Optimization of leaf morphology in relation to leaf water status: A theory.

The leaf economic traits such as leaf area, maximum carbon assimilation rate, and venation are all correlated and related to water availability. Furthermore, leaves are often broad and large in humid areas and narrower in arid/semiarid and hot and cold areas. We use optimization theory to explain these patterns. We have created a constrained optimization leaf model linking leaf shape to vein structure that is integrated into coupled transpiration and carbon assimilation processes. The model maximizes net leaf carbon gain (NPPleaf) over the loss of xylem water potential. Modeled relations between leaf traits are consistent with empirically observed patterns. As the results of the leaf shape-venation relation, our model further predicts that a broadleaf has overall higher NPPleaf compared to a narrowleaf. In addition, a broadleaf has a lower stomatal resistance compared to a narrowleaf under the same level of constraint. With the same leaf area, a broadleaf will have, on average, larger conduits and lower total leaf xylem resistance and thus be more efficient in water transportation but less resistant to cavitation. By linking venation structure to leaf shape and using water potential as the constraint, our model provides a physical explanation for the general pattern of the covariance of leaf traits through the safety-efficiency trade-off of leaf hydraulic design

Alien Registration- Martin, Yvonne E. (Limestone, Aroostook County)

https://digitalmaine.com/alien_docs/35126/thumbnail.jp

New insights into pulmonary hypertension: a role for connexin-mediated signalling

Pulmonary hypertension is a serious clinical condition characterised by increased pulmonary arterial pressure. This can lead to right ventricular failure which can be fatal. Connexins are gap junction-forming membrane proteins which serve to exchange small molecules of less than 1 kD between cells. Connexins can also form hemi-channels connecting the intracellular and extracellular environments. Hemi-channels can mediate adenosine triphosphate release and are involved in autocrine and paracrine signalling. Recently, our group and others have identified evidence that connexin-mediated signalling may be involved in the pathogenesis of pulmonary hypertension. In this review, we discuss the evidence that dysregulated connexin-mediated signalling is associated with pulmonary hypertension

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

Dysregulation of endothelial cell connexin-43 localisation in response to doxorubicin

Introduction: Anthracyclines, such as doxorubicin, remain an important class of chemotherapeutic agent however their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity. Whilst most studies have focused on cardiomyocyte impairment, circulating doxorubicin has been shown to impact human microvascular responses to doxorubicin in coronary vessels.1 Studies show increased endothelial cell permeability resulting in increased paracellular permeability due to damage to the integrity of cell-cell junctions.2 Strategies to maintain vessel integrity and prevent endothelial cell dysregulation could represent a novel therapeutic opportunity to limit the toxic effects of doxorubicin. The aim of this project was to assess the impact of doxorubicin upon endothelial gap junction proteins, in particular connexin-43 (Cx43)

Extracellular Localisation of the C-Terminus of DDX4 Confirmed by Immunocytochemistry and Fluorescence-Activated Cell Sorting

Putative oogonial stem cells (OSCs) have been isolated by fluorescence-activated cell sorting (FACS) from adult human ovarian tissue using an antibody against DEAD-box helicase 4 (DDX4). DDX4 has been reported to be germ cell specific within the gonads and localised intracellularly. White et al. (2012) hypothesised that the C-terminus of DDX4 is localised on the surface of putative OSCs but is internalised during the process of oogenesis. This hypothesis is controversial since it is assumed that RNA helicases function intracellularly with no extracellular expression. To determine whether the C-terminus of DDX4 could be expressed on the cell surface, we generated a novel expression construct to express full-length DDX4 as a DsRed2 fusion protein with unique C- and N-terminal epitope tags. DDX4 and the C-terminal myc tag were detected at the cell surface by immunocytochemistry and FACS of non-permeabilised human embryonic kidney HEK 293T cells transfected with the DDX4 construct. DDX4 mRNA expression was detected in the DDX4-positive sorted cells by RT-PCR. This study clearly demonstrates that the C-terminus of DDX4 can be expressed on the cell surface despite its lack of a conventional membrane-targeting or secretory sequence. These results validate the use of antibody-based FACS to isolate DDX4-positive putative OSCs

SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors

Background: Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear. Methods: Utilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/− mouse model was used to detect entero-endocrine cell hyperplasia with IHC. Results: Analyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/− mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease. Conclusions: Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs