bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular choreography of protein synthesis: translational control, regulation, and pathways
Authors: Chen Jin , Choi Junhong , O'Leary Seán E. , Prabhakar Arjun , Petrov Alexey , Grosely Rosslyn , Puglisi Elisabetta Viani , Puglisi Joseph D. 
Published: June 2016

AbstractTranslation of proteins by the ribosome regulates gene expression, with recent results underscoring the importance of translational control. Misregulation of translation underlies many diseases, including cancer and many genetic diseases. Decades of biochemical and structural studies have delineated many of the mechanistic details in prokaryotic translation, and sketched the outlines of eukaryotic translation. However, translation may not proceed linearly through a single mechanistic pathway, but likely involves multiple pathways and branchpoints. The stochastic nature of biological processes would allow different pathways to occur during translation that are biased by the interaction of the ribosome with other translation factors, with many of the steps kinetically controlled. These multiple pathways and branchpoints are potential regulatory nexus, allowing gene expression to be tuned at the translational level. As research focus shifts toward eukaryotic translation, certain themes will be echoed from studies on prokaryotic translation. This review provides a general overview of the dynamic data related to prokaryotic and eukaryotic translation, in particular recent findings with single-molecule methods, complemented by biochemical, kinetic, and structural findings. We will underscore the importance of viewing the process through the viewpoints of regulation, translational control, and heterogeneous pathways.
Bridging the gap betweenin vitroandin vivoRNA folding
Authors: Leamy Kathleen A. , Assmann Sarah M. , Mathews David H. , Bevilacqua Philip C. 
Published: June 2016

AbstractDeciphering the folding pathways and predicting the structures of complex three-dimensional biomolecules is central to elucidating biological function. RNA is single-stranded, which gives it the freedom to fold into complex secondary and tertiary structures. These structures endow RNA with the ability to perform complex chemistries and functions ranging from enzymatic activity to gene regulation. Given that RNA is involved in many essential cellular processes, it is critical to understand how it folds and functionsin vivo. Within the last few years, methods have been developed to probe RNA structuresin vivoand genome-wide. These studies reveal that RNA often adopts very different structuresin vivoandin vitro, and provide profound insights into RNA biology. Nonetheless, bothin vitroandin vivoapproaches have limitations: studies in the complex and uncontrolled cellular environment make it difficult to obtain insight into RNA folding pathways and thermodynamics, and studiesin vitrooften lack direct cellular relevance, leaving a gap in our knowledge of RNA foldingin vivo. This gap is being bridged by biophysical and mechanistic studies of RNA structure and function under conditions that mimic the cellular environment. To date, most artificial cytoplasms have used various polymers as molecular crowding agents and a series of small molecules as cosolutes. Studies under suchin vivo-likeconditions are yielding fresh insights, such as cooperative folding of functional RNAs and increased activity of ribozymes. These observations are accounted for in part by molecular crowding effects and interactions with other molecules. In this review, we report milestones in RNA foldingin vitroandin vivoand discuss ongoing experimental and computational efforts to bridge the gap between these two conditions in order to understand how RNA folds in the cell.
Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador
Authors: ORTEGA-PAREDES D. , BARBA P. , ZURITA J. 
Published: June 2016

SUMMARYColistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and blaCTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.
Choosing Wisely
Authors: FLECK LEONARD M. 
Published: June 2016

Abstract:The American College of Physicians in its ethics manual endorsed the idea that physicians ought to improve their ability to provide care to their patients more parsimoniously. This elicited a critical backlash; critics essentially claimed that what was being endorsed was a renamed form of rationing. In a recent article, Tilburt and Cassel argued that parsimonious care and rationing are ethically distinct practices. In this essay I critically assess that claim. I argue that in practice there is considerable overlap between what they term parsimonious care and what they define as rationing. The same is true of the Choosing Wisely campaign endorsed by the American Board of Internal Medicine. In both cases, if the goal is to control healthcare costs by reducing the use of marginally beneficial care that is not cost effective, then a public conversation about the justness of specific choices is essential.
An Ethical Analysis of Performance-Based Supplementary Payment in Turkey’s Healthcare System
Authors: KADIOGLU FUNDA GULAY 
Published: June 2016

Abstract:In 2003 Turkey introduced the Health Transition Program to develop easily accessible, high-quality, and effective healthcare services for the population. This program, like other health reforms, has three primary goals: to improve health status, to enhance financial protection, and to ensure patients’ satisfaction. Although there is considerable literature on the anticipated positive results of such health reforms, little evidence exists on their current effectiveness. One of the main initiatives of this health reform is a performance-based supplementary payment system, an additional payment healthcare professionals receive each month in addition to their regular salaries. This system may cause some ethical problems. Physicians have an ethical duty to provide high-quality care to each patient; however, pay-for-performance and other programs that create strong incentives for high-quality care set up a potential conflict between this duty and the competing interest of complying with a performance measure.
An Ethical Analysis of Assisted Reproduction Providers’ Websites in Pakistan
Authors: IRSHAD AYESHA , WERNER-FELMAYER GABRIELE 
Published: June 2016

Abstract:Assisted reproductive technologies (ARTs) and reproductive genetic technologies (RGTs) are intertwined and coevolving. These technologies are increasingly used to fulfill socially and culturally framed requests, for example, “family balancing,” or to enable postmenopausal women or homosexual couples to have genetically linked children. The areas of ART and RGT are replete with ethical issues, because different social practices and legal regulations, as well as economic inequalities within and among countries, create vulnerable groups and, therefore, the potential for exploitation. This article provides an overview of the ART and RGT landscape in Pakistan and analyzes the available online content addressing Pakistani citizens and international clients. We explored the topic in view of socioeconomic challenges in Pakistan, particularly deeply rooted poverty, lack of education, gender discrimination, and absence of regulation. As online information given by ART and RGT providers is readily available and could easily raise false hopes, make use of discriminatory statements with regard to women, and promote gender selection to meet sociocultural expectations, it should be subjected to quality control.
Relationships between sucretolerance and salinotolerance in bacteria from hypersaline environments and their implications for the exploration of Mars and the icy worlds
Authors: Fredsgaard Casper , Moore Donald B. , Al Soudi Amer F. , Crisler James D. , Chen Fei , Clark Benton C. , Schneegurt Mark A. 
Published: June 2016

AbstractThe most extremely osmotolerant microbial isolates are fungi from high-sugar environments that tolerate the lowest water activity (0.61) for growth yet reported. Studies of osmotolerant bacteria have focused on halotolerance rather than sucretolerance (ability to grow in high sugar concentrations). A collection of salinotolerant (≥10% NaCl or ≥50% MgSO4) bacterial isolates from the Great Salt Plains of Oklahoma and Hot Lake in Washington were screened for sucretolerance in medium supplemented with ≥50% fructose, glucose or sucrose. Tolerances significantly differed between solutes, even though water activities for saline media (0.92 and 0.85 for 10 and 20% NaCl Salt Plains media, respectively) were comparable or lower than water activities for high-sugar media (0.93 and 0.90 for 50 and 70% sucrose artificial nectar media, respectively). These specific solute effects were differentially expressed among individual isolates. Extrapolating the results of earlier food science studies with yeasts at high sugar concentrations to bacteria in salty environments with low water activity should be done with caution. Furthermore, the discussion of habitable Special Regions on Mars and the icy worlds should reflect an understanding of specific solute effects.
Reflecting on one's own death: The existential questions that nurses face during end-of-life care
Authors: Karlsson Margareta , Kasén Anne , Wärnå-Furu Carola 
Published: June 2016

AbstractObjective:When registered nurses care for patients at the end of life, they are often confronted with different issues related to suffering, dying, and death whether working in hospital or community care. Serious existential questions that challenge nurses’ identities as human beings can arise as a result of these situations. The aim of our study was to describe and gain a deeper understanding of nurses’ existential questions when caring for dying patients.Method:Focus-group interviews with registered nurses who shared similar experiences and backgrounds about experiences in end-of-life care were employed to gain a deeper understanding about this sensitive subject. Focus-group interviews were performed in hospice care, in community care, and in a palliative care unit in western Sweden. A qualitative hermeneutic approach was employed to interpret the data.Results:Nurses’ existential questions balanced between responsibility and guilt in relation to their patients, between fear and courage in relation to being professional caregivers and fellow human beings, and between hope and despair in relation to the other's and their own death.Significance of results:Nurses in end-of-life care experience various emotions from patients related to things physical, spatial, and temporal. When nurses encounter these emotions as expressing a patient's suffering, they lead to challenges of balancing between different feelings in relation to patients, as both professional caregivers and fellow human beings. Nurses can experience growth both professionally and as human beings when caring for patients at the end of life.
Stimulus-responsive light-harvesting complexes based on the pillararene-induced co-assembly of β-carotene and chlorophyll
Authors: Sun Yan , Guo Fang , Zuo Tongfei , Hua Jingjing , Diao Guowang 
Published: June 2016

AbstractThe locations and arrangements of carotenoids at the subcellular level are responsible for their designated functions, which reinforces the necessity of developing methods for constructing carotenoid-based suprastructures beyond the molecular level. Because carotenoids lack the binding sites necessary for controlled interactions, functional structures based on carotenoids are not easily obtained. Here, we show that carotene-based suprastructures were formed via the induction of pillararene through a phase-transfer-mediated host–guest interaction. More importantly, similar to the main component in natural photosynthesis, complexes could be synthesized after chlorophyll was introduced into the carotene-based suprastructure assembly process. Remarkably, compared with molecular carotene or chlorophyll, this synthesized suprastructure exhibits some photocatalytic activity when exposed to light, which can be exploited for photocatalytic reaction studies of energy capture and solar conversion in living organisms.
Mechanisms of increased Trichodesmium fitness under iron and phosphorus co-limitation in the present and future ocean
Authors: Walworth Nathan G. , Fu Fei-Xue , Webb Eric A. , Saito Mak A. , Moran Dawn , Mcllvin Matthew R. , Lee Michael D. , Hutchins David A. 
Published: June 2016

AbstractNitrogen fixation by cyanobacteria supplies critical bioavailable nitrogen to marine ecosystems worldwide; however, field and lab data have demonstrated it to be limited by iron, phosphorus and/or CO2. To address unknown future interactions among these factors, we grew the nitrogen-fixing cyanobacterium Trichodesmium for 1 year under Fe/P co-limitation following 7 years of both low and high CO2 selection. Fe/P co-limited cell lines demonstrated a complex cellular response including increased growth rates, broad proteome restructuring and cell size reductions relative to steady-state growth limited by either Fe or P alone. Fe/P co-limitation increased abundance of a protein containing a conserved domain previously implicated in cell size regulation, suggesting a similar role in Trichodesmium. Increased CO2 further induced nutrient-limited proteome shifts in widespread core metabolisms. Our results thus suggest that N2-fixing microbes may be significantly impacted by interactions between elevated CO2 and nutrient limitation, with broad implications for global biogeochemical cycles in the future ocean.
Mechanical perturbations trigger endothelial nitric oxide synthase activity in human red blood cells
Authors: Nagarajan Shunmugan , Raj Rajendran Kadarkarai , Saravanakumar Venkatesan , Balaguru Uma Maheswari , Behera Jyotirmaya , Rajendran Vinoth Kumar , Shathya Yogarajan , Ali B. Mohammed Jaffar , Sumantran Venil , Chatterjee Suvro 
Published: June 2016

AbstractNitric oxide (NO), a vascular signaling molecule, is primarily produced by endothelial NO synthase. Recently, a functional endothelial NO synthase (eNOS) was described in red blood cells (RBC). The RBC-eNOS contributes to the intravascular NO pool and regulates physiological functions. However the regulatory mechanisms and clinical implications of RBC-eNOS are unknown. The present study investigated regulation and functions of RBC-eNOS under mechanical stimulation. This study shows that mechanical stimuli perturb RBC membrane, which triggers a signaling cascade to activate the eNOS. Extracellular NO level, estimated by the 4-Amino-5-Methylamino-2′, 7′-Difluorofluorescein Diacetate probe, was significantly increased under mechanical stimuli. Immunostaining and western blot studies confirmed that the mechanical stimuli phosphorylate the serine 1177 moiety of RBC-eNOS and activates the enzyme. The NO produced by activation of RBC-eNOS in vortexed RBCs promoted important endothelial functions such as migration and vascular sprouting. We also show that mechanical perturbation facilitates nitrosylation of RBC proteins via eNOS activation. The results of the study confirm that mechanical perturbations sensitize RBC-eNOS to produce NO, which ultimately defines physiological boundaries of RBC structure and functions. Therefore, we propose that mild physical perturbations before, after, or during storage can improve viability of RBCs in blood banks.
The Lombard effect in male ultrasonic frogs: Regulating antiphonal signal frequency and amplitude in noise
Authors: Shen Jun-Xian , Xu Zhi-Min 
Published: June 2016

AbstractAcoustic communication in noisy environments presents a significant challenge for vocal animals because noise can interfere with animal acoustic signals by decreasing signal-to-noise ratios and masking signals. Birds and mammals increase call intensity or frequency as noise levels increase, but it is unclear to what extend this behavior is shared by frogs. Concave-eared torrent frogs (Odorrana tormota) have evolved the capacity to produce various calls containing ultrasonic harmonics and to communicate beside noisy streams. However, it is largely unclear how frogs regulate vocalization in response to increasing noise levels. We exposed male frogs to various levels of noise with playback of conspecific female courtship calls and recorded antiphonal signals and spontaneous short calls. Males were capable of rapidly adjusting fundamental frequency and amplitude of antiphonal signals as noise levels increased. The increment in fundamental frequency and amplitude was approximately 0.5 kHz and 3 dB with every 10 dB increase in noise level, indicating the presence of noise-dependent signal characteristics. Males showed the noise-tolerant adaption in response to female calls in noise level from 40 to 90 dB SPL. The results suggest that the noise-dependent signal characteristics in O. tormota have evolved as a strategy to cope with varying torrent noise.
The new and recurrent FLT3 juxtamembrane deletion mutation shows a dominant negative effect on the wild-type FLT3 receptor
Authors: Sandhöfer Nadine , Bauer Julia , Reiter Katrin , Dufour Annika , Rothenberg Maja , Konstandin Nikola P. , Zellmeier Evelyn , Tizazu Belay , Greif Philipp A. , Metzeler Klaus H. , Hiddemann Wolfgang , Polzer Harald , Spiekermann Karsten 
Published: June 2016

AbstractIn acute myeloid leukemia (AML), the Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes. Recently, a new and recurrent juxtamembrane deletion mutation (p.Q569Vfs*2) resulting in a truncated receptor was identified. The mutated receptor is expressed on the cell surface and still binds its ligand but loses the ability to activate ERK signaling. FLT3 p.Q569fs-expressing Ba/F3 cells show no proliferation after ligand stimulation. Furthermore, coexpressed with the FLT3 wild-type (WT) receptor, the truncated receptor suppresses stimulation and activation of the WT receptor. Thus, FLT3 p.Q569Vfs*2, to our knowledge, is the first FLT3 mutation with a dominant negative effect on the WT receptor.
Histone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells
Authors: Itahana Yoko , Zhang Jinqiu , Göke Jonathan , Vardy Leah A. , Han Rachel , Iwamoto Kozue , Cukuroglu Engin , Robson Paul , Pouladi Mahmoud A. , Colman Alan , Itahana Koji 
Published: June 2016

AbstractThe high proliferation rate of embryonic stem cells (ESCs) is thought to arise partly from very low expression of p21. However, how p21 is suppressed in ESCs has been unclear. We found that p53 binds to the p21 promoter in human ESCs (hESCs) as efficiently as in differentiated human mesenchymal stem cells, however it does not promote p21 transcription in hESCs. We observed an enrichment for both the repressive histone H3K27me3 and activating histone H3K4me3 chromatin marks at the p21 locus in hESCs, suggesting it is a suppressed, bivalent domain which overrides activation by p53. Reducing H3K27me3 methylation in hESCs rescued p21 expression, and ectopic expression of p21 in hESCs triggered their differentiation. Further, we uncovered a subset of bivalent promoters bound by p53 in hESCs that are similarly induced upon differentiation in a p53-dependent manner, whereas p53 promotes the transcription of other target genes which do not show an enrichment of H3K27me3 in ESCs. Our studies reveal a unique epigenetic strategy used by ESCs to poise undesired p53 target genes, thus balancing the maintenance of pluripotency in the undifferentiated state with a robust response to differentiation signals, while utilizing p53 activity to maintain genomic stability and homeostasis in ESCs.
Costs of life - Dynamics of the protein inventory of Staphylococcus aureus during anaerobiosis
Authors: Zühlke Daniela , Dörries Kirsten , Bernhardt Jörg , Maaß Sandra , Muntel Jan , Liebscher Volkmar , Pané-Farré Jan , Riedel Katharina , Lalk Michael , Völker Uwe , Engelmann Susanne , Becher Dörte , Fuchs Stephan , Hecker Michael 
Published: June 2016

AbstractAbsolute protein quantification was applied to follow the dynamics of the cytoplasmic proteome of Staphylococcus aureus in response to long-term oxygen starvation. For 1,168 proteins, the majority of all expressed proteins, molecule numbers per cell have been determined to monitor the cellular investments in single branches of bacterial life for the first time. In the presence of glucose the anaerobic protein pattern is characterized by increased amounts of glycolytic and fermentative enzymes such as Eno, GapA1, Ldh1, and PflB. Interestingly, the ferritin-like protein FtnA belongs to the most abundant proteins during anaerobic growth. Depletion of glucose finally leads to an accumulation of different enzymes such as ArcB1, ArcB2, and ArcC2 involved in arginine deiminase pathway. Concentrations of 29 exo- and 78 endometabolites were comparatively assessed and have been integrated to the metabolic networks. Here we provide an almost complete picture on the response to oxygen starvation, from signal transduction pathways to gene expression pattern, from metabolic reorganization after oxygen depletion to beginning cell death and lysis after glucose exhaustion. This experimental approach can be considered as a proof of principle how to combine cell physiology with quantitative proteomics for a new dimension in understanding simple life processes as an entity.
The role of environmental constraints in walking: Effects of steering and sharp turns on gait dynamics
Authors: Dotov Dobromir G. , Bardy Benoît G. , Dalla Bella Simone 
Published: June 2016

AbstractStride durations in gait exhibit long-range correlation (LRC) which tends to disappear with certain movement disorders. The loss of LRC has been hypothesized to result from a reduction of functional degrees of freedom of the neuromuscular apparatus. A consequence of this theory is that environmental constraints such as the ones induced during constant steering may also reduce LRC. Furthermore, obstacles may perturb control of the gait cycle and also reduce LRC. To test these predictions, seven healthy participants walked freely overground in three conditions: unconstrained, constrained (constant steering), and perturbed (frequent 90° turns). Both steering and sharp turning reduced LRC with the latter having a stronger effect. Competing theories explain LRC in gait by positing fractal CPGs or a biomechanical process of kinetic energy reuse. Mediation analysis showed that the effect of the experimental manipulation in the current experiment depends partly on a reduction in walking speed. This supports the biomechanical theory. We also found that the local Hurst exponent did not reflect the frequent changes of heading direction. This suggests that the recovery from the sharp turn perturbation, a kind of relaxation time, takes longer than the four to seven meters between successive turns in the present study.