The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes.

Altered Ca2+ handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. However, whether Ca2+ directly regulates sarcomere structure has remained elusive. Using a zebrafish ncx1 mutant, we explored the impacts of impaired Ca2+ homeostasis on myofibril integrity. We found that the E3 ubiquitin ligase murf1 is upregulated in ncx1-deficient hearts. Intriguingly, knocking down murf1 activity or inhibiting proteasome activity preserved myofibril integrity, revealing a MuRF1-mediated proteasome degradation mechanism that is activated in response to abnormal Ca2+ homeostasis. Furthermore, we detected an accumulation of the murf1 regulator FoxO in the nuclei of ncx1-deficient cardiomyocytes. Overexpression of FoxO in wild type cardiomyocytes induced murf1 expression and caused myofibril disarray, whereas inhibiting Calcineurin activity attenuated FoxO-mediated murf1 expression and protected sarcomeres from degradation in ncx1-deficient hearts. Together, our findings reveal a novel mechanism by which Ca2+ overload disrupts myofibril integrity by activating a Calcineurin-FoxO-MuRF1-proteosome signaling pathway

Using Positive Psychology to Bolster Student Success at GateWay Community College

Supported by a situational analysis and review of positive psychological literature, this paper outlines an application plan to support GateWay Community College’s ‘experiential learning with a purpose\u27 vision which focuses on infusing meaning into students’ career development and learning. This vision was articulated by Kerry Sanderson, Director of Career Services, and Jessica Brosilo, Service Learning Center Coordinator, in the form of three guiding principles for our work: 1) accessing large student populations, 2) developing students\u27 personal meaning and understanding of purpose through career goals, and 3) cultivating a broader view of success beyond career goals. Future-mindedness and self-efficacy emerged as key pillars in an integrative system for building meaning, along with the importance of persistence which surfaced through our discussions with Sanderson and Brosilo and our review of the Maricopa County Community College District and GateWay Community College’s joint strategic direction on student support goals. Our application plan rests on these three pillars: future-mindedness, self-efficacy, and meaning – with persistence running as a key thread throughout. The plan resides on three key processes: 1) administering a foundational, future-oriented writing exercise for incoming students that also cultivates foundations for self-efficacy and goal setting; 2) administering a growth mindset, belonging and self-efficacy intervention focused on messaging and environmental for incoming students, and 3) ongoing programming for students that supports purpose and meaning as well as student persistence

Jeremy Safran: a hero's journey

In this essay I explore Jeremy Safran’s intellectual career as a hero’s journey or monomyth within the specific context of psychotherapy research. I argue that he fits such model in the sense that his work – though deeply informed by theories – was singularly focused and driven by his own sense of his role and mission within the profession. Rather than attempting to review in detail the entire scope or specific parts of his research contributions, I look at his scholarship as a kind of quest, a pursuit that was trans-theoretical but unified by foundational questions about the unique nature of the relationship between therapist and patient

Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)

Background: The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Despite comprising up to 5% of the genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due to antigenic variation. In this model, pir genes are called cir s and may be involved in this mechanism, allowing evasion of host immune responses. In order to fully understand the role(s) of CIR proteins during P. chabaudi infection, a detailed characterization of the cir gene family was required. Results: The cir repertoire was annotated and a detailed bioinformatic characterization of the encoded CIR proteins was performed. Two major sub-families were identified, which have been named A and B. Members of each sub-family displayed different amino acid motifs, and were thus predicted to have undergone functional divergence. In addition, the expression of the entire cir repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified. In addition, some differences were observed in the pattern of expression between the cir subgroups at the peak of P. chabaudi infection. Finally, specific cir genes were expressed at different time points during asexual blood stages. Conclusions: In conclusion, the large number of cir genes and their expression throughout the intraerythrocytic cycle of development indicates that CIR proteins are likely to be important for parasite survival. In particular, the detection of dominant cir transcripts at the peak of P. chabaudi infection supports the idea that CIR proteins are expressed, and could perform important functions in the biology of this parasite. Further application of the methodologies described here may allow the elucidation of CIR sub-family A and B protein functions, including their contribution to antigenic variation and immune evasion

Clarice Lispector e Franz Kafka: trilhas e vislumbres

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Literatura.Neste trabalho privilegio o argumento de que as personagens de Clarice entram repentina, estranha e surpreendentemente num estado de revelação de seu ser, ganhando assim, existência de humanos. Na busca dessa existência, Clarice assimilou a herança kafkiana que se refere a um mundo de opressão e angústia. Clarice e Kafka, através do poder narrativo projetam suas inquietações, externam seus anseios e compõem sua visão de mundo, sempre em busca do mistério, da essência, por meio das indagações sobre a vida e a morte em si mesmos. Porém, numa fração de segundo, seus personagens deparam-se com uma revelação fulminante capaz de os arrancar da inércia, do contato frio com o miserável cotidiano. O caminho percorrido nesse trabalho passa inicialmente pelo momento inaugural de Clarice Lispector e pela forma como foi recebida pela crítica nacional e estrangeira, bem como pelo fato de a escritora também ter se dedicado à pintura como forma de reproduzir a realidade no desenho. Em seguida, percorro a trilha das singularidades entre Kafka e Clarice: o primeiro cresceu sob as influências de três culturas: a judaica, a tcheca e a alemã. Clarice era ucraniana-judia e escrevia em português, deste modo toda a sua obra ergue-se num espaço entre sua origem judaica e sua condição de brasileira. Ainda seguindo a trilha das singularidades entre os dois escritores, aparece a função da animalidade como meio de contraste com a existência humana. Na última parte alguns contos de Clarice e Kafka são analisados para comprovar que através da linguagem acontece o mergulho, a viagem apenas de ida para Kafka e de ida e volta para Clarice

Decreased airway epithelial ion transport was associated with the severity of the respiratory syncytial virus infection and complications in infants

Abstract The respiratory syncytial virus (RSV) primarily infects airway epithelial cells. It also decreases airway epithelial sodium transport, especially through the epithelial sodium channel (ENaC) (1), which is crucial for osmosis-based fluid absorption across respiratory epithelium. Meanwhile, the electrochemical balance is maintained by secretion of chloride ions through apical chloride channels, including the cystic fibrosis transmembrane conductance regulator (CFTR) (1). In animals, ENaC inhibition has caused middle ear fluid collection in acute otitis media (AOM) (2).Peer reviewe

Enhanced Metabolite Productivity of Escherichia coli Adapted to Glucose M9 Minimal Medium

High productivity of biotechnological strains is important to industrial fermentation processes and can be constrained by precursor availability and substrate uptake rate. Adaptive laboratory evolution (ALE) of Escherichia coli MG1655 to glucose minimal M9 medium has been shown to increase strain fitness, mainly through a key mutation in the transcriptional regulator rpoB, which increases flux through central carbon metabolism and the glucose uptake rate. We wanted to test the hypothesis that a substrate uptake enhancing rpoB mutation can translate to increased productivity in a strain possessing a heterologous metabolite pathway. When engineered for heterologous mevalonate production, we found that E. coli rpoB E672K strains displayed 114–167% higher glucose uptake rates and 48–77% higher mevalonate productivities in glucose minimal M9 medium. This improvement in heterologous mevalonate productivity of the rpoB E672K strain is likely mediated by the elevated glucose uptake rate of such strains, which favors overflow metabolism toward acetate production and availability of acetyl-CoA as precursor. These results demonstrate the utility of adaptive laboratory evolution (ALE) to generate a platform strain for an increased production rate for a heterologous product

BRITE-Constellation: Data processing and photometry

The BRITE mission is a pioneering space project aimed at the long-term photometric monitoring of the brightest stars in the sky by means of a constellation of nano-satellites. Its main advantage is high photometric accuracy and time coverage inaccessible from the ground. The main aim of this paper is the presentation of procedures used to obtain high-precision photometry from a series of images acquired by the BRITE satellites in two modes of observing, stare and chopping. We developed two pipelines corresponding to the two modes of observing. The assessment of the performance of both pipelines is presented. It is based on two comparisons, which use data from six runs of the UniBRITE satellite: (i) comparison of photometry obtained by both pipelines on the same data, which were partly affected by charge transfer inefficiency (CTI), (ii) comparison of real scatter with theoretical expectations. It is shown that for CTI-affected observations, the chopping pipeline provides much better photometry than the other pipeline. For other observations, the results are comparable only for data obtained shortly after switching to chopping mode. Starting from about 2.5 years in orbit, the chopping mode of observing provides significantly better photometry for UniBRITE data than the stare mode. This paper shows that high-precision space photometry with low-cost nano-satellites is achievable. The proposed meth- ods, used to obtain photometry from images affected by high impulsive noise, can be applied to data from other space missions or even to data acquired from ground-based observations

Prognostic value of renal fractional flow reserve in blood pressure response after renal artery stenting (PREFER study)

Background: The aim of our study was to determine a potential relationship between restingtranslesional pressures ratio (Pd/Pa ratio), renal fractional fl ow reserve (rFFR) and bloodpressure response after renal artery stenting.Methods: Thirty fi ve hypertensive patients (49% males, mean age 64 years) with at least60% stenosis in angiography, underwent renal artery stenting. Translesional systolic pressuregradient (TSPG), Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures)and hyperemic rFFR — after intrarenal administration of papaverine — were measured beforestent implantation. Ambulatory blood pressure measurements (ABPM) were recorded beforethe procedure and after 6 months. The ABPM results were presented as blood pressure changesin subgroups of patients with normal (≥ 0.9) vs. abnormal (< 0.9) Pd/Pa ratio and normal(≥ 0.8) vs. abnormal (< 0.8) rFFR.Results: Median Pd/Pa ratio was 0.84 (interquartile range 0.79–0.91) and strongly correlatedwith TSPG (r = –0.89, p < 0.001), minimal lumen diameter (MLD; r = 0.53, p < 0.005)and diameter stenosis (DS; r = –0.51, p < 0.005). Median rFFR was 0.78 (0.72–0.82). Similarly,signifi cant correlation between rFFR and TSPG (r = –0.86, p < 0.0001), as well as withMLD (r = 0.50, p < 0.005) and DS (r = –0.51, p < 0.005) was observed. Procedural successwas obtained in all patients. Baseline Pd/Pa ratio and rFFR did not predict hypertension responseafter renal artery stenting. Median changes of 24-h systolic/diastolic blood pressure werecomparable in patients with abnormal vs. normal Pd/Pa ratio (–4/–3 vs. 0/2 mm Hg; p = NS)and with abnormal vs. normal rFFR (–2/–1 vs. –2/–0.5 mm Hg, respectively).Conclusions: Physiological assessment of renal artery stenosis using Pd/Pa ratio and papaverine-induced renal fractional fl ow reserve did not predict hypertension response after renalartery stenting