Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular pH changes induced by injection of cyclic nucleotides into gastropod neurones.

Injections of cyclic AMP (cAMP) or cyclic GMP (cGMP) into identifiable gastropod neurones under voltage clamp induced reversible cytoplasmic pH changes which were measured using the indicator dye Arsenazo III and pH micro‐electrodes. Similar injections of 5' AMP or 5' GMP did not induce such effects. In about one‐half of the population of neurones examined, cAMP injections (0.1‐10 mM) induced pH decreases with latencies of 1‐5 min and maximum response times 12‐25 min post‐injection. Comparable injections of cGMP into these cells resulted in decreases with latencies less than 1 min and maximum response times 5‐10 min. The amplitude and duration of these pHi decreases were dose dependent. In the other half of the population of neurones tested, cAMP injection induced an immediate alkalinization lasting 5‐10 min followed by an acidification which displayed a maximum response time within the same range as those in the first group. cGMP injection into these cells induced only acidifications with faster peak responses than with cAMP. Since cGMP did not elicit alkalinizing responses, the slower response time of the first group of cells with cAMP may reflect an always present underlying alkalinization. The nucleotide‐induced acidification was potentiated in neurones bathed in the phosphodiesterase inhibitor IBMX. Injections of non‐hydrolysable cAMP analogues also induced acidifications which were longer lasting than comparable doses of cyclic AMP. These results indicate that the elevated [H+]i was not simply due to hydrolysis of the injected cyclic nucleotide. The pHi changes were invariably of much longer duration than a nucleotide‐induced inward current (Connor & Hockberger, 1984) and persisted in Na‐free salines which eliminated the current response. These results support the notion that cyclic nucleotide elevation can affect cellular metabolic processes distinct from effects on ion transport mechanisms.
Cell-free fetal DNA in the plasma of pregnant women with severe fetal growth restriction.

OBJECTIVE Although there have been reports of increased fetal nucleated erythrocytes in the blood of pregnant women who are carrying growth-restricted fetuses, there have been no reports of quantification of fetal DNA concentration in the plasma of women with fetal growth restriction. We quantified fetal DNA concentration in the plasma of pregnant women with preeclampsia and/or fetal growth restriction. STUDY DESIGN We examined maternal plasma from 9 pregnant women with fetal growth restriction and 9 with preeclampsia and from 20 women who were gestational age-matched normal control subjects. All women carried a male fetus. DNA was extracted from 1.5-mL plasma samples, and the DYS14 and beta-globin gene were analyzed by real-time quantitative polymerase chain reaction. RESULTS The concentration of fetal DNA was significantly higher in subjects with preeclampsia than in fetal growth restriction subjects and normal control subjects. Fetal DNA concentrations in fetal growth restriction subjects were similar to those of normal control subjects. The concentration of total DNA (beta-globin) was significantly higher in subjects with preeclampsia when compared with healthy control subjects. CONCLUSION We demonstrated that there was no increase in fetal DNA in the plasma of pregnant women with fetal growth restriction and that most fetal DNA in maternal plasma originates from trophoblasts.
Multitargeted therapies for multiple myeloma

Multiple myeloma (MM) comprises 1% of all malignancies and 10% of all hematological malignancies. MM is a malignancy of plasma cells in the bone marrow where complex and dynamic interactions with the bone marrow microenvironment lead to tumor progression, skeletal destruction and angiogenesis. Despite the discovery of several novel treatments against MM, including the proteasome inhibitor bortezomib, it is considered to be an incurable disease with an average 4–5 years overall survival.
A Non-Invasive Great Exhale Breath Analysis Tool to Detect Respiratory Illness Using IOMT

Air is one of the most important things in human life. However, the denser the activity that triggers the growth of the air. Lung disease is one of the main respiratory problems caused due to pollutant air. Medically, Lung diseases like asthma, pneumonia are difficult to cure. One condition that affects people everywhere and poses a severe issue in low- and middle-income nations is asthma and pneumonia, which accounts for 80% of patient fatalities when symptoms go untreated. Respiratory illness is highly affected by environmental pollution. In proposed system, array of sensors continuously monitors the exhale air quality and processes the data, checks it against predefined thresholds, and triggers a phone call alert through a GSM modem if any of the air quality parameters exceed the desired range. This provides timely notifications to the user, allowing them to respond accordingly and potentially to avoid respiratory problems due to poor air quality.
Recommendations for blood pressure measurement in animals: summary of an AHA scientific statement from the Council on High Blood Pressure Research, Professional and Public Education Subcommittee.

Accurate and meaningful measurements of blood pressure (BP) are often critical to the interpretation of studies of vascular biology, atherosclerosis, and other forms of cardiovascular disease. Although many research scientists have embraced advanced molecular technologies for studying cardiovascular function and disease pathogenesis, a surprising number of the same investigators continue to use suboptimal techniques for measuring BP in experimental animals. To address this problem and assist investigators in selecting optimal methods for BP monitoring, the American Heart Association (AHA) has developed a scientific statement on recommendations for BP measurement in experimental animals. These recommendations for BP measurement are briefly summarized in this article. The complete text and discussion of the recommendations are published online in Arteriosclerosis, Thrombosis, and Vascular Biology as well as in print in other AHA journals.1 Comprehensive recommendations for BP measurement in humans have also been developed and are published in the AHA journal Hypertension . 2 See …
Comparison of the AT1-receptor blockers candesartan, irbesartan and losartan for inhibiting renal microvascular constriction

Angiotensin II (Ang II) type 1 (AT1) receptor blockers differ in their affinity for the AT1-receptor, suggesting a dissimilar potency for inhibiting Ang II-induced vascular constriction. In the present study, we compared the effects of candesartan, irbesartan and losartan on the renal microvascular constriction to locally-formed Ang II, using isolated, perfused hydronephrotic rat kidneys. Addition of 1 nmol/L angiotensin I (Ang I, the precursor of Ang II) significantly reduced the diameters of interlobular arteries (ILAs; -47.6±2.6%), afferent arterioles (AAs; -43.6±2.3%) and efferent arterioles (EAs; -31.6±2.4%). Candesartan and irbesartan were more potent in antagonising the constriction to Ang I than losartan. By contrast, candesartan and irbesartan differed only slightly in potency. After a washing period of 60 minutes with drug-free medium, a second application of Ang I failed to induce vasoconstriction only in candesartan-treated kidneys. Pretreatment of hydronephrotic kidneys with candesartan, to further explore its antagonistic properties, shifted the dose-response curves of Ang II approximately 2 log units to the right without reducing the maximal Ang II-induced constriction of ILAs, AAs or EAs. Additionally, dose-response curves of Ang II were similar after short (10 minutes) and prolonged (60 minutes) preincubation with candesartan. Our findings indicate that candesartan and irbesartan are more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan. The inhibitory effect of candesartan is more prolonged, suggesting a slow dissociation from the AT1-receptor. Additionally, candesartan was found to block the Ang II-induced constriction of renal microvessels in a surmountable manner.
Effects of T cells on platelet-derived growth factor-like protein secretion from endothelial cells.

The cause of accelerated graft arteriosclerosis after heart transplantation is unknown. To examine whether the interactions of T cells and endothelial cells (ECs) could contribute to the cause of this phenomenon, T cells were co-incubated with human umbilical artery endothelial cells (HUAEC) and human vein endothelial cells (HUVEC) and the resulting conditioned medium supernatant was assayed for the presence of platelet-derived growth factor (PDGF)-like protein. PDGF-like protein secretion was significantly greater from HUAECs co-incubated with T cells at T-cell/HUAEC ratios of 30:1 (6.9 +/- 1.1 fmol/10(6) ECs) and 10:1 (6.0 +/- 1.1 fmol/10(6) ECs) than the combined background secretion from HUAECs and T cells incubated separately (3.6 +/- 0.8 fmol/10(6) ECs) (p less than 0.05). PDGF-like protein secretion above background levels from HUAECs was significantly greater, however, than from HUVECs co-incubated with T cells at T-cell/HUVEC ratios of 30:1 (1.0 +/- 0.4 fmol/10(6) ECs) and 10:1 (0.75 +/- 0.36 fmol/10(6) ECs) (p less than 0.05). In four experiments, preincubation of HUAECs with gamma-interferon induced HLA-DR antigen expression but actually caused a decrease in T-cell-induced PDGF-like protein secretion above background levels (3.0 +/- 0.6 fmol/10(6) ECs) when compared to nonstimulated HUAECs (4.0 +/- 0.4 fmol/10(6) ECs; p less than 0.05). PDGF-like protein secretion was minimal at 1 hour and increased over time to a maximum at 24 hours. The conclusion is that T cells are capable of inducing secretion of a very potent mitogen, PDGF-like protein, from endothelial cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Nrf2-deficient female mice develop lupus-like autoimmune nephritis.

BACKGROUND NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcriptional activator essential for the coordinate transcriptional induction of antioxidant enzymes and phase II drug metabolizing enzymes through the antioxidant response element/electrophile response element. The Nrf2-deficient mice were found to develop normally under standard laboratory conditions. However, upon closer examination, we found that aged female Nrf2-deficient mice displayed a shortened lifespan and developed severe glomerulonephritis. The present study investigated the glomerulonephritis findings in Nrf2-deficient mice. METHODS To evaluate glomerular lesions of Nrf2-deficient mice, histological and functional analyses were performed. The amounts of serum immunoglobulins, anti-double-stranded (ds) DNA antibody, and lipid peroxidation using thiobarbituric acid reactive substances (TBARS) also were measured. RESULTS Nrf2-deficient female mice over 60 weeks of age developed severe nephritis characterized by cellular proliferation, lobular formation, crescent formation, and subepithelial electron-dense deposits. In immunofluorescent assays, Nrf2-deficient female mice showed mesangial deposits and massive granular deposits of IgG, IgM, and C3 along the capillary walls. Higher serum levels of IgG, anti-dsDNA antibody, lower creatinine clearance, and slight splenomegaly also were found in Nrf2-deficient female mice. A higher concentration of TBARS also was found in Nrf2-deficient female mice. CONCLUSIONS These data indicate that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis and suggest that nrf2 is one of the genes determining susceptibility to autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may clarify the mechanisms leading to the development of lupus disease.
Desmosterolosis—phenotypic and molecular characterization of a third case and review of the literature

Desmosterolosis, a rare disorder of cholesterol biosynthesis, is caused by mutations in DHCR24, the gene encoding the enzyme 24‐dehydrocholesterol reductase (DHCR24). To date, desmosterolosis has been described in only two patients. Here we report on a third patient with desmosterolosis who presented after delivery with relative macrocephaly, mild arthrogryposis, and dysmorphic facial features. Brain MRI revealed hydrocephalus, thickening of the tectum and massa intermedia, mildly effaced gyral pattern, underopercularization, and a thin corpus callosum. The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA in yeast. The patient was found to be a compound heterozygote for c.281G>A (p.R94H) and c.1438G>A (p.E480K) mutations. Structural and evolutionary analyses showed that residue R94 resides at the flavin adenine dinucleotide (FAD) binding site and is strictly conserved throughout evolution, while residue E480 is less conserved, but the charge shift substitution is accompanied by drastic changes in the local protein environment of that residue. We compare the phenotype of our patient with previously reported cases. © 2011 Wiley‐Liss, Inc.
Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop

Background: SpeB is a protease secreted from the pathogenic bacterium Streptococcus pyogenes. Results: Apo and inhibitor complex structures of SpeB reveal conformational changes associated with activation and binding. Conclusion: The glycine-rich C-terminal active site loop is required for substrate recognition and product release. Significance: Crystal structures and mutagenesis afford insights into the specificity of SpeB and the functional role of the active site loops in binding biological substrates. Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 Å resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC50 values for trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.
Longitudinal Assessment of Maternal Parenting Capacity Variables and Child Adjustment Outcomes in Pediatric Cancer

This preliminary investigation aimed to longitudinally examine parenting capacity variables, namely parental overprotection, perceived child vulnerability, and parenting stress and their relation to child adjustment in mothers of children on treatment for cancer. As part of a larger study, biological mothers (N=22) completed measures of parental overprotection, perceived child vulnerability, parenting stress, and child adjustment at Time 1 and a follow-up time point. Analyses were conducted to determine whether (1) levels of parental overprotection, perceived child vulnerability, and parenting stress declined from Time 1 to follow-up and (2) if Time 1 parenting capacity variables were associated with child adjustment at follow-up. Results revealed that parental overprotection, perceived child vulnerability, and parenting stress declined from Time 1 to follow-up, and levels of parental overprotection, perceived child vulnerability, and parenting stress at Time 1 were significantly related to child adjustment at follow-up. Collectively, the preliminary findings of this study indicate that mothers of children with cancer evidence improved parenting capacity over time. Furthermore, it seems that Time 1 parenting capacity variables are significantly related to later child adjustment.
Microwave Noise and FET Devices

In this article, a short presentation of available FET technologies (GaAs MESFET, ΠI-V HEMT, and silicon CMOS) has been presented. Why minimum NF is suitable to benchmark different low-noise technologies has been discussed. Following this, basic concepts related to thermal noise in FETs and the reason why such technologies feature outstanding low-noise performance was illustrated/ and a short survey of minimum NF evolution has been presented. InP HEMT technology undoubtedly constitutes the best low-noise technology (especially to address applications in W or G Band). The noise performance of silicon MOSFET technology/ which is widely used in many applications because of its low cost, does not outperform that of GaAs pHEMT technology/ unless channel engineering is performed.
Current Expectations for Newborns Undergoing the Arterial Switch Operation

Background:The arterial switch operation (ASO) represents a remarkable success story in the surgical treatment of cyanotic congenital heart disease. This study is designed to assess recent outcomes after the ASO in babies presenting with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA). Methods:One hundred twenty-five consecutive neonatal and infant ASOs were performed by 2 surgeons at Texas Children's Hospital between July 1, 1995 and October 1, 2003. Patients with TGA and TBA were offered ASO irrespective of patient size and associated cardiac malformations. Primary cardiac diagnoses included TGA with intact ventricular septum (TGA/IVS, n = 79, 63%), TGA with ventricular septal defect (TGA/VSD, n = 37, 30%), and Taussig Bing Anomaly (TBA, n = 9, 7%). Results:With complete follow-up, we observed a 30-day mortality rate of 1.6% (n = 2) with 2 late deaths (1.6%), for an overall actuarial survival rate of 96.3% at 7 years. Although there was a significant incidence of complex coronary ostial origin and branching including single coronary (n = 8, 6.4%) and intramural coronary artery (n = 8, 6.4%), this was not associated with increased operative risk. All patients are fully saturated and NYHA functional class I at latest clinic visit (0.3 to 88.4 months postoperatively). There have been no late coronary events. Of 121 survivors, 7 patients (5.8%) have required cardiovascular reoperation at an average of 15.3 ± 11.7 months postoperatively (range, 3.6 to 30.6 months) for an actuarial freedom from reoperation of 90% at 7 years. Conclusions:Using current methodologies, the ASO can be performed safely and with a low incidence of need for reoperation on intermediate follow-up. Recent experience indicates operative survival rates approaching 100%.
GIGANTEA directly activates Flowering Locus T in Arabidopsis thaliana

Plants perceive environmental signals such as day length and temperature to determine optimal timing for the transition from vegetative to floral stages. Arabidopsis flowers under long-day conditions through the CONSTANS (CO)–FLOWERING LOCUS T (FT) regulatory module. It is thought that the environmental cues for photoperiodic control of flowering are initially perceived in the leaves. We have previously shown that GIGANTEA (GI) regulates the timing of CO expression, together with FLAVIN-BINDING, KELCH REPEAT, F BOX protein 1. Normally, CO and FT are expressed exclusively in vascular bundles, whereas GI is expressed in various tissues. To better elucidate the role of tissue-specific expression of GI in the flowering pathway, we established transgenic lines in which GI is expressed exclusively in mesophyll, vascular bundles, epidermis, shoot apical meristem, or root. We found that GI expressed in either mesophyll or vascular bundles rescues the late-flowering phenotype of the gi-2 loss-of-function mutant under both short-day and long-day conditions. Interestingly, GI expressed in mesophyll or vascular tissues increases FT expression without up-regulating CO expression under short-day conditions. Furthermore, we examined the interaction between GI and FT repressors in mesophyll. We found that GI can bind to three FT repressors: SHORT VEGETATIVE PHASE (SVP), TEMPRANILLO (TEM)1, and TEM2. Finally, our chromatin immunoprecipitation experiments showed that GI binds to FT promoter regions that are near the SVP binding sites. Taken together, our data further elucidate the multiple roles of GI in the regulation of flowering time.
Averaging for a Fully Coupled Piecewise-Deterministic Markov Process in Infinite Dimensions

In this paper we consider the generalized Hodgkin-Huxley model introduced in Austin (2008). This model describes the propagation of an action potential along the axon of a neuron at the scale of ion channels. Mathematically, this model is a fully coupled piecewise-deterministic Markov process (PDMP) in infinite dimensions. We introduce two time scales in this model in considering that some ion channels open and close at faster jump rates than others. We perform a slow-fast analysis of this model and prove that, asymptotically, this ‘two-time-scale’ model reduces to the so-called averaged model, which is still a PDMP in infinite dimensions, for which we provide effective evolution equations and jump rates.