bluuebunny/crossref_metadata_2025 huggingface dataset:
E-cigarette Quit Attempts in Emerging Adults: Motivations for Attempts and Predictors of Cessation Barriers
Authors: Holt Laura J , Petrey Anna M , Bravo Adrian J , Folivi Folly ,   Stimulant Norms and Prevalence (SNAP) Study Team, Bravo Adrian J , Mary William , Conner Bradley T , Holt Laura J , Looby Alison , Prince Mark A , Schepis Ty S , Yeung Ellen W
Published: November 2024

Introduction

Although young adults use electronic nicotine delivery systems (ENDS) more often than any other demographic group, most are interested in cessation; however, little is known about their cessation experiences. The present study examined characteristics associated with quit attempts, reasons for quitting and resources utilized, and psychological symptoms (ie, depression, anxiety, anxiety sensitivity, attention-deficit/hyperactivity disorder [ADHD]) associated with cessation barriers.

Methods

College-attending adults from six US institutions who endorsed lifetime ENDS use (N = 2007; 75% female) completed a 1-hour online survey between Fall 2022 and Spring 2023.

Results

More than half of participants (53%) made a cessation attempt; of those participants, more than half (53%) made multiple attempts. Male sex; college region; earlier ENDS initiation; higher ENDS dependence; disposable or pod device use; and past 30-day combustible use were associated with cessation attempts. Health concerns motivated many quit attempts (44%), although participants identified a range of reasons that converged with prior research. Unassisted cessation methods were most common (eg, cold turkey [68%], willpower [53%]). Although utilized far less often, replacing vaping with another activity, support from family/friends, nicotine replacement, and prescription cessation medications were perceived to be helpful. Anxiety sensitivity and ADHD symptoms were associated with more barriers to cessation, particularly with affect management and withdrawal.

Conclusions

ENDS quit attempts are common among young adults, particularly males and those with higher dependence, but largely are unassisted. Encouraging the use of multiple interventions and tailoring interventions to those with psychological vulnerabilities are critical next steps to improving young adults’ success with ENDS cessation.

Implications

Young adults are motivated to quit ENDS for a wide range of intra- and interpersonal reasons. However, their limited uptake of ENDS cessation resources suggests an opportunity to better publicize and increase access to these resources, particularly to digital resources, nicotine replacement therapy, and prescription cessation medications. To be maximally effective, cessation interventions should be multipronged and address the unique challenges faced by individuals with greater anxiety sensitivity and ADHD symptoms, prominent issues in this developmental stage.
Fostering inclusion in medical training: accommodations for hearing loss
Authors: Belingheri M , Riva M A , Brambilla S , Paladino M E
Published: November 2024

This article explores two case reports of healthcare students with hearing impairments in an Italian university and the accommodations provided during their clinical training. The first student, with bilateral sensorineural hearing loss, used the Contec Visual Electronic Stethoscope CMS-VE, which amplifies the sound up to 32 times and supports earphones while wearing hearing aids. The second student, with profound bilateral sensorineural hearing loss and cochlear implants, utilized the Littmann CORE Digital Stethoscope, which amplifies the sound up to 40 times and transmits it via Bluetooth. Both students successfully acquired essential clinical skills, demonstrating that tailored technological accommodations can significantly enhance learning outcomes. This article underscores the critical role of early disability detection and the implementation of support strategies by occupational health physicians. These case reports highlight the importance of innovative solutions in promoting inclusion and ensuring equal opportunities in medical education and future workplaces.
Transcription factors PuNAC37/PuWRKY74 and E3 ubiquitin ligase PuRDUF2 inhibit volatile ester synthesis in ‘Nanguo’ pear
Authors: Zang Nannan , Li Xiaojing , Zhang Zhuoran , Liu Weiting , Qi Liyong , Yang Yueming , Sun Qitian , Yin Zepeng , Wang Aide
Published: November 2024

As major contributors to flavor in many fruit species, volatile esters are useful for investigating the regulation of the biosynthesis pathways of volatile aroma compounds in plants. Ethylene promotes the biosynthesis of volatile esters during fruit storage while accelerating fruit ripening; thus, the ethylene perception inhibitor 1-methylcyclopropene (1-MCP) is employed to prolong the shelf life of fruits. However, the mechanisms by which 1-MCP regulates volatiles synthesis remain unclear. In this study, we analyzed the pathway of 1-MCP-mediated volatile ester synthesis in ‘Nanguo’ pear (Pyrus ussuriensis). 1-MCP significantly decreased volatile ester synthesis during storage. Comparative transcriptome analysis showed that the genes encoding two transcription factors (PuNAC37 and PuWRKY74) and a RING-type E3 ubiquitin ligase that have a domain of unknown function (PuRDUF2) were expressed at high levels, whereas ALCOHOL ACYLTRANSFERASE 1 (PuAAT1), encoding an enzyme responsible for volatile ester synthesis, was expressed at low levels in 1-MCP-treated fruit. Moreover, PuNAC37 inhibited the expression of PuWRKY74 via transcriptional regulation, whereas PuNAC37 and PuWRKY74, after directly binding to the promoter of PuAAT1, synergistically inhibited its expression in 1-MCP-treated fruit. In addition, in vitro and in vivo ubiquitination experiments revealed that PuRDUF2 functions as an E3 ubiquitin ligase that ubiquitinates PuAAT1, causing its degradation via the 26S proteasome pathway following 1-MCP treatment. Subsequent PuAAT1 degradation resulted in a reduction of volatile esters during fruit storage. Our findings provide insights into the complex transcriptional regulation of volatile ester formation in ‘Nanguo’ pears and contribute to future research on AAT protein ubiquitination in other species.
Democracy and Climate Change for Realists: An Integrated Empirical and Normative Assessment
Authors: Maloy J S
Published: November 2024

When scholars consider the relation between domestic political regimes and global climate change, they typically rely on assumptions about liberal democracy's core competencies with respect to environmental protection in general. As a result, an ostensibly normative debate pitting democracy against “eco-authoritarianism” depends for its resolution on causal theory and empirical analysis. I offer an integrated assessment of both empirical (causal) and normative (ethical) theories on democracy, autocracy, and climate change, concluding that democracy's superiority is less compellingly supported than regime-neutrality. Theoretically, the causal logic of environmentally protective democracy cannot readily be extended to climate change as a distinctive political problem. Empirically, my review of global statistical analyses of regime type and climate change reveals that the evidence is more consistent with regime-neutrality than democratic advantage. Regime-neutrality, in turn, revitalizes difficult normative arguments about trade-offs between democratic freedom and climatic stability. Something resembling the “win-win” situation of climate-fixing democracy may still be salvaged, theoretically. But political science's search for this outcome should take a realist turn: abandoning the liberal-authoritarian dichotomy in favor of a new one, pitting post-liberal forms of democracy against climate-fixing hybrid regimes.
The influence of intentions on dream content
Authors: Fechner Julia , Born Maren , Mancini Massimiliano , Akata Zeynep , Haag Philipp , Diekelmann Susanne , Born Jan
Published: November 2024

Study Objectives

The “Zeigarnik effect” refers to the phenomenon where future intentions are remembered effectively only as long as they are not executed. This study investigates whether these intentions, which remain active during sleep, influence dream content.

Methods

After an adaptation night, each of the 19 participants (10 women and 9 men) received three different task plans in the evening before the experimental night, each describing how to perform specific tasks. One of the task plans (completed) was then to be executed before the sleep period, another task (uncompleted) was told to be executed in the next morning, and on the third task (interrupted) participants were interrupted during the enactment before sleep and told to resume it the next morning. Polysomnography and multiple awakenings were conducted, resulting in 86 dream reports, 36 in NREM stage 2, and 50 in rapid eye movement sleep. After a traditional rating-based analysis of dream reports yielded inconsistent results, we analyzed the reports using a transformer-based assessment of dream incorporation, which quantified the semantic similarity between the dreams and pre-sleep tasks.

Results

The number of dreams showing above-criterion similarity to the respective task was significantly lower for the completed than the uncompleted or interrupted tasks (p < .05, χ2 test). This pattern was confirmed through a forced choice approach, where—based on the similarity of single sentences of the dream reports—each dream report was allocated to one of the three task plans (p < 0.01, one-tailed χ2 test).

Conclusions

Active intentions increase the likelihood of dream content being semantically similar to these intentions.
Influence of added 1,25(OH)2D3-glycoside on nursery pig growth performance, bone measurements, and cytokine concentrations
Authors: Becker Larissa L , Tokach Mike D , Woodworth Jason C , Goodband Robert D , DeRouchey Joel M , Devlikamov Murat R , Rahe Michael C , Siepker Christopher L , Sitthicharoenchai Panchan , Gebhardt Jordan T
Published: November 2024

A total of 2,268 crossbred pigs (L337 × 1050, PIC; initially 5.5 ± 0.18 kg) were used in a 42-d growth study to evaluate the effects of 1,25(OH)2D3-glycoside provided from a plant extract on growth performance, bone characteristics, and serum criteria of nursery pigs. Pigs were weaned at approximately 21 d of age and randomly assigned to 1 of the 3 dietary treatments in a randomized complete block design. A total of 84 pens were used with 27 pigs per pen and 28 replications per treatment with pens blocked by BW and date of entry into the facility. Treatment diets were corn–soybean meal-based and consisted of a control diet (1,653 IU/kg of vitamin D3), or the control diet with 1.2 or 2.0 μg of 1,25(OH)2D3-glycoside/kg. Blood samples were collected from 25 gilts/treatment on days 21 and 42 to assess 25(OH)D3, cytokine concentrations, and antibody titers. At the end of the study, 10 pigs per treatment were euthanized and the right fibula, metacarpal, second and 10th ribs were collected to determine bone density, breaking strength, and percentage bone ash. Overall, there was a tendency (linear, P = 0.067) for a reduction in G:F as added 1,25(OH)2D3-glycoside increased, but no significant effects on final BW, ADG, ADFI, or mortality were observed. There were no treatment × bone interactions for bone breaking strength and bone ash. Percentage bone ash increased (linear, P = 0.030) across all bones as 1,25(OH)2D3-glycoside increased. Treatment did not affect bone ash weight and breaking strength. Metacarpals and 10th ribs had the greatest bone ash weight followed by the fibula with the second ribs having the lowest (P < 0.05). Metacarpals had greater breaking strength compared to all other bones, followed by the fibula and 10th rib, with the second rib having the lowest (P < 0.001). There was a bone × treatment interaction for bone density, where increasing 1,25(OH)2D3-glycoside increased bone density for the second rib (P = 0.012), but there was no treatment difference for other bones. There was no difference between treatments for antibody titers, 25(OH)D3 status, or circulating cytokine concentrations except for IL-8 concentrations which decreased (linear, P = 0.037) as 1,25(OH)2D3-glycoside increased. In summary, adding 1.2 or 2.0 μg 1,25(OH)2D3-glycoside/kg provided from a plant extract to a diet already containing 1,653 IU/kg of vitamin D3 had no effect on growth or the evaluated serum parameters; however, increasing 1,25(OH)2D3-glycoside increased percentage bone ash.
Building a Border: The Material Transit of Scientific Labor
Authors: Menchaca Celeste R
Published: November 2024

The U.S.-Mexico Boundary Commission (1849–1855) was a joint effort between the two countries to survey the new border, as designated by the Treaty of Guadalupe Hidalgo (1848) and later the Gadsden Purchase (1854). This article examines the scientific corps of the U.S. Boundary Commission and its dual role in manufacturing a national border and scientific personhood. While studies on exploration and empire generally examine the cartographic output of these state-sponsored missions, this article centers on the embodied practices of surveying. It considers how the technical procedures and practices of surveying produced spaces of scientific knowledge and scientific subjects. When U.S. surveyors traveled to the Indigenous territories of what was formerly northern Mexico in 1849, they began their fieldwork—observing, collecting, and recording the natural phenomena that surrounded them. I argue that as they moved through space, they contoured the nation—creating a field coherent to the state via their scientific work. Their fieldwork was a mobile technology of place-making. Assembling the astronomical and surveying equipment, positioning their bodies with the utmost care to record the motion of stars, igniting flashes of gunpowder to mark time, laboring for hours calculating spherical triangles, and uprooting trees that obstructed sight lines were all acts that constituted both the surveyor and the border. I draw on textbooks, memoirs, congressional reports, and commission records to demonstrate how engineers of the U.S. Boundary Commission crafted themselves as they built a border.
The role of type 2 diabetes in the severity of adult asthma
Authors: Pham Alisa , Corcoran Rose , Foer Dinah
Published: November 2024

Purpose of review

This review summarizes recent basic, translational, and clinical research on type 2 diabetes (T2D) and its relationship with asthma severity in the context of T2D mechanisms and asthma outcomes.

Recent findings

Several clinical asthma outcomes, such as lung function and exacerbations, demonstrate a strong association between T2D and asthma and support that T2D contributes to worse asthma outcomes. Multiple mechanisms underlying those observed associations, and their representative biomarkers, have been proposed. However, prospective, controlled human studies in the context of both T2D and asthma are limited.

T2D is associated with worse asthma outcomes and more severe asthma. Yet patients with more severe or uncontrolled asthma are also at a higher risk for systemic steroid exposure, which worsens glycemic control and metabolic dysregulation. Preclinical and translational studies point to metabolic dysregulation as a driver of airway inflammation. Addressing these metabolic pathways through T2D treatment may, in turn, directly or indirectly improve clinical asthma outcomes. While additional research is needed to identify biomarkers of risk and treatment response in metabolic asthma, this review highlights the importance of considering T2D as a clinically relevant asthma comorbidity.
The Changes in Dietary Intake and Tolerance for Chinese Food after Bariatric Surgery in Taiwan
Authors: Lin Yu-Ning , Lin Ke-Shin , Ng Chong Beng , Yen Mu-Hsin , Lin Shi-Yun , Liu Keng-Hao
Published: November 2024

Background

This study aimed to investigate changes in dietary intake and food tolerance after bariatric surgery in the Taiwanese population with a focus on Taiwanese dietary patterns.

Materials and Methods

The study enrolled 100 patients who had undergone bariatric surgery and were followed for 1 year, recording patient characteristics, laboratory data, and dietary conditions. Food tolerance was assessed using a questionnaire at 1, 3, 6, 9, and 12 months after the operation. The surgical methods, changes in body condition, laboratory results, and tolerance scores were analyzed.

Results

The results showed an average decrease in body mass index (BMI) of 11.2 kg/m2 and improvements in metabolic parameters after 1 year of surgery. Calorie and protein intake decreased sharply one month after surgery but increased over the following year. Food tolerance varied for different types of foods and at different time points, with dry rice and bread showing poor tolerance (<3 at post-op 1 month). However, congee, eggs, soybean, fruits, and milk had relatively better tolerance scores (>3.5) in the early post-op period. Nuts, yogurt, and cheese were less commonly tried, which may be related to Taiwanese dietary habits.

Conclusions

Our study provides the analysis of dietary intake and food tolerance after bariatric surgery in the Taiwanese population. We observed that soft-textured protein sources, such as tofu and seafood, along with cooked vegetables, are well-tolerated and beneficial in the early post-op period. Additionally, dairy products like milk and yogurt can be incorporated to support nutritional needs. Poor tolerance of dry rice and bread, which are staples in the Taiwanese diet, suggests that dietary adjustments are crucial for improved food tolerance and quality of life.
Adrenal oncocytoma: a rare presentation of a benign 18F-fluorodeoxyglucose PET avid virilising adrenal tumour
Authors: Lee Danielle , Green Jonathan , Crane James , Taylor David R. , Reynolds Saira , Ng Wen , Jacob Koshy , Whitelaw Benjamin , Aylwin Simon , Galata Gabriele , Lewis Dylan , Seager Matthew
Published: November 2024

A woman in her 70s presented with features of hyperandrogenism including clitoral enlargement and deepening of her voice. Biochemical investigations revealed raised plasma androgens and urinary androgen metabolites and imaging findings showed a highly F-18 fluorodeoxyglucose (FDG)-PET avid left adrenal tumour initially suspected to be a malignant adrenocortical carcinoma (ACC). She subsequently underwent an uncomplicated laparoscopic adrenalectomy where complete resection of her tumour was achieved. Histopathological analysis demonstrated a benign adrenal oncocytoma with no evidence of malignancy. This case illustrates a rare presentation of a functioning virilising adrenal oncocytoma as a benign mimic of ACC.
Kosakonia calanthes sp. nov., a plant growth-promoting bacterium, isolated from Calanthe triplicata leaves in China
Authors: Wu Pengyu , Zhang Yutian , Xiong Zhilei , Shan Qiantong , Shi Kuo , Lou Yajuan , Wang Ziyang , Wang Yuanmeng , Luo Jiancheng
Published: November 2024

A Gram-stain-negative, facultatively aerobic, rod-shaped and motile bacterium, designated as CCTCC AB 2023082T, was isolated from leaves of Calanthe triplicata in China. Optimal growth occurred at 4–45 ℃ and pH 4.0–10.0 and in the presence of 0–7% (w/v) NaCl. The major fatty acids of the strain CCTCC AB 2023082T were C16 : 0, sum of C16 : 1 ω7c/C16 : 1 ω6c, C17 : 0 cyclo and C18 : 1 ω7c. The polar lipids included unidentified lipids, phospholipids, phosphatidylethanolamine, phosphatidylglycerol and amino phospholipid. The DNA G+C content of strain CCTCC AB 2023082T was 54.2 mol%. 16S rRNA gene sequence analysis indicated that strain CCTCC AB 2023082T formed a distinct lineage within the genus Kosakonia and exhibited the highest similarity to Kosakonia quasisacchari, with a 97.9% 16S rRNA gene sequence similarity. Moreover, the preliminary analysis of the organism’s genome suggested its potential as a biostimulant for augmenting plant growth. According to its genotypic, phenotypic, phylogenetic and chemotaxonomic characteristics, strain CCTCC AB 2023082T should be categorized as a novel species in the genus Kosakonia. The novel species was named Kosakonia calanthes sp. nov., and its type strain is CCTCC AB 2023082T (=JCM 36393T).
Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication
Authors: Kirigin Elisa , Okpara Michael Obinna , Matandirotya Lorraine , Ruck Jamie-Lee , Weaver Frederick , Jackson Zoe , Chakraborty Abir , Veale Clinton Gareth Lancaster , Whitehouse Adrian , Edkins Adrienne Lesley
Published: November 2024

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a DNA virus that causes Kaposi’s sarcoma, a cancer of endothelial origin. KSHV uses the activity of host molecular chaperones like Hsp70 and Hsp90 for the folding of host and viral proteins required for productive infection. Hsp70 and Hsp90 chaperones form proteostasis networks with several regulatory proteins known as co-chaperones. Of these, Hsp90–Hsp70-organizing protein (HOP) is an early-stage co-chaperone that regulates the transfer of folding substrate proteins between the Hsp70 and Hsp90 chaperone systems. While the roles for Hsp90 and Hsp70 in KSHV biology have been described, HOP has not previously been studied in this context despite its prominent interaction with both chaperones. Here, we demonstrate a novel function for HOP as a new host factor required for effective lytic replication of KSHV in primary effusion cell lines.
Dysbiosis–epigenetics–immune system interaction and ageing health problems
Authors: Ataollahi Eshkoor Sima , Fanijavadi Sara
Published: November 2024

An erratum
of this article has been published full details can be found at

10.1099/jmm.0.001961

Background. The growing interest in microbiota–epigenetics–immune system research stems from the understanding that microbiota, a group of micro-organisms colonized in the human body, can influence the gene expression through epigenetic mechanisms and interaction with the immune system. Epigenetics refers to changes in gene activity that are not caused by the alteration in the DNA sequence itself.

Discussion. The clinical significance of this research lies in the potential to develop new therapies for diseases linked to the imbalance of these microbial species (dysbiosis), such as cancer and neurodegenerative diseases. The intricate interaction between microbiota and epigenetics involves the production of metabolites and signalling molecules that can impact our health by influencing immune responses, metabolism and inflammation. Understanding these interactions could lead to novel therapeutic strategies targeting microbiota–epigenetic pathways to improve health outcomes.

Conclusion. In this context, we aim to review and emphasize the current knowledge and key concepts that link the microbiota to epigenetics and immune system function, exploring their relevance to the development and maintenance of homeostasis and susceptibility to different diseases later in life. We aim to elucidate key concepts concerning the interactions and potential effects among the human gut microbiota, epigenetics, the immune system and ageing diseases linked to dysbiosis.
Oncogenic GNAQ/11-induced remodeling of the IP3/Calcium signaling pathway protects Uveal Melanoma against Calcium-driven cell death
Authors: Céline Garcia , Louis Roussel , Sarah Massaad , Laura Brard , Rita La Rovere , Sophie Tartare-Deckert , Corine Bertolotto , Geert Bultynck , Sabrina Leverrier-Penna , Aubin Penna
Published: November 2024

Despite being considered a rare tumor, uveal melanoma (UVM) is the most common adult intraocular malignancy. With a poor prognosis and limited treatment options, up to 50% of patients develop metastases, primarily in the liver. A range of mutations and chromosomal aberrations with significant prognostic value has been associated with UVM pathogenesis. The most frequently mutated genes are GNAQ and GNA11, which encode the α subunits of Gq proteins and are described as driver mutations that activate multiple signaling cascades involved in cell growth and proliferation. Directly downstream of Gαq/11 activation, PLCβ engagement leads to sustained production of DAG and IP3. While the DAG/PKC/RasGRP3/MAPK signaling branch has been identified as an essential component of UVM unregulated proliferation, the role of IP3-mediated signals has been largely overlooked.

Here, we demonstrate that, whilst maintaining Ca²⁺ homeostasis, UVM cells have developed a decoupling mechanism between IP3 and ER Ca²⁺ release by altering IP3 receptor (IP3R) expression. This correlation was observed in human UVM tumors, where IP3Rs were found to be downregulated. Critically, when IP3R3 expression was restored, UVM cells exhibited an increased tendency to undergo spontaneous cell death and became more sensitive to pro-apoptotic modulators of IP3R-mediated Ca²⁺ signaling, such as staurosporine and the Bcl2-IP3R disrupter peptide BIRD2.

Finally, inhibition of the Gαq/11 signaling pathway revealed that IP3R expression is negatively regulated by GNAQ/11 oncogenic activation. Hence, we demonstrated that by remodeling IP3R expression, GNAQ/11 oncogenes protect UVM cells against IP3-triggered Ca²⁺ overload and cell death. Therefore, the GNAQ/11 pathway not only drives proliferation through DAG activity but also provides a protective mechanism to evade IP3/Ca²⁺-mediated cell death. These dual functions could potentially be exploited in novel combinatorial therapeutic strategies to effectively block UVM cell proliferation while simultaneously sensitizing them to cell death.
Quantitative genetics of photosynthetic trait variation in maize
Authors: Ali Waqar , Grzybowski Marcin , Torres-Rodríguez J. Vladimir , Li Fangyi , Shrestha Nikee , Mathivanan Ramesh Kanna , de Bernardeaux Gabriel , Hoang Khang , Mural Ravi V. , Roston Rebecca L. , Schnable James C. , Sahay Seema
Published: November 2024

Natural genetic variation in photosynthesis-related traits can aid both in identifying genes involved in regulating photosynthetic processes and developing crops with improved productivity and photosynthetic efficiency. However, rapidly fluctuating environmental parameters create challenges for measuring photosynthetic parameters in large populations under field conditions. We measured chlorophyll fluorescence and absorbance-based photosynthetic traits in a maize diversity panel in the field using an experimental design that allowed us to estimate and control multiple confounding factors. Controlling the impact of day of measurement and light intensity as well as patterns of two-dimensional spatial variation in the field substantially increased heritability with the heritability of 7 out of 14 traits measured exceeding 0.4. We were able to identify high confidence GWAS signals associated with variation in four spatially corrected traits (the quantum yield of photosystem II, non-photochemical quenching, redox state of QA, and relative chlorophyll content). Insertion alleles forArabidopsisorthologs of three candidate genes exhibited phenotypes consistent with our GWAS results. Collectively these results illustrate the potential of applying best practices from quantitative genetics research to address outstanding questions in plant physiology and understand the mechanisms underlying natural variation in photosynthesis.

Highlights

●

Controlling spatial and environmental confounding factors increased heritability of photosynthetic traits.

●

GWAS identified high confidence signals associated with variation in relative chlorophyll, ΦPSII, ΦNPQ, and qL.

●

Insertion alleles of theArabidopsisorthologs of maize candidate genes exhibited photosynthesis related phenotypes consistent with the GWAS results.
Label-free multiplex microscopic imaging by image-to-image translation overcoming the trade-off between pixel- and image-level similarity
Authors: Morikura Takashi , Funahashi Akira
Published: November 2024

Establishment of multiplex microscopic imaging without labeling is indispensable for understanding complex interactions of subcellular components. Toward the establishment of label-free multiplex microscopic imaging, image-to-image translation models that extract images of multiple subcellular components from bright-field images via nonlinear processing have attracted attention. However, the performance of conventional models is limited by a trade-off relationship between pixel- and image-level similarity, which degrades imaging performance. Here, we developed an image-to-image Wasserstein Schrödinger Bridge model to achieve high-performance image-to-image translation at the pixel level using Schrödinger Bridge while minimizing Wasserstein distance at the image level. Our model dramatically outperformed the conventional models at both levels simultaneously, reducing the mean squared error by 410-fold and improving the structural similarity index measure by 17.1-fold. Label-free multiplex microscopic imaging based on our model paves a way for the analysis of the interactions of subcellular components.
Coral restoration is only practical when local human pressure levels are low
Authors: Brookson Cole B. , Greiner Ariel
Published: November 2024

Coral reefs are threatened by interacting local (fishing, coastal development) and global (climate change) stressors that degrade coral cover. Adding coral to the reef (coral restoration) is gaining prominence as a management strategy, however it is unclear whether restoration alone can ensure self-sustaining high coral cover under interacting stressors. We assess how much restoration is needed for a self-sustaining healthy coral reef using a mathematical model and real-world restoration case studies. We find that a reef with low macroalgal cover and high coral recruitment requires low restoration to ensure self-sustaining high coral cover but as nutrient enrichment and fishing increase, more restoration is required. Thus, if the reef is facing high local human stressors, restoration is unlikely to ensure self-sustaining high coral cover, suggesting that under such conditions conservation resources should first be allocated towards reducing the impact of stressors, prior to any restoration.
An abundance ofaliCandaliDgenes were identified in saliva using a novel multiplex qPCR to characterize group II non-encapsulated pneumococci with improved specificity
Authors: Laxton Claire S. , Toekiran Femke L. , Lin Tzu-Yi , Lomeda Beta D. , Hislop Maikel S. , Keller Lance , Allicock OrchMid M. , Wyllie Anne L.
Published: November 2024

Background

Surveillance of pneumococcus is reporting increasing prevalence of non-encapsulated pneumococci (NESp). NESp are an important reservoir for genetic exchange among streptococci, including for antimicrobial resistance (AMR), and are increasingly implicated in disease. Disease-associated NESp commonly carry the virulence genespspK,oraliCandaliDin theircpslocus instead of capsule genes. While molecular methods targeting the cps region are widely used for serotyping encapsulated strains, there are few assays available for classification of NESp, meaning it is not widely undertaken. Therefore, we exploited these genes as targets for a novel qPCR assay for detecting and classifying NESp strains with improved efficiency and specificity.

Methods

We conducted bioinformatic analysis on sequences from 30 NESp and 23 other mitis-group streptococcal sequences and developed a multiplex-qPCR, targetingpspK,aliDand two regions ofaliC. The assay was validated using 11 previously characterised, and 5 uncharacterised NESp isolates. We then applied the assay to DNA extracted from culture-enriched saliva, and isolated and characterised suspected NESp colonies, with confirmation by whole genome sequencing.

Results

Bioinformatic analyses demonstrated that previously published primers foraliCandaliDhad low pneumococcal-specificity but indicated that targeting two regions ofaliCwould improve species-specificity, without compromising sensitivity. Our novel multiplex assay accurately typed all isolates. When screening saliva, we found a high prevalence ofaliCandaliD, even in samples negative for pneumococcal geneslytAandpiaB. Isolated colonies which werealiCandaliDpositive could be differentiated as non-pneumococcal streptococci using our assay.

Conclusion

Our multiplex-qPCR assay can be used to efficiently screen even highly polymicrobial samples, such as saliva, for NESp genes, to detect and differentiate potentially pathogenic NESp clades from closely related mitis-group streptococci. This will allow for a better understanding of the true prevalence of NESp, and their impact upon pneumococcal carriage, disease, and AMR.
Environmental DNA vs. Community Science: Strengths and Limitations for Urban Odonata Surveys
Authors: Uche-Dike Rhema , Tolman Ethan , Benischek Christian , Schneider Magnolia , Kohli Manpreet K. , Bush Jonas , Frandsen Paul B. , Errigo Isabella , Frankel Wendy , Gnojewski Kristin , Chmura Kim , Jordan Dick , Kittler Hannah , Liao Michel , Tobin Trinity , Su Cindy , Castillo Gracie , Derdarian Ethan , Wei Maleah , Fernandez-Jaurez Santiago , Tamano Towako , Gallafent Ben , Jenson James , Walser Christoph A. , Ware Jessica L. , Beatty Christopher D.
Published: November 2024

The study of insect decline remains a major frontier in insect biodiversity and conservation. Despite growing concern about accelerating rates of insect decline generally, relatively little data has been compiled about species of aquatic insects. Data is particularly lacking on the distribution of aquatic insects in urban ecosystems. Here, we compare environmental DNA (eDNA) metabarcoding and community science observation as means of monitoring Odonata within an urban system in Southwest Idaho. We show that the distribution of Odonata across this urban landscape is not uniform and that both monitoring methods have different strengths and weaknesses. We found that eDNA metabarcoding was very sensitive to the identification of genera from underrepresented families in the region, but was unable to distinguish between closely related genera, particularly from localities where eDNA could accumulate more damage. On the other hand, community science observations effectively identified the presence of genera from more speciose families but missed the presence of relatively rare species, and those that had a short flight season. These findings suggest that, in our study system, eDNA and community science are highly complementary of each other. In cases where only one method is employed for a monitoring or conservation project, care should be given to account for the biases of each approach.
Global evolutionary patterns ofYersinia pestisand its spread into Africa
Authors: Mas Fiol Guillem , Lemoine Frédéric , Mornico Damien , Bouvier Guillaume , Andrades Valtueña Aida , Duchene Sebastian , Campagne Pascal , Balière Charlotte , Kwasiborski Aurélia , Caro Valérie , Beau Rémi , Savin Cyril , Céspedes Manuel , Rajerison Minoarisoa , Shako Jean-Christophe , Carniel Elisabeth , Slavin Philip , Rascovan Nicolás , Pizarro-Cerdá Javier
Published: November 2024

The zoonotic pathogenYersinia pestis, the etiologic agent of plague, has caused three major pandemics and diversified in different lineages currently established in endemic areas worldwide1–3. However, some regions like continental Africa have been poorly covered within the global diversity and epidemiological history of this pathogen2,4–6. Here, we report the whole-genome sequences of 1,124Y. pestisisolates collected from endemic areas worldwide over 116 years, nearly doubling the available genomic data for the species. By integrating population genomics and historical research, we retrace the introduction of multipleY. pestislineages into continental Africa, revealing the diversity of the 1.ANT lineage, its historical emergence and its spread to and within Africa since the late 17th century. We identify key mechanisms of genome evolution, including signatures of adaptive evolution present in virulence and biofilm-related genes such as RovA, a master virulence regulator, which likely play a role in the pathogen’s adaptation and endemic persistence. Additionally, our findings reveal an increased trajectory of genome degradation and expansion of IS elements in different lineages. This trend appears especially pronounced in 1.ANT genomes, promoting the remarkable genomic variation within this lineage. Taken together, our findings shed light on the introduction and evolutionary history of plague in Africa and provide a comprehensive framework for understanding the global diversity and genome evolution ofY. pestis, revealing potential factors contributing to its long-term adaptation in endemic areas.
A “non-muscle” α-actinin is an intrinsic component of the cardiac Z-disc and regulates sarcomere turnover, contractility, and heart remodeling
Authors: Hayes James B , Ritter Dylan , Neininger-Castro Abigail C , Willet Alaina H , Caplan Leah R , Wang Yu , Liu Xiao , Taneja Nilay , Sanchez Zachary C , Smart Kyra , Reinhart-King Cynthia A , Liu Qi , Tyska Matthew J , Tabdanov Erdem D , Wells Quinn S , Knapik Ela W , Burnette Dylan T
Published: November 2024

Cardiac sarcomeres generate the fundamental forces behind each heartbeat and are thought to contain only muscle-specific cytoskeletal proteins. We show that a widely expressed actin cross-linking protein, α-actinin 4 (ACTN4), is a sarcomere component of the human and zebrafish heartin vivoand in human iPSC-derived cardiac myocytes (CMs)in vitro. A confluence of biochemical experiments, immunofluorescence, and AI modeling suggest ACTN4 forms a heterodimeric complex with muscle-specific ACTN2 at the cardiac Z-disc, the cardiac sarcomere border. ACTN4 depletion from human iPSC-CMs stabilizes canonical sarcomere proteins and drives contractility-dependent cellular hypertrophy while ACTN4 overexpression destabilizes sarcomeres. ACTN4 depletion from zebrafish embryos specifically increases ventricular contractility which drives atrial enlargement, suggesting biomechanically driven atrial remodeling. ACTN4-associated phenotypes in both model systems lack hallmarks of cardiac disease models and an ACTN4 variant in humans is associated with reduced risk for disease. Our findings suggest a “non-muscle” actinin regulates heart contractility and influences clinical outcomes related to heart failure.
Actin filament assembly driven by distributive polymerases clustered on membrane surfaces
Authors: Mullins R. Dyche , Skruber Kristen
Published: November 2024

Actin filaments created by the Arp2/3 complex form branched networks, that grow and push against cellular membranes. We employ theory and simulation to describe how membrane surfaces accelerate filament assembly via clustering of proteins that bind actin monomers and/or profilin-actin complexes. Briefly, thermal fluctuations drive filament tips on constrained, two-dimensional random walks across the membrane, where they encounter multiple actin-charged polymerases. At low actin concentrations, filament elongation is limited by delivery of monomers to the membrane surface; at high actin concentrations, elongation depends on how quickly fluctuating filaments search the membrane. Surface-mediated polymerization can outpace solution-mediated elongation, even at high actin concentrations (>200 µM). The finite time required for profilin dissociation decreases the advantage conferred by surface-associated polymerases, but only in the absence of force. Load forces enhance the effect of surface polymerases, which can both accelerate elongation and increase the force required to stall filament assembly.
Cavin1 binding nanobodies reveal structural flexibility and regulated interactions of the N-terminal coiled-coil domain
Authors: Gao Ya , Tillu Vikas A. , Wu Yeping , Rae James , Hall Thomas E. , Chen Kai-en , Weeratunga Saroja , Guo Qian , Livingstone Emma , Tham Wai-Hong , Parton Robert G. , Collins Brett M.
Published: November 2024

Caveolae are abundant plasma membrane structures that regulate signalling, membrane homeostasis, and mechanoprotection. Their formation is driven by caveolins and cavins and their coordinated interactions with lipids. We have developed nanobodies against the trimeric HR1 coiled-coil domain of Cavin1. We identify specific nanobodies that do not perturb Cavin1 membrane binding and localise to caveolae when expressed in cells. The crystal structure of a nanobody HR1 complex reveals a symmetric 3:3 architecture as validated by mutagenesis. In this structure, the C-terminal half of the HR1 domain is disordered suggesting the nanobody has stabilised an open conformation previously identified as important for membrane interactions. Mutational analysis of a conserved buried hydrogen-bonded His-Thr pair proximal to this region reveals selective regulation of cavin2/cavin3 association. These studies provide new insights into Cavin domains required for assembly of multiprotein caveolar assemblies and describe new nanobody tools for structural and functional studies of caveolae.
Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine
Authors: Bartlett Mitchell J. , Stopera Carolyn J. , Cowen Stephen L. , Sherman Scott J. , Falk Torsten
Published: November 2024

Sub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson’s disease case reports. In this study, we examined the effects on L-DOPA-induced dyskinesia of two statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard preclinical LID model. Sub-anesthetic ketamine attenuated the development of AIMs, while lovastatin only showed anti-dyskinetic activity at the beginning of the priming but did not prevent the development of LID. The polar pravastatin blocked the long-term anti-dyskinetic effects of ketamine, while the non-polar lovastatin did not. This study shows different classes of statins affect LID differentially, points to an important drug interaction and further supports ongoing clinical testing of sub-anesthetic ketamine to treat LID in individuals with Parkinson’s disease.
Genome-wide association study of frost tolerance inVicia fabareveals syntenic loci in cool-season legumes and highlights relevant candidate genes
Authors: Imbert Baptiste , Kreplak Jonathan , Lejeune-Hénaut Isabelle , Magnin-Robert Jean-Bernard , Boutet Gilles , Marget Pascal , Aubert Grégoire , Burstin Judith , Tayeh Nadim
Published: November 2024

Cool-season grain legumes are mostly grown over spring and summer due to poor frost tolerance. However, fall-sown varieties often provide higher yields, earlier harvests and avoid late-season drought and heat. Understanding the genetic determinism and molecular basis of frost tolerance is therefore crucial for developing high-performing winter varieties. This study aimed to (1) investigate the genetic architecture of frost tolerance inVicia fabaL. using 247 accessions phenotyped under four field environments, and (2) explore the conservation of frost tolerance loci in cool-season legumes using the OrthoLegKB translational research database. A genome-wide association study identified nineteenV. fabagenomic regions with a high density of markers significantly associated with frost tolerance, on all chromosomes. Mapping of frost tolerance QTL fromV. fabaand related species obtained from the literature onto their respective reference genomes and their integration into OrthoLegKB revealed synteny of major QTL acrossV. faba,Pisum sativum, and/orMedicago truncatula, particularly near clusters ofCBF/DREB1genes. Frost tolerance QTL at theP. sativum Lelocus, which controls internode length, were also syntenic with a frost tolerance QTL inV. faba. Synteny between frost tolerance QTL and those controlling phenology and physiology was found at other loci, suggesting pleiotropy. Finally, expression data fromP. sativumandC. arietinumaccessions grown under low temperature were considered as information source to highlight potential candidate genes underlying the conserved QTL. Overall, these results provide a valuable resource for understanding and improving frost tolerance inV. fabaand other cool-season legumes, including orphan crops by knowledge transfer. The use of OrthoLegKB to explore the genetic and molecular determinism of target traits across species is worth generalising.
SNMF: Integrated Learning of Mutational Signatures and Prediction of DNA Repair Deficiencies
Authors: Goossens Sander , Tepeli Yasin I. , Seale Colm , Gonçalves Joana P.
Published: November 2024

Motivation

Many tumours show deficiencies in DNA damage response (DDR), which influence tumorigenesis and progression, but also expose vulnerabilities with therapeutic potential. Assessing which patients might benefit from DDR-targeting therapy requires knowledge of tumour DDR deficiency status, with mutational signatures reportedly better predictors than loss of function mutations in select genes. However, signatures are identified independently using unsupervised learning, and therefore not optimised to distinguish between different pathway or gene deficiencies.

Results

We propose SNMF, a supervised non-negative matrix factorisation that jointly optimises the learning of signatures: (1) shared across samples, and (2) predictive of DDR deficiency. We applied SNMF to mutation profiles of human induced pluripotent cell lines carrying gene knockouts linked to three DDR pathways. The SNMF model achieved high accuracy (0.971) and learned more complete signatures of the DDR status of a sample, further discerning distinct mechanisms within a pathway. Cell line SNMF signatures recapitulated tumour-derived COSMIC signatures and predicted DDR pathway deficiency of TCGA tumours with high recall, suggesting that SNMF-like models can leverage libraries of induced DDR deficiencies to decipher intricate DDR signatures underlying patient tumours.

Availability

https://github.com/joanagoncalveslab/SNMF.
Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study
Authors: Khetan Muskan , Vijayakumar Nandita , Tian Ye Ella , Herting Megan M. , Connell Michele O’ , Seal Marc , Whittle Sarah
Published: November 2024

Puberty is a critical developmental process that is associated with changes in steroid hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes) and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92 - 13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive DevelopmentSM(ABCD®) Study. We used elastic-net regression with cross- validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, were among the most important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.