Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Plastocyanin in the Adjustment of the Photosynthetic Electron Transport to the Carbon Metabolism in Tobacco1

We investigated adaptive responses of the photosynthetic electron transport to a decline in the carbon assimilation capacity. Leaves of different ages from wild-type tobacco (Nicotiana tabacum) L. var Samsun NN and young mature leaves of tobacco transformants with impaired photoassimilate export were used. The assimilation rate decreased from 280 in young mature wild-type leaves to below 50 mmol electrons mol chlorophyll−1 s−1 in older wild-type leaves or in transformants. The electron transport capacity, measured in thylakoids isolated from the different leaves, closely matched the leaf assimilation rate. The numbers of cytochrome (cyt)-bf complexes and plastocyanin (PC) decreased with the electron transport and assimilation capacity, while the numbers of photosystem I (PSI), photosystem II, and plastoquinone remained constant. The PC to PSI ratio decreased from five in leaves with high assimilation rates, to values below one in leaves with low assimilation rates, and the PC versus flux correlation was strictly proportional. Redox kinetics of cyt-f, PC, and P700 suggest that in leaves with low electron fluxes, PC is out of the equilibrium with P700 and cyt-f and the cyt-f reoxidation rate is restricted. It is concluded that the electron flux is sensitive to variations in the number of PC, relative to PSI and cyt-bf, and PC, in concert with cyt-bf, is a key component that adjusts to control the electron transport rate. PC dependent flux control may serve to adjust the electron transport rate under conditions where the carbon assimilation is diminished and thereby protects PSI against over-reduction and reactive oxygen production.
Generation of antigen-specific immunity following systemic immunization with DNA vaccine encoding CCL25 chemokine immunoadjuvant

A significant hurdle in vaccine development for many infectious pathogens is the ability to generate appropriate immune responses at the portal of entry, namely mucosal sites. The development of vaccine approaches resulting in secretory IgA and mucosal cellular immune responses against target pathogens is of great interest and in general, requires live viral infection at mucosal sites. Using HIV-1 and influenza A antigens as models, we report here that a novel systemically administered DNA vaccination strategy utilizing co-delivery of the specific chemokine molecular adjuvant CCL25 (TECK) can produce antigen-specific immune responses at distal sites including the lung and mesenteric lymph nodes in mice. The targeted vaccines induced infiltration of cognate chemokine receptor, CCR9+/CD11c+ immune cells to the site of immunization. Furthermore, data shows enhanced IFN-λ secretion by antigen-specific CD3+/CD8+ and CD3+/CD4+ T cells, as well as elevated HIV-1-specific IgG and IgA responses in secondary lymphoid organs, peripheral blood, and importantly, at mucosal sites. These studies have significance for the development of vaccines and therapeutic strategies requiring mucosal immune responses and represent the first report of the use of plasmid co-delivery of CCL25 as part of the DNA vaccine strategy to boost systemic and mucosal immune responses following intramuscular injection.
The Recombinant Human TRPV6 Channel Functions as Ca2+Sensor in Human Embryonic Kidney and Rat Basophilic Leukemia Cells*

The activation mechanism of the recently cloned human transient receptor potential vanilloid type 6 (TRPV6) channel, originally termed Ca2+ transporter-like protein and Ca2+ transporter type 1, was investigated in whole-cell patch-clamp experiments using transiently transfected human embryonic kidney and rat basophilic leukemia cells. The TRPV6-mediated currents are highly Ca2+-selective, show a strong inward rectification, and reverse at positive potentials, which is similar to store-operated Ca2+ entry in electrically nonexcitable cells. The gating of TRPV6 channels is strongly dependent on the cytosolic free Ca2+ concentration; lowering the intracellular free Ca2+ concentration results in Ca2+ influx, and current amplitude correlates with the intracellular EGTA or BAPTA concentration. This is also the case for TRPV6-mediated currents in the absence of extracellular divalent cations; compared with endogenous currents in nontransfected rat basophilic leukemia cells, these TRPV6-mediated monovalent currents reveal differences in reversal potential, inward rectification, and slope at very negative potentials. Release of stored Ca2+by inositol 1,4,5-trisphosphate and/or the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin appears not to be involved in TRPV6 channel gating in both cell lines but, in rat basophilic leukemia cells, readily activates the endogenous Ca2+ release-activated Ca2+ current. In conclusion, TRPV6, expressed in human embryonic kidney cells and in rat basophilic leukemia cells, functions as a Ca2+-sensing Ca2+ channel independently of procedures known to deplete Ca2+ stores.
Inhibition of transcription selectively reduces the level of ubiquitinated histone H2B in chromatin.

The effect of inhibiting transcription and/or replication on the steady state levels of the ubiquitinated histone isoforms was investigated. We show that treatment of chinese hamster ovary (CHO), monkey kidney (COS), human endometrial carcinoma (Hec-50 and Ishikawa) cells with actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, inhibitors of heterogeneous nuclear RNA synthesis, selectively reduced the levels of ubiquitinated (u) H2B, but not uH2A, uH2A.Z, polyubiquitinated H2A or a novel ubiquitinated histone species, in the chromatin of these cells. The level of the ubiquitinated histones was not affected when synthesis of DNA was arrested. These results show that, in general, maintenance of the levels of uH2B in chromatin is dependent upon ongoing transcription.
Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.

STUDY OBJECTIVE To determine the efficacy and toxicity of combination chemotherapy in patients with advanced, malignant pheochromocytoma. DESIGN Nonrandomized, single-arm trial. SETTING Governmental medical referral center. PATIENTS Fourteen patients with malignant pheochromocytoma confirmed by histologic tests. All patients had metastatic disease and elevated urinary catecholamine secretion. INTERVENTIONS After optimization of antihypertensive therapy, patients received cyclophosphamide, 750 mg/m2 body surface area on day 1; vincristine, 1.4 mg/m2 on day 1, and dacarbazine, 600 mg/m2 on days 1 and 2, every 21 days. MEASUREMENTS AND MAIN RESULTS Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine produced a complete and partial response rate of 57% (median duration, 21 months; range, 7 to more than 34). Complete and partial biochemical responses were seen in 79% of patients (median duration, more than 22 months; range, 6 to more than 35). All responding patients had objective improvement in performance status and blood pressure. Toxicity included expected hematologic, neurologic, and gastrointestinal effects of chemotherapy without serious sequelae. There were four minor hypotensive episodes and one minor hypertensive episode. CONCLUSIONS Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine is effective for advanced malignant pheochromocytoma. Urinary catecholamines are useful to ascertain biochemical response to therapy.
Activity restriction and prior relationship history as contributors to mental health outcomes among middle-aged and older spousal caregivers.

In a sample of cancer patients (n = 75) and spousal caregivers (24 men and 51 women), restriction in caregiver routine activities mediated associations between caregiving stress (patient symptom severity) and caregiver depressed affect and resentment. Moreover, the antecedents and affective consequences of caregiver activity restriction were consistent with the theory of communal relationships (e.g., M. S. Clark & J. Mills, 1979, 1993). If a relationship had been communal in the past (i.e., characterized by mutual concern for and responsiveness to one another's needs), activity restriction was predicted by intimacy and affectional loss (rather than by the severity of patient symptoms) and in turn predicted caregiver depressed affect. Among caregivers in less communal relationships, activity restriction was predicted by severity of patient symptoms (rather than by intimacy and affectional loss) and in turn predicted resentment of care recipients and the caregiving role.
Role of miR-124a in T cell activation and immunity in AIDS patients

The role of microRNA-124a (miR-124a) in the regulation of T cell activation and immunity in patients with AIDS, was studied to provide new insights for the study, diagnosis, alleviation and treatment of AIDS. RT-qPCR technique was used to quantitatively analyze the expression of miR-124a in peripheral blood CD4+ T cells. Dual-luciferase reporter assay system was established to report possible regulatory relations between miR-124a and its potential target gene SIRT1. RT-qPCR and western blot analysis were used to detect the expression level of mRNA and protein of the target genes in T cells. Normal CD4+ T cells from controls were transfected with miR-124a mimics and its negative control, and miR-124a inhibitor and its negative control were transfected into CD4+ T cells from patients with AIDS by T lymphocyte transfection kit to detect the relative expression level of SIRT1 mRNA and protein. The levels of interferon (IFN)-γ, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-2, IL-4 and IL-6 secreted by T helper cells were detected by enzyme-linked immunosorbent assay (ELISA). miR-124a was upregulated in CD4+ T cells of patients with AIDS. The results of firefly luciferase activity detection showed that miR-124a can directly interact with target gene SIRT1 and negatively regulate its expression. miR-124a mimics/inhibitor transfection experiments showed that overexpression of miR-124a in normal CD4+ T cells significantly reduced SIRT1 expression compared with control group, and the expression of miR-124a was positively correlated with IL-10 and TGF-β expression and negatively correlated with IFN-γ expression, but showed no correlation with other cytokines. In AIDS patients, the inhibition of expression of miR-124a in CD4+ T cells significantly increased the expression of SIRT, at the same time, the expression levels of IL-10 and TGF-β were significantly decreased, while the expression level of IFN-γ was significantly increased and no significant difference was found in the expression of other cytokines. The expression of miR-124a in CD4+ T cells of AIDS patients was upregulated and the Th2 type CD4+ T cells are activated by SIRT1 expression inhibition, which in turn enhance the immunity of HIV-infected cells. Our study provides a new molecular target for the diagnosis, alleviation and treatment of AIDS.
Soluble Transferrin Receptor-1 Levels in Mice Do Not Affect Iron Absorption

Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis. To determine the possible role of sTfR1 as a signaling mechanism for iron absorption, a hydrodynamic gene transfer technique was established to express transfected plasmid constructs of human sTfR1 (hsTfR1) and murine sTfR1 (msTfR1) from the livers of C57BL/6 mice. Iron absorption, serum iron levels and hepcidin expression were then measured. The hydrodynamic gene transfer technique proved to be an effective approach to achieving sustained expression of sTfR1 in mice. Although expression of high levels of sTfR1 significantly increased serum iron levels, repeated experiments showed that neither hsTfR1 nor msTfR1 had any effect on iron absorption or hepcidin mRNA expression levels. Thus, despite its attractiveness as a potential modifier of iron absorption, sTfR1 levels do not exert a regulatory effect on iron absorption.
Photopigments in Rhodopseudomonas capsulata cells grown anaerobically in darkness

The phototrophic bacterium Rhodopseudomonas capsulata can obtain energy for dark anaerobic growth from sugar fermentations dependent on accessory oxidants such as trimethylamine-N-oxide or dimethyl sulfoxide. Cells grown for one to two subcultures in this fashion, with fructose as the energy source, showed approximately a twofold increase in bacteriochlorophyll content (per milligram of cell protein) and developed extensive intracytoplasmic membranes in comparison with cells grown photosynthetically at saturating light intensity. Cells harvested from successive anaerobic dark subcultures, however, showed progressively lower pigment contents. After ca. 20 transfers, bacteriochlorophyll and carotenoids were barely detectable, and the amount of intracytoplasmic membrane diminished considerably. Spontaneous mutants incapable of producing normal levels of photosynthetic pigments arose during prolonged anaerobic dark growth. Certain mutants of this kind appear to have a selective advantage over wild-type cells under fermentative growth conditions. Of four pigment mutants characterized (two being completely unable to produce bacteriochlorophyll), only one retained the capacity to grow photosynthetically.
Abstract 052: Epicardial-derived Adrenomedullin Drives Cardiac Hyperplasia During Embryogenesis

The multi-functional peptide adrenomedullin ( Adm = gene, AM = protein) plays important roles in embryonic development and disease. Previous studies demonstrated that Adm knockout mice die at embryonic day 13.5 with small, disorganized hearts and hypoplastic lymphatic vessels, highlighting the importance of this peptide in normal cardiovascular development. Since Adm knockout animals are embryonic lethal, our goal was to generate and characterize a novel model of Adm over-expression to study the role of Adm during development and disease processes. Through gene targeting techniques, we generated a novel mouse model of Adm over-expression, abbreviated as Adm hi/hi . When we assessed gene expression of Adm from 10 different tissues, we found Adm hi/hi mice express 3- to 15-fold more Adm than wildtype littermates. Additionally, peptide levels of AM in lung and kidney, as well as circulating plasma levels of AM were elevated 3-fold over wildtype mice, indicating a functional increase in AM. Our initial analysis revealed that adult Adm hi/hi mice have larger heart weight to body weight ratios than wildtype littermates (4.93±0.23 vs. 5.96±0.29, n = 11-12). We found that compared to wildtype, Adm hi/hi embryos have more proliferating cells during heart development (14.46±1.11 vs. 31.97±2.84, n=4), indicating that hyperplasia drives Adm hi/hi heart enlargement. By crossing the Adm hi/hi line to different tissue-specific Cre lines, we were able to excise the stabilizing bovine growth hormone 3’UTR, thereby returning Adm expression levels back to wildtype in cells with active Cre recombinase. Using this approach, we identified the epicardium as a major source of AM during cardiac development. In conclusion, we found that AM derived primarily from the epicardium drives cardiac hyperplasia during embryonic development resulting in persistent, enlarged hearts of adult Adm hi/hi mice. Since our Adm hi/hi mice recapitulate the 3-fold plasma elevation of AM observed during human disease, this mouse line will be a useful tool for studying the role of elevated AM during disease.
In Vivo Release of Endogenous Amino Acids from the Rat Striatum: Further Evidence for a Role of Glutamate and Aspartate in Corticostriatal Neurotransmission

By means of the push‐pull cannula method, the outflow of endogenous amino acids was studied in the striatum of halothane‐anesthetized rats. Addition of K + ions (30 mM for 4 min) to the superfusion fluid increased the release of aspartate (+116%), glutamate (+ 217%), taurine (+109%), and γ‐aminobutyric acid (GABA) (−429%) whereas a prolonged decrease in the outflow of glutamine (−28%) and a delayed reduction in the efflux of tyrosine (−25%) were observed. In the absence of Ca2‐, the K+‐induced release of aspartate, glutamate, and GABA was blocked whereas the K + ‐induced release of taurine was still present. Under these conditions, the decrease in glutamine efflux was reduced and that of tyrosine was abolished. Local application of tetrodotoxin (5 μM) decreased only the outflow of glutamate (‐25%). One week following lesion of the ipsilateral sensorimotor cortex the spontaneous outflow of glutamine and of tyrosine was enhanced. Despite the lack of change in their spontaneous outflow, the K +‐evoked release of aspartate and glutamate was less pronounced in lesioned than in control animals, whereas the K + ‐evoked changes in GABA and glutamine efflux were not modified. Our data indicate that the push‐pull cannula method is a reliable approach for the study of the in vivo release of endogenous amino acids. In addition, they provide further evidence for a role for glutamate and aspartate as neuro‐transmitters of corticostriatal neurons.
Dieting and working memory: preoccupying cognitions and the role of the articulatory control process.

OBJECTIVES The study aimed to extend previous research that has demonstrated impaired cognitive function among dieters, by teasing out precisely which components of the phonological loop subsystem of working memory are affected by dieting. METHOD Participants were 92 female undergraduate students divided into three groups; current dieters (n = 19), past dieters (n = 29) and never dieters (n = 44). They completed cognitive performance tasks designed to preferentially load on the phonological store and articulatory control process components of the phonological loop, as well as self-report measures. RESULTS Current dieting to lose weight had no effect on the phonological store, as evidenced by the lack of effect on the phonological similarity effect. Dieting did, however, impede the articulatory control process, as evidenced by substantial reduction in the world length effect. This effect was partially mediated by preoccupying cognitions concerning food, weight and body shape. Further, the results mirrored those found with non-dieters under conditions of articulatory suppression. CONCLUSIONS The results clearly identify the articulatory control process as the site of the cognitive impairment suffered by dieters, and thereby offer very strong support to the preoccupying cognitions concerning food, weight and body shape that accompany dieting behaviour as the underlying mechanism.
Plurilinguisme urbain: perspectives de recherche

In diesem Aufsatz werden zunachst die Sprachideologien hinterfragt, welche der Politik der Sprachgebiete und der Amtssprachen in der Schweiz (und anderswo) zugrunde liegen. In einem zweiten Schritt wird auf die Widerspruche zwischen der offiziellen Zweisprachigkeit und der effektiven Mehrsprachigkeit in Biel hingewiesen und die Frage gestellt, welche Schulsprachenpolitik fur Regionen mit zunehmender sprachlicher Vielfalt angemessen ware. Schliesslich wird das Thema der mehrspra-chigen Repertoires angeschnitten, sowohl der Vielfalt ihrer Formen wie der unterschiedlichen Modali-taten ihres Gebrauchs. Dabei wird angedeutet, dass "essentialistische" Vorstellungen von Sprachen bzw. Sprachvarietaten mehr und mehr der Konzeption Platz gemacht haben, dass der Einsatz varia-tioneller Kompetenzen situationsangepasst geschieht und unter den Interaktionspartnern ausgehandelt wird — und dass in stadtischen Umgebungen, wie sie im Bieler Kolloquium vorgestellt wurden, besonders zahlreiche und vielfaltige Sprachpraktiken beobachtet werden konnen, welche eine besondere Chance fur die vertiefte Erforschung dieser Fragen bietet.
Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum

Abstract The Gram-positive bacterium Corynebacterium glutamicum is used for the industrial production of amino acids, e.g. of L-glutamate and L-lysine. During the last 15 years, genetic engineering and amplification of genes have become fascinating methods for studying metabolic pathways in greater detail and for the construction of strains with the desired genotypes. In order to obtain a better understanding of the central metabolism and to quantify the in vivo fluxes in C. glutamicum, the [13C]-labelling technique was combined with metabolite balancing to achieve a unifying comprehensive pathway analysis. These methods can determine the flux distribution at the branch point between glycolysis and the pentose phosphate pathway. The in vivo fluxes in the oxidative part of the pentose phosphate pathway calculated on the basis of intracellular metabolite concentrations and the kinetic constants of the purified glucose-6-phosphate and 6-phosphogluconate dehydrogenases determined in vitro were in full accordance with the fluxes measured by the [13C]-labelling technique. These data indicate that the oxidative pentose phosphate pathway in C. glutamicum is mainly regulated by the ratio of NADPH/NADP concentrations and the specific activity of glucose-6-phosphate dehydrogenase. The carbon flux via the oxidative pentose phosphate pathway correlated with the NADPH demand for L-lysine synthesis. Although it has generally been accepted that phosphoenolpyruvate carboxylase fulfills a main anaplerotic function in C. glutamicum, we recently detected that a biotin-dependent pyruvate carboxylase exists as a further anaplerotic enzyme in this bacterium. In addition to the activities of these two carboxylases three enzymes catalysing the decarboxylation of the C4 metabolites oxaloacetate or malate are also present in this bacterium. The individual flux rates at this complex anaplerotic node were investigated by using [13C]-labelled substrates. The results indicate that both carboxylation and decarboxylation occur simultaneously in C. glutamicum so that a high cyclic flux of oxaloacetate via phosphoenolpyruvate to pyruvate was found. Furthermore, we detected that in C. glutamicum two biosynthetic pathways exist for the synthesis of DL-diaminopimelate and L-lysine. As shown by NMR spectroscopy the relative use of both pathways in vivo is dependent on the ammonium concentration in the culture medium. Mutants defective in one pathway are still able to synthesise enough L-lysine for growth, but the L-lysine yields with overproducers were reduced. The luxury of having these two pathways gives C. glutamicum an increased flexibility in response to changing environmental conditions and is also related to the essential need for DL-diaminopimelate as a building block for the synthesis of the murein sacculus.