Razvoj novog proizvoda te upravljanje njegovim obilježjima tijekom životnog vijeka, zahtjevan je proces na čiji uspjeh utječe niz faktora. Poduzeća moraju optimizirati različite elemente kako bi ...proizvod bio što efikasniji, a da uvijek prati želje i zahtjeve potrošača. Predmet rada je istraživanje važnosti obilježja pametnog telefona kod pripadnika generacije Y primjenom Kano modela. cilj rada je i identificirati trendove i obilježja pametnog telefona, istražiti koja su obilježja neizostavna za pripadnike generacije Y, koja povećavaju njihovo ukupno zadovoljstvo u slučaju prisutnosti, te istražiti obilježja prema kojima su indiferentni odnosno čija prisutnost izaziva nezadovoljstvo. Primarni podaci analizirani u rezultatima istraživanja, prikupljeni su dubinskim intervjuima sa dva stručnjaka i četiri pripadnika generacije Y te anketnim upitnikom sastavljenim po uzoru na Kano model, dostavljenim elektroničkim putem na ukupno 150 ispitanika. Izviđajno istraživanje omogućilo je identifikaciju petnaest najvažnijih obilježja pametnog telefona s obzirom na trendove i očekivanja ispitanika. Opisno istraživanje omogućilo je evaluaciju svakog obilježja uz pomoć Kano tablice. Svakom je obilježju pridodana jedna od karakteristika Kano modela. Analizom je utvrđeno da veću atraktivnost kod ispitanika imaju tehnička obilježja proizvoda, dok su tržišna obilježja, poput dizajna i marke, okarakterizirana kao ona prema kojima su ispitanici indiferentni. Koristeći indekse Kano modela, kvantitativno je izraženo očekivano zadovoljstvo, odnosno nezadovoljstvo ispitanika, u ovisnosti o prisutnosti, ili neprisutnosti obilježja. Izračunom je utvrđeno da prisutnost dugotrajne baterije kod ispitanika izaziva veliko zadovoljstvo, a eventualna neprisutnost navedenog obilježja, izrazito nezadovoljstvo. Provedeno istraživanje dobar je temelj za daljnja istraživanja na navedenoj ciljnoj skupini i kategoriji proizvoda.
Razvoj novog proizvoda te upravljanje njegovim obilježjima tijekom životnog vijeka, zahtjevan je proces na čiji uspjeh utječe niz faktora. Poduzeća moraju optimizirati različite elemente kako bi ...proizvod bio što efikasniji, a da uvijek prati želje i zahtjeve potrošača. Predmet rada je istraživanje važnosti obilježja pametnog telefona kod pripadnika generacije Y primjenom Kano modela. cilj rada je i identificirati trendove i obilježja pametnog telefona, istražiti koja su obilježja neizostavna za pripadnike generacije Y, koja povećavaju njihovo ukupno zadovoljstvo u slučaju prisutnosti, te istražiti obilježja prema kojima su indiferentni odnosno čija prisutnost izaziva nezadovoljstvo. Primarni podaci analizirani u rezultatima istraživanja, prikupljeni su dubinskim intervjuima sa dva stručnjaka i četiri pripadnika generacije Y te anketnim upitnikom sastavljenim po uzoru na Kano model, dostavljenim elektroničkim putem na ukupno 150 ispitanika. Izviđajno istraživanje omogućilo je identifikaciju petnaest najvažnijih obilježja pametnog telefona s obzirom na trendove i očekivanja ispitanika. Opisno istraživanje omogućilo je evaluaciju svakog obilježja uz pomoć Kano tablice. Svakom je obilježju pridodana jedna od karakteristika Kano modela. Analizom je utvrđeno da veću atraktivnost kod ispitanika imaju tehnička obilježja proizvoda, dok su tržišna obilježja, poput dizajna i marke, okarakterizirana kao ona prema kojima su ispitanici indiferentni. Koristeći indekse Kano modela, kvantitativno je izraženo očekivano zadovoljstvo, odnosno nezadovoljstvo ispitanika, u ovisnosti o prisutnosti, ili neprisutnosti obilježja. Izračunom je utvrđeno da prisutnost dugotrajne baterije kod ispitanika izaziva veliko zadovoljstvo, a eventualna neprisutnost navedenog obilježja, izrazito nezadovoljstvo. Provedeno istraživanje dobar je temelj za daljnja istraživanja na navedenoj ciljnoj skupini i kategoriji proizvoda.
Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated ...cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS ⁺) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS ⁺ cells and (ii) hPSC-derived INS ⁺ (hPSC-INS ⁺) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS ⁺ cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS ⁺ cells into functional β cells.
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Transcriptional profiling is a key technique in the study of cell biology that is limited by the availability of reagents to uniquely identify specific cell types and isolate high quality RNA from ...them. We report a Method for Analyzing RNA following Intracellular Sorting (MARIS) that generates high quality RNA for transcriptome profiling following cellular fixation, intracellular immunofluorescent staining and FACS. MARIS can therefore be used to isolate high quality RNA from many otherwise inaccessible cell types simply based on immunofluorescent tagging of unique intracellular proteins. As proof of principle, we isolate RNA from sorted human embryonic stem cell-derived insulin-expressing cells as well as adult human β cells. MARIS is a basic molecular biology technique that could be used across several biological disciplines.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuronal activity-dependent gene expression is essential for brain development. Although transcriptional and epigenetic effects of neuronal activity have been explored in mice, such an investigation ...is lacking in humans. Because alterations in GABAergic neuronal circuits are implicated in neurological disorders, we conducted a comprehensive activity-dependent transcriptional and epigenetic profiling of human induced pluripotent stem cell-derived GABAergic neurons similar to those of the early developing striatum. We identified genes whose expression is inducible after membrane depolarization, some of which have specifically evolved in primates and/or are associated with neurological diseases, including schizophrenia and autism spectrum disorder (ASD). We define the genome-wide profile of human neuronal activity-dependent enhancers, promoters and the transcription factors CREB and CRTC1. We found significant heritability enrichment for ASD in the inducible promoters. Our results suggest that sequence variation within activity-inducible promoters of developing human forebrain GABAergic neurons contributes to ASD risk.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Short peptide tags S6 and A1, each 12 residues in length, were identified from a phage-displayed peptide library as efficient substrates for site-specific protein labeling catalyzed by Sfp and AcpS ...phosphopantetheinyl transferases (PPTases), respectively. S6 and A1 tags were selected for useful levels of orthogonality in reactivities with the PPTases: the catalytic efficiency, k cat/K m of Sfp-catalyzed S6 serine phosphopantetheinylation was 442-fold greater than that for AcpS. Conversely, the k cat/K m of AcpS-catalyzed A1 labeling was 30-fold higher than that for Sfp-catalyzed A1 labeling. S6 and A1 peptide tags can be fused to N- or C-termini of proteins for orthogonal labeling of target proteins in cell lysates or on live cell surfaces. The development of the orthogonal S6 and A1 tags represents a significant enhancement of PPTase-catalyzed protein labeling, allowing tandem or iterative covalent attachment of small molecules of diverse structures to the target proteins with high efficiency and specificity.
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Sensory experience influences the establishment of neural connectivity through molecular mechanisms that remain unclear. Here, we employ single-nucleus RNA sequencing to investigate the contribution ...of sensory-driven gene expression to synaptic refinement in the dorsal lateral geniculate nucleus of the thalamus, a region of the brain that processes visual information. We find that visual experience induces the expression of the cytokine receptor Fn14 in excitatory thalamocortical neurons. By combining electrophysiological and structural techniques, we show that Fn14 is dispensable for early phases of refinement mediated by spontaneous activity but that Fn14 is essential for refinement during a later, experience-dependent period of development. Refinement deficits in mice lacking Fn14 are associated with functionally weaker and structurally smaller retinogeniculate inputs, indicating that Fn14 mediates both functional and anatomical rearrangements in response to sensory experience. These findings identify Fn14 as a molecular link between sensory-driven gene expression and vision-sensitive refinement in the brain.
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•Visual stimulation induces a unique gene program in excitatory neurons of the dLGN•Fn14 is the most inducible molecule specific to the excitatory population•Vision-sensitive refinement is impaired in mice lacking Fn14•Changes in synaptic morphology accompany physiological deficits in mice lacking Fn14
Visual experience promotes the synaptic refinement of the retinogeniculate circuit by inducing the expression of the cytokine receptor Fn14 in excitatory neurons of the dorsal lateral geniculate nucleus of the thalamus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated ...cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS+) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS+ cells and (ii) hPSC-derived INS+ (hPSC-INS+) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS+ cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS+ cells into functional β cells. PUBLICATION ABSTRACT
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Summary
We have discovered a novel small-molecule (3-phosphinoylpropionic acid) inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa), BX 528, which had an IC
50
of 2 nM in an ...enzymatic assay and 50 nM in an in-vitro clot lysis assay, with 3,500- to 35,000-fold selectivity against other carboxypeptidases, such as CPN, CPZ and CPD, and 5- and 12-fold selectivity against CPE (CPH) and CPB, respectively. At 10 µM, BX 528 had no significant activity (< 50% inhibition or antagonism) in a panel of 137 enzymes and receptors. It had no effects on blood coagulation and platelet aggregation up to 300 and 10 µM, respectively. The plasma half-life following intravenous administration was 0.85 hours in rats and 4.5 hours in dogs. No significant metabolism was detected in human, dog or rabbit hepatic microsomes, and no significant inhibition of cytochrome P450 3A4 and 2D6 up to 30 µM. No cytotoxic or cell proliferative effects were found in three hepatic and renal cell lines up to 300 µM and no mutagenic activity was seen in the Ames II screen. There were no significant hemodynamic effects in rats and dogs up to 100 and 30 mg/kg with peak plasma drug concentrations of ~1,000 and 300 µM, respectively. In an in-vivo complement activation model in guinea pigs, BX 528 showed minimal inhibition of plasma CPN activity up to 60 mg/kg with peak plasma concentrations up to 250 µM. Thus, these data demonstrate that BX 528 is a novel, potent, selective and safe TAFIa inhibitor.
Transcriptional profiling is a key technique in the study of cell biology that is limited by the availability of reagents to uniquely identify specific cell types and isolate high quality RNA from ...them. We report a Method for Analyzing RNA following Intracellular Sorting (MARIS) that generates high quality RNA for transcriptome profiling following cellular fixation, intracellular immunofluorescent staining and FACS. MARIS can therefore be used to isolate high quality RNA from many otherwise inaccessible cell types simply based on immunofluorescent tagging of unique intracellular proteins. As proof of principle, we isolate RNA from sorted human embryonic stem cell-derived insulin-expressing cells as well as adult human beta cells. MARIS is a basic molecular biology technique that could be used across several biological disciplines.
Full text
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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