bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Distribution in a Mexican Population
Authors: de la Cruz Jasso Mercedes A , Mejía-Vilet Juan M , del Toro-Cisneros Noemí , Aguilar-León Diana E , Morales-Buenrostro Luis E , Herrera Guillermo , Uribe-Uribe Norma O
Published: October 2022

Objectives

To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population.

Methods

The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations.

Results

Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study.

Conclusions

This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands.
Functional cognitive disorder affects reaction time, subjective mental effort and global metacognition
Authors: Teodoro Tiago , Koreki Akihiro , Chen Jiaying , Coebergh Jan , Poole Norman , Ferreira Joaquim J , Edwards Mark J , Isaacs Jeremy D
Published: October 2022

We previously hypothesized that functional cognitive disorder is characterized by heightened subjective mental effort, exhausted attentional reserve and metacognitive failure.

To test this hypothesis, we administered a Stroop colour-word task in which attentional demand was varied by task difficulty (congruent versus incongruent cues) and the presence of a secondary auditory stimulus (passive or active listening to an oddball-type paradigm). We measured subjective mental effort, objective performance (reaction times and accuracy), metacognition and EEG-based biomarkers of mental workload.

We tested 19 functional cognitive disorder patients and 23 healthy controls. Patients reported higher levels of depression, anxiety, fatigue, pain, sleep disruption, dissociation and obsessiveness. They rated their memory as significantly poorer than healthy controls; however, accuracy did not differ between groups in any condition. In contrast to healthy controls, patients rated their performance as poorer on the congruent Stroop task with background noise compared to silent conditions. Functional cognitive disorder was consistently associated with slower reaction times but this was not exacerbated by increased attentional demand. Patients but not healthy controls reported greater mental workload in noisy conditions but EEG biomarkers were similar between groups, regardless of task difficulty.

Functional cognitive disorder has significant syndromic overlap with mood disorders and chronic fatigue and pain. It is associated with global metacognitive failure whereas local (task-specific) metacognition is only selectively impaired. Patients were slower than healthy controls, which might contribute to the ‘brain fog’ reported in this condition. Although subjective mental effort was increased in noisy conditions, we found no evidence of attentional exhaustion in functional cognitive disorder. Our results indicate that functional cognitive disorder is a multisystem condition affecting reaction time, subjective mental effort and global metacognition.
Common and distinct fronto-striatal volumetric changes in heroin and cocaine use disorders
Authors: Ceceli Ahmet O , Huang Yuefeng , Kronberg Greg , Malaker Pias , Miller Pazia , King Sarah G , Gaudreault Pierre-Olivier , McClain Natalie , Gabay Lily , Vasa Devarshi , Newcorn Jeffrey H , Ekin Defne , Alia-Klein Nelly , Goldstein Rita Z
Published: October 2022

Different drugs of abuse impact the morphology of fronto-striatal dopaminergic targets in both common and unique ways. While dorsal striatal volume tracks with addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter inhibitory control, rooted in cortical regions such as the inferior frontal gyrus (IFG). We hypothesized parallel grey matter volume changes associated with human heroin or cocaine use disorder: lower grey matter volume of vmPFC/NAcc in heroin use disorder and IFG in cocaine use disorder, and putamen grey matter volume to be associated with addiction severity measures (including craving) across both.

In this cross-sectional study, we quantified grey matter volume (P < 0.05-corrected) in age/sex/IQ-matched individuals with heroin use disorder (n = 32, seven females), cocaine use disorder (n = 32, six females) and healthy controls (n = 32, six females) and compared fronto-striatal volume between groups using voxel-wise general linear models and non-parametric permutation-based tests.

Overall, individuals with heroin use disorder had smaller vmPFC and NAcc/putamen volumes than healthy controls. Bilateral lower IFG grey matter volume patterns were specifically evident in cocaine versus heroin use disorders. Correlations between addiction severity measures and putamen grey matter volume did not reach nominal significance level in this sample.

These results indicate alterations in dopamine-innervated regions (in the vmPFC and NAcc) in heroin addiction. For the first time we demonstrate lower IFG grey matter volume specifically in cocaine compared with heroin use disorder, suggesting a signature of reduced inhibitory control, which remains to be tested directly using select behavioural measures. Overall, results suggest substance-specific volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.
Brain age predicts long-term recovery in post-stroke aphasia
Authors: Kristinsson Sigfus , Busby Natalie , Rorden Christopher , Newman-Norlund Roger , den Ouden Dirk B , Magnusdottir Sigridur , Hjaltason Haukur , Thors Helga , Hillis Argye E , Kjartansson Olafur , Bonilha Leonardo , Fridriksson Julius
Published: October 2022

The association between age and language recovery in stroke remains unclear. Here, we used neuroimaging data to estimate brain age, a measure of structural integrity, and examined the extent to which brain age at stroke onset is associated with (i) cross-sectional language performance, and (ii) longitudinal recovery of language function, beyond chronological age alone. A total of 49 participants (age: 65.2 ± 12.2 years, 25 female) underwent routine clinical neuroimaging (T1) and a bedside evaluation of language performance (Bedside Evaluation Screening Test-2) at onset of left hemisphere stroke. Brain age was estimated from enantiomorphically reconstructed brain scans using a machine learning algorithm trained on a large sample of healthy adults. A subsample of 30 participants returned for follow-up language assessments at least 2 years after stroke onset. To account for variability in age at stroke, we calculated proportional brain age difference, i.e. the proportional difference between brain age and chronological age. Multiple regression models were constructed to test the effects of proportional brain age difference on language outcomes. Lesion volume and chronological age were included as covariates in all models. Accelerated brain age compared with age was associated with worse overall aphasia severity (F(1, 48) = 5.65, P = 0.022), naming (F(1, 48) = 5.13, P = 0.028), and speech repetition (F(1, 48) = 8.49, P = 0.006) at stroke onset. Follow-up assessments were carried out ≥2 years after onset; decelerated brain age relative to age was significantly associated with reduced overall aphasia severity (F(1, 26) = 5.45, P = 0.028) and marginally failed to reach statistical significance for auditory comprehension (F(1, 26) = 2.87, P = 0.103). Proportional brain age difference was not found to be associated with changes in naming (F(1, 26) = 0.23, P = 0.880) and speech repetition (F(1, 26) = 0.00, P = 0.978). Chronological age was only associated with naming performance at stroke onset (F(1, 48) = 4.18, P = 0.047). These results indicate that brain age as estimated based on routine clinical brain scans may be a strong biomarker for language function and recovery after stroke.
Autonomic changes in Huntington’s disease correlate with altered central autonomic network connectivity
Authors: Schultz Jordan L , Heinzerling Amanda E , Brinker Alivia N , Harshman Lyndsay A , Magnotta Vincent A , Kamholz John A , Boes Aaron D , Nopoulos Peg C
Published: October 2022

Autonomic dysfunction has been described in patients with Huntington’s disease, but it is unclear if these changes in autonomic tone are related to the central autonomic network. We performed a pilot study to investigate the relationship between the integrity of the central autonomic network and peripheral manifestiations of autonomic dysfunction in premanifest Huntington’s disease. We recruited male participants with pre-motor-manifest Huntington’s disease and a comparison group consisting of healthy, male participants of approximately the same age. As this was a pilot study, only males were included to reduce confounding. Participants underwent a resting-state functional magnetic resonance imaging study to quantify functional connectivity within the central autonomic network, as well as a resting 3-lead ECG to measure heart rate variability with a particular focus on the parasympathetic time-domain measures of root mean square of successive differences between normal heartbeats. The pre-motor-manifest Huntington’s disease participants had significantly decreased root mean square of successive differences between normal heartbeats values compared with the healthy comparison group. The pre-motor-manifest Huntington’s disease group had significantly lower functional connectivity within the central autonomic network, which was positively correlated with root mean square of successive differences between normal heartbeats. Patients with pre-motor-manifest Huntington’s disease have reduced functional connectivity within the central autonomic network, which is significantly associated with observed changes in autonomic function.
Association between diesel exhaust exposure and mitochondrial DNA methylation
Authors: Seow Wei Jie , Hu Wei , Dai Yufei , Vermeulen Roel , Byun Hyang-Min , Wong Jason Y Y , Bassig Bryan A , Blechter Batel , Duan Huawei , Niu Yong , Downward George , Leng Shuguang , Ji Bu-Tian , Fu Wei , Xu Jun , Meliefste Kees , Yang Jufang , Ren Dianzhi , Ye Meng , Meng Tao , Bin Ping , Hosgood H Dean , Silverman Debra T , Rothman Nathaniel , Zheng Yuxin , Lan Qing
Published: October 2022

Objectives

Diesel exhaust is an established human carcinogen, however the mechanisms by which it leads to cancer development are not fully understood. Mitochondrial dysfunction is an established contributor to carcinogenesis. Recent studies have improved our understanding of the role played by epigenetic modifications in the mitochondrial genome on tumorigenesis. In this study, we aim to evaluate the association between diesel engine exhaust (DEE) exposure with mitochondrial DNA (mtDNA) methylation levels in workers exposed to DEE.

Methods

The study population consisted of 53 male workers employed at a diesel engine manufacturing facility in Northern China who were routinely exposed to diesel exhaust in their occupational setting, as well as 55 unexposed male control workers from other unrelated factories in the same geographic area. Exposure to DEE, elemental carbon, organic carbon, and particulate matter (PM2.5) were assessed. mtDNA methylation for CpG sites (CpGs) from seven mitochondrial genes (D-Loop, MT-RNR1, MT-CO2, MT-CO3, MT-ATP6, MT-ATP8, MT-ND5) was measured in blood samples. Linear regression models were used to estimate the associations between DEE, elemental carbon, organic carbon and PM2.5 exposures with mtDNA methylation levels, adjusting for potential confounders.

Results

DEE exposure was associated with decreased MT-ATP6 (difference = −35.6%, P-value = 0.019) and MT-ATP8 methylation (difference = −30%, P-value = 0.029) compared to unexposed controls. Exposures to elemental carbon, organic carbon, and PM2.5 were also significantly and inversely associated with methylation in MT-ATP6 and MT-ATP8 genes (all P-values < 0.05).

Conclusions

Our findings suggest that DEE exposure perturbs mtDNA methylation, which may be of importance for tumorigenesis.
Stratification of alopecia areata reveals involvement of CD4 T cell populations and altered faecal microbiota
Authors: Bain K A , Nichols B , Moffat F , Kerbiriou C , Ijaz U Z , Gerasimidis K , McInnes I B , Åstrand A , Holmes S , Milling S W F
Published: October 2022

Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. Autoreactive CD8 T cells are key pathogenic effectors in the skin, and AA has been associated both with atopy and with perturbations in intestinal homeostasis. This study aimed to investigate mechanisms driving AA by characterizing the circulating immunophenotype and faecal microbiome, and by stratifying AA to understand how identified signatures associated with heterogeneous clinical features of the condition. Flow cytometric analyses identified alterations in circulating B cells and CD4 T cells, while 16S sequencing identified changes in alpha and beta diversity in the faecal microbiome in AA. The proportions of transitional and naïve B cells were found to be elevated in AA, particularly in AA samples from individuals with >50% hair loss and those with comorbid atopy, which is commonly associated with extensive hair loss. Although significant changes in circulating CD8 T cells were not observed, we found significant changes in CD4+ populations. In individuals with <50% hair loss higher frequencies of CCR6+CD4 (“Th17”) and CCR6+CXCR3+CD4 (“Th1/17”) T cells were found. While microbial species richness was not altered, AA was associated with reduced evenness and Shannon diversity of the intestinal microbiota, again particularly in those with <50% hair loss. We have identified novel immunological and microbial signatures in individuals with alopecia areata. Surprisingly, these are associated with lower levels of hair loss, and may therefore provide a rationale for improved targeting of molecular therapeutics.
Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment
Authors: Epling Brian P , Rocco Joseph M , Boswell Kristin L , Laidlaw Elizabeth , Galindo Frances , Kellogg Anela , Das Sanchita , Roder Allison , Ghedin Elodie , Kreitman Allie , Dewar Robin L , Kelly Sophie E M , Kalish Heather , Rehman Tauseef , Highbarger Jeroen , Rupert Adam , Kocher Gregory , Holbrook Michael R , Lisco Andrea , Manion Maura , Koup Richard A , Sereti Irini
Published: October 2022

Background

Nirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion.

Methods

Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti–receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed.

Results

High levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2–specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8.

Conclusions

Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses.

Clinical trials registration

NCT04401436.
Demographic Representation Among Speakers and Program Committee Members at the IDWeek Conference, 2013–2021
Authors: Marcelin Jasmine R , Khazanchi Rohan , Lyden Elizabeth , Cawcutt Kelly A , Ha David R , Florez Narjust , Kullar Ravina , Ristagno Elizabeth H ,   the Introduction of Speakers at IDWeek Events Observing for Unconscious Bias over Time (INSIDE-OUT) study group, Rajapakse Nipunie , Patel Megha , Miller Amy M , Oeltjen Erin N , Semaj Sophie , Sramek Kyle T , Lindeman Christopher J , Daubach Eric C , Akinmoladun Oladapo O , Wurtz Paul J , Yang Yuhong
Published: October 2022

Background

In 2016, the IDWeek program committee was charged with ensuring gender equity in speaker sessions. Whether this charge also resulted in more opportunities for historically underrepresented speakers is unknown.

Methods

We conducted a retrospective analysis of trends in the demographic composition of IDWeek speakers and program committee members between 2013 and 2021. We used descriptive statistics to summarize data, χ2 tests to compare speaker demographics between 2013–2016 (before 2016) and 2017–2021 (after 2016), and Cochran–Armitage tests for trend. Each speaker slot was considered an independent event.

Results

A total of 5482 speaker slots were filled by 3389 individuals from 2013 to 2021. There was a linear increase in female speakers from 38.6% in 2013 to 58.4% in 2021 (P < .001). The proportion of white speakers decreased overall from 84.9% in 2013 to 63.5% in 2021. Compared with white speakers, more slots were filled by Asian speakers after 2016 versus before 2016 (20.1% vs 14.8%, respectively; P < .001). Program committee members from 2013–2021 were >80% non-Hispanic white; <5% of committee members identified as black, American Indian, Alaska Native, Native Hawaiian, Pacific Islander, or Hispanic. More program committee slots were filled by women after 2016 than before 2016 (52.7% vs 33.9%; P = .004).

Conclusions

Intentional consideration of gender equity by the program committee was associated with equitable gender representation of invited speakers at IDWeek after 2016. Gradually, the proportions of IDWeek speakers from historically excluded racial/ethnic approached their respective proportions in the IDSA membership. White speakers remained overrepresented relative to membership proportions until 2021, and gaps in program committee racial/ethnic demographic representation highlights opportunities for continued inclusion, diversity, access, and equity at IDWeek.
Bacterial community in soil and tree roots of Picea abies shows little response to clearcutting
Authors: Martinović Tijana , Kohout Petr , López-Mondéjar Rubén , Algora Gallardo Camelia , Starke Robert , Tomšovský Michal , Baldrian Petr
Published: October 2022

Clearcutting represents a standard management practice in temperate forests with dramatic consequences for the forest ecosystem. The removal of trees responsible for the bulk of primary production can result in a complex response of the soil microbiome. While studies have shown that tree root-symbiotic ectomycorrhizal fungi disappear from soil and decomposing fine roots of trees become a hotspot for fungal decomposition, the fate of the bacterial component of the soil microbiome following clearcutting is unclear. Here, we investigated the response of bacterial community composition for 2 years following clearcutting of a Picea abies stand in soil, rhizosphere and tree roots, by 16S rRNA amplicon sequencing. While in the first few months after clearcutting there was no significant response of bacterial community composition in the rhizosphere and soil, bacterial communities associated with tree roots underwent more profound changes over time. Acidobacteria were abundant in rhizosphere and soil, while Firmicutes were strongly represented in the roots. In addition, bacterial communities on decomposing roots were significantly different from those on pre-clearcut live roots. Compared with fungi, the response of bacterial communities to clearcutting was much less pronounced, indicating independent development of the two microbial domains.
The practice of hope in public health interventions: a qualitative single-case study
Authors: Broholm-Jørgensen Marie
Published: October 2022

This study examines hope practices in the context of participation in a public health intervention. Theoretically, the study builds upon Cheryl Mattingly’s notion of hope as a practice, which renders the possibility of examining participants actions, interactions and challenges with participating. This analytical lens contributes knowledge about how interventions are incorporated into participants’ hopes for a future life and the consequences of intervening in peoples’ everyday lives. The study builds on empirical material from a pilot study of the primary preventive intervention known as TOF (Tidlig Opsporing og Forebyggelse—a Danish acronym for ‘Early Detection and Prevention’) which aimed to identify high risk individuals and provide targeted preventive services. A by-product of a larger qualitative study, itself based on the TOF pilot study in 2019, this single-case study illustrates how participants’ life situation influence how they interpret and manage activities in a public health intervention. The study shows how the practice of hope in public health interventions is closely linked to participants’ own interpretations of how participation can lead to a life worth living. The findings, which show that participants’ needs, and life situation influence the ways in which they respond to an intervention, adds to the complexity in intervention research. Further, the study illustrates some of the ethical challenges that arise when researchers intervene in people’s everyday life. It reinforces the need for ongoing critical reflection and attention to be directed at how those being studied articulate and practice hope.
Aortic wrapping is life-saving in high-risk acute aortic dissection and intramural haematoma
Authors: Carrel Thierry , Sromicki Juri , Schmiady Martin , Aser Raed , Ouda Ahmed , Vogt Paul Robert
Published: October 2022

Aortic wrapping is a controversial repair in patients presenting with acute type A aortic dissection or intramural haematoma, but this method may be a potential alternative to medical treatment or conventional repair in patients aged >80 years and in those presenting with prohibitive co-morbidities such as stroke, circulatory collapse, full oral anticoagulation with the last generation drugs. We report on 5 high-risk and/or patients over 80 years who received external aortic wrapping with or without cardiopulmonary bypass during the last 18 months. All survived the procedure and could be extubated early postoperatively. No patient remained on the intensive care longer than 2 days and all were discharged without additional complications. Postoperative radiological control was acceptable and no patient had any new aortic event up to 18 months postoperatively.
Association between averaged intraoperative nociceptive response index and postoperative complications after lung resection surgery
Authors: Okamoto Takuma , Matsuki Yuka , Ogata Hiroki , Okutani Hiroai , Ueki Ryusuke , Kariya Nobutaka , Tatara Tsuneo , Hirose Munetaka
Published: October 2022

OBJECTIVES

Since postoperative complications, defined as Clavien–Dindo grade ≥II, correlate with long-term survival after lung resection surgery in patients with primary lung cancer, identification of intraoperative risk factors for postoperative complications is crucial for better perioperative management. In the present study, we investigated the possible association between intraoperative variables for use in anaesthetic management and Clavien–Dindo grade ≥II.

METHODS

In this multi-institutional observational study, consecutive adult patients undergoing video-assisted thoracic surgery for primary lung cancer under general anaesthesia from March 2019 to April 2021 were enrolled. All patients were divided into 2 groups with Clavien–Dindo grade <II and ≥II. Uni- and multivariable analyses were performed to identify intraoperative risk factors.

RESULTS

After univariable analysis between patients with Clavien–Dindo grade <II (n = 415) and ≥II (n = 121), multivariable analysis revealed higher averaged nociceptive response (NR) index during surgery (mean NR), male sex, lower body mass index, longer duration of surgery, higher blood loss and lower urine volume, as independent risk factors for postoperative complications. In sensitivity analysis, based on the cut-off value of mean NR for postoperative complications, all patients were divided into high and low mean NR groups. The incidence of postoperative complications was significantly higher in patients with high mean NR (n = 332) than in patients with low mean NR (n = 204; P < 0.001).

CONCLUSIONS

Higher mean NR, as intraoperative variables for use in anaesthetic management, is associated with the higher incidence of postoperative complications after primary lung cancer surgery.
Rational Origins of Revisionist War
Authors: Jordan Richard
Published: October 2022

The rise of China has returned attention to the links between power transitions and war. In this literature, three different causal mechanisms can be confused. This essay disentangles them. Power transitions can lead to three kinds of war: preventive, accidental, and revisionist. Formal models tend to study the first, in which a declining state tries to delay or prevent a rival’s ascent. However, major wars during great power transitions are usually initiated by the rising state, not the declining one. To describe these historical cases, less formal theories, especially neorealism and neoclassical realism, focus on accidental and revisionist wars, but these theories tend to fall back on nonrational mechanisms to connect changing power to the risk of conflict. This leaves a theoretical gap: Why would a rising, rational actor deliberately choose conflict, i.e., start a revisionist war? To suggest an answer, this essay demonstrates how a simple change in standard bargaining models—incorporating a nonzero probability of indecisive war—can ground realist intuitions on rationalist foundations. It further shows how this change leads immediately to an intuitive, formal definition of stability that aligns naturally with existing informal work. Then, contrary to existing realist theory, it shows why the rigorous analysis of realist assumptions leads to a nonmonotonic relationship between the offense/defense balance and war. It thus uses realism to inform and potentially redirect formal scholarship; it also uses formal scholarship to sharpen the logical foundations of realism and, in so doing, derive novel empirical predictions. The essay concludes by applying this synthesis to the rise of China today and indicating directions for deepening the formal/realist synthesis.
Power-Sharing: The Need to Explore the “Who” and the “Where”
Authors: Walsh Dawn
Published: October 2022

Power-sharing provisions have been included in many peace agreements intended to end intra-state violent conflict, including, for example, in Northern Ireland, Bosnia, Sudan, and Lebanon. Power-sharing has been subject to extensive scholarly examination. Many of these examinations focus on the impact of power-sharing on peace, often defined as the non-recurrence of violent conflict. However, the results of these examinations have not generated a consensus as to the value of power-sharing as a conflict management tool. This lack of consensus highlights a need to more clearly understand the effects of power-sharing. To fully comprehend the role of power-sharing, we must move away from simply asking if it is associated with the reoccurrence of violence and explore the paths through which it can contribute to different outcomes of interest, for example, group relations or stable government. Both Hartzell and Mehler (2019) and Keil and McCulloch (2021) seek to address this current weakness in our understanding of power-sharing, albeit in quite different ways. These books show that by paying closer attention to the impact of power-sharing on different outcomes, including a focus on the mechanisms that link its different power-sharing provisions to specific outcomes, we can develop a fundamentally deeper understanding of power-sharing.
Giving Suggestions: Using Quantity Requests to Increase Donations
Authors: Moon Alice , VanEpps Eric M
Published: October 2022

Across seven studies (N = 9,028), we provide evidence that quantity requests, wherein people consider multiple choice options of how much to donate (e.g., $5, $10, or $15), increase contributions compared to open-ended requests. Specifically, quantity requests encourage greater donations (study 1), even when respondents can passively choose not to donate (study 2) and even when the donation is directed toward a less popular cause (study 3). This increase in donations holds for quantity requests that start with both lower (e.g., $1) or higher (e.g., $10) donation amount options (study 4). Quantity requests also outperform other requests with multiple nonquantity donation options (e.g., multiple options of when to donate or to which charity branch to direct a donation; study 5). We offer evidence that quantity requests are effective because they simplify donation decisions by communicating normative donation magnitudes (studies 6 and 7). This clarified norm of donation magnitude boosts donation rates, which in turn leads to greater total donations. Our findings offer new conceptual insights into how quantity requests increase contributions as well as practical implications for charitable organizations to optimize contributions by leveraging the use of quantity requests.
Using genomic prediction with crop growth models enables the prediction of associated traits in wheat
Authors: Jighly Abdulqader , Thayalakumaran Thabo , O’Leary Garry J , Kant Surya , Panozzo Joe , Aggarwal Rajat , Hessel David , Forrest Kerrie L , Technow Frank , Tibbits Josquin F G , Totir Radu , Hayden Matthew J , Munkvold Jesse , Daetwyler Hans D
Published: October 2022

Crop growth models (CGM) can predict the performance of a cultivar in untested environments by sampling genotype-specific parameters. As they cannot predict the performance of new cultivars, it has been proposed to integrate CGMs with whole genome prediction (WGP) to combine the benefits of both models. Here, we used a CGM–WGP model to predict the performance of new wheat (Triticum aestivum) genotypes. The CGM was designed to predict phenology, nitrogen, and biomass traits. The CGM–WGP model simulated more heritable GSPs compared with the CGM and gave smaller errors for the observed phenotypes. The WGP model performed better when predicting yield, grain number, and grain protein content, but showed comparable performance to the CGM–WGP model for heading and physiological maturity dates. However, the CGM–WGP model was able to predict unobserved traits (for which there were no phenotypic records in the reference population). The CGM–WGP model also showed superior performance when predicting unrelated individuals that clustered separately from the reference population. Our results demonstrate new advantages for CGM–WGP modelling and suggest future efforts should focus on calibrating CGM–WGP models using high-throughput phenotypic measures that are cheaper and less laborious to collect.
A New Auto-RPA-Fluorescence Detection Platform for SARS-CoV-2
Authors: Tian Jing , Chen Biao , Zhang Bin , Li Tantan , Liang Zhiqiang , Guo Yujin , Jiao Huping , Liang Fenghong , Xiang Longquan , Lin Fanzhong , Ren Ruiwen , Liu Qingbin
Published: October 2022

Objective

The outbreak of COVID-19 caused by SARS-CoV-2 has led to a serious worldwide pandemic. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR)–based methods were recommended for routine detection of SARS-CoV-2 RNA. Because the reaction time and analytical sensitivity of qRT-PCR limits the diagnosis of SARS-CoV-2, development of a quick process of SARS-CoV-2 detection technology with high analytical sensitivity remains urgent.

Methods

We combined isothermal amplification and fluorescence detection technology to develop a new auto-recombinase polymerase amplification (RPA)-fluorescence platform that could be used in the diagnosis of SARS-CoV-2.

Results

By optimization of primers and probes, the RPA platform could detect SARS-CoV-2 nucleotides within 15 min. The limits of detection and specificity of the auto-RPA-fluorescence platform were 5 copies/µL and 100%, respectively. The accuracy of detection of the auto-RPA-fluorescence platform in the 16 positive samples was 100%.

Conclusion

The RPA platform is a potential technology for the diagnosis of SARS-CoV-2 infection.
A parameterized view on the complexity of dependence and independence logic
Authors: Kontinen Juha , Meier Arne , Mahmood Yasir
Published: October 2022

In this paper, we investigate the parameterized complexity of model checking for Dependence and Independence logic, which are well studied logics in the area of Team Semantics. We start with a list of nine immediate parameterizations for this problem, namely the number of disjunctions (i.e. splits)/(free) variables/universal quantifiers, formula-size, the tree-width of the Gaifman graph of the input structure, the size of the universe/team and the arity of dependence atoms. We present a comprehensive picture of the parameterized complexity of model checking and obtain a division of the problem into tractable and various intractable degrees. Furthermore, we also consider the complexity of the most important variants (data and expression complexity) of the model checking problem by fixing parts of the input.
Mode and Tempo of 3D Genome Evolution in Drosophila
Authors: Torosin Nicole S , Golla Tirupathi Rao , Lawlor Matthew A , Cao Weihuan , Ellison Christopher E
Published: October 2022

Topologically associating domains (TADs) are thought to play an important role in preventing gene misexpression by spatially constraining enhancer–promoter contacts. The deleterious nature of gene misexpression implies that TADs should, therefore, be conserved among related species. Several early studies comparing chromosome conformation between species reported high levels of TAD conservation; however, more recent studies have questioned these results. Furthermore, recent work suggests that TAD reorganization is not associated with extensive changes in gene expression. Here, we investigate the evolutionary conservation of TADs among 11 species of Drosophila. We use Hi-C data to identify TADs in each species and employ a comparative phylogenetic approach to derive empirical estimates of the rate of TAD evolution. Surprisingly, we find that TADs evolve rapidly. However, we also find that the rate of evolution depends on the chromatin state of the TAD, with TADs enriched for developmentally regulated chromatin evolving significantly slower than TADs enriched for broadly expressed, active chromatin. We also find that, after controlling for differences in chromatin state, highly conserved TADs do not exhibit higher levels of gene expression constraint. These results suggest that, in general, most TADs evolve rapidly and their divergence is not associated with widespread changes in gene expression. However, higher levels of evolutionary conservation and gene expression constraints in TADs enriched for developmentally regulated chromatin suggest that these TAD subtypes may be more important for regulating gene expression, likely due to the larger number of long-distance enhancer–promoter contacts associated with developmental genes.
The chromatin remodeler RSC prevents ectopic CENP-A propagation into pericentromeric heterochromatin at the chromatin boundary
Authors: Tsunemine Satoru , Nakagawa Hiromi , Suzuki Yutaka , Murakami Yota
Published: October 2022

Centromeres of most eukaryotes consist of two distinct chromatin domains: a kinetochore domain, identified by the histone H3 variant, CENP-A, and a heterochromatic domain. How these two domains are separated is unclear. Here, we show that, in Schizosaccharomyces pombe, mutation of the chromatin remodeler RSC induced CENP-ACnp1 misloading at pericentromeric heterochromatin, resulting in the mis-assembly of kinetochore proteins and a defect in chromosome segregation. We find that RSC functions at the kinetochore boundary to prevent CENP-ACnp1 from spreading into neighbouring heterochromatin, where deacetylated histones provide an ideal environment for the spread of CENP-ACnp1. In addition, we show that RSC decompacts the chromatin structure at this boundary, and propose that this RSC-directed chromatin decompaction prevents mis-propagation of CENP-ACnp1 into pericentromeric heterochromatin. Our study provides an insight into how the distribution of distinct chromatin domains is established and maintained.
APE1 assembles biomolecular condensates to promote the ATR–Chk1 DNA damage response in nucleolus
Authors: Li Jia , Zhao Haichao , McMahon Anne , Yan Shan
Published: October 2022

Multifunctional protein APE1/APEX1/HAP1/Ref-1 (designated as APE1) plays important roles in nuclease-mediated DNA repair and redox regulation in transcription. However, it is unclear how APE1 regulates the DNA damage response (DDR) pathways. Here we show that siRNA-mediated APE1-knockdown or APE1 inhibitor treatment attenuates the ATR–Chk1 DDR under stress conditions in multiple immortalized cell lines. Congruently, APE1 overexpression (APE1-OE) activates the ATR DDR under unperturbed conditions, which is independent of APE1 nuclease and redox functions. Structural and functional analysis reveals a direct requirement of the extreme N-terminal motif within APE1 in the assembly of distinct biomolecular condensates in vitro and DNA/RNA-independent activation of the ATR DDR. Overexpressed APE1 co-localizes with nucleolar NPM1 and assembles biomolecular condensates in nucleoli in cancer but not non-malignant cells, which recruits ATR and activator molecules TopBP1 and ETAA1. APE1 protein can directly activate ATR to phosphorylate its substrate Chk1 in in vitro kinase assays. W119R mutant of APE1 is deficient in nucleolar condensation, and is incapable of activating nucleolar ATR DDR in cells and ATR kinase in vitro. APE1-OE-induced nucleolar ATR DDR activation leads to compromised ribosomal RNA transcription and reduced cell viability. Taken together, we propose distinct mechanisms by which APE1 regulates ATR DDR pathways.
ChemPert: mapping between chemical perturbation and transcriptional response for non-cancer cells
Authors: Zheng Menglin , Okawa Satoshi , Bravo Miren , Chen Fei , Martínez-Chantar María-Luz , del Sol Antonio
Published: October 2022

Prior knowledge of perturbation data can significantly assist in inferring the relationship between chemical perturbations and their specific transcriptional response. However, current databases mostly contain cancer cell lines, which are unsuitable for the aforementioned inference in non-cancer cells, such as cells related to non-cancer disease, immunology and aging. Here, we present ChemPert (https://chempert.uni.lu/), a database consisting of 82 270 transcriptional signatures in response to 2566 unique perturbagens (drugs, small molecules and protein ligands) across 167 non-cancer cell types, as well as the protein targets of 57 818 perturbagens. In addition, we develop a computational tool that leverages the non-cancer cell datasets, which enables more accurate predictions of perturbation responses and drugs in non-cancer cells compared to those based onto cancer databases. In particular, ChemPert correctly predicted drug effects for treating hepatitis and novel drugs for osteoarthritis. The ChemPert web interface is user-friendly and allows easy access of the entire datasets and the computational tool, providing valuable resources for both experimental researchers who wish to find datasets relevant to their research and computational researchers who need comprehensive non-cancer perturbation transcriptomics datasets for developing novel algorithms. Overall, ChemPert will facilitate future in silico compound screening for non-cancer cells.
The novel type II toxin–antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur
Authors: Song Yingjie , Zhang Siping , Ye Zirui , Song Yongyan , Chen Lin , Tong Aiping , He Yongxing , Bao Rui
Published: October 2022

Type II toxin–antitoxin (TA) systems are widely distributed in bacterial and archaeal genomes and are involved in diverse critical cellular functions such as defense against phages, biofilm formation, persistence, and virulence. GCN5-related N-acetyltransferase (GNAT) toxin, with an acetyltransferase activity-dependent mechanism of translation inhibition, represents a relatively new and expanding family of type II TA toxins. We here describe a group of GNAT-Xre TA modules widely distributed among Pseudomonas species. We investigated PacTA (one of its members encoded by PA3270/PA3269) from Pseudomonas aeruginosa and demonstrated that the PacT toxin positively regulates iron acquisition in P. aeruginosa. Notably, other than arresting translation through acetylating aminoacyl-tRNAs, PacT can directly bind to Fur, a key ferric uptake regulator, to attenuate its DNA-binding affinity and thus permit the expression of downstream iron-acquisition-related genes. We further showed that the expression of the pacTA locus is upregulated in response to iron starvation and the absence of PacT causes biofilm formation defect, thereby attenuating pathogenesis. Overall, these findings reveal a novel regulatory mechanism of GNAT toxin that controls iron-uptake-related genes and contributes to bacterial virulence.
The Protective Role of Non-Photochemical Quenching in PSII Photo-Susceptibility: A Case Study in the Field
Authors: Han Li-Jun , Fan Da-Yong , Wang Xiang-Ping , Xu Cheng-Yang , Xia Xin-Li , Chow Wah Soon
Published: October 2022

Non-photochemical quenching (NPQ) has been regarded as a safety valve to dissipate excess absorbed light energy not used for photochemistry. However, there exists no general consensus on the photoprotective role of NPQ. In the present study, we quantified the Photosystem II (PSII) photo-susceptibilities (mpi) in the presence of lincomycin, under red light given to five shade-acclimated tree species grown in the field. Photosynthetic energy partitioning theory was applied to investigate the relationships between mpi and each of the regulatory light-induced NPQ [Y(NPQ)], the quantum yield of the constitutive nonregulatory NPQ [Y(NO)] and the PSII photochemical yield in the light-adapted state [Y(PSII)] under different red irradiances. It was found that in the low to moderate irradiance range (50–800 μmol m–2 s–1) when the fraction of open reaction centers (qP) exceeded 0.4, mpi exhibited no association with Y(NPQ), Y(NO) and Y(PSII) across species. However, when qP < 0.4 (1,500 μmol m–2 s–1), there existed positive relationships between mpi and Y(NPQ) or Y(NO) but a negative relationship between mpi and Y(PSII). It is postulated that both Y(NPQ) and Y(NO) contain protective and damage components and that using only Y(NPQ) or Y(NO) metrics to identify the photo-susceptibility of a species is a risk. It seems that qP regulates the balance of the two components for each of Y(NPQ) and Y(NO). Under strong irradiance, when both protective Y(NPQ) and Y(NO) are saturated/depressed, the forward electron flow [i.e. Y(PSII)] acts as the last defense to resist photoinhibition.
Factor of DNA methylation 1 affects woodland strawberry plant stature and organ size via DNA methylation
Authors: Zheng Guanghui , Hu Shaoqiang , Cheng Simin , Wang Liyang , Kan Lijun , Wang Zhengming , Xu Qiang , Liu Zhongchi , Kang Chunying
Published: October 2022

RNA-directed DNA methylation (RdDM) is an epigenetic process that directs silencing to specific genomic regions and loci. The biological functions of RdDM are not well studied in horticultural plants. Here, we isolated the ethyl methane-sulfonate-induced mutant reduced organ size (ros) producing small leaves, flowers, and fruits in woodland strawberry (Fragaria vesca) due to reduced cell numbers compared with that in the wild-type (WT). The candidate mutation causes a premature stop codon in FvH4_6g28780, which shares high similarity to Arabidopsis (Arabidopsis thaliana) Factor of DNA Methylation1 (FDM1) encoding an RdDM pathway component and was named FveFDM1. Consistently, the fvefdm1CR mutants generated by CRISPR/Cas9 also produced smaller organs. Overexpressing FveFDM1 in an Arabidopsis fdm1-1 fdm2-1 double mutant restored DNA methylation at the RdDM target loci. FveFDM1 acts in a protein complex with its homolog Involved in De Novo 2 (FveIDN2). Furthermore, whole-genome bisulfite sequencing revealed that DNA methylation, especially in the CHH context, was remarkably reduced throughout the genome in fvefdm1. Common and specific differentially expressed genes were identified in different tissues of fvefdm1 compared to in WT tissues. DNA methylation and expression levels of several gibberellic acid (GA) biosynthesis and cell cycle genes were validated. Moreover, the contents of GA and auxin were substantially reduced in the young leaves of fvefdm1 compared to in the WT. However, exogenous application of GA and auxin could not recover the organ size of fvefdm1. In addition, expression levels of FveFDM1, FveIDN2, Nuclear RNA Polymerase D1 (FveNRPD1), Domains Rearranged Methylase 2 (FveDRM2), and cell cycle genes were greatly induced by GA treatment. Overall, our work demonstrated the critical roles of FveFDM1 in plant growth and development via RdDM-mediated DNA methylation in horticultural crops.