bluuebunny/crossref_metadata_2025 huggingface dataset:
Social motivation in infancy is associated with familial recurrence of ASD
Authors: Marrus Natasha , Botteron Kelly N. , Hawks Zoë , Pruett John R. , Elison Jed T. , Jackson Joshua J. , Markson Lori , Eggebrecht Adam T. , Burrows Catherine A. , Zwaigenbaum Lonnie , Dager Stephen R. , Estes Annette M. , Hazlett Heather Cody , Schultz Robert T. , Piven Joseph , Constantino John N.
Published: October 2022

Pre-diagnostic deficits in social motivation are hypothesized to contribute to autism spectrum disorder (ASD), a heritable neurodevelopmental condition. We evaluated psychometric properties of a social motivation index (SMI) using parent-report item-level data from 597 participants in a prospective cohort of infant siblings at high and low familial risk for ASD. We tested whether lower SMI scores at 6, 12, and 24 months were associated with a 24-month ASD diagnosis and whether social motivation’s course differed relative to familial ASD liability. The SMI displayed good internal consistency and temporal stability. Children diagnosed with ASD displayed lower mean SMI T-scores at all ages and a decrease in mean T-scores across age. Lower group-level 6-month scores corresponded with higher familial ASD liability. Among high-risk infants, strong decline in SMI T-scores was associated with 10-fold odds of diagnosis. Infant social motivation is quantifiable by parental report, differentiates children with versus without later ASD by age 6 months, and tracks with familial ASD liability, consistent with a diagnostic and susceptibility marker of ASD. Early decrements and decline in social motivation indicate increased likelihood of ASD, highlighting social motivation’s importance to risk assessment and clarification of the ontogeny of ASD.
Signed by Valerius: an Early Imperial wall painting from the fort of Deir el-Atrash in the Egyptian Eastern Desert
Authors: Marchand Julie , Le Bomin Joachim , Bülow-Jacobsen Adam
Published: October 2022

During the 2020 excavation campaign of the French Archaeological Mission to the Egyptian Eastern Desert (MAFDO), the team in charge of the excavation of the Roman fort of Deir el-Atrash uncovered a polychrome painting on one of the original entrance tower gates from the late 1st–early 2nd c. CE. The iconographic program includes, in the top register, a horsemangeniusand a caravan of dromedaries with its driver. In the lower register, a pattern of vine stalks and leaves occupies the space. This discovery is exceptional, as very few Roman paintings have been preserved in a military context. In addition to depicting a scene of everyday desert life, the supply of the fort, the scene also illustrates the power of the Empire and its presence at its borders.
Gastrostomy tube placement in congenital cardiac surgery: a multi-institutional database study
Authors: Haughey Brena S. , Dean Peter , Spaeder Michael C. , Smith Clyde J. , Conaway Mark , White Shelby C.
Published: October 2022

Introduction:

Neonates and infants who undergo congenital cardiac surgery frequently have difficulty with feeding. The factors that predispose these patients to require a gastrostomy tube have not been well defined. We aimed to report the incidence and describe hospital outcomes and characteristics in neonates and infants undergoing congenital cardiac surgery who required gastrostomy tube placement.

Materials and method:

A retrospective review was performed on patients undergoing congenital cardiac surgery between October 2015 and December 2020. Patients were identified by International Classification of Diseases 10th Revision codes, utilising the performance improvement database Vizient® Clinical Data Base, and stratified by age at admission: neonates (<1 month) and infants (1–12 months). Outcomes were compared and comparative analysis performed between admissions with and without gastrostomy tube placement.

Results:

There were 11,793 admissions, 3519 (29.8%) neonates and 8274 (70.2%) infants. We found an increased incidence of gastrostomy tube placement in neonates as compared to infants following congenital cardiac surgery (23.1% versus 6%, p = <0.001). Outcomes in neonates and infants were similar with increased length of stay and cost in those requiring a gastrostomy tube. Gastrostomy tube placement was noted to be more likely in neonates and infants with upper airway anomalies, congenital abnormalities, hospital infections, and genetic abnormalities.

Discussion:

Age at hospitalisation for congenital cardiac surgery is a definable risk factor for gastrostomy tube requirement. Additional factors contribute to gastrostomy tube placement and should be used when counselling families regarding the potential requirement of a gastrostomy tube.
On the association between apathy and deficits of social cognition and executive functions in Huntington’s disease
Authors: Hendel Rebecca K. , Hellem Marie N.N. , Hjermind Lena E. , Nielsen Jørgen E. , Vogel Asmus
Published: October 2022

Objective:

To investigate if executive and social cognitive dysfunction was associated with apathy in a large cohort of Huntington’s disease gene expansion carriers.

Method:

Eighty premanifest and motor-manifest Huntington’s disease gene expansion carriers (Mini-Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19) and thirty-two controls were examined with the Lille Apathy Rating Scale (LARS), a tailored and quantitative measure of apathy, and a comprehensive cognitive battery on executive functions and social cognition (emotion recognition, theory of mind and sarcasm detection), as well as general correlates like demographic variables, and neuropsychiatric and cognitive screening tests.

Results:

The motor-manifest Huntington’s disease gene expansion carriers had significantly different scores on most measures of social cognition and executive functions, compared to premanifest and control participants. Apathy was significantly correlated with most executive test scores, but the Emotion Hexagon was the only social cognitive test score significantly correlated with apathy. We found that the motor score and the depression score were the only significant predictors of the apathy score, when the social cognitive and executive tests with the strongest association with the global LARS score were entered into a multiple stepwise regression model. No cognitive test score could significantly predict apathy. The model explained 21 % of the total variance.

Conclusion:

Despite being significantly correlated with apathy neuropsychological variables did not have a significant impact on apathy when variables as depression and motor symptoms were taken into account. Apathy should be considered an independent symptom of Huntington’s disease that requires specific examination.
Projecting cardiovascular deaths averted due to trans fat policies in the Eurasian Economic Union
Authors: Rieger Matthias , Rippin Holly L , Pinedo Adriana , Whiting Stephen , Farrand Clare , Wickramasinghe Kremlin , Breda Joao J
Published: October 2022

Objective:

To demonstrate the potential impact on population health if policies designed to reduce population trans fatty acid (TFA) intake are successfully implemented in the Eurasian Economic Union (EAEU) in line with the WHO’s guidelines to lower intake of TFA as a percentage of total energy intake to less than 1 %.

Design:

A projection exercise was conducted to estimate reductions in CVD-related deaths in countries of the EAEU if TFA policies are implemented in the EAEU. Plausibly causal, annual effects (in %) of Denmark’s TFA policy on the evolution of CVD mortality rates were applied to project the potential effects of recently announced TFA policies in Armenia, Belarus, Kazakhstan, Kyrgyzstan and the Russian Federation under three TFA exposure scenarios.

Settings:

Member States of the EAEU: Armenia, Belarus, Kazakhstan, Kyrgyzstan and the Russian Federation.

Participants:

Data used for the projection exercise were based on estimates from natural experimental evidence from Denmark. National CVD mortality rates used were from WHO and the Organisation for Economic Cooperation and Development datasets.

Results:

In all countries and in all scenarios, deaths averted were ≤ 5 deaths/100,000 in year 1 and rose in years 2 and 3. The highest projected impacts in the high-exposure scenario were seen in Kyrgyzstan (39 deaths/100 000), with the lowest occurring in Armenia (24 deaths/100 000).

Conclusion:

This study demonstrates the potential population health gains that can be derived from effective policies to reduce TFA in line with WHO guidance. Monitoring and surveillance systems are needed to evaluate the effectiveness of the TFA reduction policies in a national context.
Effects of public long-term care insurance on the medical service use by older people in South Korea
Authors: Cho Yoon-Min , Kwon Soonman
Published: October 2022

Public long-term care insurance (LTCI), which provides home and institutional care benefits, was introduced in July 2008 in South Korea. This study aims to evaluate the effects of the introduction of LTCI on older people's medical service use, including outpatient visits, inpatient services and longer stays (181 days or longer) in hospitals by implementing a quasi-experiment design with a generalised difference-in-difference method. The results showed that the introduction of LTCI did not change the use of outpatient medical services, although the medical costs of older people who used medical services at least once decreased by 9.4%. For the inpatient services, hospitalisation rates declined by 2.7% as a result of the LTCI. Length of stay and inpatient expenses decreased by 15.6 and 9.5%, respectively. For older people of LTC grade 2, eligible for long-term care facilities (LTCF), prolonged hospitalisation rates decreased by 1.6% due to the LTCI. In conclusion, the introduction of LTCI in South Korea has contributed to decreasing the use of inpatient services and longer stays in hospitals, which suggests that the utilisation of LTCF has become a substitute for some social admissions in hospitals.
A critical overview of tools for assessing cognition in bipolar disorder
Authors: Rossetti Maria Gloria , Girelli Francesca , Perlini Cinzia , Brambilla Paolo , Bellani Marcella
Published: October 2022

Cognitive deficits are prevalent in bipolar disorder even during the euthymic phase, having a negative impact on global functioning and quality of life. As such, more and more mental health professionals agree that neuropsychological assessment should be considered an essential component of the clinical management of bipolar patients. However, no gold standard tool has been established so far. According to bipolar disorder experts targeting cognition, appropriate cognitive tools should be brief, easy to administer, cost-effective and validated in the target population. In this commentary, we critically appraised the strengths and limitations of the tools most commonly used to assess cognitive functioning in bipolar patients, both for screening and diagnostic purposes.
More Frequent, Intense, and Extensive Rainfall Events in a Strongly Warming Arctic
Authors: Dou T. F. , Pan S. F. , Bintanja R. , Xiao C. D.
Published: October 2022

The changes in the Arctic precipitation profoundly impact the surface mass balance of ice sheet and sea ice, the extent of snow cover, as well as the land/ice surface runoff in the Arctic, particularly when it occurs in liquid form. Here, we use state‐of‐the‐art models from the Coupled Model Intercomparison Project Phase 5 to project the number of days with rainfall, the intensities and onset dates of rainfall events in the Arctic under the strong emission scenario (RCP8.5). The multi‐model mean shows that rainfall will occur more frequently in the Arctic at the end of this century (2091–2100), with larger increase in the rainy days over the Pacific and Atlantic sectors (up to 12 days/month) during the cold seasons (October–May) and over the Arctic Ocean (up to 14 days/month) during the warm seasons (June–September) as compared with the present day (2006–2015). Greater uncertainty is found in the cold seasons, which mainly comes from the high variability among different models in the Norwegian Sea. Sixty‐seven to ninety‐three percentage of the increases in rainy days is contributed by the local warming and the remainder by the increase in total precipitation. Moreover, at the end of this century, the rainfall in spring will occur much earlier than the present day by more than 1 month, and the extent of rainfall will further expand toward the center of the Arctic Ocean and the inland Greenland in the future. The changes of rainfall intensity on the Arctic land area to the climate warming are more sensitive than that on the Arctic Ocean in warm seasons (May–September). The rainfall will be further strengthened in most of the Arctic continents in summer, with the largest increase in the intensity of ∼2 mm/day along the southwest coast of Greenland. The above results are confirmed by the latest projections from CMIP6 models.
Tools for the Long Run
Authors: Kessel Mona
Published: October 2022

The first discovery of the space age was in the field of space physics and occurred with the Explorer 1 launch in 1958 and its observations of the radiation belts encircling Earth. Space physics remained a young science into 1981 when I started graduate school, so young that there were no comprehensive textbooks on the subject. It evolved quickly with missions such as Voyager, Interplanetary Monitoring Platform‐8, Hawkeye, Active‐Magnetospheric‐Particle‐Tracer‐Experiment, and ISEE in the early years. The International Solar Terrestrial Physics mission focused part of solar and space physics into Sun‐Earth‐Connections (SECs) to understand the chain of events in the Sun‐Earth system. Heliophysics was an extension and evolution of SEC, combining all of solar and space physics, maturing the whole and the individual parts into an established science.
An Investigation on the Longitudinal Variation in Mid‐Latitude Ionosphere Based on CHAMP Satellite Observations
Authors: Hu Jin , Ruan Haibing , Lei Jiuhou , Zhong Jiahao , Owolabi Charles
Published: October 2022

The longitudinal variations of the middle latitude ionosphere are investigated on the basis of in situ electron density observations from the Planar Langmuir Probe onboard the Challenging Minisatellite Payload satellite. This study specifically focused on the longitudinal variations of the ionosphere at geographic latitudes of 40° in both the Northern and Southern Hemispheres. The longitudinal variations of the ionosphere are decomposed into the spatial modes and corresponding temporal evolutions by employing the principal component analysis method, and an associated empirical model is developed. The model results indicate a significant seasonal and local time dependence of the longitudinal variation, which is obviously different in the Northern and Southern Hemispheres. Our preliminary analysis suggests that the interaction between the geomagnetic fields and the thermospheric winds results in the longitudinal variations in the ionosphere at the middle latitudes. In addition, the relative contributions of zonal and meridional winds are further discussed.
Ice Sheet and Climate Processes Driving the Uncertainty in Projections of Future Sea Level Rise: Findings From a Structured Expert Judgement Approach
Authors: Bamber J. L. , Oppenheimer M. , Kopp R. E. , Aspinall W. P. , Cooke Roger M.
Published: October 2022

The ice sheets covering Antarctica and Greenland present the greatest uncertainty in, and largest potential contribution to, future sea level rise. The uncertainty arises from a paucity of suitable observations covering the full range of ice sheet behaviors, incomplete understanding of the influences of diverse processes, and limitations in defining key boundary conditions for the numerical models. To investigate the impact of these uncertainties on ice sheet projections we undertook a structured expert judgement study. Here, we interrogate the findings of that study to identify the dominant drivers of uncertainty in projections and their relative importance as a function of ice sheet and time. We find that for the 21st century, Greenland surface melting, in particular the role of surface albedo effects, and West Antarctic ice dynamics, specifically the role of ice shelf buttressing, dominate the uncertainty. The importance of these effects holds under both a high‐end 5°C global warming scenario and another that limits global warming to 2°C. During the 22nd century the dominant drivers of uncertainty shift. Under the 5°C scenario, East Antarctic ice dynamics dominate the uncertainty in projections, driven by the possible role of ice flow instabilities. These dynamic effects only become dominant, however, for a temperature scenario above the Paris Agreement 2°C target and beyond 2100. Our findings identify key processes and factors that need to be addressed in future modeling and observational studies in order to reduce uncertainties in ice sheet projections.
Projected Changes in Increased Drought Risks Over South Asia Under a Warmer Climate
Authors: Ullah Irfan , Ma Xieyao , Asfaw Temesgen Gebremariam , Yin Jun , Iyakaremye Vedaste , Saleem Farhan , Xing Yun , Azam Kamran , Syed Sidra
Published: October 2022

Every year, millions of people are at risk due to droughts in South Asia (SA). The likely impacts of droughts are projected to increase with global warming. This study uses the new ensemble mean of 23 global climate models from the Coupled Model Intercomparison Project phase 6 (CMIP6), population and gross domestic product (GDP) projections to quantify future changes in increasing drought risks and associated socioeconomic exposure across SA and its subregions under 1.5°C and 2°C of warming. We used two shared socioeconomic pathways (SSPs), SSP2‐4.5 and SSP5‐8.5. The most likely realization copula functions are used to model the joint distribution of drought severity and duration. Simultaneously, changes in the bivariate return period are calculated under a warming climate. The frequency of 50‐year historical droughts (under a bivariate framework) might double across 80% of the SA land area under 1.5°C of warming. Conversely, 12% of SA landmasses may suffer extreme droughts under 2°C of warming. The severe drought episode frequency is expected to increase under 1.5°C (40%–75%) and 2°C (60%–90%) of warming relative to the recent climate. The largest exposure increase is projected in R2 and R4, then R1. Additionally, 75% (65%) of the SA population (GDP) could suffer from increased drought risks under the 1.5°C warmer climate, whereas the additional 0.5°C warming will lead to an unbearable regional situation. Limiting global warming to 1.5°C compared with 2°C can significantly reduce the drought risk influence in SA. These findings can help disaster‐risk managers to adopt climate‐smart management strategies.
Do Eddies Connect the Tropical Atlantic Ocean and the Gulf of Mexico?
Authors: Andrade‐Canto F. , Beron‐Vera F. J.
Published: October 2022

Consistent with satellite‐tracked trajectories of drogued drifters, but at odds with Eulerian assessment of satellite‐altimetry measurements of sea‐surface height, we show that North Brazil Currents Rings (NBCRs) are incapable of bypassing the Lesser Antilles as structures that coherently transport material. We arrive at this conclusion by applying geodesic eddy detection on the altimetric data set over nearly its entire extent. While we detect northwestward translating NBCRs that can be classified as coherent Lagrangian eddies, they typically experience strong filamentation and complete loss of coherence prior to reaching the Lesser Antilles. Moreover, the filamented material hardly penetrates into the Caribbean Sea, let alone the Gulf of Mexico, and not without substantively mixing with the ambient fluid east of the archipelago. The nature of the inability of the de‐facto oceanographic Eulerian, streamline‐based eddy detection technique to produce a correct assessment of the connectivity between the tropical Atlantic and the Gulf of Mexico is rooted in its lack of objectivity.
Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances
Authors: Tesfaye Rackeb , Huguet Guillaume , Schmilovich Zoe , Renne Thomas , Loum Mor Absa , Douard Elise , Saci Zohra , Jean-Louis Martineau , Martineau Jean Luc , Whelan Rob , Desrivieres Sylvane , Heinz Andreas , Schumann Gunter , Hayward Caroline , Elsabbagh Mayada , Jacquemont Sebastien
Published: October 2022

Sleep disturbance is prevalent in youth with Autism Spectrum Disorder (ASD). Researchers have posited that circadian dysfunction may contribute to sleep problems or exacerbate ASD symptomatology. However, there is limited genetic evidence of this. It is also unclear how insomnia risk genes identified through GWAS in general populations are related to ASD and common sleep problems like insomnia traits in ASD. We investigated the contribution of copy number variants (CNVs) encompassing circadian pathway genes and insomnia risk genes to ASD risk as well as sleep disturbances in children with ASD. We studied 5860 ASD probands and 2092 unaffected siblings from the Simons Simplex Collection (SSC) and MSSNG database, as well as 7509 individuals from two unselected populations (IMAGEN and Generation Scotland). Sleep duration and insomnia symptoms were parent reported for SSC probands. We identified 335 and 616 rare CNVs encompassing circadian and insomnia risk genes respectively. Deletions and duplications with circadian genes were overrepresented in ASD probands compared to siblings and unselected controls. For insomnia-risk genes, deletions (not duplications) were associated with ASD in both cohorts. Results remained significant after adjusting for cognitive ability. CNVs containing circadian pathway and insomnia risk genes showed a stronger association with ASD, compared to CNVs containing other genes. Circadian genes did not influence sleep duration or insomnia traits in ASD. Insomnia risk genes intolerant to haploinsufficiency increased risk for insomnia when duplicated. CNVs encompassing circadian and insomnia risk genes increase ASD liability with little to no observable impacts on sleep disturbances.
Successful treatment of cytomegalovirus retinitis with oral/intravitreal antivirals in HIV-negative patients with lymphoma
Authors: Tasiopoulou Anastasia , Urzua Cristhian A. , Lightman Susan
Published: October 2022

Objectives

To report patients with systemic lymphoma and cytomegalovirus (CMV) retinitis, treated with a combination of oral and intravitreal antiviral agents on an outpatient basis.

Methods

Retrospective cases series. Information was gathered from the database of the Uveitis clinics at Moorfields Eye Hospital, United Kingdom from December 2014 to December 2018. The inclusion criteria comprised the diagnosis of systemic lymphoma, associated with a diagnosis of CMV retinitis. Exclusion criteria were alternative ocular diagnosis, human immunodeficiency virus (HIV), primary intraocular lymphoma, or other causes of immunosuppression.

Results

All seven subjects had been under oncologist care for systemic lymphoma. CMV retinitis presented with a median of 61 months after the systemic lymphoma diagnosis. Five patients underwent a vitreous biopsy, and four of them returned PCR positive for CMV and the fifth patient had PCR positive in a blood sample. All patients were treated with oral Valganciclovir, with an induction dose of 900 mg every 12 h for up to 3 weeks until disease resolution and a maintenance dose thereafter. All but one received additional intravitreal Foscarnet injections, with a dose of 2.4 mg /0.1 ml.

Conclusions

The management of patients with systemic lymphoma and CMV retinitis with oral and intravitreal antiviral agents, resulted in effective disease control.
De novo design of immunoglobulin-like domains
Authors: Chidyausiku Tamuka M. , Mendes Soraia R. , Klima Jason C. , Nadal Marta , Eckhard Ulrich , Roel-Touris Jorge , Houliston Scott , Guevara Tibisay , Haddox Hugh K. , Moyer Adam , Arrowsmith Cheryl H. , Gomis-Rüth F. Xavier , Baker David , Marcos Enrique
Published: October 2022

Antibodies, and antibody derivatives such as nanobodies, contain immunoglobulin-like (Ig) β-sandwich scaffolds which anchor the hypervariable antigen-binding loops and constitute the largest growing class of drugs. Current engineering strategies for this class of compounds rely on naturally existing Ig frameworks, which can be hard to modify and have limitations in manufacturability, designability and range of action. Here, we develop design rules for the central feature of the Ig fold architecture—the non-local cross-β structure connecting the two β-sheets—and use these to design highly stable Ig domains de novo, confirm their structures through X-ray crystallography, and show they can correctly scaffold functional loops. Our approach opens the door to the design of antibody-like scaffolds with tailored structures and superior biophysical properties.
Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington’s disease models
Authors: Conroy Faith , Miller Rachael , Alterman Julia F. , Hassler Matthew R. , Echeverria Dimas , Godinho Bruno M. D. C. , Knox Emily G. , Sapp Ellen , Sousa Jaquelyn , Yamada Ken , Mahmood Farah , Boudi Adel , Kegel-Gleason Kimberly , DiFiglia Marian , Aronin Neil , Khvorova Anastasia , Pfister Edith L.
Published: October 2022

Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS, enabling development of CNS-targeted therapeutics. Many genetically-defined neurodegenerative disorders are dominant, favoring selective silencing of the mutant allele. In some cases, successfully targeting the mutant allele requires targeting single nucleotide polymorphism (SNP) heterozygosities. Here, we use Huntington’s disease (HD) as a model. The optimized compound exhibits selective silencing of mutant huntingtin protein in patient-derived cells and throughout the HD mouse brain, demonstrating SNP-based allele-specific RNAi silencing of gene expression in vivo in the CNS. Targeting a disease-causing allele using RNAi-based therapies could be helpful in a range of dominant CNS disorders where maintaining wild-type expression is essential.
Bias-free solar hydrogen production at 19.8 mA cm−2 using perovskite photocathode and lignocellulosic biomass
Authors: Choi Yuri , Mehrotra Rashmi , Lee Sang-Hak , Nguyen Trang Vu Thien , Lee Inhui , Kim Jiyeong , Yang Hwa-Young , Oh Hyeonmyeong , Kim Hyunwoo , Lee Jae-Won , Kim Yong Hwan , Jang Sung-Yeon , Jang Ji-Wook , Ryu Jungki
Published: October 2022

Solar hydrogen production is one of the ultimate technologies needed to realize a carbon-neutral, sustainable society. However, an energy-intensive water oxidation half-reaction together with the poor performance of conventional inorganic photocatalysts have been big hurdles for practical solar hydrogen production. Here we present a photoelectrochemical cell with a record high photocurrent density of 19.8 mA cm−2 for hydrogen production by utilizing a high-performance organic–inorganic halide perovskite as a panchromatic absorber and lignocellulosic biomass as an alternative source of electrons working at lower potentials. In addition, value-added chemicals such as vanillin and acetovanillone are produced via the selective depolymerization of lignin in lignocellulosic biomass while cellulose remains close to intact for further utilization. This study paves the way to improve solar hydrogen productivity and simultaneously realize the effective use of lignocellulosic biomass.
MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair
Authors: Yang Xiao-Wen , Han Xiao-Peng , Han Chong , London James , Fishel Richard , Liu Jiaquan
Published: October 2022

Highly conserved MutS and MutL homologs operate as protein dimers in mismatch repair (MMR). MutS recognizes mismatched nucleotides forming ATP-bound sliding clamps, which subsequently load MutL sliding clamps that coordinate MMR excision. Several MMR models envision static MutS-MutL complexes bound to mismatched DNA via a positively charged cleft (PCC) located on the MutL N-terminal domains (NTD). We show MutL-DNA binding is undetectable in physiological conditions. Instead, MutS sliding clamps exploit the PCC to position a MutL NTD on the DNA backbone, likely enabling diffusion-mediated wrapping of the remaining MutL domains around the DNA. The resulting MutL sliding clamp enhances MutH endonuclease and UvrD helicase activities on the DNA, which also engage the PCC during strand-specific incision/excision. These MutS clamp-loader progressions are significantly different from the replication clamp-loaders that attach the polymerase processivity factors β-clamp/PCNA to DNA, highlighting the breadth of mechanisms for stably linking crucial genome maintenance proteins onto DNA.
Canalized gene expression during development mediates caste differentiation in ants
Authors: Qiu Bitao , Dai Xueqin , Li Panyi , Larsen Rasmus Stenbak , Li Ruyan , Price Alivia Lee , Ding Guo , Texada Michael James , Zhang Xiafang , Zuo Dashuang , Gao Qionghua , Jiang Wei , Wen Tinggang , Pontieri Luigi , Guo Chunxue , Rewitz Kim , Li Qiye , Liu Weiwei , Boomsma Jacobus J. , Zhang Guojie
Published: October 2022

Ant colonies are higher-level organisms consisting of specialized reproductive and non-reproductive individuals that differentiate early in development, similar to germ–soma segregation in bilateral Metazoa. Analogous to diverging cell lines, developmental differentiation of individual ants has often been considered in epigenetic terms but the sets of genes that determine caste phenotypes throughout larval and pupal development remain unknown. Here, we reconstruct the individual developmental trajectories of two ant species, Monomorium pharaonis and Acromyrmex echinatior, after obtaining >1,400 whole-genome transcriptomes. Using a new backward prediction algorithm, we show that caste phenotypes can be accurately predicted by genome-wide transcriptome profiling. We find that caste differentiation is increasingly canalized from early development onwards, particularly in germline individuals (gynes/queens) and that the juvenile hormone signalling pathway plays a key role in this process by regulating body mass divergence between castes. We quantified gene-specific canalization levels and found that canalized genes with gyne/queen-biased expression were enriched for ovary and wing functions while canalized genes with worker-biased expression were enriched in brain and behavioural functions. Suppression in gyne larvae of Freja, a highly canalized gyne-biased ovary gene, disturbed pupal development by inducing non-adaptive intermediate phenotypes between gynes and workers. Our results are consistent with natural selection actively maintaining canalized caste phenotypes while securing robustness in the life cycle ontogeny of ant colonies.
Solution to the problem of bridge structure damage identification by a response surface method and an imperialist competitive algorithm
Authors: Ye Dan , Xu Zhe , Liu Yangqing
Published: October 2022

To increase the efficiency of structural damage identification (SDI) methods and timeously and accurately detect initial structural damage, this research develops an SDI method based on a response surface method (RSM) and an imperialist competitive algorithm (ICA). At first, a Latin hypercube design method is used for experimental design and selection of sample points based on RSM. Then, a high-order response surface surrogate model for the target frequency response and stiffness reduction factor is established. Finally, analysis of variance is performed to assess the overall goodness-of-fit and prediction accuracy of the established model. Then the results obtained are combined with structural dynamic response data to construct objective functions; furthermore, the optimal solution of parameter vector in the objective function is solved based on the ICA. Then damage positioning and quantification can be achieved according to location and degree of change in each parameter; finally, the RSM-ICA-based SDI method proposed is applied to damage identification of high-dimensional damaged simply-supported beam models. To verify the effectiveness of the proposed method, the damage identification results are compared with the results obtained from traditional optimization algorithms. The results indicate that: average errors in the structural stiffness parameters and natural frequency that are identified by the proposed method are 6.104% and 0.134% respectively. The RSM-ICA-based SDI method can more accurately identify the location and degree of damages with more significantly increased identification efficiency and better precision compared to traditional algorithms. This approach provides a novel means of solving SDI problems.
Fortified relaxor ferroelectricity of rare earth substituted 4-layered BaBi3.9RE0.1Ti4O15 (RE = La, Pr, Nd, and Sm) Aurivillius compounds
Authors: Patri Tirupathi , Ghosh Avijit , Mahesh M. L. V. , Babu P. D. , Mandal S. K. , Singh M. N.
Published: October 2022

In this report, the effect of rare-earth (RE3+) ion substitution on structural, microstructural, and electrical properties in barium bismuth titanate (BaBi4Ti4O15) (BBTO) Aurivillius ceramics has been investigated. The Rietveld refinements on X-ray diffraction (XRD) patterns confirm that all the samples have an orthorhombic crystal system with A21am space group. Meanwhile, temperature dependent synchrotron XRD patterns reveal that the existence of dual phase in higher temperature region. The randomly oriented plate-like grains are experimentally strived to confirm the distinctive feature of bismuth layered Aurivillius ceramics. The broad band dielectric spectroscopic investigation signifies a shifting of ferroelectric phase transition (Tm) towards low temperature region with a decrease of the RE3+-ionic radii in BBTO ceramics. The origin of diffuse ferroelectric phase transitions followed by stabilization of the relaxor ferroelectric nature at high frequency region is explained using suitable standard models. The temperature dependent ac and dc conductivity results indicate the presence of double ionized oxygen vacancies in BBTO ceramics, whereas the dominance of single ionized oxygen vacancies is observed in RE-substituted BBTO ceramics. The room temperature polarization vs. electric field (P–E) hysteresis loops are shown to be well-shaped symmetric for BBTO ceramics, whereas slim asymmetric ferroelectric characteristics developed at RE-substituted BBTO ceramics.
The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors
Authors: Yücel Kadriye Bir , Yekedüz Emre , Karakaya Serdar , Tural Deniz , Ertürk İsmail , Erol Cihan , Ercelep Özlem , Öztaş Nihan Şentürk , Arslan Çağatay , Uçar Gökhan , Küçükarda Ahmet , Sever Özlem Nuray , Kılıçkap Saadettin , Can Orçun , Yazgan Satı Coşkun , Öksüzoğlu Berna , Karadurmuş Nuri , Şendur Mehmet Ali , Ürün Yüksel
Published: October 2022

This study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:[neutrophil (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53–67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%, p < 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%, p < 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%, p < 0.001), those with bone (51.8% vs. 32.2%, p < 0.001) or central nervous system (12.9% vs. 5.8%, p = 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2–4 performance score (28.1% vs.17.7%, p = 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months, p < 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months, p < 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05–1.85, p = 0.01) and PFS (HR:1.60, 95% CI:1.24–2.05, p < 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.
Co-expression effect of LLGL2 and SLC7A5 to predict prognosis in ERα-positive breast cancer
Authors: Hisada Tomoka , Kondo Naoto , Wanifuchi-Endo Yumi , Osaga Satoshi , Fujita Takashi , Asano Tomoko , Uemoto Yasuaki , Nishikawa Sayaka , Katagiri Yusuke , Terada Mitsuo , Kato Akiko , Sugiura Hiroshi , Okuda Katsuhiro , Kato Hiroyuki , Komura Masayuki , Morita Satoshi , Takahashi Satoru , Toyama Tatsuya
Published: October 2022

Lethal giant larvae homolog 2 (LLGL2) and solute carrier family 7 member 5 (SLC7A5) have been reported to be involved in resistance to endocrine therapy. This study aimed to assess the effects of LLGL2/SLC7A5 co-expression in predicting prognosis and response to tamoxifen therapy in ERα-positive breast cancer patients according to LLGL2/SLC7A5 mRNA and protein expression in long-term follow-up invasive breast cancer tissues. We identified that low LLGL2/SLC7A5 mRNA co-expression (LLGL2low/SLC7A5low) was associated with disease-free survival (DFS) compared with other combination groups in all breast cancer patients. In ERα-positive breast cancer patients, LLGL2low/SLC7A5low showed longer DFS and overall survival (OS) compared with LLGL2high/SLC7A5high and a positive trend of longer survival compared with the other combination groups. We also observed that LLGL2low/SLC7A5low showed longer survival compared with LLGL2high/SLC7A5high in ERα-positive breast cancer patients receiving adjuvant tamoxifen therapy. Multivariate analysis demonstrated that LLGL2low/SLC7A5low was an independent favorable prognostic factor of both DFS and OS, not only in all breast cancer patients, but also in ERα-positive breast cancer patients. High co-expression of LLGL2 and SLC7A5 protein showed a positive trend of shorter survival. Our study showed that co-expression of LLGL2 and SLC7A5 mRNA is a promising candidate biomarker in early breast cancer patients.
A new antimicrobial peptide, Pentatomicin, from the stinkbug Plautia stali
Authors: Nishide Yudai , Nagamine Keisuke , Kageyama Daisuke , Moriyama Minoru , Futahashi Ryo , Fukatsu Takema
Published: October 2022

Antimicrobial peptides (AMPs) play crucial roles in the innate immunity of diverse organisms, which exhibit remarkable diversity in size, structural property and antimicrobial spectrum. Here, we describe a new AMP, named Pentatomicin, from the stinkbug Plautia stali (Hemiptera: Pentatomidae). Orthologous nucleotide sequences of Pentatomicin were present in stinkbugs and beetles but not in other insect groups. Notably, orthologous sequences were also detected from a horseshoe crab, cyanobacteria and proteobacteria, suggesting the possibility of inter-domain horizontal gene transfers of Pentatomicin and allied protein genes. The recombinant protein of Pentatomicin was effective against an array of Gram-positive bacteria but not against Gram-negative bacteria. Upon septic shock, the expression of Pentatomicin drastically increased in a manner similar to other AMPs. On the other hand, unlike other AMPs, mock and saline injections increased the expression of Pentatomicin. RNAi-mediated downregulation of Imd pathway genes (Imd and Relish) and Toll pathway genes (MyD88 and Dorsal) revealed that the expression of Pentatomicin is under the control of Toll pathway. Being consistent with in vitro effectiveness of the recombinant protein, adult insects injected with dsRNA of Pentatomicin exhibited higher vulnerability to Gram-positive Staphylococcus aureus than to Gram-negative Escherichia coli. We discovered high levels of Pentatomicin expression in eggs, which is atypical of other AMPs and suggestive of its biological functioning in eggs. Contrary to the expectation, however, RNAi-mediated downregulation of Pentatomicin did not affect normal embryonic development of P. stali. Moreover, the downregulation of Pentatomicin in eggs did not affect vertical symbiont transmission to the offspring even under heavily contaminated conditions, which refuted our expectation that the antimicrobial activity of Pentatomicin may contribute to egg surface-mediated symbiont transmission by suppressing microbial contaminants.
Label-free quantitative SWATH-MS proteomic analysis of adult myocardial slices in vitro after biomimetic electromechanical stimulation
Authors: Zabielska-Kaczorowska M. A. , Bogucka A. E. , Macur K. , Czaplewska P. , Watson S. A. , Perbellini F. , Terracciano C. M. , Smolenski R. T.
Published: October 2022

A special in vitro model maintained with ultrathin cardiac slices with a preserved architecture, multi-cellularity, and physiology of the heart tissue was used. In our experiments, we performed label-free quantitative SWATH-MS proteomic analysis of the adult myocardial slices in vitro after biomimetic electromechanical stimulation. Rat myocardial slices were stretched to sarcomere lengths (SL) within the physiological range of 1.8–2.2 μm. Electromechanically stimulated slices were compared with slices cultured without electromechanical stimulation (unloaded and nonstimulated-TW) on a liquid–air interface and with fresh myocardial slices (0 h-C). Quantitative (relative) proteomic analyses were performed using a label-free SWATH-MS technique on a high-resolution microLC-MS/MS TripleTOF 5600+ system (SCIEX). The acquired MS/MS spectra from the DDA LC–MS/MS analyses of the rat heart samples were searched against the UniProt Rattus norvegicus database (version of 15.05.2018) using the Paragon algorithm incorporated into ProteinPilot 4.5 (SCIEX) software. The highest number of differential proteins was observed in the TW group—121 when compared to the C group. In the 1.8 and 2.2 groups, 79 and 52 proteins present at a significantly different concentration from the control samples were found, respectively. A substantial fraction of these proteins were common for two or more comparisons, resulting in a list of 169 significant proteins for at least one of the comparisons. This study found the most prominent changes in the proteomic pattern related to mitochondrial respiration, energy metabolism, and muscle contraction in the slices that were stretched and fresh myocardial slices cultured without electromechanical stimulation.
Fatty acids and nutritional components of the seed oil from Wangmo red ball Camellia oleifera grown in the low-heat valley of Guizhou, China
Authors: Long Li , Gao Chao , Qiu Jie , Yang Lu , Wei Hongli , Zhou Yunchao
Published: October 2022

Wangmo red ball Camellia oleifera is the main Camellia species cultivated for oil in the low-heat valley of Guizhou, China. In this study, we evaluated the comprehensive nutritional value of Wangmo C. oleifera seed oil through fatty acid and nutritional component analyses. Twenty excellent Wangmo C. oleifera plants with stable yield and disease resistance were selected from the Camellia oleifera germplasm resource garden in the low-heat valley site of Guizhou University. The unit crown yield, fatty acid content of the seed oil, fatty acid composition and functional nutrients were determined, and the oil quality was comprehensively evaluated using principal component analysis. The fatty acid content of C. oleifera seed oil was 35.03–53.47%, suggesting likely popularization and wide application prospects. The fatty acids included SFAs, MUFAs and PUFAs, and the oleic acid content was 80%, indicating a highly stable and nutritious oil. The oil was also rich in carotenoids, polyphenols, flavonoids, β-sitosterol, squalene and α-Ve, with average content of 7.404 mg/kg, 16.062 mg/kg, 0.401 g/100 g, 265.087 mg/kg, 129.315 mg/kg and 21.505 mg/100 g, respectively. However, the correlations among the nutritional indices were weak. PCA showed that germplasms GH7, GH43, GH28, GH8 and GH31 exhibited the top five nutritional qualities. The rankings in this study provide data for identifying excellent Wangmo C. oleifera plants with high nutritional quality. Additionally, this study provides a valuable reference for the research and development of high-end edible oil and a theoretical basis for the development of economic forest species in low-heat valley areas across the world.
Nondestructive circadian profiling of starch content in fresh intact Arabidopsis leaf with two-photon fluorescence and second-harmonic generation imaging
Authors: Liao Juo-Nang , Chen Wei-Liang , Lo Chao-Yuan , Lai Man-Hong , Tsai Huang-Lung , Chang Yu-Ming
Published: October 2022

Plant chloroplasts conduct photosynthesis to convert solar energy into sugars for the carbon source essential for cell living and growth during the day. One fraction of photosynthetic products is stored in chloroplasts by forming starch granules to continue the provision of carbon energy during the night. Currently, profiling the starch temporal pattern requires either: (i) sacrificing the leaves, or (ii) generating transgenic plants at the risk of changing the metabolisms by incorporating a genetically modified granule-bound starch synthase (GBSS). In this paper, we demonstrated a nondestructive method using two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging to quantify starch granules within chloroplasts of fresh intact leaves across a day-night cycle. We did so using two Arabidopsis lines having normal and excess starch contents: wild-type (Columbia-0) and starch excess 1 (sex1). The starch granules were visualized by SHG imaging, while the chloroplasts in mesophyll cells were visualized by TPF imaging. Our results provided micron scale spatial resolution of starch distribution within leaves and showed starch circadian patterns consistent with those profiled by enzymatic assays in previous studies. We demonstrated that TPF-SHG imaging is a potential tool for revealing the real-time heterogeneity of starch circadian rhythm in leaf cells, without the need for destructive sample preparation.