bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraints and Opportunities for Detecting Land Surface Phenology in Drylands
Authors: Taylor Shawn D. , Browning Dawn M. , Baca Ruben A. , Gao Feng 
Published: May 2021

AbstractLand surface phenology (LSP) enables global scale tracking of ecosystem processes, but its utility is limited in drylands due to low vegetation cover and resulting low annual amplitudes of vegetation indices (VIs). Due to the importance of drylands for biodiversity, food security, and the carbon cycle it is necessary to understand limitations in measuring dryland dynamics. Here, using simulated data and multi-temporal unmanned aerial vehicle (UAV) imagery of a desert shrubland, we explore the feasibility of detecting LSP with respect to fractional vegetation cover, plant functional types, VI uncertainty, and two different detection algorithms. Using simulated data we found that plants with distinct VI signals, such as deciduous shrubs, can require up to 60% fractional cover to consistently detect LSP. Evergreen plants, with lower seasonal VI amplitude, require considerably higher cover and can have undetectable phenology even with 100% vegetation cover. Our evaluation of two algorithms showed that neither performed the best in all cases. Even with adequate cover, biases in phenological metrics can still exceed 20 days, and can never be 100% accurate due to VI uncertainty from shadows, sensor view angle, and atmospheric interference. We showed how high-resolution UAV imagery enables LSP studies in drylands, and highlighted important scale effects driven by within canopy VI variation. With high-resolution imagery the open canopies of drylands are beneficial as they allow for straightforward identification of individual plants, enabling the tracking of phenology at the individual level. Drylands thus have the potential to become an exemplary environment for future LSP research.
Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii
Authors: McKey Jennifer , Anbarci Dilara N. , Bunce Corey , Ontiveros Alejandra E. , Behringer Richard R. , Capel Blanche 
Published: May 2021

AbstractMorphogenetic events during development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. Development of the rete ovarii correlated with events of ovary morphogenesis. Using genetic mouse models in which the oviduct and rete ovarii are perturbed, we found the oviduct is required for ovary encapsulation. This study reveals novel relationships among the ovary and surrounding tissues and paves the way for functional investigation of the relationship between architecture and differentiation of the mammalian ovary.
Machine learning-guided acyl-ACP reductase engineering for improved in vivo fatty alcohol production
Authors: Greenhalgh Jonathan C. , Fahlberg Sarah A. , Pfleger Brian F. , Romero Philip A. 
Published: May 2021

AbstractFatty acyl reductases (FARs) catalyze the reduction of thioesters to alcohols and are key enzymes for the microbial production of fatty alcohols. Many existing metabolic engineering strategies utilize these reductases to produce fatty alcohols from intracellular acyl-CoA pools; however, acting on acyl-ACPs from fatty acid biosynthesis has a lower energetic cost and could enable more efficient production of fatty alcohols. Here we engineer FARs to preferentially act on acyl-ACP substrates and produce fatty alcohols directly from the fatty acid biosynthesis pathway. We implemented a machine learning-driven approach to iteratively search the protein fitness landscape for enzymes that produce high titers of fatty alcohols in vivo. After ten design-test-learn rounds, our approach converged on engineered enzymes that produce over twofold more fatty alcohols than the starting natural sequences. We further characterized the top identified sequence and found its improved alcohol production was a result of an enhanced catalytic rate on acyl-ACP substrates, rather than enzyme expression or KM effects. Finally, we analyzed the sequence-function data generated during the enzyme engineering to identify sequence and structure features that influence fatty alcohol production. We found an enzyme’s net charge near the substrate-binding site was strongly correlated with in vivo activity on acyl-ACP substrates. These findings suggest future rational design strategies to engineer highly active enzymes for fatty alcohol production.
AxonDeep: Automated Optic Nerve Axon Segmentation in Mice with Deep Learning
Authors: Deng Wenxiang , Hedberg-Buenz Adam , Soukup Dana A. , Taghizadeh Sima , Wang Kai , Anderson Michael G. , Garvin Mona K. 
Published: May 2021

AbstractPurposeOptic nerve damage is the principal feature of glaucoma and contributes to vision loss in many diseases. In animal models, nerve health has traditionally been assessed by human experts that grade damage qualitatively or manually quantify axons from sampling limited areas from histologic cross sections of nerve. Both approaches are prone to variability and are time consuming. First-generation automated approaches have begun to emerge, but all have significant shortcomings. Here, we seek improvements through use of deep-learning approaches for segmenting and quantifying axons from cross sections of mouse optic nerve.MethodsTwo deep-learning approaches were developed and evaluated: (1) a traditional supervised approach using a fully convolutional network trained with only labeled data and (2) a semi-supervised approach trained with both labeled and unlabeled data using a generative-adversarial-network framework.ResultsFrom comparisons with an independent test set of images with manually marked axon centers and boundaries, both deep-learning approaches outperformed an existing baseline automated approach and similarly to two independent experts. Performance of the semi-supervised approach was superior and implemented into AxonDeep.ConclusionAxonDeep performs automated quantification and segmentation of axons from healthy appearing nerves, and those with mild to moderate degrees of damage, similar to that of experts without the variability and constraints associated with manual performance.Translational RelevanceUse of deep learning for axon quantification provides rapid, objective, and higher throughput analysis of optic nerve that would otherwise not be possible.
Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion
Authors: Kim Jong Hyuk , Schulte Ashley J. , Sarver Aaron L. , Angelos Mathew G. , Frantz Aric M. , Forster Colleen L. , O’Brien Timothy D. , Cornax Ingrid , O’Sullivan M. Gerard , Cheng Nuojin , Lewellen Mitzi , Oseth LeAnn , Kumar Sunil , Bullman Susan , Pedamallu Chandra Sekhar , Goyal Sagar M. , Meyerson Matthew , Lund Troy C. , Alfoldi Jessica , Breen Matthew , Lindblad-Toh Kerstin , Dickerson Erin B. , Kaufman Dan S. , Modiano Jaime F. 
Published: May 2021

AbstractHemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells, a trait that was not observed in xenografts from canine osteosarcoma and lymphoma. In some cases, the xenografted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. We did not uncover a definitive transmissible etiology, but our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, originate from stromal cells that are part of the bone marrow niche and that these cells may also support the growth of hematopoietic tumors.SignificanceWe demonstrate that molecular programs supporting expansion of immune and inflammatory cells in hemangiosarcoma resemble those of bone marrow niche cells, providing insights into the potential roles of these cells - whether physiological or pathological - in creating a permissive environment for the progression of hematopoietic malignancies.
Use of an enclosed elk population to assess two non-invasive methods for estimating population size
Authors: Brazeal Jennifer L. , Sacks Benjamin N. 
Published: May 2021

AbstractNon-invasive genetic sampling and spatially explicit capture-recapture (SCR) models are used increasingly to estimate abundance of wildlife populations, but have not been adequately tested on gregarious animals such as elk (Cervus canadensis), for which correlated space use and movements violate model assumptions of independence. To evaluate the robustness and accuracy of SCR, and to assess the utility of an alternative non-invasive method for estimating density of gregarious ungulates, we utilized a tule elk (Cervus canadensis nannodes) population of known size within a fenced enclosure on the San Luis National Wildlife Refuge in central California. We evaluated fecal genetic SCR to camera trap-based random encounter model (REM) approaches to density estimation based on comparison to the true abundance. We also subsampled the dataset to explore the effects of varying search effort and elk density on the precision and accuracy of results. We found that SCR outperformed REM methods in the full datasets, and reliably provided accurate (relative bias <10%) and reasonably precise (relative standard error ≤20%) estimates of density at moderately low to high densities (6–17 elk/km2), when the subsampling scenarios yielded a minimum average of 20 recaptures. We also found that the number of samples used to construct detection histories was a reliable predictor of precision, and could be used to establish minimum sampling requirements in future population surveys of elk. Although field-testing in free-ranging populations is needed, our results suggest that non-invasive genetic SCR is a promising tool for future population studies and monitoring of elk and potentially other gregarious ungulates. In contrast, the REM estimate of density was highly inaccurate, imprecise, and highly sensitive to camera parameters.
Intranasal vasopressin like oxytocin increases social attention by influencing top-down control, but additionally enhances bottom-up control
Authors: Zhuang Qian , Zheng Xiaoxiao , Becker Benjamin , Lei Wei , Xu Xiaolei , Kendrick Keith M. 
Published: May 2021

AbstractThe respective roles of the neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) in modulating social cognition and for therapeutic intervention in autism spectrum disorder have not been fully established. In particular, while numerous studies have demonstrated effects of oxytocin in promoting social attention the role of AVP has not been examined. The present study employed a randomized, double-blind, placebo (PLC)-controlled between-subject design to explore the social- and emotion-specific effects of AVP on both bottom-up and topdown attention processing with a validated emotional anti-saccade eye-tracking paradigm in 80 male subjects (PLC = 40, AVP = 40). Our findings showed that AVP increased the error rate for social (angry, fearful, happy, neutral and sad faces) but not non-social (oval shapes) stimuli during the anti-saccade condition and reduced error rates in the pro-saccade condition. Comparison of these findings with a previous study (sample size: PLC = 33, OXT = 33) using intranasal oxytocin revealed similar effects of the two peptides on anti-saccade errors but a significantly greater effect of AVP on pro-saccades. Both peptides also produced a post-task anxiolytic effect by reducing state anxiety. Together these findings suggested that both AVP and OXT decrease goal-directed top-down attention control to social salient stimuli but that AVP more potently increased bottom-up social attentional processing.
Formylglycine-generating enzyme-like proteins constitute a novel family of widespread type VI secretion system immunity proteins
Authors: Lopez Juvenal , Le Nguyen-Hung , Moon Ki Hwan , Salomon Dor , Bosis Eran , Feldman Mario F. 
Published: May 2021

AbstractCompetition is a critical aspect of bacterial life, as it enables niche establishment and facilitates the acquisition of essential nutrients. Warfare between Gram-negative bacteria is largely mediated by the type VI secretion system (T6SS), a dynamic nanoweapon that delivers toxic effector proteins from an attacking cell to adjacent bacteria in a contact-dependent manner. Effector-encoding bacteria prevent self-intoxication and kin cell killing by the expression of immunity proteins, which prevent effector toxicity by specifically binding their cognate effector and occluding its active site. In this study, we investigate Tsi3, a previously uncharacterized T6SS immunity protein present in multiple strains of the human pathogen Acinetobacter baumannii. We show that Tsi3 is the cognate immunity protein of the antibacterial effector of unknown function Tse3. Our bioinformatic analyses indicate that Tsi3 homologs are widespread among Gram-negative bacteria, often encoded within T6SS effector-immunity modules. Surprisingly, we found that Tsi3 homologs possess a characteristic formylglycine-generating enzyme (FGE) domain, which is present in various enzymatic proteins. Our data shows that Tsi3-mediated immunity is dependent on Tse3-Tsi3 protein-protein interactions and that Tsi3 homologs from various bacteria do not protect against Tse3-dependent bacterial killing. Thus, we conclude that Tsi3 homologs are unlikely to be functional enzymes. Collectively, our work identifies FGE domain-containing proteins as important mediators of immunity against T6SS attacks and indicates that the FGE domain can be co-opted as a scaffold in multiple proteins to carry out diverse functions.ImportanceDespite the wealth of knowledge on the diversity of biochemical activities carried out by T6SS effectors, comparably little is known about the various strategies bacteria employ to prevent susceptibility to T6SS-dependent bacterial killing. Our work establishes a novel family of T6SS immunity proteins with a characteristic FGE domain. This domain is present in enzymatic proteins with various catalytic activities. Our characterization of Tsi3 expands the known functions carried out by FGE-like proteins to include defense during T6SS-mediated bacterial warfare. Moreover, it highlights the evolution of FGE domain-containing proteins to carry out diverse biological functions.
DegP initiates regulated processing of filamentous hemagglutinin in Bordetella bronchiseptica
Authors: Johnson Richard M. , Nash Zachary M. , Dedloff Margaret R. , Shook John , Cotter Peggy A. 
Published: May 2021

AbstractFilamentous hemagglutinin (FhaB) is a critical virulence factor for both Bordetella pertussis, the causal agent of whooping cough, and the closely related species Bordetella bronchiseptica. FhaB is an adhesin, suppresses inflammatory cytokine production, and protects against phagocytic cell clearance during infection. Regulated degradation of the FhaB C-terminal prodomain is required to establish a persistent infection in mice. Two proteases, CtpA in the periplasm and SphB1 on the bacterial surface, are known to mediate FhaB processing, and we recently determined that CtpA functions before, and controls the FhaB cleavage site of, SphB1. However, the data indicate that another periplasmic protease must initiate degradation of the prodomain by removing a portion of the FhaB C terminus that inhibits CtpA-mediated degradation. Using a candidate approach, we identified DegP as the initiating protease. Deletion of degP or substitution of its predicted catalytic residue resulted in reduced creation of FHA′, the main product of FhaB processing, and an accumulation of full-length FhaB in whole cell lysates. Also, FHA′ was no longer released into culture supernatants in degP mutants. Alterations of the FhaB C terminus that relieve inhibition of CtpA abrogate the need for DegP, consistent with DegP functioning prior to CtpA in the processing pathway. DegP is not required for secretion of FhaB through FhaC or for adherence of the bacteria to host cells, indicating that DegP acts primarily as a protease and not a chaperone for FhaB in B. bronchiseptica. Our results highlight a role for HtrA family proteases in activation of virulence factors in pathogenic bacteria.ImportanceTwo-partner secretion (TPS) systems are broadly distributed among Gram-negative bacteria and play important roles in bacterial pathogenesis. FhaB-FhaC is the prototypical member of the TPS family and here we identified the protease that initiates a processing cascade that controls FhaB function. Our results are significant because they provide insight into the molecular mechanism underlying the ability of Bordetella species to prevent clearance by phagocytic cells, which is critical for bacterial persistence in the lower respiratory tract. Our findings also highlight an underappreciated role for HtrA family proteases in processing specific bacterial virulence factors.
An enhanced inverted encoding model for neural reconstructions
Authors: Scotti Paul S. , Chen Jiageng , Golomb Julie D. 
Published: May 2021

AbstractHere we present a more interpretable and versatile approach for reconstructing the contents of perception, attention, and memory from neuroimaging data. Our enhanced inverted encoding model (eIEM) incorporates theoretical and methodological improvements including proper accounting of population-level tuning functions and a trial-by-trial prediction error-based metric where reconstruction quality is measured in meaningful units. Added functionality and improved flexibility is further gained via eIEM’s novel goodness-of-fit feature: for trial-by-trial reconstructions, goodness-of-fits are obtained independently (non-circularly) to prediction error and can be applied to any IEM procedure or decoding metric, resulting in improved reconstruction quality and brain-behavior correlations, and more creative applications. We validate eIEM from methodological principles, simulated neuroimaging datasets, and three pre-existing fMRI datasets spanning perception, attention, and working memory. Notably, eIEM is easy to apply and broadly accessible – our Python package (https://pypi.org/project/inverted-encoding)implements eIEM in one line of code – and is easily modifiable to compare performance metrics and/or scale up to more complex models.
Influence of environmental temperature on mouth-form plasticity in Pristionchus pacificus acts through daf-11-dependent cGMP signaling
Authors: Lenuzzi Maša , Witte Hanh , Riebesell Metta , Rödelspereger Cristian , Hong Ray L. , Sommer Ralf J. 
Published: May 2021

AbstractMouth-form plasticity in the nematode Pristionchus pacificus has become a powerful system to identify the genetic and molecular mechanisms associated with phenotypic (developmental) plasticity. In particular, the identification of developmental switch genes that can sense environmental stimuli and reprogram developmental processes has confirmed long-standing evolutionary theory. Together with the associated gene regulatory networks, these developmental switch genes have been important to show that plasticity is consistent with the Modern Synthesis of evolution. However, how these genes are involved in the direct sensing of the environment, or if the switch genes act downstream of another, primary environmental sensing mechanism, remains currently unknown. Here, we study the influence of environmental temperature on mouth-form plasticity. Using forward and reverse genetic technology including CRISPR/Cas9, we show that mutations in the guanylyl cyclase Ppa-daf-11, the Ppa-daf-25/AnkMy2 and the cyclic nucleotide-gated channel Ppa-tax-2 eliminate the response to elevated temperatures. Together, our study indicates that DAF-11, DAF-25 and TAX-2 have been co-opted for environmental sensing during mouth-form plasticity regulation in P. pacificus. This work suggests that developmental switch genes integrate environmental signals including perception by cGMP signaling.
Maturation of Human Long-lived Plasma Cells Results in Resistance to Apoptosis by Transcriptional and Epigenetic Regulation
Authors: Joyner Chester J. , Ley Ariel M. , Nguyen Doan C. , Ali Mohammad , Corrado Alessia , Tipton Christopher , Scharer Christopher D. , Mi Tian , Woodruff Matthew C , Hom Jennifer , Boss Jeremy M. , Duan Meixue , Gibson Greg , Roberts Danielle , Andrews Joel , Lonial Sagar , Sanz Inaki , Lee F. Eun-Hyung 
Published: May 2021

ABSTRACTAntibody secreting cells (ASC) circulate after vaccination and migrate to the bone marrow (BM) where a subset known as long-lived plasma cells (LLPC) persist and secrete antibodies for a lifetime. The mechanisms of how circulating ASC become LLPC are not well elucidated. Here, we show that human blood ASCs have distinct morphology, transcriptomes, and epigenetics compared to BM LLPC. LLPC acquire transcriptional and epigenetic changes in the apoptosis pathway to support their survival. Upregulation of pro-survival gene expression accompanies downregulation of pro-apoptotic gene expression in LLPC. While pro-apoptotic gene loci are less accessible, pro-survival gene loci are not always accompanied by accessibility changes. Importantly, we show similar LLPC morphological and transcriptional maturation of blood ASC in response to the novel in vitro BM mimetic. In all, our study demonstrates that blood ASC in the BM microniche must undergo morphological and molecular changes to mature into apoptotic-resistant LLPC.