Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men.
An altered rpoS allele contributes to the avirulence of Salmonella typhimurium LT2

Virulent Salmonella typhimurium strains differ from the attenuated laboratory strain LT2 at the rpoS locus. It was previously shown that the rpoS gene in strain LT2 contains a rare UUG start codon (I. S. Lee, J. Lin, H. K. Hall, B. Bearson, and J. W. Foster, Mol. Microbiol. 17:155-167, 1995). This difference is responsible for the inability of LT2 to display a sustained log-phase acid tolerance response. We show that the altered rpoS allele (rpoS(LT2)) also affects the stationary-phase acid tolerance response in Salmonella. By transducing the rpoS(LT2) allele into virulent strain backgrounds and crossing wild-type rpoS allele into strain LT2, we demonstrate that the rpoS(LT2) allele contributes to the attenuation of strain LT2. We examined the effect of the rpoS allele on invasion and found that the rpoS status of the cell had no effect on the ability of the strains to invade intestinal epithelial cells in tissue culture. Enumeration of bacteria from tissues of infected mice indicated that the presence of the rpoS(LT2) allele affected the ability of S. typhimurium to reach the liver and spleen and to persist in several tissues at 6 days postinfection. This is likely due, at least in part, to a decrease in spv gene expression in these mutants. We demonstrate that strains containing the rpoS(LT2) allele are not only sensitive to pH 3.0 (acid stress) but are also sensitive to the DNA-damaging agent methyl methanesulfonate. However, these strains appear to survive stationary-phase and oxidative stresses as well as strains containing a wild-type rpoS allele. Despite an increased sensitivity to acid stress and DNA damage, strains containing either an rpoS-null mutation or the rpoS(LT2) allele survived in J774 cells and bone marrow-derived macrophages as well as did otherwise isogenic strains with a wild-type rpoS allele.
Classification and phylogenetic relationships of African tilapiine fishes inferred from mitochondrial DNA sequences.

African cichlid fishes are composed of two major lineages, the haplochromines and the tilapiines. Whereas the phylogenetic relationships of the haplochromines have been studied extensively, primarily because of their spectacular adaptive radiations in the Great Lakes of East Africa, little is known about the relationships among the tilapiine species, despite the fact that they have become an important component of African, indeed world, aquaculture. To remedy this situation, molecular phylogenetic analysis of tilapiine fishes was undertaken. A segment of mitochondrial DNA encompassing the terminal part of the tRNA(Pro) gene and the most variable part of the control region was amplified by the polymerase chain reaction with DNA samples isolated from 42 tilapiine species, and the amplification products were subjected to heteroduplex analysis and sequencing. Phylogenetic trees based on 68 sequences revealed the existence of 11 sequence groups and 11 single-sequence branches. The groups, designated Ti1 through Ti11, were distinguished by specific combinations of diagnostic substitutions, formation of monophyletic clusters, and separation by genetic distances in excess of 0.04. Although the relationships among the groups could not be resolved, the sequences separated Oreochromis and Sarotherodon from Tilapia, as defined by Trewavas. The Oreochromis sequences clustered with the Sarotherodon sequences and thus supported the hypothesis that the mouthbrooding behavior of the tilapiine fishes evolved only once from the substrate-spawning behavior. Since on phylogenetic trees the O. alcalicus (sub)species were always separated from O. amphimelas by other Oreochromis species, it was concluded that the adaptation to life in water with a high salt concentration and high pH values evolved independently at least twice in the tilapiine fishes. The tilapiines diverged from the haplochromines more than 8 million years ago; most of the intragroup divergences among the tilapiines took place an estimated 1.1 to 6 million years ago.
Microencapsulation of Cells Producing Therapeutic Proteins: Optimizing Cell Growth and Secretion

Microencapsulation of genetically engineered cells may have important applications as delivery systems for therapeutic proteins. However, optimization of the microcapsules with regard to mechanical stability, cell growth, and secretion of proteins is necessary in order to evaluate the future use of this delivery technology. We have explored the growth, survival, and secretion of therapeutic proteins from 293-EBNA cells producing endostatin (293 endo cells) and JJN3 myeloma cells producing hepatocyte growth factor (HGF) that have been embedded in various types of alginate capsules. Parameters that affect capsule integrity such as homogenous and inhomogenous gel cores and addition of an outer poly-l-lysine (PLL)–alginate coating were evaluated in relation to cell functions. When cells were encapsulated, the PLL layer was found to be absolutely required for the capsule integrity. The JJN3 and 293 endo cells displayed completely different growth and distribution patterns of live and dead cells within the microcapsules, as shown by 3D pictures reconstructed from images taken with confocal laser scanning microscopy (CLSM). Encapsulated JJN3 cells showed a bell-shaped growth and HGF secretion curve over a time period of 5 months. The 293 endo cells reached a plateau phase in growth after 23 days postencapsulation; however, after around 30 days a fraction of the microcapsules started to disintegrate. Microcapsule disintegration occurred with time irrespective of capsule and cell type, showing that alginate microcapsules possessing relatively high gel strength are not strong enough to keep proliferating cells within the microcapsules for prolonged time periods. Although this study shows that the stability of an alginate-based cell factory can be increased by a PLL–alginate coating, further improvement is necessary with regard to capsule integrity as well as controlling the cell growth before this technology can be used for therapy.
Compilation of all genes encoding two-component phosphotransfer signal transducers in the genome of Escherichia coli.

Bacteria have devised sophisticated His-Asp phosphorelay signaling systems for eliciting a variety of adaptive responses to their environment, which are generally referred to as the "two-component regulatory system. " The widespread occurrence of the His-Asp phosphorelay signaling in both prokaryotes and eukaryotes implies that it is a powerful device for a wide variety of adaptive responses of cells to their environment. The two-component signal transducers contain one or more of three common and characteristic phosphotransfer signaling domains, named the "transmitter, receiver, and histidine-containing phosphotransfer (HPt) domains. " The recently determined entire genomic sequence of Escherichia coli allowed us to compile systematically a complete list of genes encoding such two-component signal transduction proteins. The results of such an effort, made in this study, revealed that at least 62 open reading frames (ORFs) were identified as putative members of the two-component signal transducers in this single species. Among them, 32 were identified as response regulator and 23 were identified as orthodox sensory kinases. In addition, E. coli has five hybrid sensory kinases. The precise location of each ORF was mapped on a physical map of the entire E. coli genome. All of these ORFs were then compiled and annotated extensively.
Genetic Instabilities in (CTG·CAG) Repeats Occur by Recombination*

The expansion of triplet repeat sequences (TRS) associated with hereditary neurological diseases is believed from prior studies to be due to DNA replication. This report demonstrates that the expansion of (CTG·CAG) n in vivo also occurs by homologous recombination as shown by biochemical and genetic studies. A two-plasmid recombination system was established in Escherichia coli with derivatives of pUC19 (harboring the ampicillin resistance gene) and pACYC184 (harboring the tetracycline resistance gene). The derivatives contained various triplet repeat inserts ((CTG·CAG), (CGG·CCG), (GAA·TTC), (GTC·GAC), and (GTG·CAC)) of different lengths, orientations, and extents of interruptions and a control non-repetitive sequence. The availability of the two drug resistance genes and of several unique restriction sites on the plasmids enabled rigorous genetic and biochemical analyses. The requirements for recombination at the TRS include repeat lengths >30, the presence of CTG·CAG on both plasmids, and recA andrecBC. Sequence analyses on a number of DNA products isolated from individual colonies directly demonstrated the crossing-over and expansion of the homologous CTG·CAG regions. Furthermore, inversion products of the type [(CTG)13(CAG)67]·[(CTG)67(CAG)13] were isolated as the apparent result of “illegitimate” recombination events on intrahelical pseudoknots. This work establishes the relationships between CTG·CAG sequences, multiple fold expansions, genetic recombination, formation of new recombinant DNA products, and the presence of both drug resistance genes. Thus, if these reactions occur in humans, unequal crossing-over or gene conversion may also contribute to the expansions responsible for anticipation associated with several hereditary neurological syndromes.
Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR

Dendritic cell specific intracellular adhesion molecule–3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.
Injectable in situ cross-linkable nanocomposites of biodegradable polymers and carbon nanostructures for bone tissue engineering

This study investigates the effects of nanostructure size and surface area on the rheological properties of un-cross-linked poly(propylene fumarate) (PPF) nanocomposites and the mechanical properties of cross-linked nanocomposites as a function of the nanostructure loading. Three model carbon nanostructures were examined, C60 fullerenes, ultra-short single-walled carbon nanotubes (US-tubes) and single-walled carbon nanotubes (SWNTs). Rheological measurements showed that C60 and US-tube un-cross-linked nanocomposites exhibited viscous-like characteristics with the complex viscosity independent of frequency for nanostructure concentrations up to 1 wt%. Compressive and flexural mechanical testing demonstrated significant mechanical reinforcement of US-tube and SWNT nanocomposites as compared to cross-linked polymer alone, with an up to twofold increase in the mechanical properties. Scanning electron microscopy examination of the fracture surface of cross-linked US-tube nanocomposite revealed lack of aggregation of US-tubes. Although sol fraction studies did not provide any evidence of additional cross-linking, due to the presence of US-tubes in the nanocomposites, transmission electron microscopy studies suggested the crystallization of PPF on the surface of US-tubes which can contribute to the mechanical reinforcement of the US-tube nanocomposites. These results demonstrate that the rheological properties of un-cross-linked nanocomposites depend mainly on the carbon nanostructure size, whereas the mechanical properties of the cross-linked nanocomposites are dependent on the carbon nanostructure surface area. The data also suggest that US-tube nanocomposites are suitable for further consideration as injectable scaffolds for bone tissue engineering applications.
Mutational landscape of yeast mutator strains

Significance Deficiencies in genome maintenance genes (so-called mutator genes) result in increased mutagenesis that impacts cell evolvability. How the mutational processes drive the evolution of genome structure is not well understood. Here, we used high-throughput sequencing to characterize the mutation events (from punctual mutations to large chromosomal rearrangements) that occurred in mutation accumulation lines derived from a broad set of yeast mutator strains. Establishing genome-wide mutation profiles revealed that each mutator exhibits a unique and sometimes complex mutational signature. Our results also show how the dynamics of mutation accumulation can generate different genomes. The acquisition of mutations is relevant to every aspect of genetics, including cancer and evolution of species on Darwinian selection. Genome variations arise from rare stochastic imperfections of cellular metabolism and deficiencies in maintenance genes. Here, we established the genome-wide spectrum of mutations that accumulate in a WT and in nine Saccharomyces cerevisiae mutator strains deficient for distinct genome maintenance processes: pol32Δ and rad27Δ (replication), msh2Δ (mismatch repair), tsa1Δ (oxidative stress), mre11Δ (recombination), mec1Δ tel1Δ (DNA damage/S-phase checkpoints), pif1Δ (maintenance of mitochondrial genome and telomere length), cac1Δ cac3Δ (nucleosome deposition), and clb5Δ (cell cycle progression). This study reveals the diversity, complexity, and ultimate unique nature of each mutational spectrum, composed of punctual mutations, chromosomal structural variations, and/or aneuploidies. The mutations produced in clb5Δ/CCNB1, mec1Δ/ATR, tel1Δ/ATM, and rad27Δ/FEN1 strains extensively reshape the genome, following a trajectory dependent on previous events. It comprises the transmission of unstable genomes that lead to colony mosaicisms. This comprehensive analytical approach of mutator defects provides a model to understand how genome variations might accumulate during clonal evolution of somatic cell populations, including tumor cells.
Blood-stage malaria vaccines — recent progress and future challenges

Abstract Plasmodium falciparum malaria is a major global health problem, responsible for up to 1 million deaths each year. Major efforts have been made to develop an effective vaccine against this disease, to reduce the associated morbidity and mortality. There has already been considerable progress, with the first vaccine against the pre-erythrocytic stages of P. falciparum now en route to licensure. There remains, however, a strong scientific rationale for the development of a highly effective additional vaccine component against the blood stages of the parasite, which could be deployed in conjunction with partially effective control measures against the pre-erythrocytic stages. Here, recent progress in the clinical development of blood-stage vaccines is reviewed, including methods of antigen selection, the limitations of in-vitro assays for selecting vaccines for clinical development, and the results of recently published clinical trials. This review seeks to summarize recent developments in our understanding of immunity to blood-stage parasites, as well as the relevant key advances made in vaccine technologies over the last decade. The future challenges that face this field of vaccine research are also described.
Survey of Plasmid-Associated Genetic Markers in Enterobacteriaceae with Reduced Susceptibilities to Cephalosporins

ABSTRACT Clinical isolates of Enterobacteriaceae with reduced susceptibilities to cephalosporins were collected from 1993 to 2000. The organisms were screened for the extended-spectrum β-lactamase (ESBL) phenotype, and plasmid extracts were screened for genetic markers by hybridization. A blaTEM probe was derived from pUC19; other probes were derived from pACM1, the plasmid responsible for the first known appearance of an ESBL in our institution. These probes included blaSHV, int, aac(3)-Ia, dfrA1, IS6100, tetA, IncM markers, and Anon 13, a marker for the Klebsiella pneumoniae chromosomal sequences that flank blaSHV-5. There were 42 hybridization patterns among 237 isolates. Patterns designated pACM1-like occurred in 44% of the isolates (eight species) and were always associated with the clavulanic acid (CA)-susceptible ESBL phenotype. The TEM marker was not predictive of the ESBL phenotype. Mapping indicated the presence of an SHV marker and up to 7.5 kb of its flanking chromosomal sequences in three non-IncM plasmids obtained in transformation experiments. We theorize that this DNA segment spread to other plasmids from pACM1-like sources. CA insensitivity became more frequent with time and was usually associated with either the TEM marker or the absence of both bla markers. One plasmid-encoded enzyme with characteristics of an AmpC β-lactamase was observed in a transformant lacking both TEM and SHV markers. Although SHV type ESBLs were a continuing source of reduced susceptibility to cephalosporins in our institution, organisms with different resistance mechanisms were added to the hospital microflora in later years. These changes might be related, in part, to ESBL control strategies implemented in 1995.
Environmental Policy on the Back of an Envelope: A Cobb-Douglas Model is Not Just a Teaching Tool

To clarify and interpret the workings of a large computable general equilibrium (CGE) model of environmental policy in the U.S., we build an aggregated Cobb-Douglas (CD) model that can be solved easily and analytically. Its closed-form expressions show exactly how key parameters determine the sign and size of effects from a large new carbon tax on emissions, revenue, prices, output, and welfare. Data and parameters from the detailed, dynamic CGE model of Goulder and Hafstead (2018) are used in the CD model to calculate results that can be compared with theirs. Results from the CD model track those from the large CGE model quite closely, even though the CD model omits much detail such as the number of sectors, intermediate inputs, and international trade. A CGE model is quite useful to generate detailed numerical results and to reflect on particular aspects of environmental policy, but the simpler CD model provides a transparent view of exactly how the policy affects key outcomes.
Comparative study of hemolytic substances produced by coagulase-negative Staphylococcus strains

Hemolytic substances H7, H62, and E56, produced by Staphylococcus haemolyticus 7 and 62 and S. epidermidis 56, respectively, were purified. H7 and H62 are probably similar on the basis of their isoelectric focusing profiles in 8 M urea and complete immunological identity as revealed by immunodiffusion with rabbit anti-H7 and anti-E56 sera. For E56, we observed seven bands instead of three in isoelectric focusing and only partial immunological identity with H7 and H62. However, H7 and E56 were similar with regard to the following characteristics: hemolytic spectra against different erythrocytes, kinetics of erythrocyte lysis, heat stability, and inhibition by phosphatidylcholine. E56 was not active at a temperature lower than or equal to 25 degrees C, and its activity increased more rapidly with increased temperature compared with H7. For both substances, the complexes obtained by molecular filtration on Ultrogel AcA54 and the purified peptides by reverse-phase high-pressure liquid chromatography showed some hemolytic activity. These results suggest that a particular association or the presence of a given peptide could enhance the activity.
Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.

BACKGROUND Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown. METHODS In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease. RESULTS In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group. CONCLUSIONS Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).