bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to ad libitum milk allowance by crossbred dairy and dairy–beef calves in an automated feeding system
Authors: Arens Sara C , Sharpe Kirsten T , Schutz Michael M , Heins Bradley J 
Published: June 2023

Abstract
The objective of this study was to compare three-breed rotational crossbred calves sired by Holstein, Jersey, Montbéliarde, Normande, Viking Red, and Limousin bulls with Holstein’s calves fed a high milk allowance for growth, milk consumption, health scores, and profitability in an automated group feeding system. Breed groups were Holstein (n = 16), crossbreds of Montbéliarde, Viking Red, and Holstein (n = 24), crossbreds of Jersey, Normande, and Viking Red (n = 6), and Limousin crossbred beef × dairy (n = 45) calves. Calves were randomly assigned within the breed to one of two treatments from September 2019 to June 2020 at the University of Minnesota West Central Research and Outreach Center in Morris, MN. The five breed groups were balanced across the two treatment groups. Treatment groups were fed 8 L/d (8 L) or ad libitum (AL) milk allowance, and calves were introduced to the automated feeder at day 5 and were weaned at 56 d. Milk feeding behaviors (drinking speeds) were collected from the automatic feeding system and analyzed by feeding and breed groups. Body weights were recorded at birth and weekly through weaning. The health scores of calves were recorded twice per week. Variables included in the statistical model for analyses were fixed effects of birthweight, the season of birth, breed group, and treatment group. Calves fed AL had a greater weaning weight (P = 0.001; 106.4 kg vs. 91.4 kg) and greater (P = 0.001) average daily gain (ADG; 1.11 kg/d vs. 0.87 kg/d) than calves fed 8 L, respectively. The calves fed AL (1,064 mL/min) had a slower drinking speed (P = 0.01) than calves fed 8 L (1,467 mL/min). Most breed groups were not different for weaning weight or ADG across the 56 d. Daily milk consumption per calf was lower (P = 0.009) for Limousin crossbred calves compared with Holstein and crossbred dairy calves. As expected, AL calves had higher (P = 0.001) milk cost ($189.52) than the 8 L calves ($140.71). The average cost per kilogram of gain was similar for calves fed 8 L ($2.89/kg) compared to AL ($3.00/kg) calves. Overall, the Limousin crossbred calves had the least milk cost ($152.75) compared with Holstein ($175.67) calves and Montbéliarde, Viking Red, and Holstein crossbred calves ($177.13). The results from this study found that although feeding calves AL resulted in greater milk consumption and higher cost than 8 L calves, there may be an economic advantage with costs per kilogram of gain to feeding calves ad libitum if increased growth rates are realized.
Body mass index as a predictor of the outcomes of acute clozapine toxicity: a cross-sectional study
Authors: Sagah Ghada A , Fayed Manar M 
Published: June 2023

Abstract
Acute antipsychotic overdose is frequently reported nowadays. Clozapine is one of the atypical agents that are highly lipophilic, highly protein-bound, has a large volume of distribution, and accumulates in the brain and other tissues. Obesity is an essential factor controlling patients’ treatment and clinical course. The current study aimed to study the prognostic value of body mass index (BMI) in patients with acute clozapine poisoning. All patients were evaluated on admission using the Poison Severity Score (PSS) and Glasgow Coma Score (GCS). The BMI was calculated. Mortality and the need for ICU admission were defined as primary outcomes, whereas secondary outcomes included cardiovascular complications and the need for mechanical ventilation. Thirty-eight patients presented with acute clozapine poisoning. The mean age of included patients was 25.2 ± 6. Patients were categorized regarding BMI into average weight (26.3%), overweight (31.6%), and obese (42.1%). Pearson’s correlation indicated a significant positive correlation between BMI and respiratory rate (r = .364, p = .025). A significant negative correlation existed between BMI and GCS (r = .674, p ≤ .001). ROC curve reveals that BMI is an excellent predictor for the requirement of mechanical ventilation area under the curve (AUC &gt; .9), a fair predictor of ICU admission AUC (.747). BMI had a sensitivity of 100% and specificity of 51.7 for the prediction of ICU admission. In conclusion, obesity increased the severity of toxicity and the incidence of poor clinical outcomes in patients with acute clozapine poisoning.
Negative phototropism of the shoots helps temperate liana Hedera helix L. to locate host trees under habitat conditions
Authors: Wyka Tomasz P 
Published: June 2023

Abstract
Lianas employ a variety of searching mechanisms to find support; however, it is not clear to what extent environmental signals are used to help direct the search. Several adventitious root climbers have been shown to bend away from light and grow toward darker areas or objects, in one case including actual tree trunks. In the literature, this negative phototropism (NP) has also been informally and inconsistently reported from a temperate root climber Hedera helix L. (common ivy). In this study, rigorous laboratory tests have confirmed the occurrence of NP in both seedlings and prostrate shoots of H. helix. Furthermore, a field experiment with potted ivy seedlings placed around tree trunks demonstrated their ability to remotely locate trees. This finding was corroborated by a survey of growth directions in wild-growing prostrate ivy shoots in two woodland habitats. An additional outdoor experiment showed that the ability to locate support is expressed in shade but supressed by full sun conditions. These results show that H. helix uses NP to locate support and indicate that this ability is a component of the species’ shade escape strategy.
Utilizing nullomers in cell-free RNA for early cancer detection
Authors: Montgomery Austin , Tsiatsianis Georgios Christos , Mouratidis Ioannis , Chan Candace S.Y. , Athanasiou Maria , Papanastasiou Anastasios D. , Kantere Verena , Vathiotis Ioannis , Syrigos Konstantinos , Yee Nelson S. , Georgakopoulos-Soares Ilias 
Published: June 2023

AbstractEarly detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are short sequences that are absent from the human genome but can resurface due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer resurfacing across exonic regions of the genome. We identify nullomer resurfacing mutational hotspots within tumor genes and report that certain mutational signatures are associated with nullomer resurfacing. We show that DNA mismatch repair and homologous recombination repair can be detected from the nullomer profile and provide evidence that nullomers can be used to identify neoepitopes and other targets for precision oncology. Finally, we provide evidence for the identification of nullomers in cell free RNA from peripheral blood samples, enabling early detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.
Neural network-derived electrocardiographic features have prognostic significance and important phenotypic and genotypic associations
Authors: Sau Arunashis , Ribeiro Antonio H. , McGurk Kathryn A. , Pastika Libor , Bajaj Nikesh , Ardissino Maddalena , Chen Jun Yu , Wu Huiyi , Shi Xili , Hnatkova Katerina , Zheng Sean , Britton Annie , Shipley Martin , Andršová Irena , Novotný Tomáš , Sabino Ester , Giatti Luana , Barreto Sandhi M , Waks Jonathan W. , Kramer Daniel B. , Mandic Danilo , Peters Nicholas S. , O’Regan Declan P. , Malik Marek , Ware James S. , Ribeiro Antonio Luiz P. , Ng Fu Siong 
Published: June 2023

AbstractBackgroundSubtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology.HypothesisNovel neural network (NN)-derived ECG features can predict future cardiovascular disease and mortalityMethods and ResultsWe extracted 5120 NN-derived ECG features from an AI-ECG model trained for six simple diagnoses and applied unsupervised machine learning to identify three phenogroups. In the derivation cohort (CODE, 1,558,421 subjects), the three phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared to phenogroup A (HR 1.20, 95% CI 1.17-1.23, p < 0.0001). The predictive ability of the phenogroups was retained in a group with physician confirmed normal ECGs. We externally validated our findings in five diverse cohorts (Figure) and found phenogroup B had a significantly greater risk of mortality in all cohorts. Phenome-wide association study (PheWAS) showed phenogroup B had a higher rate of future AF, ischaemic heart disease, AV block, heart failure, VT, and cardiac arrest.Phenogroup B had increased cardiac chamber volumes and decreased cardiac output. A single-trait GWAS yielded four loci. SCN10A, SCN5A and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. Gradient-weighted Class Activation Mapping (Grad-CAM) identified the terminal QRS and terminal T wave as important regions of the ECG for identification of phenogroup B.ConclusionNN-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.
Role ofBicDRin bristle shaft construction, tracheal development, and support ofBicDfunctions
Authors: Jejina Aleksandra , Ayala Yeniffer , Hernández Greco , Suter Beat 
Published: June 2023

AbstractCell polarization requires asymmetric localization of numerous mRNAs, proteins, and organelles. The movement of cargo towards the minus end of microtubules mostly depends on cytoplasmic dynein motors, which function as multiprotein complexes. In the dynein/dynactin/Bicaudal-D (DDB) transport machinery, Bicaudal-D (BicD) links the cargo to the motor. Here we focus on the role ofBicD-related(BicDR) and its contribution to microtubule-dependent transport processes.Drosophila BicDRis required for the normal development of bristles and dorsal trunk tracheae. Together withBicD,it contributes to the organization and stability of the actin cytoskeleton in the not-yet-chitinized bristle shaft and the localization of Spn-F and Rab6 at the distal tip. We show thatBicDRsupports the function ofBicDin bristle development and our results suggest that BicDR transports cargo more locally whereas BicD is more responsible for delivering functional cargo over the long distance to the distal tip. We identified the proteins that interact with BicDR and appear to be BicDR cargo in embryonic tissues. For one of them, EF1γ, we showed thatEF1γgenetically interacts with BicD andBicDRin the construction of the bristles.
InCellCryst - A streamlined approach to structure elucidation usingin cellulocrystallized recombinant proteins
Authors: Schönherr Robert , Boger Juliane , Lahey-Rudolph J. Mia , Harms Mareike , Kaiser Jaqueline , Nachtschatt Sophie , Wobbe Marla , Duden Rainer , König Peter , Bourenkov Gleb P. , Schneider Thomas R. , Redecke Lars 
Published: June 2023

AbstractWith the advent of serial X-ray crystallography on microfocus beamlines at free-electron laser and synchrotron facilities, the demand for protein microcrystals has significantly risen in recent years. However, by conventional methods extensive efforts are usually required to purify proteins and produce sufficiently homogeneous microcrystals. Here, we present InCellCryst, an advanced pipeline for producing homogeneous microcrystals directly within living insect cells. Our baculovirus-based cloning system enables the production of crystals from completely unmodified proteins as well as the screening of different cellular compartments to maximize chances for protein crystallization. By optimizing cloning procedures, recombinant virus production, crystallization and crystal detection, X-ray diffraction data can be collected 24 days after the start of target gene cloning. Furthermore, new strategies for serial synchrotron diffraction data collection directly from crystals within living cells abolish the need to purify the recombinant protein or the associated microcrystals.
VAMP2 regulates phase separation of alpha-synuclein
Authors: Agarwal Aishwarya , Raza Farheen , Hilcenko Christine , Stott Katherine , Morone Nobuhiro , Warren Alan J. , Lautenschläger Janin 
Published: June 2023

SummaryAlpha-synuclein (aSYN) is a small synaptic protein that is linked to Parkinson’s disease (PD) and other synucleinopathies. aSYN has been shown to undergo protein phase separation. We found that aSYN phase separation, in vitro and in cells, is regulated by vesicle-associated membrane protein 2 (VAMP2), the vesicular SNARE protein. We show that aSYN phase separation is promoted by C-terminal electrostatic interaction, which in cells is mediated via interaction with VAMP2. The condensate formation is specific for the R-SNARE VAMP2 and critically dependent on aSYN’s capacity to bind to lipid membranes. In vitro, the addition of VAMP2 decreases the saturation concentration of aSYN phase separation, which is mediated by its juxtamembrane domain. Our results delineate a molecular mechanism for the regulation of aSYN phase separation, indicating a potential switch from the dispersed to the phase-separated state during vesicle cycling.HighlightsAlpha-synuclein phase separation is regulated by electrostatic interactionsVAMP2 initiates alpha-synuclein condensation in cellsPositive charges within the juxtamembrane domain of VAMP2 initiate alpha-synuclein phase separation in vitroAlpha-synuclein condensates nucleate on lipid membranes and assemble vesicular structures in cells
Ionizing radiation responses appear incidental to desiccation responses in the bdelloid rotiferAdineta vaga
Authors: Moris Victoria C. , Bruneau Lucie , Berthe Jérémy , Heuskin Anne-Catherine , Penninckx Sébastien , Ritter Sylvia , Weber Uli , Durante Marco , Danchin Etienne G. J. , Hespeels Boris , Van Doninck Karine 
Published: June 2023

AbstractBackgroundThe remarkable resistance to ionizing radiation found in anhydrobiotic organisms, such as some bacteria, tardigrades, and bdelloid rotifers has been hypothesized to be incidental to the desiccation resistance. Both stresses produce reactive oxygen species and cause damage to DNA and other macromolecules. However, this hypothesis has only been investigated in a few species.ResultsIn this study, we analyzed the transcriptomic response of the bdelloid rotiferAdineta vagato desiccation and to low- (X-rays) and high- (Fe) LET radiation to highlight the molecular and genetic mechanisms triggered by both stresses. We identified numerous genes encoding antioxidants, but also chaperones, that are constitutively highly expressed, which may contribute to the protection of proteins against oxidative stress during desiccation and ionizing radiation. We also detected a transcriptomic response common to desiccation and ionizing radiation with the over-expression of genes mainly involved in DNA repair and protein modifications but also genes with unknown functions being bdelloid-specific. A distinct transcriptomic response specific to rehydration was also found, with the over-expression of genes mainly encoding Late Embryogenesis Abundant proteins, specific Heat Shock Proteins, and glucose repressive proteins.ConclusionsThese results suggest that the extreme resistance of bdelloid rotifers to radiation might indeed be a consequence of their capacity to resist complete desiccation. This study paves the way to functional genetic experiments onA. vagatargeting promising candidate proteins playing central roles in radiation and desiccation resistance.
Polymer biodegradation byHalanaerobiumpromotes reservoir souring during hydraulic fracturing
Authors: Scheffer Gabrielle , Chakraborty Anirban , Amundson Kaela K. , Khan Rohan , Wilkins Michael J. , Wrighton Kelly , Evans Paul , Hubert Casey R. J. 
Published: June 2023

AbstractHydraulically fractured shale reservoirs have facilitated studies of unexplored niches in the continental deep biosphere. Members of the genusHalanaerobiumare ubiquitous in these environments. Polymers like guar gum used as gelling agents in hydraulic fracturing fluids are known to be fermentable substrates, but metabolic pathways encoding these processes have not been characterized. To explore this, produced water samples from the Permian Basin were incubated at 30°C to simulate above-ground storage conditions, and at 60°C to simulate subsurface reservoir conditions. Guar metabolism coincided withHalanaerobiumenrichment only at 30°C, revealing genes for polymer biodegradation through the mixed-acid fermentation pathway in different metagenome-assembled genomes (MAGs). Whereas thiosulfate reduction to sulfide is often invoked to explain the dominance ofHalanaerobiumin these settings,Halanaerobiumgenomes did not uncover genes for this metabolism. Sulfide production was observed in 60°C incubations, with corresponding enrichment ofDesulfohalobiumandDesulfovibrionaceaethat possess complete pathways for coupling mannose and acetate oxidation to sulfate reduction. These findings outline how production of fermentation intermediates (mannose, acetate) byHalanaerobiumin topside settings can result in reservoir souring when these metabolites are introduced into the subsurface through produced water re-use.ImportanceHydraulically fractured shale oil reservoirs are ideal for studying extremophiles such as thermohalophiles. During hydraulic fracturing, reservoir production water is stored in surface ponds prior to re-use. Microorganisms in these systems therefore need to withstand various environmental changes such as the swing between warm downhole oil reservoir temperatures and cooler surface conditions. This study follows this water cycle during fracking and the associated microbial metabolic potential. Of particular interest are members of the genusHalanaerobium, that have been reported to reduce thiosulfate contributing to souring of oil reservoirs. Here, we show that someHalanaerobiumstrains were unable to grow under oil reservoir temperatures and do not possess genes for thiosulfate reduction. Rather, it is likely that these organisms metabolize complex organics in fracking fluids at lower temperatures, thereby generating substrates that support reservoir souring by thermophilic sulfate-reducing bacteria at higher temperatures.
The Effects of Nitric Oxide on Choroidal Gene Expression
Authors: Merkley Makenzie B. , Soriano Diana , Jones Kenneth L. , Summers Jody A. 
Published: June 2023

ABSTRACTPurposeNitric oxide (NO) is recognized as an important biological mediator that controls several physiological functions, and evidence is now emerging that this molecule may play a significant role in the postnatal control of ocular growth and myopia development. We therefore sought to understand the role that nitric oxide plays in visually-guided ocular growth in order to gain insight into the underlying mechanisms of this process.MethodsChoroids were incubated in organ culture in the presence of the NO donor, PAPA-NONOate (1.5 mM). Following RNA extraction, bulk RNA-seq was used to quantify and compare choroidal gene expression in the presence and absence of PAPA-NONOate. We used bioinformatics to identify enriched canonical pathways, predicted diseases and functions, and regulatory effects of NO in the choroid.ResultsUpon treatment of normal chick choroids with the NO donor, PAPA-NONOate, we identified a total of 837 differentially expressed genes (259 upregulated genes, 578 down-regulated genes) compared with untreated controls. Among these, the top five upregulated genes were LSMEM1, STEAP4, HSPB9, and CCL19, and the top five down-regulated genes were CDCA3, SMC2, a novel gene (ENSALGALG00000050836), an uncharacterized gene (LOC107054158), and SPAG5. Bioinformatics predicted that NO treatment will activate pathways involved in cell and organismal death, necrosis, and cardiovascular system development, and inhibit pathways involved in cell proliferation, cell movement, and gene expression.ConclusionsThe findings reported herein may provide insight into possible effects of NO in the choroid during visually regulated eye growth, and help to identify targeted therapies for the treatment of myopia and other ocular diseases.
TFAP2 paralogs regulate midfacial development in part through a conservedALXgenetic pathway
Authors: Nguyen Timothy T , Mitchell Jennyfer M , Kiel Michaela D , Jones Kenneth L , Williams Trevor J , Nichols James T , Otterloo Eric Van 
Published: June 2023

ABSTRACTCranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation ofTfap2aandTfap2bin the murine neural crest even during the late migratory phase results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of bothTfap2members dysregulated numerous midface GRN components involved in midface fusion, patterning, and differentiation. Notably,Alx1/3/4(Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulatesAlxgene expression.TFAP2andALXco-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion,tfap2amutant zebrafish present abnormalalx3expression patterns, and the two genes display a genetic interaction in this species. Together, these data demonstrate a critical role for TFAP2 in regulating vertebrate midfacial development in part through ALX transcription factor gene expression.
A transcriptional cell atlas identifies the decline in the AT2 niche in aged human lungs
Authors: Liu Xue , Zhang Xuexi , Yao ChangFu , Liang Jiurong , Noble Paul W. , Jiang Dianhua 
Published: June 2023

SUMMARYAging poses a global public health challenge, associated with molecular and physiological changes in the lungs. It increases susceptibility to acute and chronic lung diseases, yet the underlying molecular and cellular drivers in aged populations are not fully appreciated. To systematically profile the genetic changes associated with age, we present a single-cell transcriptional atlas comprising nearly half a million cells from the healthy lungs of human subjects spanning various ages, sexes, and smoking statuses. Most annotated cell lineages in aged lungs exhibit dysregulated genetic programs. Specifically, the aged alveolar epithelial cells, including both alveolar type II (AT2) and type I (AT1) cells, demonstrate loss of epithelial identities, heightened inflammaging characterized by increased expression of AP-1 transcription factor and chemokine genes, and significantly increased cellular senescence. Furthermore, the aged mesenchymal cells display a remarkable decrease in Collagen and Elastin transcription. The decline of the AT2 niche is further exacerbated by a weakened endothelial cell phenotype and a dysregulated genetic program in macrophages. These findings highlight the dysregulation observed in both AT2 stem cells and their supportive niche cells, potentially contributing to the increased susceptibility of aged populations to lung diseases.