bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of heavy metals in blood of nesting Kemp’s Ridley turtles (Lepidochelys kempii) at Rancho Nuevo sanctuary, Tamaulipas, Mexico
Authors: Zavala-Félix Kevin Alan , Reyes-López Miguel Angel , Camacho-Sánchez Fátima Yedith , Acosta-Sánchez Héctor Hugo , Hart Catherine E. , Zavala-Norzagaray Alan A. , Leal-Sepúlveda Valeria , Espinoza-Romo Brenda Aracely , Leal-Moreno Renato , Aguirre A. Alonso , Ley-Quiñónez César Paúl 
Published: May 2022

AbstractThe concentrations of heavy metals and metalloids including As, Zn, Cu, Se, Pb, Hg and Cd, were determined in the blood of nesting Kemp’s ridley turtles (Lepidochelys kempii) at Rancho Nuevo sanctuary, Tamaulipas, Mexico during 2018-2020. The sequential concentrations of metals analyzed were Zn> Se> Cu> As> Pb; while Cd and Hg concentrations were below the limits of detection (0.01 µg g−1). No significant differences were observed between the concentrations of metals (p> 0.05) by year, except Se levels, possibly resulting from recorded seasonal differences in turtle size. No relationships among turtle size vs metal concentration were observed. In conclusion, heavy metals concentrations in the blood of nesting Kemp’s ridley turtles may be a reflex of the ecosystem in which the turtles develop, that is, with low bioavailability of metals observed in the trophic webs in the Gulf of Mexico.
The petrous bone contains high concentrations of osteocytes: one possible reason why ancient DNA is better preserved in this bone
Authors: Ibrahim Jamal , Brumfeld Vlad , Addadi Yoseph , Rubin Sarah , Weiner Steve , Boaretto Elisabetta 
Published: May 2022

AbstractThe characterization of ancient DNA in fossil bones is providing invaluable information on the genetics of past human and other animal populations. These studies have been aided enormously by the discovery that ancient DNA is relatively well preserved in the petrous bone compared to most other bones. The reasons for this better preservation are however not well understood. Here we examine the hypothesis that one reason for better DNA preservation in the petrous bone is that fresh petrous bone contains more DNA than other bones. We therefore determined the concentrations of osteocyte cells occluded inside lacunae within the petrous bone and compared these concentrations to other bones from the domestic pig using high resolution microCT. We show that the concentrations of osteocyte lacunae in the inner layer of the pig petrous bone adjacent to the otic chamber are about three times higher than in the temporal bone, as well as the cortical bone of the femur. The sizes and shapes of the lacuna in the inner layer of the petrous bone are similar to those in the femur. We also confirm that the petrous bone lacunae do contain osteocytes using a histological stain for DNA. We therefore conclude that one possible reason for better preservation of ancient DNA in the petrous bone is that this bone initially contains up to three times more DNA than other bones, and hence during diagenesis more DNA is likely to be preserved. We also note that the osteocytes in the inner layer of the petrous bone may have a function in hearing.
SARS-CoV-2 Infects Peripheral and Central Neurons Before Viremia, Facilitated by Neuropilin-1
Authors: Joyce Jonathan D. , Moore Greyson A. , Goswami Poorna , Harrell Telvin L. , Taylor Tina M. , Hawks Seth A. , Green Jillian C. , Jia Mo , Yallayi Neeharika , Leslie Emma H. , Duggal Nisha K. , Thompson Christopher K. , Bertke Andrea S. 
Published: May 2022

AbstractNeurological symptoms associated with COVID-19, acute and long-term, suggest SARS-CoV-2 affects both central and peripheral nervous systems. Although studies have shown olfactory and hematogenous entry into the brain and neuroinflammation, little attention has been paid to the susceptibility of the peripheral nervous system to infection or to alternative routes of CNS invasion. We show that neurons in the central and peripheral nervous system are susceptible to productive infection with SARS-CoV-2. Infection of K18-hACE2 mice, wild-type mice, golden Syrian hamsters, and primary neuronal cultures demonstrate viral RNA, protein, and infectious virus in peripheral nervous system neurons and satellite glial cells, spinal cord, and specific brain regions. Moreover, neuropilin-1 facilitates SARS-CoV-2 neuronal infection. Our data show that SARS-CoV-2 rapidly invades and establishes a productive infection in the peripheral and central nervous system via direct invasion of neurons prior to viremia, which may underlie some cognitive and sensory symptoms associated with COVID-19.
Art2 mediates selective endocytosis of methionine transporters during adaptation to sphingolipid depletion
Authors: Hepowit Nathaniel L. , Moon Bradley , Dickson Robert C. , MacGurn Jason A. 
Published: May 2022

SummaryAccumulating evidence in several model organisms indicates that reduced sphingolipid biosynthesis promotes longevity, although underlying mechanisms remain unclear. In yeast, sphingolipid depletion induces a state resembling amino acid restriction, which we hypothesized may be due to altered stability of amino acid transporters at the plasma membrane. To test this, we measured surface abundance for a diverse panel of membrane proteins in the presence of myriocin, a sphingolipid biosynthesis inhibitor. Unexpectedly, we found that surface levels of most proteins examined were either unaffected or increased during myriocin treatment, consistent with an observed decrease in bulk endocytosis. In contrast, sphingolipid depletion triggered selective endocytosis of the methionine transporter Mup1. Unlike methionine-induced Mup1 endocytosis, myriocin triggers Mup1 endocytosis that requires the Rsp5 adaptor Art2, C-terminal lysine residues, and the formation of K63-linked ubiquitin polymers. These findings reveal cellular adaptation to sphingolipid depletion by ubiquitin-mediated remodeling of nutrient transporter composition at the cell surface.
Lysogenized phages of methanotrophic bacteria show a broad and untapped genetic diversity
Authors: Stahn Miranda , Grigonyte Aurelija M. , Orata Fabini D. , Collins David A. , Rieder Liam , Kalyuzhnaya Marina G. , Millard Andrew , Stein Lisa Y. , Sauvageau Dominic 
Published: May 2022

AbstractMethanotrophs are a unique class of bacteria with the ability to metabolize single-carbon compounds such as methane. They play an important role in the global methane cycle and have great potential as industrial platforms for the bioconversion of methane from industrial waste streams into valuable products, such as biofuels and bioplastics. However, many aspects of methanotroph biology have yet to be elucidated, including the prevalence and impact of lysogenized bacteriophages (phages), which can greatly affect both the ecology and the industrial performance of these bacteria.The present study investigates the presence of putative prophages in three gammaproteobacterial (Methylobacter marinus A45, Methylomicrobium album BG8, Methylomonas denitrificans FJG1) and two alphaproteobacterial (Methylosinus trichosporium OB3b, Methylocystis sp. Rockwell) methanotrophs using four programs predicting putative phage sequences (PhageBoost, PHASTER, Phigaro, and Island Viewer). Mitomycin C was used to trigger induction of prophages, which was monitored through infection dynamics. Successfully induced phages from M. marinus A45 (MirA1, MirA2), M. album BG8 (MirB1), and M. trichosporium OB3b (MirO1) were isolated and characterized using transmission electron microscopy. Subsequently, bioinformatic analyses (BLAST and phylogenetics) were performed on three induced phages to obtain a profile of their respective genetic makeup. Their broad diversity and differences from previously known phages, based on whole genome and structural gene sequences, suggest they each represent a new phage family, genus and species: “Britesideviridae Inducovirus miraone”, “Patronusviridae Enigmavirus miratwo”, and “Kainiviridae Tripudiumvirus miroone” represented by isolates MirA1, MirA2, and MirO1, respectively.
Mechanism of treatment-free remission in patients with chronic myeloid leukemia revealed by a computational model of CML evolution
Authors: Lai Xiulan , Jiao Xiaopei , Zhang Haojian , Lei Jinzhi 
Published: May 2022

AbstractIn the past few years, international treatment guidelines for chronic myeloid leukemia (CML) have incorporated recommendations for attempting discontinuation of treatment with tyrosine kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of treatment-free remission (TFR). Multiple clinical studies have shown consistent results that 40%-50% patients can achieve long-term TFR after TKI discontinuation, and most relapse patients undergo molecular recurrence within 6 months after TKI discontinuation, however the underling mechanisms remain unclear. To understand the mechanism of TFR in patients with CML, we consider the competition between leukemia stem cell and bone marrow microenvironment, and develop a mathematical model to investigate the CML progression dynamics. Model simulations are consistent with clinical observation of CML progression, and reveal a mechanism of dimorphic response after TKI discontinuation. Our model predicts that neoplasitic microenvironment is significant for CML occurrence and progression. We furthermore discuss the prediction of TFR based on the change rates of microenvironment index and leukemia stem cells ratio prior TKI discontinuation.
Radiation and diversification of GATA-domain-containing proteins in the genus Caenorhabditis
Authors: Darragh Antonia C. , Rifkin Scott A. 
Published: May 2022

AbstractTranscription factors are defined by their DNA-binding domains (DBDs). The binding affinities and specificities of a transcription factor to its DNA binding sites can be used by an organism to fine-tune gene regulation and so are targets for evolution. Here we investigate the evolution of GATA-type transcription factors (GATA factors) in the Caenorhabditis genus. Based upon comparisons of their DBDs, these proteins form 13 distinct groups. This protein family experienced a burst of gene duplication in several of these groups along two short branches in the species tree, giving rise to subclades with very distinct complements of GATA factors. By comparing extant gene structures, DBD sequences, genome locations, and selection pressures we reconstructed how these duplications occurred. Although the paralogs have diverged in various ways, the literature shows that at least eight of the DBD groups bind to similar G-A-T-A DNA sequences. Thus, despite gene duplications and divergence among DBD sequences, most Caenorhabditis GATA factors appear to have maintained similar binding preferences, which could create the opportunity for developmental system drift. We hypothesize that this limited divergence in binding specificities contributes to the apparent disconnect between the extensive genomic evolution that has occurred in this genus and the absence of significant anatomical changes.
Epitranscriptomic Modification of MicroRNA Increases Atherosclerosis Susceptibility
Authors: He Ming , Dong Jianjie , Zhang Yuqing , Han So Yun , Wang Chen , Gongol Brendan , Kang Jian , Huang Hsi-Yuan , Shyy John Y-J. 
Published: May 2022

AbstractEmerging evidence indicates that oxidative stress causes the hydroxylation of guanine (G) to generate 8-oxo-7,8-dihydro guanosine (8OH-G) in microRNAs (miRs), which induces the guanine-to-uracil (G-to-U) transversion and thus changes the miR targetomes. However, whether and how the 8OH-G-modified miRs are involved in vascular endothelial dysfunction and atherogenesis were unexplored. Using 8OH-G crosslinking immunoprecipitation miR sequencing (8OH-G CLIP-miR-seq), we found that 8OH-G miR-483 were among the most enriched 8OH-G miR species in ECs induced by ox-LDL. Transcriptomic profiling by RNA-seq indicated that the G-to-U transversion of miR-483 altered the original mRNA targeting efficacy and allows 8OH-G miR-483 to recognize new mRNA target sites. A reduced ratio of 8OH-G miR-483 to miR-483 in lung ECs was found in the endothelial-specific miR-483 transgenic (EC-miR-483 Tg) mice. Moreover, reduction of atherosclerosis was significant in EC-miR-483 Tg mice administrated AAV8-PCSK9 and fed an atherogenic diet. In situ miR hybridization revealed an increased 8OH-G miR-483 level in the intima of human atherosclerotic arteries. Collectively, this study demonstrates that the redox burden incurred by cardiovascular risk factors is a culprit of the miR-483 to 8OH-G miR-483 transversion. Such epitranscriptomic modification of miR-483 causes endothelial dysfunction and increases atherosclerosis susceptibility via its targetomes shift.
S. cerevisiae cells can grow without the Pds5 cohesin subunit
Authors: Choudhary Karan , Itzkovich Ziv , Alonso-Perez Elisa , Bishara Hend , Dunn Barbara , Sherlock Gavin , Kupiec Martin 
Published: May 2022

ABSTRACTDuring DNA replication, the newly created sister chromatids are held together until their separation at anaphase. The cohesin complex is in charge of creating and maintaining sister-chromatid cohesion (SCC) in all eukaryotes. In S. cerevisiae cells, cohesin is composed of two elongated proteins, Smc1 and Smc3, bridged by the kleisin Mcd1/Scc1. The latter also acts as a scaffold for three additional proteins, Scc3/Irr1, Wpl1/Rad61, and Pds5. Although the HEAT-repeat protein Pds5 is essential for cohesion, its precise function is still debated. Deletion of the ELG1 gene, encoding a PCNA unloader, can partially suppress the temperature-sensitive pds5-1 allele, but not a complete deletion of PDS5. We carried out a genetic screen for high copy number suppressors and another for spontaneously arising mutants, allowing the survival of a pds5Δ elg1Δ strain. Our results show that cells remain viable in the absence of Pds5 provided that there is both an elevation in the level of Mcd1 (which can be due to mutations in the CLN2 gene, encoding a G1 cyclin), and an increase in the level of SUMO-modified PCNA on chromatin (caused by lack of PCNA unloading in elg1Δ mutants). The elevated SUMO-PCNA levels increase the recruitment of the Srs2 helicase, which evicts Rad51 molecules from the moving fork, creating ssDNA regions that serve as sites for increased cohesin loading and SCC establishment. Thus, our results delineate a double role for Pds5 in protecting the cohesin ring and interacting with the DNA replication machinery.IMPORTANCESister chromatid cohesion is vital for faithful chromosome segregation, chromosome folding into loops, and gene expression. A multisubunit protein complex known as cohesin holds the sister chromatids from S-phase until the anaphase stage. In this study, we explore the function of the essential cohesin subunit Pds5 in the regulation of sister chromatid cohesion. We performed two independent genetic screens to bypass the function of the Pds5 protein. We observe that Pds5 protein is a cohesin stabilizer, and elevating the levels of Mcd1 protein along with SUMO-PCNA accumulation on chromatin can compensate for the loss of the PDS5 gene. In addition, Pds5 plays a role in coordinating the DNA replication and sister chromatid cohesion establishment. This work elucidates the function of cohesin subunit Pds5, the G1 cyclin Cln2, and replication factors PCNA, Elg1 and Srs2 in the proper regulation of sister chromatid cohesion.
Colony size frequency distribution across gradients of reef health in disturbed coral reefs in Northeast Peninsular Malaysia
Authors: Bernard Gilles Gael Raphael , Kellam Alexandra Lucie , Szereday Sebastian 
Published: May 2022

AbstractCoral reefs globally are experiencing chronic stress leading to the deterioration of health and functionality. Analysis of size frequency distribution (SFD) of hard corals enables post hoc assessments of major demographic events (e.g., recruitment and mortality) that follow ecological disturbances. Here, we present an evaluation of current reef health, SFD and recruitment of 37 morpho-taxa in Northeast Peninsular Malaysia. Results highlight stress viable demographic structure of massive taxa (e.g., massivePorites) and significant differences of SFD across gradients of reef health, whereby degraded sites were predominantly characterized by negatively skewed (e.g., large colonies) and leptokurtic (e.g., high population turnover) distribution of dominant hard coral taxa. Ultimately, results suggest that locally coral reef degradation can exceed tipping points, after which annual monsoon conditions and degraded reef substrates interact to reinforce and manifest negative feedback loops, thereby impeding demographic recovery, and altering coral SFD and population assemblage.
Contrasting parental roles shape sex differences in poison frog space use but not navigational performance
Authors: Pašukonis Andrius , Serrano-Rojas Shirley Jennifer , Fischer Marie-Therese , Loretto Matthias-Claudio , Shaykevich Daniel A. , Rojas Bibiana , Ringler Max , Roland Alexandre-Benoit , Marcillo-Lara Alejandro , Ringler Eva , Rodríguez Camilo , Coloma Luis A. , O’Connell Lauren A. 
Published: May 2022

AbstractSex differences in vertebrate spatial abilities are typically interpreted under the adaptive specialization hypothesis, which posits that male reproductive success is linked to larger home ranges and better navigational skills. The androgen spillover hypothesis counters that enhanced male spatial performance may be a byproduct of higher androgen levels. Animal groups that include species where females are expected to outperform males based on life-history traits are key for disentangling these hypotheses. We investigated the association between sex differences in reproductive strategies, spatial behavior, and androgen levels in three species of poison frogs. We tracked individuals in natural environments to show that contrasting parental sex roles shape sex differences in space use, where the sex performing parental duties shows wider-ranging movements. We then translocated frogs from their home areas to test their navigational performance and found that the caring sex outperformed the non-caring sex only in one out of three species. In addition, males across species displayed more explorative behavior than females. Furthermore, androgen levels correlated with explorative behavior and homing accuracy. Our findings suggest that poison frog reproductive strategies shape space use patterns but not navigational performance, providing counterevidence to the prevailing view of adaptive sex differences in spatial abilities.
Reliable detection of pyrazinamide antitubercular activity in vitro
Authors: Gouzy Alexandre , Healy Claire , Schnappinger Dirk , Ehrt Sabine 
Published: May 2022

AbstractPyrazinamide (PZA) is a pivotal antibiotic for the chemotherapy of tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis (Mtb). PZA is notorious for its poor in vitro activity which complicates phenotypic PZA-susceptibility testing (PPST) and likely causes inappropriate treatment of TB patients. Here, we show that PZA activity can be reliably detected using an acidic and lipid-rich culture medium mimicking conditions Mtb encounters during an infection. Our growth model could facilitate PPST to improve the treatment of TB patients and ameliorate the global surveillance of PZA resistance.
Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity
Authors: Kitamura Akira , Fujimoto Ai , Kawashima Rei , Lyu Yidan , Sasaki Kotetsu , Hamada Yuta , Moriya Kanami , Kurata Ayumi , Takahashi Kazuho , Brielmann Reneé , Bott Laura C. , Morimoto Richard I. , Kinjo Masataka 
Published: May 2022

AbstractCarboxy terminal fragments (CTFs) of TDP-43 contain an intrinsically disordered region (IDR) and form cytoplasmic condensates containing amyloid fibrils. Such condensates are toxic and associated with pathogenicity in amyotrophic lateral sclerosis. However, the molecular details of how the domain of TDP-43 CTFs leads to condensation and cytotoxicity remain elusive. Here, we show that truncated RNA/DNA-recognition motif (RRM) at the N-terminus of TDP-43 CTFs leads to the structural transition of the IDR, whereas the IDR itself of TDP-43 CTFs is difficult to assemble even if they are proximate intermolecularly. Hetero-oligomers of TDP-43 CTFs that have recruited other proteins are more toxic than homo-oligomers, implicating loss-of-function of the endogenous proteins by such oligomers is associated with cytotoxicity. Furthermore, such toxicity of TDP-43 CTFs was cell-nonautonomously affected in the nematodes. Therefore, misfolding and oligomeric characteristics of the truncated RRM at the N-terminus of TDP-43 CTFs define their condensation properties and toxicity.
Opsin-free optical neuromodulation and electrophysiology enabled by a soft monolithic infrared multifunctional neural interface
Authors: Meneghetti Marcello , Kaur Jaspreet , Sui Kunyang , Sørensen Jakob F. , Berg Rune W. , Markos Christos 
Published: May 2022

ABSTRACTControlling neuronal activity with high spatial resolution using multifunctional and minimally invasive neural interfaces constitutes an important step towards developments in neuroscience and novel treatments for brain diseases. While infrared neuromodulation is an emerging technology for controlling the neuronal circuitry, it lacks soft implantable monolithic interfaces capable of simultaneously delivering light and recording electrical signals from the brain while being mechanically brain-compatible. Here, we have developed a soft fibre-based device based on high-performance thermoplastics which are >100-fold softer than silica glass. The presented fibre-implant is capable of safely neuromodulating the brain activity in localized cortical domains by delivering infrared laser pulses in the 2 μm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo in adult rats while immunohistochemical analysis of the tissue indicated limited microglia and monocytes response introduced by the fibre and the infrared pulses. We expect our devices to further enhance infrared neuromodulation as a versatile approach for fundamental research and clinically translatable therapeutic interventions.
Deep mutational scanning of essential bacterial proteins can guide antibiotic development
Authors: Dewachter Liselot , Brooks Aaron N. , Noon Katherine , Cialek Charlotte , Clark-ElSayed Alia , Schalck Thomas , Krishnamurthy Nandini , Versées Wim , Vranken Wim , Michiels Jan 
Published: May 2022

AbstractDeep mutational scanning is a powerful approach to investigate a wide variety of research questions including protein function and stability. We performed deep mutational scanning on three essentialE. coliproteins (FabZ, LpxC and MurA) involved in cell envelope synthesis using high-throughput CRISPR genome editing. This allowed us to study the effect of the introduced mutations in their original genomic context. Using more than 17,000 variants of FabZ, LpxC and MurA from the saturation editing libraries constructed here, we have interrogated protein function and the importance of individual amino acids in supporting viability. Additionally, we have exploited these libraries to study resistance development against antimicrobial compounds that target the selected proteins. Our results show that, among the three proteins studied, MurA is the superior antimicrobial target due to its low mutational flexibility which decreases the chance of acquiring resistance-conferring mutations that simultaneously preserve MurA function. Additionally, we were able to rank anti-LpxC lead compounds for further development guided by the number of resistance-conferring mutations against each compound. Our results show that deep mutational scanning studies can be used to guide drug development, which we hope will contribute towards the development of urgently needed novel antimicrobial therapies.