bluuebunny/crossref_metadata_2025 huggingface dataset:
PCV ALONE IN GRADE 2 AND GRADE 3 OLIGODENDROGLIOMA – LONG-TERM RESULTS FROM A UK TERTIARY CARE CENTRE
Authors: Kalra Dr Babusha , Creak Dr Antonia , Lee Dr Ernest , Welsh Dr Liam , Solda Dr Francesca , Rosenfelder Dr Nicola , Klobukowski Dr Lukasz
Published: October 2024

AIMS

Oligodendroglioma is a subgroup of gliomas which affects young adults and has a favourable overall survival (OS) ranging between 31.5 to 56.6.% at 10 years. Standard management of these tumours is maximal safe resection followed by adjuvant radiotherapy and systemic chemotherapy with Procarbazine, Lomustine and Vincristine (PCV), or surveillance where appropriate. PCV alone is an option that helps defer or avoid radiotherapy and its neurocognitive side effects in a selected group of patients. Our retrospective study analyses outcomes with PCV alone in Oligodendroglioma.

METHOD

We screened patient records between 1999 to 2021 and identiﬁed 31 patients who had a histological diagnosis of grade 2/3 oligodendroglioma (with conﬁrmation of 1p19qcodeletion on molecular testing) and received PCV alone after surgery (biopsy/ tumour resection).

RESULTS

Out of 31 patients, twenty-six patients were grade 2 and ﬁve patients were grade 3 oligodendroglioma. Median age was 44 years and male: female was 15:16. Median follow up was 9.5 years. Twenty-ﬁve patients (80%) presented with seizures. 80% of patients had tumour resection & twenty four patients received 5 or more cycles of PCV alone as ﬁrst-line oncological treatment. There was no signiﬁcant difference in outcomes for grade2/3 tumours. Eighteen patients (58%) had local tumour relapse. Fourteen patients (45%) underwent salvage radiotherapy. Median time to radiotherapy was 7 years. Median OS was 19.4 years and median progression free survival (PFS) was 13.3 years. 9 deaths were reported.

CONCLUSION

PCV chemotherapy alone is an effective adjuvant treatment option for selected patients with oligodendroglioma, with a favourable PFS and OS shown in our series. Its use may allow deferral of radiotherapy and avoidance of associated neurocognitive side effects which can have a detrimental effect of quality of life for these young patients.
EPIGENETIC MODULATION OF STEMNESS AND DIFFERENTIATION BY VALPROIC ACID IN MEDULLOBLASTOMA
Authors: Roesler Prof Rafael , Freire Ms Natalia Hogetop , de Farias Dr Caroline Brunetto , Brunetto Dr André , Jaeger Dr Mariane , Brunetto Dr Algemir , Herlinger Dr Alice Laschuk , Gregianin Dr Lauro
Published: October 2024

AIMS

Changes in epigenetic processes, including histone acetylation, are proposed as key events affecting tumor cell function and the initiation and progression of pediatric brain cancers. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we report VPA-induced alterations in features related to stemness and differentiation in medulloblastoma (MB) cells.

METHOD

Human MB cells were treated with different concentrations of VPA and cell viability was measured with a trypan exclusion assay. Cell cycle was evaluated with ﬂow cytometry. Expansion of MB cancer stem cells (CSCs) was evaluated by a neurosphere formation assay. Reverse transcriptase polymerase chain reaction (RT-qPCR) was used to analyze mRNA expression and Western Blot to analyze protein levels. H3K9 histone acetylation (H3K9ac) was measured with immunoﬂuorescence, and chromatin Immunoprecipitation (ChIP) was used to evaluate the occupancy of gene promoter regions by H3K9ac.

RESULTS

VPA reduced MB cell viability and expansion of MB CSCs, induced morphological changes consistent with neuronal differentiation, and increased expression of differentiation markers tubulin beta 3 class III (TUBB3) and enolase 2 (ENO2). Expression of stemness markers SOX2 and Nestin was differentially affected by VPA in cells representative of SHH or Group 3/4 MB molecular subgroups. VPA increased H3K9ac and its occupancy of promoter regions of TP53 and CDKN1A genes.

CONCLUSION

Our results indicate that VPA may exert antitumor effects in MB by inﬂuencing histone acetylation, which may result in modulation of stemness and stimulation of neuronal differentiation.
AUDIT TO EVALUATE CURRENT RADIOTHERAPY (RT) PLANNING PATHWAY: COULD CURRENT PRACTICE BE IMPROVED BY THE TIMING OF MAGNETIC RESONANCE IMAGING (MRI)?
Authors: Thurgood Ms Carol
Published: October 2024

AIMS

To evaluate the current guidance for glioblastoma (GBM) and primary brain radiotherapy (RT) planning. Current practice in this centre utilises pre and post-surgical MRI for RT target delineation. This study aims to explore the practicality and impact of scheduling an RT planning-speciﬁc MRI no more than 2 weeks before RT treatment start date (TSD). Time from surgery to RT TSD will also be explored.

METHOD

Fifty GBM patients, treated between August 2022 and October 2023, were audited retrospectively. Included patients were treated with radical intent and must have had surgery or biopsy. Age, gender or performance status (PS) were excluded from audit criteria. Age of MRI used for RT planning and surgery to TSD was noted.

RESULTS

Early results showed that the average age of MRI used for RT planning was 7 weeks old and Surgery to TSD was 7 weeks. A new pathway was introduced after 37 patients as these results were considered unacceptable. The new pathway included 1 reserved MRI appointment and one reserved RT Mask/CT appointment per week. 13 patients’ pathways were audited after introduction of the new pathway. The results showed that the average age of MRI used for RT planning was 2 weeks old and surgery to TSD was 6 weeks.

CONCLUSION

Limitations of the audit included disparity between number of patients before and after introduction of the new pathway. This was because of the time limitation for completion of the study. Improvement was seen in timing of MRI to TSD. However, the small improvement in timing of surgery to TSD was impacted by human factors rather than organisational inﬂuence, for example, surgical deconditioning, delays for wound healing and patient choice. This study has shown that the ideal timing of MRI can be achieved.
Managing Cancer and Living Meaningfully in adults with brain metastases: A NIH ORBIT model phase II feasibility and proof-of-concept trial
Authors: Loughan Ashlee R , Lanoye Autumn , Willis Kelcie , Braun Sarah Ellen , Davies Alexandria , Rodin Gary , Thacker Leroy , Fox Amber , Kleva Christopher , Zarrella Giuliana , Mazzeo Suzanne , Svikis Dace , Swartz Leigh
Published: October 2024

Background

Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy designed to help patients with advanced cancer cope with the practical and profound challenges of their illness. However, no study has systematically examined CALM in adults with brain metastases, despite the well-documented incidence of distress in this growing population. The primary aim of this trial was to assess the feasibility and acceptability of CALM in adults with brain metastases.

Methods

Patients with brain metastases (N = 13) and elevated symptoms of depression and/or death anxiety enrolled in this single-arm trial. CALM was administered in 6 biweekly sessions, with outcomes assessed at baseline and post-intervention. Feasibility was assessed based on established metrics including enrollment and retention rates. Acceptability was measured by post-session surveys and post-intervention interviews. Preliminary signal change on measures of psychological distress was explored.

Results

Of the 13 enrolled participants, 11 completed baseline assessments and initiated treatment: 73% female, Mage = 58 years (SD = 12.9; range = 37–75). Nine completed the study (81% retention rate). Overall, participants reported high perceived benefits and would recommend the program to others. Baseline to post-intervention assessments indicated improvements in depression, death anxiety, generalized anxiety, post-traumatic stress, suicidal ideation, and spiritual well-being. Life quality, substance use, and fear of cancer recurrence remained relatively stable.

Conclusions

CALM is feasible and acceptable and may improve psychological distress in adults with brain metastases. The findings of this study align with our previous trial of patients with malignant glioma and support a future National Institute of Health Obesity Related Behavioral Intervention Trials phase II randomized pilot trial of CALM in neuro-oncology.

Trial Registration Number

NCT05087095 registered on March 23, 2022.
Integrated detrital rutile and detrital zircon ages: a new perspective on the tectonic evolution of South China
Authors: Zou Hao , Li Hongkui , Li Zhongquan , Wang Danlin , Safonova Inna , Cao Huawen , Jin Xin , Chen Haifeng , Huang Changcheng
Published: October 2024

Paleogeographic reconstructions are of key importance for understanding the history of continental breakups and amalgamations during Earth’s history. A special case is the history of the Asian continent, which, compared to other continents, consists of several large cratons and numerous smaller continental blocks. The history of the assembly of South China remains controversial in terms of the timing, Late Neoproterozoic or Early Paleozoic, and the participating continental blocks, e.g. Yangtze, Cathaysia, India and Australia. Detrital rutile U-Pb dating has significant potential with regard to deciphering tectonic settings as rutile frequently crystallizes during orogenic events associated with the processes of collision and subduction. Detrital zircon U-Pb dating is a perfect instrument for identifying the provenance characteristics and age characteristics of sedimentary sources. An integration of these two methods of dating offers better opportunities for reconstructing tectonic settings. This paper presents a first attempt to reconstruct the Neoproterozoic to Early Paleozoic tectonic history and paleogeography of the whole South China based on U-Pb geochronology of rutile and zircon and Hf-in-zircon isotopes from Lower Jurassic Baitianba Formation sedimentary rocks of the western margin of the Yangtze Block, a major part of South China. Our obtained integrated U-Pb rutile and zircon age data show three main age populations of 960–940 Ma, 630–610 Ma and 530–520 Ma. The new U-Pb detrital rutile and zircon ages, compared with former data from Gondwana and Australia, suggest that Yangtze amalgamated with Cathaysia to form South China during the Sibao orogeny at 960–940 Ma. The detrital rutile and zircons of the new 630–610 Ma age group could have been delivered from western Australia during the Late Neoproterozoic to Cambrian Paterson-Petermann orogeny. The abundant 530–520 Ma detrital rutile and zircon ages fit well with the coeval zircon age populations recorded in Gondwana-derived terranes, like India and Indochina.
Prize-Based Incentives for Smoking Cessation Among People With HIV: A Sequential Multiple Assignment Randomized Trial
Authors: Ledgerwood David M , Lundahl Leslie H , Greenwald Mark K , Cohn Jonathan , Arfken Cynthia L
Published: October 2024

Introduction

Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The purpose of this study was to assess the efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response.

Methods

During phase I, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in phase II to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically verified smoking reduction and 7-day abstinence prevalence at posttreatment, 6-month, and 12-month follow-up.

Results

Phase I responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6 and 12 months) if they received low-magnitude incentives. Notably, initial exposure to CM versus SoC did not increase the rate of phase I response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early-treatment nonresponders.

Conclusions

Weekly CM sessions in the first 4 weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation.

Implications

This represents the first trial to examine the use of CM for smoking cessation among PWH within the context of a SMART design.

Clinical Trial Registration:  NCT01965405 (https://clinicaltrials.gov/study/NCT01965405)
Community Mobilization to Guide the Public Health Response During the 2022 Ontario Mpox Outbreak: A Brief Report
Authors: Tan Darrell H S , Awad Adam , Zygmunt Austin , Murray James , Warshafsky Daniel , Mishra Sharmistha , Griffiths Dane
Published: October 2024

The 2022 mpox epidemic predominantly affected gay, bisexual, and other men who have sex with men (GBM). Led by a provincial community program and co-galvanized by clinician-researchers, GBM community leaders in Ontario coordinated a robust response, representing a reproducible strategy for community engagement and mobilization during future epidemics.
Virus Load Kinetics in Lassa Fever Patients Treated With Ribavirin: A Retrospective Cohort Study From Southern Nigeria
Authors: Ogbaini-Emovon Ephraim , Akpede George , Okogbenin Sylvanus , Osagiede Emmanuel , Tobin Ekaete , Asogun Danny , Okokhere Peter , Okonofua Martha , Akpede Nosa , Akhideno Peter , Erameh Cyril , Rafiu Mojeed , Azubuike Chukwuemeka , Iraoya Kelly , Iruolagbe Chris , Erohubie Christian , Ahmed Dazumi , Ediawe Osahogie , Okoguale Joseph , Eifediyi Reuben , Odia Ikponmwonsa , Agbukor Jacqueline , Adomeh Donatus , Odike Maxy A C , Ovienria Wilson , Elkanem Anieno , Muoebenam Ekene B , Ojide Kingsley C , Pallasch Elisa , Müller Jonas , Hinzmann Julia , Günther Stephan , Pahlmann Meike , Thielebein Anke , Duraffour Sophie , Oestereich Lisa , Krumkamp Ralf
Published: October 2024

Background

The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin.

Methods

We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction–confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients.

Results

The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5–12) days. Median (IQR) Ct values on admission (t0) were lower among patients who died (21 [20–27]) than in those who survived (34 [30–37]; P < .01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86–0.98). The median time to viral clearance (IQR) was 10 (5–15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization.

Conclusions

Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3–4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols.
Clinical and economic impact of pharmacist interventions to identify drug-related problems in multidisciplinary cancer care: a prospective trial
Authors: Giraud Jean-Stéphane , Korb-Savoldelli Virginie , Perrin Germain , Jouinot Anne , Sabatier Brigitte , Batista Rui , Ribault Matthieu , De Percin Sixtine , Villeminey Clémentine , Videau Margaux , Blanchet Benoit , Goldwasser Francois , Degrassat-Theas Albane , Thomas-Schoemann Audrey
Published: October 2024

Background

The prescription of antitumor drugs has often been associated with drug-related problems. Pretherapeutic multidisciplinary risk assessment programs including pharmaceutical care have been established to secure the initiation of injectable and oral antitumor therapies. This prospective cross-sectional double-center study evaluated the clinical and economic impact of the pharmacist in detecting drug-related problems in patients initiating antitumor therapies.

Materials and Methods

Following pharmaceutical consultations, pharmaceutical interventions were validated by a multidisciplinary team. A committee of independent clinical experts assessed the potential clinical impact of drug-drug interactions. The association of clinical variables with pharmaceutical interventions was tested using a multivariate logistic regression model. Pharmacist cost of the program was assessed by valuing pharmacists’ time at their salaries and compared with potentially avoided costs.

Results

Four hundred thirty-eight patients with solid tumors were included: 62% males, mean age of 65 ± 13 years, and average of 6 medications. Half of the patients required at least one pharmaceutical intervention and independent factors associated with pharmaceutical interventions were the number of medications (5-9 vs <5: OR = 2.91 [95% CI 1.82-4.65], P < .001) and the type of antitumor treatment (immunotherapy vs intravenous chemotherapy: OR = 0.35 [95% CI 0.18-0.68], P = .002). One hundred seventy-four out of 266 pharmaceutical interventions (130 patients) involved clinically significant drug-drug interactions. Pharmacist costs were estimated to range between €4899 and €6125. Average costs were estimated at €11.4-14.3 per patient. Avoided hospitalization costs were estimated to be €180 633.

Conclusion

Clinical pharmacists contribute to the cost-effective reduction of drug-related problems in pre-therapeutic assessment programs for patients with cancer.
Weather events influence survival and recruitment of Coereba flaveola (Bananaquit) in the Caribbean
Authors: Boal Clint W , Bibles Brent D
Published: October 2024

The West Indies is considered a biodiversity hotspot and a priority for ecological conservation efforts. Understanding how environmental conditions influence the survival of resident avifauna is an important information need given the predicted increases in drought and the frequency and intensity of severe storms in the region. Throughout much of the Caribbean, Coereba flaveola (Bananaquit) are widespread and abundant, traits that may facilitate understanding their response to environmental changes in the region. We used a 10-yr capture–mark–recapture data set to examine C. flaveola survival, recruitment, population growth, and age structure in the context of monthly and seasonal precipitation and temperatures, drought conditions, and occurrence and intensity of storm events. Our models suggested wing length, occurrence of storms, and drought all influenced survival. Both the incidence of storms and drier-than-average conditions in the preceding wet season (April–June) decreased survival. The sex of bird and net hours influenced capture probability, but weather influences on recruitment were equivocal. During nonstorm years, mean population growth was stable at 1.019 (95% confidence interval [CI]: 0.962, 1.098) but dropped to 0.843 (95% CI: 0.795, 0.846) in storm years. Increasing frequency of storms, such as back-to-back years, would likely push the growth rate lower. A protracted pattern of increased storm frequency, especially if coupled with a subsequent drought during the wet season, may lead to localized extirpations or strongly reduced populations.
Targeted nuclear degranulation of neutrophils promotes the progression of pneumonia in ulcerative colitis
Authors: Shao Yiming , Zheng Qibing , Zhang Xiaobei , Li Ping , Gao Xingxin , Zhang Liming , Xu Jiahong , Meng Lingchao , Tian Yanyun , Zhang Qinqin , Zhou Guangxi
Published: October 2024

Background

Both intestinal and pulmonary systems are parts of the mucosal immune system, comprising ∼80% of all immune cells. These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.

Methods

In this study, we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence, flow cytometry, and Western blotting to confirm the incidence of “nucleus-directed degranulation” in vitro. Subsequently, we conducted a precise analysis using arivis software. Furthermore, using the DSS mouse model of colitis and tissue clearing technologies, we validated the “targeted nuclear degranulation” of neutrophils and their migration to the lungs in an inflammatory intestinal environment.

Result

In this study, we found that among patients with ulcerative colitis, the migration of neutrophils with “targeted nuclear degranulation” from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections. Notably, patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation. Using DSS mice, we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections. These neutrophils rapidly released a high amount of neutrophil extracellular traps to mediate the progression of lung inflammation. Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.

Conclusion

This study revealed that neutrophils accelerate lung inflammation progression in colitis, offering new insights and potential treatment targets for lung infections for patients with colitis.
Different multicellular trichome types coordinate herbivore mechanosensing and defense in tomato
Authors: Sun Chao , Wei JinBo , Gu XinYun , Wu MinLiang , Li Meng , Liu YiXi , An NingKai , Wu KeMeng , Wu ShaSha , Wu JunQing , Xu MeiZhi , Wu Jia-Chen , Wang Ya-Ling , Chao Dai-Yin , Zhang YouJun , Wu Shuang
Published: October 2024

Herbivore-induced wounding can elicit a defense response in plants. However, whether plants possess a surveillance system capable of detecting herbivore threats and initiating preparatory defenses before wounding occurs remains unclear. In this study, we reveal that tomato (Solanum lycopersicum) trichomes can detect and respond to the mechanical stimuli generated by herbivores. Mechanical stimuli are preferentially perceived by long trichomes, and this mechanosensation is transduced via intra-trichome communication. This communication presumably involves calcium waves, and the transduced signals activate the jasmonic acid signaling pathway in short glandular trichomes, resulting in the upregulation of the Woolly (Wo)-SlMYC1 regulatory module for terpene biosynthesis. This induced defense mechanism provides plants with an early warning system against the threat of herbivore invasion. Our findings represent a perspective on the role of multicellular trichomes in plant defense and the underlying intra-trichome communication.
Four MYB transcription factors regulate suberization and nonlocalized lignification at the root endodermis in rice
Authors: Chen Xingxiang , Liu Kui , Luo Tingting , Zhang Baolei , Yu Jinyu , Ma Dan , Sun Xiaoqian , Zheng Huawei , Xin Boning , Xia Jixing
Published: October 2024

In response to variable environments, rice (Oryza sativa) roots have developed lignified and suberized diffusion barriers at the endodermis to permit selective nutrient uptake for optimal growth. Here, we demonstrate that endodermal suberization and nonlocalized lignification are redundantly regulated by 4 MYB transcription factors: OsMYB39a, OsMYB41, OsMYB92a, and OsMYB92b. These transcription factors function downstream of the OsMYB36a/b/c, CASPARIAN STRIP INTEGRITY FACTOR (OsCIF)–SCHENGEN3 (OsSGN3), and stress-inducible signaling pathways in rice. Knockout of all 4 MYB genes resulted in the complete absence of endodermal suberin lamellae (SL) and almost no lignin deposition between the Casparian strip and the cortex-facing lignified band at cell corners under all conditions examined. In contrast, endodermis-specific overexpression of any of these MYB genes was sufficient to induce strong endodermal suberization and nonlocalized lignification near the root tip. Furthermore, OsMYB92a-overexpressing lines showed an altered ionomic profile and enhanced salinity tolerance. Transcriptome analysis identified 152 downstream genes regulated by OsMYB39a/41/92a/92b, including the key SL formation gene OsCYP86A1 and other genes involved in endodermal lignification and suberization under normal and stress conditions. Our results provide important insights into the molecular mechanisms underlying suberization and nonlocalized lignification at the root endodermis and their physiological significance in ion homeostasis and acclimation to environmental stress.
Arabidopsis calcium-dependent protein kinases 4/5/6/11 negatively regulate hydrotropism via phosphorylation of MIZU-KUSSEI1
Authors: Ju Chuanfeng , Javed Laiba , Fang Yanjun , Zhao Yuqing , Cao Chenyu , Deng Yuan , Gao Yaqi , Sun Lv , Wang Cun
Published: October 2024

Hydrotropism facilitates the orientation of plant roots toward regions of elevated water potential, enabling them to absorb adequate water. Although calcium signaling plays a crucial role in plant response to water tracking, the exact regulatory mechanisms remain a mystery. Here, we employed the Arabidopsis (Arabidopsis thaliana) hydrotropism-specific protein MIZU-KUSSEI1 (MIZ1) as bait and found that calcium-dependent protein kinases 4/5/6/11 (CPK4/5/6/11) interacted with MIZ1 in vitro and in vivo. The cpk4/5/6/11 mutant exhibited increased sensitivity to water potential and enhanced root tip curvature. Furthermore, CPK4/5/6/11 primarily phosphorylated MIZ1 at Ser14/36 residues. Additionally, CPK-mediated phosphorylation of MIZ1 relieved its inhibitory effect on the activity of the endoplasmic reticulum–localized Ca2+ pump ECA1, altering the balance between cytoplasmic Ca2+ inflow and outflow, thereby negatively regulating the hydrotropic growth of plants. Overall, our findings unveil the molecular mechanisms by which the CPK4/5/6/11-MIZ1 module functions in regulating plant hydrotropism responses and provide a theoretical foundation for enhancing plant water use efficiency and promoting sustainable agriculture.
TYPHON proteins are RAB-dependent mediators of the trans-Golgi network secretory pathway
Authors: Baral Anirban , Gendre Delphine , Aryal Bibek , Fougère Louise , Di Fino Luciano Martin , Ohori Chihiro , Sztojka Bernadette , Uemura Tomohiro , Ueda Takashi , Marhavý Peter , Boutté Yohann , Bhalerao Rishikesh P
Published: October 2024

The trans-Golgi network (TGN), a key compartment in endomembrane trafficking, participates in both secretion to and endocytosis from the plasma membrane. Consequently, the TGN plays a key role in plant growth and development. Understanding how proteins are sorted for secretion or endocytic recycling at the TGN is critical for elucidating mechanisms of plant development. We previously showed that the protein ECHIDNA is essential for phytohormonal control of hypocotyl bending because it mediates secretion of cell wall components and the auxin influx carrier AUXIN RESISTANT 1 (AUX1) from the TGN. Despite the critical role of ECHIDNA in TGN-mediated trafficking, its mode of action remains unknown in Arabidopsis (Arabidopsis thaliana). We therefore performed a suppressor screen on the ech mutant. Here, we report the identification of TGN-localized TYPHON 1 (TPN1) and TPN2 proteins. A single amino acid change in either TPN protein causes dominant suppression of the ech mutant's defects in growth and AUX1 secretion, while also restoring wild-type (WT)-like ethylene-responsive hypocotyl bending. Importantly, genetic and cell biological evidence shows that TPN1 acts through RAS-ASSOCIATED BINDING H1b (RABH1b), a TGN-localized RAB-GTPase. These results provide insights into ECHIDNA-mediated secretory trafficking of cell wall and auxin carriers at the TGN, as well as its role in controlling plant growth.
Widespread adaptive evolution in angiosperm photosystems provides insight into the evolution of photosystem II repair
Authors: Robbins Elizabeth H J , Kelly Steven
Published: October 2024

Oxygenic photosynthesis generates the initial energy source that fuels nearly all life on Earth. At the heart of the process are the photosystems, which are pigment binding multiprotein complexes that catalyze the first step of photochemical conversion of light energy into chemical energy. Here, we investigate the molecular evolution of the plastid-encoded photosystem subunits at single-residue resolution across 773 angiosperm species. We show that despite an extremely high level of conservation, 7% of residues in the photosystems, spanning all photosystem subunits, exhibit hallmarks of adaptive evolution. Through in silico modeling of these adaptive substitutions, we uncover the impact of these changes on the predicted properties of the photosystems, focusing on their effects on cofactor binding and intersubunit interface formation. By analyzing these cohorts of changes, we reveal that evolution has repeatedly altered the interaction between Photosystem II and its D1 subunit in a manner that is predicted to reduce the energetic barrier for D1 turnover and photosystem repair. Together, these results provide insight into the trajectory of photosystem adaptation during angiosperm evolution.
The Tetratricopeptide repeat protein TaTPR-B1 regulates spike compactness in bread wheat
Authors: Zhu Jun , Huang Feng , Zhai Huijie , Zheng Yi , Yu Jiazheng , Chen Zhaoyan , Fan Yujie , Zhao Huanhuan , Sun Qixin , Liang Rongqi , Ni Zhongfu
Published: October 2024

Spike compactness (SC) is strongly associated with wheat (Triticum aestivum L.) grain yield. In this study, we conducted a quantitative trait locus (QTL) analysis using a doubled haploid (DH) population derived from a cross between two common wheat varieties with contrasting spike morphology, revealing 16 stable QTLs associated with SC. The effect of a major QTL, QSc.cau-6B.1, was validated in 231 F7 recombinant inbred lines (RILs) derived from the same cross as the DH population. Using two residual heterozygous lines (RHLs), we delimited QSc.cau-6B.1 to an approximately 0.5-Mbp physical interval containing four high-confidence genes. The tetratricopeptide repeat-TraesCS6B03G1214400 (TaTPR-B1) was the priority candidate gene according to sequence and expression variations between near-isogenic lines. Accordingly, TaTPR-B1 knockout in the common wheat variety ‘CB037’ significantly increased SC compared to the wild type (WT). Conversely, TaTPR-B1 overexpression in the common wheat variety ‘Fielder’ significantly decreased SC compared to the WT. Moreover, we developed a PCR-based marker targeting the 32-bp insertion/deletion (InDel) between the two TaTPR-B1 alleles, which could be practical and valuable in modern wheat breeding programs for diagnostic purposes. Collectively, these findings provide insight into the genetic basis of SC in common wheat and present a valuable target with a breeder-friendly diagnostic marker for gene pyramid breeding.
Morality and political economy from the vantage point of economics
Authors: Enke Benjamin
Published: October 2024

Political disagreement is increasingly moral, rather than economic, in nature, raising the question how the fields of political economy and moral psychology relate to each other. While these disciplines were initially deeply intertwined, cross-disciplinary exchange became rare throughout the 20th century. More recently, the tide has shifted again—social scientists of different backgrounds recognized that morality and politico-economic outcomes influence each other in rich bidirectional ways. Because psychologists and economists possess distinct and complementary skill sets, part of this movement consists of productive “economic imperialism”—economists leveraging their empirical toolkit to test and substantiate theories from moral psychology at scale or in the wild. To illustrate this, I present two case studies of recent economics research on prominent ideas in moral psychology. First is the theory that morality is ultimately functional—that it evolved as a form of “psychological and biological police” to enforce cooperation, such as in economic production and exchange. Second is that the structure of morality shapes political views and polarization, including on economic issues such as taxation and redistribution. I conclude from these case studies that economists have much to gain from integrating more ideas from moral psychology, and that moral psychologists will be able to make an even more compelling case if they engage with research in economics.
Why partisans feel hated: Distinct static and dynamic relationships with animosity meta-perceptions
Authors: Lees Jeffrey , Cikara Mina , Druckman James N
Published: October 2024

Partisans hold inaccurate perceptions of the other side. What drives these inaccuracies? We address this question with a focus on partisan animosity meta-perceptions (i.e. how much a partisan believes opposing partisans hate them). We argue that predictors can relate to meta-perceptions statically (e.g. at a specific point in time, do partisans who post more about politics on social media differ in their meta-perceptions relative to partisans who post less?) or dynamically (e.g. does a partisan who increases their social media political posting between two defined time points change their meta-perceptions accordingly?). Using panel data from the 2020 US presidential election, we find variables display distinct static and dynamic relationships with meta-perceptions. Notably, between individuals, posting online exhibits no (static) relationship with meta-perceptions, while within individuals, those who increased their postings over time (dynamically) became more accurate. The results make clear that overly general statements about meta-perceptions and their predictors, including social media activity, are bound to be wrong. How meta-perceptions relate to other factors often depends on contextual circumstances at a given time.
How rational inference about authority debunking can curtail, sustain, or spread belief polarization
Authors: Radkani Setayesh , Landau-Wells Marika , Saxe Rebecca
Published: October 2024

In polarized societies, divided subgroups of people have different perspectives on a range of topics. Aiming to reduce polarization, authorities may use debunking to lend support to one perspective over another. Debunking by authorities gives all observers shared information, which could reduce disagreement. In practice, however, debunking may have no effect or could even contribute to further polarization of beliefs. We developed a cognitively inspired model of observers’ rational inferences from an authority’s debunking. After observing each debunking attempt, simulated observers simultaneously update their beliefs about the perspective underlying the debunked claims and about the authority’s motives, using an intuitive causal model of the authority’s decision-making process. We varied the observers’ prior beliefs and uncertainty systematically. Simulations generated a range of outcomes, from belief convergence (less common) to persistent divergence (more common). In many simulations, observers who initially held shared beliefs about the authority later acquired polarized beliefs about the authority’s biases and commitment to truth. These polarized beliefs constrained the authority’s influence on new topics, making it possible for belief polarization to spread. We discuss the implications of the model with respect to beliefs about elections.
Attraction to politically extreme users on social media
Authors: Zimmerman Federico , Bailey David D , Muric Goran , Ferrara Emilio , Schöne Jonas , Willer Robb , Halperin Eran , Navajas Joaquín , Gross James J , Goldenberg Amit
Published: October 2024

Political segregation is a pressing issue, particularly on social media platforms. Recent research suggests that one driver of segregation is political acrophily—people's preference for others in their political group who have more extreme (rather than more moderate) political views. However, acrophily has been found in lab experiments, where people choose to interact with others based on little information. Furthermore, these studies have not examined whether acrophily is associated with animosity toward one's political out-group. Using a combination of a survey experiment (N = 388) and an analysis of the retweet network on Twitter (3,898,327 unique ties), we find evidence for users' tendency for acrophily in the context of social media. We observe that this tendency is more pronounced among conservatives on Twitter and that acrophily is associated with higher levels of out-group animosity. These findings provide important in- and out-of-the-lab evidence for understanding acrophily on social media.
Measuring norm pluralism and perceived polarization in US politics
Authors: Panizza Folco , Dimant Eugen , Kimbrough Erik O , Vostroknutov Alexander
Published: October 2024

Recent research has shown how norms shape political and economic decision-making. Much of this work assumes that a single norm influences the behavior of all people, but in fact, many situations are characterized by the existence of competing normative viewpoints. We apply a method for measuring belief in the simultaneous existence of multiple norms. Such multiplicity arises naturally when norms are associated with distinctive groups, and thus political polarization can be characterized, in part, as a product of diverging norms between groups. We thus assess the validity of our measurement technique by testing whether it can recover polarization on seven salient political issues on which US Democrats and Republicans tend to hold different views. We then compare the norms elicited by our method to the norms of Democrats and Republicans elicited in a separate sample using an established and validated—but methodologically less rich—measurement approach. Our study uncovers a wide range of co-existing views between and within political groups. Partisans understand their group’s norms and hold personal views that align with them. They can also recognize the diversity and polarization in US public opinion by identifying norms specific to political parties and acknowledging the variety of views within their own parties, which may indicate internal divisions. This research underscores the importance of nuanced approaches to political norms that go beyond party lines. By acknowledging a plurality of views, we can encourage productive discussions and bridge ideological divides.
Unraveling polarization: Insights into individual and collective dynamics
Authors: Kish Bar-On Kati , Dimant Eugen , Lelkes Yphtach , Rand David G
Published: October 2024

Polarization poses a critical threat to the stability of nations around the world, as it impacts climate change, populism, democracy, and global health. This perspective examines the conceptual understanding, measurement challenges, and potential interventions for polarization. Our analysis highlights the distinction and interactions between the individual and collective levels of polarization, conceptually, methodologically, and in terms of interventions. We conclude by pointing out future directions for understanding polarization and highlighting the interrelations between polarization and other social phenomena.
A potential evolutionary trap for the extended phenotype of a nematomorph parasite
Authors: Sawada Yuna , Sato Nozomu , Osawa Takeshi , Matsumoto Kazuma , Chiu Ming-Chung , Okada Ryuichi , Sakura Midori , Sato Takuya
Published: October 2024

Human activities introduce new environmental cues to wild organisms, leading to maladaptive behavioral and life history decisions known as the “evolutionary trap.” This trap is thought to be a major conservation concern for free-living organisms. However, it has never been studied in endosymbionts, one of the most successful and diverse life forms on Earth. Here, we examine this trap in the extended phenotype of a parasite that exploits the visual system of hosts to alter host behavior for its benefit. Arboreal mantids infected by nematomorph parasites are drawn to horizontally polarized light, thereby inducing them to enter the water. In this study, we found that the degree of linear polarization (DOP) of reflected light served as a reliable environmental cue for identifying perennial waters, where nematomorphs can survive in their aquatic life stage without drying out. Infected mantids exhibit attraction to horizontally polarized light with higher DOP in behavioral assays and jumped into pools reflecting light with higher DOP in field experiments. The asphalt road reflected horizontally polarized light closely resembling the polarization levels observed in perennial waters, likely leading to a higher prevalence of mantids on asphalt roads compared with those found in natural arboreal habitats. In a field experiment, we observed infected mantids walking on asphalt roads more often than on cement roads. These findings imply that evolutionary traps can endanger endosymbionts beyond their hosts that directly perceive environmental cues.
Maternity care coordinator’s experiences at the department of Veteran Affairs
Authors: Ndakuya-Fitzgerald Florine , Farkas Amy , Lopez Alexa A , Whittle Jeff , Haeger Kristin O , Mu Qiyan
Published: October 2024

The Veterans Health Administration (VHA) provides maternity care by paying for Veterans to receive pregnancy-related care in community settings and by utilizing maternity care coordinators (MCCs) at each medical facility. The purpose of this qualitative descriptive study was to understand the MCC’s experiences performing their role across VA facilities. Thirty MCCs were recruited and interviewed virtually using Microsoft Teams. Interviews were recorded and transcribed verbatim. Using thematic analysis, transcripts were coded, and themes were derived. MCC’s roles include being a liaison, care coordinator, and supporter. MCCs improve Veterans’ care during pregnancy and postpartum by education, monitoring health status, and connecting Veterans to providers within VA and the community. Across VA facilities, there was variation in how MCCs engaged with Veterans and in the services provided. A challenge shared was the lack of dedicated time to the role. In the VA, MCCs are valuable in ensuring high-quality care coordination of pregnant/postpartum Veterans despite the fragmentation of care between VA and community providers. To improve inconsistencies in how the MCC program is implemented, systematic strategies such as ensuring dedicated time are needed.
The efficient enforcement challenge of secured transactions law reforms in civil law systems—self-help repossession, strict foreclosure, and other methods for the acceleration of enforcement of security interests
Authors: Tajti (Thaythy) Tibor
Published: October 2024

Although the forging of an efficient system for enforcement of security interest is one of the central expectations of secured transaction law reforms in civil law systems, the results hardly give reason for satisfaction. As the reforms tend to be supported and influenced by various international organizations’ projects (especially the World Bank, the European Bank for Reconstruction and Development, the International Institute for the Unification of Private Law, and the United Nations Commission on International Trade Law), most out-of-court methods of enforcement of security interests have played a central role. Yet due to civil law’s general hostility towards self-help as such, either the introduction of the concept has been rejected or the local limited-reach kin have been merely ‘paper tigers’. Similarly, although security interests on several types of collateral (accounts, investment property) or on the workhorse of the English financial system—the floating charge—have also been enforced extrajudicially (save the exceptions), little attention has been attributed to these enforcement modalities. The same applies to strict foreclosure in civil law systems still being prohibited, or restricted, and thus rarely resorted to, due to the inherited hostility towards the doctrine of lex commissoria. Rethinking local laws on preliminary and temporary court orders to match them with such globally known ex parte preliminary measures as the English Mareva Injunction or the French Saisie Conservatoire, which allow creditors to swiftly freeze debtors’ assets and thus substitute self-help repossession, has also been given short shrift. The enforcement segment, consequently, remains the Achilles’ heel of secured transaction law reforms in civil law systems. This article desires to contribute to reform literature by addressing these deficiencies and by offering tested, fully or partially fitting, functional equivalents of self-help repossession.
Retirement through rose-colored glasses: greater positivity bias in retired relative to working older adults
Authors: Ferguson Lorena A , Harikumar Amritha , Leal Stephanie L
Published: October 2024

Retirement has been associated with declines in memory beyond typical age-related memory decline. This may impact the ability to remember distinct events, as older adults (OA) are susceptible to interference in memory across experiences with overlapping features. Impaired hippocampal pattern separation, a computation that allows for the disambiguation of similar experiences as unique events, is thought to underlie age-related impairment in memory. Furthermore, positive experiences tend to be better remembered than neutral or negative experiences in aging. Socioemotional selectivity theory suggests that awareness of a limited remaining lifespan leads OA to prioritize emotionally fulfilling experiences, often leading to a bias towards positive information compared to negative or neutral information. However, the potential role of retirement in contributing to these age-related changes in memory has yet to be examined. Memory measures that tax hippocampal pattern separation may be more sensitive to memory impairment in retirement compared to standard memory measures. Retirement may exacerbate awareness of reduced remaining time, such that retired OA may experience a greater positivity bias in memory than their working peers. Here, we utilized an emotional memory task that taxes hippocampal pattern separation to examine memory in age-matched retired and working OA. We found that retired OA show selective impairments for memories with high interference and a greater positivity bias in memory compared to their working peers. These findings suggest that retirement may accelerate age-related memory changes, including greater susceptibility to interference as well as a bias toward remembering positive relative to neutral information.