GSCs) than GBM cells. Importantly, we found that the expression level of GRP78 is a key factor in determining the sensitivity of differentiated GBM cells or GSCs to TAK-243. Mechanistically, UBA1 inhibition disrupts global protein ubiquitination in GBM cells, thereby inducing ER stress and UPR. UPR activates the PERK/ATF4 and IRE1α/XBP signaling axes. These findings indicate that UBA1 inhibition could be an attractive strategy that may be potentially used in the treatment of patients with GBM, and GRP78 can be used as a molecular marker for personalized treatment by targeting UBA1.
In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host
Authors: Launay A. , Wu C.-J. , Dulanto Chiang A. , Youn J.-H. , Khil P. P. , Dekker J. P.
Published: July 2021

Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor β1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool over 45 months revealed a clonal lineage that had undergone extensive within-host genetic and phenotypic diversification. Twenty of 24 isolates shared an E9G substitution in the DNA polymerase III ε-subunit active site, resulting in a proofreading deficiency. Within this proofreading-deficient clade, multiple lineages with mutations in DNA repair genes and altered mutational spectra emerged and dominated clinical cultures for more than 12 months. Multiple enzymes of the tricarboxylic acid cycle and gluconeogenesis pathways were repeatedly mutated, suggesting rapid metabolic adaptation to the human environment. Furthermore, an excess of G:C > T:A transversions suggested that oxidative stress shaped genetic diversification during adaptation. We propose that inactivation of DNA proofreading activity in combination with prolonged, but sub-lethal, oxidative attack resulting from the underlying host immunodeficiency facilitated rapid genomic adaptation. These findings suggest a fundamental role for host immune phenotype in shaping pathogen evolution following zoonotic infection.
RNase κ promotes robust piRNA production by generating 2′,3′-cyclic phosphate-containing precursors
Authors: Shigematsu Megumi , Kawamura Takuya , Morichika Keisuke , Izumi Natsuko , Kiuchi Takashi , Honda Shozo , Pliatsika Venetia , Matsubara Ryuma , Rigoutsos Isidore , Katsuma Susumu , Tomari Yukihide , Kirino Yohei
Published: July 2021

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated sex determination in Bombyx embryos, indicating the crucial roles of BmRNase κ in piRNA biogenesis and embryonic development. Our results reveal a BmRNase κ-engaged piRNA biogenesis pathway, in which the generation of cP-RNAs promotes robust piRNA production.
Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia
Authors: Ajiro Masahiko , Awaya Tomonari , Kim Young Jin , Iida Kei , Denawa Masatsugu , Tanaka Nobuo , Kurosawa Ryo , Matsushima Shingo , Shibata Saiko , Sakamoto Tetsunori , Studer Lorenz , Krainer Adrian R. , Hagiwara Masatoshi
Published: July 2021

Approximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet to be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion is specifically promoted by a small molecule splice modulator, RECTAS, even though IKBKAP-FD exon 20 has a suboptimal 5′ splice site due to the IVS20 + 6 T > C mutation. Knockdown experiments reveal that exon 20 inclusion is suppressed in the absence of serine/arginine-rich splicing factor 6 (SRSF6) binding to an intronic splicing enhancer in intron 20. We show that RECTAS directly interacts with CDC-like kinases (CLKs) and enhances SRSF6 phosphorylation. Consistently, exon 20 splicing is bidirectionally manipulated by targeting cellular CLK activity with RECTAS versus CLK inhibitors. The therapeutic potential of RECTAS is validated in multiple FD disease models. Our study indicates that small synthetic molecules affecting phosphorylation state of SRSFs is available as a new therapeutic modality for mechanism-oriented precision medicine of splicing diseases.
Kinship networks of seed exchange shape spatial patterns of plant virus diversity
Authors: Delêtre Marc , Lett Jean-Michel , Sulpice Ronan , Spillane Charles
Published: July 2021

By structuring farmers’ informal networks of seed exchange, kinship systems play a key role in the dynamics of crop genetic diversity in smallholder farming systems. However, because many crop diseases are propagated through infected germplasm, local seed systems can also facilitate the dissemination of seedborne pathogens. Here, we investigate how the interplay of kinship systems and local networks of germplasm exchange influences the metapopulation dynamics of viruses responsible for the cassava mosaic disease (CMD), a major threat to food security in Africa. Combining anthropological, genetic and plant epidemiological data, we analyzed the genetic structure of local populations of the African cassava mosaic virus (ACMV), one of the main causal agents of CMD. Results reveal contrasted patterns of viral diversity in patrilineal and matrilineal communities, consistent with local modes of seed exchange. Our results demonstrate that plant virus ecosystems have also a cultural component and that social factors that shape regional seed exchange networks influence the genetic structure of plant virus populations.
Mechanistic insight into bacterial entrapment by septin cage reconstitution
Authors: Lobato-Márquez Damián , Xu Jingwei , Güler Gizem Özbaykal , Ojiakor Adaobi , Pilhofer Martin , Mostowy Serge
Published: July 2021

Septins are cytoskeletal proteins that assemble into hetero-oligomeric complexes and sense micron-scale membrane curvature. During infection with Shigella flexneri, an invasive enteropathogen, septins restrict actin tail formation by entrapping bacteria in cage-like structures. Here, we reconstitute septin cages in vitro using purified recombinant septin complexes (SEPT2-SEPT6-SEPT7), and study how these recognize bacterial cells and assemble on their surface. We show that septin complexes recognize the pole of growing Shigella cells. An amphipathic helix domain in human SEPT6 enables septins to sense positively curved membranes and entrap bacterial cells. Shigella strains lacking lipopolysaccharide components are more efficiently entrapped in septin cages. Finally, cryo-electron tomography of in vitro cages reveals how septins assemble as filaments on the bacterial cell surface.
A multi-step nucleation process determines the kinetics of prion-like domain phase separation
Authors: Martin Erik W. , Harmon Tyler S. , Hopkins Jesse B. , Chakravarthy Srinivas , Incicco J. Jeremías , Schuck Peter , Soranno Andrea , Mittag Tanja
Published: July 2021

Compartmentalization by liquid-liquid phase separation (LLPS) has emerged as a ubiquitous mechanism underlying the organization of biomolecules in space and time. Here, we combine rapid-mixing time-resolved small-angle X-ray scattering (SAXS) approaches to characterize the assembly kinetics of a prototypical prion-like domain with equilibrium techniques that characterize its phase boundaries and the size distribution of clusters prior to phase separation. We find two kinetic regimes on the micro- to millisecond timescale that are distinguished by the size distribution of clusters. At the nanoscale, small complexes are formed with low affinity. After initial unfavorable complex assembly, additional monomers are added with higher affinity. At the mesoscale, assembly resembles classical homogeneous nucleation. Careful multi-pronged characterization is required for the understanding of condensate assembly mechanisms and will promote understanding of how the kinetics of biological phase separation is encoded in biomolecules.
Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors
Authors: Cretu Constantin , Gee Patricia , Liu Xiang , Agrawal Anant , Nguyen Tuong-Vi , Ghosh Arun K. , Cook Andrew , Jurica Melissa , Larsen Nicholas A. , Pena Vladimir
Published: July 2021

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning the selection of branch and 3′ splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.
A tool for identifying green solvents for printed electronics
Authors: Larsen Christian , Lundberg Petter , Tang Shi , Ràfols-Ribé Joan , Sandström Andreas , Mattias Lindh E. , Wang Jia , Edman Ludvig
Published: July 2021

The emerging field of printed electronics uses large amounts of printing and coating solvents during fabrication, which commonly are deposited and evaporated within spaces available to workers. It is in this context unfortunate that many of the currently employed solvents are non-desirable from health, safety, or environmental perspectives. Here, we address this issue through the development of a tool for the straightforward identification of functional and “green” replacement solvents. In short, the tool organizes a large set of solvents according to their Hansen solubility parameters, ink properties, and sustainability descriptors, and through systematic iteration delivers suggestions for green alternative solvents with similar dissolution capacity as the current non-sustainable solvent. We exemplify the merit of the tool in a case study on a multi-solute ink for high-performance light-emitting electrochemical cells, where a non-desired solvent was successfully replaced by two benign alternatives. The green-solvent selection tool is freely available at: www.opeg-umu.se/green-solvent-tool.
Initiating polyketide biosynthesis by on-line methyl esterification
Authors: Li Pengwei , Chen Meng , Tang Wei , Guo Zhengyan , Zhang Yuwei , Wang Min , Horsman Geoff P. , Zhong Jin , Lu Zhaoxin , Chen Yihua
Published: July 2021

Aurantinins (ARTs) are antibacterial polyketides featuring a unique 6/7/8/5-fused tetracyclic ring system and a triene side chain with a carboxyl terminus. Here we identify the art gene cluster and dissect ART’s C-methyl incorporation patterns to study its biosynthesis. During this process, an apparently redundant methyltransferase Art28 was characterized as a malonyl-acyl carrier protein O-methyltransferase, which represents an unusual on-line methyl esterification initiation strategy for polyketide biosynthesis. The methyl ester bond introduced by Art28 is kept until the last step of ART biosynthesis, in which it is hydrolyzed by Art9 to convert inactive ART 9B to active ART B. The cryptic reactions catalyzed by Art28 and Art9 represent a protecting group biosynthetic logic to render the ART carboxyl terminus inert to unwanted side reactions and to protect producing organisms from toxic ART intermediates. Further analyses revealed a wide distribution of this initiation strategy for polyketide biosynthesis in various bacteria.