bluuebunny/crossref_metadata_2025 huggingface dataset:
Frobenius splitting of Schubert varieties of semi-infinite flag manifolds
Authors: Kato Syu
Published: July 2021

We exhibit basic algebro-geometric results on the formal model of semi-infinite flag varieties and its Schubert varieties over an algebraically closed field

${\mathbb K}$

of characteristic

$\neq 2$

from scratch. We show that the formal model of a semi-infinite flag variety admits a unique nice (ind-)scheme structure, its projective coordinate ring has a

$\mathbb {Z}$

-model and it admits a Frobenius splitting compatible with the boundaries and opposite cells in positive characteristic. This establishes the normality of the Schubert varieties of the quasi-map space with a fixed degree (instead of their limits proved in [K, Math. Ann. 371 no.2 (2018)]) when

$\mathsf {char}\, {\mathbb K} =0$

or

$\gg 0$

, and the higher-cohomology vanishing of their nef line bundles in arbitrary characteristic

$\neq 2$

. Some particular cases of these results play crucial roles in our proof [47] of a conjecture by Lam, Li, Mihalcea and Shimozono [60] that describes an isomorphism between affine and quantum K-groups of a flag manifold.
Multisociety statement on coronavirus disease 2019 (COVID-19) vaccination as a condition of employment for healthcare personnel
Authors: Weber David J. , Al-Tawfiq Jaffar A. , Babcock Hilary M. , Bryant Kristina , Drees Marci , Elshaboury Ramy , Essick Katharine , Fakih Mohamad , Henderson David K. , Javaid Waleed , Juffras Diane , Jump Robin L.P. , Lee Francesca , Malani Anurag N. , Mathew Trini A. , Murthy Rekha K. , Nace David , O’Shea Tara , Pettigrew Erica , Pettis Ann Marie , Schaffzin Joshua K. , Shenoy Erica S. , Vaishampayan Julie , Wiley Zanthia , Wright Sharon B. , Yokoe Deborah , Young Heather
Published: July 2021

This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).
A high-protein diet containing inulin/oligofructose supports body weight gain associated with lower energy expenditure and carbohydrate oxidation, and alters faecal microbiota in C57BL/6 mice
Authors: Koch Franziska , Derno Michael , Langhammer Martina , Tuchscherer Armin , Hammon Harald M. , Mielenz Manfred , Metges Cornelia C. , Kuhla Björn
Published: July 2021

Prebiotic supplements and high-protein (HP) diets reduce body weight and modulate intestinal microbiota. Our aim was to elucidate the combined effect of an inulin/oligofructose (FOS) and HP diet on body weight gain, energy metabolism and faecal microbiota. Forty male C57BL/6NCrl mice were fed a control (C) diet for 2 weeks and allocated to a C or HP (40 % protein) diet including no or 10 % inulin/FOS (C + I and HP + I) for 4 weeks. Inulin/FOS was added in place of starch and cellulose. Body weight, food intake, faecal energy and nitrogen were determined. Indirect calorimetry and faecal microbiota analysis were performed after 3 weeks on diets. Body weight gain of HP-fed mice was 36 % lower than HP + I- and C-fed mice (P< 0⋅05). Diet digestibility and food conversion efficiency were higher in HP + I- than HP-fed mice (P< 0⋅01), while food intake was comparable between groups. Total energy expenditure (heat production) was 25 % lower in HP + I- than in C-, HP- and C + I-fed mice (P< 0⋅001). Carbohydrate oxidation tended to be 24 % higher in HP- than in HP + I-fed mice (P< 0⋅05). Faecal nitrogen excretion was 31–45 % lower in C-, C + I- and HP + I- than in HP-fed mice (P< 0⋅05). FaecalBacteroides–PrevotellaDNA was 2⋅3-fold higher in C + I- and HP + I- relative to C-fed mice (P< 0⋅05), butClostridium leptumDNA abundances was 79 % lower in HP + I- than in HP-fed mice (P< 0⋅05). We suggest that the higher conversion efficiency of dietary energy of HP + I but not C + I-fed mice is caused by higher digestibility and lower heat production, resulting in increased body mass.
Nutritional status and high adherence to the Mediterranean diet in Colombian school children and teenagers during the COVID-19 pandemic according to sex
Authors: Morales Camacho William Javier , Osma Zambrano Sonia Esperanza , Morales Camacho María Alejandra , Herrera Contreras Angie Carolina , Rangel Acevedo Angela , Duarte Valencia Edgar Julián , Camargo Cárdenas Anamaria , Nocua Alarcón Laura Ximena , Ardila Munar Lizeth Carolina , Noguera Sánchez Ana Milena , Molina Díaz Jorge Mario
Published: July 2021

The current COVID-19 pandemic has generated a series of changes in the daily routines of people, including children and teenagers, in an unprecedented way, which constitutes a global challenge in public health. Social isolation has been a prophylactic measure to prevent the spread of the virus; however, it has generated negative impacts on the physical and emotional health of parents, caregivers, children and teenagers around the world. The objective of the present study was to evaluate the effects of confinement caused by the COVID-19 pandemic at the level of nutritional status, dietary and behavioural patterns of elementary school children and teenagers in a small town of Colombia. Anthropometric parameters such as BMI Z-score, waist circumference and waist/height ratio were evaluated in 266 school children and teenagers. A questionnaire with socio-demographic, clinical and lifestyle characteristics and the KIDMED were applied to learn about nutritional aspects. A total of 102 students (38⋅3 %) were classified as having altered nutritional status, being 39 (14⋅7 %) classified as overweight and 36 (13⋅5 %) with obesity. The prevalence of high adherence to the Mediterranean diet was 12 %, 95 % CI (0⋅08, 0⋅16). Overweight was more prevalent in women (26/39, 66⋅7 %; P = 0⋅0439), and obesity was discreetly more frequent in men (19/36, 52⋅7 %; P = 0⋅7193). We observed a worrying nutritional, dietary and behavioural situation in the children and teenagers studied during the confinement associated with the COVID-19 pandemic. This unveils the need to establish strategies and/or public policies in our town that help to promote an adequate biopsychosocial development of the paediatric patient and their family group.
Stagnation of the Pensilungpa glacier, western Himalaya, India: causes and implications
Authors: Garg Purushottam Kumar , Garg Siddhi , Yousuf Bisma , Shukla Aparna , Kumar Vinit , Mehta Manish
Published: July 2021

This study investigates stagnation conditions of the Pensilungpa glacier, western Himalaya. Multiple glacier parameters (length, area, debris extent and thickness, snowline altitude (SLA), velocity, downwasting and ice cliffs) were studied using field measurements (2016–18), high-resolution imagery from GoogleEarth (2013–17) and spaceborne Landsat, ASTER and SRTM data (1993–2017) to comprehend the glacier's current state. Results show a moderate decrease in length (6.62 ± 2.11 m a−1) and area (0.11 ± 0.03% a−1), a marked increase in SLA (~6 m a−1) and debris cover (2.86 ± 0.29% a−1) and a slowdown of ~50% during 1993–2016. Notable thinning of −0.88 ± 0.04 m a−1 was observed between 2000 and 2017 showing a similar trend as field measurements during 2016–17 (−0.88 m) and 2017–18 (−1.54 m). Further, results reveal a stagnation of the lower ablation zone (LAZ). Less mass supply and heterogeneous debris growth (6.67 ± 0.41% a−1) over the previous decade resulted in slowdown, margin insulation and slope-inversion, leading to stagnation. Stagnation of LAZ caused bulging in the dynamic upper ablation zone and favored the development of supraglacial ponds and ice cliffs. Ice cliffs have grown significantly (48% in number; 41% in area during 2013–17) and their back-wasting now dominates the ablation process.
ON THE HEIGHT AND RELATIONAL COMPLEXITY OF A FINITE PERMUTATION GROUP
Authors: GILL NICK , LODÀ BIANCA , SPIGA PABLO
Published: July 2021

Let G be a permutation group on a set
$\Omega $
of size t. We say that
$\Lambda \subseteq \Omega $
is an independent set if its pointwise stabilizer is not equal to the pointwise stabilizer of any proper subset of
$\Lambda $
. We define the height of G to be the maximum size of an independent set, and we denote this quantity
$\textrm{H}(G)$
. In this paper, we study
$\textrm{H}(G)$
for the case when G is primitive. Our main result asserts that either
$\textrm{H}(G)< 9\log t$
or else G is in a particular well-studied family (the primitive large–base groups). An immediate corollary of this result is a characterization of primitive permutation groups with large relational complexity, the latter quantity being a statistic introduced by Cherlin in his study of the model theory of permutation groups. We also study
$\textrm{I}(G)$
, the maximum length of an irredundant base of G, in which case we prove that if G is primitive, then either
$\textrm{I}(G)<7\log t$
or else, again, G is in a particular family (which includes the primitive large–base groups as well as some others).
A Bayesian Alternative to Synthetic Control for Comparative Case Studies
Authors: Pang Xun , Liu Licheng , Xu Yiqing
Published: July 2021

This paper proposes a Bayesian alternative to the synthetic control method for comparative case studies with a single or multiple treated units. We adopt a Bayesian posterior predictive approach to Rubin’s causal model, which allows researchers to make inferences about both individual and average treatment effects on treated observations based on the empirical posterior distributions of their counterfactuals. The prediction model we develop is a dynamic multilevel model with a latent factor term to correct biases induced by unit-specific time trends. It also considers heterogeneous and dynamic relationships between covariates and the outcome, thus improving precision of the causal estimates. To reduce model dependency, we adopt a Bayesian shrinkage method for model searching and factor selection. Monte Carlo exercises demonstrate that our method produces more precise causal estimates than existing approaches and achieves correct frequentist coverage rates even when sample sizes are small and rich heterogeneities are present in data. We illustrate the method with two empirical examples from political economy.
Extraordinary and upper-hybrid waves in spin quantum magnetoplasmas with vacuum polarization effect
Authors: Zhu Jun , Liu Xiaoshan , Luo Yuee
Published: July 2021

The propagation of extraordinary and upper-hybrid waves in spin quantum magnetoplasmas with vacuum polarization effect is investigated. Based on the quantum magnetohydrodynamics model including Bohm potential, arbitrary relativistic degeneracy pressure and spin force, and Maxwell's equations modified by the spin current and vacuum polarization current, the dispersion relations of extraordinary and upper-hybrid waves are derived. The analytical and numerical results show that quantum effects (Bohm potential, degeneracy pressure and spin magnetization energy) and the vacuum polarization effect modify the propagation of the extraordinary wave. Under the action of a strong magnetic field, the plasma frequency is obviously increased by the vacuum polarization effect.
Justice for Millionaires?
Authors: Christensen James , Parr Tom , Axelsen David V.
Published: July 2021

In recent years, much public attention has been devoted to the existence of pay discrepancies between men and women at the upper end of the income scale. For example, there has been considerable discussion of the ‘Hollywood gender pay gap’. We can refer to such discrepancies as cases of millionaire inequality. These cases generate conflicting intuitions. On the one hand, the unequal remuneration involved looks like a troubling case of gender injustice. On the other, it’s natural to feel uneasy when confronted with the suggestion that multi-millionaires are somehow being paid inadequately. In this paper, we consider two arguments for rectifying millionaire inequality, clarifying their appeal but also identifying the obstacles that each will have to surmount in order to succeed.
Older Adults’ Perceptions of Frailty Language: A Scoping Review
Authors: Durepos Pamela , Sakamoto Mariko , Alsbury Kyla , Hewston Patricia , Borges Julia , Takaoka Alyson
Published: July 2021

There is growing interest in conceptualizing and diagnosing frailty. Less is understood, however, about older adults’ perceptions of the term “frail”, and the implications of being classified as “frail”. The purpose of this scoping review was to map the breadth of primary studies; and describe the meaning, perceptions, and perceived implications of frailty language amongst community-dwelling older adults. Eight studies were included in the review and three core themes were identified: (1) understanding frailty as inevitable age-related decline in multiple domains, (2) perceiving frailty as a generalizing label, and (3) perceiving impacts of language on health and health care utilization. Clinical practice recommendations for health care professionals working with individuals with frailty include: (1) maintaining a holistic view of frailty that extends beyond physical function to include psychosocial and environmental constructs, (2) using person-first language, and (3) using a strengths-based approach to discuss aspects of frailty.
Australian perspectives on spiritual care training in healthcare: A Delphi study
Authors: Jones Kate F. , Washington Jennifer , Kearney Matthew , Kissane David , Best Megan C.
Published: July 2021

Objective

The aim was to to establish core components of spiritual care training for healthcare professionals in Australia.

Methods

This study used the Delphi technique to undertake a consensus exercise with spiritual care experts in the field of healthcare. Participant opinion was sought on (i) the most important components of spiritual care training; (ii) preferred teaching methods; (iii) clinical scenarios to address in spiritual care training; and (iv) current spiritual assessment and referral procedures.

Results

Of the 107 participants who responded in the first round, 67 (62.6%) were female, 55 (51.4%) worked in pastoral care, and 84 (78.5%) selected Christian as their religious affiliation. The most highly ranked components of spiritual care training were “relationship between health and spirituality,” followed by “definitions of spirituality and spiritual care.” Consensus was not achieved on the item “comparative religions study/alternative spiritual beliefs.” Preferred teaching methods include case studies, group discussion, role-plays and/or simulated learning, videos of personal stories, and self-directed learning. The most highly ranked clinical scenario to be addressed in spiritual care training was “screening for spiritual concerns for any patient or resident.” When asked who should conduct an initial spiritual review with patients, consensus was achieved regarding all members of the healthcare team, with most nominating a chaplain or “whoever the patient feels comfortable with.” It was considered important for spiritual care training to address one's own spirituality and self-care. Consensus was not achieved on which spiritual care assessment tools to incorporate in training.

Significance of results

This Delphi study revealed that spiritual care training for Australian healthcare professionals should emphasize the understanding of the role of spirituality and spiritual care in healthcare, include a range of delivery methods, and focus upon the incorporation of spiritual screening. Further work is required to identify how spiritual care screening should be conducted within an Australian healthcare setting.
Effects of Work Demand and Changes in Leisure Activity on Postretirement Memory
Authors: Zulka Linn Elena , Thorvaldsson Valgeir , Hansson Isabelle , Hassing Linda B.
Published: July 2021

Abstract. This study evaluated the interactions between prior cognitive work demands and changes in cognitively stimulating leisure activities during the retirement transition and their relationship to changes in postretirement memory. We drew data ( N = 631) from five waves of repeated annual measurements as part of the HEalth, Ageing and Retirement Transitions in Sweden study. We modeled memory trajectories using piecewise growth-curve models. Findings revealed that increased cognitive stimulation from leisure activities had beneficial effects on postretirement memory development among individuals reporting previously low cognitive work demands. Our findings provide partial evidence supporting public health recommendations, stating that retirees from less intellectually demanding occupations will gain from increases in cognitive leisure following retirement.
Race and Social Class as Intersecting Social	Categories
Authors: Moore-Berg Samantha L. , Karpinski Andrew
Published: July 2021

Abstract. Race and social class are inherently confounded; however, much of the literature focuses on only one of these categories at a time during attitude assessment. Across three studies, we examined the influence of race and social class on implicit and explicit attitudes. Results indicated that participants had more positive attitudes toward high social class White and high social class Black people than low social class White and low social class Black people. Attitudes for high social class White versus high social class Black people and low social class White versus low social class Black people were more nuanced and attitude/measure dependent. Thus, this research highlights the intricacy of attitudes when considering intersectional categories.
Representation of Bi‐Directional Fluxes Between Groundwater and Surface Water in a Bucket‐Type Hydrological Model
Authors: Staudinger M. , Seibert J. , van Meerveld H. J.
Published: July 2021

In most bucket‐type hydrological models, water can only flow from the groundwater to the stream and the flux is based on the groundwater storage. However, many catchments have losing stream sections, where streamflow recharges the groundwater. We developed a formulation to represent groundwater recharge by streamwater in a bucket‐type model and tested this formulation for the Panola Mountain Research Watershed to demonstrate its function and assess its performance. The upper reach of the Panola catchment is often dry and highly affected by flow from a bedrock outcrop; further downstream the stream is perennial. We simulated streamflow with the fully lumped version of a bucket‐type model and compared it to (a) a variant with sub‐catchments to more realistically represent the low storage and quick response from the bedrock outcrop and (b) a variant that also includes the bi‐directional exchange between the groundwater and the stream. For all three model variants, we compared simulated and observed streamflow and groundwater dynamics. Although the gain in overall model performance by including the bi‐directional exchange between the groundwater and the stream was small, the explicit representation of this exchange led to better streamflow simulations during drying‐down and wetting‐up periods. For Panola the fluxes along the stream appeared less important than subsurface drainage from the upper sub‐catchment to the downstream sub‐catchment. We recommend considering the bi‐directional fluxes between groundwater and the stream in bucket‐type hydrological models where these processes are important, and the focus of the simulations is on low flow conditions.
Observations of Short‐Period Ion‐Scale Current Sheet Flapping
Authors: Richard L. , Khotyaintsev Yu. V. , Graham D. B. , Sitnov M. I. , Le Contel O. , Lindqvist P.‐A.
Published: July 2021

Kink‐like flapping motions of current sheets are commonly observed in the magnetotail. Such oscillations have periods of a few minutes down to a few seconds and they propagate toward the flanks of the plasma sheet. Here, we report a short‐period ( s) flapping event of a thin current sheet observed by the Magnetospheric Multiscale spacecraft in the dusk‐side plasma sheet following a fast Earthward plasma flow. We characterize the flapping structure using the multi‐spacecraft spatiotemporal derivative and timing methods, and we find that the wave‐like structure is propagating along the average current direction with a phase velocity comparable to the ion velocity. We show that the wavelength of the oscillating current sheet scales with its thickness as expected for a drift‐kink mode. The decoupling of the ion bulk motion from the electron bulk motion suggests that the current sheet is thin. We discuss the presence of the lower hybrid waves associated with gradients of density as a broadening process of the thin current sheet.
Volume Transport Time Series and Variability of the North Atlantic Eastern Boundary Current at Goban Spur
Authors: Moritz Martin , Jochumsen Kerstin , Kieke Dagmar , Klein Birgit , Klein Holger , Köllner Manuela , Rhein Monika
Published: July 2021

The Eastern Boundary Current is an essential part of the water mass exchange between the subtropical and subpolar North Atlantic. Here, we study the offshore branch of the European Shelf Current (ESC) over the Goban Spur slope area off Ireland. Our analysis is based on current measurements obtained from a multiyear mooring effort, complemented by ship‐board observations along a hydrographic section, satellite‐derived estimates of absolute dynamic topography with geostrophic currents, and float trajectories. These data serve to quantify the offshore branch of the ESC on intraannual to interannual timescales. From the moored observations, we derive a mean poleward along‐slope volume flux of 3.7 0.7 Sv for the period 2017–2019. Using a multilinear regression model and geostrophic surface velocities, we extend the time series to the period 1993–2019 and obtain a long‐term mean transport of 3.2 0.4 Sv. Both time series show strong variability ranging from −7.5 to 15.7 Sv. The variability is linked to a dynamic eddy field, especially a stationary cyclonic circulation pattern near the mooring array, and meandering of current branches originating from the North Atlantic Current.

We find no evidence of a consistent deep boundary current extending from the shelf break to the position of the offshore mooring (4,500 m depth), but confirm a persistent along‐slope flow at the shallower slope (1,500 m depth). Geostrophic surface velocities and float trajectories reveal that the offshore branch of the ESC does not follow a clear northward path from the eastern subtropical regions but rather indicate the intermittent character of the flow.
SARS-CoV-2 test positivity rate in Reno, Nevada: association with PM2.5 during the 2020 wildfire smoke events in the western United States
Authors: Kiser Daniel , Elhanan Gai , Metcalf William J. , Schnieder Brendan , Grzymski Joseph J.
Published: July 2021

Background

Air pollution has been linked to increased susceptibility to SARS-CoV-2. Thus, it has been suggested that wildfire smoke events may exacerbate the COVID-19 pandemic.

Objectives

Our goal was to examine whether wildfire smoke from the 2020 wildfires in the western United States was associated with an increased rate of SARS-CoV-2 infections in Reno, Nevada.

Methods

We conducted a time-series analysis using generalized additive models to examine the relationship between the SARS-CoV-2 test positivity rate at a large regional hospital in Reno and ambient PM2.5 from 15 May to 20 Oct 2020.

Results

We found that a 10 µg/m3 increase in the 7-day average PM2.5 concentration was associated with a 6.3% relative increase in the SARS-CoV-2 test positivity rate, with a 95% confidence interval (CI) of 2.5 to 10.3%. This corresponded to an estimated 17.7% (CI: 14.4–20.1%) increase in the number of cases during the time period most affected by wildfire smoke, from 16 Aug to 10 Oct.

Significance

Wildfire smoke may have greatly increased the number of COVID-19 cases in Reno. Thus, our results substantiate the role of air pollution in exacerbating the pandemic and can help guide the development of public preparedness policies in areas affected by wildfire smoke, as wildfires are likely to coincide with the COVID-19 pandemic in 2021.
CtBP1/2 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell
Authors: He YingYing , He Zhicheng , Lin Jian , Chen Cheng , Chen Yuanzhi , Liu Shubai
Published: July 2021

The C-terminal binding proteins (CtBPs), CtBP1 and CtBP2, are transcriptional co-repressor that interacts with multiple transcriptional factors to modulate the stability of chromatin. CtBP proteins were identified with overexpression in the high-grade serous ovarian carcinoma (HGSOC). However, little is known about CtBP proteins’ regulatory roles in genomic stability and DNA repair in HGSOC. In this study, we combined whole-transcriptome analysis with multiple research methods to investigate the role of CtBP1/2 in genomic stability. Several key functional pathways were significantly enriched through whole transcription profile analysis of CtBP1/2 knockdown SKOV3 cells, including DNA damage repair, apoptosis, and cell cycle. CtBP1/2 knockdown induced cancer cell apoptosis, increased genetic instability, and enhanced the sensitivity to DNA damage agents, such as γ-irradiation and chemotherapy drug (Carboplatin and etoposide). The results of DNA fiber assay revealed that CtBP1/2 contribute differentially to the integrity of DNA replication track and stability of DNA replication recovery. CtBP1 protects the integrity of stalled forks under metabolic stress condition during prolonged periods of replication, whereas CtBP2 acts a dominant role in stability of DNA replication recovery. Furthermore, CtBP1/2 knockdown shifted the DSBs repair pathway from homologous recombination (HR) to non-homologous end joining (NHEJ) and activated DNA-PK in SKOV3 cells. Interesting, blast through TCGA tumor cases, patients with CtBP2 genetic alternation had a significantly longer overall survival time than unaltered patients. Together, these results revealed that CtBP1/2 play a different regulatory role in genomic stability and DSBs repair pathway bias in serous ovarian cancer cells. It is possible to generate novel potential targeted therapy strategy and translational application for serous ovarian carcinoma patients with a predictable better clinical outcome.
Retinoblastoma cell-derived exosomes promote angiogenesis of human vesicle endothelial cells through microRNA‐92a-3p
Authors: Chen Shuilian , Chen Xi , Luo Qian , Liu Xuan , Wang Xiao , Cui Zedu , He Anqi , He Shengyu , Jiang Zihua , Wu Nandan , Chen Pei , Yu Keming , Zhuang Jing
Published: July 2021

Exosomes derived from tumor cells play a key role in tumor development. In the present study, we identified the bioactivity of exosomes released from WERI-Rb1 retinoblastoma cells in tumor angiogenesis, as well as the underlying mechanism, through biochemical methods and animal experiments. Our in vitro data showed that exosomes could be engulfed by human vesicle endothelial cells (HUVECs), significantly promote cell viability and induce an inflammatory response in HUVECs by increasing the expression of a series of related genes, such as IL-1, IL-6, IL-8, MCP-1, VCAM1, and ICAM1. Significant increases in migration and tube formation were also observed in the HUVECs incubated with exosomes. Moreover, experiments with a nude mouse xenotransplantation model showed that exosomes injected near tumors could be strongly absorbed by tumor cells. The numbers of endothelial cells and blood vessels were significantly increased in tumor tissues treated with exosomes compared to control tissues. Furthermore, to reveal the mechanism underlying exosome-mediated angiogenesis in retinoblastoma, we analyzed the levels of 12 microRNAs in the exosomes. Specifically, our data showed that miR-92a-3p was enriched in RB exosomes. Accordingly, miR-92a-3p was increased in the HUVECs incubated with these exosomes. After treatment with a miR-92a-3p inhibitor, the promoting effect of exosomes on the migration and tube formation of HUVECs was significantly abrogated. The expression of the angiogenesis-related genes mentioned above was markedly decreased in HUVECs. Similarly, treatment with a microRNA mimic also demonstrated that miR-92a-3p was involved in the angiogenesis of HUVECs. More importantly, bioinformatics analysis predicted that Krüppel-like factor 2 (KLF2), a member of the KLF family of zinc-finger transcription factors, might be an active target of miR-92a-3p. Notably, this prediction was confirmed both in vitro and in vivo. Thus, our work suggests that exosomal miR-92a-3p is involved in tumor angiogenesis and might be a promising therapeutic candidate for retinoblastoma.
Induced TRIM21 ISGylation by IFN-β enhances p62 ubiquitination to prevent its autophagosome targeting
Authors: Jin Jie , Meng Xianbin , Huo Yi , Deng Haiteng
Published: July 2021

The tripartite motif-containing protein 21 (TRIM21) plays important roles in autophagy and innate immunity. Here, we found that HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), as an interferon-stimulated gene 15 (ISG15) E3 ligase, catalyzes the ISGylation of TRIM21 at the Lys260 and Lys279 residues. Moreover, IFN-β also induces TRIM21 ISGylation at multiple lysine residues, thereby enhancing its E3 ligase activity for K63-linkage-specific ubiquitination and resulting in increased levels of TRIM21 and p62 K63-linked ubiquitination. The K63-linked ubiquitination of p62 at Lys7 prevents its self-oligomerization and targeting to the autophagosome. Taken together, our study suggests that the ISGylation of TRIM21 plays a vital role in regulating self-oligomerization and localization of p62 in the autophagy induced by IFN-β.
miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer
Authors: Guo Jing , Zhong Xuxian , Tan Qinglin , Yang Shengnan , Liao Jiaqi , Zhuge Jinke , Hong Ziyang , Deng Qiong , Zuo Qiang
Published: July 2021

Trastuzumab resistance negatively influences the clinical efficacy of the therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC), and the underlying mechanisms remain elusive. Exploring the mechanisms and finding effective approaches to address trastuzumab resistance are of great necessity. Here, we confirmed that endoplasmic reticulum (ER) stress-induced trastuzumab resistance by up-regulating miR-301a-3p in HER2-positive GC cells. Moreover, we elucidated that miR-301a-3p mediated trastuzumab resistance by down-regulating the expression of leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) and subsequently activating the expression of insulin-like growth factor 1 receptor (IGF-1R) and fibroblast growth factor receptor 1 (FGFR1) under ER stress. We also found that intercellular transfer of miR-301a-3p by exosomes disseminated trastuzumab resistance. The present study demonstrated that exosomal miR-301a-3p could serve as a non-invasive biomarker for trastuzumab resistance, which was maybe a novel potential therapeutic target to overcome trastuzumab resistance and improve the curative effect of trastuzumab in HER2-positive GC patients.
Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines
Authors: Zheng Jiashuo , Sato Mami , Mishima Eikan , Sato Hideyo , Proneth Bettina , Conrad Marcus
Published: July 2021

Sorafenib, a protein kinase inhibitor approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma, has been repeatedly reported to induce ferroptosis by possibly involving inhibition of the cystine/glutamate antiporter, known as system xc−. Using a combination of well-defined genetically engineered tumor cell lines and canonical small molecule ferroptosis inhibitors, we now provide unequivocal evidence that sorafenib does not induce ferroptosis in a series of tumor cell lines unlike the cognate system xc− inhibitors sulfasalazine and erastin. We further show that only a subset of tumor cells dies by ferroptosis upon sulfasalazine and erastin treatment, implying that certain cell lines appear to be resistant to system xc− inhibition, while others undergo ferroptosis-independent cell death. From these findings, we conclude that sorafenib does not qualify as a bona fide ferroptosis inducer and that ferroptosis induced by system xc− inhibitors can only be achieved in a fraction of tumor cell lines despite robust expression of SLC7A11, the substrate-specific subunit of system xc−.
Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells
Authors: Zhang Jiayan , Wang Hui , Imhof Simon , Zhou Xueting , Liao Shiqing , Atanasov Ivo , Hui Wong H. , Hill Kent L. , Zhou Z. Hong
Published: July 2021

Eukaryotic flagella (synonymous with cilia) rely on a microtubule-based axoneme, together with accessory filaments to carryout motility and signaling functions. While axoneme structures are well characterized, 3D ultrastructure of accessory filaments and their axoneme interface are mostly unknown, presenting a critical gap in understanding structural foundations of eukaryotic flagella. In the flagellum of the protozoan parasite Trypanosoma brucei (T. brucei), the axoneme is accompanied by a paraflagellar rod (PFR) that supports non-planar motility and signaling necessary for disease transmission and pathogenesis. Here, we employed cryogenic electron tomography (cryoET) with sub-tomographic averaging, to obtain structures of the PFR, PFR-axoneme connectors (PACs), and the axonemal central pair complex (CPC). The structures resolve how the 8 nm repeat of the axonemal tubulin dimer interfaces with the 54 nm repeat of the PFR, which consist of proximal, intermediate, and distal zones. In the distal zone, stacked “density scissors” connect with one another to form a “scissors stack network (SSN)” plane oriented 45° to the axoneme axis; and ~370 parallel SSN planes are connected by helix-rich wires into a paracrystalline array with ~90% empty space. Connections from these wires to the intermediate zone, then to overlapping layers of the proximal zone and to the PACs, and ultimately to the CPC, point to a contiguous pathway for signal transmission. Together, our findings provide insights into flagellum-driven, non-planar helical motility of T. brucei and have broad implications ranging from cell motility and tensegrity in biology, to engineering principles in bionics.
Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted
Authors: Mario Isas J. , Pandey Nitin K. , Xu Hui , Teranishi Kazuki , Okada Alan K. , Fultz Ellisa K. , Rawat Anoop , Applebaum Anise , Meier Franziska , Chen Jeannie , Langen Ralf , Siemer Ansgar B.
Published: July 2021

The first exon of the huntingtin protein (HTTex1) important in Huntington’s disease (HD) can form cross-β fibrils of varying toxicity. We find that the difference between these fibrils is the degree of entanglement and dynamics of the C-terminal proline-rich domain (PRD) in a mechanism analogous to polyproline film formation. In contrast to fibril strains found for other cross-β fibrils, these HTTex1 fibril types can be interconverted. This is because the structure of their polyQ fibril core remains unchanged. Further, we find that more toxic fibrils of low entanglement have higher affinities for protein interactors and are more effective seeds for recombinant HTTex1 and HTTex1 in cells. Together these data show how the structure of a framing sequence at the surface of a fibril can modulate seeding, protein-protein interactions, and thereby toxicity in neurodegenerative disease.
Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery
Authors: Walter Corvin , Marada Adinarayana , Suhm Tamara , Ernsberger Ralf , Muders Vera , Kücükköse Cansu , Sánchez-Martín Pablo , Hu Zehan , Aich Abhishek , Loroch Stefan , Solari Fiorella Andrea , Poveda-Huertes Daniel , Schwierzok Alexandra , Pommerening Henrike , Matic Stanka , Brix Jan , Sickmann Albert , Kraft Claudine , Dengjel Jörn , Dennerlein Sven , Brummer Tilman , Vögtle F.-Nora , Meisinger Chris
Published: July 2021

The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A, including autism spectrum disorder, microcephaly and Down syndrome.
IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes
Authors: James Olivia J. , Vandereyken Maud , Marchingo Julia M. , Singh Francois , Bray Susan E. , Wilson Jamie , Love Andrew G. , Swamy Mahima
Published: July 2021

Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect and maintain the intestinal barrier. IEL respond to epithelial cell-derived IL-15, which is complexed to the IL-15 receptor α chain (IL-15/Rα). IL-15 is essential both for maintaining IEL homeostasis and inducing IEL responses to epithelial stress, which has been associated with Coeliac disease. Here, we apply quantitative mass spectrometry to IL-15/Rα-stimulated IEL to investigate how IL-15 directly regulates inflammatory functions of IEL. IL-15/Rα drives IEL activation through cell cycle regulation, upregulation of metabolic machinery and expression of a select repertoire of cell surface receptors. IL-15/Rα selectively upregulates the Ser/Thr kinases PIM1 and PIM2, which are essential for IEL to proliferate, grow and upregulate granzyme B in response to inflammatory IL-15. Notably, IEL from patients with Coeliac disease have high PIM expression. Together, these data indicate PIM kinases as important effectors of IEL responses to inflammatory IL-15.
A chalcogenide-cluster-based semiconducting nanotube array with oriented photoconductive behavior
Authors: Tang Jiaqi , Wang Xiang , Zhang Jiaxu , Wang Jing , Yin Wanjian , Li Dong-Sheng , Wu Tao
Published: July 2021

The interesting physical and chemical properties of carbon nanotubes (CNTs) have prompted the search for diverse inorganic nanotubes with different compositions to expand the number of available nanotechnology applications. Among these materials, crystalline inorganic nanotubes with well-defined structures and uniform sizes are suitable for understanding structure–activity relationships. However, their preparation comes with large synthetic challenges owing to their inherent complexity. Herein, we report the example of a crystalline nanotube array based on a supertetrahedral chalcogenide cluster, K3[K(Cu2Ge3Se9)(H2O)] (1). To the best of our knowledge, this nanotube array possesses the largest diameter of crystalline inorganic nanotubes reported to date and exhibits an excellent structure-dependent electric conductivity and an oriented photoconductive behavior. This work represents a significant breakthrough both in terms of the structure of cluster-based metal chalcogenides and in the conductivity of crystalline nanotube arrays (i.e., an enhancement of ~4 orders of magnitude).
Mediation of lubricated air films using spatially periodic dielectrophoretic effect
Authors: Vo Quoc , Tran Tuan
Published: July 2021

A stone thrown in a lake captures air as it collides with water and sinks; likewise a rain drop falling on a flat surface traps air bubbles underneath and creates a spectacular splash. These natural occurrences, from bubble entrapment to liquid ejection, happen as air fails to escape from the closing gap between liquid and solid surfaces. Trapping of air is devastating for casting, coating, painting, and printing industries, or those intolerant of water entry noise. Attempts to eliminate the interfering air rely on either reducing the ambient pressure or modifying the solid surfaces. The former approach is inflexible in its implementation, while the latter one is inherently limited by the wetting speed of liquid or the draining capacity of air passages created on the solid. Here, we present a “divide and conquer” approach to split the thin air gap into tunnels and subsequently squeeze air out from the tunnels against its viscous resistance using spatially periodic dielectrophoretic force. We confirm the working principles by demonstrating suppression of both bubble entrapment and splash upon impacts of droplets on solid surfaces.
Arabidopsis MORC proteins function in the efficient establishment of RNA directed DNA methylation
Authors: Xue Yan , Zhong Zhenhui , Harris C. Jake , Gallego-Bartolomé Javier , Wang Ming , Picard Colette , Cao Xueshi , Hua Shan , Kwok Ivy , Feng Suhua , Jami-Alahmadi Yasaman , Sha Jihui , Gardiner Jason , Wohlschlegel James , Jacobsen Steven E.
Published: July 2021

The Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms.
Evidence for one-dimensional chiral edge states in a magnetic Weyl semimetal Co3Sn2S2
Authors: Howard Sean , Jiao Lin , Wang Zhenyu , Morali Noam , Batabyal Rajib , Kumar-Nag Pranab , Avraham Nurit , Beidenkopf Haim , Vir Praveen , Liu Enke , Shekhar Chandra , Felser Claudia , Hughes Taylor , Madhavan Vidya
Published: July 2021

The physical realization of Chern insulators is of fundamental and practical interest, as they are predicted to host the quantum anomalous Hall (QAH) effect and topologically protected chiral edge states which can carry dissipationless current. Current realizations of the QAH state often require complex heterostructures and sub-Kelvin temperatures, making the discovery of intrinsic, high temperature QAH systems of significant interest. In this work we show that time-reversal symmetry breaking Weyl semimetals, being essentially stacks of Chern insulators with inter-layer coupling, may provide a new platform for the higher temperature realization of robust chiral edge states. We present combined scanning tunneling spectroscopy and theoretical investigations of the magnetic Weyl semimetal, Co3Sn2S2. Using modeling and numerical simulations we find that depending on the strength of the interlayer coupling, chiral edge states can be localized on partially exposed kagome planes on the surfaces of a Weyl semimetal. Correspondingly, our dI/dV maps on the kagome Co3Sn terraces show topological states confined to the edges which display linear dispersion. This work provides a new paradigm for realizing chiral edge modes and provides a pathway for the realization of higher temperature QAH effect in magnetic Weyl systems in the two-dimensional limit.
DNA transposons mediate duplications via transposition-independent and -dependent mechanisms in metazoans
Authors: Tan Shengjun , Ma Huijing , Wang Jinbo , Wang Man , Wang Mengxia , Yin Haodong , Zhang Yaqiong , Zhang Xinying , Shen Jieyu , Wang Danyang , Banes Graham L. , Zhang Zhihua , Wu Jianmin , Huang Xun , Chen Hua , Ge Siqin , Chen Chun-Long , Zhang Yong E.
Published: July 2021

Despite long being considered as “junk”, transposable elements (TEs) are now accepted as catalysts of evolution. One example isMutator-like elements (MULEs, one type of terminal inverted repeat DNA TEs, or TIR TEs) capturing sequences as Pack-MULEs in plants. However, their origination mechanism remains perplexing, and whether TIR TEs mediate duplication in animals is almost unexplored. Here we identify 370 Pack-TIRs in 100 animal reference genomes and one Pack-TIR (Ssk-FB4) family in fly populations. We find that single-copy Pack-TIRs are mostly generated via transposition-independent gap filling, and multicopy Pack-TIRs are likely generated by transposition after replication fork switching. We show that a proportion of Pack-TIRs are transcribed and often form chimeras with hosts. We also find thatSsk-FB4srepresent a young protein family, as supported by proteomics and signatures of positive selection. Thus, TIR TEs catalyze new gene structures and new genes in animals via both transposition-independent and -dependent mechanisms.
Geminiviruses encode additional small proteins with specific subcellular localizations and virulence function
Authors: Gong Pan , Tan Huang , Zhao Siwen , Li Hao , Liu Hui , Ma Yu , Zhang Xi , Rong Junjie , Fu Xing , Lozano-Durán Rosa , Li Fangfang , Zhou Xueping
Published: July 2021

Geminiviruses are plant viruses with limited coding capacity. Geminivirus-encoded proteins are traditionally identified by applying a 10-kDa arbitrary threshold; however, it is increasingly clear that small proteins play relevant roles in biological systems, which calls for the reconsideration of this criterion. Here, we show that geminiviral genomes contain additional ORFs. Using tomato yellow leaf curl virus, we demonstrate that some of these small ORFs are expressed during the infection, and that the encoded proteins display specific subcellular localizations. We prove that the largest of these additional ORFs, which we name V3, is required for full viral infection, and that the V3 protein localizes in the Golgi apparatus and functions as an RNA silencing suppressor. These results imply that the repertoire of geminiviral proteins can be expanded, and that getting a comprehensive overview of the molecular plant-geminivirus interactions will require the detailed study of small ORFs so far neglected.