bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Hurricane Matthew on a Cohort of Adolescents With Asthma in North Carolina
Authors: Davis Scott A. , Carpenter Delesha M. , Loughlin Ceila E. , Garcia Nacire , Sleath Betsy
Published: August 2023

Objective:

The aim of this study was to look at a cohort of adolescents who were already enrolled in a randomized controlled trial to see (1) how demographics were associated with hurricane impact, and (2) how hurricane impact was associated with reported asthma quality of life.

Methods:

One hundred fifty-one adolescents ages 11-17 and their parents enrolled in a randomized controlled trial at 2 sites in southeastern North Carolina completed questions about asthma quality of life, demographics, and the impact of Hurricane Matthew.

Results:

The most common effects of Hurricane Matthew were that the family’s home was damaged or flooded (32.5%), the school was damaged or flooded (31.8%), and the home had mold or mildew as a result of flooding or damage (25.8%). Problems with access to care were more common for families whose adolescent was non-White (P = 0.04), on Medicaid (P = 0.05), or if the family spoke Spanish at home (P < 0.001). Being affected by the hurricane was negatively associated with asthma quality of life.

Conclusions:

Hurricane Matthew had significant impact on the health of adolescents with asthma in the affected region, especially in the most vulnerable populations. Providers should ensure that families of adolescents with asthma have a hurricane plan to mitigate impact on their children’s health.
High-energy and high-peak-power GHz burst-mode all-fiber laser with a uniform envelope and tunable intra-burst pulses
Authors: Liu Shuailin , Zhang Bin , Bu Yuanzhuang , Zhao Desheng , Zhu Xiran , Yang Linyong , Hou Jing
Published: August 2023

We report a Yb-doped all-fiber laser system generating burst-mode pulses with high energy and high peak power at a GHz intra-burst repetition rate. To acquire the uniform burst envelope, a double-pre-compensation structure with an arbitrary waveform laser diode driver and an acoustic optical modulator is utilized for the first time. The synchronous pumping is utilized for the system to reduce the burst repetition rate to 100 Hz and suppress the amplified spontaneous emission effect. By adjusting the gain of every stage, uniform envelopes with different output energies can be easily obtained. The intra-burst repetition rate can be tuned from 0.5 to 10 GHz actively modulated by an electro-optic modulator. Optimized by timing control of eight channels of analog signal and amplified by seven stages of Yb-doped fiber amplifier, the pulse energy achieves 13.3 mJ at 0.5 ns intra-burst pulse duration, and the maximum peak power reaches approximately 3.6 MW at 48 ps intra-burst pulse duration. To the best of our knowledge, for reported burst-mode all-fiber lasers, this is a record for output energy and peak power with nanosecond-level burst duration, and the widest tuning range of the intra-burst repetition rate. In particular, this flexibly tunable burst-mode laser system can be directly applied to generate high-power frequency-tunable microwaves.
Stopping problems with an unknown state
Authors: Ekström Erik , Wang Yuqiong
Published: August 2023

We extend the classical setting of an optimal stopping problem under full information to include problems with an unknown state. The framework allows the unknown state to influence (i) the drift of the underlying process, (ii) the payoff functions, and (iii) the distribution of the time horizon. Since the stopper is assumed to observe the underlying process and the random horizon, this is a two-source learning problem. Assigning a prior distribution for the unknown state, standard filtering theory can be employed to embed the problem in a Markovian framework with one additional state variable representing the posterior of the unknown state. We provide a convenient formulation of this Markovian problem, based on a measure change technique that decouples the underlying process from the new state variable. Moreover, we show by means of several novel examples that this reduced formulation can be used to solve problems explicitly.
A novel approach for variable star classification based on imbalanced learning
Authors: Zhang Jingyi , Zhang Yanxia , Kang Zihan , Li Changhua , Tao Yihan , Zhao Yongheng , Wu Xue-Bing
Published: August 2023

The advent of time-domain sky surveys has generated a vast amount of light variation data, enabling astronomers to investigate variable stars with large-scale samples. However, this also poses new opportunities and challenges for the time-domain research. In this paper, we focus on the classification of variable stars from the Catalina Surveys Data Release 2 and propose an imbalanced learning classifier based on Self-paced Ensemble (SPE) method. Compared with the work of Hosenie et al. (2020), our approach significantly enhances the classificationRecallof Blazhko RR Lyrae stars from 12% to 85%, mixed-mode RR Lyrae variables from 29% to 64%, detached binaries from 68% to 97%, and LPV from 87% to 99%. SPE demonstrates a rather good performance on most of the variable classes except RRab, RRc, and contact and semi-detached binary. Moreover, the results suggest that SPE tends to target the minority classes of objects, while Random Forest is more effective in finding the majority classes. To balance the overall classification accuracy, we construct a Voting Classifier that combines the strengths of SPE and Random Forest. The results show that the Voting Classifier can achieve a balanced performance across all classes with minimal loss of accuracy. In summary, the SPE algorithm and Voting Classifier are superior to traditional machine learning methods and can be well applied to classify the periodic variable stars. This paper contributes to the current research on imbalanced learning in astronomy and can also be extended to the time-domain data of other larger sky survey projects (LSST, etc.).
Nestedness and beta diversity of gastrointestinal helminth communities in common warthogs,Phacochoerus africanus(Suidae), at 2 localities in South Africa
Authors: Junker Kerstin , Horak Ivan G. , Boomker Joop , Krasnov Boris R.
Published: August 2023

Few studies have investigated the ecological interactions between wild species of Suidae and their parasites, leaving our knowledge concerning this host–parasite system fragmented. In the present study, we applied network studies to analyse community nestedness in helminth assemblages of common warthogs,Phacochoerus africanus(Gmelin) (Suidae). Helminth data were compiled from 95 warthogs, including young and adult males and females, from 2 different conservation areas in Mpumalanga and Limpopo Provinces, South Africa, collected monthly over a period of 1 year each. The aim was to study the effect of host sex, age and season of sampling on the structure of helminth infracommunities harboured by the warthogs and to search for non-random structural patterns in the warthog–helminth interaction networks. Furthermore, we investigated the influence of a warthog's age, sex and season of sampling on beta diversity and dark diversity of their helminth infracommunities. Lastly, we asked whether the effects of host sex, age and sampling season on helminth communities differed between the 2 localities. We found that helminth communities of warthogs were nested and host–parasite interactions were influenced by all 3 factors as well as combinations thereof. However, the resulting patterns differed at the 2 localities, indicating that local environmental processes are important drivers of community structure.
The effects of habitat loss and fragmentation on the relative abundance and conservation of Southern Black Korhaan Afrotis afra, a South African endemic
Authors: Evans Steven W.
Published: August 2023

Southern Black Korhaan is “Vulnerable” to extinction and a South African endemic that is restricted to the area of the Northern Cape Province that is west of the Great Escarpment, and to the area south of the Great Escarpment in the Western Cape, and the western section of the Eastern Cape Province. The 1990, 2014, and 2020 land use land cover (LULC) databases prepared for South Africa were used to determine the LULC categories that best describe suitable habitat for the birds using beta regressions and data on the exact locality of the birds from BirdLasser. The South African Bird Atlas Project (SABAP) reporting rates were used to determine the change in the relative abundance of the birds between the first and second SABAP. Beta regression models were compiled using the bird’s reporting rate and the total surface area, and three other landscape metrics, of the per pentad LULC categories considered to be suitable habitat for them. These models and the SABAP reporting rates revealed that Southern Black Korhaan is adversely affected by the loss of, especially, its fynbos habitat to crop agriculture. In 2020, the area of suitable habitat available to the bird was estimated to be 2,035,526 ha on terrain with a slope of ≤4°. Southern Black Korhaan remains “Vulnerable” to extinction because of the continued decline of >30% in the size of its population over three generations (31 years). The cumulative effects of habitat fragmentation and loss on Southern Black Korhaan and other threatened taxa must be mitigated by conserving and, where appropriate, rehabilitating suitable habitat (e.g. Gouritz Cluster Biosphere Reserve’s Corridors and Rehabilitation Project) in the protected areas, critical biodiversity areas, and ecosystem support areas identified in the provincial spatial conservation plans. Together these areas form a perforated landscape that ensures maximum connectivity between the remaining patches of indigenous habitat.
Agent-Based Music Live Coding: Sonic adventures in 2D
Authors: Roma Gerard
Published: August 2023

This article describes agent-based music live coding, an approach for music performance and composition based on programming a set of agents in a 2D plane. This style of programming draws from the tradition of agent-based models and facilitates interactive algorithmic control of data-driven sound synthesis methods such as wave terrain synthesis or corpus-based concatenative synthesis. The main elements are a ‘terrain’, which may be used to access different types of data, a set of agents and their trajectories, and a set of synthesis functions associated to agents. An implementation using the SuperCollider language is demonstrated.
Vitamin D and suicidality: a Chinese early adolescent cohort and Mendelian randomization study
Authors: Yuan Mengyuan , Li Yonghan , Chang Junjie , Zhang Xueying , Wang Shaojie , Cao Leilei , Li Yuan , Wang Gengfu , Su Puyu
Published: August 2023

Aims

Previous cross-sectional and case–control studies have proposed that decreased vitamin D levels are positively correlated with the risk of suicidality in adults. However, limited studies have examined the association between vitamin D and suicidality in adolescents. This study aimed to investigate the relationship between serum vitamin D and suicidality risk among early adolescents.

Methods

Data were obtained from a Chinese early adolescent cohort. In this cohort, seventh-grade students from a middle school in Anhui Province were invited to voluntarily participate in the baseline assessments and provide peripheral blood samples (in September 2019). The participants were followed up annually (in September 2020 and September 2021). Serum 25-hydroxyvitamin D [25(OH)D] and vitamin D–related single-nucleotide polymorphisms at baseline were measured in November 2021. Traditional observational and Mendelian randomization (MR) analyses were performed to examine the relationship between serum 25(OH)D at baseline and the risk of baseline and incident suicidality (i.e., suicidal ideation [SI], plans and attempts).

Results

Traditional observational analysis did not reveal a significant linear or non-linear association of serum 25(OH)D concentration with the risks of baseline and 2-year incident suicidality in the total sample (P > .05 for all). Sex-stratified analysis revealed a non-linear association between the 25(OH)D concentration and the risk of baseline SI in women (Poverall = .002; Pnon-linear = .001). Moreover, the risk of baseline SI in the 25(OH) insufficiency group was lower than that in the 25(OH) deficiency group in the total sample (odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.51–0.92, P = .012). This difference remained significant in women (OR = 0.59, 95% CI = 0.40–0.87, P = .008) but not in men (OR = 0.78, 95% CI = 0.53–1.15, P = .205). Additionally, both linear and non-linear MR analyses did not support the causal effect of serum 25(OH)D concentration on the risk of baseline, 1-year and 2-year incident suicidality (P > .05 for all).

Conclusions

This study could not confirm the causal effect of vitamin D on suicidality risk among Chinese early adolescents. Future studies must confirm these findings with a large sample size.
Contributions of shading, soybean (Glycine max) row width, and planting green on horseweed (Conyza canadensis) management compared with soil-applied residual herbicides
Authors: Fisher Justine L. , Sprague Christy L.
Published: August 2023

Glyphosate-resistant (GR) horseweed is a problematic weed for Michigan soybean growers. Additionally, rosette- and upright-horseweed growth types have been observed co-emerging during mid- to late summer in several Michigan fields. In the greenhouse, shade levels from 35% to 92% reduced rosette- and upright-horseweed biomass 31% to 99% compared with the upright growth type grown under 0% shade. Greater reductions in biomass occurred under 69% and 92% shade. Thus, increased shading by planting in narrow rows and/or planting green into cereal rye may improve horseweed suppression. A field experiment conducted over 3 site-years compared the effect of fall-planted cereal rye terminated with glyphosate 1 wk after planting (WAP; planting green) with a preemergence residual herbicide program (glyphosate + 2,4-D + flumioxazin + metribuzin) on horseweed control in soybean planted in three row widths (19, 38, and 76 cm). Planting green or applying a residual herbicide program across all row widths reduced horseweed biomass 86% to 91% and 95% to 99%, respectively, compared with soybean planted with no cover in 76-cm rows, 4 to 6 WAP. At soybean harvest, when a noneffective postemergence herbicide (glyphosate) was applied, horseweed biomass was 42% and 81% lower by planting green or applying a residual-herbicide program compared with no cover, respectively. Similarly, planting soybean in 19-cm rows reduced horseweed biomass compared with 38- and 76-cm rows. When an effective postemergence program was applied, similar horseweed biomass reductions were observed by planting green or applying a residual herbicide across all row widths. Additionally, soybean yield and economic returns were similar between planting green and applying a residual herbicide in 1 of 2 site-years. Integrating planting green and an effective postemergence herbicide program offers an alternative horseweed management strategy to applying a residual preemergence herbicide program.
Suicide Methods in Slovenia – Characteristics andTime Trends 2001–2020
Authors: Mikolič Petra , Vinko Matej , Ropret Nina , Roškar Saška
Published: August 2023

Abstract: Background: Between 2001 and 2020, Slovenia lost 8,952 lives due to suicides, two thirds of them by hanging. Aim: To analyze trends in suicide methods between 2001 and 2020 and to explore relationships between suicide methods and selected sociodemographic characteristic. Methods: We focused on methods accounting for 95.7% of all suicides. We performed joinpoint regression to examine changes in suicide rates by respective methods and multivariate logistic regression analyses to study sociodemographics associated with specific suicide methods. Results: A gender-specific annual decrease in suicide rates was observed in all methods except for sharp objects and jumping or lying in front of a moving object. Age was statistically significant in the use of firearms and jumping or lying in front of a moving object, while gender was significant in all methods. Associations were found between education, marital status, region of residence, and various suicide methods. Limitations: The results are potentially culturally specific. Conclusion: Certain sociodemographics seem to be associated with the selection of the method.
Theory Matters
Authors: Hahnel Carolin , Jung Alexander J. , Goldhammer Frank
Published: August 2023

Abstract: Following an extended perspective of evidence-centered design, this study provides a methodological exemplar of the theory-based construction of process indicators from log data. We investigated decision-making processes in web search as the target construct, assuming that individuals follow a heuristic search (focusing on search results vs. websites as a primary information source) and stopping rule (following a satisficing vs. sampling strategy). Drawing on these assumptions, we describe our reasoning for identifying the empirical evidence needed and selecting an assessment to obtain this evidence to derive process indicators that represent groups differentiated by search and stopping rule combinations. To evaluate our approach, we reanalyzed the processing behavior of 150 university students who were requested in four tasks to select a specific website from a list of five search results. We determined the process indicators per item and conducted multiple cluster analyses to investigate group recovery. For each item, we found three clusters, two of which matched our assumptions. Additionally, we explored the consistency of students’ cluster membership across items and investigated their relationship with students’ skills in evaluating online information. Based on the results, we discuss the tradeoff between construct breadth and process elaboration for deriving meaningful process indicators.
Team Psychological Capital
Authors: Marques Dominic L. , Aubé Caroline , Rousseau Vincent
Published: August 2023

Abstract: This scoping review offers a comprehensive synthesis of the literature on team PsyCap. Based on a sample of 31 studies, our review indicates that (1) researchers have been somewhat inconsistent in how they operationalize team PsyCap, (2) gaps still remain in the nomological network of team PsyCap, (3) previous studies have mostly relied on time-insensitive designs, and (4) there is a thin use of theory when it comes to the explanation of the emergence of team PsyCap. In response, we highlight how issues pertaining to composition models contribute to clarify the nature of the team PsyCap construct, we propose interesting avenues for future research, and we introduce a temporal and recurring phase model of the emergence of team PsyCap.
Global Climate Impacts of Land‐Surface and Atmospheric Processes Over the Tibetan Plateau
Authors: Huang Jianping , Zhou Xiuji , Wu Guoxiong , Xu Xiangde , Zhao Qingyun , Liu Yimin , Duan Anmin , Xie Yongkun , Ma Yaoming , Zhao Ping , Yang Song , Yang Kun , Yang Haijun , Bian Jianchun , Fu Yunfei , Ge Jinming , Liu Yuzhi , Wu Qigang , Yu Haipeng , Wang Binbin , Bao Qing , Qie Kai
Published: August 2023

The Tibetan Plateau (TP) impacts local and remote atmospheric circulations, wherein it mechanically and thermally affects air masses or airflows. Moreover, the TP provides a key channel for substance transport between the troposphere and the stratosphere. This study reviews recent advances in research regarding land–atmosphere coupling processes over the TP. The TP experiences climate warming and wetting. Climate warming has caused glacier retreat, permafrost degradation, and a general increase in vegetation density, while climate wetting has led to a significant increase in the number of major lakes, primarily through increased precipitation. Local and regional climates are affected by interactions between the land and the atmosphere. Namely, the TP drives surface pollutants to the upper troposphere in an Asian summer monsoon (ASM) anticyclone circulation, before spreading to the lower stratosphere. Further, the thermal forcing of the TP plays an essential role in the ASM. TP forcing can modulate hemispheric‐scale atmospheric circulations across all seasons. The TP interacts with remote oceans through a forced atmospheric response and is substantially affected by the evolution of the Earth's climate via promoting Atlantic meridional overturning circulation and eliminating Pacific meridional overturning circulation. The extensive influence of the TP is facilitated by its coupling with the ASM in the summer; whereas its winter influence on climate mainly occurs through Rossby waves. The observed increasing trends of temperature and precipitation over the TP are projected to continue throughout the 21st century.
Understanding an Extreme Weather Event with Science and Local Knowledge
Authors: Gonz�lez Roberto
Published: August 2023

Researchers in Mexico integrate science and community knowledge to assess the ecological and social impact of an extreme frost.
Modeling Deep Rooted Thrust Mechanism of Crustal Thickening in Eastern Tibet
Authors: Pitard P. , Replumaz A. , Thieulot C. , Doin M.‐P.
Published: August 2023

To test Eastern Tibet crustal thickening modes, we compare 2‐D numerical models of two emblematic end‐member models, with either an obstacle in the low viscosity lower crust or a thrust embedded in the high viscosity one. We show that the obstacle halts the viscous lower crustal flow potentially initiated by the weight of the high Central Tibet, generating a smooth exhumation gradient at the edge of the plateau, not observed in Eastern Tibet. On the contrary, including a low viscosity discontinuity in the upper crust, mimicking a shallow steep listric fault as inferred in the region, reproduces a sharper exhumation profile, as constrained from thermo‐kinematic inversions of thermochronological data, and the lack of foreland basin, as observed in the field. Moreover, such fault drives deformation throughout the entire crust, suggesting a deep crustal ductile shear zone limiting the more ductile deformation in the lower crust although no discontinuity is imposed.
Surface‐Forced Variability in the Nordic Seas Overturning Circulation and Overflows
Authors: Årthun Marius
Published: August 2023

Water mass transformation in the Nordic Seas and the associated overflow of dense waters across the Greenland‐Scotland Ridge (GSR) acts to maintain the lower limb of the Atlantic meridional overturning circulation. Here, we use ocean and atmospheric reanalysis to assess the temporal variability in the Nordic Seas overturning circulation between 1950 and 2020 and its relation to surface buoyancy forcing. We find that variable surface‐forced transformation of Atlantic waters in the eastern Nordic Seas can explain variations in overflow transport across the GSR. The production of dense water masses in the Greenland and Iceland Seas is of minor importance to overflow variability. The Nordic Seas overturning circulation shows pronounced multidecadal variability that is in phase with the Atlantic Multidecadal Variability (AMV) index, but no long‐term trend. As the AMV is currently transitioning into its negative phase, the next decades could see a decreased overflow from the Nordic Seas.
Seasonality Drives Carbon Emissions Along a Stream Network
Authors: Conroy Hannah D. , Hotchkiss Erin R. , Cawley Kaelin M. , Goodman Keli , Hall Robert O. , Jones Jeremy B. , Wollheim Wilfred M. , Butman David
Published: August 2023

Headwater stream networks contribute substantially to the global carbon dioxide terrestrial flux because of high turbulence and coupling with terrestrial environments. Heterogeneity within headwater stream networks, both spatially and temporally, makes measuring and upscaling these emissions challenging because measurements of carbon dioxide in streams are often limited to a few monitoring points. We modified a stream network model to reflect real measurements made under base flow and high flow conditions at Martha Creek in Stabler, WA in the US Pacific Northwest. We found that under high flow conditions, the stream network had much greater total carbon emissions than during low flow conditions (1.22 Mg C day−1 vs. 0.034 Mg C day−1). We attribute this increase to a larger overall stream network area (0.04 vs. 0.01 km2) and discharge (1.9 m3 s−1 vs. 0.005 m3 s−1) in November versus August. Our results demonstrate the need to understand the nonperennial stream reaches when calculating carbon emissions. We compared the stream network emissions with the terrestrial net ecosystem exchange (NEE) estimated by local eddy covariance measurements per watershed area (−5.5 Mg C day−1 in August and −2.2 Mg C day−1 in November). Daily stream emissions in November accounted for a much larger percentage of NEE than in August (54% vs. 0.62%). We concluded that the stream network can emit a large percentage of the forest NEE in the winter months, and annual estimates of stream network emissions must consider the flow regime throughout the year.
LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling
Authors: Li Tiancheng , Wang Han , Jiang Yukun , Chen Shuo , Huang Danyuan , Wu Zuping , Yin Xing , Zhou Chenchen , Li Yuyu , Zou Shujuan
Published: August 2023

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.
Developmental consequences of short apneas and periodic breathing in preterm infants
Authors: Yee Alicia K. , Siriwardhana Leon S. , Nixson Gillian M. , Walter Lisa M. , Wong Flora Y. , Horne Rosemary S. C.
Published: August 2023

Objective

We investigated the relationship between respiratory events experienced before and after hospital discharge and developmental outcomes at 6 months corrected age (CA).

Study design

Preterm infants born between 28–32 weeks gestational age (GA) were studied at 32–36 weeks postmenstrual age (PMA), 36–40 weeks PMA, 3- and 6-months CA. Percentage total sleep time (%TST) with respiratory events (isolated apneas, sequential apneas and periodic breathing (PB)) at each study was calculated. Stepwise multiple linear regressions determined significant predictors of developmental outcomes at 6 months.

Result

%TST with respiratory events at term were significant predictors of language (R2 = 0.165, β = −0.416) and motor (R2 = 0.180, β = −0.485) composite scores of the Bayley Scales of Infant Development at 6 months, independent of GA, birth weight and sex.

Conclusions

In clinically stable very preterm infants at term equivalent age, time spent having respiratory events, was related to a reduction in language and motor outcomes at 6 months.
SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1
Authors: Xu Xiao-Chen , Jiang Jia-Xin , Zhou Ya-Qing , He Shuai , Liu Yang , Li Yi-Qi , Wei Pan-Pan , Bei Jin-Xin , Sun Jian , Luo Chun-Ling
Published: August 2023

Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.
PRMT1 methylation of WTAP promotes multiple myeloma tumorigenesis by activating oxidative phosphorylation via m6A modification of NDUFS6
Authors: Jia Yachun , Yu Xiao , Liu Rui , Shi Luyi , Jin Hua , Yang Dan , Zhang Xiaofeng , Shen Ying , Feng Yuandong , Zhang Peihua , Yang Yi , Zhang Linlin , Zhang Pengyu , Li Zongfang , He Aili , Kong Guangyao
Published: August 2023

Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Herein, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients, which was positively correlated with MM stages. High PRMT1 expression was correlated with adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that the knockdown of PRMT1 reduced the oxidative phosphorylation (OXPHOS) of MM cells through NDUFS6 downregulation. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1, and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that the combination of PRMT1 inhibitor and bortezomib synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggeste that PRMT1 could be a potential therapeutic target in MM.
The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis
Authors: Khan Abrar Ul Haq , Ali Alaa Kassim , Marr Bryan , Jo Donghyeon , Ahmadvand Simin , Fong-McMaster Claire , Almutairi Saeedah Musaed , Wang Lisheng , Sad Subash , Harper Mary-Ellen , Lee Seung-Hwan
Published: August 2023

Natural killer (NK) cells are predominant innate lymphocytes that initiate the early immune response during infection. NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection. Tumor necrosis factor-alpha (TNFα) is a well-known inflammatory cytokine that enhances NK cell function; however, the mechanism underlying NK cell proliferation in response to TNFα is not well established. Here, we demonstrated that upon infection/inflammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity, and effector function. Notably, IL-18 can induce TNFR2 expression in NK cells, augmenting their sensitivity toward TNFα. Mechanistically, TNFα-TNFR2 signaling upregulates the expression of CD25 (IL-2Rα) and nutrient transporters in NK cells, leading to a metabolic switch toward aerobic glycolysis. Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice. Accordingly, our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation, glycolysis, and effector function.
Novel homozygous variants in PRORP expand the genotypic spectrum of combined oxidative phosphorylation deficiency 54
Authors: Smith Thomas B. , Rea Alessandro , Thomas Huw B. , Thompson Kyle , Oláhová Monika , Maroofian Reza , Zamani Mina , He Langping , Sadeghian Saeid , Galehdari Hamid , Lotan Nava Shaul , Gilboa Tal , Herman Kristin C. , McCorvie Thomas J. , Yue Wyatt W. , Houlden Henry , Taylor Robert W. , Newman William G. , O’Keefe Raymond T.
Published: August 2023

Biallelic hypomorphic variants in PRORP have been recently described as causing the autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three additional families with homozygous missense PRORP variants with pleiotropic phenotypes. Each missense variant altered a highly conserved residue within the metallonuclease domain. In vitro mitochondrial tRNA processing assays with recombinant TRMT10C, SDR5C1 and PRORP indicated two COXPD54-associated PRORP variants, c.1159A>G (p.Thr387Ala) and c.1241C>T (p.Ala414Val), decreased pre-tRNAIle cleavage, consistent with both variants impacting tRNA processing. No significant decrease in tRNA processing was observed with PRORP c.1093T>C (p.Tyr365His), which was identified in an individual with leukodystrophy. These data provide independent evidence that PRORP variants are associated with COXPD54 and that the assessment of 5′ leader mitochondrial tRNA processing is a valuable assay for the functional analysis and clinical interpretation of novel PRORP variants.
Anomalous Landau quantization in intrinsic magnetic topological insulators
Authors: Chong Su Kong , Lei Chao , Lee Seng Huat , Jaroszynski Jan , Mao Zhiqiang , MacDonald Allan H. , Wang Kang L.
Published: August 2023

The intrinsic magnetic topological insulator, Mn(Bi1−xSbx)2Te4, has been identified as a Weyl semimetal with a single pair of Weyl nodes in its spin-aligned strong-field configuration. A direct consequence of the Weyl state is the layer dependent Chern number, $$C$$
C
. Previous reports in MnBi2Te4 thin films have shown higher $$C$$
C
states either by increasing the film thickness or controlling the chemical potential. A clear picture of the higher Chern states is still lacking as data interpretation is further complicated by the emergence of surface-band Landau levels under magnetic fields. Here, we report a tunable layer-dependent $$C$$
C
 = 1 state with Sb substitution by performing a detailed analysis of the quantization states in Mn(Bi1−xSbx)2Te4 dual-gated devices—consistent with calculations of the bulk Weyl point separation in the doped thin films. The observed Hall quantization plateaus for our thicker Mn(Bi1−xSbx)2Te4 films under strong magnetic fields can be interpreted by a theory of surface and bulk spin-polarised Landau level spectra in thin film magnetic topological insulators.
Structure and regulation of full-length human leucine-rich repeat kinase 1
Authors: Metcalfe Riley D. , Martinez Fiesco Juliana A. , Bonet-Ponce Luis , Kluss Jillian H. , Cookson Mark R. , Zhang Ping
Published: August 2023

The human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human disease. Structures of LRRK2 have recently been determined, but the structure and molecular mechanisms regulating the activity of the LRRK1 as well as differences in the regulation of LRRK1 and LRRK2 remain unclear. Here, we report a cryo-EM structure of the LRRK1 monomer and a lower-resolution cryo-EM map of the LRRK1 dimer. The monomer structure, in which the kinase is in an inactive conformation, reveals key interdomain interfaces that control kinase activity as we validate experimentally. Both the LRRK1 monomer and dimer are structurally distinct compared to LRRK2. Overall, our results provide structural insights into the activation of the human LRRKs, which advance our understanding of their physiological and pathological roles.
High-performance thermomagnetic generator controlled by a magnetocaloric switch
Authors: Liu Xianliang , Chen Haodong , Huang Jianyi , Qiao Kaiming , Yu Ziyuan , Xie Longlong , Ramanujan Raju V. , Hu Fengxia , Chu Ke , Long Yi , Zhang Hu
Published: August 2023

Low grade waste heat accounts for ~65% of total waste heat, but conventional waste heat recovery technology exhibits low conversion efficiency for low grade waste heat recovery. Hence, we designed a thermomagnetic generator for such applications. Unlike its usual role as the coil core or big magnetic yoke in previous works, here the magnetocaloric material acts as a switch that controls the magnetic circuit. This makes it not only have the advantage of flux reversal of the pretzel-like topology, but also present a simpler design, lower magnetic stray field, and higher performance by using less magnetocaloric material than preceding devices. The effects of key structural and system parameters were studied through a combination of experiments and finite element simulations. The optimized max power density PDmax produced by our device is significantly higher than those of other existing active thermomagnetic, thermo, and pyroelectric generators. Such high performance shows the effectiveness of our topology design of magnetic circuit with magnetocaloric switch.
TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6
Authors: Zhao Yiqi , Lu Yongxu , Richardson Samuel , Sreekumar Meghna , Albarnaz Jonas D. , Smith Geoffrey L.
Published: August 2023

Human tripartite motif protein 5α (TRIM5α) is a well-characterized restriction factor for some RNA viruses, including HIV1–5; however, reports are limited for DNA viruses6,7. Here we demonstrate that TRIM5α also restricts orthopoxviruses and, via its SPRY domain, binds to the orthopoxvirus capsid protein L3 to diminish virus replication and activate innate immunity. In response, several orthopoxviruses, including vaccinia, rabbitpox, cowpox, monkeypox, camelpox and variola viruses, deploy countermeasures. First, the protein C6 binds to TRIM5 via the RING domain to induce its proteasome-dependent degradation. Second, cyclophilin A (CypA) is recruited via interaction with the capsid protein L3 to virus factories and virions to antagonize TRIM5α; this interaction is prevented by cyclosporine A (CsA) and the non-immunosuppressive derivatives alisporivir and NIM811. Both the proviral effect of CypA and the antiviral effect of CsA are dependent on TRIM5α. CsA, alisporivir and NIM811 have antiviral activity against orthopoxviruses, and because these drugs target a cellular protein, CypA, the emergence of viral drug resistance is difficult. These results warrant testing of CsA derivatives against orthopoxviruses, including monkeypox and variola.
Tail engagement of arrestin at the glucagon receptor
Authors: Chen Kun , Zhang Chenhui , Lin Shuling , Yan Xinyu , Cai Heng , Yi Cuiying , Ma Limin , Chu Xiaojing , Liu Yuchen , Zhu Ya , Han Shuo , Zhao Qiang , Wu Beili
Published: August 2023

Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization1,2. It has been proposed that the arrestin binds to the receptor in two different conformations, ‘tail’ and ‘core’, which were suggested to govern distinct processes of receptor signalling and trafficking3,4. However, little structural information is available for the tail engagement of the arrestins. Here we report two structures of the glucagon receptor (GCGR) bound to β-arrestin 1 (βarr1) in glucagon-bound and ligand-free states. These structures reveal a receptor tail-engaged binding mode of βarr1 with many unique features, to our knowledge, not previously observed. Helix VIII, instead of the receptor core, has a major role in accommodating βarr1 by forming extensive interactions with the central crest of βarr1. The tail-binding pose is further defined by a close proximity between the βarr1 C-edge and the receptor helical bundle, and stabilized by a phosphoinositide derivative that bridges βarr1 with helices I and VIII of GCGR. Lacking any contact with the arrestin, the receptor core is in an inactive state and loosely binds to glucagon. Further functional studies suggest that the tail conformation of GCGR–βarr governs βarr recruitment at the plasma membrane and endocytosis of GCGR, and provides a molecular basis for the receptor forming a super-complex simultaneously with G protein and βarr to promote sustained signalling within endosomes. These findings extend our knowledge about the arrestin-mediated modulation of GPCR functionalities.
Mitochondrial integrated stress response controls lung epithelial cell fate
Authors: Han SeungHye , Lee Minho , Shin Youngjin , Giovanni Regina , Chakrabarty Ram P. , Herrerias Mariana M. , Dada Laura A. , Flozak Annette S. , Reyfman Paul A. , Khuder Basil , Reczek Colleen R. , Gao Lin , Lopéz-Barneo José , Gottardi Cara J. , Budinger G. R. Scott , Chandel Navdeep S.
Published: August 2023

Alveolar epithelial type 1 (AT1) cells are necessary to transfer oxygen and carbon dioxide between the blood and air. Alveolar epithelial type 2 (AT2) cells serve as a partially committed stem cell population, producing AT1 cells during postnatal alveolar development and repair after influenza A and SARS-CoV-2 pneumonia1–6. Little is known about the metabolic regulation of the fate of lung epithelial cells. Here we report that deleting the mitochondrial electron transport chain complex I subunit Ndufs2 in lung epithelial cells during mouse gestation led to death during postnatal alveolar development. Affected mice displayed hypertrophic cells with AT2 and AT1 cell features, known as transitional cells. Mammalian mitochondrial complex I, comprising 45 subunits, regenerates NAD+ and pumps protons. Conditional expression of yeast NADH dehydrogenase (NDI1) protein that regenerates NAD+ without proton pumping7,8 was sufficient to correct abnormal alveolar development and avert lethality. Single-cell RNA sequencing revealed enrichment of integrated stress response (ISR) genes in transitional cells. Administering an ISR inhibitor9,10 or NAD+ precursor reduced ISR gene signatures in epithelial cells and partially rescued lethality in the absence of mitochondrial complex I function. Notably, lung epithelial-specific loss of mitochondrial electron transport chain complex II subunit Sdhd, which maintains NAD+ regeneration, did not trigger high ISR activation or lethality. These findings highlight an unanticipated requirement for mitochondrial complex I-dependent NAD+ regeneration in directing cell fate during postnatal alveolar development by preventing pathological ISR induction.
Red-tailed hawk algorithm for numerical optimization and real-world problems
Authors: Ferahtia Seydali , Houari Azeddine , Rezk Hegazy , Djerioui Ali , Machmoum Mohamed , Motahhir Saad , Ait-Ahmed Mourad
Published: August 2023

This study suggests a new nature-inspired metaheuristic optimization algorithm called the red-tailed hawk algorithm (RTH). As a predator, the red-tailed hawk has a hunting strategy from detecting the prey until the swoop stage. There are three stages during the hunting process. In the high soaring stage, the red-tailed hawk explores the search space and determines the area with the prey location. In the low soaring stage, the red-tailed moves inside the selected area around the prey to choose the best position for the hunt. Then, the red-tailed swings and hits its target in the stooping and swooping stages. The proposed algorithm mimics the prey-hunting method of the red-tailed hawk for solving real-world optimization problems. The performance of the proposed RTH algorithm has been evaluated on three classes of problems. The first class includes three specific kinds of optimization problems: 22 standard benchmark functions, including unimodal, multimodal, and fixed-dimensional multimodal functions, IEEE Congress on Evolutionary Computation 2020 (CEC2020), and IEEE CEC2022. The proposed algorithm is compared with eight recent algorithms to confirm its contribution to solving these problems. The considered algorithms are Farmland Fertility Optimizer (FO), African Vultures Optimization Algorithm (AVOA), Mountain Gazelle Optimizer (MGO), Gorilla Troops Optimizer (GTO), COOT algorithm, Hunger Games Search (HGS), Aquila Optimizer (AO), and Harris Hawks optimization (HHO). The results are compared regarding the accuracy, robustness, and convergence speed. The second class includes seven real-world engineering problems that will be considered to investigate the RTH performance compared to other published results profoundly. Finally, the proton exchange membrane fuel cell (PEMFC) extraction parameters will be performed to evaluate the algorithm with a complex problem. The proposed algorithm will be compared with several published papers to approve its performance. The ultimate results for each class confirm the ability of the proposed RTH algorithm to provide higher performance for most cases. For the first class, the RTH mostly got the optimal solutions for most functions with faster convergence speed. The RTH provided better performance for the second and third classes when resolving the real word engineering problems or extracting the PEMFC parameters.