bluuebunny/crossref_metadata_2025 huggingface dataset:
The Advaita Vedānta Monastic Tradition of Nampūtiri Brahmins in Kerala: Tracing the Order’s History in the Inscriptional Evidence
Authors: Nowicka Olga
Published: November 2024

This article attempts to reconstruct the origins of the Nampūtiri Advaita Vedānta maṭhas in Kerala, which constitute an independent vernacular variant of Śaṅkaran monasticism. The early history of the Nampūtiri monastic centres of Kerala still remains very much obscure. This article aims to fill the lacuna and propose a working hypothesis of order in question, tracing its sources to the local institution of a ‘temple saṃnyāsin’, referred to in the Keralan epigraphs as bhaṭāra-tiruvaṭi or paḻāra-tiruvaṭi. In order to reconstruct the early history of the local monastic tradition, I focus primarily on the available inscriptional material, which I discuss at length in the latter part of the article, that follows the elaborate description of the vernacular sampradāya based on the ethnographic material, constituting foundation for integrating the epigraphic evidence.
Landscape and diel fear cycles: linear features are perceived as risky by peccary (Dicotyles tajacu)
Authors: Esparza-Carlos Juan Pablo , Íñiguez-Dávalos Luis Ignacio , Laundré John William , Casimiro Hernández Tokya Stephanya , Arias-Del Razo Itzel
Published: November 2024

The risk of encountering a predator triggers different antipredator strategies in the prey, including spatial (landscape level), temporal (daily activity cycles), and behavioral changes. There is evidence that linear landscape attributes (e.g., dirt roads, firebreaks, trails) are used by both predators and prey, although studies examining how they react to mutual use are scarce. We propose a conceptual model that explains how prey might change their activity patterns under spatial-scale scenarios of predation risk. We test our predictions with Jaguar (Panthera onca) and Puma (Puma concolor) as predators and Collared Peccary (Dicotyles tajacu) as the prey. Peccary activity patterns differed between foraging areas with different levels of predation risk, with low-risk areas showing 2 peaks of activity around dusk, but exclusively diurnal in high-risk areas. The highest overlap coefficient (Δ^1 = 0.82) occurred when comparing peccary activity patterns near linear attributes and high-risk foraging areas, and the lowest (Δ^1 = 0.16) between high-risk foraging areas and Jaguar activity patterns, showing a completely diurnal pattern when the Jaguar was inactive. The overlap coefficient was intermediate (Δ^1 = 0.45) when comparing Puma and peccary activity patterns in high-risk areas. The observed similarity in peccary activity patterns between high-predation-risk foraging areas and linear attributes seems to indicate that the latter are also perceived as high-risk areas that lead to changes in their activity patterns.
Dermacentor species (Acari: Ixodidae) in western Canada, with detection of Dermacentor similis
Authors: Nichol Grace K , Lado Paula , Snyman Louwrens P , Dergousoff Shaun J , Weese J Scott , Greer Amy L , Clow Katie M
Published: November 2024

Numerous tick species are undergoing significant range expansion in Canada, including several Dermacentor spp Koch (Acari: Ixodidae). With the recent description of Dermacentor similis Lado in the western United States, additional research is required to determine the current range of this species. Five hundred ninety-eight Dermacentor spp. were collected from companion animals in the western Canadian provinces of British Columbia, Alberta, and Saskatchewan. Ticks were morphologically identified to species, followed by PCR and gel electrophoresis of the ITS-2 partial gene target (n = 595). Ninety-seven percent (n = 579/595) generated valid banding patterns. The banding pattern for the majority (74%, n = 206/278) of Dermacentor spp. from southern British Columbia was consistent with D. variabilis (Say), while 26% (n = 72/278) was consistent with D. andersoni Stiles. For samples from Alberta, 38% (n = 3/8) had banding patterns consistent with D. variabilis and 63% (n = 5/8) with D. andersoni. All (n = 293) ticks from Saskatchewan had banding patterns consistent with D. variabilis. After the description of D. similis was published, DNA sequencing of mitochondrial (16S rDNA gene, COI gene) and nuclear (ITS-2) markers was used to confirm the identity of 40 samples. Twenty-seven samples that had banding patterns consistent with D. variabilis from British Columbia were confirmed to be D. similis. One sample from Alberta and five from Saskatchewan were confirmed to be D. variabilis and seven samples from British Columbia were D. andersoni. The ITS-2 amplicons were not useful for differentiating between D. variabilis and D. similis. These results provide evidence of D. similis in western Canada and highlight that sequences of the mitochondrial genes are effective for distinguishing D. andersoni, D. variabilis, and D. similis.
Analyzing the Disparity in Application of the Laws Governing Foreign Fighters: A Securitization Theory Approach
Authors: İbrahim Matti Izora , Kaya Taylan Özgür
Published: November 2024

The Copenhagen School’s securitization theory provides a useful framework for analyzing how terrorism was constructed as an existential threat to international peace and security in the aftermath of 9/11. The purpose of this study is to shed light on the possible disparity in application of the laws governing foreign fighters, embodied in United Nations Security Council Resolution (UNSCR) 1373 (2001), UNSCR 2178 (2014), and EU Directive 541 (2017), as a result of the definitional vagueness in the legal frameworks. Specifically, we argue that the securitization of the terms “terrorism” and “foreign terrorist fighter” in these legal frameworks has created a precedent for categorically differentiating foreign fighters who traveled to the Syrian/Iraqi conflict as “terrorists,” while largely characterizing foreign fighters who traveled to the Russo-Ukrainian conflict as benign “volunteers” or just “foreign fighters.” We further argue that this dichotomy not only oversimplifies the complex nature of these conflicts and the motivations of the individuals involved but fails to capture the security challenges posed by far-right extremists and other ideologically motivated fighters in the Russo-Ukrainian conflict. The findings suggest whether an act is called “terrorism” or whether a foreign fighter is perceived as a foreign terrorist fighter depends more on how powerful institutions and political actors frame and present it, rather than on any inherent qualities of the act itself. The key factor is how the individual is perceived and how the act is interpreted and understood within a society.
Association of testosterone replacement therapy with atrial fibrillation and acute kidney injury
Authors: Greenberg Daniel R , Kohn Taylor P , Asanad Kian , Brannigan Robert E , Halpern Joshua A
Published: November 2024

Background

Secondary analyses of the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial revealed significantly higher rates of new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in the testosterone replacement therapy (TRT) cohort.

Aim

To validate the secondary findings of the TRAVERSE trial.

Methods

We utilized the TriNetX Research Network to identify a cohort of men ages 45-80 years old who met similar inclusion criteria to the TRAVERSE trial. We compared hypogonadal men (testosterone 100-300 ng/dL) who had a prescription for topical testosterone therapy and men who did not. Propensity score matching was used to match patient populations. Kaplan Meier survival analysis was used to determine the relative risk of new-onset AF and AKI within 3 years.

Outcomes

New-onset AF and AKI within 3 years.

Results

There were 2134 men included in each cohort after propensity score matching. Men on TRT had significantly lower testosterone (T) at the time of diagnosis compared to men not prescribed TRT (207 ± 66 ng/dL vs 246 ± 140 ng/dL, P < 0.001). Kaplan–Meier survival analysis showed a significantly increased risk of AKI among men on TRT (RR 1.53, 95% CI 1.07-2.18). However, TRT was not associated with a significantly increased risk of new-onset AF (RR 1.48, 95% CI 0.93-2.37).

Clinical Implications

Hypogonadal men with underlying cardiovascular risk factors or pre-existing cardiovascular disease who receive TRT may be at increased risk of AKI after starting therapy.

Strengths and Limitations

We evaluated a large global research database and utilized similar inclusion and exclusion to the TRAVERSE trial. However, our results are limited by the retrospective study design and reliance on documented claims data.

Conclusion

Similar to the TRAVERSE trial, our study demonstrated an increased risk of AKI among men on TRT, but did not find increased risk of AF. However, further studies are required to validate these results.
House Price Index as an early indicator of development risk to biodiversity
Authors: Acosta Alamo Marlen , Manne Lisa L , Veit Richard R
Published: November 2024

Habitat loss due to changes in land cover is one of the main causes of biodiversity decline worldwide. Habitat loss occurs disproportionately in areas of high biodiversity because these same areas are particularly suitable for development. We assessed the effect of development risk on the biodiversity of breeding birds in the United States. We compared the effect of two predictors of habitat loss on the richness, abundance, and rarity of woodland, open-habitat, and urban birds at the local and regional levels. We used the House Price Index—as a measure of development risk—and primary productivity as predictors in simulations of habitat loss. For local scale analysis, we used generalized regression models. For regional-scale habitat loss simulations, we statistically compared the results obtained from each predictor. Locally, development risk and primary productivity interacted in their effect on the richness, abundance, and rarity index of all birds. At the regional level, development risk predicted larger declines in richness and abundance and increases in the rarity of open-habitat birds following habitat loss than primary productivity. For woodland birds, both risk of development- and primary productivity-ordered habitat loss affected richness and rarity levels, while primary productivity had a larger effect on their abundance. The diversity of urban birds was less affected by habitat loss than the other groups of birds. Our study is the first to investigate the usefulness of the House Price Index as a measure of development risk and as a predictor of biodiversity. Proactively recognizing high-development risk areas affords more time for targeted conservation plans in those areas.
Associations between glycemic status and the ratio of γ-glutamyl transferase to HDL-C in middle-aged women
Authors: Wakabayashi Ichiro
Published: November 2024

Objective

The ratio of γ-glutamyl transferase to HDL-C (GGT/HDL-C) has been proposed as a discriminator of metabolic syndrome. The purpose of this study was to elucidate the relationship between GGT/HDL-C and glycemic status in women.

Methods

The subjects were 18,218 middle-aged women who had received annual health checkups in their workplaces. They were divided by habitual alcohol intake into nondrinkers, occasional drinkers, regular light drinkers, and regular heavy drinkers.

Results

In overall subjects, hemoglobin A1c level and prevalence of diabetes tended to be higher in subjects with higher GGT/HDL-C, and GGT/HDL-C tended to be higher with an increase of alcohol intake. The odds ratio for hyperglycemia in subjects with vs. subjects without high GGT/HDL-C tended to be lower with an increase of alcohol intake, and the association between high GGT/HDL-C and hyperglycemia was significantly weaker in regular heavy drinkers than in nondrinkers.

Conclusion

In middle-aged women, there were positive associations of GGT/HDL-C with alcohol intake and glycemic status, and the association between GGT/HDL-C and glycemic status tended to be weaker with an increase of alcohol intake. Thus, alcohol use should be taken into account when GGT/HDL-C is used as a discriminator of diabetes.
The hard, bloodless surface of a mirror: Patricia Highsmith’s Kierkegaardian anatomy of anxiety
Authors: Adams Don
Published: November 2024

This essay considers Patricia Highsmith’s Ripley novels in relation to the philosophy of Søren Kierkegaard, which Highsmith knew and admired, and argues for the ethical earnestness of Highsmith’s fiction. The essay interprets Tom Ripley as an implicit allegorical expression of the Kierkegaardian demonic, which is the ultimate condition of the individual living in despair, without ethical purpose or existential possibility. When read from a Kierkegaardian existentialist perspective, the Ripley novel series is revealed as an extended ethical cautionary tale for the contemporary reader in a nihilistic age of anxiety.
Implementation of a High-Reliability Organization Framework in a Large Integrated Health Care System: A Pre–Post Quasi-Experimental Quality Improvement Project
Authors: Sawyer Aaron M , Thiyarajan Sreedevi , Essen Keith , Pendley-Louis Robin , Sculli Gary L , Yackel Edward E
Published: November 2024

Introduction

The purpose of this quality improvement (QI) project was to evaluate outcomes across Veterans Health Administration (VHA) hospital facilities engaged in an enterprise-wide implementation of a high-reliability organization (HRO) framework.

Materials and Methods

This QI project relied on primary data drawn from 139 facilities nationwide from 2019 to 2023. Data sources included the All Employee Survey Patient Safety Culture (PSC) Module and patient safety reporting data derived from the Joint Patient Safety Reporting system. The project design applied a pre–post quasi-experimental design that examined within-cohort changes at pre-intervention, intervention, and 2 post-intervention follow-up timepoints. HRO interventions included a combination of training, leadership coaching, site assessments, and experiential learning. HRO interventions were initiated at 18 facilities beginning in 2019 (Cohort 1), 54 facilities in 2020 (Cohort 2), and 67 facilities in 2021 (Cohort 3). For between-cohort analyses, the relative degree of change within Cohort 1 sites was compared with all other sites.

Results

There were broad positive within-group trends for PSC scores across all sites, and domain-specific between-group differences in PSC Dimension 2—Risk Identification and Just Culture—and Dimension 4—Error Transparency and Risk Mitigation. For patient safety reporting, total events reported, and close calls increased for Cohort 1. The ratio of close calls to adverse events also increased for both Cohort 1 and all other VHA sites at post-intervention year 2.

Conclusions

The results of this QI project will inform further refinements to VHA’s efforts to implement HRO principles and practices in the nation’s largest integrated health system. In addition, the implementation practices may inform other large-scale, multi-level efforts to improve quality and patient safety.
Targeting the IDH1R132H mutation in gliomas by CRISPR/Cas precision base editing
Authors: Weber Remi , Vasella Flavio , Klimko Artsiom , Silginer Manuela , Lamfers Martine , Neidert Marian Christoph , Regli Luca , Schwank Gerald , Weller Michael
Published: November 2024

Background

Gliomas, the most frequent malignant primary brain tumors, lack curative treatments. Understanding glioma-specific molecular alterations is crucial to develop novel therapies. Among them, the biological consequences of the isocitrate dehydrogenase 1 gene mutation (IDH1R132H) remain inconclusive despite its early occurrence and widespread expression.

Methods

We thus employed CRISPR/Cas adenine base editors, which allow precise base pair alterations with minimal undesirable effects, to correct the IDH1R132H mutation.

Results

Successful correction of the IDH1R132H mutation in primary patient-derived cell models led to reduced IDH1R132H protein levels and decreased production of 2-hydroxyglutarate, but increased proliferation. A dual adeno-associated virus split intein system was used to successfully deliver the base editor in vitro and in vivo.

Conclusions

Taken together, our study provides a strategy for a precise genetic intervention to target the IDH1R132H mutation, enabling the development of accurate models to study its impact on glioma biology and serving as a framework for an in vivo gene therapy.
Cell migration simulator-based biomarkers for glioblastoma
Authors: Hou Jay , McMahon Mariah , Jubenville Tyler , Sarkaria Jann N , Chen Clark C , Odde David J
Published: November 2024

Background

Glioblastoma is the most aggressive malignant brain tumor with poor survival due to its invasive nature driven by cell migration, with unclear linkage to transcriptomic information. The aim of this study was to develop a physics-based framework connecting to transcriptomics to predict patient-specific glioblastoma cell migration.

Methods and Results

We applied a physics-based motor-clutch model, a cell migration simulator (CMS), to parameterize the migration of glioblastoma cells and define physical biomarkers on a patient-by-patient basis. We reduced the 11-dimensional parameter space of the CMS into 3 principal physical parameters that govern cell migration: motor number—describing myosin II activity, clutch number—describing adhesion level, and F-actin polymerization rate. Experimentally, we found that glioblastoma patient-derived (xenograft) cell lines across mesenchymal (MES), proneural, and classical subtypes and 2 institutions (N = 13 patients) had optimal motility and traction force on stiffnesses around 9.3 kPa, with otherwise heterogeneous and uncorrelated motility, traction, and F-actin flow. By contrast, with the CMS parameterization, we found that glioblastoma cells consistently had balanced motor/clutch ratios to enable effective migration and that MES cells had higher actin polymerization rates resulting in higher motility. The CMS also predicted differential sensitivity to cytoskeletal drugs between patients. Finally, we identified 18 genes that correlated with the physical parameters, suggesting transcriptomic data alone could potentially predict the mechanics and speed of glioblastoma cell migration.

Conclusions

We describe a general physics-based framework for parameterizing individual glioblastoma patients and connecting to clinical transcriptomic data that can potentially be used to develop patient-specific anti-migratory therapeutic strategies.
Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: A case series
Authors: Zeremski Vanja , Haage Tobias Ronny , Mougiakakos Dimitrios
Published: November 2024

Background

Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients.

Methods

Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX).

Results

We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL.

Conclusion

Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.
Evaluation of methods to estimate nocturnal bird migration activity: A comparison of radar and nocturnal flight call monitoring in the American West
Authors: Osterhaus Dylan M , Van Doren Benjamin M , Horton Kyle G , Abadi Fitsum , Wright Timothy F , Desmond Martha J
Published: November 2024

Bird migration involves the movements of billions of individuals but is difficult to study because it occurs primarily at night. We sought to improve our understanding of the methods available to study migration, particularly in understudied regions of western North America. We evaluated 2 methods: weather radar and nocturnal flight call monitoring. We analyzed variability in estimates of migration activity from each method, how estimates relate, and identified factors associated with variation in this relationship. We collected radar and flight call data from southern New Mexico in western North America during the fall migration of 2021 and 2022. Similar studies have occurred in eastern North America, but it is unknown if regional variability alters the relationship between estimates from each method. We found that estimates were positively related across a season, but relationships were variable among nights. Also, we discovered that the strength of the association between methods varied across sites, indicating that local factors may influence acoustic sampling. We determined that variation in acoustic estimates of migration activity was associated with cloud cover, crosswind, date, migrant height, migrant speed, moon illumination, tailwind, and time of night. For radar, we found crosswind, date, migrant height, migrant speed, tailwind, and time of night to be associated with variations in estimates of migration activity. Overall, our findings support those of previous studies from eastern North America and demonstrate that, despite regional differences, estimates from each method are also correlated in western North America. Our findings provide new insight into factors associated with variation in estimates of migration activity from 2 widely used methods and an improved understanding of factors that impact migration behavior.
Prey selection by Chordeiles minor (Common Nighthawk) does not reflect differences in prey availability between breeding and nonbreeding grounds
Authors: Stein Eliza D , Fariña Nestor , Villalba Olga , Cockle Kristina L , Zubarán Gastón E , Snider Allison M , Baldo Diego , Cox James A , Taylor Sabrina S
Published: November 2024

Predators may adjust their diets to match their energy needs and food availability, but these adjustments have not been explored for migratory aerial insectivores outside of the breeding grounds. We found that Chordeiles minor (Common Nighthawk), a long-distance migrant and member of the rapidly declining aerial insectivore guild, exhibited similar levels of diet richness, diet diversity, and prey selectivity on the breeding and nonbreeding grounds, despite large differences in prey abundance. We examined the diets and prey communities of C. minor during 2 breeding seasons in Florida, USA, and 2 nonbreeding seasons in Corrientes Province, Argentina (2020 to 2022). We used DNA metabarcoding to identify insect prey in C. minor fecal samples, and we employed Malaise and UV light traps to assess abundance and composition of aerial insect prey communities. Abundance and richness of available prey were significantly higher on the nonbreeding grounds than on the breeding grounds. Even so, C. minor exhibited similar within-sample and within-population diet richness, Shannon and Simpson diversities, and prey preferences at both sites. Adults differed in their consumption of Lepidoptera between sites: adults on the nonbreeding grounds preferred Lepidoptera over all other orders, whereas adults on the breeding grounds consumed Lepidoptera less frequently than expected. We suggest that breeding adult C. minor may deliver Lepidoptera to their young instead of consuming this prey. At both sites, C. minor showed preference for Hemiptera and Hymenoptera–both large-bodied, nutrient-rich prey–suggesting that these generalist predators exhibit less diet flexibility than previously thought and thus may be vulnerable to changes in prey communities at multiple points in the annual cycle.
The Legal Fabrique of Global Security Governance
Authors: Mignot-Mahdavi Rebecca
Published: November 2024

This article scrutinizes diverse institutions and processes within the framework of the global security architecture to unveil the intricate legal fabrique of global security governance (GSG). This fabrique encompasses both the processes and outcomes of norm production in these sites of GSG. The legal norms produced—regardless and sometimes because of their formal non-bindingness—interlace to form tight webs of norms. These webs of norms, in turn, stabilize practices that wield significant effects on individuals and societies, spanning domestic and transnational realms. A major implication of this argument is that, while international law ostensibly adheres to a dichotomy between soft and hard law, this demarcation reveals a conceptual framework that might, at best, be illusory and at worst, stand as one of the most misleading constructs within orthodox international legal thought. Recognizing that the norms originating from multiple sites of GSG form and reveal a tight, cohesive legal fabrique opens avenues, not only for refining existing theoretical reflections and international legal vocabularies on global (security) governance but also for recognizing the pivotal significance of this legal fabrique.
Caribbean Court of Justice (CCJ)
Authors: Berry David S.
Published: November 2024

The four judgments issued by the Caribbean Court of Justice in its original jurisdiction over the period 2022–2023 usher in several firsts. Belize v. Trinidad and Tobago was the first state-to-state dispute under Article 211(a) of the Revised Treaty of Chaguaramas (RTC). The Court also first addressed the issue of whether a state could bring a claim on behalf of a national (i.e., diplomatic protection). The case of Ellis Richards et al. v. Trinidad and Tobago was the first to consider Article 30 of the RTC, a provision which excludes activities involving the exercise of governmental authority from the scope of Chapter Three. In the same period, the Court considered issues related to evidence, the relation of CARICOM to the WTO system, and whether potential new claimants can be added to an original jurisdiction case.
Know your limits; miniCOI metabarcoding fails with key marine zooplankton taxa
Authors: Albaina Aitor , Garić Rade , Yebra Lidia
Published: November 2024

Eleven years after the publication of the first work applying deoxyribonucleic acid (DNA) metabarcoding to zooplankton communities, the commonly known “miniCOI” barcode is widely used, becoming the marker of choice. However, several primer combinations co-exist for this barcode and a critical evaluation of their performance is needed. This article reviews the misperformance of miniCOI metabarcoding with marine zooplankton communities, comparing them to microscopy and/or other universal markers. In total, misperformances were reported for 26 zooplankton taxa, including 18 copepods and five tunicates. We report a detection failure with Class Appendicularia and contrasting performances for Oithona similis (from good correspondence to detection failure), two worldwide abundant taxa with a crucial role in the marine pelagic realm. A combination of forward primer mismatches, the presence of long poly-T inserts and a low number of reference sequences would explain the failure to detect appendicularians. However, the contrasting performance with O. similis would correspond to distinct numbers of mismatches in the forward primer in different lineages within this cryptic taxon. This is reinforced by the report of similar patterns with other locally abundant zooplankton taxa. Therefore, we strongly call for the use of miniCOI in combination with alternative methods capable of addressing these limitations.
Protective Factors Predict Resilient Outcomes in Clinical High-Risk Youth with the Highest Individualized Psychosis Risk Scores
Authors: Cadenhead Kristin S , Addington Jean , Bearden Carrie E , Cannon Tyrone D , Cornblatt Barbara A , Keshavan Matcheri , Mathalon Daniel H , Perkins Diana O , Stone William , Walker Elaine F , Woods Scott W
Published: November 2024

Background and Hypothesis

Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator.

Study Design

CHR participants (N = 572) from NAPLS3 were assessed on the Risk Calculator. Those who scored in the top half of the distribution and had 2 years of follow-up (N = 136) were divided into those who did not convert to psychosis (resilient, N = 90) and those who did (nonresilient, N = 46). Groups were compared based on candidate protective factors that were not part of the Risk Calculator. Better functional outcome was also examined as an outcome measure of resiliency. Study Results: Exploratory analyses suggest that Hispanic heritage, social engagement, desirable life experiences, premorbid functioning and IQ are all potential protective factors that predict resilient outcomes. Reduced startle reactivity, brain area and volume were also associated with greater resilience.

Conclusions

The primary focus of CHR research has been the risk and prediction of psychosis, while less is known about protective factors. Clearly, a supportive childhood environment, positive experiences, and educational enrichment may contribute to better premorbid functioning and brain development, which in turn contribute to more resilient outcomes. Therapies focused on enhancing protective factors in the CHR population are logical preventive interventions that may benefit this vulnerable population. Future CHR research might use similar models to develop a “protective index” to predict resilient outcomes.
Second generation multiple channeling using platelet-rich plasma enhances cartilage repair through recruitment of endogenous MSCs in bone marrow
Authors: Lee Min Ji , Jiang Jian , Kim Soo Hyun , Jo Chris Hyunchul
Published: November 2024

In the treatment of cartilage defects, a key factor is the adequate and specific recruitment of endogenous stem cells to the site of injury. However, the limited quantity and capability of endogenous bone marrow stem cells (BM MSCs) often result in the formation of fibrocartilage when using bone marrow stimulation (BMS) procedures. We engineered second-generation platelet-rich plasma (2G PRP) with defibrinogenating and antifibrinolytic agents for injection into the condyle of the right femur, followed by multiple channeling (MCh) 5 days later. This approach aims to enhance repair by promoting the local proliferation and migration of BM MSCs to the full-thickness knee cartilage defect (ftKD). In our in vitro study, 2G PRP increased the number of endogenous BM MSCs and their ability to migrate toward an IL-1β-induced inflammatory condition. This significance was further confirmed by in vivo proliferation results after injection of 2G PRP into the condyle of rats. Fifty-four healthy male Sprague-Dawley rats were divided into 3 groups (ftKD, MCh, 2G MCh) for 3 time points (2 weeks, 4 weeks, 8 weeks). The 2G MCh (2G PRP injection + MCh) groups significantly improved cartilage formation at 4 and 8 weeks compared to the ftKD and MCh groups. The 2G MCh initiated cartilage repair earlier than MCh and significantly enhanced up to 8 weeks. This study demonstrated that 2G PRP increased the number of BM MSCs through the enhancement of proliferation and recruitment into the injured site, thereby improving articular cartilage repair.
Trehalose biosynthetic genes are involved in the development and pathogenesis in the poplar canker fungus Cytospora chrysosperma
Authors: Xu Siying , Li Quansheng , Jin Haojie , Li Aining , Wang Yonglin
Published: November 2024

Poplar Cytospora canker, caused by Cytospora chrysosperma, is one of the most destructive and widespread poplar diseases worldwide, especially in northern China. However, our current understanding of its pathogenic mechanisms remains limited. Here, we showed that trehalose biosynthetic genes, such as trehalose-6-phosphate synthase 1 (Tps1), trehalose-6-phosphate phosphatase (Tps2), and the regulatory subunit (Tps3), play important roles in the development and virulence of C. chrysosperma. The targeted deletion mutants showed reduced trehalose synthesis and were defective in hyphal growth and conidiation. Deletion of any of the three genes attenuated virulence in poplar twigs and stronger poplar defense responses were triggered once inoculated by the mutants. Additionally, the mutants exhibited increased sensitivity to H2O2 and cell wall stressors. Taken together, the finding suggests that trehalose biosynthetic genes contribute to fungal development, stress responses, and full virulence in C. chrysosperma.
Nondestructive Seed Genotyping via Microneedle-Based DNA Extraction
Authors: Li Mingzhuo , Poonam Aditi Dey , Cui Qirui , Hsieh Tzungfu , Jagadeesan Sumeetha , Bruce Wes , Vogel Jonathan T. , Sessions Allen , Cabrera Antonio , Saville Amanda C. , Ristaino Jean , Paul Rajesh , Wei Qingshan
Published: November 2024

Crop breeding plays an essential role in addressing food security by enhancing crop yield, disease resistance, and nutritional value. However, the current crop breeding process faces multiple challenges and limitations, especially in genotypic evaluations. Traditional methods for seed genotyping remain labor-intensive, time-consuming, and cost-prohibitive outside of large-scale breeding programs. Here, we present a handheld microneedle (MN)-based seed DNA extraction platform for rapid, nondestructive, and in-field DNA isolation from crop seeds for instant marker analysis. Using soybean seeds as a case study, we demonstrated the use of polyvinyl alcohol (PVA) MN patches for the successful extraction of DNA from softened soybean seeds. This extraction technology maintained high seed viability, showing germination rates of 82% and 79%, respectively, before and after MN sampling. The quality of MN-extracted DNA was sufficient for various genomic analyses, including PCR, LAMP, and whole genome sequencing. Importantly, this MN patch method also allowed for the identification of specific genetic differences between soybean varieties. Additionally, we designed a 3D-printed extraction device, which enabled multiplexed seed DNA extraction in a microplate format. In the future, this method could be applied at scale and in-field for crop seed DNA extraction and genotyping analysis.
Detection of airborneCoccidioidesspores using lightweight portable air samplers affixed to uncrewed aircraft systems in California’s Central Valley
Authors: Radosevich Molly T. , Dobson Sarah , Weaver Amanda K. , Lampman Phinehas , Kollath Daniel , Couper Lisa , Campbell Grace , Taylor John W. , Remais Justin V. , Kobziar Leda , Markwiese James , Head Jennifer R.
Published: November 2024

Coccidioidomycosis is an emerging fungal infection caused by inhalation ofCoccidioidesspp. spores. While airborne dispersal is critical toCoccidioidestransmission, limited recovery of the pathogen from air has hindered understanding of the aerosolization and transport of spores. Here, we examine uncrewed aircraft systems (UAS) with portable, active air samplers as a novel means of capturing aerosolizedCoccidioidesand characterizing emissions and exposure risk. We sampled in September 2023 in eastern San Luis Obispo County, California, in an area with confirmedCoccidioides immitisin soils. We completed 41 20-minute flights across 14 sites using UAS equipped with an 8 L/min bioaerosol sampler and a low-cost particulate matter sensor. We sampled source soils and air under ambient conditions using one UAS at 1-10 m above ground level, and under a simulated high-dust event using two UAS, one at <2 m height and one at 5-12 m. We detectedCoccidioidesDNA in two of 41 air samples (4.9%), both under ambient conditions at 8 m above ground level, representing the highest known height of airborneCoccidioidesdetection. Spatially explicit UAS-based sampling could enhance understanding ofCoccidioidesaerobiology and enable detection in hard-to-reach or hazardous air masses, including dust storms and wildfire smoke.

Synopsis

UAS-based air sampling for bioaerosols, including pathogenicCoccidioidesspp., opens new possibilities for characterizing the aerosolization and transport of fungal spores and other airborne pathogens.
Switch of TIR signaling by a Ca2+sensor activates ADR1 recognition of pRib-AMP-EDS1-PAD4 for stomatal immunity
Authors: Wang Hanling , Tan Jiaxin , Cui Xiulin , Bai Yuhan , Gao Shang , Staskawicz Brian , Song Susheng , Yan Chuangye , Qi Tiancong
Published: November 2024

Plants swiftly close stomata upon detecting pathogen entry, a crucial defense termed stomatal immunity. The process is initiated by cell-surface pattern recognition receptors (PRRs) that perceive pathogen-associated molecular patterns (PAMPs) and evoke a series of early cellular responses including calcium ions (Ca2+) influx, and is conducted by the intracellular nucleotide-binding leucine-rich-repeat receptors (NLRs) ADR1s within an EDS1-PAD4-ADR1 module. However, the underlying mechanisms linking PRR signaling to the NLRs ADR1s remain unclear. Here, we show that theNicotiana benthamianaToll/interleukin-1 receptor (TIR)-only protein Stomatal TIR1 (STIR1) produces the immune molecule pRib-AMP, induces formation of EDS1-PAD4-ADR1 complexes, and mediates stomatal immunity. The Inhibitor of Stomatal Immunity C2-domain protein 1 (ISIC1) interacts with and constrains STIR1 function at basal condition, whereas upon pathogen infection, ISIC1 senses Ca2+signals and de-represses STIR1 signaling. Cryo-electron microscopy structure of pathogen infection-elicitedArabidopsisAtEDS1-AtPAD4-AtADR1-L2 complex reveals the pRib-AMP binding to AtEDS1-AtPAD4 receptor and the AtADR1-L2 recognition of pRib-AMP-AtPAD4-AtEDS1 for stomatal immunity. Collectively, this study uncovers a repression/de-repression mechanism linking PRR signaling to NLRs by a Ca2+sensor/TIR-only node, and elucidates an NLR recognition mechanism of the pRib-AMP-EDS1-PAD4 complex in governing innate immunity.

Synopsis

At basal condition, the Ca2+sensor ISIC1 interacts with and inhibits the TIR-only protein STIR1; upon pathogen infection, ISIC1 perceives Ca2+signal and releases STIR1 to produce pRib-AMP; the EDS1-PAD4 receptor binds pRib-AMP and is recognized by the NLR ADR1-L2, thereby activating stomatal immunity.
Targeted disruption of linkage-specific ubiquitylation reveals a key role of K29-linked ubiquitylation in epigenome integrity
Authors: Arroyo-Gomez Javier , Wang Juanjuan , Guérillon Claire , Isaakova Ekaterina , Reverón-Gómez Nazaret , Koutrouli Mikaela , Rahmanto Aldwin Suryo , Mitrofanov Katrine , Ingham Andreas , Schovsbo Sofie , Weischenfeldt Katrine , Coscia Fabian , Typas Dimitris , Völker-Albert Moritz , Solis Victor , Jensen Lars Juhl , Groth Anja , Mund Andreas , Beli Petra , Shearer Robert F , Mailand Niels
Published: November 2024

Linkage-specific ubiquitin chains dictate the functional outcome of numerous critical ubiquitin-dependent signaling processes. However, the functions and targets of several poly-ubiquitin topologies remain poorly defined due to a paucity of tools for their specific detection and manipulation. To remedy this knowledge gap, we applied a cell-based ubiquitin replacement strategy enabling targeted conditional abrogation of each of the seven lysine-based ubiquitin chain types in human cells to profile system-wide impacts of disabling formation of individual chain types. Focusing on K29-linked ubiquitylation, we reveal a strong association of this linkage type with chromatin-associated proteins and show that the H3K9me3 methyltransferase SUV39H1 is a prominent cellular target of this modification. We demonstrate that K29-linked ubiquitylation is essential for proteasomal degradation of SUV39H1 despite its extensive modification by K48-linked ubiquitylation, and that K29-linked ubiquitylation of SUV39H1 is catalyzed and reversed by TRIP12 and TRABID, respectively. Preventing K29-linked ubiquitylation-mediated control of SUV39H1 stability deregulates the H3K9me3 landscape, but not other histone marks. Collectively, our ubiquitin replacement cell line panel and datasets provide valuable resources for illuminating cellular functions of linkage-specific ubiquitin chains and establish a key role of K29-linked ubiquitylation in epigenome integrity.
Evolutionary strategies ofKlebsiellaphages in a host-diverse environment
Authors: Ferriol-González Celia , Domingo-Calap Pilar
Published: November 2024

Phage-host interactions have been studied using one or a few phages and hosts in simple, controlled systems. Here, we implemented an experimental design to evolve a 12-phage cocktail in a highly diverse environment, including a combination of 39Klebsiellaspp. capsular types. Our results showed how phages modulate their host range through different strategies, adopting a more generalist lifestyle or maintaining their host specificity, depending on the versatility of receptor binding proteins. Some of these proteins were mutational hotspots during the evolution experiment, mainly due to their intrinsic versatility, allowing a broader or narrower host range, and host diversity in the environment. Other mutations found in evolved phages were associated with evading bacterial defense systems or improving fitness on current hosts. Ecological dynamics between phages and hosts, including prophage activation and recombination events, also determined the fate of phage populations. In addition, single phage evolution experiments were performed to validate the results, allowing a model of receptor binding protein evolution and host range modulation to be proposed. This work is a step forward in the understanding of phage-host interactions and the appropriate implementation of phages as biomedical tools, providing insights into their impact in complex environments such as the human microbiota.
Efficient Sampling of PROTAC-Induced Ternary Complexes
Authors: Zhao Hongtao , Schiesser Stefan , Tyrchan Christian , Czechtizky Werngard
Published: November 2024

Proteolysis targeting chimeras (PROTACs) are bifunctional small molecules that recruit an E3 ligase to a target protein, leading to ubiquitin transfer and subsequent proteasomal degradation. The formation of ternary complexes is a crucial step in PROTAC-induced protein degradation, and gaining structural insights is essential for rational PROTAC design. In this study, we present a novel approach for efficiently sampling PROTAC-induced ternary complexes, which has been validated using 40 co-crystallized ternary complex structures. In comparison to protein-protein docking-based integrative approaches, our method achieved an impressive success rate of 97% and 50% retrospectively, measured by Cα-RMSD to the crystal structure within 10 and 4 Å, respectively, with an average CPU time of 4 hours. Notably, utilizing unbound protein structures, the Cα-RMSD values between the predicted and experimental structures were consistently within 7 Å across six WDR5-PROTAC-VHL ternary structures. Our open-source software enables the modeling of ternary structures in a single step and holds promise for enhancing PROTAC design efforts.

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Characterizing the Responses of Camelina and Sorghum to Environmental Stress through a Multi-Modal Approach
Authors: Seitz Kati A. , Morales Demosthenes P. , Bristow Steven T. , Pauer Erica G. , Ryan Duncan P. , Newell Raymond T. , Hanson David T. , Werner James H.
Published: November 2024

Due to their sessile nature, plants are unable to escape environmental factors that negatively impact health, resulting in losses to agricultural productivity. Rapid, non-invasive tools to detect plant stress response are essential for optimizing resource efficiency and mitigating the effects of extreme environmental pressures. However, many existing methods are either invasive, incompatible with other measurement techniques, or have not been applied to a wide range of varying environmental factors. In this study, we assess the physiological responses of four week old camelina (Camelina sativa) and sorghum (Sorghum bicolor) to chitosan, cold, drought, and both acute and chronic salt stress. Several plant characteristics were measured in parallel during stress exposure, including fluorescence and gas exchange parameters (MultispeQ and LI-6800), tissue electrical impedance with wearable biosensors (Multi-PIP), and biochemical properties via Fourier-transform infrared (FTIR) spectroscopy. We compiled unique profiles for whole plant physiological changes in response to environmental stress, demonstrating that certain aspects of plant health and makeup underwent alterations on differing temporal scales. This finding emphasizes the need for a comprehensive multi-modal approach to rapidly and accurately perform remote sensing of plant health in the field. Physiological parameters such as leaf impedance were also observed to rapidly change in response to treatment and can be leveraged to detect very early signs of plant perturbation. This research establishes the utility of a holistic phenotyping approach to inform agricultural strategies aimed at enhancing crop resilience under changing environmental conditions.
Replisome passage through the cohesin ring
Authors: Glaser Samson , Molodtsov Maxim I. , Diffley John F. X. , Uhlmann Frank
Published: November 2024

Following eukaryotic genome replication, the two newly synthesised sister chromatids remain paired by the ring-shaped cohesin complex, enabling their faithful segregation to daughter cells during cell divisions1. Cohesin topologically embraces DNA already before DNA replication2–5, and replisome passage through the cohesin ring is thought of as a fail-safe mechanism ensuring that cohesin entraps both replication products6,7. Whether replisomes indeed pass through cohesin rings remains unknown. Here, we use biochemical reconstitution4,8,9and single molecule fluorescence microscopy to directly visualise replisome-cohesin encounters. We find that the translocating eukaryotic replicative Cdc45-Mcm2-7-GINS (CMG) helicase is frequently an obstacle to cohesin, but that the likelihood with which CMG passes cohesin increases in the presence of replisome components with known sister chromatid cohesion functions7,10–14, or by preventing cohesin from freely sliding along the template DNA. Cohesin retains topological DNA entrapment during CMG passage, suggesting that the helicase passes through the ring. The passage frequency increases further when fully reconstituted replisomes encounter cohesin rings, resulting in successful establishment of cohesion between the two replication products. Our findings demonstrate the existence of a simple mechanism that links genome replication with chromosome segregation, replisome passage through cohesin rings.