The Transcription Factor NFAT5 Is Required for Cyclin Expression and Cell Cycle Progression in Cells Exposed to Hypertonic Stress

Background: Hypertonicity can perturb cellular functions, induce DNA damage-like responses and inhibit proliferation. The transcription factor NFAT5 induces osmoprotective gene products that allow cells to adapt to sustained hypertonic conditions. Although it is known that NFAT5-deficient lymphocytes and renal medullary cells have reduced proliferative capacity and viability under hypertonic stress, less is understood about the contribution of this factor to DNA damage responses and cell cycle regulation. Methodology/Principal Findings: We have generated conditional knockout mice to obtain NFAT5−/− T lymphocytes, which we used as a model of proliferating cells to study NFAT5-dependent responses. We show that hypertonicity triggered an early, NFAT5-independent, genotoxic stress-like response with induction of p53, p21 and GADD45, downregulation of cyclins, and cell cycle arrest. This was followed by an NFAT5-dependent adaptive phase in wild-type cells, which induced an osmoprotective gene expression program, downregulated stress markers, resumed cyclin expression and proliferation, and displayed enhanced NFAT5 transcriptional activity in S and G2/M. In contrast, NFAT5−/− cells failed to induce osmoprotective genes and exhibited poorer viability. Although surviving NFAT5−/− cells downregulated genotoxic stress markers, they underwent cell cycle arrest in G1/S and G2/M, which was associated with reduced expression of cyclins E1, A2 and B1. We also show that pathologic hypertonicity levels, as occurring in plasma of patients and animal models of osmoregulatory disorders, inhibited the induction of cyclins and aurora B kinase in response to T cell receptor stimulation in fresh NFAT5−/− lymphocytes. Conclusions/Significance: We conclude that NFAT5 facilitates cell proliferation under hypertonic conditions by inducing an osmoadaptive response that enables cells to express fundamental regulators needed for cell cycle progression.Molecular and Cellular Biolog

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Aggression, deviance, and personality adaptation as antecedents and consequences of alienation and involvement in high school

Alienation from, or involvement in, the social and educational systems of the high school are investigated in an effort to determine the extent that school experiences may influence aggressive and deviant behavior in school and personality styles or orientations. Drawing upon longitudinal data collected from 250 boys followed from grades 8 through 12, potential antecedent-consequence relationships between dimensions of alienation and involvement and these two basic types of student outcomes are examined by cross-lagged panel analyses. Differences between cross-lagged panel correlations provide evidence that student reactions and attachments to school manifest relationships with aggression, deviance, and personality, serving as both antecedents and consequences of these student adaptations. The major findings provide evidence that (1) boys who more frequently break school rules and engage in aggressive or deviant behavior may often come to have more negative attitudes toward school staff and less involvement in school; and (2) student involvement and participation in school life can influence certain aspects of adolescent personality. Possible evidence of reciprocal causation is presented and discussed, as are additional theoretical and methodological implications of the data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45259/1/10964_2005_Article_BF01537471.pd

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease

A Voxel-Based Individual Tree Stem Detection Method Using Airborne LiDAR in Mature Northeastern U.S. Forests

This paper describes a new method for detecting individual tree stems that was designed to perform well in the challenging hardwood-dominated, mixed-species forests common to the northeastern U.S., where canopy height-based methods have proven unreliable. Most prior research in individual tree detection has been performed in homogenous coniferous or conifer-dominated forests with limited hardwood presence. The study area in central Pennsylvania, United States, includes 17+ tree species and contains over 90% hardwoods. Existing methods have shown reduced performance as the proportion of hardwood species increases, due in large part to the crown-focused approaches they have employed. Top-down approaches are not reliable in deciduous stands due to the inherent complexity of the canopy and tree crowns in such stands. This complexity makes it difficult to segment trees and accurately predict tree stem locations based on detected crown segments. The proposed voxel column-based approach has advantages over both traditional canopy height model-based methods and computationally demanding point-based solutions. The method was tested on 1125 reference trees, ≥10 cm diameter at breast height (DBH), and it detected 68% of all reference trees and 87% of medium and large (sawtimber-sized) trees ≥28 cm DBH. Significantly, the commission rate (false predictions) was negligible as most raw false positives were confirmed in follow-up field visits to be either small trees below the threshold for recording or trees that were otherwise missed during the initial ground survey. Minimizing false positives was a priority in tuning the method. Follow-up in-situ evaluation of individual omission and commission instances was facilitated by the high spatial accuracy of predicted tree locations generated by the method. The mean and maximum predicted-to-reference tree distances were 0.59 m and 2.99 m, respectively, with over 80% of matches within <1 m. A new tree-matching method utilizing linear integer programming is presented that enables rigorous, repeatable matching of predicted and reference trees and performance evaluation. Results indicate this new tree detection method has potential to be operationalized for both traditional forest management activities and in providing the more frequent and scalable inventories required by a growing forest carbon offsets industry

Endobronchial Ultrasound-guided Sampling of Centrally Located Intrapulmonary Tumors Provides Suitable Material for Diagnostic and Molecular Testing

BACKGROUND: Curvilinear endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a key diagnostic and staging procedure for patients with suspected lung cancer. However, sampling centrally located intrapulmonary tumors is feasible but less well established. MATERIALS AND METHODS: We retrospectively evaluated the diagnostic utility of EBUS-TBNA in patients who underwent sampling of centrally located intrapulmonary tumors. Diagnostic accuracy, sample suitability for molecular testing, and complications were assessed. RESULTS: Between January 2015 and April 2021, 102 EBUS-TBNA procedures sampled centrally located intrapulmonary tumors in 99 patients. The median age was 70 [interquartile range, 63 to 75] years and 51% (51/99) were male. The commonest site was the right upper lobe (n=42/99; 42%). The median tumor size was 29 [interquartile range, 21 to 35] mm. The diagnostic yield was 88/102 (86%) with a false negative rate of 14% (14/102). In addition to intrapulmonary tumor sampling, lymph nodes were sampled in 65/102 procedures and 30/65(46%) were positive for lung cancer. Cancer was diagnosed in 87/99 (88%) cases. When requested, molecular testing was adequate in ≥94% of samples. Complications included minor bleeding in 6/102 (6%) with 2 requiring cold saline instillation, desaturation in 1/102 (1%), and tachycardia in 1/102(1%). One procedure was abandoned due to patient tachycardia. Delayed complications occurred in 1 patient who was hospitalized ≤7 days with pneumonia. CONCLUSION: EBUS-TBNA sampling of centrally located intrapulmonary tumors provides similar diagnostic accuracy to lymph node sampling, provides suitable material for molecular testing, and has a low complication rate.Not heldPublished version, accepted version (12 months embrago