Miracle-dz/UniFAR-FTUs huggingface dataset:
Limb functional recovery is impaired in fibroblast growth factor-2 deficient (FGF2) mice despite chronic ischemia-induced vascular growth

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2−/ −), developmental vessel growth or ischemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischemic injury. Wildtype (WT) or Fgf2−/− mice were subjected to hindlimb ischemia for up to 42-days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischemic limbs at various timepoints. Recovery of ischemic limb function was delayed in Fgf2−/− mice. Yet, vascular growth response to ischemia was similar between WT and Fgf2−/− hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2−/− ischemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2−/− ischemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischemic injury and delays functional limb use. the underlying functional defect of wound that the loss of Fgf2 expression. In parallel, these inflammatory cells secreted ECM remodeling proteins that may also be destructive to ischemic limb recovery. These results support a more nuanced role for Fgf2 expression in the ischemic mouse hindlimb beyond regulation of vascular growth.
Quantum Fields on BTZ Black Holes

In this thesis we investigate some aspects of Quantum Fields on BTZ black holes in 1+1 and 1+2 dimensions. More specifically, we study how a ground state in AdS spacetime becomes a thermal state when restricted to the exterior region of the BTZ black hole. This ground state is for the quantum linear real scalar field which satisfies the Klein-Gordon equation and also, in the 1+2 dimensional case, for a general QFT satisfying the axioms of Algebraic Quantum Field Theory in Curved Spacetime. We also study how these states map to states on the conformal boundary of AdS spacetime. In order to do this we use Algebraic Holography, Boundary-limit Holography and Pre-Holography. As a preparation, we give an exposition of AdS spacetime, we review the principal aspects of the 1+1 and 1+2 dimensional BTZ black holes and their mapping to the boundary of AdS spacetime. In both cases they map to part of the boundary of AdS spacetime. In the 1+1 case we find that the restriction of the equivalent global vacuum or the Poincar\'{e} vacuum on the boundary becomes a thermal state (KMS state) when restricted to the BTZ black hole. In the 1+2 case we find that the Poincar\'{e} vacuum becomes a thermal state too when restricted to the exterior of the BTZ black hole. In both cases the temperature of the state is $\textsf{T}=\frac{\kappa}{2\pi}$, where $\kappa$ is the surface gravity. In 1+2 dimensions we give as a concrete model the quantum linear real scalar field. When we study these states in the boundary of AdS spacetime we use standard techniques of Conformal Field Theory. One of the main conclusions we get from our investigation is that in certain sense the Hawking effect in the eternal BTZ black hole maps to the Unruh effect on the boundary of AdS spacetime. In the final part of this thesis we study the brick wall model for these black holes for the quantum linear real scalar field. In both cases we obtain the two point function for the vacuum and thermal states in the bulk and on the boundary. We also study the expectation value of the renormalized energy-momentum tensor in 1+1 dimensions for the conformal massless quantum real scalar field. Most of this thesis fits in the framework of AdS/CFT in QFT which is more limited than AdS/CFT correspondence in string theory.
Rapid evolution of in vivo -selected sequences and structures replacing twenty percent of a subviral RNA

The 356 nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) is composed of 5 ′ sequences from a second TCV satRNA (satD) and 3 ′ sequences derived from TCV. SHAPE structure mapping revealed that 76 nt in the poorly-characterized satD-derived region form an extended hairpin (H2). Pools of satC in which H2 was replaced with 76, 38, or 19 random nt were co-inoculated with TCV helper virus onto plants and satC fitness assessed using in vivo functional selection (SELEX). The most functional progeny satCs, including one as fit as wild-type, contained a 38-39 nt H2 region that adopted a hairpin structure and exhibited an increased ratio of dimeric to monomeric molecules. Some progeny of satC with H2 deleted featured a duplication of 38 nt, partially rebuilding the deletion. Therefore, H2 can be replaced by a 38-39 nt hairpin, sufficient for overall structural stability of the 5 ′ end of satC.
Commonly Used Surrogates for Baseline Renal Function Can Impact Acute Kidney Injury Classification and Prognosis

Studies of acute kidney injury (AKI) commonly lack data on pre-admission renal function, often substituting an inpatient or imputed serum creatinine (SCr) as an estimate for “baseline” renal function. We examined the error introduced when applying methods to estimate “baseline” on AKI classification and mortality. Within a cohort of 4863 adults with a known outpatient baseline admitted to Vanderbilt University Hospital between 10/07 and 10/08, the following surrogates were studied: (1) an eGFR of 75 ml/min/1.73m 2 as suggested by the Acute Dialysis Quality Initiative (ADQI), (2) a minimum inpatient SCr, and (3) the first admission SCr. We calculated AKI incidence and mortality rates using each surrogate, and assessed their ability to correctly classify AKI incidence and mortality compared to the most recent outpatient SCr between 7-365 days before admission. Using both imputed and minimum baseline SCr values inflated AKI incidence (38.3% and 35.9% vs. 25.5%; p<0.001), reflecting low specificities of 77% and 80%, respectively. In contrast, using an admission SCr baseline underestimated AKI incidence (13.7% vs. 25.5%, p<0.001), demonstrating a low sensitivity of 39%. Using any surrogate led to frequent misclassification of patient deaths as following AKI and differences for both in-hospital and 60-day mortality rates. In summary, commonly used surrogates for baseline SCr result in bi-directional misclassification of AKI incidence and prognosis in a hospitalized setting.
Cdc42 controls progenitor cell differentiation and (cid:1) -catenin turnover in skin

Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of (cid:1) -catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3 (cid:1) . Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of (cid:1) -catenin. In the absence of Cdc42, degradation of (cid:1) -catenin was increased corresponding to a decreased phosphorylation of GSK3 (cid:1) at Ser 9 and an increased phosphorylation of axin, which is known to be required for binding of (cid:1) -catenin to the degradation machinery. Cdc42-mediated regulation of (cid:1) -catenin turnover was completely dependent on PKC (cid:2) , which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of (cid:1) -catenin turnover is important for terminal differentiation of HF progenitor cells in vivo. GSK3 (cid:1) is part of a multiprotein complex that contains, among other molecules, APC and axin. Wnt signaling via the frizzled (Frz)-LPR receptor inhibits via disheveled (dsh) GSK3 (cid:1) activity, increasing the concentration of cytosolic (cid:1) -catenin. ( A ) Activated Cdc42 can bind to a cytosolic complex of Par6–Par3–PKC (cid:2) , leading to inhibition of GSK3 (cid:1) activity by PKC (cid:2) -dependent phosphorylation of GSK3 (cid:1) . This leads to reduced phosphorylation of axin and decreased phosphorylation and degradation of (cid:1) -catenin. Free cytosolic (cid:1) -catenin can then go to the nucleus and, together with a transcription factor of the LEF/TCF family (LEF-1), induce the expression of HF-specific genes. ( B ) Loss of Cdc42 results in a reduced phosphorylation and an increased activity of GSK3 (cid:1) . This leads to an increased phosphorylation of axin, an increased degradation of free (cid:1) -catenin and, consequently, decreased levels of nuclear (cid:1) -catenin so that HF-specific genes cannot be induced. Instead, the default pathway of epidermal differentiation is used. Since plakoglobin is degraded by the same pathway as (cid:1) -catenin, plakoglobin is also decreased in the absence of Cdc42, resulting in a reduction of junctional (cid:1) -catenin and plakoglobin and, secondarily, a reduced transport of E-cadherin to the cell membrane. In suprabasal keratinocytes and in vitro, Akt activation compensates for the loss of Cdc42, leading to normal phosphorylation of GSK3 (cid:1) and normal levels of cytosolic (cid:1) -catenin.
Heme Causes Pain in Sickle Mice via Toll-Like Receptor 4-Mediated Reactive Oxygen Species- and Endoplasmic Reticulum Stress-Induced Glial Activation

Aims: Lifelong pain is a hallmark feature of sickle cell disease (SCD). How sickle pathobiology evokes pain remains unknown. We hypothesize that increased cell-free heme due to ongoing hemolysis activates toll-like receptor 4 ( TLR4 ), leading to the formation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Together, these processes lead to spinal microglial activation and neuroinﬂammation, culminating in acute and chronic pain. Results: Spinal heme levels, TLR4 transcripts, oxidative stress, and ER stress were signiﬁcantly higher in sickle mice than controls. In vitro , TLR4 inhibition in spinal cord microglial cells attenuated heme-induced ROS and ER stress. Heme treatment led to a time-dependent increase in the characteristic features of sickle pain (mechanical and thermal hyperalgesia) in both sickle and control mice; this effect was absent in TLR4-knockout sickle and control mice. TLR4 deletion in sickle mice attenuated chronic and hypoxia/reoxygenation (H/R)-evoked acute hyperalgesia. Sickle mice treated with the TLR4 inhibitor resatorvid; selective small-molecule inhibitor of TLR4 (TAK242) had signiﬁcantly reduced chronic hyperalgesia and had less severe H/R-evoked acute pain with quicker recovery. Notably, reducing ER stress with salubrinal ameliorated chronic hyperalgesia in sickle mice. Innovation: Our ﬁndings demonstrate the causal role of free heme in the genesis of acute and chronic sickle pain and suggest that TLR4 and/or ER stress are novel therapeutic targets for treating pain in SCD. Conclusion: Heme-induced microglial activation via TLR4 in the central nervous system contributes to the initiation and maintenance of sickle pain via ER stress in SCD. Antioxid. Redox Signal . 34, 279–293. TLR4 contributes to chronic hyperalgesia in sickle phenylindole; DHE, dihydroethidium; TEM, transmission electron microscopy. Color images are available online.
Character Identification as a Moderator of the Relationship Between Social Norms and Sexual Risk-Reduction Intentions and Behavior: Findings from an eHealth Entertainment-Education Intervention Targeting Men who Have Sex with Men

Normative based research found that norms are significant predictors of safe sex behavioral intentions and behavior. Research shows that group identity moderates the relationship between norms and intentions/behavior. The present study used the theory of normative social behavior to evaluate whether identification with characters in an HIV-prevention interactive video moderated the relationship between sexual risk-taking norms and risk reduction intentions/behavior. Participants included 540 men between the ages 18 and 30 enrolled in a randomized controlled trial with a 3-month follow-up. We found support for the hypothesized interaction. At low levels of character identification, the negative relationship between sexual risk-taking norms and risk reduction intentions was strong. However, as character identification increased, the link between norms and intentions became weaker. The mean intentions score of high risk norm participants was elevated to the level reported by low risk norm participants, demonstrating the favorable effect of character identification on narrative persuasion in entertainment-education. The utility of a social norms approach to health behavior change will be discussed in the context of eHealth interventions.
Cis and trans-acting elements involved in the activation of Arabidopsis thaliana Al gene encoding the translation elongation factor EF-1 a

In A. thaliana the translation elongation factor EF-1 a is encoded by a small multigenic family of four members (A1-A4). The Al gene promoter has been dissected and examined in a transient expression system using the GUS reporter gene. Deletion analysis has shown that several elements are involved in the activation process. One cis-acting domain, the TEF 1 box, has been accurately mapped 100 bp upstream of the transcription initiation site. This domain is the target for trans-acting factors identified in nuclear extracts prepared from A. thaliana. Homologies are found between the TEF 1 box and sequences present at the same location within the A2, A3 and A4 promoters. This observation, together with those obtained from gel retardation assays performed using DNA fragments from the A4 promoter, suggest that the activation process mediated by the TEF 1 element is conserved among the A. thaliana EF-1 a genes. Analysis of nearly full length cDNA clones has shown that in addition to a single intron located within the coding region, the Al gene contains a second intron located within the 5' non coding region. Such an intron is also present within the A2, A3 and A4 genes. This 5' intervening sequence appears to be essential to obtain a maximum GUS activity driven by the Al gene promoter.
Bisphenol-A (BPA) Exposure Alters Endometrial Progesterone Receptor Expression in the Non-human Primate

OBJECTIVE— To evaluate the effect of BPA on endometrial PR expression in non-human primates and human cells. BPA is a xenoestrogen endocrine disruptor. Both BPA exposure and diminished progesterone action have been associated with pregnancy loss, endometriosis and endometrial hyperplasia/cancer. DESIGN— Controlled trial in primates. SETTING— University Animals— African green monkeys INTERVENTIONS— After oophorectomy, BPA (50 μ g/kg/day), estradiol, both or vehicle control were administered. Estradiol and BPA were used in Ishikawa cells. MAIN OUTCOME MEASURES— PR expression using IHC and qPCR. RESULTS— PR expression was increased in estradiol treated primates compared to controls. Exposure to the combination of estradiol and BPA resulted in decreased PR expression compared to estradiol exposure alone (p<0.01). In Ishikawa cells treated with estradiol, PR expression increased 5.1 fold, however, when Ishikawa cells were simultaneously treated with estradiol and BPA, PR expression was decreased to 0.6 fold that of cells treated with estradiol alone (p<0.05). CONCLUSION— BPA alone functions as a weak estrogen. However, when administered with estradiol, BPA diminishes estradiol induced PR expression. The estrogen-like effect of BPA reported in exposed humans may be mediated by PR blockade and a resultant decrease in the estrogen inhibition normally imparted by progesterone. Diminished PR expression may underlie previous reports linking BPA exposure to endometrial dysfunction in humans.
Contribution of Non-Esterified Fatty Acids to Insulin Resistance in the Elderly with Normal Fasting but Diabetic 2h Post Challenge Plasma Glucose Levels: Baltimore Longitudinal Study of Aging

Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose (NFG) <100mg/dl and plasma glucose with diabetic 2h plasma glucose (DGT) ≥ 200mg/dl after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts them at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75g) on two or more occasions. We measured plasma levels of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines and their soluble receptors, as well as NEFAs. We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were >65 yrs old. They were then matched by age, sex and BMI to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose (NFG) levels <100mg/dl in accordance with American Diabetes Association (ADA): Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other two groups, except at the 2h time, when their insulin levels were higher than NGT (P<0.05). Although there was a clear trend for differences in the insulinogenic index (II 0–20 min ), the areas under the curves for insulin, systolic BP, adiponectin and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all three groups. NEFA levels were significantly elevated in the fasting state (P<0.05) in the IPH compared to NGT, with IGT intermediate between the other two groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (NGT-11.9 vs. IGT-7.6 vs. IPH-3.0, μ mol/l·min − 1 ). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT.
Nucleic Acids Research

Although pancreatic ribonucleases are extensively studied proteins, little information is available on nucleic acids coding for these enzymes. Here, for the first time, the structure of a gene coding for such an enzyme, the well known bovine pancreatic ribonuclease, is reported. The coding region of this gene is devoid of introns, whereas the-5' untranslated sequence of the pancreatic transcript contains an intron of 735 nucleotides. This intervening sequence is endowed with signals (CAAT and TATA boxes) which might act as regulatory elements. The structural organization of this gene suggests that the sequence coding for the bovine pancreatic ribonuclease might be expressed under the control of two different promoters.
Cross-talk Between MiR-29c and TGF- β 3 is Mediated by an Epigenetic Mechanism in Leiomyoma

Objective— To determine the expression of miR-29c and its target gene transforming growth factor- β 3 (TGF- β 3) in leiomyoma and the mechanisms of their reciprocal regulation. DESIGN— Experimental study SETTING— Academic research laboratory PATIENT(S)— Women undergoing hysterectomy for leiomyoma. Intervention— Over and under expression of miR-29c; blockade of DNA methyltransferase 1 (DNMT1). MAIN OUTCOME MEASURE(S)— and its target gene TGF- β 3 in leiomyoma and the effects of TGF- β 3 and blockade of DNMT1 on miR-29c expression. Results— Leiomyoma expressed significantly lower levels of miR-29c but higher expression of TGF- β 3 compared with matched myometrium. The expression of TGF- β 3 and miR-29c were independent of race/ethnicity. Using 3’UTR luciferase reporter assay we confirmed that TGF- β 3 is a direct target of miR-29c in leiomyoma smooth muscle cells (LSMC). Gain-of-function of miR-29c in LSMC inhibited the expression of TGF- β 3 at protein and mRNA levels, whereas loss-of-function of miR-29c had the opposite effect. Treatment of LSMC with TGF- β 3 inhibited the expression of miR-29c while it stimulated DNMT1 expression. Knockdown of DNMT1 through transfection with siRNA significantly decreased the expression of TGF- β 3, and induced miR-29c expression. Knockdown of DNMT1 also attenuated the inhibitory effect of TGF- β 3 on miR-29c expression. Furthermore, we demonstrated that TGF- β 3 increased the methylation level of miR-29c promoter in LSMC. Conclusion— There is an inverse relationship in the expression of There is a cross talk between TGF- β 3 and miR-29c in leiomyoma wherein TGF- β 3 inhibits the expression of miR-29c through an epigenetic mechanism involving DNMT1.
Effects of chronic ethanol exposure on the expression of GLT-1 and neuroplasticity-related proteins in the nucleus accumbens of alcohol-preferring rats

Chronic ethanol exposure induces impairments in CNS excitatory and inhibitory activity. These impairments are associated with glutamatergic dysfunction, including altered neuroplasticity. This study examined the effects of 6-week ethanol (15% and 30% v/v) consumption, by male alcohol-preferring P rats, on protein expression associated with neuroplasticity and glutamate transporter-1 (GLT-1) function. The latter regulates intra- and extra-synaptic glutamate levels. We focused on the shell and core subregions of the nucleus accumbens (Acb); i.e., shell (AcbSh) and core (AcbCo), for these measures. Chronic ethanol exposure increased the expression of BDNF, Arc and phosphorylated (p)-post-synaptic density protein-95 (p-PSD-95) in the AcbSh of P rats. Moreover, the ratio of phospho-neuronal nitric oxide synthase (p-nNOS) to total nNOS was also increased in the AcbSh. These changes in BDNF, Arc and p-nNOS/nNOS ratio were not observed in the AcbCo. Furthermore, chronic ethanol exposure reduced GLT-1 expression in the AcbSh. Alternatively, treatment with ceftriaxone (CEF), a known GLT-1 upregulator, abolished the effect HA and FA participated in study design and conceptualization, drafted and revised the manuscript, performed brain dissection, protein assay, and Western blot assay, and collected the data. BA and WW performed protein quantification and western blot assays, collected the data and helped with the editing of manuscript. RLB conceptualized and designed the study, critically revised the manuscript for intellectual content, performed drinking measurements, and approved the final version of the manuscript. YS conceptualized and designed the study, critically revised the manuscript for intellectual content, and approved the final version of the manuscript. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of interest The authors declare no conflicts of interest. of chronic ethanol exposure on BDNF expression in the AcbSh. Overall, the present findings confirm that chronic ethanol consumption modulates activity-associated synaptic proteins, including BDNF, Arc and nNOS in a subregion-specific (i.e., in the AcbSh but not AcbCo) manner. Thus, alterations in mesocorticolimbic glutamatergic homeostasis and neuroplasticity are possible functional targets for the treatment of alcohol use disorders.