bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive alien insects represent a clear but variable threat to biodiversity
Authors: Clarke David A. , McGeoch Melodie A. 
Published: June 2022

AbstractInvasive alien insects as a driver of biodiversity change are an important yet understudied component of the general threat of biological invasions. The environmental impacts of invasive alien insects are varied and widespread, with evidence to suggest that an insect species global maximum impact is likely to increase in severity as it increases its non-native distribution. Two potential explanations are that large geographic distributions include environmental heterogeneity and increase resource availability, or that there are intrinsic factors of widely-spread species that also facilitate greater impacts. Determining which explanation is more likely, and developing a more comprehensive and general understanding of the environmental impacts of invasive alien species, can be assisted by addressing the information shortfalls highlighted in this research.
The effect ofDrosophila attP40background on the glomerular organization of Or47b olfactory receptor neurons
Authors: Duan Qichen , Estrella Rachel , Carson Allison , Chen Yang , Volkan Pelin C. 
Published: June 2022

AbstractBacteriophage integrase-directed insertion of transgenic constructs into specific genomic loci has been widely used byDrosophilacommunity. TheattP40landing site located on the second chromosome gained popularity because of its high inducible transgene expression levels. Here, unexpectedly, we found that homozygousattP40chromosome disrupts normal glomerular organization of Or47b olfactory receptor neuron (ORN) class inDrosophila. This effect is not likely to be caused by the loss of function ofMsp300, where theattP40docking site is inserted. Moreover, the attP40background seems to genetically interact with the second chromosomeOr47b-GAL4driver, which results in a similar glomerular defect. Whether the ORN phenotype is caused by the neighboring genes aroundMsp300locus in the presence ofattP40-based insertions or a second unknown mutation in theattP40background remains elusive. Our findings tell a cautionary tale about using this popular transgenic landing site, highlighting the importance of rigorous controls to rule out theattP40landing site-associated background effects.
Single cell preparations ofMycobacterium tuberculosisdamage the mycobacterial envelope and disrupt macrophage interactions
Authors: Mittal Ekansh , Roth Andrew T. , Seth Anushree , Singamaneni Srikanth , Beatty Wandy , Philips Jennifer A. 
Published: June 2022

AbstractFor decades, investigators have studied the interaction ofMycobacterium tuberculosis(Mtb) with macrophages, which serve as a major cellular niche for the bacilli. Because Mtb are prone to aggregation, investigators rely on varied methods to disaggregate the bacteria for these studies. Here, we examined the impact of routinely used preparation methods on bacterial cell envelop integrity, macrophage inflammatory responses, and intracellular Mtb survival. We found that both gentle sonication and filtering damaged the mycobacterial cell envelope and markedly impacted the outcome of macrophage infections. Unexpectedly, sonicated bacilli were hyperinflammatory, eliciting dramatically higher TLR2-dependent gene expression and elevated secretion of IL-1β and TNF-α. Despite evoking enhanced inflammatory responses, sonicated bacilli replicated normally in macrophages. In contrast, Mtb that had been passed through a filter induced little inflammatory response, and they were attenuated in macrophages. Previous work suggests that the mycobacterial cell envelope lipid, phthiocerol dimycocerosate (PDIM), dampens macrophage inflammatory responses to Mtb. However, we found that the impact of PDIM depended on the method used to prepare Mtb. In conclusion, widely used methodologies to disaggregate Mtb may introduce experimental artifacts in Mtb-host interaction studies, including alteration of host inflammatory signaling, intracellular bacterial survival, and interpretation of bacterial mutants.
Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity
Authors: Grajchen Elien , Loix Melanie , Baeten Paulien , Côrte-Real Beatriz F. , Hamad Ibrahim , Haidar Mansour , Dehairs Jonas , Broos Jelle Y. , Ntambi James M. , Zimmermann Robert , Breinbauer Rolf , Stinissen Piet , Hellings Niels , Kooij Gijs , Giera Martin , Swinnen Johannes V. , Broux Bieke , Kleinewietfeld Markus , Hendriks Jerome J.A. , Bogie Jeroen F.J. 
Published: June 2022

AbstractThe imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T cell (Treg) differentiation and augments autoimmunity in an animal model of MS. Guided by RNA sequencing and lipidomics analysis, we found that absence ofScd1promotes hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders.
A multivariate brain signature for reward
Authors: Speer Sebastian P.H. , Keysers Christian , Smidts Ale , Boksem Maarten A.S. , Wager Tor D. , Gazzola Valeria 
Published: June 2022

AbstractThe processing of rewards and losses are crucial for learning to adapt to an ever changing environment. Dysregulated reward processes are prevalent in mental health and substance use disorders. While many human brain measures related to reward have been based on activity in individual brain regions, recent studies indicate that many affective and motivational processes are encoded in distributed systems that span multiple regions. Consequently, decoding these processes using individual regions yields small effect sizes and limited reliability, whereas predictive models based on distributed patterns yield much larger effect sizes and excellent reliability. To create such a predictive model for the processes of rewards and losses, from now on termed the Brain Reward Signature (BRS), we trained a LASSO-PCR model to predict the signed magnitude of monetary rewards and losses on the Monetary Incentive Delay task (MID; N = 39) and achieved a high significant decoding performance (92% for decoding rewards versus losses). We subsequently demonstrate the generalizability of our signature on another version of the MID in a different sample (92% decoding accuracy for rewards versus losses; N = 12) and on a gambling task from a large sample (73% decoding accuracy for rewards versus losses, N = 1084) from the Human Connectome Project. Lastly, we also provided preliminary evidence for specificity to rewarding outcomes by illustrating that the signature map generates estimates that significantly differ between rewarding and negative feedback (92% decoding accuracy) but do not differ for conditions that differ in disgust rather than reward in a novel Disgust-Delay Task (N = 39). We thus created a BRS that can be used to make specific, generalizable and reproducible predictions about brain responses to rewards and losses.
Temporal and spatial frameworks supporting plant responses to vegetation proximity
Authors: Pastor-Andreu Pedro , Moreno-Romero Jordi , Urdin-Bravo Mikel , Palau-Rodriguez Julia , Paulisic Sandi , Kastanaki Elizabeth , Vives-Peris Vicente , Gomez-Cadenas Aurelio , Rodríguez-Villalón Antía , Martínez-García Jaime F. 
Published: June 2022

ABSTRACTAfter perception of vegetation proximity by the phytochrome photoreceptors, shade-avoider plants initiate a set of responses known as the Shade Avoidance Syndrome (SAS). The shade-induced de-repression of active phytochrome B (phyB) releases the repression imposed over the PHYTOCHROME INTERACTING FACTORs (PIFs). InArabidopsis thalianaseedlings, this mechanism triggers rapid and massive changes in gene expression, increases auxin production in a SHADE AVOIDANCE 3-dependent manner and promotes hypocotyl elongation. Other components, such as phyA and ELONGATED HYPOCOTYL 5 (HY5), also participate in the shade regulation of the hypocotyl elongation response repressing it. However, it is less clear how phyA and HY5 interact with PIFs to regulate this response. Our physiological, genetic, cell biology and transcriptomic analyses showed that these components are organized in two main branches, and incorporate into the model for the regulation of shade-induced hypocotyl elongation the temporal and spatial functional importance of the various SAS regulators analyzed in here. They also indicated that PIFs and HY5, belonging to separate branches, target common genes whose expression is rapidly modulated by shade. This transcriptional relationship, however, changes after longer shade-treatments, suggesting that it is a dynamic convergence point to modulate the hypocotyl elongation.
Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations
Authors: Attard Thomas , Welburn Julie P.I. , Marsh Joseph 
Published: June 2022

AbstractCells rely heavily on microtubules for several processes, including cell division and molecular trafficking. Mutations in the different tubulin-α and -β proteins that comprise microtubules have been associated with various diseases and are often dominant, sporadic and congenital. While the earliest reported tubulin mutations affect neurodevelopment, mutations are also associated with other disorders such as bleeding disorders and infertility. We performed a systematic survey of tubulin mutations across all isotypes in order to improve our understanding of how they cause disease, and increase our ability to predict their phenotypic effects. Both protein structural analyses and computational variant effect predictors were very limited in their utility for differentiating between pathogenic and benign mutations. This was even worse for those genes associated with non-neurodevelopmental disorders. We selected tubulin-α and -β disease mutations that were most poorly predicted for experimental characterisation. These mutants co-localise to the mitotic spindle in HeLa cells, suggesting they may exert dominant-negative effects by altering microtubule properties. Our results show that tubulin mutations represent a blind spot for current computational approaches, being much more poorly predicted than mutations in most human disease genes. We suggest that this is likely due to their strong association with dominant-negative and gain-of-function mechanisms.
Genetic parameters for resistance to gastrointestinal nematodes in sheep: a meta-analysis
Authors: Hayward Adam D. 
Published: June 2022

ABSTRACTGastrointestinal nematodes (GIN) are damaging parasites of global sheep populations. The key weapons in fighting GIN have been anthelmintic drugs, but the emergence of drug-resistant parasites has meant that alternative control methods are needed. One of these alternatives is to breed for enhanced host resistance to GIN, and decades of research have estimated the genetic contribution to different measures of resistance to GIN and their genetic correlations with other desirable performance traits. It is clear that parasite resistance is a heritable trait that can be selected for. Despite this consensus, estimates of both heritability of resistance and genetic correlations with other traits vary widely between studies, and the reasons for this variation have not been examined. This study provides a comprehensive and quantitative meta-analysis of genetic parameters for resistance to GIN in sheep, including measures of worm burden (faecal egg counts, FEC), anti-parasite immunity (GIN-specific antibodies), and parasite-induced pathology (FAMACHA© scores). Analysis of 591 heritability estimates from 121 studies revealed a global heritability estimate for resistance to GIN of 0.25 (95%CI = 0.22 – 0.27) that was stable across breeds, ages, geographical location and analytical methods. Meanwhile, analysis of 559 genetic correlations from 54 studies revealed that resistance to GIN overall has a positive genetic correlation of +0.10 (95%CI = 0.02 – 0.19) with performance traits, and that this was consistent across breeds, ages, sexes and analytical methods. Importantly, the direction of the genetic correlation varied with the resistance trait measured: while FEC and FAMACHA© scores were favourably correlated with performance traits, adaptive immune markers were unfavourably correlated, suggesting that selection for enhanced immune responses to GIN could reduce animal performance. Overall, the results suggest that breeding for resistance to GIN should continue to form part of integrated management programs to reduce the impact of parasites on health and performance, but that selection for enhanced immune responses should be avoided.
Identification of secreted proteins by comparison of protein abundance in conditioned media and cell lysates
Authors: Abbineni Prabhodh S. , Tang Vi T. , Veiga Leprevost Felipe da , Basrur Venkatesha , Xiang Jie , Nesvizhskii Alexey I. , Ginsburg David 
Published: June 2022

AbstractAnalysis of the full spectrum of secreted proteins in cell culture is complicated by leakage of intracellular proteins from damaged cells. To address this issue, we compared the abundance of individual proteins between the cell lysate and the conditioned medium, reasoning that secreted proteins should be relatively more abundant in the conditioned medium. Marked enrichment for signal-peptide-bearing proteins with increasing conditioned media to cell lysate ratio, as well loss of this signal following brefeldin A treatment, confirmed the sensitivity and specificity of this approach. The subset of proteins demonstrating increased conditioned media to cell lysate ratio in the presence of Brefeldin A identified candidates for unconventional secretion via a pathway independent of ER to Golgi trafficking.
Quantitative mapping of synaptic periactive zone architecture and organization
Authors: Del Signore Steven J. , Mitzner Margalit G. , Silveira Anne M. , Fai Thomas G. , Rodal Avital A. 
Published: June 2022

1.AbstractFollowing exocytosis at active zones, synaptic vesicle membranes and membrane-bound proteins must be recycled. The endocytic machinery that drives this recycling accumulates in the periactive zone (PAZ), a region of the synapse adjacent to active zones, but the organization of this machinery within the PAZ, and how PAZ composition relates to active zone release properties remains unknown. The PAZ is also enriched for cell adhesion proteins, but their function at these sites is poorly understood. Here, using Airyscan and STED imaging ofDrosophilasynapses, we develop a quantitative framework describing the organization and ultrastructure of the PAZ. Different endocytic proteins localize to distinct regions of the PAZ, suggesting that sub-domains are specialized for distinct biochemical activities, stages of membrane remodeling, or synaptic functions. We find that the accumulation and distribution of endocytic but not adhesion PAZ proteins correlate with the abundance of the scaffolding protein Bruchpilot at active zones - a structural correlate of release probability. These data suggest that endocytic and exocytic activities are spatially correlated. Taken together, our results provide a new approach to quantify synaptic architecture and identify novel relationships between the exocytic and endocytic apparatus at the synapse.
Experiments on osmotically driven flow in idealized elastic membranes
Authors: Nakad Mazen , Domec Jean-Christophe , Sevanto Sanna , Katul Gabriel 
Published: June 2022

AbstractThe phloem provides a pathway for products of photosynthesis to be transported to different parts of the plant for consumption or storage. The Münch pressure flow hypothesis (PFH) is considered the leading framework to mathematically represent this transport. It assumes that osmosis provides the necessary pressure differences to drive the fluid flow and sucrose within the phloem. Mathematical models utilizing the PFH approximate the phloem by a relatively rigid semi-permeable tube. However, the phloem consists of living cells that contract and expand in response to pressure fluctuations. The effect of membrane elasticity on osmotically driven sucrose front speed has rarely been considered and frames the scope here. Laboratory experiments were conducted to elucidate the elastic-to-plastic pressure-deformation relation in membranes and their effect on sucrose front speeds. It is demonstrated that membrane elasticity acts to retard the sucrose front speed. The retardation emerges because some of the osmotic pressure performs mechanical work to expand the membrane instead of pressurizing water. These results offer a novel perspective about the much discussed presence of sieve plates through-out the phloem acting as structural dampers.
The phoenix hypothesis of speciation
Authors: Yamaguchi Ryo , Wiley Bryn , Otto Sarah P. 
Published: June 2022

AbstractGenetic divergence among allopatric populations builds reproductive isolation over time and is thought to be the major mechanism underlying the formation of new species. This process is accelerated when populations face a changing environment, but abrupt change also places populations at risk of extinction. Here we use simulations of Fisher’s geometric model with explicit population dynamics to explore the genetic changes that occur in the face of extreme environmental changes to which populations must adapt or go extinct. We show that evolutionary rescue leads to the fixation of mutations whose effects are larger on average and that these mutations are more likely to lead to reproductive isolation, compared with populations not at risk of extinction. We refer to the formation of new species from the ashes of populations in decline as the phoenix hypothesis of speciation. The phoenix hypothesis predicts more substantial hybrid fitness breakdown among populations surviving a higher extinction risk. The hypothesis was supported when many loci underlie adaptation. When, however, there was only a small number of potential rescue mutations, we found that mutations fixed in different populations were more likely to be identical, with parallel changes reducing isolation. With a limited genomic potential for adaptation, we find support for a modified version of the phoenix hypothesis where reproductive isolation builds fastest in populations subject to an intermediate extinction risk. While processes driving extinction lead to the loss of lineages with deep evolutionary histories, they may also generate new taxa, albeit taxa with minimal genetic differences.
Epigenetic reprogramming of melanoma cell state through fatty acid β-oxidation and Toll-like receptor 4 signaling
Authors: Huang Ting-Hsiang , Ma Yilun , Montal Emily , Suresh Shruthy , Tagore Mohita M. , Corbin Alexandra , Lumaquin Dianne , Campbell Nathaniel R. , Baggiolini Arianna , Koche Richard P. , White Richard M. 
Published: June 2022

SummaryTumor cells respond to a host of factors from the local microenvironment. Microenvironmental fatty acids can be used by melanoma cells for fuel, but their effects on transcription and epigenetics are still unclear. Here, we show that the fatty acid β-oxidation (FAO) pathway integrates signaling and epigenetics to drive melanoma progression. Using transgenic zebrafish and human cell lines, we find that octanoate, a medium-chain fatty acid, increases tumorigenesis. Octanoate is metabolized via the FAO/ACLY axis into acetyl-CoA, leading to increased histone acetylation. Transcriptomic and epigenetic analyses demonstrate a convergence of inflammatory gene signatures in octanoate-treated melanoma cells. This signature is mediated by TLR4/MyD88 signaling, which is activated by saturated fatty acids like octanoate. Genetic inactivation of either FAO enzymes or TLR4/MyD88 inhibits alterations in histone acetylation, and rescues octanoate-tumor promoting effects. Together, these data demonstrate clear evidence linking fatty acid metabolism and epigenetics to melanoma pathogenesis through TLR4 signaling.
TOM-1/Tomosyn acts with the UNC-6/Netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans
Authors: Mahadik Snehal S. , Lundquist Erik A. 
Published: June 2022

AbstractIn the polarity/protrusion model of growth cone repulsion from UNC-6/Netrin, UNC-6 first polarizes the VD growth cone via the UNC-5 receptor, and then regulates protrusion asymmetrically across the growth cone based on this polarity. Through the UNC-40/DCC receptor, UNC-6 stimulates protrusion dorsally, and through UNC-5 inhibits protrusion ventrally and laterally, resulting in net dorsal growth. Previous studies showed that UNC-5 inhibits growth cone protrusion via the flavin monooxygenases and potential destabilization of F-actin, and via UNC-33/CRMP and restriction of microtubule + end entry into the growth cone. To explore the role of vesicle fusion in growth cone protrusion, we analyzed tom-1/tomosyn mutants. Tomosyn normally occludes formation of the SNARE complex by interacting with and inhibiting Syntaxin and thus preventing vesicle fusion. VD growth cones of tom-1 null mutants were similar to wild-type. However, tom-1 null mutants suppressed the effects of constitutively-activated MYR::UNC-5, which alone causes small growth cones with little protrusion. This suggests that TOM-1 is normally required for the inhibitory effects of MYR::UNC-5 on growth cone protrusion. tom-1 encodes long and short isoforms, and results here indicate that tom-1S is required downstream of UNC-5 to inhibit protrusion, whereas the tom-1L has a pro-protrusive role. unc-64/Syntaxin mutants displayed reduced growth cone protrusion, suggesting that TOM-1 inhibits growth cone protrusion by inhibiting UNC-64/Syntaxin, similar to its role in neurotransmission. TOM-1L, TOM-1S, and UNC-64/Syntaxin were all required for VD growth cone polarity of protrusion, indicating that regulated vesicle fusion is required for the establishment and/or maintenance of VD growth cone polarity. These studies show that, in addition to effects on actin and microtubules, UNC-5 might inhibit VD growth cone protrusion by inhibiting growth cone vesicle fusion and thus the ability of growth cones to add plasma membrane necessary for protrusive growth.