bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Microfluidic Transistor for Liquid Signal Processing
Authors: Gopinathan Kaustav A. , Mishra Avanish , Mutlu Baris R. , Edd Jon F. , Toner Mehmet 
Published: June 2023

Abstract/SummaryMicrofluidics have enabled significant advances in molecular biology1–3, synthetic chemistry4,5, diagnostics6,7, and tissue engineering8. However, there has long been a critical need in the field to manipulate fluids and suspended matter with the precision, modularity, and scalability of electronic circuits9–11. Just as the electronic transistor enabled unprecedented advances in the control of electricity on an electronic chip, a microfluidic analogue to the transistor could enable improvements in the complex, scalable control of reagents, droplets, and single cells on an autonomous microfluidic chip. Prior works on creating a microfluidic analogue to the electronic transistor12–14could not replicate the transistor’s saturation behavior, which is crucial to perform analog amplification15and is fundamental to modern circuit design16. Here we exploit the fluidic phenomenon offlow-limitation17to develop a microfluidic element with flow-pressure characteristics completely analogous to the current-voltage characteristics of the electronic transistor. As this microfluidic transistor successfully replicates all of the key operating regimes of the electronic transistor (linear, cut-off and saturation), we are able to directly translate a variety of fundamental electronic circuit designs into the fluidic domain, including the amplifier, regulator, level shifter, logic gate, and latch. Finally, we demonstrate a “smart” particle dispenser that senses single suspended particles, performs liquid signal processing, and accordingly controls the movement of said particles in a purely fluidic system without electronics. By leveraging the vast repertoire of electronic circuit design, microfluidic transistor-based circuits are easy to integrate at scale, eliminate the need for external flow control, and enable uniquely complex liquid signal processing and single-particle manipulation for the next generation of chemical, biological, and clinical platforms.
Enhancing gene co-expression network inference for the malaria parasitePlasmodium falciparum
Authors: Li Qi , Button-Simons Katrina A , Sievert Mackenzie AC , Chahoud Elias , Foster Gabriel F , Meis Kaitlynn , Ferdig Michael T , Milenković Tijana 
Published: June 2023

AbstractBackgroundMalaria results in more than 550,000 deaths each year due to drug resistance in the most lethalPlasmodium(P.) speciesP. falciparum. A fullP. falciparumgenome was published in 2002, yet 44.6% of its genes have unknown functions. Improving functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance.ResultsGenes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks inP. falciparumhave been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for allP. falciparumgenes. We evaluate each inferred network based on how well it predicts existing gene-Gene Ontology (GO) term annotations using network clustering and leave-one-out cross-validation. We assess overlaps of the different networks’ edges (gene co-expression relationships) as well as predicted functional knowledge. The networks’ edges are overall complementary: 47%-85% of all edges are unique to each network. In terms of accuracy of predicting gene functional annotations, all networks yield relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached is below 15%. All networks having low recall means that none of them capture a large amount of all existing gene-GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene-gene interactions and predicted gene-GO term annotations for future use and wet lab validation by the malaria community.ConclusionsThe different networks seem to capture different aspects of theP. falciparumbiology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible.Supplementary dataAttached.Availability and implementationAll data and code are available athttps://nd.edu/~cone/pfalGCEN/.Contacttmilenko@nd.edu
Interactions Between the Histone Variant H2Av and the Suppressor of Hairy wing Insulator Influence the DNA Damage Response and Lymph Gland Development inDrosophila
Authors: Simmons James Ryan , Kemp Justin D. J. , Labrador Mariano 
Published: June 2023

AbstractGenome architecture is regulated by chromatin insulator proteins, and misregulation of insulator function is associated with genome instability and transcriptional regulatory defects in both vertebrates andDrosophila. Indeed, mutations of the sole insulator protein in humans, CTCF, are carcinogenic and mutations in theDrosophilainsulator proteinSuppressor of Hairy wing[Su(Hw)] lead to chromosomal rearrangements. However, the mechanism that links the DNA damage response and the regulation of transcription with insulator function is not yet understood. Here we show that enrichment of Su(Hw) insulator proteins at insulator sites increases after DNA damage. Additionally, Su(Hw) is necessary for phosphorylation of the histone variant H2Av in response to both UV treatment and X-ray irradiation. The requirement of Su(Hw) for H2Av phosphorylation appears to be tissue-specific, since H2Av is phosphorylated in response to DNA damage also in neurons, where Su(Hw) is not normally expressed. Similarly, we provide evidence that Su(Hw) and H2Av work together to ensure proper development of the lymph gland inDrosophilalarvae. We show that H2Av regulates formation of the larval lymph gland, and mutation of H2Av causes formation of large melanotic tumors that are rescued by mutation ofsu(Hw)in theHis2Av810mutant background. Double mutants ofsu(Hw)-andHis2Av810also form supernumerary lymph gland lobes that are larger than in wild type. Our findings support a role for the Su(Hw) in the DNA damage response through the regulation of H2Av phosphorylation and suggest that Su(Hw) and H2Av also work together to ensure proper development of the lymph gland.
WITHDRAWN: Prevalence of coronary artery disease among COVID-19 patients: a systematic review and meta-analysis
Authors: Akhtar Naushaba , Padhi Bijaya Kumar , Shamim Muhammad Aaqib , Gandhi Nandhni Chiruganam , Satapathy Prakisini , Pati Sanghamitra , Nowrouzi-Kia Behdin , Chattu Vijay Kumar 
Published: June 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to a complete change in methods and results. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the first author.
A novel family of sugar-specific phosphodiesterases that remove zwitterionic modifications ofN-acetylglucosamine
Authors: Fossa Samantha L. , Anton Brian P. , Kneller Daniel W. , Petralia Laudine M.C. , Boisvert Madison L. , Ganatra Mehul B. , Vainauskas Saulius , Chan S. Hong , Hokke Cornelis H. , Foster Jeremy M. , Taron Christopher H. 
Published: June 2023

ABSTRACTThe zwitterions phosphorylcholine (PC) and phosphoethanolamine (PE) are often found esterified to certain sugars in polysaccharides and glycoconjugates in a wide range of biological species. One such modification involves PC attachment to the 6-carbon ofN-acetylglucosamine (GlcNAc-6-PC) in N-glycans and glycosphingolipids (GSLs) of parasitic nematodes, a modification that helps the parasite evade host immunity. Knowledge of enzymes involved in the synthesis and degradation of PC and PE modifications is limited. More detailed studies on such enzymes would contribute to a better understanding of the function of PC modifications and have potential application in the structural analysis of zwitterion-modified glycans. In this study, we used functional metagenomic screening to identify phosphodiesterases encoded in a human fecal DNA fosmid library that remove PC from GlcNAc-6-PC. A novel bacterial phosphodiesterase was identified and biochemically characterized. This enzyme (termed GlcNAc-PDase) shows remarkable substrate preference for GlcNAc-6-PC and GlcNAc-6-PE, with little or no activity on other zwitterion-modified hexoses. The identified GlcNAc-PDase protein sequence is a member of the large endonuclease/exonuclease/phosphatase (EEP) superfamily where it defines a distinct subfamily of related sequences of previously unknown function, mostly fromClostridiumbacteria species. Finally, we demonstrate use of GlcNAc-PDase to confirm the presence of GlcNAc-6-PC in N-glycans and GSLs of the parasitic nematodeBrugia malayiin a glycoanalytical workflow.
Ribosome profiling reveals the fine-tuned response ofEscherichia colito mild and severe acid stress
Authors: Schumacher Kilian , Gelhausen Rick , Kion-Crosby Willow , Barquist Lars , Backofen Rolf , Jung Kirsten 
Published: June 2023

SummaryThe ability to respond to acidic environments is crucial for neutralophilic bacteria.Escherichia colihas a well-characterized regulatory network that triggers a multitude of defense mechanisms to counteract excess of protons. Nevertheless, systemic studies of the transcriptional and translational reprogramming ofE. colito different degrees of acid stress have not yet been performed. Here, we used ribosome profiling and RNA sequencing to compare the response ofE. coli(pH 7.6) to sudden mild (pH 5.8) and severe near-lethal acid stress (pH 4.4) conditions that mimic passage through the gastrointestinal tract. We uncovered new differentially regulated genes and pathways, key transcriptional regulators, and 18 novel acid-induced candidate sORFs. By using machine learning leveraging large compendia of publicly availableE. coliexpression data, we were able to distinguish between the response to acid stress and general stress. These results expand the acid resistance network and provide new insights into the fine-tuned response ofE. colito mild and severe acid stress.
Identifying Membrane Protein-Lipid Interactions with Lipidomic Lipid Exchange-Mass Spectrometry
Authors: Zhang Guozhi , Odenkirk Melanie T. , Janczak Colleen M. , Lee Ray , Richardson Kevin , Wang Zhihan , Aspinwall Craig A. , Marty Michael T. 
Published: June 2023

ABSTRACTLipids can play important roles in modulating membrane protein structure and function. However, it is challenging to identify natural lipids bound to membrane proteins in complex bilayers. Here, we developed lipidomic lipid exchange-mass spectrometry (LX-MS) to study the lipid affinity for membrane proteins on a lipidomic scale. We first mix membrane protein nanodiscs with empty nanodiscs that have no embedded membrane proteins. After allowing lipids to passively exchange between the two populations, we separate the two types of nanodiscs and perform lipidomic analysis on each with liquid chromatography and mass spectrometry. Enrichment of lipids in the membrane protein nanodiscs reveals the affinity of individual lipids for binding the target membrane protein. We apply this approach to study three membrane proteins. With theE. coliammonium transporter AmtB and aquaporin AqpZ in nanodiscs withE. colipolar lipid extract, we detected binding of cardiolipin and phosphatidyl-glycerol lipids to the proteins. With the acetylcholine receptor in nanodiscs with brain polar lipid extract, we discovered a complex set of lipid interactions that depended on the head group and tail composition. Overall, lipidomic LX-MS provides a detailed understanding of the lipid binding affinity and thermodynamics for membrane proteins in complex bilayers and provides a unique perspective on the chemical environment surrounding membrane proteins.
A mitochondrial sirtuin shapes the intestinal microbiota by controlling lysozyme expression
Authors: Knop Mirjam , Treitz Christian , Bettendorf Stina , Bossen Judith , von Frieling Jakob , Doms Shauni , Bruchhaus Iris , Kühnlein Ronald P. , Baines John F. , Tholey Andreas , Roeder Thomas 
Published: June 2023

AbstractSirtuins act as cellular sensors in the gut that control a substantial change in gut properties in response to environmental changes. Here we show that the only mitochondrial sirtuin ofDrosophila, dSirt4, is strongly up-regulated by a protein-reduced diet. Flies with a dSirt4 defect show strong changes in the protein pattern and physiological properties of their intestine. One of the most notable effects was the strong induction of lysozyme gene expression in the intestine, which also translates into enhanced lysozyme activity. This effect was cell autonomous, as it was also observed in flies withdsirt4was exclusively silenced in enterocytes of the intestine. Although this strongly increased lysozyme expression, it did not reduce total bacterial load in the intestine, but rather changed the composition of the microbiota by reducing the number of gram-positive bacteria. This effect on microbiota composition can be attributed to the dSirt4-dependent lysozyme expression, as it was absent in a lysozyme-deficient background.dSirt4deficiency in enterocytes reduced lifespan of flies, which was also observed in those flies experiencing ectopic lysozyme overexpression in enterocytes. This implies that strong lysozyme expression leads to a dysbiotic state associated with reduced lifespan.
Deferoxamine as adjunct therapeutics for tuberculosis
Authors: Kaushik Sandeep R. , Yadav Nidhi , Gupta Ashish , Sahu Sukanya , Bhalla Nikhil , Dagar Poonam , Mohapatra Amit Kumar , Sarangi Adyasha , Sharma Taruna , Biswal Bichitra , Pandey Amit Kumar , Nanda Ranjan Kumar 
Published: June 2023

AbstractDysregulated iron metabolism is reported in tuberculosis patients; therefore, it represents an opportunity for developing host-directed therapeutics. This study monitored the antimycobacterial properties of an iron chelator, i.e., Deferoxamine (DFO/D), and its impact on the transcript and metabolite levels ofMycobacterium tuberculosis(Mtb)in vitro. Forin vivovalidation, a group of mice received ferric carboxymaltose to create an iron overload condition, and controls were aerosol-infected with Mtb H37Rv. Mtb-infected mice received isoniazid (INH/H) and rifampicin (RIF/R) in combination with or without DFO before tissue-specific CFU assay, liver metabolite screening and iron quantification using mass spectrometry. DFO showed antimycobacterial properties comparable to INHin vitro. DFO treatment deregulated (log2DFO/control>±1.0) Mtb transcript (n=137) levels, the majority of which encode for iron-containing proteins and proteins involved in stress response. DFO treatment up-regulated Rv3622c (PE32), Rv2353c (PPE39) and Rv3022A (PE29) genes and conditional knocking down of ABC transporter likeirtAby anhydrotetracycline (Atc) inducible CRISPR interference (CRISPRi) approach compromised Mtb growth showing their potential involvement in iron metabolism. Global Mtb metabolite analysis using GC-MS identified a set of 5 deregulated metabolites indicating a perturbed pentose phosphate pathway and inositol phosphate metabolism in the host upon DFO treatment. Iron-overloaded mice exhibited significantly higher tissue mycobacterial burden at two weeks post-infection, and the efficacy of INH and RIF were compromised, corroborating with previous reports. Iron chelation by DFO or combined with/adjunct to RIF and INH significantly reduced the lung/tissue mycobacterial burden at four weeks post-treatment, specifically in the first (∼0.5 log) and second weeks (∼0.5 log) of treatment. The intracellular pro-inflammatory cytokine levels in the lung CD4+ T cells of INH and RIF-treated groups with or without DFO were similar, suggesting DFO has a direct role in Mtb survival and metabolism rather than improved infection, and the efficacy of INH and RIF were compromised, corroborating with previous reports. DFO adjunct to RIF and INH treatment significantly altered liver arginine biosynthesis, which directly neutralizes ammonia and is immune-supportive. Conventionally, DFO is used for treating acute iron toxicity that is common in thalassemic patients, and this study demonstrates DFO has potential as adjunct therapeutics for tuberculosis.Graphical abstract
A structural and dynamic visualization of the interaction between the microtubule-associated protein 7 (MAP7) and microtubules
Authors: Adler Agnes , Bangera Mamata , Bahri Salima , van Ingen Hugo , Moores Carolyn A. , Baldus Marc 
Published: June 2023

AbstractMicrotubules (MTs) are key components of the eukaryotic cytoskeleton and are essential for intracellular organization, organelle trafficking and mitosis. MT tasks depend on binding and interactions with MT-associated proteins (MAPs). MT-associated protein 7 (MAP7) has the unusual ability of both MT binding and activating kinesin-1-mediated cargo transport along MTs. Additionally, the protein is reported to stabilize MTs with its 112 amino-acid long MT-binding domain (MTBD). Here we investigate the structural basis of the interaction of MAP7 MTBD with the MT lattice. Using a combination of solid and solution-state nuclear magnetic resonance (NMR) spectroscopy with electron microscopy, fluorescence anisotropy and isothermal titration calorimetry, we shed light on the binding mode of MAP7 to MTs at an atomic level. Our results show that a combination of interactions between MAP7 and MT lattice extending beyond a single tubulin dimer and including tubulin C-terminal tails contribute to formation of the MAP7-MT complex.
Copper reduces the virulence of bacterial communities at environmentally relevant concentrations
Authors: Lear Luke , Padfield Dan , Hesse Elze , Kay Suzanne , Buckling Angus , Vos Michiel 
Published: June 2023

AbstractIncreasing environmental concentrations of metals as a result of anthropogenic pollution are significantly changing many microbial communities. While there is evidence metal pollution can result in increased antibiotic resistance, the effects of metal pollution on virulence remains largely undetermined. Here, we experimentally test whether metal stress alters the virulence of bacterial communities. We do this by incubating three wastewater influent communities under different environmentally relevant copper concentrations for three days. We then quantify the virulence of the community using theGalleria mellonellainfection model, and test if differences are due to changes in the rate of biomass accumulation (productivity), copper resistance, or community composition (quantified using 16S amplicon sequencing). The virulence of the communities was found to be reduced by the highest copper concentration, but not to be affected by the lower concentration. As well as reduced virulence, communities exposed to the highest copper concentration were less diverse and had lower productivity. This work highlights that metal pollution may decrease virulence in bacterial communities, but at a cost to diversity and productivity.
Inter and Intralaminar Excitation of Parvalbumin Interneurons in Mouse Barrel Cortex
Authors: Scheuer Kate S. , Jansson Anna M. , Zhao Xinyu , Jackson Meyer B. 
Published: June 2023

AbstractParvalbumin (PV) interneurons are inhibitory fast-spiking cells with essential roles in directing the flow of information through cortical circuits. These neurons set the balance between excitation and inhibition, control rhythmic activity, and have been linked to disorders including autism spectrum and schizophrenia. PV interneurons differ between cortical layers in their morphology, circuitry, and function, but how their electrophysiological properties vary has received little attention. Here we investigate responses of PV interneurons in different layers of primary somatosensory barrel cortex (BC) to different excitatory inputs. With the genetically-encoded hybrid voltage sensor, hVOS, we recorded voltage changes simultaneously in many L2/3 and L4 PV interneurons to stimulation in either L2/3 or L4. Decay-times were consistent across L2/3 and L4. Amplitude, half-width, and rise-time were greater for PV interneurons residing in L2/3 compared to L4. Stimulation in L2/3 elicited responses in both L2/3 and L4 with longer latency compared to stimulation in L4. These differences in latency between layers could influence their windows for temporal integration. Thus PV interneurons in different cortical layers of BC show differences in response properties with potential roles in cortical computations.Key points summaryExcitatory synaptic responses were imaged in parvalbumin (PV) interneurons in slices of mouse barrel cortex using a targeted genetically-encoded voltage sensor. This approach revealed simultaneous voltage changes in approximately 20 neurons pre slice in response to stimulation.PV interneurons residing in layer 2/3 had larger amplitudes, longer half-widths, and longer rise-times than PV interneurons residing in layer 4.Responses of PV interneurons residing in either layer 2/3 or layer 4 had shorter latencies to stimulation of layer 4 compared to stimulation of layer 2/3.Excitatory synaptic transmission to PV interneurons varies with layer of residence and source of excitation.