Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytochrome P-450 ω-hydroxylase senses O2 in hamster muscle, but not cheek pouch epithelium, microcirculation.

The goal of this study was to investigate the role of cytochrome P-450 ω-hydroxylase in mediating O2-induced constriction of arterioles in the microcirculation of the hamster. Male Golden hamsters were anesthetized with pentobarbital sodium, and the cremaster muscle or cheek pouch was prepared for observation by intravital microscopy. Arteriolar diameters were measured during elevations of superfusate[Formula: see text] from ∼5 to 150 mmHg. Arteriolar responses to elevated [Formula: see text] were determined in the cremaster muscle, in the retractor muscle where it inserts on the cheek pouch, and in the epithelial portion of the cheek pouch. Elevation of superfusion solution[Formula: see text] caused a vigorous constriction of arterioles in the cremaster and retractor muscles and in the epithelial portion of the cheek pouch. Superfusion with 10 μM 17-octadecynoic acid, a suicide substrate inhibitor of cytochrome P-450 ω-hydroxylase, and intravenous infusion of N-methylsulfonyl-12,12-dibromododec-11-enamide, a mechanistically different and highly selective inhibitor of cytochrome P-450 ω-hydroxylase, caused a significant reduction in the magnitude of O2-induced constriction of arterioles in the cremaster and retractor muscles. However, arteriolar constriction in response to elevated[Formula: see text] was unaffected by 17-octadecynoic acid or N-methylsulfonyl-12,12-dibromododec-11-enamide in the epithelial portion of the cheek pouch. These data confirm that there are regional differences in the mechanism of action of O2 on the microcirculation and indicate that cytochrome P-450 ω-hydroxylase senses O2 in the microcirculation of hamster skeletal muscle, but not in the cheek pouch epithelium.
Polyamine depletion is associated with an increase in JunD/AP-1 activity in small intestinal crypt cells.

Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of protooncogene (Jun and Fos) subunits that bind to a common DNA site, the AP-1 binding site. The proteins of c-Jun, JunB, and Fos are essential for initiation of the cell cycle. Conversely, the activation of the junD gene slows cell growth in some cell types. The current study tests the hypothesis that polyamines influence cell growth by altering the balance of positive and negative Jun/AP-1 activities in intestinal epithelial cells. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Administration of α-difluoromethylornithine (DFMO), a specific inhibitor for polyamine synthesis, for 4 and 6 days completely depleted cellular polyamine levels, while AP-1 binding activity was significantly increased. Spermidine, when given together with DFMO, restored AP-1 binding activity toward normal. The increased AP-1 complexes in polyamine-deficient cells were dramatically supershifted by the anti-JunD antibody but not by antibodies against c-Jun, JunB, or Fos proteins. There were significant increases in JunD mRNA and protein in DFMO-treated cells, although expression of the c- fos, c- jun, and junB genes decreased. The increase in JunD/AP-1 activity in DFMO-treated cells was associated with a significant decrease in cell division. Exposure of control quiescent cells to 5% dialyzed serum increased c-Jun/AP-1 but not JunD/AP-1 activities. DFMO prevented the stimulation of c-Jun/AP-1 activity induced by 5% dialyzed serum. These results indicate that 1) polyamine depletion is associated with an increase in AP-1 binding activity and 2) the increase in AP-1 activity in the DFMO-treated cells was primarily contributed by an increase in the JunD/AP-1. These findings suggest that polyamines regulate cell growth at least partially by modulating the balance of positive and negative Jun/AP-1 activities in the intestinal mucosa.
Watershed reengineering: Making Streams Programmable

Most high-performance data processing (aka big-data) systems allow users to express their computation using abstractions (like map-reduce) that simplify the extraction of parallelism from applications. Most frameworks, however, do not allow users to specify how communication must take place: that element is deeply embedded into the run-time system (RTS), making changes hard to implement. In this work we describe our reengineering of the Watershed system, a framework based on the filter-stream paradigm and focused on continuous stream processing. Like other big-data environments, watershed provided object-oriented abstractions to express computation (filters), but the implementation of streams was an RTS element. By isolating stream functionality into appropriate classes, combination of communication patterns and reuse of common message handling functions (like compression and blocking) become possible. The new architecture even allow the design of new communication patterns, for example, allowing users to choose MPI, TCP or shared memory implementations of communication channels as their problem demand. Applications designed for the new interface showed reductions in code size on the order of 50%and above in some cases, with no significant performance penalty.
Labral Augmentation with Native Tissue Preservation with a 7.5-Year Follow-up: A Case Report

Case: Arthroscopic labral repair has resulted in excellent functional outcomes. However, extensive labral damage or diminutive size of the labrum may preclude a repair. In these cases, labral augmentation serves as an operative treatment option. We report the case of a labral augmentation with 7.5 years of follow-up, including intraoperative reexamination, which highlights the ability of an iliotibial band autograft to incorporate with the native labrum. Conclusion: When indicated in an appropriate patient, labral augmentation with an iliotibial band autograft is an established technique that can result in an excellent outcome.
Differential activation of the SMαA promoter in smooth vs. skeletal muscle cells by bHLH factors.

E-box/basic helix-loop-helix (bHLH)-dependent regulation of promoters for skeletal muscle-specific genes is well established, but similar regulation of smooth muscle-selective promoters has not been reported. Using transient transfection assays of smooth muscle α-actin (SMαA) promoter-chloramphenicol acetyltransferase (CAT) reporter constructs in rat vascular smooth muscle cells (SMCs) and L6 skeletal myotubes, we identified two activator elements, smE1 and smE2, with sequences corresponding to E-box (5'-CAnnTG-3') motifs. In L6 myotubes, 4-bp mutations of smE1 or smE2 E-box motif alone completely abolished promoter activity. In contrast, mutation of smE1 and smE2 was required to reduce promoter activity in SMCs. Supershift analyses identified a myogenin-containing complex as the predominant smE1 and smE2 binding activity in skeletal muscle, and myogenin overexpression transactivated the promoter. Supershift analyses with SMC extracts demonstrated that the bHLH protein upstream stimulatory factor (USF) bound smE1, and USF overexpression transactivated the promoter in an smE1-dependent manner. In summary, our results provide novel evidence implicating E-box elements in directing expression of the SMαA promoter through distinct bHLH factor complexes in skeletal vs. smooth muscle.
Climate change and mammals: evolutionary versus plastic responses

Phenotypic plasticity and microevolution are the two primary means by which organisms respond adaptively to local conditions. While these mechanisms are not mutually exclusive, their relative magnitudes will influence both the rate of, and ability to sustain, phenotypic responses to climate change. We review accounts of recent phenotypic changes in wild mammal populations with the purpose of critically evaluating the following: (i) whether climate change has been identified as the causal mechanism producing the observed change; (ii) whether the change is adaptive; and (iii) the relative influences of evolution and/or phenotypic plasticity underlying the change. The available data for mammals are scant. We found twelve studies that report changes in phenology, body weight or litter size. In all cases, the observed response was primarily due to plasticity. Only one study (of advancing parturition dates in American red squirrels) provided convincing evidence of contemporary evolution. Subsequently, however, climate change has been shown to not be the causal mechanism underlying this shift. We also summarize studies that have shown evolutionary potential (i.e. the trait is heritable and/or under selection) in traits with putative associations with climate change and discuss future directions that need to be undertaken before a conclusive demonstration of plastic or evolutionary responses to climate change in wild mammals can be made.
Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments.
Mechanics solutions for deflection and cracking in concrete

Serviceability failures in reinforced concrete elements that are the result of excessive cracking or deflection are relatively common, particularly for slender sections such as slabs. The calculation of member deflection is typically carried out by applying an elastic deflection equation with an effective flexural rigidity that is a function of the full-interaction uncracked and cracked flexural rigidities. The effective flexural rigidity achieves two purposes: it allows for variations in cracking along the member length; and approximates tension stiffening, that is slip between the reinforcement and adjacent concrete, as this is not accounted for in standard full interaction analyses. Although much research has been conducted to define effective flexural rigidity, the resulting equations are typically empirical calibrations or allow for bond without allowing for bond slip. In this paper, a new partial-interaction approach for quantifying the flexural rigidity of a cracked section based on a recently deve.
The Cross-Domain Re-interpretation of Artistic Ideas

The goal of this study was to investigate the translation of creative works into other domains. We tested whether people were able to recognize which works of art were inspired by which pieces of music. Three expert painters created four paintings, each of which was the artist's interpretation of one of four different pieces of instrumental music. Participants were able to identify which paintings were inspired by which pieces of music at statistically significant above chance levels. The findings support the hypothesis that creative ideas can exist in an at least somewhat domain independent state of potentiality and become more well defined as they are actualized in accordance with the constraints of a particular domain.
Constitutive expression of interleukin-1α precursor promotes human vascular smooth muscle cell proliferation.

Vascular smooth muscle cell (VSMC) proliferation plays a critical role in the failure of vascular surgeries and contributes to the development of atherosclerotic lesions. Evidence that interleukin-1 (IL-1) is a mitogen for cultured VSMC has implicated its release by activated macrophages in the development of atherosclerosis. VSMC also produce IL-1, including the precursor form of IL-1α. However, it is not known whether IL-1α precursor is processed to mature IL-1α or released from VSMC, nor is it known whether either precursor or mature IL-1α functions as an autocrine growth factor. The goals of the present study were to establish whether proliferation is enhanced in human VSMC transfectants producing IL-1α constitutively at levels comparable to those produced after activation, and to determine which domains of IL-1α are important for its activity. Human VSMC were stably transfected with expression vectors directing constitutive expression of either full-length IL-1α precursor [IL-1α-(1-271)], its NH2-terminal domain [IL-1α-(1-112)], or mature IL-1α [IL-1α-(113-271)]. Both IL-1α-(1-271) and IL-1α-(113-271) stable transfectants produced moderate levels of IL-1α (0.2-1.0 ng/106cells) and released low levels of IL-1α into the supernatant (<20 pg/ml). VSMC stably transfected with either IL-1α-(1-271) or IL-1α-(113-271) expression plasmids proliferated rapidly compared with nontransfected or vector-transfected VSMC and displayed a distinct morphology characterized by elongated, spindle-shaped cells. Stable transfection with IL-1α-(1-271) was somewhat more effective than transfection with IL-1α-(113-271). Interestingly, VSMC transfected with IL-1α-(113-271) expression plasmids also expressed IL-1α-(1-271) mRNA, suggesting that IL-1α-(113-271) activates an IL-1-induced IL-1 autocrine loop. In contrast, neither proliferation rates nor morphology was affected by stable transfection with IL-1α-(1-112) expression plasmids. Exogenous IL-1 receptor antagonist partially reversed the enhanced DNA synthesis in VSMC transfected with either IL-1α-(1-271) or IL-1α-(113-271) expression plasmids, suggesting that the pro-proliferative effect of VSMC-derived IL-1α is at least partially mediated by signaling via the type I IL-1 receptor. These results demonstrate that IL-1α precursor is an autocrine growth factor for human VSMC and further indicate that amino acids 113-271 play a crucial role in its actions.
Epidermal growth factor: a potent vasoconstrictor in experimental hypertension.

We have tested the hypothesis that growth factor signaling pathways are augmented in hypertension, a disease associated with vascular smooth muscle cell growth. Thoracic aorta was dissected from deoxycorticosterone acetate-salt (DOCA-salt) and one kidney, one clip (1K, 1C) hypertensive rats and from sham normotensive rats for use in isolated tissue bath experiments. Systolic blood pressure was significantly higher in DOCA-salt and 1K, 1C than in normotensive sham rats: 192 ± 7, 185 ± 10, and 117 ± 4 mmHg, respectively. Although virtually no contraction to epidermal growth factor (EGF) was observed in endothelium-denuded sham rat aorta [1 ± 1% phenylephrine (PE) (10 μmol/l)-induced contraction], the maximal EGF-induced contraction was 45 ± 7% in endothelium-denuded aorta from DOCA-salt hypertensive rats and 39 ± 7% in aorta from 1K, 1C rats. Although slightly attenuated, a contraction to EGF was still observed in endothelium-intact aortic strips from 28-day DOCA-salt hypertensive rats. We also conducted concentration-response curves to EGF on days 1, 3, 5, 7, 14, and 21 of DOCA-salt therapy. A significant contraction to EGF in aorta from DOCA-salt rats was observed on day 14, when DOCA-salt rats had significantly higher blood pressure than sham rats: 188 ± 6 and 122 ± 3 mmHg, respectively. Transforming growth factor-α, an agonist of the EGF receptor, contracted DOCA-salt rat aorta (30 ± 7% PE-induced contraction) but not sham aorta (3 ± 3%). The EGF receptor tyrosine kinase inhibitor 4,5-dianilinophthalimide (10 μmol/l), the mitogen-activated protein kinase kinase inhibitor PD-098059 (10 μmol/l), and the L-type voltage-gated calcium channel inhibitor diltiazem (1 mol/l), but not the cyclooxygenase inhibitor indomethacin (10 μmol/l), virtually abolished EGF-induced contraction (85, 98, and 99% reduction, respectively). These data support a striking difference in EGF signaling between normotensive and hypertensive animals. Furthermore, they provide evidence that growth factors should be considered vasoconstrictors as well as growth modulators in hypertension.
Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis.

To test the hypothesis that nitric oxide (NO) deficiency occurs in end-stage renal disease (ESRD), NO oxidation products (NO2 + NO3 = NOx) and cGMP were measured in blood, urine, and dialysate effluent of peritoneal dialysis (PD) patients and compared with blood and urine of healthy subjects. All subjects were on a controlled low-nitrate diet (∼330 μmol/day). NOx and cGMP outputs were significantly reduced in PD patients (334 ± 50 μmol/24 h and 55 ± 13 nmol/24 h, respectively) vs. controls (823 ± 101 μmol/24 h and 149 ± 46 nmol/24 h). Plasma arginine was borderline low, plasma citrulline was elevated and plasma levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine were approximately five time higher in PD patients (2.2 ± 0.3 μM) vs. controls (0.4 ± 0.1 μM). Although blood pressure (BP) was not different between groups at the time of study, 10 of 11 PD patients were on medication for hypertension. These studies demonstrate that total NO production is low in ESRD, and with appropriate caution, we conclude that this NO deficiency may contribute to the increased BP that occurs in ESRD.
Mechanism of Ca2+ release and entry during contraction elicited by norepinephrine in rat resistance arteries.

The intracellular Ca2+ stores and the mechanisms of Ca2+ entry produced by norepinephrine (NE) were investigated in small mesenteric resistance arteries of the rat. In Ca2+-free medium, NE (10 μM) elicited a transient increase in both intracellular free Ca2+concentration ([Ca2+]i) and tension that were both drastically reduced by caffeine and only partially reduced by the two sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, despite the presence of SERCA2a and SERCA2b isoforms in the medial smooth muscle layer of the artery. After depletion of intracellular Ca2+ stores with 10 μM NE, addition of exogenous CaCl2 (2.5 mM) produced large and sustained increases in both [Ca2+]iand contraction of the arteries provided that the agonist was continuously present. In these conditions, the responses to CaCl2 were inhibited by the voltage-dependent Ca2+ entry blocker nitrendipine (1 μM), the putative inhibitor of receptor-operated Ca2+ entry SKF-96365 (30 μM), and NiCl2 (1 mM). The inhibition produced by SKF-96365 and NiCl2 was greater than that of nitrendipine. Also, the responses to CaCl2 were greatly reduced or abolished in the presence of the Na+/Ca2+exchanger inhibitors 1,3-dimethyl-2-thiourea, 3',4'-dichlorobenzamil, MgCl2, and amiloride or after omission of NaCl in the medium. Also, protein kinase C inhibitors, calphostin C and staurosporine, and tyrosine kinase inhibitors, genistein and tyrphostin 23, both reduced the responses to CaCl2. The inhibitory effect of protein kinase C inhibitor and tyrosine kinase were additive. These results suggest that NE releases Ca2+ from intracellular stores that are caffeine sensitive and partially sensitive to SERCA inhibitors. They indicate that in addition to Ca2+ influx via nitrendipine-sensitive and SKF-96365-sensitive channels, Na+/Ca2+exchanger participates in the CaCl2-induced contraction produced in NE-exposed vessels. The pathway leading to Ca2+ entry probably involves tyrosine kinase and protein kinase C. All the above mechanisms require ongoing receptor stimulation.
Postcranial skeletal anatomy of the holotype and referred specimens of Buitreraptor gonzalezorum Makovicky, Apesteguía and Agnolín 2005 (Theropoda, Dromaeosauridae), from the Late Cretaceous of Patagonia

Here we provide a detailed description of the postcranial skeleton of the holotype and referred specimens of Buitreraptor gonzalezorum. This taxon was recovered as an unenlagiine dromaeosaurid in several recent phylogenetic studies and is the best represented Gondwanan dromaeosaurid discovered to date. It was preliminarily described in a brief article, but a detailed account of its osteology is emerging in recent works. The holotype is the most complete specimen yet found, so an exhaustive description of it provides much valuable anatomical information. The holotype and referred specimens preserve the axial skeleton, pectoral and pelvic girdles, and both fore- and hindlimbs. Diagnostic postcranial characters of this taxon include: anterior cervical centra exceeding the posterior limit of neural arch; eighth and ninth cervical vertebral centra with lateroventral tubercles; pneumatic foramina only in anteriormost dorsals; middle and posterior caudal centra with a complex of shallow ridges on lateral surfaces; pneumatic furcula with two pneumatic foramina on the ventral surface; scapular blade transversely expanded at mid-length; well-projected flexor process on distal end of the humerus; dorsal rim of the ilium laterally everted; and concave dorsal rim of the postacetabular iliac blade. A paleohistological study of limb bones shows that the holotype represents an earlier ontogenetic stage than one of the referred specimens (MPCA 238), which correlates with the fusion of the last sacral vertebra to the rest of the sacrum in MPCA 238. A revised phylogenetic analysis recovered Buitreraptor as an unenlagiine dromaeosaurid, in agreement with previous works. The phylogenetic implications of the unenlagiine synapomorphies and other characters, such as the specialized pedal digit II and the distal ginglymus on metatarsal II, are discussed within the evolutionary framework of Paraves.
Comparison of the immune response during acute and chronic Staphylococcus aureus infection

Staphylococcus aureus bacteria are able to grow in a planktonic state that is associated with acute infections and in biofilms that are associated with chronic infections. Acute infections, such as skin infections, are often self-limiting. However, chronic infections, such as implant infections, can be difficult to clear and may require surgical intervention. The host immune response may contribute to the different outcomes often associated with these two disease types. We used proteomic arrays and two murine models for an initial, descriptive characterization of the contribution of the host immune response to outcomes of acute versus chronic S. aureus disease. We compared the immune responses between a model of self-limiting skin and soft tissue infection caused by the planktonic form of S. aureus versus a model of surgical mesh implant infection, which we show to be caused by a bacterial biofilm. The significantly altered host cytokines and chemokines were largely different in the two models, with responses diminished by 21 days post-implantation in surgical mesh infection. Because bacterial levels remained constant during the 21 days that the surgical mesh infection was followed, those cytokines that are significantly increased during chronic infection are not likely effective in eradicating biofilm. Comparison of the levels of cytokines and chemokines in acute versus chronic S. aureus infection can provide a starting point for evaluation of the role of specific immune factors that are present in one disease manifestation but not the other.