bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting TPC2 sensitizes acute lymphoblastic leukemia cells to chemotherapeutics by impairing lysosomal function
Authors: Geisslinger Franz , Müller Martin , Chao Yu-Kai , Grimm Christian , Vollmar Angelika M. , Bartel Karin 
Published: August 2022

AbstractDespite novel therapy regimens and extensive research, chemoresistance remains a challenge in leukemia treatment. Of note, recent studies revealed lysosomes as regulators of cell death and chemotherapy response, suggesting this organelle is a novel target for chemosensitization. Interestingly, drug-resistant VCR-R CEM acute lymphoblastic leukemia (ALL) cells have an increased expression of the lysosomal cation channel Two-Pore-Channel 2 (TPC2) compared to drug-naïve CCRF-CEM ALL cells. Concurrently, knockout (KO) of TPC2 sensitized drug-resistant VCR-R CEM cells to treatment with cytostatics. The chemosensitizing effect could be confirmed in several cell lines as well as in heterogeneous, patient-derived xenograft ALL cells, using the pharmacological TPC2 inhibitors naringenin and tetrandrine. We reveal that a dual mechanism of action mediates chemo sensitization by loss of lysosomal TPC2 function. First, because of increased lysosomal pH, lysosomal drug sequestration is impaired, leading to an increased nuclear accumulation of doxorubicin and hence increased DNA damage. Second, lysosomes of TPC2 KO cells are more prone to lysosomal damage as a result of morphological changes and dysregulation of proteins influencing lysosomal stability. This leads to induction of lysosomal cell death (LCD), evident by increased cathepsin B levels in the cytosol, truncation of pro-apoptotic Bid, as well as the reversibility of cell death by co-treatment with the cathepsin B inhibitor CA-074Me in TPC2 KO cells. In summary, this study establishes TPC2 as a novel, promising, druggable target for combination therapy approaches in ALL to overcome chemoresistance, which could be exploited in the clinic in the future. Additionally, it unravels LCD signaling as an important death-inducing component upon loss of TPC2 function.
Photochemical spin-state control of binding configuration for tailoring organic color center emission in carbon nanotubes
Authors: Zheng Yu , Han Yulun , Weight Braden M. , Lin Zhiwei , Gifford Brendan J. , Zheng Ming , Kilin Dmitri , Kilina Svetlana , Doorn Stephen K. , Htoon Han , Tretiak Sergei 
Published: August 2022

AbstractIncorporating fluorescent quantum defects in the sidewalls of semiconducting single-wall carbon nanotubes (SWCNTs) through chemical reaction is an emerging route to predictably modify nanotube electronic structures and develop advanced photonic functionality. Applications such as room-temperature single-photon emission and high-contrast bio-imaging have been advanced through aryl-functionalized SWCNTs, in which the binding configurations of the aryl group define the energies of the emitting states. However, the chemistry of binding with atomic precision at the single-bond level and tunable control over the binding configurations are yet to be achieved. Here, we explore recently reported photosynthetic protocol and find that it can control chemical binding configurations of quantum defects, which are often referred to as organic color centers, through the spin multiplicity of photoexcited intermediates. Specifically, photoexcited aromatics react with SWCNT sidewalls to undergo a singlet-state pathway in the presence of dissolved oxygen, leading to ortho binding configurations of the aryl group on the nanotube. In contrast, the oxygen-free photoreaction activates previously inaccessible para configurations through a triplet-state mechanism. These experimental results are corroborated by first principles simulations. Such spin-selective photochemistry diversifies SWCNT emission tunability by controlling the morphology of the emitting sites.
Tuning lower dimensional superconductivity with hybridization at a superconducting-semiconducting interface
Authors: Kamlapure Anand , Simonato Manuel , Sierda Emil , Steinbrecher Manuel , Kamber Umut , Knol Elze J. , Krogstrup Peter , Katsnelson Mikhail I. , Rösner Malte , Khajetoorians Alexander Ako 
Published: August 2022

AbstractThe influence of interface electronic structure is vital to control lower dimensional superconductivity and its applications to gated superconducting electronics, and superconducting layered heterostructures. Lower dimensional superconductors are typically synthesized on insulating substrates to reduce interfacial driven effects that destroy superconductivity and delocalize the confined wavefunction. Here, we demonstrate that the hybrid electronic structure formed at the interface between a lead film and a semiconducting and highly anisotropic black phosphorus substrate significantly renormalizes the superconductivity in the lead film. Using ultra-low temperature scanning tunneling microscopy and spectroscopy, we characterize the renormalization of lead’s quantum well states, its superconducting gap, and its vortex structure which show strong anisotropic characteristics. Density functional theory calculations confirm that the renormalization of superconductivity is driven by hybridization at the interface which modifies the confinement potential and imprints the anisotropic characteristics of the semiconductor substrate on selected regions of the Fermi surface of lead. Using an analytical model, we link the modulated superconductivity to an anisotropy that selectively tunes the superconducting order parameter in reciprocal space. These results illustrate that interfacial hybridization can be used to tune superconductivity in quantum technologies based on lower dimensional superconducting electronics.
Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection
Authors: Vornhagen Jay , Roberts Emily K. , Unverdorben Lavinia , Mason Sophia , Patel Alieysa , Crawford Ryan , Holmes Caitlyn L. , Sun Yuang , Teodorescu Alexandra , Snitkin Evan S. , Zhao Lili , Simner Patricia J. , Tamma Pranita D. , Rao Krishna , Kaye Keith S. , Bachman Michael A. 
Published: August 2022

AbstractMembers of the Klebsiella pneumoniae species complex frequently colonize the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases (N = 85), where colonizing and invasive isolates were identical strain types, were matched to asymptomatically colonizing controls (N = 160). Thirty-seven genes are associated with infection, 27 of which remain significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes are not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many genes are plasmid borne, and for some, the relationship with infection is mediated by gut dominance. Five genes were validated in a geographically-independent cohort of colonized patients. This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella.
Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets
Authors: Mathur L. , Szalai B. , Du N. H. , Utharala R. , Ballinger M. , Landry J. J. M. , Ryckelynck M. , Benes V. , Saez-Rodriguez J. , Merten C. A. 
Published: August 2022

AbstractAnti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the right combination is challenging and would benefit from high-content, high-throughput combinatorial screens directly on patient biopsies. However, such screens require a large amount of material, normally not available from patients. To address these challenges, we present a scalable microfluidic workflow, called Combi-Seq, to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout for drug effects. We devise a deterministic combinatorial DNA barcoding approach to encode treatment conditions, enabling the gene expression-based readout of drug effects in a highly multiplexed fashion. We apply Combi-Seq to screen the effect of 420 drug combinations on the transcriptome of K562 cells using only ~250 single cell droplets per condition, to successfully predict synergistic and antagonistic drug pairs, as well as their pathway activities.
Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections
Authors: Stærke Nina Breinholt , Reekie Joanne , Nielsen Henrik , Benfield Thomas , Wiese Lothar , Knudsen Lene Surland , Iversen Mette Brouw , Iversen Kasper , Fogh Kamille , Bodilsen Jacob , Juhl Maria Ruwald , Lindvig Susan Olaf , Øvrehus Anne , Madsen Lone Wulff , Klastrup Vibeke , Andersen Sidsel Dahl , Juhl Anna Karina , Andreasen Signe Rode , Ostrowski Sisse Rye , Erikstrup Christian , Fischer Thea K. , Tolstrup Martin , Østergaard Lars , Johansen Isik Somuncu , Lundgren Jens , Søgaard Ole Schmeltz 
Published: August 2022

AbstractSARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.
Xist exerts gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis
Authors: Yang Tianqi , Ou Jianhong , Yildirim Eda 
Published: August 2022

AbstractX chromosome inactivation (XCI) is a dosage compensation phenomenon that occurs in females. Initiation of XCI depends on Xist RNA, which triggers silencing of one of the two X chromosomes, except for XCI escape genes that continue to be biallelically expressed. In the soma XCI is stably maintained with continuous Xist expression. How Xist impacts XCI maintenance remains an open question. Here we conditionally delete Xist in hematopoietic system of mice and report differentiation and cell cycle defects in female hematopoietic stem and progenitor cells (HSPCs). By utilizing female HSPCs and mouse embryonic fibroblasts, we find that X-linked genes show variable tolerance to Xist loss. Specifically, XCI escape genes exhibit preferential transcriptional upregulation, which associates with low H3K27me3 occupancy and high chromatin accessibility that accommodates preexisting binding of transcription factors such as Yin Yang 1 (YY1) at the basal state. We conclude that Xist is necessary for gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis.
mRNA vaccines induce rapid antibody responses in mice
Authors: Gebre Makda S. , Rauch Susanne , Roth Nicole , Gergen Janina , Yu Jingyou , Liu Xiaowen , Cole Andrew C. , Mueller Stefan O. , Petsch Benjamin , Barouch Dan H. 
Published: August 2022

AbstractmRNA vaccines can be developed and produced quickly, making them prime candidates for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. Thus, we sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first compared the immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA (4 µg/mouse), but not DNA (50 µg/mouse), immunization. Comparing innate responses hours post immunization, the mRNA vaccine induced increased levels of IL-5, IL-6, and MCP-1 cytokines which maybe promoting humoral responses downstream. We then evaluated the immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines of the same HIV-1 envelope antigen in mice. Again, induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7–14 following DNA, protein, and RhAd52 vaccination. Thus, eliciting rapid humoral immunity may be a unique and advantageous property of mRNA vaccines for controlling infectious disease outbreaks.
Transfer learning based generalized framework for state of health estimation of Li-ion cells
Authors: Sahoo Subhasmita , Hariharan Krishnan S. , Agarwal Samarth , Swernath Subramanian B. , Bharti Roshan , Han Seongho , Lee Sangheon 
Published: August 2022

AbstractEstimating the state of health (SOH) of batteries powering electronic devices in real-time while in use is a necessity. The applicability of most of the existing methods is limited to the datasets that are used to train the models. In this work, we propose a generic method for SOH estimation with much wider applicability. The key problem is the identification of the right feature set which is derived from measurable voltage signals. In this work, relative rise in voltage drop across cell resistance with aging has been used as the feature. A base artificial neural network (ANN) model has been used to map the generic relation between voltage and SOH. The base ANN model has been trained using limited battery data. Blind testing has been done on long cycle in-house data and publicly available datasets. In-house data included both laboratory and on-device data generated using various charge profiles. Transfer learning has been used for public datasets as those batteries have different physical dimensions and cell chemistry. The mean absolute error in SOH estimation is well within 2% for all test cases. The model is robust across scenarios such as cell variability, charge profile difference, and limited variation in temperature.
The major urinary protein gene cluster knockout mouse as a novel model for translational metabolism research
Authors: Greve Sarah , Kuhn Gisela A. , Saenz-de-Juano Mara D. , Ghosh Adhideb , von Meyenn Ferdinand , Giller Katrin 
Published: August 2022

AbstractScientific evidence suggests that not only murine scent communication is regulated by major urinary proteins, but that their expression may also vary in response to metabolism via a yet unknown mechanism. Major urinary proteins are expressed mainly in the liver, showing a sexually dimorphic pattern with substantially higher expression in males. Here, we investigate the metabolic implications of a major urinary protein knockout in twelve-week-old male and female C57BL/6N mice during ad libitum feeding. Despite both sexes of major urinary protein knockout mice displayed numerically increased body weight and visceral adipose tissue proportions compared to sex-matched wildtype mice, the main genotype-specific metabolic differences were observed exclusively in males. Male major urinary protein knockout mice exhibited plasma and hepatic lipid accumulation accompanied by a hepatic transcriptome indicating an activation of lipogenesis. These findings match the higher major urinary protein expression in male compared to female wildtype mice, suggesting a more distinct reduction in energy requirements in male compared to female major urinary protein knockout mice. The observed sex-specific anabolic phenotype confirms a role of major urinary protein in metabolism and, since major urinary proteins are not expressed in humans, suggests the major urinary protein knockout mouse as a potential alternative model for translational metabolism research which needs to be further elucidated.
Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients
Authors: Sirera Guillem , Videla Sebastián , Saludes Verónica , Castellà Eva , Sanz Carolina , Ariza Aurelio , Clotet Bonaventura , Martró Elisa 
Published: August 2022

AbstractHIV-infected individuals could be at a greater risk for developing lung cancer than the general population due to the higher prevalence in the former of human papillomavirus (HPV) in the oral cavity and higher smoking rates. Our aim was to assess HPV prevalence and E6 viral oncogene transcription in lung cancer samples from HIV-infected individuals. This was a single-center, retrospective study of a cohort of HIV-1-infected patients diagnosed with and treated for lung cancer. Pathological lung samples archived as smears or formalin-fixed paraffin-embedded blocks were subjected to HPV genotyping, detection of human p16 protein and assessment for HPV E6 mRNA expression.Lung cancer samples from 41 patients were studied, including squamous cell carcinoma (32%), adenocarcinoma (34%), non-small cell cancer (27%), and small cell cancer (7%). HPV DNA was detected in 23 out of 41 (56%, 95% CI 41–70%) of samples and high-risk (HR)-HPV types were detected in 16 out of 41 (39%, 95% CI 26–54%), HPV-16 being the most prevalent [13/16 (81.3%, 95% CI 57.0–93%]. In samples with sufficient material left: expression of p16 was detected in 3 out of 10 (30%) of HR-HPV DNA-positive tumors and in 3 out of 7 (43%) of the negative ones; and E6 mRNA was detected in 2 out of 10 (20%) of HPV-16-positive samples (squamous lung cancers). These two patients had a background of a previous HPV-related neoplasia and smoking. HR-HPV DNA detection was prevalent in lung cancers in HIV-infected patients. However, viral oncogene expression was limited to patients with previous HPV-related cancers.
Increased aerosol concentrations in the High Arctic attributable to changing atmospheric transport patterns
Authors: Pernov Jakob Boyd , Beddows David , Thomas Daniel Charles , Dall´Osto Manuel , Harrison Roy M. , Schmale Julia , Skov Henrik , Massling Andreas 
Published: August 2022

AbstractThe Arctic environment has changed profoundly in recent decades. Aerosol particles are involved in numerous feedback mechanisms in the Arctic, e.g., aerosol-cloud/radiation interactions, which have important climatic implications. To understand changes in different Arctic aerosol types and number concentrations, we have performed a trend analysis of particle number size distributions, their properties, and their associated air mass history at Villum Research Station, northeastern Greenland, from 2010 to 2018. We found that, during spring, the total/ultrafine mode number concentration and the time air masses spent over the open ocean is significantly increasing, which can be ascribed to transport patterns changing to more frequent arrival from the ice-free Greenland Sea. We found that, during summer, the total/ultrafine mode number concentration, the occurrence of the Nucleation cluster (i.e. newly formed particles from gas to particle conversion), and the time air masses spent over the open ocean is significantly increasing. This can also be attributed to changing transport patterns, here with air masses arriving more frequently from Baffin Bay. Finally, we found that, during autumn, the ultrafine number concentration and the occurrence of the Pristine cluster (i.e. clean, natural Arctic background conditions) is significantly increasing, which is likely due to increasing amounts of accumulated precipitation along the trajectory path and decreasing time air masses spent above the mixed layer, respectively. Our results demonstrate that changing circulation and precipitation patterns are the factors predominantly affecting the trends in aerosol particle number concentrations and the occurrence of different aerosol types in northeastern Greenland.
2D semiconductors for specific electronic applications: from device to system
Authors: Huang Xiaohe , Liu Chunsen , Zhou Peng 
Published: August 2022

AbstractThe shrinking of transistors has hit a wall of material degradation and the specialized electronic applications for complex scenarios have raised challenges in heterostructures integration. Intriguingly, two-dimensional (2D) materials have excellent performance even at monolayer. The rich band structures and the lattice-mismatch-free heterostructures can further develop specific mechanisms to meet the demands of various electronic systems. Here we review the progress of 2D semiconductors to develop specific electronic applications from devices to systems. Focusing on the ultra-thin high-performance nanosheets for transistor channels, we consider channel optimization, contact characteristics, dielectric integration. Then we examined 2D semiconductors for specific electronic functions including computing, memory and sense. Finally, we discuss the specific applications of functionalized arrays aiming at problems that are difficult to solve with bulk materials, like the fusion of memory and computation and the all-in-one system.
Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages
Authors: Huang Wei-Chiao , Mabrouk Moustafa T. , Zhou Luwen , Baba Minami , Tachibana Mayumi , Torii Motomi , Takashima Eizo , Locke Emily , Plieskatt Jordan , King C. Richter , Coelho Camila H. , Duffy Patrick E. , Long Carole , Tsuboi Takafumi , Miura Kazutoyo , Wu Yimin , Ishino Tomoko , Lovell Jonathan F. 
Published: August 2022

AbstractA vaccine targeting multiple stages of thePlasmodium falciparumparasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infectiveP. falciparumpre-erythrocytic vaccines. Pfs230, a sexual-stageP. falciparumsurface protein, is currently in trials as the basis for a transmission-blocking vaccine, which inhibits parasite development in the mosquito vector. Here, recombinant full-length CSP and a Pfs230 fragment (Pfs230D1+) are co-displayed on immunogenic liposomes to induce immunity against both infection and transmission. Liposomes contain cobalt-porphyrin phospholipid (CoPoP), monophosphoryl lipid A and QS-21, and rapidly bind His-tagged CSP and Pfs230D1+ upon admixture to form bivalent particles that maintain reactivity with conformational monoclonal antibodies. Use of multicolor fluorophore-labeled antigens reveals liposome binding upon admixture, stability in serum and enhanced uptake in murine macrophages in vitro. Bivalent liposomes induce humoral and cellular responses against both CSP and Pfs230D1+. Vaccine-induced antibodies reduce parasite numbers in mosquito midguts in a standard membrane feeding assay. Mice immunized with liposome-displayed antigens or that passively receive antibodies from immunized rabbits have reduced parasite liver burden following challenge with transgenic sporozoites expressingP. falciparumCSP.