Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Vulnerability of CA1 versus CA3 Pyramidal Neurons After Ischemia: Possible Relationship to Sources of Zn2+ Accumulation and Its Entry into and Prolonged Effects on Mitochondria

Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca2+ entry, it is apparent that Zn2+ also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn2+-binding proteins such as metallothionein-III (MT-III). Using mouse hippocampal slices to study acute oxygen glucose deprivation (OGD)-triggered neurodegeneration, we found evidence for early contributions of excitotoxic Ca2+ and Zn2+ accumulation in both CA1 and CA3, as indicated by the ability of Zn2+ chelators or Ca2+ entry blockers to delay pyramidal neuronal death in both regions. However, using knock-out animals (of MT-III and vesicular Zn2+ transporter, ZnT3) and channel blockers revealed substantial differences in relevant Zn2+ sources, with critical contributions of presynaptic release and its permeation through Ca2+- (and Zn2+)-permeable AMPA channels in CA3 and Zn2+ mobilization from MT-III predominating in CA1. To assess the consequences of the intracellular Zn2+ accumulation, we used OGD exposures slightly shorter than those causing acute neuronal death; under these conditions, cytosolic Zn2+ rises persisted for 10–30 min after OGD, followed by recovery over ∼40–60 min. Furthermore, the recovery appeared to be accompanied by mitochondrial Zn2+ accumulation (via the mitochondrial Ca2+ uniporter MCU) in CA1 but not in CA3 neurons and was markedly diminished in MT-III knock-outs, suggesting that it depended upon Zn2+ mobilization from this protein. SIGNIFICANCE STATEMENT The basis for the differential vulnerabilities of CA1 versus CA3 pyramidal neurons is unclear. The present study of events during and after acute oxygen glucose deprivation highlights a possible important difference, with rapid synaptic entry of Ca2+ and Zn2+ contributing more in CA3, but with delayed and long-lasting accumulation of Zn2+ within mitochondria occurring in CA1 but not CA3 pyramidal neurons. These data may be consistent with observations of prominent mitochondrial dysfunction as a critical early event in the delayed degeneration of CA1 neurons after ischemia and support a hypothesis that mitochondrial Zn2+ accumulation in the early reperfusion period may be a critical and targetable upstream event in the injury cascade.
Tectonic setting and processes of mud volcanism on the Mediterranean Ridge accretionary complex: evidence from Leg 160.

Mud volcanism was initiated when overpressured muds rose through the Mediterranean Ridge accretionary prism. Early mud volcanism was marked by eruption of coarse clastic sediments forming small cones of debris flow deposits and turbidites, followed by eruption of large volumes of clast-rich matrix-supported debris flows. Eruption was accompanied by progressive subsidence to form moat-like features. Later, clast-poor mud flows spread laterally and built up a flat-topped cone (Napoli mud volcano). Clasts in the mud volcano sediments are mainly angular and up to 0.5 m in size. These clasts are dominated by claystone, sandstone, and limestone of early‐middle Miocene age that were previously accreted. Matrix material of the mud breccias probably originated from Messinian evaporite-rich sediments located within the decollement zone beneath the accretionary wedge, at an estimated depth of 5-7 km. Pressure release triggered hydrofracturing of poorly consolidated mud near the seafloor. Eruption was accompanied by release of large volumes of hydrocarbon gas. Conditions were suitable for gas hydrate genesis at shallow depths beneath the seafloor at the Milano mud volcano. The mud volcanism is probably related to backthrusting concentrated along the rear of the accretionary wedge near a backstop of continental crust to the north. Clasts within the mud breccias were mainly derived from the North African passive margin, but subordinate lithoclastic ophiolite-related material was also derived from the north, probably from now largely obliterated higher thrust sheets of Crete. Comparisons show that in contrast to other mud volcanoes both on the seafloor (Barbados) and on land (Trinidad), which are usually relatively transient fea tures, mud volcanism on the Mediterranean Ridge has persisted for >1 m.y. A revised hypothesis of mud volcanism at the Ocean Drilling Program sites is proposed, in relation to progressive tectonic evolution of the Mediterranean Ridge accretionary complex.
Activation of c-Src in cells bearing v-Crk and its suppression by Csk

The protein product of the CT10 virus, p47gag-crk (v-Crk), which contains Src homology region 2 (SH2) and 3 (SH3) domains but lacks a kinase domain, is believed to cause an increase in cellular protein tyrosine phosphorylation. A candidate tyrosine kinase, Csk (C-terminal Src kinase), has been implicated in c-Src Tyr-527 phosphorylation, which negatively regulates the protein tyrosine kinase of pp60c-src (c-Src). To investigate how c-Src kinase activity is regulated in vivo, we first looked at whether v-Crk can activate c-Src kinase. We found that cooverexpression of v-Crk and c-Src caused elevation of c-Src kinase activity, resulting in an increase of tyrosine phosphorylation of cellular proteins and morphological transformation of rat 3Y1 fibroblasts. v-Crk and c-Src complexes were not detected, although v-Crk bound to a variety of tyrosine-phosphorylated proteins in cells overexpressing v-Crk and c-Src. Overexpression of Csk in these transformed cells caused reversion to normal phenotypes and also reduced the level of c-Src kinase activity. However, Csk did not cause reversion of cells transformed by v-Src or c-Src527F, in which Tyr-527 was changed to Phe. These results strongly suggest that Csk acts on Tyr-527 of c-Src and suppresses c-Src kinase activity in vivo. Because Csk can suppress transformation by cooverexpression of v-Crk and c-Src, we suggest that v-Crk causes activation of c-Src in vivo by altering the phosphorylation state of Tyr-527.
Allergic sensitization owing to ‘second‐hand’ cat exposure in schools

Background: Environmental allergen loads play an important role in triggering symptoms in atopic individuals. While a number of previous studies have shown that cat allergens (Fel d 1) can be found in school dust samples, no study has provided evidence that public places contribute to increased atopic sensitization rates in children.
Transduction of Neural Precursor Cells with TAT‐Heat Shock Protein 70 Chaperone: Therapeutic Potential Against Ischemic Stroke after Intrastriatal and Systemic Transplantation

Novel therapeutic concepts against cerebral ischemia focus on cell‐based therapies in order to overcome some of the side effects of thrombolytic therapy. However, cell‐based therapies are hampered because of restricted understanding regarding optimal cell transplantation routes and due to low survival rates of grafted cells. We therefore transplanted adult green fluorescence protein positive neural precursor cells (NPCs) either intravenously (systemic) or intrastriatally (intracerebrally) 6 hours after stroke in mice. To enhance survival of NPCs, cells were in vitro protein‐transduced with TAT‐heat shock protein 70 (Hsp70) before transplantation followed by a systematic analysis of brain injury and underlying mechanisms depending on cell delivery routes. Transduction of NPCs with TAT‐Hsp70 resulted in increased intracerebral numbers of grafted NPCs after intracerebral but not after systemic transplantation. Whereas systemic delivery of either native or transduced NPCs yielded sustained neuroprotection and induced neurological recovery, only TAT‐Hsp70‐transduced NPCs prevented secondary neuronal degeneration after intracerebral delivery that was associated with enhanced functional outcome. Furthermore, intracerebral transplantation of TAT‐Hsp70‐transduced NPCs enhanced postischemic neurogenesis and induced sustained high levels of brain‐derived neurotrophic factor, glial cell line‐derived neurotrophic factor, and vascular endothelial growth factor in vivo. Neuroprotection after intracerebral cell delivery correlated with the amount of surviving NPCs. On the contrary, systemic delivery of NPCs mediated acute neuroprotection via stabilization of the blood‐brain‐barrier, concomitant with reduced activation of matrix metalloprotease 9 and decreased formation of reactive oxygen species. Our findings imply two different mechanisms of action of intracerebrally and systemically transplanted NPCs, indicating that systemic NPC delivery might be more feasible for translational stroke concepts, lacking a need of in vitro manipulation of NPCs to induce long‐term neuroprotection. STEM CELLS2012;30:1297–1310
Cysteine-scanning Mutagenesis around Transmembrane Segments 1 and 11 and Their Flanking Loop Regions of Tn10-encoded Metal-Tetracycline/H+ Antiporter*

Putative transmembrane helices (TM) 1 and 11 in the metal-tetracycline/H+ antiporter are predicted to be close to each other on the basis of disulfide cross-linking experiments of the double-cysteine mutants in the periplasmic loop regions (Kubo, Y., Konishi, S., Kawabe, T., Nada, S., and Yamaguchi, A. (2000) J. Biol. Chem. 275, 5270–5274). In this study, each amino acid from Asn-2 to Gly-44 in the putative TM1 and loop1–2 regions or that from Ser-328 to Gly-366 in TM11 and its flanking regions was individually replaced with cysteine. With respect to the TM1 region, 10 mutants, from T5C to L14C, were all not reactive withN-ethylmaleimide (NEM), and from D15C to I22C, NEM-reactive and non-reactive mutations periodically appeared every two residues. Three mutants, M23C to V25C, were all NEM-reactive, but the degree of the latter two mutants was very low. Seven mutants, from L26C to E32C, were all highly reactive with NEM. Therefore, the region of TM1 is composed of the 21 amino acid residues from Thr-5 to Val-25. It is a partially amphiphilic helix, that is, the N-terminal (cytoplasmic) half is embedded in the hydrophobic interior, and the C-terminal (periplasmic) half faces a water-filled channel. With respect to TM11, nine mutants, from S328C to G336C, and six mutants, from L361C to G366C, were all reactive with NEM. On the other hand, out of the 24 mutants, from L337C to S360C, 17 were not reactive with NEM, and the 7 NEM-reactive mutants were scattered, indicating that this region is a transmembrane segment. The 7 residues from Val-347 to Phe-353 including Pro-350 formed a central hydrophobic core, and the 7 NEM-reactive mutations were periodically distributed in its flanking regions, indicating that both ends of TM11 face a water-filled channel. Ala-354 is located at about 1/3 of the length from the periplasmic end of TM11. Disulfide cross-linking experiments on double-cysteine mutants having the combination of A354C and a cysteine-scanning mutation in the loop1–2 region indicated that loop1–2 is very flexible and close to the periplasmic end of TM11. Tetracycline prevented the cross-linking formation between the periplasmic ends of TM1 and TM11; however, it did not affect the cross-linking between loop1–2 and TM11, indicating that the substrate-induced conformational change involves a shift in the relative locations of TM1 and TM11.
On How the Introducing of a New $\theta$ Function Symbol Into Arithmetic's Formalism Is Germane to Devising Axiom Systems that Can Appreciate Fragments of Their Own Hilbert Consistency

A new $\theta$ function primitive is proposed that almost achieves the combined efficiency of the addition, multiplication and successor growth operations. This $\theta$ function symbol enables the constructing of an "IQFS(PA+)" axiom system that can corroborate a fragmentary definition of its own Hilbert consistency, while it will simultaneously verify isomorphic counterparts of all Peano Arithmetic's $\Pi_1$ theorems. Many propositions and intermediate results are also established. Only one intermediate result, which most readers will intuit should be true, does remain formally unproven.
Schools and obesity prevention: creating school environments and policies to promote healthy eating and physical activity.

CONTEXT Research consistently shows that the majority of American children do not consume diets that meet the recommendations of the Dietary Guidelines for Americans, nor do they achieve adequate levels of daily physical activity. As a result, more children are overweight today than at any other time in U.S. history. Schools offer many opportunities to develop strategies to prevent obesity by creating environments in which children eat healthfully and engage regularly in physical activity. METHODS This article discusses the role of schools in obesity prevention efforts. Current issues in schools' food and physical activity environments are examined, as well as federal, state, and local policies related to food and physical activity standards in schools. The article is organized around four key areas: (1) school food environments and policies, (2) school physical activity environments and policies, (3) school body mass index measurements, and (4) school wellness policies. Recommendations for accelerating change also are addressed. FINDINGS The article found that (1) competitive foods (foods sold outside of federally reimbursed school meals) are widely available in schools, especially secondary schools. Studies have related the availability of snacks and drinks sold in schools to students' high intake of total calories, soft drinks, total fat and saturated fat, and lower intake of fruits and vegetables; (2) physical activity can be added to the school curriculum without academic consequences and also can offer physical, emotional, and social benefits. Policy leadership has come predominantly from the districts, then the states, and, to a much lesser extent, the federal government; (3) few studies have examined the effectiveness or impact of school-based BMI measurement programs; and (4) early comparative analyses of local school wellness policies suggest that the strongest policies are found in larger school districts and districts with a greater number of students eligible for a free or reduced-price lunch. CONCLUSIONS Studies show that schools have been making some progress in improving the school food and physical activity environments but that much more work is needed. Stronger policies are needed to provide healthier meals to students at schools; limit their access to low-nutrient, energy-dense foods during the school day; and increase the frequency, intensity, and duration of physical activity at school.
Utility of PCR in diagnosing pulmonary tuberculosis

At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management.
Money, Financial Stability and Efficiency

Most analyses of banking crises assume that banks use real contracts. However, in practice contracts are nominal and this is what is assumed here. We consider a standard banking model with aggregate return risk, aggregate liquidity risk and idiosyncratic liquidity shocks. We show that, with non-contingent nominal deposit contracts, the first-best efficient allocation can be achieved in a decentralized banking system. What is required is that the central bank accommodates the demands of the private sector for fiat money. Variations in the price level allow full sharing of aggregate risks. An interbank market allows the sharing of idiosyncratic liquidity risk. In contrast, idiosyncratic (bank-specific) return risks cannot be shared using monetary policy alone; real transfers are needed.
Implication of NPM1 phosphorylation and preclinical evaluation of the nucleoprotein antagonist N6L in prostate cancer

Despite the advent of several new treatment options over the past years, advanced/metastatic prostate carcinoma (PCa) still remains incurable, which justifies the search for novel targets and therapeutic molecules. Nucleophosmin (NPM1) is a shuttling nucleoprotein involved in tumor growth and its targeting could be a potential approach for cancer therapy. We previously demonstrated that the multivalent pseudopeptide N6L binds to NPM1 potently affecting in vitro and in vivo tumor cell growth of various tumor types as well as angiogenesis. Furthermore, NPM1 binds to androgen receptor (AR) and modulate its activity. In this study, we first investigated the implication of the NPM1 and its Thr199 and Thr234/237 phosphorylated forms in PCa. We showed that phosphorylated forms of NPM1 interact with androgen receptor (AR) in nucleoplasm. N6L treatment of prostate tumor cells led to inhibition of NPM1 phosphorylation in conjunction with inhibition of AR activity. We also found that total and phosphorylated NPM1 were overexpressed in castration-resistant PCa. Assessment of the potential therapeutic role of N6L in PCa indicated that N6L inhibited tumor growth both in vitro and in vivo when used either alone or in combination with the standard-of-care first- (hormonotherapy) and second-line (docetaxel) treatments for advanced PCa. Our findings reveal the role of Thr199 and Thr234/237 phosphorylated NPM1 in PCa progression and define N6L as a new drug candidate for PCa therapy.
Physiological studies in aerobic batch cultivations of Saccharomyces cerevisiae strains harboring the MEL1 gene

Physiological studies of Saccharomyces cerevisiae strains harboring the MEL1 gene were carried out in aerobic batch cultivations on glucose–galactose mixtures and on the disaccharide melibiose, which is hydrolyzed by the enzyme melibiase (Mel1, EC 3.2.1.22) into a glucose and a galactose moiety. The strains examined (T200, T256, M24, and TH1) were all derived from the bakers' and distillers' strain of S. cerevisiae, DGI 342. All the strains showed a significant higher ethanol yield when growing on glucose, and half the biomass yield, compared with growth on galactose. The maximum specific uptake rates were 2.5–3.3‐fold higher on glucose than on galactose for all the strains examined, and hence, ethanol production was pronounced on glucose due to respiro‐fermentative metabolism. The T256 strain and the T200 strain having the MEL1 gene inserted in the HXK2 locus and the LEU2 locus, respectively, hydrolyzed melibiose with low specific hydrolysis rates of 0.03 C‐mol/g/h and 0.04 C‐mol/g/h, respectively. This resulted in high biomass yields on melibiose in the order of 10 g/C‐mol compared with 3.7 g/C‐mol for M24 and 1.6 g/C‐mol for TH1. The M24 strain, constructed by classical breeding, and the mig1/gal80 disrupted and melibiase‐producing strain TH1, were superior in their ability to hydrolyze melibiose into glucose and galactose showing specific melibiose hydrolysis rates of 0.17 C‐mol/g/h and 0.24 C‐mol/g/h, respectively. Hence, high ethanol yields on melibiose were obtained with these two strains. Growth on the glucose–galactose mixtures showed a reduction of glucose control successfully obtained in the M24 strain and the TH1 strain. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 68: 252–259, 2000.
The Relation Between Power Output, Oxygen Uptake and Heart Rate in Male Athletes

As the exercise intensity is often expressed as percentage of either maximal workload (%Wmax), percentage of maximal heart rate (%HRmax), or as percentage of maximal oxygen uptake, the relationship between %Wmax, %VO2max, and %HRmax was determined in 53 male cyclists. All subjects performed an incremental maximal cycle ergometer test. In all athletes examined, a linear relation between power output, oxygen uptake and heart rate was observed. The relationships between %Wmax and %VO2max as well as between %Wmax and %HRmax were linear (r = 0.98 and r = 0.97; p < 0.001). It is concluded that studies which are different in expression of exercise intensity (%Wmax or %VO2max) can be compared and that the relation between %Wmax and %HRmax needs to be determined individually when an appropriate individualized training intensity based on heart rate is required.
A Qualitative Examination of Barriers and Motivators to Smoking Cessation among HIV Positive African

Purpose: To identify barriers and motivators to smoking cessation among HIVpositive African American men-who-have-sex with men (MSM) who smoke. Procedures: A convenience sample of smokers was recruited for this study using a range of outreach approaches. Focus groups (N = 4) were conducted that examined: quit experiences, barriers to and motivators of cessation, cultural beliefs, and community norms. Established qualitative methods were used to conduct and analyze the focus groups. Findings: Participants (N = 31) reporting being diagnosed with HIV+ for M = 12 years. More than 60% reported a quit attempt in the past year. Knowledge was about effective smoking cessation treatments and the negative impact of smoking on the management of HIV was low. Barriers to smoking cessation included: low-self-efficacy, environmental, cultural, emotional, and provider factors. Motivators included: finances, health, appearance, and changing social norms. Conclusions: Study findings point to a number of barriers to and facilitators of smoking cessation in this population. Study results have implications for clinical practice, outreach and awareness campaigns, and future research.