Miracle-dz/UniFAR-FTUs huggingface dataset:
The Capability of Tyramine Production and Correlation between Phenotypic and Genetic Characteristics of Enterococcus faecium and Enterococcus faecalis Strains

The aim of this study was to investigate the diversity of tyramine production capability of four Enterococcus strains in buffered systems in relation to their genetic characteristics and environmental conditions. Cells of the strains Enterococcus faecalis EF37 and ATCC 29212, and E. faecium FC12 and FC643 were re-suspended in phosphate/citrate buffers with different pH, NaCl concentration and incubation temperature. At intervals, cell viability and tyramine production were assessed by plate counting and HPLC analysis, respectively. The activity of a purified tyrosine decarboxylase (TDC) was determined under the same conditions, as a reference. Reduced loss in cell viability was observed in all the tested conditions, except for pH 4 after 24 h. The TDC activity was greatly heterogeneous within the enterococci: EF37 and FC12 produced the higher tyramine concentrations, ATCC 29212 showed a reduced decarboxylase activity, while EF643 did not accumulate detectable amounts of tyramine in all the conditions assayed. Among the considerate variables, temperature was the most influencing factor on tyramine accumulation for enterococcal cells. To further correlate the phenotypic and genetic characteristics of the enterococci, the TDC operon region carrying the genes tyrosine decarboxylase (tyrDC), tyrosine/tyramine permease (tyrP), and Na+/H+ antiporter (nhaC-2) was amplified and sequenced. The genetic organization and nucleotide sequence of this operon region were highly conserved in the enterococcal strains of the same species. The heterogeneity in tyramine production found between the two E. faecalis strains could be ascribed to different regulation mechanisms not yet elucidated. On the contrary, a codon stop was identified in the translated tyrDC sequence of E. faecium FC643, supporting its inability to accumulate tyramine in the tested conditions. In addition, the presence of an additional putative tyrosine decarboxylase with different substrate specificity and genetic organization was noticed for the first time. Concluding, the high TDC activity heterogeneity within enterococci determined different accumulation of tyramine, depending on different genetic determinants, regulation mechanisms, and environmental factors. The present research contributes to elucidate the genetic characteristics of enterococcal strains and correlate specific mutations to their different strain-dependent tyraminogenic activity.
Mitochondrial DNA Diversity in Indigenous Populations of the Southern Extent of Siberia, and the Origins of Native American Haplogroups

In search of the ancestors of Native American mitochondrial DNA (mtDNA) haplogroups, we analyzed the mtDNA of 531 individuals from nine indigenous populations in Siberia. All mtDNAs were subjected to high‐resolution RFLP analysis, sequencing of the control‐region hypervariable segment I (HVS‐I), and surveyed for additional polymorphic markers in the coding region. Furthermore, the mtDNAs selected according to haplogroup/subhaplogroup status were completely sequenced. Phylogenetic analyses of the resulting data, combined with those from previously published Siberian arctic and sub‐arctic populations, revealed that remnants of the ancient Siberian gene pool are still evident in Siberian populations, suggesting that the founding haplotypes of the Native American A‐D branches originated in different parts of Siberia. Thus, lineage A complete sequences revealed in the Mansi of the Lower Ob and the Ket of the Lower Yenisei belong to A1, suggesting that A1 mtDNAs occasionally found in the remnants of hunting‐gathering populations of northwestern and northern Siberia belonged to a common gene pool of the Siberian progenitors of Paleoindians. Moreover, lineage B1, which is the most closely related to the American B2, occurred in the Tubalar and Tuvan inhabiting the territory between the upper reaches of the Ob River in the west, to the Upper Yenisei region in the east. Finally, the sequence variants of haplogroups C and D, which are most similar to Native American C1 and D1, were detected in the Ulchi of the Lower Amur. Overall, our data suggest that the immediate ancestors of the Siberian/Beringian migrants who gave rise to ancient (pre‐Clovis) Paleoindians have a common origin with aboriginal people of the area now designated the Altai‐Sayan Upland, as well as the Lower Amur/Sea of Okhotsk region.
Midbrain Auditory Neurons Integrate Excitation and Inhibition to Generate Duration Selectivity: An In Vivo Whole-Cell Patch Study in Anurans

Sound duration can play a pivotal role in the reproductive behavior of anuran amphibians. Here, we report the first whole-cell recordings from duration-selective neurons in the anuran torus semicircularis, in vivo. We show that most short-pass duration-selective cells exhibited short-latency inhibition and delayed excitation. The duration of the inhibition increased with tone burst duration. Hence, for long-duration tone bursts, inhibition overlapped with excitation, reducing or eliminating spikes; no postinhibitory rebound was present. Other short-pass cells, however, showed inhibition only for long-duration tone bursts. Bandpass duration selectivity also involved interplay between inhibition and excitation; inhibition negated excitation with tone bursts that exceeded the optimum duration. Additionally, however, bandpass selectivity arose from stimulus-dependent excitation; tone bursts of sufficiently long duration were required to elicit excitation. Similarly, long-pass neurons showed inhibition and duration-dependent enhancement of excitation; long-pass selectivity resulted from enhanced excitation outlasting the transient inhibition or, in some cases, excitation overriding concurrent inhibition. Last, we evaluated the stimulus specificity of duration-selective neurons to variations in pulse repetition rate. We show that (1) most neurons that exhibited long-pass selectivity for tone-burst duration nonetheless responded to short-duration pulses when repeated at particular rates, and (2) some neurons that showed selectivity for tone burst duration also showed selectivity for pulse train duration. These novel response profiles appear to result from interplay between inhibition and time- and activity-dependent changes in excitation strength. These findings are discussed in the context of prevailing models of duration selectivity and acoustic communication in anurans.
Comparison of Reward Modulation in the Frontal Eye Field and Caudate of the Macaque

The frontal eye field (FEF) influences saccade generation via direct projections to the superior colliculus and an indirect pathway through the basal ganglia. To test whether different reward information is represented in the FEF and the basal ganglia, we recorded from the FEF and the caudate nucleus in monkeys performing an asymmetrically rewarded memory-guided saccade task. A peripheral cue at one of two opposing positions was flashed briefly to indicate the saccade target. In a given block, one position was associated with big reward and the other with small reward. Big-reward position was alternated between blocks. In this task, the FEF and caudate displayed similar prevalence of neuronal activity before cue onset that was larger in blocks with specific big reward–cue position associations. They also exhibit comparable reward modulation of visual responses that were spatially selective. In contrast, visual responses that were specific to expected reward size, instead of spatial locations, were commonly observed in caudate but rarely seen in the FEF. Thus, both the FEF and basal ganglia may contribute to reward bias in saccade generation, with the FEF providing spatially relevant reward information and the basal ganglia providing additional reward-specific information.
Corporate social responsibility and marketing: An integrative framework

This article introduces a conceptualization of corporate social responsibility (CSR) that emphasizes the role and potential contribution of the marketing discipline. The proposed framework first depicts CSR initiatives as the actions undertaken to display conformity to both organizational and stakeholder norms. Then, the article discusses the managerial processes needed to monitor, meet, and even exceed, stakeholder norms. Finally, the analysis explains how CSR initiatives can generate increased stakeholder support.
The Peptide Sequence of Diacyl Lipopeptides Determines Dendritic Cell TLR2-Mediated NK Activation

Natural killer (NK) cells are lymphocyte effectors that are activated to control certain microbial infections and tumors. Many NK-activating and regulating receptors are involved in regulating NK cell function. In addition, activation of naïve NK cells is fundamentally triggered by cytokines or myeloid dendritic cells (mDC) in various modes. In this study, we synthesized 16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2Cys) lipopeptides with sequences designed from lipoproteins of Staphylococcus aureus, and assessed their functional properties using mouse (C57BL/6) bone marrow-derived DC (BMDC) and NK cells. NK cell activation was evaluated by three criteria: IFN-γ production, up-regulation of NK activation markers and cytokines, and NK target (B16D8 cell) cytotoxicity. The diacylated lipopeptides acted as TLR2 ligands, inducing up-regulation of CD25/CD69/CD86, IL-6, and IL-12p40, which represent maturation of BMDC. Strikingly, the Pam2Cys lipopeptides induced mouse NK cell activation based on these criteria. Cell-cell contact by Pam2Cys peptide-stimulated BMDC and NK cells rather than soluble mediators released by stimulated BMDC induced activation of NK cells. For most lipopeptides, the BMDC TLR2/MyD88 pathway was responsible for driving NK activation, while some slightly induced direct activation of NK cells via the TLR2/MyD88 pathway in NK cells. The potential for NK activation was critically regulated by the peptide primary sequence. Hydrophobic or proline-containing sequences proximal to the N-terminal lipid moiety interfered with the ability of lipopeptides to induce BMDC-mediated NK activation. This mode of NK activation is distinctly different from that induced by polyI:C, which is closely associated with type I IFN-inducing pathways of BMDC. These results imply that the MyD88 pathway of BMDC governs an alternative NK-activating pathway in which the peptide sequence of TLR2-agonistic lipopeptides critically affects the potential for NK activation.
Coordinated Expression of FLOWERING LOCUS T and DORMANCY ASSOCIATED MADS-BOX-Like Genes in Leafy Spurge

Leafy spurge (Euphorbia esula L.) is a noxious perennial weed that produces underground adventitious buds, which are crucial for generating new vegetative shoots following periods of freezing temperatures or exposure to various control measures. It is also capable of flowering and producing seeds, but requires vernalization in some cases. DORMANCY ASSOCIATED MADS-BOX (DAM) genes have been proposed to play a direct role in the transition to winter-induced dormancy and maintenance through regulation of the FLOWERING LOCUS T (FT) gene, which also is likely involved in the vernalization process. To explore the regulation of FT and DAM during dormancy transitions in leafy spurge, the transcript accumulation of two previously cloned DAM splice variants and two different previously cloned FT genes was characterized. Under long-photoperiods (16 h light), both DAM and FT transcripts accumulate in a diurnal manner. Tissue specific expression patterns indicated the tissues with high DAM expression had low FT expression and vice versa. DAM expression is detected in leaves, stems, shoot tips, and crown buds. FT transcripts were detected mainly in leaves and flowers. Under dormancy inducing conditions, DAM and FT genes had an inverse expression pattern. Additionally, chromatin immunoprecipitation assays were performed using DAM-like protein specific antibodies to demonstrate that DAM or related proteins likely bind to cryptic and/or conserved CArG boxes in the promoter regions of FT genes isolated from endodormant crown buds. These results are consistent with the hypothesis that DAM proteins play a crucial role in leafy spurge dormancy transition and maintenance, potentially by negatively regulating the expression of FT.
A novel low complexity multichannel Cosine Modulated Filter Bank using IFIR technique for Nearly Perfect Reconstruction

This paper presents a design of low-complexity multichannel Nearly Perfect Reconstruction (NPR) Cosine Modulated Filter Bank (CMFB). CMFBs are used extensively because of the ease implementation and they have the advantage of high stopband attenuation. But this leads to certain limitations because it would require large number of filter coefficients and longer delays when the number of channels is more e.g. 32-band or 64-band CMFB. Large number of filter coefficients would imply that increased computational complexity. Here the prototype filter is designed using interpolated finite impulse response (IFIR) technique. The stretched factor is chosen in such a way so that computational cost will be reduced and minimizes the value of error parameters. The IFIR approach leads to reduction in stopband energy as well as Side-Lobe-Fall-off-Rate (SLFOR) in magnitude response of the prototype filter. One example has been included to illustrate the effectiveness of the proposed technique over the existing design methods. Here, an earlier approach to prototype filter design based on the Kaiser window is implemented using an IFIR approach. Savings in computational complexity and improvement in performance with respect to the previous works are shown.
Mutations in the S4 Region Isolate the Final Voltage-dependent Cooperative Step in Potassium Channel Activation

Charged residues in the S4 transmembrane segment play a key role in determining the sensitivity of voltage-gated ion channels to changes in voltage across the cell membrane. However, cooperative interactions between subunits also affect the voltage dependence of channel opening, and these interactions can be altered by making substitutions at uncharged residues in the S4 region. We have studied the activation of two mutant Shaker channels that have different S4 amino acid sequences, ILT (V369I, I372L, and S376T) and Shaw S4 (the S4 of Drosophila Shaw substituted into Shaker), and yet have very similar ionic current properties. Both mutations affect cooperativity, making a cooperative transition in the activation pathway rate limiting and shifting it to very positive voltages, but analysis of gating and ionic current recordings reveals that the ILT and Shaw S4 mutant channels have different activation pathways. Analysis of gating currents suggests that the dominant effect of the ILT mutation is to make the final cooperative transition to the open state of the channel rate limiting in an activation pathway that otherwise resembles that of Shaker. The charge movement associated with the final gating transition in ILT activation can be measured as an isolated component of charge movement in the voltage range of channel opening and accounts for 13% (∼1.8 e0) of the total charge moved in the ILT activation pathway. The remainder of the ILT gating charge (87%) moves at negative voltages, where channels do not open, and confirms the presence of Shaker-like conformational changes between closed states in the activation pathway. In contrast to ILT, the activation pathway of Shaw S4 seems to involve a single cooperative charge-moving step between a closed and an open state. We cannot detect any voltage-dependent transitions between closed states for Shaw S4. Restoring basic residues that are missing in Shaw S4 (R1, R2, and K7) rescues charge movement between closed states in the activation pathway, but does not alter the voltage dependence of the rate-limiting transition in activation.
Urothelial Bladder Carcinoma and Viral Infections: Different Association with Human Polyomaviruses and Papilloma Viruses

Bladder cancer is the second most commonly occurring genitourinary cancer in adults. The interaction of different carcinogenic and co-carcinogenic agents are responsible for bladder urothelial carcinoma: alcohol and smoking habits, Schistosoma haematobium infection, exposition to chemicals, analgesic and antineoplastic drugs prolonged use. Recently also viral infections have been associated to this pathology. In this study the correlation between viral infections and bladder carcinoma has been evaluated. A group of 32 patients affected by primary bladder neoplasia has been analysed. A control group of 20 autoptic samples of healthy bladder was analysed. The DNA of the following viruses has been searched by Polymerase chain reaction (PCR): Adenovirus, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Human Papillomaviruses (HPV), Polyomaviruses (BKV and JCV). In the examined population the association bladder carcinoma-HPV, found by others, has not been confirmed. The high percentage of human polyomaviruses present in the samples is a statistically significant data (p=0.0087) and allows to presume that BKV and JCV may play a role in the aetiology of bladder tumor. In particular the polyomavirus BK, which is found in significative percentage both in single infection (p=0.0036) and in co-infections with other viral species (p=0.035), may be an important co-factor in the pathogenesis of bladder carcinoma.
Diagnostic test accuracy of simple instruments for identifying frailty in community-dwelling older people: a systematic review.

BACKGROUND frailty is a state of vulnerability to adverse outcomes. Routine identification of frailty is recommended in international guidance. This systematic review investigates the diagnostic test accuracy (DTA) of simple instruments for identifying frailty in community-dwelling older people. METHODS the review methodology followed Cochrane procedures. Databases were searched from January 1990 to October 2013. Prospective studies assessing the DTA of simple instruments for identifying frailty in community-dwelling older people (aged ≥65 years) as index tests against a reference standard phenotype model, cumulative deficit frailty index or comprehensive geriatric assessment were eligible for inclusion. Sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios were calculated for index tests. Risk of bias was assessed using the QUADAS-2 checklist. RESULTS three studies involving 3,261 participants were included. Median frailty prevalence was 10.5%. Seven index tests were assessed: gait speed, timed-up-and-go test, PRISMA 7 questionnaire, self-reported health, general practitioner clinical assessment, polypharmacy and Groningen Frailty Index. For a gait speed of <0.8 m/s, the sensitivity = 0.99 and specificity = 0.64. For the PRISMA 7, the sensitivity = 0.83 and specificity = 0.83. For the timed get-up-and-go test of 10 s, the sensitivity = 0.93 and specificity = 0.62. DTA was notably lower for all other index tests. All three studies were judged at unclear risk of bias. DISCUSSION slow gait speed, PRISMA 7 and the timed get-up-and-go test have high sensitivity for identifying frailty. However, limited specificity implies many false-positive results which means that these instruments cannot be used as accurate single tests to identify frailty.
Successful treatment of reactive airways dysfunction syndrome by high-dose vitamin D

Reactive airways dysfunction syndrome is a controversial and poorly understood condition produced by inhalational injury from gas, vapors, or fumes. The symptoms mimic asthma, but appear unresponsive to asthma treatments. If symptoms persist for more than 6 months, there is a risk that they can become chronic. For these cases, effective treatments are lacking and quality of life is poor. We describe the first use of high-dose vitamin D in a patient with this condition, who fulfilled the 1995 American College of Chest Physicians criteria for this syndrome. The patient we describe presented an extremely difficult management problem and was refractory to conventional treatments, but responded to high-dose oral vitamin D supplements.
Evaluation of the Effect of PEGylated Single-Walled Carbon Nanotubes on Viability and Proliferation of Jurkat Cells

Among the numerous nanosized drug delivery systems currently under investigation, carbon nanotubes (CNTs), regardless of being single or multiple-walled, offer several advantages and are considered as promising candidates for drug targeting. Despite the valuable potentials of CNTs in drug delivery, their toxicity still remains an important issue. After the PEGylation of single-walled CNTs (SWCNTs) with phospholipid-PEG (Pl-PEG) conjugates to prepare water-dispersible nanostructures, the present study was designed to evaluate whether the functionalization with Pl-PEG derivatives could alter the cytotoxic response of cells in culture, affect their viability and proliferation. In-vitro cytotoxicity screens were performed on cultured Jurkat cells. The SWCNTs samples used in this exposure were pristine SWCNTs, Pl-PEG 2000/5000-SWCNTs at various concentrations. Jurkat cells were first incubated for 3 h at 37°C with test materials and seeded in 6-well culture plates at a given concentration. The plates were then incubated for 24, 48 and 72 h at 37°C in a 5% CO2 humidified incubator. Cell Viability and proliferation assay were performed using trypan blue exclusion test and the cell cycle kinetic status of Jurkat cells was analyzed by flow cytometry. Cell morphology was finally studied using double staining technique and a fluorescence microscope. We found that, regardless of the duration of exposure, functionalized SWCNTs were substantially less toxic, compared to pure SWCNTs and that the molecular weight of Pl-PEGs played an important role at higher concentrations. In conclusion, our noncovalent protocol seemed to be effective for increasing SWCNTs biocompatibility.
Platelet Aggregates in Ischemic Heart Disease

Platelets in patients with myocardial ischemia show more sensitivity to aggregating agents (1-3), and blood heparinneutralizing activity, primarily attributable to Platelet Factor 4, is increased (4). Platelets produce thromboxane A2, a potent platelet aggregating agent and vasoconstrictor that acts on isolated porcine and bovine coronary arteries (5, 6). Thromboxane B2, a stable metabolite of thromboxane A2 in platelets, was reported to increase in the plasma of patients with Prinzmetal's angina (7). Infusion of thromboxane A2 into coronary arteries of rabbits caused acute myocardial infarction and sudden cardiac death (8). Sudden cardiac death was significantly reduced during the early treatment period of patients with documented myocardial infarction in a randomized, clinical trial of sulfinpyrazone (anturane), an agent that inhibits intravascular platelet consumption (9, 10). Platelet activation in circulation can be followed by measurement of platelet aggregates in venous blood, as was observed in patients with arterial insufficiency by Wu and Hoak (11), and with acute cerebral ischemia by Dougherty et al. (12). Gryglewski et al. (13) observed that platelet aggregates disappeared from venous blood following infusion of prostacyclin. We studied the occurrence of platelet aggregates in venous blood in regard to the type and location of myocardial infarction; the phase of myocardial ischemia (stable versus unstable angina); the temporal relationship between an episode of ischemia and an increase in platelet aggregates; and the possible correlation of these to such factors as patient's age, platelet count, leukocytosis, and enzyme elevation.