bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct and sustained intracellular delivery of exogenous molecules using acoustic-transfection with high frequency ultrasound
Authors: Yoon Sangpil , Kim Min Gon , Chiu Chi Tat , Hwang Jae Youn , Kim Hyung Ham , Wang Yingxiao , Shung K. Kirk 
Published: February 2016

AbstractControlling cell functions for research and therapeutic purposes may open new strategies for the treatment of many diseases. An efficient and safe introduction of membrane impermeable molecules into target cells will provide versatile means to modulate cell fate. We introduce a new transfection technique that utilizes high frequency ultrasound without any contrast agents such as microbubbles, bringing a single-cell level targeting and size-dependent intracellular delivery of macromolecules. The transfection apparatus consists of an ultrasonic transducer with the center frequency of over 150 MHz and an epi-fluorescence microscope, entitled acoustic-transfection system. Acoustic pulses, emitted from an ultrasonic transducer, perturb the lipid bilayer of the cell membrane of a targeted single-cell to induce intracellular delivery of exogenous molecules. Simultaneous live cell imaging using HeLa cells to investigate the intracellular concentration of Ca2+ and propidium iodide (PI) and the delivery of 3 kDa dextran labeled with Alexa 488 were demonstrated. Cytosolic delivery of 3 kDa dextran induced via acoustic-transfection was manifested by diffused fluorescence throughout whole cells. Short-term (6 hr) cell viability test and long-term (40 hr) cell tracking confirmed that the proposed approach has low cell cytotoxicity.
Negative outcomes evoke cyclic irrational decisions in Rock, Paper, Scissors
Authors: Dyson Benjamin James , Wilbiks Jonathan Michael Paul , Sandhu Raj , Papanicolaou Georgios , Lintag Jaimie 
Published: February 2016

AbstractRock, Paper, Scissors (RPS) represents a unique gaming space in which the predictions of human rational decision-making can be compared with actual performance. Playing a computerized opponent adopting a mixed-strategy equilibrium, participants revealed a non-significant tendency to over-select Rock. Further violations of rational decision-making were observed using an inter-trial analysis where participants were more likely to switch their item selection at trialn + 1following a loss or draw at trialn, revealing the strategic vulnerability of individuals following the experience of negative rather than positive outcome. Unique switch strategies related to each of these trialnoutcomes were also identified: after losing participants were more likely to ‘downgrade’ their item (e.g., Rock followed by Scissors) but after drawing participants were more likely to ‘upgrade’ their item (e.g., Rock followed by Paper). Further repetition analysis revealed that participants were more likely to continue their specific cyclic item change strategy into trialn + 2. The data reveal the strategic vulnerability of individuals following the experience of negative rather than positive outcome, the tensions between behavioural and cognitive influences on decision making and underline the dangers of increased behavioural predictability in other recursive, non-cooperative environments such as economics and politics.
Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites
Authors: Möginger Uwe , Resemann Anja , Martin Christopher E. , Parameswarappa Sharavathi , Govindan Subramanian , Wamhoff Eike-Christian , Broecker Felix , Suckau Detlev , Pereira Claney Lebev , Anish Chakkumkal , Seeberger Peter H. , Kolarich Daniel 
Published: February 2016

AbstractProduction of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM197). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM197 and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated.
MicroRNA-101 targets von Hippel-Lindau tumor suppressor (VHL) to induce HIF1α mediated apoptosis and cell cycle arrest in normoxia condition
Authors: Liu Ning , Xia Wu-Yan , Liu Shan-Shan , Chen Hai-Yan , Sun Lei , Liu Meng-Yao , Li Lin-Feng , Lu Hong-Min , Fu Yu-Jie , Wang Pei , Wu Hailong , Gao Jian-Xin 
Published: February 2016

AbstractThe activation/inactivation of HIF1α is precisely regulated in an oxygen-dependent manner. HIF1α is essential for hypoxia induced apoptosis and cell cycle arrest. Several recent studies indicated that the expression of miRNAs can be modulated by hypoxia. However, the involvement of miRNAs in the regulation of HIF1α induction remains elusive. In present study, we demonstrated thatmiR-101was rapidly and transiently induced after hypoxia in breast cancer cells. Over-expression ofmiR-101significantly inhibited cell proliferation in breast cancer cells through increased apoptosis and cell cycle arrest in normoxia condition. This inhibitory phenomenon seems due tomiR-101-mediated induction of HIF1α, because we identified thatVHL, a negative regulator of HIF1α, is a novel target ofmiR-101and over-expression ofmiR-101decreased VHL levels and subsequently stabilized HIF1α and induced its downstream targetVEGFA. Furthermore, we demonstrated that siRNA-mediated knockdown of VHL or HIF1α overexpression could also induce apoptosis and cell cycle arrest whereas enforced expression of VHL, administration of anti-miR-101oligos or treatment of 2-MeOE2, an inhibitor of HIF1α, could rescue cells from such inhibition. These results reveal a novel regulatory mechanism of HIF1α induction in normoxia and suggest thatmiR-101mediated proliferation inhibition may through HIF1α mediated apoptosis and cell cycle arrest.
Facile and Chemically Pure Preparation of YVO4:Eu3+ Colloid with Novel Nanostructure via Laser Ablation in Water
Authors: Wang Haohao , Odawara Osamu , Wada Hiroyuki 
Published: February 2016

AbstractA YVO4:Eu3+ colloid with an interesting nanostructure was formed by pulsed laser ablation in deionized water without any additives or surfactants. Analyses of particle morphology, composition and optical properties were accomplished by SEM, TEM, EDS PL and UV-vis. Ovoid-like particles formed by the agglomeration of numerous nanocrystals were observed by SEM and TEM, while EDS with area-mode analysis revealed that the content of dopant ion was well retained within the nanoparticles. In addition, the formation mechanism is deduced and discussed for the first time in this research. The findings of this study could provide new insights into the understanding of laser-induced oxide materials and offer an opportunity for other research groups to pursue red emitting nanophosphors with outstandingly purity.
Transcriptional Regulation of Atp-Dependent Chromatin Remodeling Factors: Smarcal1 and Brg1 Mutually Co-Regulate Each Other
Authors: Haokip Dominic Thangminlen , Goel Isha , Arya Vijendra , Sharma Tapan , Kumari Reshma , Priya Rashmi , Singh Manpreet , Muthuswami Rohini 
Published: February 2016

AbstractThe ATP-dependent chromatin remodeling factors regulate gene expression. However, it is not known whether these factors regulate each other. Given the ability of these factors to regulate the accessibility of DNA to transcription factors, we postulate that one ATP-dependent chromatin remodeling factor should be able to regulate the transcription of another ATP-dependent chromatin remodeling factor. In this paper, we show that BRG1 and SMARCAL1, both members of the ATP-dependent chromatin remodeling protein family, regulate each other. BRG1 binds to the SMARCAL1 promoter, while SMARCAL1 binds to the brg1 promoter. During DNA damage, the occupancy of SMARCAL1 on the brg1 promoter increases coinciding with an increase in BRG1 occupancy on the SMARCAL1 promoter, leading to increased brg1 and SMARCAL1 transcripts respectively. This is the first report of two ATP-dependent chromatin remodeling factors regulating each other.
Postural Changes in Measures of Arterial Stiffness in Hypertensive Subjects on Antihypertensive Drug Therapy: A Prospective, Pilot Study
Authors: Jun Du , Cheong Chin , Sule Ashish 
Published: February 2016

AbstractProspective study with a controlled arm to know if there are variations of measures of arterial stiffness with posture in subjects with hypertension on antihypertensive medications.We studied postural variations of measures of arterial stiffness in 21 subjects with diagnosed hypertension on antihypertensive medications and compared them with 21 normotensive subjects. All subjects underwent pulse-wave analysis on SphygmoCor in the morning between 8 am to 10 am initially in supine and then in sitting position after 3 minutes. Summary measures on demographics, and blood pressure characteristics at sitting and supine positions are obtained. Differences between characteristics at supine and sitting position are compared using nonparametric paired test of Wilcoxon signed-rank test. A value of p < 0.05 was accepted as statistically significant.Antihypertensive medications decreased the supine aortic augmentation pressure (AAP) and augmentation index (AI) but not significantly. When subgroups of patients with antihypertensive treatment were analyzed, it was noted that angiotensin-converting enzyme inhibitor and angiotensin receptor blocker group (12) decreased AAP and AI significantly in supine position compared with patients on other antihypertensive medications (9) (p-value 0.034 and 0.038, respectively). There was no significant difference in other groups of calcium channel blockers, β-blockers, or diuretics. However, in normotensive control arm, there was an increase in AAP and AI in the supine position.In hypertensive subjects, on antihypertensive, there was reduction in AAP and AI in supine position compared with those of normotensives. The significance of the decrease in AAP and AI in supine position on antihypertensive needs to be studied further.
Identification of amino acid networks governing catalysis in the closed complex of class I terpene synthases
Authors: Schrepfer Patrick , Buettner Alexander , Goerner Christian , Hertel Michael , van Rijn Jeaphianne , Wallrapp Frank , Eisenreich Wolfgang , Sieber Volker , Kourist Robert , Brück Thomas 
Published: February 2016

SignificanceClass I terpene synthases are essential in biosynthesis of bioactive terpenoids (e.g., Taxol). Identification of structure–function correlations is hampered by highly dynamic carbocation-driven reactions and the limited availability of catalytically relevant crystal structures. We provide the closed, catalytically active conformations of taxadiene synthase (TXS) and various taxonomically unrelated class I terpene synthases in complex with their catalytically relevant carbocationic intermediates. Our methodology allows direct prediction and validation of universal structural features that govern the highly dynamic catalytic processes of class I terpene synthases. Our data enabled delineation of a discrete reaction pathway for TXS and allowed targeted enzyme engineering to generate alternate macrocyclic core structures, which can act as synthons for bioactive lead structures.
Microbiological Contamination of Drugs during Their Administration for Anesthesia in the Operating Room
Authors: Gargiulo Derryn A. , Mitchell Simon J. , Sheridan Janie , Short Timothy G. , Swift Simon , Torrie Jane , Webster Craig S. , Merry Alan F. 
Published: February 2016

AbstractAbstract
Anesthesiologists were asked to make bolus injections of all drugs, except propofol and antibiotics, through a 0.2-μm filter in a prospective, open, microbiological audit of 300 cases. Microorganisms with the potential to cause infections were isolated from the 0.2-μm filters of 19 (6.3%) of the 300 cases.

Background
The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections.

Methods
A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-µm filter was performed. The authors cultured microorganisms, if present, from the 0.2-µm filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case.

Results
Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants’ average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult).

Conclusions
Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation.
Intralymphatic Proliferation of T-cell Lymphoid Blasts in the Setting of Hidradenitis Suppurativa
Authors: Calamaro Paola , Cerroni Lorenzo 
Published: February 2016

Abstract:
Intralymphatic proliferation of T-cell lymphoid blasts (IPTCLBs) is a rare, recently described entity, associated with cutaneous inflammatory conditions and characterized by intralymphatic proliferation of highly proliferating, blastoid T lymphocytes expressing CD30, thus mimicking an intravascular lymphoma. In all reported cases, the intralymphatic proliferation was associated with an underlying inflammatory condition, with no clonal T-cell receptor rearrangement, no signs of systemic or cutaneous lymphoma, and excellent prognosis. The authors present a new case of IPTCLB arising in a patient with hidradenitis suppurativa. Histological examination revealed a dilated follicle embedded within a fibrotic stroma surrounded by a dense lymphoid infiltrate characterized by the presence of dilated small vessels filled with atypical medium-to-large sized blastoid lymphocytes expressing a CD4+ T phenotype. There was also expression of CD30, but negativity for cytotoxic markers and Epstein-Barr virus. The proliferation index was high and the vessels showed expression of D2-40, confirming their lymphatic nature. No signs of systemic lymphoma could be detected after routine investigations, and the patient is alive and in good general health. IPTCLB is a rare benign entity that presents with worrying, potentially misleading histopathological features that mimic those observed in intravascular lymphoma. Careful histological and phenotypic investigations and correlation with the clinical features are necessary for a proper diagnosis.
Providing Guidance for Patients With Moderate-to-Severe Psoriasis Who are Candidates for Biologic Therapy
Authors: Aldredge Lakshi M. , Young Melodie S. 
Published: February 2016

ABSTRACT
Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient’s life course.
Fine-scale human population structure in southern Africa reflects ecological boundaries
Authors: Uren Caitlin , Kim Minju , Martin Alicia R , Bobo Dean , Gignoux Christopher R , van Helden Paul D , Möller Marlo , Hoal Eileen G , Henn Brenna M 
Published: February 2016

AbstractRecent genetic studies have established that the KhoeSan populations of southern Africa are distinct from all other African populations and have remained largely isolated during human prehistory until about 2,000 years ago. Dozens of different KhoeSan groups exist, belonging to three different language families, but very little is known about population history within southern Africa. We examine new genome-wide polymorphism data and whole mitochondrial genomes for more than one hundred South Africans from the ≠Khomani San and Nama populations of the Northern Cape, analyzed in conjunction with 19 additional southern African populations. Our analyses reveal fine-scale population structure in and around the Kalahari Desert. Surprisingly, this structure does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. Regardless of subsistence strategy, the indigenous Khoe-speaking Nama pastoralists and the N|u-speaking ≠Khomani (formerly hunter-gatherers) share recent ancestry with other Khoe-speaking forager populations that forms a rim around the Kalahari Desert. We reconstruct earlier migration patterns and estimate that the southern Kalahari populations were among the last to experience gene flow from Bantu-speakers, approximately 14 generations ago. We conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited impact from eastern African genetic diffusion.
Signal and Specificity of Protein Ubiquitination for Proteasomal Degradation
Authors: Yin Yandong , Yang Jin 
Published: February 2016

AbstractThe eukaryotic ubiquitin system regulates essential cell events such as DNA repair, protein homeostasis, and signal transduction. Like many biochemical processes, ubiquitination must ensure signaling efficiency and in the meantime maintain substrate specificity. We examine this signal-specificity relationship by theoretical models of polyubiquitinations that tag proteins for the proteasomal degradation. Parsimonious models provide explicit formulas to key measurable quantities and offer guiding insights into the signal-specificity tradeoffs under varying structures and kinetics. Models with measured kinetics from two primary cell-cycle ligases (SCF and APC) explain mechanisms of chain initiation, elongation slowdown, chain-length dependence of E3-substrate affinity, and deubiquitinases. We find that substrate discrimination over ubiquitin transfer rates is consistently more efficient than over substrate-E3 ligase binding energy, regardless of circuit structure, parameter value, and dynamics. E3-associated substrate deubiquitination increases the discrimination over the former and in the meantime decreases the latter, further widening their difference. Both discrimination strategies might be simultaneously explored by an E3 system to effectively proofread substrates as we demonstrated by analyzing experimental data from the CD4-Vpu-SCF system. We also identify that sequential deubiquitination circuit may act as a specificity switch, by which a modest change in deubiquitination and/or processivity can greatly increase substrate discrimination without much compromise in degradation signal. This property may be utilized as a gatekeeper mechanism to direct a temporal polyubiquitination and thus degradation order of substrates with small biochemical differences.
A novel approach to identifying marker genes and estimating the cellular composition of whole blood from gene expression profiles
Authors: Shannon Casey P. , Balshaw Robert , Chen Virginia , Hollander Zsuzsanna , Toma Mustafa , McManus Bruce M. , FitzGerald J. Mark , Sin Don D. , Ng Raymond T. , Tebbutt Scott J. 
Published: February 2016

AbstractMeasuring genome-wide changes in transcript abundance in circulating peripheral whole blood cells is a useful way to study disease pathobiology and may help elucidate biomarkers and molecular mechanisms of disease. The sensitivity and interpretability of analyses carried out in this complex tissue, however, are significantly affected by its dynamic heterogeneity. It is therefore desirable to quantify this heterogeneity, either to account for it or to better model interactions that may be present between the abundance of certain transcripts, some cell types and the indication under study. Accurate enumeration of the many component cell types that make up peripheral whole blood can be costly, however, and may further complicate the sample collection process. Many approaches have been developed to infer the composition of a sample from high-dimensional transcriptomic and, more recently, epigenetic data. These approaches rely on the availability of isolated expression profiles for the cell types to be enumerated. These profiles are platform-specific, suitable datasets are rare, and generating them is expensive. No such dataset exists on the Affymetrix Gene ST platform. We present a freely-available, and open source, multi-response Gaussian model capable of accurately predicting the composition of peripheral whole blood samples from Affymetrix Gene ST expression profiles. This model outperforms other current methods when applied to Gene ST data and could potentially be used to enrich the >10,000 Affymetrix Gene ST blood gene expression profiles currently available on GEO.Key PointsWe introduce a model that accurately predicts the composition of blood from Affymetrix Gene ST gene expression profiles.This model outperforms existing methods when applied to Affymetrix Gene ST expression profiles from blood.