bluuebunny/crossref_metadata_2025 huggingface dataset:
Naturalizations have led to homogenization of the Malesian flora in the Anthropocene
Authors: Holmes Rachael , Pelser Pieter , Barcelona Julie , Tjitrosoedirdjo Sri Sudarmiyati , Wahyuni Indah , van Kleunen Mark , Pyšek Petr , Essl Franz , Kreft Holger , Dawson Wayne , Wijedasa Lahiru , Kortz Alessandra , Hejda Martin , Berrio Juan Carlos , Siregar Iskandar , Williams Mark
Published: December 2023

Aim

Worldwide, floras are becoming homogenized at global scales, but regional patterns vary. Here, we present the first assessment for the Malesian phytogeographical region in terms of the timing of introductions, direction, magnitude and drivers of floristic change due to alien plant naturalizations.

Location

Malesian phytogeographic region, including Southeast Asia and the Pacific.

Taxon

Tracheophyta (vascular plants).

Methods

We compiled data on first records of naturalized plants in Malesia to investigate temporal trends in the rate and origin of introductions. We then calculated β‐diversity (including turnover and nestedness) for the native, naturalized and Anthropocene (native + naturalized) floras for each pair of island groups (36 pairs), and a homogenization index for the native and Anthropocene floras, using presence/absence data for 31,580 plant species. Mantel tests were used to investigate the geographic, climatic and anthropogenic correlates of dissimilarity and homogenization.

Results

Around 75% of all naturalized species documented to date were already reported for the first time within Malesia prior to 1950. This has led to homogenization between the historic (native) and contemporary (Anthropocene) floras for all island group pairs. Turnover was the most important process for driving compositional dissimilarity between island groups in Malesia in the native and Anthropocene floras, but homogenization resulted from decreases in nestedness and turnover. Differences in average taxonomic homogenization for island groups were associated with differences in their level of anthropogenic modification.

Main Conclusions

This study improves current understanding of the direction and drivers of floristic homogenization in one of the world's most diverse tropical regions. Alien plant introductions carry a long historical legacy in Malesia, and naturalizations of these plants have led to overall taxonomic homogenization of the region's flora. Expected increases in the magnitude of human modification, without appropriate policy, will likely lead to further reductions in the floristic uniqueness of island groups.
The relationship between obstructive sleep apnea and haemoglobin A1c and the moderating role of glycaemic status in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: López‐Cepero Andrea , Pérez Cynthia M. , González‐Lorenzo Keyla , Suárez Erick , Ramos Alberto R. , Teng Yanping , Avilés‐Santa M. Larissa
Published: December 2023

This study investigated the relationship between obstructive sleep apnea and haemoglobin A1c (HbA1c) among Hispanics/Latinos in the United States and assessed whether this relationship was moderated by glycaemic status. This was a cross‐sectional analysis of the Hispanic Community Health Study/Study of Latinos cohort. The sample consisted of 13,394 participants with valid measures of obstructive sleep apnea, HbA1c, and study covariates. Obstructive sleep apnea was assessed with the apnea–hypopnea index and categorised as obstructive sleep apnea if the apnea–hypopnea index was ≥5 events/h. HbA1c measures were obtained through fasting blood samples. Fasting plasma glucose (FPG), 2‐h post‐load plasma glucose (2h‐PG) and use of antihyperglycaemic medications were used to define glycaemic status (i.e., normoglycaemia [FPG < 5.6 mmol/L (< 100 mg/dL) and 2h‐PG < 7.8 mmol/L (140 mg/dL)], prediabetes [FPG 5.6‐6.9 mmol/L (100‐125 mg/dL), and/or 2h‐PG 7.8‐11.0 mmol/L (140‐199 mg/dL)], diabetes without treatment [FPG > 7.0 mmol/L (≥ 126 mg/dL) and/or 2h‐PG ≥ 11.1 mmol/L (≥ 200 mg/dL)], and diabetes with treatment. Multivariable linear regression was used to calculate adjusted least square means. Overall, 25.9% of the sample had obstructive sleep apnea and 49.2% had normal glycaemic levels, 36.1% had prediabetes, 6.5% diabetes without receiving treatment, and 8.3% diabetes and undergoing treatment for it. Participants with obstructive sleep apnea had significantly higher adjusted mean HbA1c (adjusted mean [standard error] 5.85 [0.03)]) than those without (5.70 [0.02)]; p < 0.001). Models stratified by diabetes status showed that the association between obstructive sleep apnea (versus not) and higher HbA1c was only for participants with normal glycaemic status (adjusted mean [standard error] 5.27 [0.01] versus 5.30 [0.01]; p = 0.013) and prediabetes (5.59 [0.01] versus 5.66 [0.01]; p < 0.001). In conclusion, obstructive sleep apnea was associated with higher HbA1c in a diverse sample of Hispanic/Latino adults in the United States. This association was present only for participants with normal glycaemic status or with prediabetes. Studies are needed to further understand the clinical implications of the association between obstructive sleep apnea and HbA1c according to glycaemic status.
How gradients of climate and soil determine Mediterranean annual‐rich dryland vegetation
Authors: von Lampe Friedemann , Link Roman Mathias , Bergmeier Erwin
Published: December 2023

Questions

Dryland annual plant communities constitute the most species‐rich small‐scale vegetation in the Mediterranean. Nevertheless, the composition and diversity of these units and the factors controlling their variation are still insufficiently understood. Therefore, we investigated species composition and richness patterns in relation to important environmental gradients provided by climate and soil.

Location

Central Crete, Greece.

Methods

The study is based on 82 plots of 4 m2sampled at altitudes between 11 and 1400 m a.s.l. We conducted vegetation relevés and soil analyses. We used generalised additive models to model species richness and community characteristics along the studied gradients. We then performed distance‐based redundancy analysis to determine the main environmental factors influencing species composition. To determine species of diagnostic value for bedrock types, we applied an indicator species analysis. Correlation tests were used to test the performance of the South Aegean Plant Indicator Values on our dataset.

Results

We recorded 347 taxa (species and subspecies) of 43 plant families, and mean species numbers of 47.2 ± 12.5 per plot. While overall species richness varied only slightly along the analysed environmental gradients, significant changes were observed for relative proportions of species from different life forms and families. Soil pH and elevation had the highest influence on the variation in species composition (21.0% explained). We found 22 species indicative of calcareous rock and 24 species indicative of lime‐deficient rock types. The South Aegean Plant Indicator Values were relatively strongly correlated with environmental variables.

Conclusions

Results indicate considerable species turnover both along climatic (elevation) and soil gradients, highlighting the special importance of soil pH. The data provided by our study are expected to supply relevant ecological background information for a pending classification of East Mediterranean annual‐rich vegetation.
Impacts of climate timescale on the stability of trait–environment relationships
Authors: Famiglietti Caroline A. , Worden Matthew , Anderegg Leander D. L. , Konings Alexandra G.
Published: December 2023

Predictive relationships between plant traits and environmental factors can be derived at global and regional scales, informing efforts to reorient ecological models around functional traits. However, in a changing climate, the environmental variables used as predictors in such relationships are far from stationary. This could yield errors in trait–environment model predictions if timescale is not accounted for.

Here, the timescale dependence of trait–environment relationships is investigated by regressing in situ trait measurements of specific leaf area, leaf nitrogen content, and wood density on local climate characteristics summarized across several increasingly long timescales.

We identify contrasting responses of leaf and wood traits to climate timescale. Leaf traits are best predicted by recent climate timescales, while wood density is a longer term memory trait. The use of sub‐optimal climate timescales reduces the accuracy of the resulting trait–environment relationships.

This study concludes that plant traits respond to climate conditions on the timescale of tissue lifespans rather than long‐term climate normals, even at large spatial scales where multiple ecological and physiological mechanisms drive trait change. Thus, determining trait–environment relationships with temporally relevant climate variables may be critical for predicting trait change in a nonstationary climate system.
Plant hormones mediate the interaction between oak acorn germination and rodent hoarding behaviour
Authors: Li Ying , Yang Xifu , Feng Enping , Zhao Kunming , Zhang Zhibin
Published: December 2023

The interaction between animals and plants for seed dispersal and predation has received much attention; however, the underlying physiological mechanisms driving the responses of both seeds and animals remain unclear.

We conducted a series of behaviour and physiology experiments to examine the role of plant hormones in regulating seed germination and rodent hoarding behaviour in the Quercus variabilis and Leopoldamys edwardsi systems.

We found that acorns that were partially consumed by rodents had increased gibberellin (GA) levels and shortened germination time. Rodents preferred scatter‐hoarded abscisic acid (ABA)‐treated and intact acorns but consumed germinated and GA‐treated acorns; such treatment differences disappeared for inactivated acorns by boiling water. Moreover, we found that seven potential compounds may be linked to seed germination and rodent hoarding behaviour.

Our results indicate that acorns of oak showed rapid germination when facing predation risk, while rodents could identify the germination status of seeds for hoarding; GA and ABA may play an important role in regulating seed germination of oak and hoarding behaviour of rodents.
The fungal pathogen Ustilago maydis targets the maize corepressor RELK2 to modulate host transcription for tumorigenesis
Authors: Huang Luyao , Ökmen Bilal , Stolze Sara Christina , Kastl Melanie , Khan Mamoona , Hilbig Daniel , Nakagami Hirofumi , Djamei Armin , Doehlemann Gunther
Published: December 2023

Ustilago maydis is a biotrophic fungus that causes tumor formation on all aerial parts of maize. U. maydis secretes effector proteins during penetration and colonization to successfully overcome the plant immune response and reprogram host physiology to promote infection.

In this study, we functionally characterized the U. maydis effector protein Topless (TPL) interacting protein 6 (Tip6). We found that Tip6 interacts with the N‐terminus of RELK2 through its two Ethylene‐responsive element binding factor‐associated amphiphilic repression (EAR) motifs. We show that the EAR motifs are essential for the virulence function of Tip6 and critical for altering the nuclear distribution pattern of RELK2.

We propose that Tip6 mimics the recruitment of RELK2 by plant repressor proteins, thus disrupting host transcriptional regulation. We show that a large group of AP2/ERF B1 subfamily transcription factors are misregulated in the presence of Tip6.

Our study suggests a regulatory mechanism where the U. maydis effector Tip6 utilizes repressive domains to recruit the corepressor RELK2 to disrupt the transcriptional networks of the host plant.
The self‐compatibility is acquired after polyploidization: a case study of Brassica napus self‐incompatible trilinear hybrid breeding system
Authors: Dou Shengwei , Zhang Tong , Wang Lulin , Yang Chuang , Quan Chengtao , Liang Xiaomei , Ma Chaozhi , Dai Cheng
Published: December 2023

Self‐incompatibility plays a vital role in angiosperms, by preventing inbreeding depression and maintaining genetic diversity within populations. Following polyploidization, many angiosperm species transition from self‐incompatibility to self‐compatibility.

Here, we investigated the S‐locus in Brassicaceae and identified distinct origins for the sRNA loci, SMI and SMI2 (SCR Methylation Inducer 1 and 2), within the S‐locus. The SMI loci were found to be widespread in Cruciferae, whereas the SMI2 loci were exclusive to Brassica species.

Additionally, we discovered four major S‐haplotypes (BnS‐1, BnS‐6, BnS‐7, and BnS‐1300) in rapeseed. Overexpression of BnSMI‐1 in self‐incompatible Brassica napus (‘S‐70S1300S6’) resulted in a significant increase in DNA methylation in the promoter regions of BnSCR‐6 and BnSCR‐1300, leading to self‐compatibility. Conversely, by overexpressing a point mutation of BnSmi‐1 in the ‘S‐70S1300S6’ line, we observed lower levels of DNA methylation in BnSCR‐6 and BnSCR‐1300 promoters. Furthermore, the overexpression of BnSMI2‐1300 in the ‘SI‐326S7S6’ line inhibited the expression of BnSCR‐7 through transcriptional repression of the Smi2 sRNA from the BnS‐1300 haplotype.

Our study demonstrates that the self‐compatibility of rapeseed is determined by S‐locus sRNA‐mediated silencing of SCR after polyploidization, which helps to further breed self‐incompatible or self‐compatible rapeseed lines, thereby facilitating the utilization of heterosis.
Shifting Parental Age Differences in High‐Income Countries: Insights and Implications
Authors: Dudel Christian , Cheng Yen‐hsin Alice , Klüsener Sebastian
Published: December 2023

Age differences within couples are of considerable importance for the power relations between partners. These age differences become particularly relevant when couples transition to having a(nother) child, as such an event often results in a renegotiation of the gendered division of labor. Surprisingly, the literature on female empowerment and fertility postponement has so far paid little attention to parental age differences. This paper makes use of a new data set to present a demographic analysis of trends in parental age differences at childbirth in 15 high‐income countries, covering a period in which all of these countries experienced changes in gender relations and fertility postponement. The general trends in rising mean ages at childbirth have evolved quite similarly among men and women. However, we demonstrate that these similarities hide previously unexplored and highly gendered disparities in parental age differences. Older mothers report much smaller mean parental age differences than younger mothers, and this age pattern among mothers has further polarized over time. By contrast, older fathers report larger parental age differences than younger fathers, while the disparities by age among fathers have not changed much over time. We discuss the relevance of our findings at both the individual and the societal level.
The isoprene‐responsive phosphoproteome provides new insights into the putative signalling pathways and novel roles of isoprene
Authors: Weraduwage Sarathi M. , Whitten Douglas , Kulke Martin , Sahu Abira , Vermaas Josh V. , Sharkey Thomas D.
Published: December 2023

Many plants, especially trees, emit isoprene in a highly light‐ and temperature‐dependent manner. The advantages for plants that emit, if any, have been difficult to determine. Direct effects on membranes have been disproven. New insights have been obtained by RNA sequencing, proteomic and metabolomic studies. We determined the responses of the phosphoproteome to exposure of Arabidopsis leaves to isoprene in the gas phase for either 1 or 5 h. Isoprene effects that were not apparent from RNA sequencing and other methods but were apparent in the phosphoproteome include effects on chloroplast movement proteins and membrane remodelling proteins. Several receptor kinases were found to have altered phosphorylation levels. To test whether potential isoprene receptors could be identified, we used molecular dynamics simulations to test for proteins that might have strong binding to isoprene and, therefore might act as receptors. Although many Arabidopsis proteins were found to have slightly higher binding affinities than a reference set of Homo sapiens proteins, no specific receptor kinase was found to have a very high binding affinity. The changes in chloroplast movement, photosynthesis capacity and so forth, found in this work, are consistent with isoprene responses being especially useful in the upper canopy of trees.
The AT‐hook protein AHL29 promotes Bacillus subtilis colonization by suppressing SWEET2‐mediated sugar retrieval in Arabidopsis roots
Authors: Wu Yun‐Chien , Yu Chien‐Wen , Chiu Jo‐Yu , Chiang Yu‐Hsuan , Mitsuda Nobutaka , Yen Xu‐Chen , Huang Tzu‐Pi , Chang Tzu‐Fang , Yen Cen‐Jie , Guo Woei‐Jiun
Published: December 2023

Beneficial Bacillus subtilis (BS) symbiosis could combat root pathogenesis, but it relies on root‐secreted sugars. Understanding the molecular control of sugar flux during colonization would benefit biocontrol applications. The SWEET (Sugar Will Eventually Be Exported Transporter) uniporter regulates microbe‐induced sugar secretion from roots; thus, its homologs may modulate sugar distribution upon BS colonization. Quantitative polymerase chain reaction revealed that gene transcripts of SWEET2, but not SWEET16 and 17, were significantly induced in seedling roots after 12 h of BS inoculation. Particularly, SWEET2‐β‐glucuronidase fusion proteins accumulated in the apical mature zone where BS abundantly colonized. Yet, enhanced BS colonization in sweet2 mutant roots suggested a specific role for SWEET2 to constrain BS propagation, probably by limiting hexose secretion. By employing yeast one‐hybrid screening and ectopic expression in Arabidopsis protoplasts, the transcription factor AHL29 was identified to function as a repressor of SWEET2 expression through the AT‐hook motif. Repression occurred despite immunity signals. Additionally, enhanced SWEET2 expression and reduced colonies were specifically detected in roots of BS‐colonized ahl29 mutant. Taken together, we propose that BS colonization may activate repression of AHL29 on SWEET2 transcription that would be enhanced by immunity signals, thereby maintaining adequate sugar secretion for a beneficial Bacillus association.
Distribution of proteinase K‐resistant anti‐α‐synuclein immunoreactive axons in the cardiac plexus is unbiased to the left ventricular anterior wall
Authors: Fukasawa Nei , Maeda Miku , Sugiyama Yoshifumi , Fukuda Takahiro , Shimoda Masayuki
Published: December 2023

Lewy body disease (LBD) is characterized by the appearance of Lewy neurites and Lewy bodies, which are predominantly composed of α‐synuclein. Notably, the cardiac plexus (CP) is one of the main targets of LBD research. Although previous studies have reported obvious differences in the frequency of Lewy body pathology (LBP) in the CP, none of them have confirmed whether LBP preferably appears in any part of the CP. Thus, we aimed to clarify the emergence and/or propagation of LBP in the CP. In this study, 263 consecutive autopsy cases of patients aged ≥50 years were included, with one region per case selected from three myocardial perfusion areas (MPAs) and subjected to proteinase K and then immunohistochemically stained with anti‐α‐synuclein antibodies to assess LBP. We stained all three MPAs in 17 cases with low‐density LBP and observed the actual distribution of LBP. LBP were identified in the CP in 20.2% (53/263) of patients. Moreover, we found that LBP may appear in only one region of MPAs, mainly in the young‐old group (35.3% (6/17) of patients). These findings suggest that it is possible to underestimate LBP in the CP, especially in the young‐old group, by restricting the search to only one of the three MPAs.
How to study democratic backsliding
Authors: Druckman James N.
Published: December 2023

The twenty‐first century has been one of democratic backsliding. This has stimulated wide‐ranging scholarship on the causes of democratic erosion. Yet an overarching framework that identifies actors, behaviors, and decision processes has not been developed. I offer such a structure that includes elites (e.g., elected officials, the judiciary), societal actors (e.g., social movements, interest groups, media), and citizens. I discuss erosive threats stemming from each actor and the concomitant role of psychological mechanisms. The framework highlights the challenge of arriving at a holistic explanation of erosion within a given country during a finite period. It also accentuates why scholars should regularly consider the implications of their specific findings for democratic stability. I conclude by discussing various lessons and suggestions for how to study democratic backsliding.
A comparison of cohorts of children with cerebral palsy from a population register and hospital admission data: A data linkage study
Authors: Paget Simon P. , McIntyre Sarah , Lain Samantha , Goldsmith Shona , Nassar Natasha
Published: December 2023

Background

Administrative health data, such as hospital admission data, are often used in research to identify children/young people with cerebral palsy (CP).

Objectives

To compare sociodemographic, clinical details and mortality of children/young people identified as having CP in either a CP population registry or hospital admission data.

Methods

We identified two cohorts of children/young people (birth years 2001–2010, age at study end or death 2 months to 19 years 6 months) with a diagnosis of CP from either (i) the New South Wales (NSW)/Australian Capital Territory (ACT) CP Register or (ii) NSW hospital admission data (2001–2020). Using record linkage, these data sources were linked to each other and NSW Death, Perinatal, and Disability datasets. We determined the sensitivity and positive predictive value (PPV) of CP diagnosis in hospital admission data compared with the NSW/ACT CP Register (gold standard). We then compared the sociodemographic and clinical characteristics and mortality of the two cohorts available through record linkage using standardised mean difference (SMD).

Results

There were 1598 children/young people with CP in the NSW/ACT CP Register and 732–2439 children/young people with CP in hospital admission data, depending on the case definition used. The sensitivity of hospital admission data for diagnosis of CP ranged from 0.40–0.74 and PPV 0.47–0.73. Compared with children/young people with CP identified in the NSW/ACT CP Register, a greater proportion of those identified in hospital admission data (one or more admissions with G80 case definition) were older, lived in major cities, had comorbidities including epilepsy, gastrostomy use, intellectual disability and autism, and died during the study period (SMD > 0.1).

Conclusions

Sociodemographic and clinical characteristics differ between cohorts of children/young people with CP identified using a CP register or hospital admission data. Those identified in hospital admission data have higher rates of comorbidities and death, suggesting some may have progressive conditions and not CP. These differences should be considered when planning and interpreting research using various data sources.
Effects of long‐acting injectable progesterone supplementation at early dioestrus on pregnancy maintenance in beef and dairy recipient cattle
Authors: Neto Adomar Laurindo , Ruas Felipe Lopes , Santo Bruno Silva Espírito , Mattos Ana Clara Degan , Silva Júnior Borges , Júnior Marcos Flávio Diniz , Pereira Danilo Fonseca Cardoso , Lacerda Izabelle Pereira , Carvalho José Oliveira , Pugliesi Guilherme
Published: December 2023

We tested in the present study the hypothesis that supplementation with long‐acting P4 (iP4) at different times of the initial dioestrus improves pregnancy rates in dairy and beef recipients submitted to fixed‐time embryo transfer (FTET). Recipients from commercial farms had their oestrous cycle synchronized with an E2/P4‐based protocol in three experiments (Exp. 1 to 3). In Exp. 1, dairy heifers (n = 76) and cows (n = 104) were randomly assigned to two experimental groups: the control group (n = 89) and the iP4D4 group (n = 91). For Exps. 2 and 3, suckled beef recipients were used. In Exp. 2, recipients were assigned to two experimental groups: Control group (n = 147) and iP4D7 group (n = 144); whereas in Exp. 3, recipients were randomly assigned to three experimental groups: Control group (n = 85), iP4‐D4 group (n = 86) and iP4D7 group (n = 81). Recipients in the iP4D4 and iP4‐D7 groups received an i.m. administration of 150 mg iP4, on D4 or D7 (D0 was the day of expected oestrus). On D7, all recipients were evaluated by transrectal ultrasonography and those that had a CL received a fresh or vitrified in vitro‐producedembryo. In Exp. 2 and 3, the CL area was also determined by ultrasonography at the time of FTET. The pregnancy diagnosis was performed at 30 days in Exp. 1, 57 days in Exp. 2, and between 40 and 72 days of pregnancy in Exp. 3. In Exp. 1, the pregnancy rate did not differ (p > .1) between the Control group (38.2% [34/89]) and iP4D4 group (49.5% [45/91]); yet, a parity effect indicated a greater (p < .05) pregnancy rate in heifers (57.9% [44/76]) than cows (30.8% [32/104]). In Exp. 2, the pregnancy rate was greater (p < .05) in the iP4D7 group (45.0% [65/144]) than in the Control group (34.0% [50/147]). Also, a greater (p = .08) pregnancy rate was observed for recipients with a small CL (≤2.75 cm2) that were treated with iP4 on the day of FTET than the control recipients (46.4% [32/69] vs. 32.6% [28/86]). In Exp. 3, no significant effects (p > .1) of the treatment group or CL size were detected on pregnancy rates at days 30 and 60. In conclusion, the beneficial effects of iP4 supplementation at early dioestrus on pregnancy maintenance may vary according to the experimental conditions, but its use at the time of FTET can be used as an alternative to enhance the fertility of beef recipients in challenging conditions in commercial herds.
Risk science applied to major risk events in history
Authors: Thekdi Shital , Aven Terje
Published: December 2023

Major risk events in history are often labeled as black swans or as unforeseeable given the risk policies and procedures existing at the time. Hindsight suggests that many of these events could have been foreseeable. This article explores past risk events, (1) analyzes how risk science principles apply to those events, and (2) studies gaps and opportunities for risk science using the lenses of consequences, uncertainty, and knowledge as they relate to evidence used for risk assessment prior to the risk event. New insights are obtained, relating to general foundational risk science issues and a classification system for characterizing the integrity and quality of evidence in risk studies. The analysis results are used to identify how risk science approaches contribute to the overall management of risk and societal safety, and where improvements can be obtained.
Team‐based learning in the internal medicine clerkship didactics
Authors: Garb Madeline , Jenkins Melissa , Cruz Elaine
Published: December 2023

Background

Active‐learning approaches, such as team‐based learning, are infrequently used in internal medicine clerkship didactics even though there is increasing evidence to suggest medical students prefer it over traditional lecture‐based learning. In this study, five team‐based learning sessions were incorporated into three blocks of a 12‐week internal medicine clerkship.

Methods

The goal of this quasi‐experimental study was to compare learner engagement, satisfaction and preference between team‐based learning and lecture‐based learning in the internal medicine clerkship didactics. Outcomes were compared using the Classroom Engagement Survey, a satisfaction questionnaire and the Team‐Based Learning Student Assessment Instrument (TBL‐SAI).

Findings

There was a statistically significant difference in the classroom engagement scores between team‐ and lecture‐based learning (P < 0.0001) with a median of 39.0 and 33.0 in the team‐based learning and lecture‐based learning groups. For learning preference, the median TBL‐SAI score was substantially above neutral. Across all team‐based learning sessions, 100% of students were satisfied or strongly satisfied with the learning style as a valuable experience and as a way to learn course material, and only one student was not satisfied or strongly satisfied with team‐based learning to improve problem solving skills.

Discussion

The classroom engagement and learning style preference findings were consistent with previously published data in other clerkship settings. Student satisfaction was more consistent with team‐based learning than with the lecture‐based learning, which may be because of the consistent format whereas lecture‐based learning style was faculty dependent.

Conclusion

Students preferred team‐based learning and had improved engagement and satisfaction when compared to lecture‐based learning. This study provides evidence in favour of team‐based learning as a strategy to incorporate active learning in clerkship didactics.
A rapid and highly efficient sorghum transformation strategy using GRF4‐GIF1/ternary vector system
Authors: Li Junpeng , Pan Wenbo , Zhang Shuai , Ma Guojing , Li Aixia , Zhang Huawei , Liu Lijing
Published: December 2023

Sorghum is an important crop for food, forage, wine and biofuel production. To enhance its transformation efficiency without negative developmental by‐effects, we investigated the impact of GRF4‐GIF1 chimaera and GRF5 on sorghum transformation. Both GRF4‐GIF1 and GRF5 effectively improved the transformation efficiency of sorghum and accelerated the transformation process of sorghum to less than 2 months which was not observed when using BBM‐WUS. As agrobacterium  effectors increase the ability of T‐DNA transfer into plant cells, we checked whether ternary vector system can additively enhance sorghum transformation. The combination of GRF4‐GIF1 with helper plasmid pVS1‐VIR2 achieved the highest transformation efficiency, reaching 38.28%, which is 7.71‐fold of the original method. Compared with BBM‐WUS, overexpressing GRF4‐GIF1 caused no noticeable growth defects in sorghum. We further developed a sorghum CRISPR/Cas9 gene‐editing tool based on this GRF4‐GIF1/ternary vector system, which achieved an average gene mutation efficiency of 41.36%, and null mutants were created in the T0 generation.
Brillouin-zone definition in non-reciprocal Willis monatomic lattices
Authors: Al Ba'ba'a Hasan B.
Published: December 2023

Brillouin-zone (BZ) definition in a class of non-reciprocal Willis monatomic lattices (WMLs) is analytically quantified. It is shown that BZ boundaries only shift in response to non-reciprocity in one-dimensional WMLs, implying a constant BZ width, with asymmetric dispersion diagrams exhibiting unequal wavenumber ranges for forward and backward going waves. An extension to square WMLs is briefly discussed, analogously demonstrating the emergence of shifted and irregularly shaped BZs, which maintain constant areas regardless of non-reciprocity strength.
Dynamic changes of vocal tract dimensions with sound pressure level during messa di voce
Authors: Burk Fabian , Traser Louisa , Burdumy Michael , Richter Bernhard , Echternach Matthias
Published: December 2023

The messa di voce (MdV), which consists of a continuous crescendo and subsequent decrescendo on one pitch is one of the more difficult exercises of the technical repertoire of Western classical singing. With rising lung pressure, regulatory adjustments both on the level of the glottis and the vocal tract are required to keep the pitch stable. The dynamic changes of vocal tract dimensions with the bidirectional variation of sound pressure level (SPL) during MdV were analyzed by two-dimensional real-time magnetic resonance imaging (25 frames/s) and synchronous audio recordings in 12 professional singer subjects. Close associations in the respective articulatory kinetics were found between SPL and lip opening, jaw opening, pharynx width, uvula elevation, and vertical larynx position. However, changes in vocal tract dimensions during plateaus of SPL suggest that perceived loudness could have been varied beyond the dimension of SPL. Further multimodal investigation, including the analysis of sound spectra, is needed for a better understanding of the role of vocal tract resonances in the control of vocal loudness in human phonation.
EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors
Authors: Li Dan , Guo Xianling , Yang Kun , Yang Yuening , Zhou Weilin , Huang Yong , Liang Xiao , Su Jinhua , Jiang Lin , Li Jing , Fu Maorong , He Haixia , Yang Jinrong , Shi Huashan , Yang Hanshuo , Tong Aiping , Chen Nianyong , Hu Jiankun , Xu Qing , Wei Yu-Quan , Wang Wei
Published: December 2023

The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM is a biomarker of epithelial tumors, but the clinical feasibility of CAR-T therapy targeting EpCAM is lacking. Here, we report pre- and clinical investigations of EpCAM–CAR-T cells for solid tumors. We demonstrated that EpCAM–CAR-T cells costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models and EpCAM-humanized mice. Notably, in clinical trials for epithelial tumors (NCT02915445), 6 (50%) of the 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%) experienced reversible grade 3 leukopenia, and no higher-grade toxicity reported. Efficacy analysis determined two patients as partial response. Three patients showed >23 months of progression-free survival, among whom one patient experienced 2-year progress-free survival with detectable CAR-T cells 200 days after infusion. These data demonstrate the feasibility and tolerability of EpCAM–CAR-T therapy.
Toward a continuum description of lubrication in highly pressurized nanometer-wide constrictions: The importance of accurate slip laws
Authors: Codrignani Andrea , Peeters Stefan , Holey Hannes , Stief Franziska , Savio Daniele , Pastewka Lars , Moras Gianpietro , Falk Kerstin , Moseler Michael
Published: December 2023

The Reynolds lubrication equation (RLE) is widely used to design sliding contacts in mechanical machinery. While providing an excellent description of hydrodynamic lubrication, friction in boundary lubrication regions is usually considered by empirical laws, because continuum theories are expected to fail for lubricant film heightsh0≪ 10 nm, especially in highly loaded tribosystems with normal pressurespn≫ 0.1 GPa. Here, the performance of RLEs is validated by molecular dynamics simulations of pressurized (withpn= 0.2 to 1 GPa) hexadecane in a gold converging-diverging channel with minimum gap heightsh0= 1.4 to 9.7 nm. Forpn≤ 0.4 GPa andh0≥ 5 nm, agreement with the RLE requires accurate constitutive laws for pressure-dependent density and viscosity. An additional nonlinear wall slip law relating wall slip velocities to local shear stresses extends the RLE’s validity to even the most severe loading conditionpn= 1 GPa andh0= 1.4 nm. Our results demonstrate an innovative route for continuum modeling of highly loaded tribological contacts under boundary lubrication.
Inhibition of Parkinson’s disease–related LRRK2 by type I and type II kinase inhibitors: Activity and structures
Authors: Sanz Murillo Marta , Villagran Suarez Amalia , Dederer Verena , Chatterjee Deep , Alegrio Louro Jaime , Knapp Stefan , Mathea Sebastian , Leschziner Andres E.
Published: December 2023

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial Parkinson’s disease (PD) and a risk factor for the sporadic form. Increased kinase activity was shown in patients with both familial and sporadic PD, making LRRK2 kinase inhibitors a major focus of drug development efforts. Although much progress has been made in understanding the structural biology of LRRK2, there are no available structures of LRRK2 inhibitor complexes. To this end, we solved cryo–electron microscopy structures of LRRK2, wild-type and PD-linked mutants, bound to the LRRK2-specific type I inhibitor MLi-2 and the broad-spectrum type II inhibitor GZD-824. Our structures revealed an active-like LRRK2 kinase in the type I inhibitor complex, and an inactive DYG-out in the type II inhibitor complex. Our structural analysis also showed how inhibitor-induced conformational changes in LRRK2 are affected by its autoinhibitory N-terminal repeats. The structures provide a template for the rational development of LRRK2 kinase inhibitors covering both canonical inhibitor binding modes.
Noncanonical MAVS signaling restrains dendritic cell–driven antitumor immunity by inhibiting IL-12
Authors: Wu Lingling , Hong Xiaochuan , Yang Chao , Yang Yuanqin , Li Wenwen , Lu Lu , Cai Meichun , Cao Dongqing , Zhuang Guanglei , Deng Liufu
Published: December 2023

Mitochondrial antiviral signaling protein (MAVS)–mediated cytosolic RNA sensing plays a central role in tumor immunogenicity. However, the effects of host MAVS signaling on antitumor immunity remain unclear. Here, we demonstrate that the host MAVS pathway supports tumor growth and impairs antitumor immunity, whereas MAVS deficiency in dendritic cells (DCs) promotes tumor-reactive CD8
+
T cell responses. Specifically, CD8
+
T cell priming capacity was enhanced by MAVS ablation in a type I interferon–independent, but IL-12–dependent, manner. Mechanistically, loss of the RIG-I/MAVS cascade activated the noncanonical NF-κB pathway and in turn induced IL-12 production by DCs. MAVS-restrained IL-12 promoted cross-talk between CD8
+
T cells and DCs, which was licensed by IFN-γ. Moreover, ablation of host MAVS sensitized tumors to immunotherapy and attenuated radiation resistance, thereby facilitating the maintenance of effector CD8
+
T cells. These findings demonstrate that the host MAVS pathway acts as an immune regulator of DC-driven antitumor immunity and support the development of immunotherapies that antagonize MAVS signaling in DCs.
CD8 T
regs
SQa-1shing transplant rejection
Authors: Bracey Nathan A. , Maltzman Jonathan S.
Published: December 2023

MHC-E restricted CD8
+
regulatory T cells have a restricted TCR repertoire and eliminate pathogenic CD4 T cells to mediate immune responses.
Redeveloping antigen detection kits for the diagnosis of rat hepatitis E virus
Authors: Chen Zihao , Li Guanghui , Situ Jianwen , Li Zhiyong , Guo Shaoqi , Huang Yang , Wu Shusheng , Tang Zimin , Wen Guiping , Wang Siling , Fang Mujin , Wang Yingbin , Yu Hai , Sridhar Siddharth , Zheng Zizheng , Xia Ningshao
Published: December 2023

The emergence of
Rocahepevirus ratti
[species HEV
ratti
(
r
HEV)] as a causative agent of hepatitis E in humans presents a new potential threat to global public health. The
R. ratti
genotype 1 (
r
-1 HEV) variant only shares 50%–60% genomic identity with
Paslahepevirus balayani
[species HEV
balayani
(
b
HEV)] variants, which are the main causes of hepatitis E infection in humans. Here, we report antigen diagnoses for
r
-1 HEV and
b
HEV using an enzymatic immunoassay (EIA) method. We detected recombinant virus-like particles protein (HEV 239) of
r
HEV and
b
HEV using a collection of hepatitis E virus (HEV)-specific monoclonal antibodies. Two optimal candidates, the capture antibody P#1-H4 and the detection antibodies C145 (P#1-H4*/C145
#
) and C158 (P#1-H4*/C158
#
), were selected to detect antigen in infected rat samples and
r
-1 HEV- or
b
HEV-infected human clinical samples. The two candidates showed similar diagnostic efficacy to the Wantai HEV antigen kit in
b
HEV-infected clinical samples. Genomic divergence resulted in low diagnostic efficacy of the Wantai HEV antigen kit (0%, 0 of 10) for detecting
r
-1 HEV infection. Compared with the P#1-H4*/C145
#
candidate (80%, 8 of 10), the P#1-H4*/C158
#
candidate had excellent diagnostic efficacy in
r
-1 HEV-infected clinical samples (100%, 10 of 10). The two candidates bind to a discrete antigenic site that is highly conserved across
r
HEV and
b
HEV. P#1-H4*/C145
#
and P#1-H4*/C158
#
are efficacious candidate antibody combinations for rat HEV antigen detection.
Enteropathogenic
E. coli
infection co-elicits lysosomal exocytosis and lytic host cell death
Authors: Shtuhin-Rahav Raisa , Olender Aaron , Zlotkin-Rivkin Efrat , Bouman Etan Amse , Danieli Tsafi , Nir-Keren Yael , Weiss Aryeh M. , Nandi Ipsita , Aroeti Benjamin
Published: December 2023

Enteropathogenic
Escherichia coli
(EPEC) is a primary human enteric bacterial pathogen causing acute diarrhea in children. EPEC colonizes the small intestine, and the disease is induced, in part, by the ability of the pathogen to utilize a type III secretion machinery to inject a battery of proteins, termed “effectors,” from the bacterial cytoplasm into the intestinal enterocytes. Host cell responses to the infecting pathogen are also essential for disease development. Despite intensive research, the mechanisms of EPEC infection and host cell responses need to be better understood. Here, we show that specific EPEC type III secreted effectors, EspF and Map, induce lytic host cell death and also lysosomal exocytosis (LE), resulting in the secretion of lysosomal enzymes into the extracellular environment and the appearance of the lysosomal membrane proteins, Lamp-1, on the infected cell surface. The mitochondrial cytotoxicity and the guanine nucleotide exchange factor domains of Map have been identified to be involved in these processes. In contrast, EspZ, an EPEC effector that protects against lytic cell death, also inhibits LE. Our results combined suggest that LE and host cell death are tightly interconnected processes. The mechanisms and functional significance of these processes on EPEC infection are discussed.

IMPORTANCE

Enteropathogenic
Escherichia coli
(EPEC) infection is a significant cause of gastroenteritis, mainly in children. Therefore, studying the mechanisms of EPEC infection is an important research theme. EPEC modulates its host cell life by injecting via a type III secretion machinery cell death modulating effector proteins. For instance, while EspF and Map promote mitochondrial cell death, EspZ antagonizes cell death. We show that these effectors also control lysosomal exocytosis, i.e., the trafficking of lysosomes to the host cell plasma membrane. Interestingly, the capacity of these effectors to induce or protect against cell death correlates completely with their ability to induce LE, suggesting that the two processes are interconnected. Modulating host cell death is critical for establishing bacterial attachment to the host and subsequent dissemination. Therefore, exploring the modes of LE involvement in host cell death is crucial for elucidating the mechanisms underlying EPEC infection and disease.
Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection
Authors: Bhavsar Disha , Singh Gagandeep , Sano Kaori , Gleason Charles , Srivastava Komal ,   PARIS Study Group, Carreno Juan Manuel , Simon Viviana , Krammer Florian , Oostenink Annika , Salimbangon Ashley-Beathrese , Monahan Brian , Cognigni Christian , Andre Dalles , Bielak Dominika , Cai Gianna Y. , Kleiner Giulio , Kang Hyun Min , Mauldin Jacob , Mischka Jacob , Nardulli Jessica , Sullivan Leeba , Bermúdez-González Maria C. , Fried Miriam , Kesteren Morgan Van , Lyttle Neko , Morris Sara , Yellin Temima , Chen Yuexing
Published: December 2023

Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.

IMPORTANCE

Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.
Genome sequence of a measles virus strain with a novel loss of stop codon mutation in the phosphoprotein gene
Authors: Zubach Vanessa , Schulz Helene , Kim Kihun , Hole Darian , Severini Alberto , Hiebert Joanne
Published: December 2023

Measles virus genotype B3 coding-complete genome sequence from a 2019 case showed a novel mutation in the phosphoprotein (P) gene that abrogates the established stop codon. A downstream stop codon has been identified, resulting in a putative P that would be 19 amino acids longer than wild type.
The role of autophagy in tick-endosymbiont interactions: insights from
Ixodes scapularis
and
Rickettsia buchneri
Authors: Wang Xin-Ru , Cull Benjamin , Oliver Jonathan D. , Kurtti Timothy J. , Munderloh Ulrike G.
Published: December 2023

Approximately 80 identified tick species are recognized as vectors and impact global public health by transmitting a wide range of pathogens; however, little is known about the interactions of ticks with the microbiome that they harbor, let alone their bacterial symbionts. In this study, we used the black-legged tick,
Ixodes scapularis
Say (Acari: Ixodidae), a vector of seven human pathogens in the United States, and utilized
Rickettsia buchneri sensu stricto
ISO7
T
(Rickettsiales: Rickettsiaceae), a spotted fever group (SFG) rickettsia that is an endosymbiont of
I. scapularis,
to investigate the role of autophagy in symbiont and tick interactions. We found that the expression profile of most autophagy family member proteins (ATGs) is down-regulated after
R. buchneri
infection in tick cell cultures. The autophagic process was observed by assessment of autophagosome formation and maturation
in vitro
(tick cell culture) and
in vivo
(tick ovary) in the presence of
R. buchneri
, whereas apoptosis was not induced. We further showed that
R. buchneri
infection triggered the accumulation of plasma membranes within cells. Suppressing autophagy via
Atg8
siRNA interference inhibited intracellular rickettsial replication. This research indicates that autophagy regulation is important for the maintenance of
R. buchneri
in its
I. scapularis
tick host and provides more clues to solve the tick-symbiont interaction puzzle.

IMPORTANCE

Ticks are second only to mosquitoes in their importance as vectors of disease agents; however, tick-borne diseases (TBDs) account for the majority of all vector-borne disease cases in the United States (approximately 76.5%), according to Centers for Disease Control and Prevention reports. Newly discovered tick species and their associated disease-causing pathogens, and anthropogenic and demographic factors also contribute to the emergence and re-emergence of TBDs. Thus, incorporating different tick control approaches based on a thorough knowledge of tick biology has great potential to prevent and eliminate TBDs in the future. Here we demonstrate that replication of a transovarially transmitted rickettsial endosymbiont depends on the tick’s autophagy machinery but not on apoptosis. Our findings improve our understanding of the role of symbionts in tick biology and the potential to discover tick control approaches to prevent or manage TBDs.