Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational analysis of the vesicular stomatitis virus glycoprotein G for membrane fusion domains

The spike glycoprotein G of vesicular stomatitis virus (VSV) induces membrane fusion at low pH. We used linker insertion mutagenesis to characterize the domain(s) of G glycoprotein involved in low-pH-induced membrane fusion. Two or three amino acids were inserted in frame into various positions in the extracellular domain of G, and 14 mutants were isolated. All of the mutants expressed fully glycosylated proteins in COS cells. However, only seven mutant G glycoproteins were transported to the cell surface. Two of these mutants, D1 and A6, showed wild-type fusogenic properties. The mutant A2 had a temperature-sensitive defect in the transport of the mutant G glycoprotein to the cell surface. The other four mutants, H2, H5, H10, and A4, although present in cell surface, failed to induce cell fusion when cells expressing these mutant glycoproteins were exposed to acidic pH. These four mutant G proteins could form trimers, indicating that the defect in fusion was not due to defective oligomerization. One of these mutations, H2, is within a region of conserved, uncharged amino acids that has been proposed as a possible fusogenic sequence. The mutation in H5 was about 70 amino acids downstream of the mutation in H2, while mutations in H10 and A4 were about 300 amino acids downstream of the mutation in H2. Conserved sequences were also noted in the H10 and A4 segment. The results suggest that in the case of VSV G glycoprotein, the fusogenic activity may involve several spatially separated regions in the extracellular domain of the protein.
Neuronal Inputs and Outputs of Aging and Longevity

An animal’s survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging.
The Value of Aneurysm Volume and Myocardial Strain Rate for Evaluating Cardiac Function of Ischemia‐Related Left Ventricular Aneurysm in a Rabbit Model Using Real Time Three‐Dimensional Echocardiographic Imaging Combined with Speckle Tracking Imaging

The aim of this study was to evaluate the effect of left ventricular aneurysm (LVA) volume and myocardial strain on left ventricular function in a rabbit model using real time three‐dimensional echocardiographic imaging (RT‐3DE) combined with two‐dimensional speckle tracking imaging (2D‐STI).
Lipopolysaccharide (LPS)-induced Macrophage Activation and Signal Transduction in the Absence of Src-Family Kinases Hck, Fgr, and Lyn

Lipopolysaccharide (LPS) stimulates immune responses by interacting with the membrane receptor CD14 to induce the generation of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6. The mechanism by which the LPS signal is transduced from the extracellular environment to the nuclear compartment is not well defined. Recently, an increasing amount of evidence suggests that protein tyrosine kinases especially the Src-family kinases Hck, Fgr, and Lyn, play important roles in LPS signaling. To directly address the physiological function of Hck, Fgr and Lyn in LPS signaling, a genetic approach has been used to generate null mutations of all three kinases in a single mouse strain. hck −/− fgr −/− lyn −/− mice are moderately healthy and fertile; macrophages cultured from these mice express normal levels of CD14 and no other Src-family kinases were detected. Although the total protein phosphotyrosine level is greatly reduced in macrophages derived from hck −/− fgr −/− lyn −/− mice, functional analyses indicate that both elicited peritoneal (PEMs) and bone marrow–derived macrophages (BMDMs) from triple mutant mice have no major defects in LPS-induced activation. Nitrite production and cytokine secretion (IL-1, IL-6, and TNF-α) are normal or even enhanced in hck −/− fgr −/− lyn −/− macrophages after LPS stimulation. The development of tumor cell cytotoxicity is normal in triple mutant BMDMs and only partially impaired in PEMs after LPS stimulation. Furthermore, the activation of the ERK1/2 and JNK kinases, as well as the transcription factor NF-κB, are the same in normal and mutant macrophages after LPS stimulation. The current study provides direct evidence that three Src-family kinases Hck, Fgr, and Lyn are not obligatory for LPS-initiated signal transduction.
The Arabidopsis thaliana Type I Isopentenyl Diphosphate Isomerases Are Targeted to Multiple Subcellular Compartments and Have Overlapping Functions in Isoprenoid Biosynthesis[W]

To form the building blocks of isoprenoids, isopentenyl diphosphate (IPP) isomerase activity, which converts IPP to dimethylallyl diphosphate (DMAPP), appears to be necessary in cytosol, plastids, and mitochondria. Arabidopsis thaliana contains only two IPP isomerases (Isopentenyl Diphosphate Isomerase1 [IDI1] and IDI2). Both encode proteins with N-terminal extensions similar to transit peptides and are expressed in all organs, with IDI1 less abundant than IDI2. Examination of enhanced green fluorescent protein fusions established that IDI1 is mainly in the plastid, whereas IDI2 is mainly in the mitochondria. Both proteins are also in the cytosol as a result of their translation from naturally occurring shorter transcripts lacking transit peptides, as demonstrated by 5′ rapid amplification of cDNA ends cloning. IPP isomerase activity in the cytosol was confirmed by uniform labeling of IPP- and DMAPP-derived units of the cytoplasmic isoprenoid product, sitosterol, when labeled mevalonate was administered. Analysis of mutant lines showed that double mutants were nonviable, while homozygous single mutants had no major morphological or chemical differences from the wild type except for flowers with fused sepals and underdeveloped petals on idi2 mutants. Thus, each of the two Arabidopsis IPP isomerases is found in multiple but partially overlapping subcellular locations, and each can compensate for the loss of the other through partial redundancy in the cytosol.
Implementing a Pathway for the Management of Acute Coronary Syndrome Leads to Improved Compliance With Guidelines and a Decrease in Angina Symptoms

&NA; We describe our experience with the Advanced Cardiac Admission Program (ACAP) at our institution. The ACAP program is a hospital‐wide implementation of critical pathways‐based management of all cardiac patients. Data review of patients admitted for acute coronary syndromes from the ACAP–PAIN database and a comparative study of outcomes before and after implementation of the pathways‐based assessment and treatment protocols. In the pre‐ACAP and post‐ACAP patient groups, antiplatelet use at admission improved from 50% to 75% (p<.01), ACE‐I use improved from 32% to 54% (p<.0001), statins use increased from 35% to 62% (p<.0001), and smoking cessation awareness increased from 15% to 86% (p<.0001). At 1‐year follow‐up, 84% of patients with CAD were treated with statins, and 47% had LDL cholesterol <100 mg/dL, compared with 20% and 9%, respectively, with conventional treatment before ACAP implementation (p<.0001). Recurrent angina symptoms and nonfatal myocardial infarction rates decreased from 28.5% to 13% (p=.02), and 15% to 5% (p=0.03), respectively. Pathway‐based programs like ACAP significantly enhance administration of guidelines‐based cardioprotective medications both during hospital stay and at 1‐year follow‐up.
Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes.
ANN and MLR Model of Specific Fuel Consumption for Pyrolysis Oil Blended with Diesel used in a Single Cylinder Diesel Engine: A Comparative Study

The main objective of the research is to compare the accurateness of Artificial Neural Networks (ANN) and Multiple Linear Regressions (MLR) model for Specific Fuel Consumption for pyrolysis oil blended with diesel used in a single cylinder diesel engine. In this study, parameters i.e. Injection Timing, Injection Pressure, Compression Ratio, and Load are taken. Artificial Neural Networks (ANN) and Multiple Linear Regressions (MLR) models were prepared using the results of Experiments to predict Specific Fuel Consumption for pyrolysis oil blended with diesel used in a single cylinder diesel engine. The results show that ANN prediction is more accurate than MLR prediction.
A field study on the usability of a nearby search app for finding and exploring places and events

Commercial apps for nearby search on mobile phones such as Qype, AroundMe, Foursquare, or Wikitude have gained huge popularity among smartphone users. Understanding the way how people use and interact with such applications is fundamental for improving the functionality and the user interface design. In our two-step field study, we developed and evaluated mobEx, a mobile app for faceted exploration of social media data on Android phones. mobEx unifies the data sources of related commercial applications in the market by retrieving information from various providers. The goal of our study was to find out, if the subjects understood the metaphor of a time-wheel as novel user interface feature for finding and exploring places and events and how they use it. In addition, mobEx offers a grid-based navigation menu and a list-based navigation menu for exploring the data. Here, we were interested in gaining some qualitative insights about which type of navigation approach the users prefer when they can choose between them. We have collected qualitative user feedback via questionnaires. We also conducted a quantitative user study, where we evaluated user-generated logging data over a period of three weeks with a group of 18 participants. Our results show that the time-wheel can serve as an intuitive way to explore timedependent resources such as events. In addition, it seems that the grid-based navigation approach is the preferable choice when exploring large spaces of faceted data.
Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis.

OBJECTIVE To evaluate the prognostic utility of serum COMP level measured with a new sandwich ELISA, by correlating COMP level with outcome measures of osteoarthritis (OA) progression. DESIGN Patients (N=48) had symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-III and met ACR criteria. These patients were evaluated prospectively as part of a double-blind drug trial of 3 years' duration and represented the placebo arm of the study. Serum COMP levels were measured by sandwich ELISA with monoclonal antibodies 16-F12 and 17-C10 at baseline and at study end and levels were correlated with changes in (1) joint space width (JSW), (2) K-L grade, (3) Lequesne, and (4) WOMAC indices, over 3 years. RESULTS The change in JSW over 3 years, summed for both knees, correlated positively with serum COMP level at baseline as well as at study end. Patients were sorted by level of progression based upon a change in K-L grade summed for both knees over 3 years; patients who progressed by two K-L grades were shown to have had significantly higher COMP levels at baseline as well as at study end. Baseline and study end COMP levels did not correlate with the change of Lequesne or WOMAC indices. Baseline COMP levels correlated strongly with end serum COMP levels. CONCLUSION Serum COMP has the potential to be a prognostic marker of disease progression. High COMP levels, persisting over the 3-year study period in the patients with radiographic progression, indicated differences in disease activity detectable throughout the entire follow-up interval.
Predicting Fluid Responsiveness by Passive Leg Raising: A Systematic Review and Meta-Analysis of 23 Clinical Trials*

Objective:Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables. Data Sources:PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles. Study Selection:Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders. Data Extraction:Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve. Data Synthesis:Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79–92), pooled specificity of 92% (95% CI, 88–96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92–0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising–induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% [95% CI, 44–70] and specificity of 83% [95% CI, 68–92] vs sensitivity of 85% [95% CI, 78–90] and specificity of 92% [95% CI, 87–94], respectively; p < 0.001). Conclusions:Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising–induced change in a flow variable.
CXCR3/CXCR3 Ligand Biological Axis Impairs RENCA Tumor Growth by a Mechanism of Immunoangiostasis1

Metastatic renal cell carcinoma (RCC) responds poorly to chemo- or radiation therapy but appears to respond to systemic immunotherapy (i.e., IL-2 and/or IFN-α), albeit with only 5–10% durable response. The CXCR3/CXCR3 ligand biological axis plays an important role in mediating type 1 cytokine-dependent cell-mediated immunity, which could be beneficial for attenuating RCC if optimized. We found that systemic IL-2 induced the expression of CXCR3 on circulating mononuclear cells but impaired the CXCR3 ligand chemotactic gradient from plasma to tumor by increasing circulating CXCR3 ligand levels in a murine model of RCC. Moreover, the antitumor effect of systemic IL-2 was CXCR3-dependent, as IL-2 failed to inhibit tumor growth and angiogenesis in CXCR3−/− mice. We hypothesized that the immunotherapeutic effect of the CXCR3/CXCR3 ligand biological axis could be optimized by first priming with systemic IL-2 to induce CXCR3 expression on circulating mononuclear cells followed by enhancing the intratumor CXCR3 ligand levels to establish optimal CXCR3-dependent chemotactic gradient. We found that combined systemic IL-2 with an intratumor CXCR3 ligand (CXCL9) lead to significantly greater reduction in tumor growth and angiogenesis, increased tumor necrosis, and increased intratumor infiltration of CXCR3+ mononuclear cells, as compared with either IL-2 or CXCL9 alone. The enhanced antitumor effect of the combined strategy was associated with a more optimized CXCR3-dependent chemotactic gradient and increased tumor-specific immune response. These data suggest that the combined strategy of systemic IL-2 with intratumor CXCR3 ligand is more efficacious than either strategy alone for reducing tumor-associated angiogenesis and augmenting tumor-associated immunity, the concept of immunoangiostasis.
Binding of Citreoviridin to Human Serum Albumin: Multispectroscopic and Molecular Docking

Citreoviridin (CIT), a mycotoxin produced by Penicillium citreonigrum, is a common contaminant of wide range of agriproducts and detrimental to human and animal health. In this study, the interaction of CIT with human serum albumin (HSA) is researched by steady-state fluorescence, ultraviolet-visible (UV-Vis) absorption, circular dichroism (CD) methods, and molecular modeling. The association constants, binding site numbers, and corresponding thermodynamic parameters are used to investigate the quenching mechanism. The alternations of HSA secondary structure in the presence of CIT are demonstrated with UV-Vis, synchronous fluorescence, and CD spectra. The molecular modeling results reveal that CIT can bind with hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is obtained via fluorescence resonance energy transfer method.
Zika Virus Promotes Neuronal Cell Death in a Non-Cell Autonomous Manner by Triggering the Release of Neurotoxic Factors

Zika virus (ZIKV) has recently caused a worldwide outbreak of infections associated with severe neurological complications, including microcephaly in infants born from infected mothers. ZIKV exhibits high neurotropism and promotes neuroinflammation and neuronal cell death. We have recently demonstrated that N-methyl-d-aspartate receptor (NMDAR) blockade by memantine prevents ZIKV-induced neuronal cell death. Here, we show that ZIKV induces apoptosis in a non-cell autonomous manner, triggering cell death of uninfected neurons by releasing cytotoxic factors. Neuronal cultures infected with ZIKV exhibit increased levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and glutamate. Moreover, infected neurons exhibit increased expression of GluN2B and augmented intracellular Ca2+ concentration. Blockade of GluN2B-containing NMDAR by ifenprodil normalizes Ca2+ levels and rescues neuronal cell death. Notably, TNF-α and IL-1β blockade decreases ZIKV-induced Ca2+ flux through GluN2B-containing NMDARs and reduces neuronal cell death, indicating that these cytokines might contribute to NMDAR sensitization and neurotoxicity. In addition, ZIKV-infected cultures treated with ifenprodil exhibits increased activation of the neuroprotective pathway including extracellular signal-regulated kinase and cAMP response element-binding protein, which may underlie ifenprodil-mediated neuroprotection. Together, our data shed some light on the neurotoxic mechanisms triggered by ZIKV and begin to elucidate how GluN2B-containing NMDAR blockade can prevent neurotoxicity.
The Influence of Learning on Evolution: A Mathematical Framework

The Baldwin effect can be observed if phenotypic learning influences the evolutionary fitness of individuals, which can in turn accelerate or decelerate evolutionary change. Evidence for both learning-induced acceleration and deceleration can be found in the literature. Although the results for both outcomes were supported by specific mathematical or simulation models, no general predictions have been achieved so far. Here we propose a general framework to predict whether evolution benefits from learning or not. It is formulated in terms of the gain function, which quantifies the proportional change of fitness due to learning depending on the genotype value. With an inductive proof we show that a positive gain-function derivative implies that learning accelerates evolution, and a negative one implies deceleration under the condition that the population is distributed on a monotonic part of the fitness landscape. We show that the gain-function framework explains the results of several specific simulation models. We also use the gain-function framework to shed some light on the results of a recent biological experiment with fruit flies.
Multiple access channels with combined cooperation and partial cribbing

In this paper we study the multiple access channel (MAC) with combined cooperation and partial cribbing and characterize its capacity region. Cooperation means that the two encoders send a message to one another via a rate-limited link prior to transmission, while partial cribbing means that each of the two encoders obtains a deterministic function of the other encoder's output with or without delay. Prior work in this field dealt separately with cooperation and partial cribbing. However, by combining these two methods we can achieve significantly higher rates. Remarkably, the capacity region does not require an additional auxiliary random variable (RV) since the purpose of both cooperation and partial cribbing is to generate a common message between the encoders. In the proof we combine methods of block Markov coding, backward decoding, double rate-splitting, and joint typicality decoding. Furthermore, we present the Gaussian MAC with combined one-sided cooperation and quantized cribbing. For this model, we give an achievability scheme that shows how many cooperation or quantization bits are required in order to achieve a Gaussian MAC with full cooperation/cribbing capacity region. After establishing our main results, we show that in a state-dependent MAC with cooperation, where the state is known at a partially cribbing encoder and at the decoder, only one auxiliary RV is needed to incorporate both the cribbing and the cooperation. However, there are cases where more than one auxiliary RV is needed, e.g., when the cooperation and cribbing are not used for the same purposes. We present a MAC with an action-dependent state where the action is based on the cooperation but not on the cribbing. Therefore, in this case more than one auxiliary RV is needed. We deduce a general rule for this result.