bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a novel metabolic strategy used by drug‐resistant tumor cells
Authors: Harper Mary‐Ellen , Antoniou Andreas , Villalobos‐Menuey Elizabeth , Russo Alicia , Trauger Richard , Vendemelio Minda , George Amanda , Bartholomew Richard , Carlo Dennis , Shaikh Azhar , Kupperman Jami , Newell Evan W. , Bespalov Ivan A. , Wallace Susan S. , Liu Ye , Rogers Jeffrey R. , Gibbs Gregory L. , Leahy Jack L. , Camley Robert E. , Melamede Robert , Newell M. Karen 
Published: October 2002

ABSTRACTAcquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug‐resistant cells from drug‐sensitive cells. This strategy may serve to protect drug‐resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug‐resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug‐resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.—Harper, M.‐E., Antoniou, A., Villalobos‐Menuey, E., Russo, A., Trauger, R., Vendemelio, George, A. M., Bartholomew, R., Carlo, D., Shaikh, A., Kupperman, J., Newell, E. W., Bespalov, I. A., Wallace, S. S., Liu, Y., Rogers, J. R., Gibbs, G. L., Leahy, J. L., Camley, R. E., Melamede, R., Newell, M. K. Characterization of a novel metabolic strategy used by drug‐resistant tumor cells. FASEB J. 16, 1550–1557 (2002)
Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AβP (1–40) and (1–42) peptides
Authors: Arispe Nelson , Doh Michael 
Published: October 2002

ABSTRACTCell degeneration in Alzheimer's disease is mediated by a toxic mechanism that involves interaction of the AβP peptide with the plasma membrane of the target cell. We report here that PC12 cells become resistant to the cytotoxic action of AβP when incubated in a medium that enriches cholesterol levels of the surface membrane. On the other hand, making cholesterol‐deficient membranes by either cholesterol extraction with cyclodextrin or by inhibiting de novo synthesis of cholesterol makes PC12 cells more vulnerable to the action of AβP. Increasing cholesterol content of PS liposomes also suppresses AβP‐dependent liposome aggregation. We suggest that by modifying the fluidity of the neuronal membranes, cholesterol modulates the incorporation and pore formation of AβP into cell membranes. This idea is supported by our finding that the enhanced cytotoxicity generated by lowering the membrane cholesterol content can be reversed by AβP calcium channel blockers Zn2+ and tromethamine.—Arispe, N., Doh, M. Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AβP (1–40) and (1–42) peptides. FASEB J. 16, 1526–1536 (2002)
Yersinia enterocolitica
Type III Secretion:
yscM1
and
yscM2
Regulate
yop
Gene Expression by a Posttranscriptional Mechanism That Targets the 5′ Untranslated Region of
yop
mRNA
Authors: Cambronne Eric D. , Schneewind Olaf 
Published: October 2002

ABSTRACT

Pathogenic
Yersinia
spp. secrete Yops (
Yersinia
outer proteins) via the type III pathway. The expression of
yop
genes is regulated in response to environmental cues, which results in a cascade of type III secretion reactions.
yscM1
and
yscM2
negatively regulate the expression of
Yersinia enterocolitica yop
genes. It is demonstrated that
yopD
and
lcrH
are required for
yscM1
and
yscM2
function and that all four genes act synergistically at the same regulatory step. Further, SycH binding to the protein products of
yscM1
and
yscM2
can activate
yop
gene expression even without promoting type III transport of YscM1 and YscM2. Reverse transcription-PCR analysis of
yopQ
mRNA as well as
yopQ
and
yopE
gene fusion experiments with the
npt
(neomycin phosphotransferase) reporter suggest that
yscM1
and
yscM2
regulate expression at a posttranscriptional step. The 178-nucleotide 5′ untranslated region (UTR) of
yopQ
mRNA was sufficient to confer
yscM1
and
yscM2
-mediated regulation on the fused reporter, as was the 28-nucleotide UTR of
yopE
. The sequence 5′-AUAAA-3′ is located in the 5′
yop
UTRs, and mutations that alter the sequence motif either reduced or abolished
yscM1-
and
yscM2
-mediated regulation. A model is proposed whereby YopD, LcrH, YscM1, YscM2, and SycH regulate
yop
expression in response to specific environmental cues and by a mechanism that may involve binding of some of these factors to a specific target sequence within the UTR of
yop
mRNAs.
Environmental Response and Autoregulation of
Clostridium difficile
TxeR, a Sigma Factor for Toxin Gene Expression
Authors: Mani Nagraj , Lyras Dena , Barroso Lisa , Howarth Pauline , Wilkins Tracy , Rood Julian I. , Sonenshein Abraham L. , Dupuy Bruno 
Published: October 2002

ABSTRACT

TxeR, a sigma factor that directs
Clostridium difficile
RNA polymerase to recognize the promoters of two major toxin genes, was shown to stimulate its own synthesis. Whether expressed in
C. difficile
,
Clostridium perfringens
, or
Escherichia coli
, TxeR stimulated transcription of fusions of the
txeR
promoter region to reporter genes. As is the case for the
tox
genes,
txeR
expression was responsive to the cellular growth phase and the constituents of the medium. That is, the level of expression in broth culture was low during the exponential growth phase, but rapidly increased as cells approached the stationary phase. In the presence of excess glucose, expression from the
txeR
promoter was repressed. The results support a model for toxin gene expression in which synthesis of TxeR is induced by specific environmental signals. The increased level of TxeR then permits high-level expression of the toxin genes. The study of
txeR
gene regulation in
C. difficile
was made possible by introduction of a mobilizable, replicative plasmid via conjugation with
E. coli
.
Rectal deformation management with IGRT in prostate radiotherapy: Can it be managed with rigid alignment alone?
Authors: Polizzi Mitchell , Weiss Elisabeth , Jan Nuzhat , Ricco Anthony , Kim Siyong , Urdaneta Alfredo , Rosu‐Bubulac Mihaela 
Published: January 2024

AbstractPurposeIt is challenging to achieve appropriate target coverage of the prostate with Image Guided Radiation Therapy (IGRT) while simultaneously constraining rectal doses within planned values when there is significant variability in rectal filling and shape. We investigated if rectum planning goals can be fulfilled using rigid CBCT‐based on‐board alignment to account for interfraction rectal deformations.MethodsDelivered rectal doses corresponding to prostate alignment (“PR”) and anterior rectum alignment (“AR”) for 239 daily treatments from 13 patients are reported. Rectal doses were estimated by rigidly mapping the planned dose on the daily CT derived from the daily CBCT according to respective alignment shifts. Rectum V95% (rV95%) was used for analyses.ResultsCompared to “PR”, “AR” alignment increased rV95% for an average of 34.4% across all patients. rV95% (cc) averaged over all fractions was significant from planning values for 10/13 patients for “PR” and for 9/13 for “AR”. 3/13 patients had reproducible anatomy. Of patients with non‐reproducible anatomy, three had dosimetrically more favorable, while seven had less favorable anatomies. Most shift differences (82.3%) between the “PR” and “AR” alignments larger than 2 mm resulted in rV95% changes larger than 2 cc. Most shift differences (82.2%) of 2 mm or less between the “PR” and “AR” alignments resulted in rV95% changes less than 2 cc. The average percentage of fractions among patients in which anterior or posterior shifts for “AR” and “PR” alignment was larger than the PTV margins was 9.1% (0.0%–37.5%) and 1.3% (0%–10%).ConclusionRectal deformation and subsequent inconsistent interfraction separation between prostate and rectal wall translate into anatomical changes that cannot always be mitigated with rigid alignment. If systematic differences exist due to a non‐reproducible planning anatomy, attempts to restore the planned rectal doses through anterior rectum alignment produce rather small improvements and may result in unacceptable target underdosage.
Single‐Cell Transcriptomic Analysis Reveals the Alleviating Effect of Anemoside B4 on Murine Diabetic Nephropathy
Authors: Zhang Chunting , Zhang Qian , Luo Piao , Liu Jing , Zhao Wentong , Liu Xueying , Li Junmao , Pang Huanhuan , Li Xiaoran , Yang Shilin , Gao Hongwei , Feng Yulin , Wang Jigang 
Published: January 2024

AbstractIn diabetic kidney disease (DKD), inflammation exacerbated by oxidative stress (ROS) is pivotal. This study investigates the impact of Anemoside B4 (B4), an anti‐inflammatory drug, on kidney cell populations in DKD mice using single‐cell RNA sequencing (scRNA‐seq) and mass spectrometry‐based proteomics, focusing on its hypoglycemic, anti‐inflammatory, and anti‐fibrotic properties. Compared to the DKD group, B4 treatment reduces blood lipid metabolism levels, renal inflammation, and fibrosis in mice. Through scRNA‐seq, 14 distinct renal cell clusters are identified, primarily proximal tubular (PT) cells. In DKD mice, PT subtype cells exhibited elevated SPP1 expression, promoting macrophage M1 polarization, inflammatory cell infiltration, and renal fibrosis—all reversed by B4. Macrophage analysis revealed enrichment of the marker gene interlukin‐1β (IL‐1β) in renal macrophage polarization during diabetic nephropathy. B4 effectively mitigated macrophage polarization, alleviating inflammation and fibrosis, confirmed by Western blot. Fibroblast analysis demonstrated reduced fibrosis with B4 treatment, consistent with hematoxylin and eosin staining and Immunofluorescence findings. Notably, oxidative stress contributed to these changes. In conclusion, B4 alleviated kidney inflammation and fibrosis in DKD mice by mitigating macrophage polarization and addressing oxidative stress, providing valuable insights into its multifaceted therapeutic potential.
A novel symmetrically structured protonated ionic liquids for alkane de‐aromatization
Authors: Geng Chuanqi , Wu Xiaojia , Jin Dongyu , Du Chencan , Tu Yuming , Zhou Zhiyong , Ren Zhongqi 
Published: January 2024

AbstractThe efficient separation of aromatics/alkanes is important for the efficient utilization of fossil resources. Based on the influence of ionic symmetry structure on the polarity, melting point, interaction force, and spatial site resistance of ionic liquid solvents, a protonic ionic liquid with anionic and cationic double symmetry structure [DMI][FeCl4] was designed and synthesized for alkane de‐aromatization process, which enhances the Van der Waals forces dominated by dispersed forces with aromatics, and thus enhances the extraction efficiency of aromatic. For the binary system of dodecane/decalin + tetralin/1‐methylnaphthalene, and two simulated oil systems of six‐component straight‐sun diesel fuel and hydrofinishing LCO, [DMI][FeCl4] showed excellent de‐aromatization effects. The selectivity coefficients for monocyclic and bicyclic aromatic hydrocarbons can reach 150 and 480, respectively. When used in the de‐aromatization process of real oils, about 40% of the aromatic hydrocarbons can be removed by a single extraction using a 1:5 O/A ratio.
Novel CHRNA3 variants identified in a patient with bladder dysfunction, dysautonomia, and gastrointestinal dysmotility
Authors: Anand Asha , Hildebrandt Clara C. , Shenoy Vivek , Sutherland Richard W. 
Published: January 2024

AbstractCongenital anomalies of the kidney and urinary tract (CAKUT) are estimated to be responsible for 20%–50% of congenital anomalies and are also a leading etiology of early‐onset renal disease. Primary CAKUT are caused by genetic factors that impair proper in‐utero genitourinary tract development and secondary CAKUT result from the influence of environmental factors. The CHRNA3 gene, which encodes the Alpha‐3 subunit of the nicotinic acetylcholine receptor, is hypothesized to be associated with Megacystis‐microcolon‐intestinal hyperperistalsis syndrome. More recently, pathogenic variants in CHRNA3 have been identified in individuals with CAKUT as well as individuals with panautonomic failure. Here we present a patient with neurogenic bladder, vesicoureteral reflux, mydriasis, and gastrointestinal dysmotility found to have novel compound heterozygous variants in CHRNA3. These findings support the consideration of CHRNA3 disruption in the differential for CAKUT with dysautonomia and gastrointestinal dysmotility.
An unusual diagnosis of alpha‐mannosidosis with ocular anomalies: Behind the scenes of a hidden copy number variation
Authors: Uguen Kevin , Redon Sylvia , Rouault Karen , Pensec Marine , Benech Caroline , Schutz Sacha , Zanlonghi Xavier , Nadjar Yann , Le Maréchal Cédric , Férec Claude , Audebert‐Bellanger Séverine 
Published: January 2024

AbstractAlpha‐mannosidosis is a rare autosomal recessive lysosomal storage disorder caused by biallelic mutations in the MAN2B1 gene and characterized by a wide clinical heterogeneity. Diagnosis for this multisystemic disorder is confirmed by the presence of either a deficiency in the lysosomal enzyme acid alpha‐mannosidase or biallelic mutations in the MAN2B1 gene. This diagnosis confirmation is crucial for both clinical management and genetic counseling purposes. Here we describe a late diagnosis of alpha‐mannosidosis in a patient presenting with syndromic intellectual disability, and a rare retinopathy, where reverse phenotyping played a pivotal role in interpreting the exome sequencing result. While a first missense variant was classified as a variant of uncertain significance, the phenotype‐guided analysis helped us detect and interpret an in‐trans apparent alu‐element insertion, which appeared to be a copy number variant (CNV) not identified by the CNV caller. A biochemical analysis showing abnormal excretion of urinary mannosyloligosaccharide and an enzyme assay permitted the re‐classification of the missense variant to likely pathogenic, establishing the diagnosis of alpha‐mannosidosis. This work emphasizes the importance of reverse phenotyping in the context of exome sequencing.
Parenchymal CSF fraction is a measure of brain glymphatic clearance and positively associated with amyloid beta deposition on PET
Authors: Zhou Liangdong , Nguyen Thanh D. , Chiang Gloria C. , Wang Xiuyuan H. , Xi Ke , Hu Tsung‐Wei , Tanzi Emily B. , Butler Tracy A. , de Leon Mony J. , Li Yi 
Published: January 2024

AbstractINTRODUCTIONMapping of microscopic changes in the perivascular space (PVS) of the cerebral cortex, beyond magnetic resonance‐visible PVS in white matter, may enhance our ability to diagnose Alzheimer's disease (AD) early.METHODSWe used the cerebrospinal fluid (CSF) water fraction (CSFF), a magnetic resonance imaging–based biomarker, to characterize brain parenchymal CSF water, reflecting microscopic PVS in parenchyma. We measured CSFF and amyloid beta (Aβ) using 11C Pittsburgh compound B positron emission tomography to investigate their relationship at both the subject and voxel levels.RESULTSOur research has demonstrated a positive correlation between the parenchymal CSFF, a non‐invasive imaging biomarker indicative of parenchymal glymphatic clearance, and Aβ deposition, observed at both individual and voxel‐based assessments in the posterior cingulate cortex.DISCUSSIONThis study shows that an increased parenchymal CSFF is associated with Aβ deposition, suggesting that CSFF could serve as a biomarker for brain glymphatic clearance, which can be used to detect early fluid changes in PVS predisposing individuals to the development of AD.Highlights
Cerebrospinal fluid fraction (CSFF) could be a biomarker of parenchymal perivascular space.
CSFF is positively associated with amyloid beta (Aβ) deposition at subject level.
CSFF in an Aβ+ region is higher than in an Aβ– region in the posterior cingulate cortex.
Correspondence is found between Aβ deposition and glymphatic clearance deficits measured by CSFF.
Synthesis of a biocompatible fluorinated multiblock copolymer surfactant for water‐in‐fluorocarbon droplets and its application in droplet digital polymerase chain reaction
Authors: Feng Ruijie , Li Zeqin , Zhu Junyan , Zhang Yayun , Fang Hao , Xue Jinbing , Wang Jinxian , Lyu Renliang , Luo Gangyin 
Published: January 2024

AbstractDroplet digital polymerase chain reaction (ddPCR) technology has attracted considerable attention in recent years. A multiblock surfactant based on perfluompolyethers (PFPE) has been widely used in droplet‐based microfluidics and is known to provide high droplet stability and biocompatibility. We developed a multiblock copolymer surfactant synthesized by adjusting the proportions of the intermediates to enhance the stabilities of droplets at high temperatures. The surfactants were synthesized via amidation reactions that coupled the PFPE and diamine polyethylene glycol (PEG), and the introduction of triethylamine, as a catalyst, made the reaction more efficient. The as‐synthesized surfactants were used to generate water‐in‐ fluorocarbon (W/F) droplets with a microfluidic device and a ddPCR device was used to evaluate the performance of the droplets. When the molar ratio (PFPE‐PEG:PFPE‐PEG‐PFPE) was 2:1 and the concentration reached 2 wt%, the droplets showed good thermal stability. Surfactant showed the best performance, lowering the interfacial tension to 2.5 mN/m, when it's critical micelle concentration (CMC) exceeded 50 mg/L. Furthermore, the use of an alkaline solution (pH = 9–10) as the washing buffer, improved the biocompatible of the surfactant. When applied to the detection of λDNA, the limit of detection was 0.52 copies/μL. The as‐synthesized surfactants showed promise in generating biocompatible and thermally stable droplets and providing a new surfactant option for future ddPCR technology.
Equation of state and anisotropy of pressure of magnetars
Authors: Li Yong‐Hong , Ma Wen‐Qi , Wang Hui 
Published: January 2024

AbstractMagnetars are the neutron stars with the highest magnetic fields up to 1015–1016 G. It has been proposed that they are also responsible for a variety of extra‐galactic phenomena, ranging from giant flares in nearby galaxies to fast radio bursts. Utilizing a relativistic mean field model and a variable magnetic field configuration, we investigate the effects of strong magnetic fields on the equation of state and anisotropy of pressure of magnetars. It is found that the mass and radius of low‐mass magnetars are weakly enhanced under the action of the strong magnetic field, and the anisotropy of pressure can be ignored. Unlike other previous investigations, the magnetic field is unable to violate the mass limit of the neutron stars.
Engineering Escherichia coli for constitutive production of monophosphoryl lipid A vaccine adjuvant
Authors: Jin Hyunjung , Ji Yuhyun , An Jinsu , Ha Da Hui , Lee Ye‐Ram , Kim Hye‐Ji , Lee Choon Geun , Jeong Wooyeon , Kwon Ick Chan , Yang Eun Gyeong , Kim Ki Hun , Lee Chankyu , Chung Hak Suk 
Published: January 2024

AbstractDuring the COVID‐19 pandemic, expedient vaccine production has been slowed by the shortage of safe and effective raw materials, such as adjuvants, essential components to enhance the efficacy of vaccines. Monophosphoryl lipid A (MPLA) is a potent and safe adjuvant used in human vaccines, including the Shingles vaccine, Shingrix. 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL), a representative MPLA adjuvant commercialized by GSK, was prepared via chemical conversion of precursors isolated from Salmonella typhimurium R595. However, the high price of these materials limits their use in premium vaccines. To combat the scarcity and high cost of safe raw materials for vaccines, we need to develop a feasible MPLA production method that is easily scaled up to meet industrial requirements. In this study, we engineered peptidoglycan and outer membrane biosynthetic pathways in Escherichia coli and developed a Escherichia coli strain, KHSC0055, that constitutively produces EcML (E. coli‐produced monophosphoryl lipid A) without additives such as antibiotics or overexpression inducers. EcML production was optimized on an industrial scale via high‐density fed‐batch fermentation, and obtained 2.7 g of EcML (about 135,000 doses of vaccine) from a 30‐L‐scale fermentation. Using KHSC0055, we simplified the production process and decreased the production costs of MPLA. Then, we applied EcML purified from KHSC0055 as an adjuvant for a COVID‐19 vaccine candidate (EuCorVac‐19) currently in clinical trial stage III in the Philippines. By probing the efficacy and safety of EcML in humans, we established KHSC0055 as an efficient cell factory for MPLA adjuvant production.
A highly efficient cell culture method using oxygen‐permeable PDMS‐based honeycomb microwells produces functional liver organoids from human induced pluripotent stem cell‐derived carboxypeptidase M liver progenitor cells
Authors: Utami Tia , Danoy Mathieu , Khadim Rubina Rahaman , Tokito Fumiya , Arakawa Hiroshi , Kato Yukio , Kido Taketomo , Miyajima Atsushi , Nishikawa Masaki , Sakai Yasuyuki 
Published: January 2024

AbstractRecent advancements in bioengineering have introduced potential alternatives to liver transplantation via the development of self‐assembled liver organoids, derived from human‐induced pluripotent stem cells (hiPSCs). However, the limited maturity of the tissue makes it challenging to implement this technology on a large scale in clinical settings. In this study, we developed a highly efficient method for generating functional liver organoids from hiPSC‐derived carboxypeptidase M liver progenitor cells (CPM+ LPCs), using a microwell structure, and enhanced maturation through direct oxygenation in oxygen‐permeable culture plates. We compared the morphology, gene expression profile, and function of the liver organoid with those of cells cultured under conventional conditions using either monolayer or spheroid culture systems. Our results revealed that liver organoids generated using polydimethylsiloxane‐based honeycomb microwells significantly exhibited enhanced albumin secretion, hepatic marker expression, and cytochrome P450‐mediated metabolism. Additionally, the oxygenated organoids consisted of both hepatocytes and cholangiocytes, which showed increased expression of bile transporter‐related genes as well as enhanced bile transport function. Oxygen‐permeable polydimethylsiloxane membranes may offer an efficient approach to generating highly mature liver organoids consisting of diverse cell populations.