bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent transcriptional response to thermal stress among life stages could constrain coral adaptation to climate change
Authors: Ruggeri Maria , Zhang Yingqi , Aglyamova Galina V. , Kenkel Carly D. 
Published: May 2022

AbstractThe ability for adaptation to keep pace with environmental change largely depends on how efficiently selection can act on heritable genetic variation. Complex life cycles may either promote or constrain adaptation depending on the integration or independence of fitness-related traits over development. Reef-building corals exhibit complex life cycles and are sensitive to increasing temperatures, highlighting the need to understand the heritable potential of the thermal stress response and how it is regulated over development. Here we used tag-based RNA-seq to profile global gene expression in inshore and offshoreP. astreoidesadults and their offspring recruits in response to a 16-day heat stress, and larvae from separate families in response to a 4-day heat stress, to test whether gene expression patterns differentiating adult populations, and potentially underlying differences in thermal tolerance, persist in thermally naive life stages. Host developmental stage had a major effect on both host and symbiont expression, despite symbionts being directly inherited from parent colonies, and modulated the response to thermal stress, suggesting the holobiont response to selection varies across life stages. Populations also exhibited origin-specific treatment responses, but the magnitude of the response differed among populations and life stages. Inshore parents and their juvenile offspring exhibited a more robust response to heat stress compared to offshore-origin corals, indicating expression plasticity may be heritable. However, larval populations exhibited the opposite response, possibly due to stage-specific differences or exposure duration. Overall, this study shows that putatively adaptive regulatory variation can be heritable, but the identity of thermally responsive genes are stage-specific, which will have major implications for predicting the evolutionary response of corals in a changing environment.
Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification
Authors: Reilly Molly B. , Tekieli Tessa , Cros Cyril , Aguilar G. Robert , Lao James , Toker Itai Antoine , Vidal Berta , Leyva-Díaz Eduardo , Bhattacharya Abhishek , Cook Steven J. , Smith Jayson J. , Kovacevic Ismar , Gulez Burcu , Fernandez Robert , Bradford Elizabeth F. , Ramadan Yasmin H. , Kratsios Paschalis , Bao Zhirong , Hobert Oliver 
Published: May 2022

ABSTRACTHomeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 12 homeobox genes in 20 distinct neuron classes that are mostly unrelated by location, function and lineage history. 10 of these 20 neuron classes had no homeobox gene function ascribed to them before, while in the other 10 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analysis, 111 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.
Minimal functional domains of the core polarity regulator Dlg
Authors: Khoury Mark J. , Bilder David 
Published: May 2022

ABSTRACTThe compartmentalized domains of polarized epithelial cells arise from mutually antagonistic actions between the apical Par complex and the basolateral Scrib module. In Drosophila, the Scrib module proteins Scribble (Scrib) and Discs-large (Dlg) are required to limit Lgl phosphorylation at the basolateral cortex, but how Scrib and Dlg could carry out such a ‘protection’ activity is not clear. We tested Protein Phosphatase 1α (PP1) as a potential mediator of this activity but demonstrate that a significant component of Scrib and Dlg regulation of Lgl is PP1-independent and found no evidence for a Scrib-Dlg-PP1 protein complex. However, the Dlg SH3 domain plays a role in Lgl protection and, in combination with the N-terminal region of the Dlg HOOK domain, in recruitment of Scrib to the membrane. We identify a ‘minimal Dlg’ comprised of the SH3 and HOOK domains that is both necessary and sufficient for Scrib localization and epithelial polarity function in vivo.Summary StatementA minimal SH3-HOOK fragment of Dlg is sufficient to support epithelial polarity through mechanisms independent of the PP1 phosphatase.
Long Term Virucidal Activity of Rosin Soap on Surfaces
Authors: Bell Stephen H , Fairley Derek J , Kettunen Hannele , Vuorenmaa Juhani , Orte Juha , Bamford Connor G G , McGrath John W 
Published: May 2022

AbstractMicrobiocidal products for decontaminating both animate and inanimate surfaces that may act as vectors for disease transmission are a well-established method for inactivating viruses of clinical significance. There are a wide variety of such microbiocidal products that can be purchased commercially, many with different active ingredients. We have recently shown that Rosin soap (derived from Tall Oil that has been produced by trees) is a highly effective virucidal product against enveloped viruses like influenza A virus and SARS-CoV-2 when tested in solution. Here we further demonstrate that Rosin soap retains its virucidal activity against influenza A virus and SARS-CoV-2 when applied to surfaces, such as plastic, glass and steel, either before or after virus inoculation. The virucidal activity extended out to seven days post administration. Together, our results show the potential for Rosin soap-based disinfectants to be used as a surface coating to protect against clinically relevant enveloped viruses, such as influenza viruses and coronaviruses.
Then and NOW: A Prospective Population-Level Validation of the Abbott ID NOW SARS-CoV-2 Device Implemented in Multiple Settings for Testing Asymptomatic and Symptomatic Individuals
Authors: Stokes William , Venner Allison A. , Buss Emily , Tipples Graham , Berenger Byron M. 
Published: May 2022

ABSTRACTIMPORTANCESince December, 2020, the ID NOW was implemented for use in 4 different populations across Alberta: in mobile units as part of community outbreak response, COVID-19 community collection sites, emergency shelters and addiction treatment facilities (ES), and hospitals.OBJECTIVEDiagnostic evaluation of the ID NOW in various real world settings among symptomatic and asymptomatic individualsDESIGNDepending on the implemented site, the ID NOW was tested on patients with symptoms suggestive of COVID-19, asymptomatic close contacts or asymptomatic individuals as part of outbreak point prevalence screening. From Jan – April, a select number of sites also switched from using oropharyngeal swabs to combined oropharyngeal + nasal (O+N) swabs. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse-transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results.RESULTSA total of 129,112 paired samples were analyzed (16,061 RT-PCR positive). 81,697 samples were from 42 COVID-19 community collection sites, 16,924 from 69 rural hospitals, 1,927 from 9 ES, 23,802 samples from 6 mobile units that responded to 356 community outbreaks, and 4,762 from 3 community collection sites and 1 ES using O+N swabs for ID NOW testing. ID NOW sensitivity was highest among symptomatic individuals presenting to community collection sites [92.5%, 95% confidence interval (CI) 92.0-93.0%, n=10,633 RT-PCR positive] and lowest for asymptomatic individuals associated with community outbreaks (73.9%, 95% CI 69.8-77.7%, n=494 RT-PCR positive). Specificity was greater than 99% in all populations tested, but positive predictive value (PPV) was lower among asymptomatic populations (82.4–91.3%) compared to symptomatic populations (96.0-96.9%). There was no statistically significant differences in sensitivity with respect to age, gender, NP vs OP swab for RT-PCR confirmation, variants of concern, or with combined oropharyngeal and nasal swabs using COVID-19 ID NOW testing.CONCLUSIONSSensitivity of ID NOW SARS-CoV-2 testing is highest when used on symptomatic community populations not seeking medical care. Sensitivity and PPV drops by approximately 10% when tested on asymptomatic populations. Using combined oropharyngeal and nasal swabs did not improve ID NOW performance.
Genomic characteristics and clinical significance of CD56+ Circulating Tumor Cells in Small Cell Lung Cancer
Authors: Ricordel C. , Chaillot L. , Vlachavas E. I. , Logotheti M. , Jouannic A. , Desvallees T. , Lecuyer G. , Aubry M. , Kontogianni G. , Mastrokalou C. , Jouan F. , Jarry U. , Corre R. , Guen Y. Le , Guillaudeux T. , Lena H. , Chatziioannou A. , Pedeux R. 
Published: May 2022

AbstractIntroductionCirculating Tumor Cells (CTC) have been studied in various solid tumors but clinical utility of CTC in Small Cell Lung Cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics.Patients and methodsCTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to Whole-exome-sequencing (WES).ResultsPhenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+CTC at diagnosis. High numeration of CD56+CTC (>7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway).ConclusionsWe report a versatile method of CD56+CTC detection in SCLC. Numeration of CD56+CTC at diagnosis is correlated with disease extension. Isolated CD56+CTC are tumorigenic and a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.
Protein complex prediction using Rosetta, AlphaFold, and mass spectrometry covalent labeling
Authors: Drake Zachary C. , Seffernick Justin T. , Lindert Steffen 
Published: May 2022

AbstractStructural mass spectrometry offers several techniques for the characterization of protein structures. Covalent labeling (CL) in combination with mass spectrometry can be used as an analytical tool to study and determine structural properties of protein-protein complexes. Degrees of modification obtained from CL experiments for specific labeled residues can be compared between the unbound and bound states of complexes. This analysis can yield insights into structural features of these protein assemblies, specifically the proximity of specific residues to the protein-protein interface. However, this data is sparse and does not unambiguously elucidate protein structure. Thus, computational algorithms are needed to deduce structure from the CL data. In this work we present a novel hybrid method that combines models of protein complex subunits generated with AlphaFold with differential CL data via a CL-guided protein-protein docking in Rosetta. In a benchmark set, the RMSD (root-mean-square deviation) of the best-scoring models was below 3.6 Å for 5/5 complexes with inclusion of CL data, whereas the same quality was only achieved for 1/5 complexes without CL data. The average improvement in RMSD observed upon inclusion of CL data was 5.2 Å. This study suggests that our integrated approach can successfully use data obtained from CL experiments to distinguish between nativelike and non-nativelike models.Significance StatementStructural mass spectrometry can be a powerful and versatile approach to characterize the structure of protein complexes. Data obtained from covalent labeling mass spectrometry can provide insights into higher order protein structure (particularly with respect to residue interactions and solvent accessibility) but needs to be supplemented by computational techniques to elucidate accurate, atomic-detail structural information. Here, we present a method to combine bioanalytical data obtained from covalent labeling with models generated using AlphaFold to accurately predict protein-protein complexes in Rosetta. Differential covalent labeling data can be used to determine the proximity of residues to the binding interface of complexes which we utilized to analyze computational models and improve structure prediction algorithms.
Keeping it close: The role of a Campus COVID Support Team (CCST) in sustaining a safe and healthy university campus during COVID-19
Authors: McDonnell Karen A , Vyas Amita , Castel Amanda , Nagaraj Nitasha , Landry Megan 
Published: May 2022

AbstractIt has been over 24 months since the start of the COVID-19 pandemic forced university campuses to shut down and then reopen under new safety guidelines. Now as we move into the subsequent years of the pandemic, we can look back and evaluate what has worked, improvements to be made, and plans for providing a sustained response for a campus community. In this article we detail one campus response to the COVID-19 pandemic and directions being taken to ensure a sustained campus COVID support team (CCST) is in hand to ensure the health and safety of the university community. The CCST was created to serve as a one-stop-shop to help the university community navigate COVID-19 policies and procedures. The responsibilities of the CCST include conducting case investigations for any positive COVID-19 tests within the university community, contact tracing for authorized university affiliates, epidemiological surveillance and mitigation efforts, and communication through real-time analysis and dashboards. Continuous monitoring procedures demonstrated the CCST conducted all case investigations within the post-testing 24-hour window, thus keeping the university test-positivity rate below 3%. Quality improvement surveys demonstrated a high level of satisfaction with the CCST efforts and provided areas for improvement and sustainability. Having a public health faculty led CCST enabled the university to act swiftly when COVID-19 positive cases were emerging and deter widespread campus COVID-19 outbreaks. The CCST timeliness and connectivity to the campus has demonstrated benefits to the health and safety of the campus.HighlightsUniversities are their own communities and having on campus COVID support teams can mitigate potential COVID-19 outbreaks.Having a public health driven Campus COVID Support Team that can conduct case investigations within 24 hours of a positive test result has demonstrated benefits to taking responsive measures.Continuous quality improvement efforts including surveys of the Campus COVID Support Team should be implemented for any COVID service efforts.
Essential oils of plants and their combinations as an alternative adulticides against Anopheles gambiae (Diptera: Culicidae) populations
Authors: Balboné Mahamoudou , Sawadogo Ignace , Soma Dieudonné Diloma , Drabo Samuel Fogné , Namountougou Moussa , Bayili Koama , Romba Rahim , Meda Georges Benson , Nebié Honorat Charles Roger , Dabire Roch K. , Bassolé Imae□l H. N. , Gnankine Olivier 
Published: May 2022

AbstractThe persistence of malaria and the increasing of resistance of Anopheles gambiae species to chemicals remain major public health concerns in sub-Saharan Africa. Faced to these concerns, the search for alternative vector control strategies as use of essential oils need to be implemented. Here, the five essential oils (EOs) from Cymbopogon citratus, Cymbopogon nardus, Eucalyptus camaldulensis, Lippia multiflora, Ocimum americanum obtained by hydro distillation were tested according to WHO procedures on Anopheles gambiae “Kisumu” and field strains collected in “Vallée du Kou”. Also, the binary combinations of C. nardus and O. americanum were examined. As results, among the EOs tested, L. multiflora was the most efficient regarding KDT50 and KDT95 and rate of morality values. Our current study showed that C8 (C.n 80% : O.a 20%) and C9 (C.n 90% : O.a 10%), were more toxic to Anopheles gambiae strain VK with the mortality rates reaching 80.7 and 100% at the 1% concentration, respectively. These two binary combinations shown a synergistic effect on the susceptible population. However, only C9 showed a synergistic effect on VK population. The bioactivity of the two EOs, Cymbopogon nardus and Ocimum americanum, was improved by the combinations at certain proportions and may constitute an alternative to pyrethroid resistance.
Immune defense in Drosophila melanogaster depends on diet, sex and mating status
Authors: Rai Kshama Ekanath , Yin Han , Bengo Arnie Lynn C. , Cheek Madison , Courville Robert , Bagheri Elnaz , Ramezan Reza , Behseta Sam , Shahrestani Parvin 
Published: May 2022

AbstractPost-mating immunosuppression has been widely accepted as a female trait in Drosophila melanogaster. Our results challenge this notion by presenting a mating-immunity trade-off in males as well as in females. When inoculated with the fungal pathogen, Beauveria bassiana, both males and females die faster compared to inoculated virgins, and survival is lower when inoculated flies are continuously mated compared to a single day of mating. Past studies with Beauveria bassiana have shown females to be more susceptible to infection than males. Our results challenge this finding as well, showing that the direction of sexual dimorphism in immune defense depends on mating status, specific Beauveria bassiana strain, and fly genotype. Moreover, we show that survival after fungal infection is largely influenced by diet, and that post-infection dietary improvements can help enhance survival. Post-mating suppression in Drosophila survival of B. bassiana infection presents study opportunities with potential applications for biological control of insect vectors of human disease and insect crop pests.
PfHDAC1 is an essential regulator of parasite asexual growth with its altered genomic occupancy and activity associated with artemisinin drug resistance in Plasmodium falciparum
Authors: Kanyal Abhishek , Davies Heledd , Deshmukh Bhagyashree , Farheen Dilsha , Treeck Moritz , Karmodiya Krishanpal 
Published: May 2022

AbstractPlasmodium falciparum is a deadly protozoan parasite and the causative agent of malaria, which accounts for close to 200 million cases and 400,000 deaths every year. It has been identified to possess a tightly regulated gene expression profile that is integrally linked to its timely development during the intraerythrocytic stage. Epigenetic modifiers of the histone acetylation code have been identified as key regulators of the parasite’s transcriptome. In this study, we characterize the solitary class I histone deacetylase PfHDAC1 and demonstrate that phosphorylation is required for its catalytic activity. PfHDAC1 binds to and regulates parasite genes responsible for housekeeping and stress-responsive functions. We show that PfHDAC1 activity in parasites is crucial for normal intraerythrocytic development and that its cellular abundance is correlated with parasitemia progression. We further show that PfHDAC1 has differential abundance and genomic occupancy in artemisinin drug-resistant vs sensitive parasites and that inhibition of its deacetylase activity can modulate the sensitivity of parasites to the drug. We also identify that artemisinin exposure can interfere with PfHDAC1 phosphorylation and its genomic occupancy. Collectively, our results demonstrate PfHDAC1 to be an important regulator of basic biological functions in parasites while also deterministic of responses to environmental stresses such as antimalarial drugs.
The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites
Authors: Looker Oliver , Dans Madeline G. , Bullen Hayley E. , Sleebs Brad E. , Crabb Brendan S. , Gilson Paul R. 
Published: May 2022

AbstractPlasmodium falciparum parasites which cause malaria, traffic hundreds of proteins into the red blood cells (RBCs) they infect. These exported proteins remodel their RBCs enabling host immune evasion through processes such as cytoadherence that greatly assist parasite survival. As resistance to all current anti-malarial compounds is rising new compounds need to be identified and those that could inhibit parasite protein secretion and export would both rapidly reduce parasite virulence and ultimately lead to parasite death. To identify compounds that inhibit protein export we used transgenic parasites expressing an exported nanoluciferase reporter to screen the Medicines for Malaria Venture Malaria box of 400 anti-malarial compounds with mostly unknown targets. The most potent inhibitor identified in this screen was MMV396797 whose application led to export inhibition of both the reporter and endogenous exported proteins. MMV396797 mediated blockage of protein export and slowed the rigidification and cytoadherence of infected RBCs - modifications which are both mediated by parasite-derived exported proteins. Overall, we have identified a new protein export inhibitor in P. falciparum whose target though unknown, could be developed into a future anti-malarial that rapidly inhibits parasite virulence before eliminating parasites from the host.SynopsisPlasmodium falciparum exports proteins into its host cell to perform a myriad of functions required for survival. We adapted an assay to screen for small molecules that inhibit protein secretion and export. Screening the 400-compound Medicines for Malaria Venture (MMV) Malaria Box uncovered several potential export inhibitors. The most promising of these compounds, MMV396797, blocked protein export at the parasite and reduced host rigidification and cytoadherence, two functions which are mediated by exported proteins.