Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Determinants of Tetracycline Resistance in Clinical Streptococcus pneumoniae Serotype 1 Isolates from Niger

Streptococcus pneumoniae serotype 1 is the first cause of pneumococcal meningitis Niger. To determine the underlying mechanism of resistance to tetracycline in serotype 1 Streptococcus pneumoniae, a collection of 37 isolates recovered from meningitis patients over the period of 2002 to 2009 in Niger were analyzed for drug susceptibility, and whole genome sequencing (WGS) was performed for molecular analyses. MIC level was determined for 31/37 (83.8%) isolates and allowed detection of full resistance (MIC = 8 µg) in 24/31 (77.4%) isolates. No resistance was found to macrolides and quinolones. Sequence-types deduced from WGS were ST217 (54.1%), ST303 (35.1%), ST2206 (5.4%), ST2839 (2.7%) and one undetermined ST (2.7%). All tetracycline resistant isolates carried a Tn5253 like element, which was found to be an association of two smaller transposons of Tn916 and Tn5252 families. No tet(O) and tet(Q) genes were detected. However, a tet(M) like sequence was identified in all Tn5253 positive strains and was found associated to Tn916 composite. Only one isolate was phenotypically resistant to chloramphenicol, wherein a chloramphenicol acetyl transferase (cat) gene sequence homologous to catpC194 from the Staphylococcus aureus plasmid pC194 was detected. In conclusion, clinical Streptococcus pneumoniae type 1 isolated during 2002 to 2009 meningitis surveillance in Niger were fully susceptible to macrolides and quinolones but highly resistant to tetracycline (77.4%) through acquisition of a defective Tn5253 like element composed of Tn5252 and Tn916 transposons. Of the 31 tested isolates, only one was exceptionally resistant to chloramphenicol and carried a Tn5253 transposon that contained cat gene sequence.
Cervical Laminoplasty: The History and the Future

Cervical laminoplasty was developed as an alternative to cervical laminectomy for treatment of cervical myelopathy, in which hinges are created to lift the lamina. Various techniques of laminoplasty have since been developed after two prototype techniques: Hirabayashi’s open-door laminoplasty and Kurokawa’s spinous process splitting (double-door) laminoplasty. Several in vitro studies report superior biomechanical stability of the cervical spine after laminoplasty compared with laminectomy. In clinical situation, randomized control studies are scarce and superiority of one procedure over another is not uniformly shown. Lack of hard evidence supporting the purported advantages of laminoplasty over laminectomy, that is, reduced rate of postoperative instability and kyphosis development, while preserving range of motion (ROM), has been a weak selling point. Currently, laminoplasty is performed by majority of spine surgeons in Japan, but is rarely performed in the United States and Europe. Recent development in laminoplasty is preservation of muscle attachment, which enabled dynamic stabilization of the cervical spine by neck extensor muscles. After treatment with new laminoplasty techniques with active postoperative neck ROM exercises, postoperative instability, kyphosis, axial neck pain, and loss of ROM seems minimal. Well-designed clinical trials to show the effectiveness and long-term outcome of this surgical procedure are warranted.
Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter.

We isolated and characterized a novel K-Cl cotransporter, KCC3, from human placenta. The deduced protein contains 1,150 amino acids. KCC3 shares 75-76% identity at the amino acid level with human, pig, rat, and rabbit KCC1 and 67% identity with rat KCC2. KCC3 is 40 and 33% identical to two Caenorhabditis elegans K-Cl cotransporters and ∼20% identical to other members of the cation-chloride cotransporter family (CCC), two Na-K-Cl cotransporters (NKCC1, NKCC2), and the Na-Cl cotransporter (NCC). Hydropathy analysis indicates a typical KCC topology with 12 transmembrane domains, a large extracellular loop between transmembrane domains 5 and 6 (unique to KCCs), and large NH2 and COOH termini. KCC3 is predominantly expressed in kidney, heart, and brain, and is also expressed in skeletal muscle, placenta, lung, liver, and pancreas. KCC3 was localized to chromosome 15. KCC3 transiently expressed in human embryonic kidney (HEK)-293 cells fulfilled three criteria for increased expression of K-Cl cotransport: stimulation of cotransport by swelling, treatment with N-ethylmaleimide, or treatment with staurosporine.
Measuring and Using Skew in the Study of Social Behavior and Evolution

Unequal distribution of benefits from cooperation is a fundamental feature of social behavior, and many quantitative measures of this skew have been proposed. Overall group size and productivity affect each of the measures somewhat differently depending on their formulation. Some of the differences are due to whether the index is intended to measure skew relative to a random distribution or relative to the maximum possible skew. Sampling errors, however, will tend to make smaller and less productive groups seem more skewed than they actually are. Differential survival or residence times of group members add a second factor that can result in skew independent of behavioral mechanisms. Thus, significant biases can result in indices that do not account for random processes or differential survival within groups. Seven published skew indices plus a new index (B) that combines observed variance with the expected binomial variance were tested across simulations that compared groups varying in resource distribution probabilities, size, or productivity. Only the B index always avoided error through correctly adjusting for group size, productivity, and differential residence times. Thus, the B index has the best potential to be a benchmark value that can be used for identifying evolutionary patterns in social behavior, both across and especially within species. Although skew indices have been applied mostly to shared reproduction, the B index is suitable to any situation where group members divide benefits. Skew indices potentially can identify and test evolutionary scenarios across a wide range of behavioral interactions, such as dominance hierarchies, information exchange, and parental care.
Limited effect of refined carbohydrate dietary supplementation on colonization of the gastrointestinal tract of healthy subjects by Candida albicans.

BACKGROUND Infections due to Candida albicans occur readily in situations in which ample glucose is available. In mice, dietary refined carbohydrate supplementation leads to higher rates of Candida growth in the gastrointestinal tract and favors mucosal invasion. OBJECTIVE The modulating properties of dietary carbohydrate supplementation on colonization of the human gastrointestinal tract by C. albicans were evaluated. DESIGN A 2-step study was conducted in 28 healthy volunteers. First, we determined the subjects' habitual uptake of refined carbohydrates and correlated these data with the C. albicans blastoconidia concentration in the mouth washes and feces of subjects with no intervention. Second, we compared C. albicans counts in the specimens before, during, and after a high-sugar diet. RESULTS No correlation between C. albicans counts in the specimens and the habitual uptake of refined carbohydrates was observed. A high-sugar diet did not increase the frequency of C. albicans-positive samples, the number of subjects positive for C. albicans in the mouth washes, or the concentration of candidal blastoconidia in the samples of the 28 subjects. However, in selected subjects with elevated counts of oral C. albicans, we observed an increase in fecal C. albicans counts in response to the diet. CONCLUSIONS The effect of adding a high amount of refined carbohydrates to the diet of healthy human subjects has a limited influence on Candida colonization. Follow-up studies should define whether selected patient groups might benefit from dietary restriction of refined carbohydrates.
Efficacy of oral iodized peanut oil is greater than that of iodized poppy seed oil among Indonesian schoolchildren.

BACKGROUND Oral iodized poppy seed oil is an appropriate measure for controlling iodine deficiency in areas where iodized salt is not yet available. However, a more effective and cheaper iodized oil preparation is needed. OBJECTIVE The aim of this study was to compare the efficacy of iodized peanut oil with that of iodized poppy seed oil. DESIGN Schoolchildren aged 8-10 y were supplemented with a single oral dose of iodized peanut oil (P200, P400, or P800 mg I), iodized poppy seed oil (PS400 mg I), or peanut oil (placebo). The concentration of urinary iodine (UI) was measured at 0, 4, 12, 25, and 50 wk, whereas thyroid volume and serum thyrotropin and free thyroxine concentrations were measured at 0, 25, and 50 wk. RESULTS UI was higher in all treatment groups than in the placebo group, except at baseline. UI in the P200 group was not significantly different from that in the PS400 group at all times of measurement. In a comparison of preparations supplying 400 mg I conducted by using a mathematical model, iodine retention from the peanut oil preparation was 3 times that from the poppy seed oil, and the protection period for peanut oil was twice as long as that for the poppy seed oil (P < 0.001 for both). The reduction in thyroid volume was greater in the treatment groups than in the placebo group (P < 0.001). No significant differences in serum hormone concentrations were observed between groups before or after treatment. CONCLUSION Iodized peanut oil is more efficacious in controlling iodine deficiency than is iodized poppy seed oil containing the same amount of iodine.
Response of rainbow trout (Oncorhynchus mykiss) to supplements of individual essential amino acids in a semipurified diet, including an estimate of the maintenance requirement for essential amino acids.

We studied the effects of increasing dietary concentrations of each of the following amino acids on growth, feed intake, feed conversion ratio and composition of gain in rainbow trout in six dose-response experiments: L-lysine, L-tryptophan, L-histidine, L-valine, L-leucine and L-isoleucine. Semipurified diets containing 20.1 MJ digestible energy/kg dry matter, with wheat gluten and crystalline amino acids as sole sources of amino acids, were fed to rainbow trout [initial mean body weight (BW) 40-51 g, depending on the amino acid studied]. In one series of 24 diets, lysine concentration ranged from 4.5 to 58.0 g/kg dry matter; in five further series of 12 diets each, concentrations ranged from (in g/kg dry matter): tryptophan, 1.3 to 5.6; histidine, 2.6 to 13.5; valine, 6.2 to 34.2; leucine, 10.0 to 42.0 and isoleucine, 5.0 to 15.3. Each diet was fed to a group of 20 fish for 53-64 d, depending on the amino acid studied. Dry matter intake, weight gain, feed conversion ratio, protein concentration of gain and total protein deposition followed exponential response functions. To achieve 95% of the maximum protein deposition, dietary concentrations of 27.7 g lysine, 2.0 g tryptophan, 5.8 g histidine, 15.7 g valine, 13.6 g leucine and 13.7 g isoleucine/kg dry matter were required. Maintenance requirements, estimated from exponential functions for protein deposition, were [in mg/(100 g BW.d)]: lysine, 1.93; tryptophan, 1.05; histidine, 1.07; valine, 2.92; leucine, 8.26 and isoleucine, 0.91. This corresponds to 4% of the requirement for protein deposition for lysine and isoleucine but 32% for leucine, with the other amino acids being intermediate. Therefore, different dietary amino acid requirement patterns were derived from protein deposition data depending on the chosen level of performance.
Loss of MiR‐424‐3p, not miR‐424‐5p, confers chemoresistance through targeting YAP1 in non‐small cell lung cancer

MiR‐424 has been discovered to be involved in the chemoresistance of lung cancer. However, the underlying mechanism by which miR‐424 played role in chemoresistance has been unknown. Here, in our study, to investigate the role of miR‐424 in non‐small cell lung cancer (NSCLC), we have detected the expression of miR‐424‐3p and ‐5p in NSCLC tissues and paired normal control. Moreover, to explore the role of miR‐424‐3p in NSCLC cells, miR‐424‐3p and ‐5p were both re‐expressed and knocked down using transient transfection with their respective mimics and inhibitors. Cell viability, migration, and invasion were evaluated using MTT, wound‐healing and Transwell assays, respectively. It was found that down‐regulation of miR‐424‐3p was pronouncedly associated with NSCLC progression and overall prognosis; and that both miR‐424‐3p and ‐5p were markedly capable of preventing the proliferation, migration, and invasion in NSCLC cells. Additionally, it is miR‐424‐3p but not miR‐424‐5p that enhances the chemo‐sensitivity of NSCLC cells through targeting YAP1. Mechanistically, YAP1 was identified as down‐stream target of miR‐424‐3p. Together, it was for the first time in our study found that it is loss of miR‐424‐3p not miR‐424‐5p that enables chemoresistance through targeting YAP1 in NSCLC, supporting that miR‐424‐3p could be used as therapeutic target in the curing of NSCLC with chemoresistance. © 2016 Wiley Periodicals, Inc.
Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging

Lysosomes keep neuronal stem cells young An important consequence of aging is loss of regenerative capacity in stem cells, particularly those of the nervous system. Leeman et al. isolated quiescent and activated stem cells from mice and compared their transcriptomes. The findings emphasize the role of large lysosomes in quiescent neuronal stem cells in which aggregated proteins accumulate. Treatments that stimulated lysosomal function allowed aged quiescent stem cells to clear protein aggregates and restored the cells' ability to be activated. Such restoration of stem cell function might alleviate compromised proteostasis in aging. Science, this issue p. 1277 Characterization of aging neuronal stem cells points to lysosomes as a key factor in maintaining stemness. In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.
n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease.

BACKGROUND Data on the association of n-3 fatty acid content in serum lipids with mortality in patients with coronary artery disease (CAD) are limited. OBJECTIVE We hypothesized that a high proportion of n-3 fatty acids in serum lipids would be associated with reduced risks of death and coronary events in patients with established CAD. DESIGN We measured dietary intakes via food records and the fatty acid composition of serum cholesteryl esters (CEs) in 285 men and 130 women with CAD (x age: 61 y; range: 33-74 y). The patients participating in the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) study were followed up for 5 y. RESULTS During the follow-up, 36 patients died, 21 had myocardial infarctions, and 12 had strokes. The relative risks (RRs) of death adjusted for cardiovascular disease risk factors for subjects in the highest tertile of fatty acids in CEs compared with those in the lowest tertile were 0.33 (95% CI: 0.11, 0.96) for alpha-linolenic acid, 0.33 (0.12, 0.93) for eicosapentaenoic acid, and 0.31 (0.11, 0.87) for docosahexaenoic acid (P for trend = 0.063, 0.056, and 0.026, respectively). A high proportion of eicosapentaenoic acid in CEs was associated with a low risk of CAD death. Compared with no consumption, consumption of fish tended to be associated with a lower risk of death [1-57 g/d, RR = 0.50 (0.20, 1.28); > 57 g/d, RR = 0.37 (0.14, 1.00); P for trend = 0.059]. CONCLUSION High proportions of n-3 fatty acids in serum lipids are associated with a substantially reduced risk of death.
The action operator for continuous-time histories

We define the action operator for the consistent histories formalism, as the quantum analog of the classical action functional, for the simple harmonic oscillator case. We conclude that the action operator is the generator of time transformations, and is associated with the two types of time evolution of the standard quantum theory: the wave-packet reduction and the unitary time evolution. We construct the corresponding classical histories and demonstrate the relevance with the quantum histories. Finally, we show the relation of the action operator to the decoherence functional.
A prospective study of calcium intake from diet and supplements and risk of ischemic heart disease among men.

BACKGROUND Calcium intake is thought to have a protective effect on the risk of developing ischemic heart disease (IHD), but the existing data are inconsistent. OBJECTIVE The objective was to assess the relation between calcium intake and risk of IHD among men. DESIGN Men in the Health Professionals Follow-up Study who returned a dietary questionnaire in 1986 (n = 39 800) were followed up for 12 y. Intakes of calcium and other nutrients were assessed in 1986, 1990, and 1994. The endpoints of total IHD (nonfatal myocardial infarction and fatal IHD) incidence were ascertained by medical record review. Other IHD risk factors were recorded biennially. RESULTS During 12 y of follow-up (415 965 person-years), we documented 1458 cases of IHD: 1030 of nonfatal myocardial infarction and 428 of fatal IHD. After control for standard IHD risk factors, the relative risk of developing IHD among men in the highest (median intake = 1377 mg/d) compared with the lowest (median intake = 523 mg/d) calcium intake quintile was 0.97 (95% CI: 0.81, 1.16; P for trend = 0.64), for vitamin D intake was 1.00 (95% CI: 0.80, 1.24; P for trend = 0.66), and for total dairy product intake was 1.01 (95% CI: 0.83, 1.23; P for trend = 0.57). For supplemental calcium intake, the relative risk of developing IHD in a comparison of the highest quintile with nonusers of supplements was 0.87 (95% CI: 0.64, 1.19; P for trend = 0.31). CONCLUSION The results suggest that neither dietary nor supplemental intakes of calcium are appreciably associated with the risk of IHD among men.
A noninternalized nondesensitized truncated AT1A receptor transduces an amplified ANG II signal.

The structural determinants of the rat angiotensin (ANG) II AT1A receptor involved in receptor internalization, desensitization, and activation are investigated by producing six mutants that had progessively larger deletions of the cytoplasmic tail (-13, -19, -24, -31, -46, and -56 residues, respectively). After stable transfection of the cDNAs into Chinese hamster ovary cells, all mutants, except the most truncated, exhibit normal [Sar1]ANG II affinities [dissociation constant ( K d) = 0.19-0.70 nM] compared with the wild-type (WT) receptor ( K d = 0.62 nM) and are able to activate a Gq/11protein and a phospholipase C as measured by the ANG II-induced inositol phosphate (IP) turnover in the different clones. However, one of these mutants, Δ329 (deletion of 31 residues), exhibits a peculiar phenotype. This mutant shows a reduced ligand-induced internalization as measured by the acid-washing procedure (only 32% of receptors are internalized vs. 83% for WT). Moreover, the Δ329 mutant is less desensitized by a pretreatment with either ANG II (15% desensitization of ANG II-stimulated IP turnover vs. 60% for WT receptor) or the phorbol ester phorbol 12-myristate 13-acetate (no desensitization vs. 29% for WT receptor). These functional modifications of the Δ329 mutant are associated with the transduction of an amplified signal as demonstrated on both IP turnover and an integrated physiological effect of ANG II. Taken together, these data indicate that the sequence329SLSTKMS335of the rat AT1A receptor is involved in both receptor internalization and desensitization. This is the first demonstration that a desensitization- and internalization-defective AT1Areceptor mutant is also hyperreactive and mediates augmented cellular responses.
Caspase‐3 regulates the migration, invasion and metastasis of colon cancer cells

Caspase‐3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase‐3 has also non‐apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase‐3 in tumor progression remain to be defined clearly. In our study, we established caspase‐3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase‐3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase‐3 gene knockout appeared to cause reduced EMT phenotypes when compared to parental HCT116 cells. Indeed, they showed significantly increased E‐cadherin expression, reduced N‐cadherin, Snail, Slug and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase‐3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastasis.
Ablation of lung endothelial injury after pacing-induced heart failure is related to alterations in Ca2+ signaling.

We have previously shown that ANG II increases microvascular permeability in normal dog lungs but not after pacing-induced heart failure. This study investigated how ANG II induces permeability in isolated blood-perfused canine lung lobes and what alterations occur during heart failure. In normal lobes, the protein kinase C (PKC) inhibitors staurosporine (500 nM) or chelerythrine (10 μM) did not modify ANG II-induced increases in the capillary filtration coefficient ( K f,c, ml ⋅ min-1 ⋅ cmH2O-1 ⋅ 100 g-1; an index of microvascular permeability), suggesting that PKC is not involved. Thapsigargin (150 nM) was used to stimulate capacitative Ca2+ entry in lobes from control dogs and dogs paced at 245 beats/min for 4 wk to induce heart failure. In control lobes, K f,c rose after thapsigargin, from 0.06 ± 0.01 to 0.17 ± 0.03 ml ⋅ min-1 ⋅ cmH2O-1 ⋅ 100 g-1 (mean ± SE, P < 0.05) but did not change in the paced group. A Ca2+ ionophore, A-23187, increased K f,c in both control (10 μM; 0.05 ± 0.01 to 0.17 ± 0.05 ml ⋅ min-1 ⋅ cmH2O-1 ⋅ 100 g-1, P < 0.05) and pace (5 μM; 0.06 ± 0.01 to 0.21 ± 0.07 ml ⋅ min-1 ⋅ cmH2O-1 ⋅ 100 g-1, P < 0.05) lobes, indicating that increasing intracellular Ca2+ is sufficient to induce pulmonary microvascular permeability after pacing. We conclude that during heart failure, Ca2+ signaling within the pulmonary microvascular endothelium is altered.