Claudin-5 relieves cognitive decline in Alzheimer's disease mice through suppression of inhibitory GABAergic neurotransmission.

Alzheimer's disease (AD) is characterized by progressive cognitive decline, which is considered as the most common form of dementia in the elderly. Recently, it is suggested that impaired cerebrovascular function may precede the onset of AD. Claudin-5, which is the most enriched tight junction protein, has been reported to prevent the passage of damaging material at the blood-brain barrier. However, whether claudin-5 impacts AD has no direct evidence. We found a decrease level of claudin-5 in the hippocampus of AD and elder mice. And intravenous injection of claudin-5 improved learning and memory ability in these mice, while knockout of the protein led to impaired learning and memory and long-term potentiation in adult control mice. Furthermore, the effects of claudin-5 are mediated by suppressing inhibitory GABAergic neurotransmission. Our results suggest benefit effects of claudin-5 on learning and memory, which may provide a new treatment strategy for AD.

Association between sleep quality and central obesity among southern Chinese reproductive-aged women.

BACKGROUND: The connections between sleep quality and central obesity among reproductive-aged women are not clear. The study aimed to explore the association between sleep quality and central obesity among Chinese reproductive-aged women and identify the independent contributions of sociodemographic characteristics, health-related factors, and sleep quality to central obesity. METHODS: In this cross-sectional survey, the minimal sample sizes were 2404 subjects; 2449 Chinese women aged 18-49 participated in this study. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Central obesity as the outcome of interest was a binary variable; women were categorized as with versus without central obesity measured by waist circumference (WC). The independent contribution of sociodemographic characteristics (Cluster 1), health-related variables (Cluster 2), and sleep quality (Cluster 3) to central obesity was derived from the corresponding R2 change (individual R2 change/total R2 × 100%), using clustered multiple logistic regression analyses. RESULTS: The risk of central obesity increased significantly with poor sleep quality (assessed by global PSQI score) [adjusted odds ratio (OR) = 2.20 per SD increase; 95% confidence interval (CI) = 1.28-3.78; P = 0.004], increased sleep disturbance score (adjusted OR = 1.11 per SD increase; 95% CI = 1.01-1.22; P = 0.042) and decreased subjective sleep quality score (adjusted OR = 0.81 per SD increase; 95% CI = 0.73-0.90; P < 0.001). The independent contribution of sleep quality was 9.9%, less than those of sociodemographic (73.3%) and health-related (16.8%) variables. Among complaints related to sleep disturbance, the inability to breathe comfortably, and having bad dreams showed significant associations with central obesity. CONCLUSIONS: There exists some degree of correlation between sleep quality and central obesity among Chinese reproductive-aged women. These findings underscore the need for future public health guidelines to formulate some detailed strategies to improve sleep quality, such as preventing and intervening risk factors that influence sleep quality and suggesting optimal sleep duration, which might effectively reduce the incidence of central obesity in this population group.

Educational experience of male students in a baccalaureate nursing program in China.

Hampered by culture norms and social values, the proportion of male nursing students in China is low. Their learning experience will add weight to culturally valid nursing education. This study explored Chinese male nursing students' educational experience in a baccalaureate nursing program. A qualitative approach was used, with a purposive sample of 14 participants. Data were collected through semi-structured interviews and analyzed for thematic content. Four theme clusters emerged from the findings: choosing nursing as a career, challenges to studying nursing by gender, dilemma to nursing profession and personal benefits of studying nursing. Most of the participants passively chose nursing major. The data provided evidence that Chinese culture hindered male engaged in nursing. Low admission scores of nursing in NCEE provide an opportunity to recruit male student. Positive aspects of gender neutral portrayal of nursing help to recruit more male nursing students.

A calcium sensor calcineurin B-like 9 negatively regulates cold tolerance via calcium signaling in Arabidopsis thaliana.

Calcineurin B-like protein 9 (CBL9) plays important roles in response to ABA, K+ deprivation in plants. However, whether CBL9 modulates plant adaptation to low-temperature stress is elusive. In this study, we demonstrated that the cbl9 mutants increased freezing tolerance under both cold-acclimating and nonacclimating conditions in Arabidopsis. Cold-induced changes of cytosolic free calcium concentration ([Ca2+]cyt) were then monitored by aequorin-expressed Arabidopsis plants. The results showed that the cold-triggered increases in [Ca2+]cyt levels in cbl9 mutants were clearly higher than those in wild type (WT) plants, while cold-affected changes in free calcium concentration within cytosolic microdomains adjacent to the vacuolar membrane ([Ca2+]md) in cbl9 mutants were similar to those in WT plants. In addition, treatments of seedlings with Ca2+ chelator ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and Ca2+ channel blocker lanthanum chloride markedly inhibit changes of [Ca2+]cyt in cbl9 mutants, while the inhibition of calcium release by lithium chloride from intracellular pools demonstrated consistent suppression of [Ca2+]cyt in cbl9 mutants and WT plants. Together, these results indicate that CBL9 negatively modulates cold tolerance through decreasing [Ca2+]cyt in Arabidopsis.

Modulation of Guard Cell Turgor and Drought Tolerance by a Peroxisomal Acetate-Malate Shunt.

In plants, stomatal movements are tightly controlled by changes in cellular turgor pressure. Carbohydrates produced by glycolysis and the tricarboxylic acid cycle play an important role in regulating turgor pressure. Here, we describe an Arabidopsis mutant, bzu1, isolated in a screen for elevated leaf temperature in response to drought stress, which displays smaller stomatal pores and higher drought resistance than wild-type plants. BZU1 encodes a known acetyl-coenzyme A synthetase, ACN1, which acts in the first step of a metabolic pathway converting acetate to malate in peroxisomes. We showed that BZU1/ACN1-mediated acetate-to-malate conversion provides a shunt that plays an important role in osmoregulation of stomatal turgor. We found that the smaller stomatal pores in the bzu1 mutant are a consequence of reduced accumulation of malate, which acts as an osmoticum and/or a signaling molecule in the control of turgor pressure within guard cells, and these results provided new genetic evidence for malate-regulated stomatal movement. Collectively, our results indicate that a peroxisomal BZU1/ACN1-mediated acetate-malate shunt regulates drought resistance by controlling the turgor pressure of guard cells in Arabidopsis.

AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic Acid Responses through the MKK5-MPK6 Kinase Cascade.

The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction module involved in transducing extracellular signals to the nucleus for appropriate cellular adjustment. This cascade essentially consists of three components: a MAPK kinase kinase (MAPKKK), a MAPK kinase, and a MAPK, connected to each other by the event of phosphorylation. Here, we report the characterization of a MAPKKK, ABA-INSENSITIVE PROTEIN KINASE1 (AIK1), which regulates abscisic acid (ABA) responses in Arabidopsis (Arabidopsis thaliana). T-DNA insertion mutants of AIK1 showed insensitivity to ABA in terms of both root growth and stomatal response. AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. The activity of AIK1 is induced by ABA in Arabidopsis and tobacco (Nicotiana benthamiana), and the Arabidopsis protein phosphatase type 2C, ABI1, a negative regulator of ABA signaling, restricts AIK1 activity by dephosphorylation. Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. The single mutant seedlings of mpk6 and mkk5 have similar phenotypes to aik1, but mkk4 does not. AIK1 was localized in the cytoplasm and shown to activate MKK5 by protein phosphorylation, which was an ABA-activated process. Constitutively active MKK5 in aik1 mutant seedlings complements the ABA-insensitive root growth phenotype of aik1 The activity of MPK6 was increased by ABA in wild-type seedlings, but its activation by ABA was impaired in aik1 and aik1 mkk5 mutants. These findings clearly suggest that the AIK1-MKK5-MPK6 cascade functions in the ABA regulation of primary root growth and stomatal response.

Abscisic Acid as an Internal Integrator of Multiple Physiological Processes Modulates Leaf Senescence Onset in Arabidopsis thaliana.

Many studies have shown that exogenous abscisic acid (ABA) promotes leaf abscission and senescence. However, owing to a lack of genetic evidence, ABA function in plant senescence has not been clearly defined. Here, two-leaf early-senescence mutants (eas) that were screened by chlorophyll fluorescence imaging and named eas1-1 and eas1-2 showed high photosynthetic capacity in the early stage of plant growth compared with the wild type. Gene mapping showed that eas1-1 and eas1-2 are two novel ABA2 allelic mutants. Under unstressed conditions, the eas1 mutations caused plant dwarf, early germination, larger stomatal apertures, and early leaf senescence compared with those of the wild type. Flow cytometry assays showed that the cell apoptosis rate in eas1 mutant leaves was higher than that of the wild type after day 30. A significant increase in the transcript levels of several senescence-associated genes, especially SAG12, was observed in eas1 mutant plants in the early stage of plant growth. More importantly, ABA-activated calcium channel activity in plasma membrane and induced the increase of cytoplasmic calcium concentration in guard cells are suppressed due to the mutation of EAS1. In contrast, the eas1 mutants lost chlorophyll and ion leakage significant faster than in the wild type under treatment with calcium channel blocker. Hence, our results indicate that endogenous ABA level is an important factor controlling the onset of leaf senescence through Ca(2+) signaling.

A Receptor-Like Kinase Mediates Ammonium Homeostasis and Is Important for the Polar Growth of Root Hairs in Arabidopsis.

Ammonium (NH4+) is both a necessary nutrient and an important signal in plants, but can be toxic in excess. Ammonium sensing and regulatory mechanisms in plant cells have not been fully elucidated. To decipher the complex network of NH4+ signaling, we analyzed [Ca2+]cyt-associated protein kinase (CAP) genes, which encode signaling components that undergo marked changes in transcription levels in response to various stressors. We demonstrated that CAP1, a tonoplast-localized receptor-like kinase, regulates root hair tip growth by maintaining cytoplasmic Ca2+ gradients. A CAP1 knockout mutant (cap1-1) produced elevated levels of cytoplasmic NH4+. Furthermore, root hair growth of cap1-1 was inhibited on Murashige and Skoog medium, but NH4+ depletion reestablished the Ca2+ gradient necessary for normal growth. The lower net NH4+ influx across the vacuolar membrane and relatively alkaline cytosolic pH of cap1-1 root hairs implied that mutation of CAP1 increased NH4+ accumulation in the cytoplasm. Furthermore, CAP1 functionally complemented the npr1 (nitrogen permease reactivator protein) kinase yeast mutant, which is defective in high-affinity NH4+ uptake via MEP2 (methylammonium permease 2), distinguishing CAP1 as a cytosolic modulator of NH4+ levels that participates in NH4+ homeostasis-regulated root hair growth by modulating tip-focused cytoplasmic Ca2+ gradients.

NADPH oxidase AtrbohD and AtrbohF function in ROS-dependent regulation of Na⁺/K⁺homeostasis in Arabidopsis under salt stress.

Maintaining cellular Na(+)/K(+) homeostasis is pivotal for plant survival in saline environments. However, knowledge about the molecular regulatory mechanisms of Na(+)/K(+) homeostasis in plants under salt stress is largely lacking. In this report, the Arabidopsis double mutants atrbohD1/F1 and atrbohD2/F2, in which the AtrbohD and AtrbohF genes are disrupted and generation of reactive oxygen species (ROS) is pronouncedly inhibited, were found to be much more sensitive to NaCl treatments than wild-type (WT) and the single null mutant atrbohD1 and atrbohF1 plants. Furthermore, the two double mutant seedlings had significantly higher Na(+) contents, lower K(+) contents, and resultant greater Na(+)/K(+) ratios than the WT, atrbohD1, and atrbohF1 under salt stress. Exogenous H(2)O(2) can partially reverse the increased effects of NaCl on Na(+)/K(+) ratios in the double mutant plants. Pre-treatments with diphenylene iodonium chloride, a widely used inhibitor of NADPH oxidase, clearly enhanced the Na(+)/K(+) ratios in WT seedlings under salt stress. Moreover, NaCl-inhibited inward K(+) currents were arrested, and NaCl-promoted increases in cytosolic Ca(2+) and plasma membrane Ca(2+) influx currents were markedly attenuated in atrbohD1/F1 plants. No significant differences in the sensitivity to osmotic or oxidative stress among the WT, atrbohD1, atrbohF1, atrbohD1/F1, and atrbohD2/F2 were observed. Taken together, these results strongly suggest that ROS produced by both AtrbohD and AtrbohF function as signal molecules to regulate Na(+)/K(+) homeostasis, thus improving the salt tolerance of Arabidopsis.

Plasma membrane-associated proline-rich extensin-like receptor kinase 4, a novel regulator of Ca signalling, is required for abscisic acid responses in Arabidopsis thaliana.

Plant roots respond to environmental stresses or the exogenous plant hormone abscisic acid (ABA) by undergoing marked physiological and morphological changes. We show here that PERK4, a gene that encodes a member of the Arabidopsis thaliana proline-rich extensin-like receptor kinase family, plays an important role in ABA responses. Mutation of PERK4 by T-DNA insertion decreased sensitivity to ABA with respect to seed germination, seedling growth and primary root tip growth. The effect on root growth was due to enhanced cell elongation rather than cell division. The cytosolic free calcium concentration and Ca(2+) channel currents were lower in perk4 root cells than in wild-type cells in the presence of ABA. Root growth was similar in wild-type and perk4 plants after the application of a Ca(2+) channel blocker. PERK4 localised to the plasma membrane, and was shown to be an ABA- and Ca(2+)-activated protein kinase. Our data suggest that the receptor-like kinase encoded by PERK4 functions at an early stage of ABA signalling to inhibit root cell elongation by perturbing Ca(2+) homeostasis.