Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptosis in capillary endothelial cells in ageing skeletal muscle

The age‐related loss of skeletal muscle mass and function (sarcopenia) is a consistent hallmark of ageing. Apoptosis plays an important role in muscle atrophy, and the intent of this study was to specify whether apoptosis is restricted to myofibre nuclei (myonuclei) or occurs in satellite cells or stromal cells of extracellular matrix (ECM). Sarcopenia in mouse gastrocnemius muscle was characterized by myofibre atrophy, oxidative type grouping, delocalization of myonuclei and ECM fibrosis. Terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labelling (TUNEL) indicated a sharp rise in apoptosis during ageing. TUNEL coupled with immunostaining for dystrophin, paired box protein‐7 (Pax7) or laminin‐2α, respectively, was used to identify apoptosis in myonuclei, satellite cells and stromal cells. In adult muscle, apoptosis was not detected in myofibres, but was restricted to stromal cells. Moreover, the age‐related rise in apoptotic nuclei was essentially due to stromal cells. Myofibre‐associated apoptosis nevertheless occurred in old muscle, but represented < 20% of the total muscle apoptosis. Specifically, apoptosis in old muscle affected a small proportion (0.8%) of the myonuclei, but a large part (46%) of the Pax7+ satellite cells. TUNEL coupled with CD31 immunostaining further attributed stromal apoptosis to capillary endothelial cells. Age‐dependent rise in apoptotic capillary endothelial cells was concomitant with altered levels of key angiogenic regulators, perlecan and a perlecan domain V (endorepellin) proteolytic product. Collectively, our results indicate that sarcopenia is associated with apoptosis of satellite cells and impairment of capillary functions, which is likely to contribute to the decline in muscle mass and functionality during ageing.
Altered Synaptic Dynamics during Normal Brain Aging

What is the neuroanatomical basis for the decline in brain function that occurs during normal aging? Previous postmortem studies have blamed it on a reduction in spine density, though results remain controversial and spine dynamics were not assessed. We used chronic in vivo two-photon imaging of dendritic spines and axonal boutons in somatosensory cortex for up to 1 year in thy1 GFP mice to test the hypothesis that aging is associated with alterations in synaptic dynamics. We find that the density of spines and en passant boutons (EPBs) in pyramidal cells increases throughout adult life but is stable between mature (8–15 months) and old (>20 months) mice. However, new spines and EPBs are two to three times more likely to be stabilized over 30 d in old mice, although the long-term retention (over months) of stable spines is lower in old animals. In old mice, spines are smaller on average but are still able to make synaptic connections regardless of their size, as assessed by serial section electron microscopy reconstructions of previously imaged dendrites. Thus, our data suggest that age-related deficits in sensory perception are not associated with synapse loss in somatosensory cortex (as might be expected) but with alterations in the size and stability of spines and boutons observed in this brain area. The changes we describe here likely result in weaker synapses that are less capable of short-term plasticity in aged individuals, and therefore to less efficient circuits.
CDK6 protects epithelial ovarian cancer from platinum‐induced death via FOXO3 regulation

Epithelial ovarian cancer (EOC) is an infrequent but highly lethal disease, almost invariably treated with platinum‐based therapies. Improving the response to platinum represents a great challenge, since it could significantly impact on patient survival. Here, we report that silencing or pharmacological inhibition of CDK6 increases EOC cell sensitivity to platinum. We observed that, upon platinum treatment, CDK6 phosphorylated and stabilized the transcription factor FOXO3, eventually inducing ATR transcription. Blockage of this pathway resulted in EOC cell death, due to altered DNA damage response accompanied by increased apoptosis. These observations were recapitulated in EOC cell lines in vitro, in xenografts in vivo, and in primary tumor cells derived from platinum‐treated patients. Consistently, high CDK6 and FOXO3 expression levels in primary EOC predict poor patient survival. Our data suggest that CDK6 represents an actionable target that can be exploited to improve platinum efficacy in EOC patients. As CDK4/6 inhibitors are successfully used in cancer patients, our findings can be immediately transferred to the clinic to improve the outcome of EOC patients.
Spatiotemporal Consistency of Four Gross Primary Production Products and Solar‐Induced Chlorophyll Fluorescence in Response to Climate Extremes Across CONUS in 2012

Large spatial‐scale effects of climate extremes on gross primary production (GPP), the largest terrestrial carbon flux, are highly uncertain even as these extremes increase in frequency and extent. Here we report the impacts of spring warming and summer drought in 2012 on GPP across the contiguous United States (CONUS) using estimates from four GPP models: Vegetation Photosynthesis Model (VPM), MOD17A2H V006, Carnegie‐Ames‐Stanford Approach, and Simple Biosphere/Carnegie‐Ames‐Stanford Approach. VPM simulations are driven by Moderate Resolution Imaging Spectroradiometer, North American Regional Reanalysis climate data, and C3 and C4 cropland maps from the United States Department of Agriculture Cropland Data Layer data set. Across 25 eddy covariance flux tower sites, GPP estimates from VPM (GPPVPM) showed better accuracy in terms of cross‐site variability and interannual variability (R2 = 0.84 and 0.46, respectively) when compared to MOD17 GPP. We further assessed the spatial and temporal (seasonal) consistency between GPP products and the Global Ozone Monitoring Experiment‐2 solar‐induced chlorophyll fluorescence over CONUS during 2008–2014. The results suggested that GPPVPM agrees best with solar‐induced chlorophyll fluorescence across space and time, capturing seasonal dynamics and interannual variations. Anomaly analyses showed that increased GPP during the spring compensated for the reduced GPP during the summer, resulting in near‐neutral changes in annual GPP for the CONUS. This study demonstrates the importance of assessing the impacts of different types and timing of climate extremes on GPP and the need to improve light use efficiency models by incorporating C3 and C4 plant functional types.
Physics from Computer Science: a Position Statement

In this statement we provide some examples of transdisciplinaryjourneys, from one ﬁeld to another, and back. In particular, thequantuminformaticendeavoris not just a matter of feedingphys-ical theory into the general ﬁeld of natural computation, bu t alsoone of using high-level methods developed in Computer Scienceto improve on the quantum physical formalism itself, and theunderstanding thereof. We highlight a seemingly contradictoryphenomenon: passing to an abstract, categorical quantum infor-matic formalism leads directly to a simple and elegant graphicalformulation of quantum theory itself, which for example makesthe design of some importantquantuminformaticprotocolscom-pletely transparent. It turns out that essentially all of the quan-tum informatic machinery can be recovered from this graphicalcalculus. But in turn, this graphical formalism provides a bridgebetween methods of logic and computer science, and some of themost exciting developments in the mathematics of the past twodecades: namely those arising from the Jones polynomial invari-ant of knots and links, the Temperley-Lieb Algebra and relatedstructures.
Epigallocatechin Gallate Inhibits Biofilm Formation by Ocular Staphylococcal Isolates

ABSTRACT Epigallocatechin gallate (EGCg), the main polyphenol component of green tea, has several antibacterial properties. Here we show that sub-MICs of EGCg appear to decrease slime production, therefore inhibiting biofilm formation by ocular staphylococcal isolates previously characterized for the presence of ica genes by the Congo red agar plate assay and for adhesion to microtiter plates.
Local Conformational Stability of HIV-1 gp120 in Unliganded and CD4-Bound States as Defined by Amide Hydrogen/Deuterium Exchange

ABSTRACT The binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (P value = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction.
Cell-to-cell HIV-1 spread and its implications for immune evasion

Purpose of reviewThe ability of HIV-1 to move between cells via direct cell–cell transmission is currently receiving a lot of attention. This review will discuss cell–cell spread of HIV-1 in terms of cellular and molecular mechanisms and will consider the evidence for immune and therapeutic evasion. Recent findingsRecent studies relating to the cell biology of HIV-1 cell–cell spread have sparked considerable renewed interest in the field. However, questions are being raised concerning both the mechanisms of viral spread between immune cells and the implications for immune evasion. SummaryThe re-emergence of HIV-1 cell–cell spread as a highly efficient mechanism for viral dissemination in vitro has raised the possibility that this finding may be central to viral spread in vivo and may strongly influence pathogenesis.
Ecophenotypic variability during times of evolutionary stasis in Middle Devonian Actinopteria (Bivalvia, Pterioidea) from New York

Abstract. We examine the morphological variation of a Paleozoic pterineid during a time of relative ecological and taxonomic stability in the Middle Devonian Appalachian Basin in central and eastern New York. We discuss the taxonomic status of the Middle Devonian bivalve Actinopteria boydi (Conrad, 1842) and quantify the variability of its shell disk as well as the width and angle of the auricles and sulci of this otherwise character-poor bivalve species using geometric morphometric techniques employing Cartesian landmarks. We compare variants from three stratigraphic levels (Skaneateles, Ludlowville, and Moscow formations) and from different habitats characterized by lithofacies. The phenotypic variation observed in our data does not amount to an overall directional shift in morphology, i.e., they constitute reversible changes of morphology in a single variable taxon. Our study finds small-scale variation in morphology that represents evidence for ecophenotypic variation through ~3–4 Myr. Differences in substrate coupled with water energy seem to impact this taxon's morphology. Although no clearly separated groups can be observed, material from muddy facies develops variants with, on average, rounder and broader shell disks than are found in material from silty facies. This morphology could have increased the flow rate of water channeled over the posterior shell portion thereby improving filtration rate, which is especially beneficial in environments with low water energy.
Association of motor milestones, SMN2 copy and outcome in spinal muscular atrophy types 0–4

Proximal hereditary spinal muscular atrophy (SMA) is caused by homozygous deletion of the survival motor neuron (SMN) 1 gene and has a wide range of severity.1 Onset may occur prenatally up to the fourth decade of life, and motor deficits range from neonatal hypotonia to mild weakness in adulthood. The current classification of SMA distinguishes five SMA types (ie, type 0–4) based on the combination of age at onset and two acquired gross motor milestones.1 ,2 Distinction of additional subtypes based on differences in the age at onset, first for SMA type 3 (ie, 3a and 3b) and more recently for type 1 (ie, 1a–1c), has been proposed. This may help to further clarify differences in prognosis within SMA types and to balance baseline characteristics in clinical trials. We aimed to gain further insight into the added predictive value of motor milestones for the occurrence of SMA outcome or common complications, that is, death, respiratory insufficiency, scoliosis surgery and loss of ambulation. We included SMN2 copy number in our analysis, since this is the most important genetic biomarker of severity.3 We enrolled patients with SMA types 1–4 between September 2010 and August 2014. Methods are described in the online supplementary file. The clinical diagnosis of SMA was genetically confirmed in 200 patients. SMN2 copy number varied from 1 to 5 and overlapped between SMA types. SMN2 copy number correlated inversely with SMA type (p<0.001; table 1). Clinical characteristics are summarised in table 1. View this table: Table 1 Patient characteristics ### supplementary file [jnnp-2016-314292supp.pdf] Motor milestones defined SMA type 1–3 in case of discrepancies with age of onset. SMA classification was eventually changed in 18 patients (9%) because of acquisition of new motor milestones. We included 42 patients with SMA type 1 (table 1). Three patients had the most severe phenotype, type 0/1a, …
Cell surface shaving of Candida albicans biofilms, hyphae, and yeast form cells

We used a brief trypsin treatment followed by peptide separation and identification using nano‐LC followed by off‐line MS/MS to identify the surface proteins on live Candida albicans organisms growing in biofilms and planktonic yeast cells and hyphae. One hundred thirty‐one proteins were present in at least two of the three replicates of one condition and distributed in various combinations of the three growth conditions. Both previously reported and new surface proteins were identified and these were distributed between covalently attached proteins and noncovalently attached proteins of the cell wall.
Platelet-rich plasma.

Blood is first drawn from a patient with a syringe using sterile technique and then centrifuged (spun) and separated out into three layers. The bottom layer is made up of red blood cells, the middle layer consists of platelets and white blood cells and the top layer is plasma. The total volume of platelet rich plasma that is collected is approximately 5millileters or one teaspoon. Once it is prepared it is stable for up to eight hours, however once it is “activated” it must be used within ten minutes. The PRP is then delivered directly to the area of injury, and often times used with the assistance of an ultrasound machine. UNC
A Multidimensional Model of Venture Growth

An integrated model of venture growth isdeveloped based on management theory, organizational behavior theory,organization theory, and entrepreneurship models. The model is tested by gathering responses from 307 companies from the architectural wood working industry. Five research domains are identified as antecedents to venture performance: personality traits and general motives, personal competencies, situationally specific motivation, competitive strategies, and the business environment. Goals of the research are: (1) to test whether a multi-level model that sampled relevant concepts from individual, organizational, and environmental domains would predict firm performance successfully; (2) to test whether each domainwould contribute something to the prediction, and (3) to explore alternativeforms of the relationship among the domains and performance. Findings indicate that individual, organizational, and environmental research domains predict venture growth better when the connection of complex indirect relationships among them is included than when only multiple simultaneous direct effects are studied. In addition, it is found that all the domains enter into the prediction of venture growth when these total effects are considered, indicating that venture growth cannot be adequately explained from a single perspective. (JSD)
Leaf Vitamin C Contents Modulate Plant Defense Transcripts and Regulate Genes That Control Development through Hormone Signaling Online version contains Web-only data. Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.010538.

Vitamin C deficiency in the Arabidopsis mutant vtc1 causes slow growth and late flowering. This is not attributable to changes in photosynthesis or increased oxidative stress. We have used the vtc1 mutant to provide a molecular signature for vitamin C deficiency in plants. Using statistical analysis, we show that 171 genes are expressed differentially in vtc1 compared with the wild type. Many defense genes are activated, particularly those that encode pathogenesis-related proteins. Furthermore, transcript changes indicate that growth and development are constrained in vtc1 by the modulation of abscisic acid signaling. Abscisic acid contents are significantly higher in vtc1 than in the wild type. Key features of the molecular signature of ascorbate deficiency can be reversed by incubating vtc1 leaf discs in ascorbate. This finding provides evidence that many of the observed effects on transcript abundance in vtc1 result from ascorbate deficiency. Hence, through modifying gene expression, vitamin C contents not only act to regulate defense and survival but also act via phytohormones to modulate plant growth under optimal conditions.
Anticipatory affect during action preparation: evidence from backward compatibility in dual-task performance

ABSTRACT Upcoming responses in the second of two subsequently performed tasks can speed up compatible responses in the temporally preceding first task. Two experiments extend previous demonstration of such backward compatibility to affective features: responses to affective stimuli were faster in Task 1 when an affectively compatible response effect was anticipated for Task 2. This emotional backward-compatibility effect demonstrates that representations of the affective consequences of the Task 2 response were activated before the selection of a response in Task 1 was completed. This finding is problematic for the assumption of a serial stimulus-response translation stage. It also shows that the affective consequence of a response is anticipated during, and has an impact on stimulus-response translation, which implies that action planning considers codes representing and predicting the emotional consequences of actions. Implications for the control of emotional actions are discussed.
Quantifying mountain system recharge in the upper San Pedro basin, Arizona, Using geochemical tracers

Use of geochemical tracers has improved our conceptual and quantitative understanding of mountain system recharge (MSR) in the Upper San Pedro Basin, Arizona. These isotopic, major anion, and noble gas tracers resolved the location, rate and seasonality of recharge as well as groundwater flowpaths and residence times. Detectable anthropogenic C and tritium revealed less than 50 years residence times for the fast fraction of flow on the mountain block and in riparian areas. Maximum C residence times of over 10,000 years occurred for basin groundwater entering the San Pedro River riparian area. Groundwater fluxes determined from C imply MSR rates between 2 × 10 m/yr and 9 × 10 m/yr. Stable isotopic signatures indicate that MSR has a 40-90% contribution from winter precipitation and a 10-60% contribution from summer precipitation. Geochemical data is recommended to help calibrate groundwater flow models and substantially reduce uncertainty in the estimated MSR rate.
Sympathetically Mediated Changes in Capacitance: Redistribution of the Venous Reservoir as a Cause of Decompensation

“To be accepted as a paradigm, a theory must seem better than its competitors, but it need not, and in fact never does, explain all the facts with which it can be confronted. ” Thomas Kuhn, The Structure of Scientific Revolutions ### Heard on Rounds “A 57-year-old patient with a history of heart failure states that she began experiencing worsening shortness of breath 4 days prior to admission, with lower extremity edema developing 1 day prior to admission. She is compliant with her medications, though has had similar admissions previously. She states that her weight at home increased by “a couple of pounds” 2 days ago and that she increased her diuretic dose but her symptoms worsened. She says that she generally adheres to her low salt diet, but admits to eating pretzels 5 days ago. The physical examination showed BP 136/84, HR 94, weight 3 lbs above baseline, elevated JVP, basilar rales, and 1+ pedal edema. ” As the intern finishes the presentation, the Senior expresses surprise that the patient's weight had increased only 3 pounds, and comments about salt and volume overload leading to acute decompensated heart failure (ADHF). The Attending adds that recent data reveal that many patients presenting with ADHF have minimal or no weight gain, but that there is no clear mechanism to explain this phenomenon. They set in place plans for diuresis, increasing vasodilators, and further patient education. On the surface, there is nothing remarkable about this case, and the usual approaches to treat this entity have remained remarkably consistent since the advent of loop diuretics over 50 years ago: salt restriction, patient education, uptitration of medications if not already at optimal doses, and diuresis. However, approximately 1 in 4 such patients are readmitted to the hospital within 30 days,1 and the disease continues to progress. It is clear …
Determination of Phenolic Content in Different Barley Varieties and Corresponding Malts by Liquid Chromatography-diode Array Detection-Electrospray Ionization Tandem Mass Spectrometry

A simple and reliable method for the simultaneous determination of nine phenolic compounds in barley and malted barley was established, using liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS). The phenolic compounds can be easily detected with both systems, despite significant differences in sensitivity. Concentrations approximately 180-fold lower could be achieved by mass spectrometry analysis compared to diode array detection, especially for the flavan-3-ols (+)-catechin and (−)-epicatechin, which have poor absorptivity in the UV region. Malt samples were characterized by higher phenolic content comparing to corresponding barley varieties, revealing a significant increase of the levels of (+)-catechin and (−)-epicatechin during the malting process. Moreover, the industrial malting is responsible for modification on the phenolic profile from barley to malt, namely on the synthesis or release of sinapinic acid and epicatechin. Accordingly, the selection of the malting parameters, as well as the barley variety plays an important role when considering the quality and antioxidant stability of beer.