bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative functional morphology indicates niche partitioning among sympatric marine reptiles
Authors: Foffa Davide , Young Mark T. , Brusatte Stephen L.
Published: May 2024

Mesozoic marine ecosystems were dominated by diverse lineages of aquatic tetrapods. For over 50 Ma in the Jurassic until the Early Cretaceous, plesiosaurians, ichthyosaurians and thalattosuchian crocodylomorphs coexisted at the top levels of trophic food webs. We created a functional dataset of continuous craniomandibular and dental characters known from neontological studies to be functionally significant in modern aquatic tetrapods. We analysed this dataset with multivariate ordination and inferential statistics to assess functional similarities and differences in the marine reptile faunas of two well-sampled Jurassic ecosystems deposited in the same seaway: the Oxford Clay Formation (OCF, Callovian–early Oxfordian, Middle–Late Jurassic) and the Kimmeridge Clay Formation (KCF, Kimmeridgian–Tithonian, Late Jurassic) of the UK. Lower jaw-based macroevolutionary trends are similar to those of tooth-based diversity studies. Closely related species cluster together, with minimal overlaps in the morphospace. Marine reptile lineages were characterized by the distinctive combinations of features, but we reveal multiple instances of morphofunctional convergence among different groups. We quantitatively corroborate previous observations that the ecosystems in the OCF and KCF were markedly distinct in faunal composition and structure. Morphofunctional differentiation may have enabled specialization and was an important factor facilitating the coexistence of diverse marine reptile assemblages in deep time.
Identification of causative fungus from sterile abscess using metagenomics followed by in situ hybridization
Authors: Oki Hiroya , Niwa Ryotaro , Pranee Somboonthum , Motooka Daisuke , Onda Yoshiyuki , Nakata Jun , Nakajima Hiroko , Oka Yoshihiro , Sugiyama Haruo , Yoshii Yuka , Anzai Naoyuki , Nakamura Shota , Iida Tetsuya
Published: May 2024

Introduction:  Invasive fungal infections require early diagnosis for treatment. Microscopic observation of biopsy and blood culture are the gold standard for identification of the causative fungus, but it is difficult to identify the causative pathogen by a sterile abscess biopsy.
Case Presentation: We present a case report of breakthrough invasive trichosporonosis in a 65-year-old Japanese male with acute myeloid leukemia (AML) receiving antifungal prophylaxis. Blood cultures showed no fungal growth, and a liver biopsy and a removed spleen with abscess showed fragmented fungi, but no fungal identification was possible. This report demonstrates that retrospective analyses were able to identify the causative fungus.
Conclusion: We narrowed down the candidate fungi by deep sequencing of the ITS1 region of fungal genome and confirmed that the fungus observed in the specimen was T. asahii by in situ hybridization using a DNA probe targeting 26S rRNA.
Evaluation of Susceptibility Status of Some Clinical Bacterial Isolates to Generations of Cephalosporins Sold in Kano
Authors: Ibrahim Safiyya Atiku , Muhammad Bashir , Rabiu Ismail , Muhammed Abdulazeez
Published: May 2024

Introduction: The circulation of substandard antibiotics is believed to aggravate the evil effect of Antibiotic resistance (AR) globally.  AR knows no boundaries and pose a serious threat to existing antibiotics Gap statement: Sabon Gari market is chosen due to reports of substandard antibiotics. It's a major distribution centre for pharmaceuticals, yet research on its impact and extent of substandard drugs is lacking. Aim: This study aims to evaluate the susceptibility status of some clinical Bacterial isolates (E. coli, K. pneumoniae, S. aureus, S. pneumoniae, P. aeruginosa and Salmonella sp.) to generations of Cephalosporins purchased from drug distributors in Sabon Gari Market Kano. Methodology: Antimicrobial susceptibility pattern of the test isolates was determined by disc diffusion method. Fourier Transform Infrared Spectroscopy (FT-IR) analysis was used to confirm the functional group of the active ingredients of all the antibiotics tested. Molecular identification of resistant gene (CTX-M1) were carried out using PCR. Results: Market survey reveals that Cephalexin 61% (first generation), Cefuroxime 72% (Second generation) and Cefexime 68%, Cefpodoxime 79%, Ceftriazone 63%, Ceftazidime 70% and Cefotaxime 45% (third generation) and Cefepime 84% (fourth generation) were the most commonly sold Cephalosporins, with different brands and company names.  In all the antibiotics tested, similar activity was observed in the branded antibiotics as compared with the standard antibiotics, with no significant difference observed. Exactly 20% of E. coli and K. pneumoniae were resistant while 80% of S. aureus, S. pneumoniae, Pseudomonas, and Salmonella sp. were susceptible. CTX-M1 resistant gene was identified E. coli and K. pneumoniae which further confirms their resistance to Cefotaxime and ceftriaxone antibiotics. Conclusion: Branded cephalosporins sold in Kano were effective as standard antibiotics with good bioavailability and compliance with the standards formulation of medicine, thus fit for human intake.
Duration of Morning Hyperinsulinemia Determines Hepatic Glucose Uptake and Glycogen Storage Later in the Day
Authors: Waterman Hannah L. , Moore Mary Courtney , Smith Marta S. , Farmer Ben , Scott Melanie , Edgerton Dale S. , Cherrington Alan D.
Published: May 2024

The second meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 hours of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, we administered the same total amount of insulin either over 2h in the first (Ins2h-A) or second (Ins2h-B) half of the morning, or over the entire 4h (Ins4h) of the morning. In the 4h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared to the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp.

New and noteworthy

Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin’s ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.
Red harvester ant nests impact soil compaction but not temperature in peri-urban habitats of the Lower Rio Grande Valley
Authors: Hernandez Geovanni , Penn Hannah J. , Cano Richard , Elliott-Vidaurri Lilly V. , Choudhury Robin A.
Published: May 2024

Ants are vital ecosystem engineers that can influence soil properties, subsequent soil processes, and associated biota via underground nest construction. Harvester ants consume seeds and are often found in arid areas, frequently altering soil chemistry and bulk density of the soils in and around their nest sites. Many species of harvester ants also intentionally remove vegetation around nest openings, creating cones or discs of bare soil that may further alter soil temperatures. However, much of the work investigating the impacts of harvester ants on soil properties has occurred in shrubland and grassland settings rather than suburban environments. We aimed to determine ifPogonomyrmex barbatus(Smith) (Hymenoptera: Formicidae) nests in a suburban habitat in the Lower Rio Grande Valley in Texas similarly altered soil properties. First, we measured active nest disc size to determine changes and colony persistence. Then we assessed soil compaction and surface temperature along a gradient centered on the disc. We found that disc size did not increase throughout the two-year observation period and that nests with smaller discs were less likely to persist between years. While we did not observe any changes in surface temperature across the gradient, we found a significant increase in soil compaction with greater distance from the center of the disc. These data indicate that increased nest size increases the extent of soil impacted. The impacts of nests reducing soil compaction, particularly within a suburban landscape with precipitation run-off issues and a highly disturbed plant community should be addressed in future studies.
Oligosaccharyltransferase is involved in targeting to ER-associated degradation
Authors: Shenkman Marina , Ogen-Shtern Navit , Patel Chaitanya , Groisman Bella , Pasmanik-Chor Metsada , Schermann Sonya M. , Körner Roman , Lederkremer Gerardo Z.
Published: May 2024

Most membrane and secretory proteins undergo N-glycosylation, catalyzed by oligosaccharyltransferase (OST), a membrane-bound complex in the endoplasmic reticulum (ER). Proteins failing quality control are degraded via ER-associated degradation (ERAD), involving retrotranslocation to cytosolic proteasomes. Using SILAC proteomics, we identified OST subunits as key interactors with a misfolded ER protein bait, suggesting unexpected involvement in ERAD. Previous reports implied additional roles for OST subunits beyond N-glycosylation, such as quality control by ribophorin I. We tested OST engagement in glycoprotein and non-glycosylated protein ERAD; overexpression or partial knockdown of OST subunits interfered with ERAD in conditions that did not affect glycosylation. Effects were studied on misfolded membrane proteins, BACE476 and asialoglycoprotein receptor H2a, and the luminal α1-antitrypsin NHK variant. OST appears to participate in late ERAD stages, interacting with the E3 ligase HRD1 and facilitating retrotranslocation. Molecular dynamics simulations suggest membrane thinning by OST transmembrane domains, possibly assisting retrotranslocation via membrane distortion.
Variant effect predictor correlation with functional assays is reflective of clinical classification performance
Authors: Livesey Benjamin J. , Marsh Joseph A.
Published: May 2024

Background

Understanding the relationship between protein sequence and function is crucial for accurate genetic variant classification. Variant effect predictors (VEPs) play a vital role in deciphering this complex relationship, yet evaluating their performance remains challenging for several reasons including data circularity, where the same or related data is used for training and assessment. High-throughput experimental strategies like deep mutational scanning (DMS) offer a promising solution.

Results

In this study, we extend upon our previous benchmarking approach, assessing the performance of 97 different VEPs using DMS experiments from 36 different human proteins. In addition, a new pairwise, VEP-centric ranking method reduces the impact of missing predictions on the overall ranking. We observe a remarkably high correspondence between VEP performance in DMS-based benchmarks and clinical variant classification, especially for predictors that have not been directly trained on human clinical variants.

Conclusions

Our results suggest that comparing VEP performance against diverse functional assays represents a reliable strategy for assessing their relative performance in clinical variant classification. However, major challenges in clinical interpretation of VEP scores persist, highlighting the need for further research to fully leverage computational predictors for genetic diagnosis. We also address practical considerations for end users in terms of choice of methodology.
Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice
Authors: Beeve Alec T , Hassan Mohamed G , Li Anna , Migotsky Nicole , Silva Matthew J , Scheller Erica L
Published: May 2024

Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5-days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified sections of the mid-diaphysis using RadialQuant. In control animals, anabolic loading induced maximal periosteal bone formation at the site of peak compression, as has been reported previously. Loading did not significantly change overall periosteal nerve density. However, a trending 28% increase in periosteal axons was noted at the site of peak compression in loaded limbs. Neurectomy depleted 88% of all periosteal axons, with near-total depletion on load-responsive surfaces. Neurectomy alone also caused de novo bone formation on the lateral aspect of the mid-diaphysis. However, neurectomy did not inhibit load-induced increases in periosteal bone area, mineralizing surface, or bone formation rate. Rather, neurectomy spatially redistributed load-induced bone formation towards the lateral tibial surface with a reduction in periosteal bone formation at the posterolateral apex (-63%) and enhancement at the lateral surface (+1360%). Altogether, this contributed to comparable load-induced changes in cortical bone area fraction (+4.4% in controls; +5.4% in neurectomized). Our results show that local skeletal innervation modulates but is not required for skeletal adaptation to applied load. This supports the continued use of loading and weight-bearing exercise as an effective strategy to increase bone mass, even in patients with peripheral nerve damage or dysfunction.
Machine Learning Approaches for Skin Neoplasm Diagnosis
Authors: Asaduzzaman Abu , Thompson Christian C. , Uddin Md J.
Published: May 2024

Approaches for skin neoplasm diagnosis include physical exam, skin biopsy, lab tests of biopsy samples, and image analyses. These approaches often involve error-prone and time-consuming processes. Recent studies show that machine learning has promises to effectively classify skin images into different classes such as melanoma and melanocytic nevi. In this work, we investigate machine learning approaches to enhance the performance of computer-aided diagnosis (CADx) systems to diagnose skin diseases. In the proposed CADx system, generative adversarial network (GAN) is used to identify (and remove) fake images. Exploratory data analysis (EDA) is applied to normalize the original dataset for preventing model overfitting. Synthetic minority over-sampling technique (SMOTE) is employed to rectify class imbalances in the original dataset. To accurately classify skin images, the following four machine learning models are utilized: linear discriminant analysis (LDA), support vector machine (SVM), convolutional neural network (CNN), and an ensemble CNN-SVM. Experimental results using the HAM10000 dataset demonstrate the ability of the machine learning models to improve CADx performance in treating skin neoplasm. Initially, the LDA, SVM, CNN, and ensemble CNN-SVM show 49%, 72%, 77%, and 79% accuracy, respectively. After applying GAN, EDA, and SMOTE, the LDA, SVM, CNN, and ensemble CNN-SVM show 76%, 83%, 87%, and 94% accuracy, respectively. We plan to explore other machine learning models and datasets in our next endeavor.
Antennal sensilla diversity in diurnal and nocturnal fireflies (Coleoptera, Lampyridae)
Authors: Pacheco Yelena M. , Mann Ethan , Da Silveira Luiz F. L. , Bybee Seth M. , Branham Marc A. , McHugh Joseph V. , Stanger-Hall Kathrin F.
Published: May 2024

Insects use their antennae to collect environmental information. While the structural diversity of insect antennae is immediately obvious, the diversity of the minute antennal sensilla that interact with the environmental stimuli and translate them into sensory input, is largely unknown for many insect groups. This includes the beetle family Lampyridae, which includes nocturnal species that use bioluminescent signals during mate search, and diurnal species that rely exclusively on pheromones to identify and locate a potential mate. Diurnal species tend to have relatively larger antennae, and diurnal males have larger antennae than their females. It is generally assumed that antennal size reflects sensilla numbers, but this remains to be tested. Here we use Scanning Electron Microscopy to document the sensilla diversity of both males and females of three diurnal and four nocturnal firefly species, as well as total sensilla numbers, densities and their distribution along the antenna. We identified 14 sensilla morphotypes across the seven species, including 12 morphotypes that are new for Lampyridae. Mechanosensilla (3 morphotypes) were the most abundant and conserved sensilla across firefly species, and the distribution of chemosensilla (9 morphotypes) was unexpectedly variable across species. We hypothesized that the differences in mating signals between diurnal and nocturnal fireflies would be reflected in their chemosensilla counts or densities. As predicted, diurnal and nocturnal fireflies did not differ in their mechanoreceptor counts or densities, nor did males and females. In contrast, firefly males had significantly more chemoreceptors (and higher densities) than females and the interaction term (activity by sex) was also significant: diurnal males had significantly more chemoreceptors than nocturnal males, highlighting the importance of pheromones for diurnal species. Based on a series of predictions, we also identified a pheromone sensilla candidate for each species that will facilitate functional testing in future studies.
Effects of floral sex allocation and phenology on the within-flower selfing rate and female reproductive success inPulsatilla alpina, a perennial herb with strong inbreeding depression
Authors: Chen Kai-Hsiu , Pannell John R.
Published: May 2024

Within-flower self-pollination should be the major source of self-fertilization in mixed-mating species presenting single or few flowers simultaneously. It is also an often unmeasured source of selfing in species with many flowers open simultaneously. In general, the rate of within-flower selfing is expected to depend on the number of pistils and stamens, the timing of flowering, and subsidiary floral traits in self-compatible species in which pistil and stamen numbers vary. Accordingly, the intensity and direction of selection on these traits should depend on the level of inbreeding depression. Here, we measured the dependence of the within-flower selfing rate on floral sex allocation, phenology, petal length, and floral stalk height in a population of the perennial herb Pulsatilla alpina (Ranunculaceae) in which most individuals had single flowers. We estimated inbreeding depression in the population by comparing inbreeding coefficients between parents and seed progeny using microsatellite markers. We then estimated selection on the measured traits via female reproductive success at the flower level and compared our estimates with a hypothetical scenario in which inbreeding depression was assumed to be absent. We estimated inbreeding depression to be 0.93. The within-flower selfing rate varied widely among flowers and depended positively on stamen number and negatively on pistil number and flowering date, supporting the predictions of a mass-action model. The dependence of the selfing rate on the measured floral traits consistently predicted (non-linear) patterns of selection under high inbreeding depression that were distinct from those under a hypothetical scenario of no inbreeding depression. Synthesis: While previous research has emphasized the importance of mass-action mating on selfing among flowers of plants with large floral displays, our results demonstrate its importance for selfing within individual flowers. They also demonstrate the importance of accounting for both the selfing rate and inbreeding depression when inferring selection on floral and other traits via female fitness.
Antidepressant prescribing inequalities in people with comorbid depression and type 2 diabetes: a UK primary care electronic health record study
Authors: Ng Y , Hayes J , Jeffery A
Published: May 2024

Aims

To compare the likelihood of being prescribed an antidepressant in depressed individuals with and without type 2 diabetes.

Methods

We performed a matched cohort study using primary care record data from the UK Clinical Practice Research Datalink. We used multivariable logistic regression to compare antidepressant prescribing during the first five years of starting oral antidiabetic medication to a comparison group without type 2 diabetes, matched based on GP practice, age and sex. We performed subgroup analyses stratified by sex, age and ethnicity.

Results

People with type 2 diabetes and depression were 75% less likely to be prescribed an antidepressant compared to people with depression alone (odds ratio (OR) 0.25, 95% confidence interval (CI) 0.25 to 0.26). This difference was greater in males (OR 0.23, 95% CI, 0.22 to 0.24), people older than 56 years (OR 0.23, 95% CI, 0.22 to 0.24), or from a minoritised ethnic background (Asian OR 0.14, 95% CI 0.12-0.14; Black OR 0.12, 95% CI 0.09-0.14).

Conclusions

There may be inequalities in access to antidepressant treatment for people with type 2 diabetes, particularly those who are male, older or from minoritised ethnic backgrounds.
Neural Network Correlates of Apathy, Disinhibition, and Executive Dysfunction in Active-Duty United States Special Operations Forces
Authors: Gilmore Natalie , McKinney Isabella R. , Tseng Chieh-En J. , Greve Douglas N. , Maffei Chiara , Healy Brian C. , Zürcher Nicole R. , Hooker Jacob M. , Tromly Samantha L. , Perl Daniel P. , Dams-O’Connor Kristen , Mac Donald Christine L. , Edlow Brian L. , Bodien Yelena G.
Published: May 2024

United States Special Operations Forces (SOF) experience neurobehavioral symptoms that can adversely affect training and combat operations. Understanding the neurobiological basis for these symptoms may guide prevention and treatment. In 29 male active-duty SOF with mean (SD) 17(4) years of service, we tested whether self-reported symptoms of apathy, disinhibition, and executive dysfunction measured by the Frontal Systems Behavior Scale, were related to functional magnetic resonance imaging and positron emission tomography biomarkers (translocator protein and tau) of the limbic, salience, and executive control networks. Higher disinhibition was associated with lower functional connectivity and higher tau signal within the salience network.
Allosteric inhibition of CXCR1 and CXCR2 abrogates Th2/Th17-associated Allergic Lung Inflammation in Mice
Authors: Hosoki Koa , Govindhan Annamalai , Knight John M , Sur Sanjiv
Published: May 2024

Background

IL4, IL5, IL13, and IL17-producing CD4 T helper 2 (Th2)-cells and IL17-producing CD4 T helper 17 (Th17)-cells contribute to chronic eosinophilic and neutrophilic airway inflammation in asthma and allergic airway inflammation. Chemokines and their receptors are upregulated in Th2/Th17-mediated inflammation. However, the ability of CXCR1 and CXCR2 modulate Th2 and Th17-cell-mediated allergic lung inflammation has not been reported.

Methods

Mice sensitized and challenged with cat dander extract (CDE) mount a vigorous Th2-Th17-mediated allergic lung inflammation. Allosteric inhibitor of CXCR1 and CXCR2, ladarixin was orally administered in this model. The ability of ladarixin to modulate allergen-challenge induced recruitment of CXCR1 and CXCR2-expressing Th2 and Th17-cells and allergic lung inflammation were examined.

Results

Allergen challenge in sensitized mice increased mRNA expression levels ofIl4, Il5, Il13, Il6, Il1β, Tgfβ1, Il17, Il23, Gata3,andRorc, and induced allergic lung inflammation characterized by recruitment of CXCR1- and CXCR2-expressing Th2-cells, Th17-cells, neutrophils, and eosinophils. Allosteric inhibition of CXCR1 and CXCR2 vigorously blocked each of these pro-inflammatory effects of allergen challenge. CXCL chemokines induced a CXCR1 and CXCR2-dependent proliferation of IL4, IL5, IL13, and IL17 expressing T-cells.

Conclusion

Allosteric inhibition of CXCR1 and CXCR2 abrogates blocks recruitment of CXCR1- and CXCR2-expressing Th2-cells, Th17-cells, neutrophils, and eosinophils in this mouse model of allergic lung inflammation. We suggest that the ability of allosteric inhibition of CXCR1 and CXCR2 to abrogate Th2 and Th17-mediated allergic inflammation should be investigated in humans.
Knockout ofcryptochrome 1disrupts circadian rhythm and photoperiodic diapause induction in the silkworm,Bombyx mori
Authors: Tobita Hisashi , Kiuchi Takashi
Published: May 2024

Most insects enter diapause, a state of physiological dormancy crucial for enduring harsh seasons, with photoperiod serving as the primary cue for its induction, ensuring proper seasonal timing of the process. Although the involvement of the circadian clock in the photoperiodic time measurement has been demonstrated through knockdown or knockout of clock genes, the precise molecular mechanisms in this context remain unclear. In bivoltine strains of the silkworm,Bombyx mori, embryonic diapause is maternally controlled and affected by environmental conditions experienced by mother moths during embryonic and larval stages. Previous research highlighted the role of core clock genes, includingperiod(per),timeless(tim),Clock(Clk) andcycle(cyc), in photoperiodic diapause induction inB. mori. In this study, we focused on another clock gene,cryptochrome 1(cry1), which functions as a photoreceptor implicated in photoentrainment of the circadian clock across various insect species. Phylogenetic analysis and conserved domain identification confirmed the presence of bothDrosophila-typecry(cry1) and mammalian-typecry(cry2) genes in theB. morigenome, akin to other lepidopterans. Temporal expression analysis revealed highercry1gene expression during the photophase and lower expression during the scotophase, with knockouts of core clock genes (per,tim,Clkandcyc) disrupting this temporal expression pattern. Using CRISPR/Cas9-mediated genome editing, we established acry1knockout strain in p50T, a bivoltine strain exhibiting clear photoperiodism during both embryonic and larval stages. Although the wild-type strain displayed circadian rhythm in eclosion under continuous darkness, thecry1knockout strain exhibited arrhythmic eclosion, implicatingB. mori cry1in the circadian clock feedback loop governing behavior rhythms. Females of thecry1knockout strain failed to induce photoperiodic diapause during both embryonic and larval stages, mirroring the diapause phenotype of the wild-type individuals reared under constant darkness, indicating thatB. moriCRY1 contributes to photoperiodic time measurement as a photoreceptor. Furthermore, photoperiodic diapause induction during the larval stage was abolished in acry1/timdouble-knockout strain, suggesting that photic information received by CRY1 is relayed to the circadian clock. Overall, this study represents the first evidence ofcry1involvement in insect photoperiodism, specifically in diapause induction.

Highlights

Knockouts of core clock genes disrupted the rhythmic expression ofcryptochrome 1(cry1).

Acry1knockout strain was established using CRISPR/Cas9.

Thecry1knockout strain lost its eclosion rhythm.

Knockout ofcry1disrupted photoperiodic diapause induction.

Females of acry1/timdouble knockout strain produced only non-diapause eggs regardless of larval photoperiod.

Graphical abstract
Successful Cardiac Resynchronization Therapy Reduces Negative Septal Work in Patient-Specific Models of Dyssynchronous Heart Failure
Authors: Craine Amanda , Krishnamurthy Adarsh , Villongco Christopher T. , Vincent Kevin , Krummen David E. , Narayan Sanjiv M. , Kerckhoffs Roy C. P. , Omens Jeffrey H. , Contijoch Francisco , McCulloch Andrew D.
Published: May 2024

In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work.

We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.
Parallel rapid phenotypic differentiation along climatic gradients in multiple introduced lineages of an alien plant species
Authors: Matsuhashi Saeko , Kudoh Hiroshi , Oguro Michio , Sakai Satoki
Published: May 2024

Widespread plant species are faced with various climatic gradients and undergo clinal differentiation. Alien species which have been introduced repeatedly can be used to investigate the parallel processes of clinal differentiation during their range expansions.Cardamine hirsutaL. has been unintentionally introduced to Japan at least three times and has become widely distributed across Japan. To elucidate the processes of clinal differentiation, we conducted a common garden experiment using three lineages ofC. hirsuta(North, East, and West). We tested for phenotypic differentiation among and within the lineages, and for a common pattern of clinal variations in phenotypic traits. We detected differentiations of flowering phenology and body size within and among the lineages. The East lineage showed delayed flowering phenology and larger mass, whereas the West lineage showed rapid flowering phenology and smaller mass. In addition, three patterns of variation between climate factors in seed source habitats and phenotypic traits were detected in all three lineages: higher temperature was related to earlier flowering and lower leaf number at the start of flowering, and more hours of sunshine were related to shorter flowering period. These patterns imply independent and parallel differentiations in the three lineages. These results suggest that analyses of distinct lineages allow repeated observations of differentiation processes and rapid responses of species during successful distribution in new environments.
Automated segmentation of epilepsy surgical resection cavities: comparison of four methods to manual segmentation
Authors: Courtney Merran R , Sinclair Benjamin , Neal Andrew , Nicolo John-Paul , Kwan Patrick , Law Meng , O'Brien Terence J , Vivash Lucy
Published: May 2024

Accurate resection cavity segmentation on MRI is important for neuroimaging research involving epilepsy surgical outcomes. Manual segmentation, the gold standard, is highly labour intensive. Automated pipelines are an efficient potential solution; however, most have been developed for use following temporal epilepsy surgery. Our aim was to compare the accuracy of four automated segmentation pipelines following surgical resection in a mixed cohort of subjects following temporal or extra temporal epilepsy surgery. We identified 4 open-source automated segmentation pipelines. Epic-CHOP and ResectVol utilise SPM-12 within MATLAB, while Resseg and Deep Resection utilise 3D U-net convolutional neural networks. We manually segmented the resection cavity of 50 consecutive subjects who underwent epilepsy surgery (30 temporal, 20 extratemporal). We calculated Dice similarity coefficient (DSC) for each algorithm compared to the manual segmentation. No algorithm identified all resection cavities. ResectVol (n=44, 88%) and Epic-CHOP (n=43, 86%) were able to detect more resection cavities than Resseg (n=22, 44%, P<0.001) and Deep Resection (n=21, 42%, P<0.001). The SPM-based pipelines (Epic-CHOP and ResectVol) performed better than the deep learning-based pipelines in the overall and extratemporal surgery cohorts, however there was no difference between methods in the temporal surgery cohort. These pipelines could be applied to machine learning studies of outcome prediction to improve efficiency in pre-processing data, however human quality control is still required.
STEMorph: A Set of Morphed Emotional Face Stimuli from Angry to Happy Derived fromNimStim
Authors: Katebi Mohammad Ebrahim , Ghafari Mohammad Hossein , Ghafari Tara
Published: May 2024

Emotion recognition through facial expressions is crucial for interpreting social cues. However, it is often influenced by biases, i.e, systematic recognition advantages for particular emotions. Nevertheless, these biases are inconsistently reported across studies, likely due to methodological variations which underline the necessity for a standardized approach. Traditional face morphing methods can create unnatural-looking stimuli, and may confound the interpretation of emotions. To address this issue, we here introduceSTEMorph, a validated stimulus set based on the NimStim set. We employed neutral-anchored morphing and neural-network-generated masks to ensure the natural appearance and integrity of the depicted emotions. We validated our stimulus set by having participants rate each face on a 9-point scale ranging from angry to happy, assessing the perceived emotional intensity.STEMorph’svalidity was confirmed through linear regression analysis, showing a strong correlation between subjective ratings and targeted emotional states. Moreover, aligning with previous research highlighting gender as a key factor in emotion recognition,STEMorphalso exhibits variations in ratings across gender subgroups.STEMorph’sreliability was confirmed through a two-week follow-up rating session with a subgroup of the same participants. By introducing a controlled, validated, and ecologically valid stimulus set of emotional faces,STEMorphpaves the way for further investigations into facial emotion recognition, deepening our understanding of this vital aspect of human interaction.
Time of first contact determines cooperator success in a cross-feeding consortium
Authors: Los Rachel , Fecker Tobias , van Touw P.A.M. , van Tatenhove-Pel Rinke J. , Idema Timon
Published: May 2024

Microbial communities are characterised by complex interaction, including cooperation and cheating, which have significant ecological and applied implications. However, the factors determining the success of cooperators in the presence of cheaters remain poorly understood. Here, we investigate the dynamics of cooperative interactions in a cross-feeding consortium using individual-based simulations and an engineeredL. cremoristoy consortium. Our simulations reveal first contact time between cooperators as a critical predictor for cooperator success. By manipulating the relative distances between cooperators and cheaters or the background growth rates, influenced by the cost of co-operation, we can modulate this first contact time and influence cooperator success. Our study underscores the importance of cooperators coming into contact with each other on time, which provides a simple and generalizable framework for understanding and designing cooperative interactions in microbial communities. These findings contribute to our understanding of cross-feeding dynamics and offer practical insights for synthetic and biotechnological applications.
Effects of systemic oxytocin receptor activation and blockade on risky decision making in female and male rats
Authors: Faraji Mojdeh , Viera-Resto Omar A. , Berrios Brenden J. , Bizon Jennifer L. , Setlow Barry
Published: May 2024

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, “safe” food reward and a large, “risky” food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Neither drug affected task performance in males. In females, however, both oxytocin and L-368,899 caused a dose-dependent reduction in preference for large risky reward. Control experiments showed that these effects could not be accounted for by alterations in food motivation or shock sensitivity. Together, these results reveal a sex-dependent effect of oxytocin signaling on risky decision making in rats.
plantMASST - Community-driven chemotaxonomic digitization of plants
Authors: Gomes Paulo Wender P. , Mannochio-Russo Helena , Schmid Robin , Zuffa Simone , Damiani Tito , Quiros-Guerrero Luis-Manuel , Caraballo-Rodríguez Andrés Mauricio , Zhao Haoqi Nina , Yang Heejung , Xing Shipei , Charron-Lamoureux Vincent , Chigumba Desnor N. , Sedio Brian E. , Myers Jonathan A. , Allard Pierre-Marie , Harwood Thomas V. , Tamayo-Castillo Giselle , Kang Kyo Bin , Defossez Emmanuel , Koolen Hector H. F. , da Silva Milton Nascimento , e Silva Consuelo Yumiko Yoshioka , Rasmann Sergio , Walker Tom W. N. , Glauser Gaëtan , Chaves-Fallas José Miguel , David Bruno , Kim Hyunwoo , Lee Kyu Hyeong , Kim Myeong Ji , Choi Won Jun , Keum Young-Sam , de Lima Emilly J. S. P. , de Medeiros Lívia Soman , Bataglion Giovana A. , Costa Emmanoel V. , da Silva Felipe M. A. , Carvalho Alice Rhelly V. , Reis José Diogo E. , Pamplona Sônia , Jeong Eunah , Lee Kyungha , Kim Geum Jin , Kil Yun-Seo , Nam Joo-Won , Choi Hyukjae , Han Yoo Kyong , Park Si Young , Lee Ki Yong , Hu Changling , Dong Yilun , Sang Shengmin , Morrison Colin R. , Borges Ricardo Moreira , Teixeira Andrew Magno , Lee Seo Yoon , Lee Bum Soo , Jeong Se Yun , Kim Ki Hyun , Rutz Adriano , Gaudry Arnaud , Bruelhart Edouard , Kappers Iris F. , Karlova Rumyana , Meisenburg Mara , Berdaguer Roland , Tello J. Sebastián , Henderson David , Cayola Leslie , Wright S. Joseph , Allen David N. , Anderson-Teixeira Kristina J. , Baltzer Jennifer L. , Lutz James A. , McMahon Sean M. , Parker Geoffrey G. , Parker John D. , Northen Trent R. , Bowen Benjamin P. , Pluskal Tomáš , van der Hooft Justin J. J. , Carver Jeremy J. , Bandeira Nuno , Pullman Benjamin S. , Wolfender Jean-Luc , Kersten Roland D. , Wang Mingxun , Dorrestein Pieter C.
Published: May 2024

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.
Optimizing Coarse-Grained Models for Large-Scale Membrane Protein Simulation
Authors: Wen Chen Yun , Luo Yun Lyna , Madsen Jesper J.
Published: May 2024

Coarse-grained (CG) models have been developed for studying membrane proteins at physiologically relevant scales. Such methods, including popular CG lipid models, exhibit stability and efficiency at moderate scales, but they can become impractical or even unusable beyond a critical size due to various technical issues. Here, we report that these scale-dependent issues can arise from progressively slower relaxation dynamics and become confounded by unforeseen instabilities observed only at larger scales. To address these issues, we systemically optimized a 4-site solvent-free CG lipid model that is suitable for conducting micron-scale molecular dynamics simulations of membrane proteins under various membrane properties. We applied this lipid model to explore the long-range membrane deformation induced by a large mechanosensitive ion channel, PIEZO. We show that the optimized CG models are powerful in elucidating the structural and dynamic interplay between PIEZO and the membrane. Furthermore, we anticipate that our methodological insights can prove useful for resolving issues stemming from scale-dependent limitations of similar CG methodologies.
Patterning, regulation, and role of FoxO/DAF-16 in the early embryo
Authors: Mauro Michael S. , Martin Sophia L. , Dumont Julien , Shirasu-Hiza Mimi , Canman Julie C.
Published: May 2024

Insulin resistance and diabetes are associated with many health issues including higher rates of birth defects and miscarriage during pregnancy. Because insulin resistance and diabetes are both associated with obesity, which also affects fertility, the role of insulin signaling itself in embryo development is not well understood. A key downstream target of the insulin/insulin-like growth factor signaling (IIS) pathway is the forkhead family transcription factor FoxO (DAF-16 inC. elegans). Here, we used quantitative live imaging to measure the patterning of endogenously tagged FoxO/DAF-16 in the early worm embryo. In 2-4-cell stage embryos, FoxO/DAF-16 initially localized uniformly to all cell nuclei, then became dramatically enriched in germ precursor cell nuclei beginning at the 8-cell stage. This nuclear enrichment in early germ precursor cells required germ fate specification, PI3K (AGE-1)- and PTEN (DAF-18)-mediated phospholipid regulation, and the deubiquitylase USP7 (MATH-33), yet was unexpectedly insulin receptor (DAF-2)- and AKT-independent. Functional analysis revealed that FoxO/DAF-16 acts as a cell cycle pacer for early cleavage divisions–without FoxO/DAF-16 cell cycles were shorter than in controls, especially in germ lineage cells. These results reveal the germ lineage specific patterning, upstream regulation, and cell cycle role for FoxO/DAF-16 during earlyC. elegansembryogenesis.
Low copy CRISPR-Cas13d mitigates collateral RNA cleavage
Authors: Hart Sydney K. , Wessels Hans-Hermann , Méndez-Mancilla Alejandro , Müller Simon , Drabavicius Gediminas , Choi Olivia , Sanjana Neville E.
Published: May 2024

While CRISPR-Cas13 systems excel in accurately targeting RNA, the potential for collateral RNA degradation poses a concern for therapeutic applications and limits broader adoption for transcriptome perturbations. We evaluate the extent to which collateral RNA cleavage occurs whenRfxCas13d is delivered via plasmid transfection or lentiviral transduction and find that collateral activity only occurs with high levels ofRfxCas13d expression. Using transcriptome-scale and combinatorial CRISPR pooled screens in cell lines with low-copyRfxCas13d, we find high on-target knockdown, without extensive collateral activity regardless of the expression level of the target gene. In contrast, transfection ofRfxCas13d, which yields higher nuclease expression, results in collateral RNA degradation. Further, our analysis of a high-fidelity Cas13 variant uncovers a marked decrease in on-target efficiency, suggesting that its reduced collateral activity may be due to an overall diminished nuclease capability.
Perineuronal nets in motor circuitry regulate the performance of learned vocalizations in songbirds
Authors: Wan Xinghaoyun , Wang Angela S. , Storch Daria-Salina , Li Vivian Y. , Sakata Jon T.
Published: May 2024

The accurate and reliable production of learned behaviors can be important for survival and reproduction; for example, the performance of learned vocalizations (e.g., speech and birdsong) modulates the efficacy of social communication in humans and songbirds. Consequently, it is critical to understand the factors that regulate the performance of learned behaviors. Across various taxa, neural circuits that regulate motor learning are replete with perineuronal nets (PNNs), extracellular matrices that surround neurons and shape neural dynamics and plasticity. Perineuronal nets in circuits for sensory and cognitive processes have been found to affect sensory processing and behavioral plasticity. However, the function of PNNs in motor circuits remains largely unknown. Here, we analyzed the causal contribution of PNNs in motor circuitry to the performance of learned vocalizations in songbirds. Songbirds like the zebra finch are powerful models for this endeavor because the performance of their learned songs is regulated by activity within discrete and specialized circuits (i.e., song system) that are dense with PNNs. We first report that developmental increases in the density and intensity of PNNs throughout the song system [including in the motor nucleus HVC (acronym used as proper name)] are associated with developmental increases in song performance. We next discovered that enzymatically degrading PNNs in HVC acutely affected song performance. In particular, PNN degradation caused song structure to deviate from pre-surgery song due to changes in syllable sequencing and production. Collectively, our data provide compelling evidence for a causal contribution of PNNs to the performance of learned behaviors.

SIGNIFICANCE STATEMENT

Motor circuits are replete with perineuronal nets (PNNs) but little is known about their contribution to motor performance. Here, we analyzed how PNNs within vocal motor circuits modulate the ability of songbirds to consistently produce their learned songs. We report that developmental increases in PNN expression in vocal circuitry were associated with developmental increases in the ability to consistently perform their learned song. Moreover, degrading PNNs in the vocal motor nucleus HVC reduced the ability of adult birds to accurately produce their learned song. Our findings indicate a causal contribution of PNNs in motor circuitry to the performance of learned behaviors and, because PNNs are expressed in brain areas regulating speech, suggest that PNNs could modulate speech production in humans.