Miracle-dz/UniFAR-FTUs huggingface dataset:
Tsukushi Modulates Xnr2, FGF and BMP Signaling: Regulation of Xenopus Germ Layer Formation

Background Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-β family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-β-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination. Methodology/Principal Findings Here, we show that Xenopus Tsukushi (X-TSK), a member of the secreted small leucine rich repeat proteoglycan (SLRP) family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals. Conclusions/Significance Based on our observations, we propose a novel mechanism by which X-TSK refines the field of positional information by integration of multiple pathways in the extracellular space.
Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection. Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection. Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.
Postpartum depression and help-seeking behaviors in immigrant Hispanic women.

OBJECTIVES To describe perceptions of immigrant Hispanic women experiencing symptoms of postpartum depression (PPD) and to identify barriers to seeking mental health services. DESIGN Qualitative descriptive. SETTING Community health clinic. PARTICIPANTS Twenty immigrant Hispanic women scoring positive for symptoms of PPD receiving health care at a community health clinic who declined mental health services participated in audiotaped interviews held in their homes. METHODS Following Institutional Review Board approval and informed consent, interviews were conducted with study participants. Transcribed data were analyzed as appropriate for qualitative inquiry. RESULTS Some of the women did not recognize and/or denied their symptoms attributing their sadness to financial concerns, family relationships, and/or work stressors. Study participants articulately described their symptoms and identified personal barriers including beliefs about emotional health, the perceived stigma of mental illness, hesitancy to seek treatment for symptoms of PPD, and cultural beliefs about motherhood and the role of women. Social barriers included inadequate social support, immigration status, and limited English proficiency. Health care delivery barriers included financial and time constraints and lack of child care and transportation. CONCLUSION Limited social networks and barriers to health care should be addressed to foster positive outcomes. Mental health services should be embedded with primary health care or obstetric care clinics to facilitate access. Personal and professional support can make a significant contribution to the reduction of symptoms of PPD.
LARGE-AMPLITUDE LOVE WAVES

Summary In the context of the finite elasticity theory, we consider a model for compressible solids called ‘compressible neo-Hookean material’. We show how finite-amplitude inhomogeneous plane wave solutions and finite-amplitude unattenuated solutions can combine to form a finite-amplitude Love wave. We take a layer of finite thickness overlying a solid half-space, both made of different prestressed compressible neo-Hookean materials. We derive an exact solution of the equations of motion and boundary conditions and also obtain results for the energy density and the energy flux of the waves. Finally, we investigate the special case when the interface between the layer and the substrate is in a principal plane of the prestrain. A numerical example is given.
Evaluation of Plant Extracts as Antifungal Agents Against Fusarium solani (Mart.) Sacc.

Experiments were carried out to test the aqueous extracts of twenty plants for their antifungal activity against Fusarium solani the causal of dry rot disease of potato. The obtained results showed a differential activity of the plant extracts against the mycelium growth. The combined leaf extracts of Lawsonia alba and stem extracts of Acacia catechu in general showed a strong enhancement in activities over the individual extract of each against the mycelium growth. The seed extracts of Dedonia viscosa also showed strong inhibitory effect against the test fungi. The petal extracts of Mimosa hamata, leaf extracts of Acacia arabicae, Jacranda mimosaefolia and Ocimum sanctum showed appreciable good inhibitory effect against the test fungi. Potato (Solanum tuberosum L.) is the world's fourth kept in dark between the filter papers at room temperature important food crop after wheat, rice and maize because of till completely dry. Each plant sample was individually its great yield potential and high nutritive value for grounded into powder for preparation of extract. The human. FAO data show that in 2005, for the first time, the fungus Fusarium solani (IARI 5155 F) used for the study developing world's potato production exceeded that of was obtained from the Division of Plant Pathology, IARI, the developed world and India ranks third contributing New Delhi. The fungal cultures were maintained at 4°C on around 7.5% to the world's production. Ever increasing Yeast Glucose Agar medium with periodic sub-culturing. world population requires the production of huge quantity of potato but our efforts are hampered due to Antifungal Activity Test: The plant part extract (15% w/v) various biotic as well as abiotic factors. Among the biotic was prepared by brewing in hot water. Fifteen g dry factors, Fusarium solani (Mart.) Sacc. was first described powder of each plant sample was weighed and put in a by C.F. P. Von Martius in 1842 from rotted tubers of potato cheesecloth bag and suspended in 100ml of boiling (1). Dry rot of potato caused by Fusarium solani is an distilled water for 20 minutes. The extract was allowed to internationally important disease of potato resulting in stand for some time and decanted off into the flask and about 25 to 60% loss in yield in different countries and final volume was raised to 100ml by adding boiled distilled attempts have been made to manage the disease by water. The supernatant was used for assay. The treating with chemical compounds, biological agents as antifungal activity of each plant part extract was reported by Wharton and Kirk (2). In the present study, determined by measuring the mycelia growth inhibition of efficacy of twenty plant extracts including combined tested fungi as described by Bragulat et al. (3). A known plants extracts for antifungal activity against dry rot volume of 15% plant sample extract was supplemented pathogen was tested. with yeast extract, glucose and agar. The medium was
Phase I dose escalation of single-agent vinblastine in dogs.

BACKGROUND Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. HYPOTHESIS The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. ANIMALS Twenty-three dogs with lymphoma or cutaneous mast cell tumors. METHODS Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. RESULTS VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. CONCLUSIONS AND CLINICAL IMPORTANCE In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.
Cognition

A defining aspect of being human is an ability to reason about the world by generating and adapting ideas and hypotheses. Here we explore how this ability develops by comparing children’s and adults’ active search and explicit hypothesis generation patterns in a task that mimics the open-ended process of scientific induction. In our experiment, 54 children (aged 8 . 97±1 . 11 ) and 50 adults performed inductive inferences about a series of causal rules through active testing. Children were more elaborate in their testing behavior and generated substantially more complex guesses about the hidden rules. We take a ‘computational constructivist’ perspective to explaining these patterns, arguing that these inferences are driven by a combination of thinking (generating and modifying symbolic concepts) and exploring (discovering and investigating patterns in the physical world). We show how this framework and rich new dataset speak to questions about developmental differences in hypothesis generation, active learning and inductive generalization. In particular, we find children’s learning is driven by less fine-tuned construction mechanisms than adults’, resulting in a greater diversity of ideas but less reliable discovery of simple explanations. ‘‘We think we understand the rules when we become adults but what we really experience is a narrowing of the imagination. ’’
ON ALGEBRAICALLY INTEGRABLE OUTER BILLIARDS

We prove that if the outer billiard map around a plane oval is algebraically integrable in a certain non-degenerate sense then the oval is an ellipse. In this note, an outer billiard table is a compact convex domain in the plane bounded by an oval (closed smooth strictly convex curve) C. Pick a point x outside of C. There are two tangent lines from x to C; choose one of them, say, the right one from the view-point of x, and reflect x in the tangency point. One obtains a new point, y, and the transformation T : x 7→ y is the outer (a.k.a. dual) billiard map. We refer to [3, 4, 5] for surveys of outer billiards. If C is an ellipse then the map T possesses a 1-parameter family of invariant curves, the homothetic ellipses; these invariant curves foliate the exterior of C. Conjecturally, if an outer neighborhood of an oval C is foliated by the invariant curves of the outer billiard map then C is an ellipse – this is an outer version of the famous Birkhoff conjecture concerning the conventional, inner billiards. In this note we show that ellipses are rigid in a much more restrictive sense of algebraically integrable outer billiards; see [2] for the case of inner billiards.
Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial

Objectives To determine the effects of adding an oxytocin infusion to bolus oxytocin on blood loss at elective caesarean section. Design Double blind, placebo controlled, randomised trial, conducted from February 2008 to June 2010. Setting Five maternity hospitals in the Republic of Ireland. Participants 2069 women booked for elective caesarean section at term with a singleton pregnancy. We excluded women with placenta praevia, thrombocytopenia, coagulopathies, previous major obstetric haemorrhage (>1000 mL), or known fibroids; women receiving anticoagulant treatment; those who did not understand English; and those who were younger than 18 years. Intervention Intervention group: intravenous slow 5 IU oxytocin bolus over 1 minute and additional 40 IU oxytocin infusion in 500 mL of 0.9% saline solution over 4 hours (bolus and infusion). Placebo group: 5 IU oxytocin bolus over 1 minute and 500 mL of 0.9% saline solution over 4 hours (placebo infusion) (bolus only). Main outcomes Major obstetric haemorrhage (blood loss >1000 mL) and need for an additional uterotonic agent. Results We found no difference in the occurrence of major obstetric haemorrhage between the groups (bolus and infusion 15.7% (158/1007) v bolus only 16.0% (159/994), adjusted odds ratio 0.98, 95% confidence intervals 0.77 to 1.25, P=0.86). The need for an additional uterotonic agent in the bolus and infusion group was lower than that in the bolus only group (12.2% (126/1033) v 18.4% (189/1025), 0.61, 0.48 to 0.78, P<0.001). Women were less likely to have a major obstetric haemorrhage in the bolus and infusion group than in the bolus only group if the obstetrician was junior rather than senior (0.57, 0.35 to 0.92, P=0.02). Conclusion The addition of an oxytocin infusion after caesarean delivery reduces the need for additional uterotonic agents but does not affect the overall occurrence of major obstetric haemorrhage. Trial Registration Current Controlled Trials ISRCTN17813715.
Assisted large fragment insertion by Red/ET-recombination (ALFIRE)—an alternative and enhanced method for large fragment recombineering

Functional genomics require manipulation and modification of large fragments of the genome. Such manipulation has only recently become more efficient due to the discovery of different techniques based on homologous recombination. However, certain limitations of these strategies still exist since insertion of homology arms (HAs) is often based on amplification of DNA sequences with PCR. Large quantities of PCR products longer than 4–5 kb can be difficult to obtain and the risk of mutations or mismatches increases with the size of the template that is being amplified. This can be overcome by adding HAs by conventional cloning techniques, but with large fragments such as entire genes the procedure becomes time-consuming and tedious. Second, homologous recombination techniques often require addition of antibiotic selection genes, which may not be desired in the final construct. Here, we report a method to overcome the size and selection marker limitations by a two- or three-step procedure. The method can insert any fragment into small or large episomes, without the need of an antibiotic selection gene. We have humanized the mouse luteinizing hormone receptor gene (Lhcgr) by inserting a ∼55 kb fragment from a BAC clone containing the human Lhcgr gene into a 170 kb BAC clone comprising the entire mouse orthologue. The methodology is based on the rationale to introduce a counter-selection cassette flanked by unique restriction sites and HAs for the insert, into the vector that is modified. Upon enzymatic digestion, in vitro or in Escherichia coli, double-strand breaks are generated leading to recombination between the vector and the insert. The procedure described here is thus an additional powerful tool for manipulating large and complex genomic fragments.
Impaired Endothelium-Derived Hyperpolarizing Factor–Mediated Dilations and Increased Blood Pressure in Mice Deficient of the Intermediate-Conductance Ca2+-Activated K+ Channel

The endothelium plays a key role in the control of vascular tone and alteration in endothelial cell function contributes to several cardiovascular disease states. Endothelium-dependent dilation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarizing factor (EDHF). EDHF signaling is thought to be initiated by activation of endothelial Ca2+-activated K+ channels (KCa), leading to hyperpolarization of the endothelium and subsequently to hyperpolarization and relaxation of vascular smooth muscle. In the present study, we tested the functional role of the endothelial intermediate-conductance KCa (IKCa/KCa3.1) in endothelial hyperpolarization, in EDHF-mediated dilation, and in the control of arterial pressure by targeted deletion of KCa3.1. KCa3.1-deficient mice (KCa3.1−/−) were generated by conventional gene-targeting strategies. Endothelial KCa currents and EDHF-mediated dilations were characterized by patch-clamp analysis, myography and intravital microscopy. Disruption of the KCa3.1 gene abolished endothelial KCa3.1 currents and significantly diminished overall current through KCa channels. As a consequence, endothelial and smooth muscle hyperpolarization in response to acetylcholine was reduced in KCa3.1−/− mice. Acetylcholine-induced dilations were impaired in the carotid artery and in resistance vessels because of a substantial reduction of EDHF-mediated dilation in KCa3.1−/− mice. Moreover, the loss of KCa3.1 led to a significant increase in arterial blood pressure and to mild left ventricular hypertrophy. These results indicate that the endothelial KCa3.1 is a fundamental determinant of endothelial hyperpolarization and EDHF signaling and, thereby, a crucial determinant in the control of vascular tone and overall circulatory regulation.
Ability Versus Effort Attributional Feedback: Differential Effects on Self-Efficacy and Achievement

This experiment explored the effects of ability and effort attributional feedback given during subtraction competency development on children's perceived self-efficacy and achievement. Children who were deficient in subtraction skills received training on subtraction operations and engaged in problem solving, during which they periodically received ability attributional feedback for their progress, effort feedback, ability + effort feedback, or no attributional feedback. Children given only ability feedback demonstrated the highest subtraction skill and self-efficacy; the effort and ability + effort conditions did not differ, but each outperformed the no-feedback condition. Future research should examine in greater detail how children process attributional information and its effects on achievement outcomes.
Steady-state and Transient Kinetics of Escherichia coli Nitric-oxide Dioxygenase (Flavohemoglobin)

Escherichia coli expresses an inducible flavohemoglobin possessing robust NO dioxygenase activity. At 37 °C, the enzyme shows a maximal turnover number (V max) of 670 s−1 andK m values for NADH, NO, and O2 equal to 4.8, 0.28, and ∼100 μm, respectively. Individual reduction, ligand binding, and NO dioxygenation reactions were examined at 20 °C, where V max is ∼94 s−1. Reduction by NADH occurs in two steps. NADH reduces bound FAD with a rate constant of ∼15 μm −1s−1, and heme iron is reduced by FADH2 with a rate constant of 150 s−1. Dioxygen binds tightly to reduced flavohemoglobin, with association and dissociation rate constants equal to 38 μm −1 s−1and 0.44 s−1, respectively, and the oxygenated flavohemoglobin dioxygenates NO to form nitrate. NO also binds reversibly to reduced flavohemoglobin in competition with O2, dissociates slowly, and inhibits NO dioxygenase activity at [NO]/[O2] ratios of 1:100. Replacement of the heme pocket B10 tyrosine with phenylalanine increases the O2 dissociation rate constant ∼80-fold and reduces NO dioxygenase activity ∼30-fold, demonstrating the importance of the tyrosine hydroxyl for O2 affinity and NO scavenging activity. At 37 °C,V max/K m (NO) is 2,400 μm −1 s−1, demonstrating that the enzyme is extremely efficient at converting toxic NO into nitrate under physiological conditions.
Prolactin in partial epilepsy: An indicator of limbic seizures

A study was performed to evaluate changes in serum prolactin levels after simple and complex partial seizures, and to identify which specific anatomical structures must be involved in seizures for postictal elevation of prolactin levels to occur. Seventy‐eight seizures were studied in patients with electrodes implanted bilaterally into amygdala, hippocampus, hippocampal gyrus, and frontal sites. All 38 complex partial seizures had bilateral limbic ictal discharges, and each was followed by a significant increase in prolactin concentration (mean peak, 50.8 ng/ml; range, 16.0 to 150.0 ng/ml). Eight of 10 simple partial seizures with unilateral high‐frequency regional limbic discharges were followed by prolactin elevation (mean peak, 28.2 ng/ml; range, 13.4 to 44 ng/ml). Thirty simple partial seizures with other ictal limbic discharges or without limbic discharges were not followed by an elevated prolactin level. The data indicate that serum prolactin levels always rise after complex partial seizures involving the temporal lobes, and rise after certain simple partial seizures involving limbic structures. Thus, measurement of the prolactin level can help identify which simple partial seizures involve mesial temporal lobe structures. Limbic structures serve to trigger prolactin release, which may depend upon spread of the seizure to subcortical structures.
Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells

We describe a new modality of interaction between coats and membrane tethers that provides insight into the question of what mechanisms define specific subcellular location of tethers. We propose that clathrin-dependent mechanisms segregate class C vps/HOPS (HOmotypic fusion and Protein Sorting) tethers to specialized domains of mammalian cells bearing complex architectures.