Hypoxia Sensing in Plants: On a Quest for Ion Channels as Putative Oxygen Sensors.

Over 17 million km2 of land is affected by soil flooding every year, resulting in substantial yield losses and jeopardizing food security across the globe. A key step in resolving this problem and creating stress-tolerant cultivars is an understanding of the mechanisms by which plants sense low-oxygen stress. In this work, we review the current knowledge about the oxygen-sensing and signaling pathway in mammalian and plant systems and postulate the potential role of ion channels as putative oxygen sensors in plant roots. We first discuss the definition and requirements for the oxygen sensor and the difference between sensing and signaling. We then summarize the literature and identify several known candidates for oxygen sensing in the mammalian literature. This includes transient receptor potential (TRP) channels; K+-permeable channels (Kv, BK and TASK); Ca2+ channels (RyR and TPC); and various chemo- and reactive oxygen species (ROS)-dependent oxygen sensors. Identified key oxygen-sensing domains (PAS, GCS, GAF and PHD) in mammalian systems are used to predict the potential plant counterparts in Arabidopsis. Finally, the sequences of known mammalian ion channels with reported roles in oxygen sensing were employed to BLAST the Arabidopsis genome for the candidate genes. Several plasma membrane and tonoplast ion channels (such as TPC, AKT and KCO) and oxygen domain-containing proteins with predicted oxygen-sensing ability were identified and discussed. We propose a testable model for potential roles of ion channels in plant hypoxia sensing.

Functional dissection of KATP channel structures reveals the importance of a conserved interface.

ATP-sensitive potassium channels (KATP) are inhibited by ATP but activated by Mg-ADP, coupling the intracellular ATP/ADP ratio to the potassium conductance of the plasma membrane. Although there has been progress in determining the structure of KATP, the functional significance of the domain-domain interface in the gating properties of KATP channels remains incompletely understood. In this study, we define the structure of KATP as two modules: KATPcore and SURABC. Based on this model, we identified two functionally important interfaces between these two modules, namely interface I and interface II. Further structure-guided mutagenesis experiments indicate that destabilizing interface II by deleting ECL3 on the SUR1 subunit impairs KNtp-independent Mg-ADP activation, demonstrating the essential role of intramolecular interactions between KATPcore and SURABC in Mg-ADP activation. Additionally, interface II is functionally conserved between SUR1 and SUR2, and the hydrophobic residue F351 on ECL3 of SUR1 is crucial for maintaining the stability of this interface.

Effect of salbutamol on the measurement of single-breath diffusing capacity.

BACKGROUND AND OBJECTIVE: The bronchodilation and cardiovascular effects of bronchodilators may alter alveolar ventilation and perfusion distribution, which could subsequently affect single-breath diffusing capacity of the lungs for carbon monoxide (DL ,CO) measurements. The aim of this study was to investigate the effect of salbutamol on DL ,CO in subjects with and without airway obstruction and reversibility. METHODS: Sixty subjects were investigated with 20 in each of the three groups: normal spirometry; irreversible obstruction; and reversible obstruction. Baseline spirometry, plethysmographic lung volumes, DL ,CO, pulse rate and arterial blood gases were measured. The same testing sequence was repeated after administration of a placebo inhaler and again after 400 µg salbutamol. RESULTS: Salbutamol did not affect the mean alveolar volume (VA ) (P > 0.05), transfer coefficient for carbon monoxide (DL ,CO/VA , KCO) (P > 0.05) or DL ,CO (P > 0.05) in the normal and irreversible obstruction groups. In the reversible obstruction group, salbutamol caused an increase in the mean VA compared with placebo (P < 0.001). However, the mean KCO was reduced (P < 0.001). The mean change in DL ,CO was not significant (P > 0.05). A considerable reduction in DL ,CO was found after salbutamol in four subjects in the reversible group as a result of a minor increase in VA and substantial decrease in KCO. No statistical difference in pulse rate or arterial blood gases values was detected. CONCLUSIONS: Salbutamol had no effect on the mean DL ,CO in any group. However, salbutamol may considerably reduce DL ,CO in some individuals with reversibility secondary to its effects on VA and KCO.

Relationships of computed tomography-based small vessel indices of the lungs with ventilation heterogeneity and high transfer coefficients in non-smokers with asthma.

Background: The mechanism of high transfer coefficients of the lungs for carbon monoxide (Kco) in non-smokers with asthma is explained by the redistribution of blood flow to the area with preserved ventilation, to match the ventilation perfusion. Objectives: To examine whether ventilation heterogeneity, assessed by pulmonary function tests, is associated with computed tomography (CT)-based vascular indices and Kco in patients with asthma. Methods: Participants were enrolled from the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) study that included a prospective asthmatic cohort. Pulmonary function tests including Kco, using single breath methods; total lung capacity (TLC), using multiple breath methods; and CT, were performed on the same day. The ratio of the lung volume assessed using single breath methods (alveolar volume; VA) to that using multiple breath methods (TLC) was calculated as an index of ventilation heterogeneity. The volume of the pulmonary small vessels <5 mm2 in the whole lung (BV5 volume), and number of BV5 at a theoretical surface area of the lungs from the plural surface (BV5 number) were evaluated using chest CT images. Results: The low VA/TLC group (the lowest quartile) had significantly lower BV5 number, BV5 volume, higher BV5 volume/BV5 number, and higher Kco compared to the high VA/TLC group (the highest quartile) in 117 non-smokers, but not in 67 smokers. Multivariable analysis showed that low VA/TLC was associated with low BV5 number, after adjusting for age, sex, weight, lung volume on CT, and CT emphysema index in non-smokers (not in smokers). Conclusion: Ventilation heterogeneity may be associated with low BV5 number and high Kco in non-smokers (not in smokers). Future studies need to determine the dynamic regional system in ventilation, perfusion, and diffusion in asthma.

Activating the Extra Redox Couple of Co2+/Co3+ for a Synergistic K/Co Co-Substituted and Carbon Nanotube-Enwrapped Na3V2(PO4)3 Cathode with a Superior Sodium Storage Property.

Na3V2(PO4)3 (NVP) materials have emerged as a promising cathode for sodium ion batteries (SIBs). Herein, NVP is successfully optimized by dual-doping K/Co and enwrapping carbon nanotubes (CNTs) through a sol-gel method. Naturally, the occupation of K and Co in the Na1 sites and V sites can efficiently stabilize the crystal cell and provide the expanded Na+ transport channels. The existence of tubular CNTs could restrict the crystal grain growth and effectively downsize the particle size and provide a shorter pathway for the migration of electrons and ions. Moreover, the amorphous carbon layers combined with the conductive CNTs form a favorable network for the accelerated electronic transportation. Furthermore, the ex situ XPS characterization reveals that an extra redox reaction pair of Co2+/Co3+ is successfully activated at the high voltage range, resulting in superior capacity and energy density property for KC0.05/CNTs composites. Comprehensively, the optimized KC0.05/CNTs electrode exhibits a distinctive electrochemical property. It delivers an initial reversible capacity of 119.4 mA h g-1 at 0.1 C, surpassing the theoretic value for the NVP system (117.6 mA h g-1). Moreover, the KC0.05/CNT electrode exhibits the initial capacity of 113.2 mA h g-1 at 5 C and 105.8 mA h g-1 at 10 C, and the maintained capacities at 500 cycles are 105.8 and 100.8 mA h g-1 with outstanding retention values of 96.6 and 95.3%. Notably, it releases capacities of 99.8 and 84.5 mA h g-1 at 50 and 100 C, and the capacity retention values at 2500 cycles are 66.2 and 58.8 mA h g-1, respectively. What is more, the KC0.05/CNTs//Bi2Se3 asymmetric full cell exhibits a high capacity of 191.4 mA h g-1 at 2.65 V, with the energy density being as high as 507 W h kg-1, demonstrating the eminent practical application potential of KC0.05/CNTs in SIBs.

Constructing hierarchical heterojunction structure for K/Co co-substituted Na3V2(PO4)3 by integrating carbon quantum dots.

Na3V2(PO4)3 (NVP) has been widely adopted as cathode in sodium ion battery devices. Nevertheless, the weak intrinsic conductivity and serious structural collapse limit the further development. Herein, a simultaneous modified strategy of doping K/Co and integrating carbon quantum dots (CQD) is proposed. Substituting K+ is beneficial to afford amount of Na+ transport within the stabled and expanded lattice. The introduction of Co2+ generates beneficial hole carriers to improve conductivity. Furthermore, the bonding of conductive CQD guides to obtain nano-sized NVP grains, reducing the pathway for ionic migration to accelerate the diffusion capability. Importantly, a unique p-n type heterojunction construction is established in the interface between CQD (n-type) and NVP (p-type). This heterojunction structure enhances the mobility of electrons owing to the free pathways, in which the electrons transport in a relatively lower energy level without the scatter and collision of anions dopants. Ultimately, K0.1Na2.95V1.95Co0.05(PO4)3@CQD exhibits with the best energy output level. It's initial capacity under 5C is 109.8 mA h g-1 and the retention is 87.6% after cycle 400 cycles. Even at 20 and 50C, its output is 93.5 and 82.6 mA h g-1 for 1st and 66.6 and 52.1 mA h g-1 for 1000th cycle, respectively. Finally, an asymmetric full cell test confirms its application practically.

Longstanding hypersensitivity pneumonitis and its response to roflumilast: A review of its likely immunological effects.

We describe the case of a 42yr old man with evidence of hypersensitivity pneumonitis referred with cough and breathlessness for several years which had further deteriorated in the prior 12 months. He had known atopic asthma without evidence of activation. A chest CT scan showed widespread ground glass change in his lung fields. He had feather bedding at home and in his youth cleaned aviaries. His forced vital capacity and lung volumes were reduced along with oxygen saturations at rest (92% on air), overnight (83% on air) and upon walking (78%). Steroids were commenced for a total of 6 months with little consistent improvement in symptoms or objective measures and with no change in his CT scan appearance. As a result, a trial of roflumilast (a phosphodiesterase-4 inhibitor) was commenced due to its range of immunological effects and in order to avoid long-term immune suppression with mycophenolate motefil in a young patient. On roflumilast treatment his cough and breathlessness improved at 4 weeks and the chest crackles cleared. An interval Chest CT scan showed resolution of the ground glass change with improved CT scores that are maintained 2 yrs. All oxygen measures improved and nocturnal oxygen was discontinued. His Lung function has remained largely stable on roflumilast and symptoms of cough and breathlessness have resolved. This case report reviews the immunology of hypersensitivity pneumonitis and the likely actions of Roflumilast relevant to this condition. It is the first published case report documenting its use in hypersensitivity pneumonitis.

New Insights into Plant TPK Ion Channel Evolution.

Potassium (K) is a crucial element of plant nutrition, involved in many physiological and molecular processes. K+ membrane transporters are playing a pivotal role in K+ transport and tissue distribution as well as in various plant stress responses and developmental processes. Two-pore K+-channels (TPKs) are essential to maintain plant K+ homeostasis and are mainly involved in potassium transport from the vacuoles to the cytosol. Besides vacuolar specialization, some TPK members display different membrane localization including plasma membrane, protein storage vacuole membrane, and probably the organelles. In this manuscript, we elucidate the evolution of the voltage-independent TPK (two-pore K+-channels) family, which could be represented in some species by one pore, K+-inward rectifier (Kir)-like channels. A comprehensive investigation of existing databases and application of modern bioinformatic tools allowed us to make a detailed phylogenetic inventory of TPK/KCO3 (KCO: potassium channel, outward rectifying) channels through many taxa and gain insight into the evolutionary origin of TPK family proteins. Our results reveal the fundamental evolutional difference between the first and second pores, traced throughout multiple taxa variations in the ion selection filter motif, presence of thansposon, and methylation site in the proximity of some KCO members and suggest virus-mediated horizontal transfer of a KCO3-like ancestor by viruses. Additionally, we suggest several interconnected hypotheses to explain the obtained results and provide a theoretical background for future experimental validation.

Using hyperpolarized 129Xe gas-exchange MRI to model the regional airspace, membrane, and capillary contributions to diffusing capacity.

Hyperpolarized 129Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of 129Xe gas-exchange MRI to estimate accessible alveolar volume (VA), membrane conductance, and capillary blood volume contributions to DLCO. 129Xe ventilated volume (VV) was related to VA by a scaling factor kV = 1.47 with 95% confidence interval [1.42, 1.52], relative 129Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient kB = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient kR = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient KCO, which was then multiplied by image-estimated VA to obtain DLCO. The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting 129Xe-derived DLCO correlated strongly (R2 = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use 129Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DLCO clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally.NEW & NOTEWORTHY The diffusing capacity for carbon monoxide (DLCO) is perhaps one of the most comprehensive physiological measures used in pulmonary medicine. Here, we spatially resolve and estimate its key components-accessible alveolar volume, membrane, and capillary blood volume conductances-using hyperpolarized 129Xe MRI of ventilation, interstitial barrier uptake, and red blood cell transfer. This image-derived DLCO correlates strongly with measured values in 142 subjects with a broad range of pulmonary disorders.

Three Month Follow-Up of Patients With COVID-19 Pneumonia Complicated by Pulmonary Embolism.

Background: Previous studies have demonstrated persistent dyspnoea and impairment of respiratory function in the follow-up of patients who have recovered from COVID-19 pneumonia. However, no studies have evaluated the clinical and functional consequences of COVID-19 pneumonia complicated by pulmonary embolism. Objective: The aim of our study was to assess the pulmonary function and exercise capacity in COVID-19 patients 3 months after recovery from pneumonia, either complicated or not by pulmonary embolism. Methods: This was a retrospective, single-centre, observational study involving 68 adult COVID-19 patients with a positive/negative clinical history of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Three months after recovery all patients underwent spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), and 6 minute walk test (6MWT). In addition, high-resolution computed tomography (HRCT) of the lung was carried out and CT-pulmonary angiography was conducted only in the PE+ subgroup. Patients with a previous diagnosis of PE or chronic lung diseases were excluded from the study. Results: Of the 68 patients included in the study, 24 had previous PE (PE+) and 44 did not (PE-). In comparison with the PE- subgroup, PE+ patients displayed a FVC% predicted significantly lower (87.71 ± 15.40 vs 98.7 ± 16.7, p = 0.009) and a significantly lower DLCO% predicted (p = 0.023). In addition, a higher percentage of patients were dyspnoeic on exercise, as documented by a mMRC score ≥1 (75% vs 54.3%, p < 0.001) and displayed a SpO2 <90% during 6MWT (37.5% vs 0%, p < 0.001). HRCT features suggestive of COVID-19 pneumonia resolution phase were present in both PE+ and PE- subjects without any significant difference (p = 0.24) and abnormalities at CT pulmonary angiography were detected in 57% of the PE+ subgroup. Conclusion: At the 3 month follow-up, the patients who recovered from COVID-19 pneumonia complicated by PE showed more dyspnoea and higher impairment of pulmonary function tests compared with those without PE.

Lung function improvements in emphysema following pneumonia.

We describe two cases of patients with emphysema who, in the lead up to hyperinflation intervention, developed pneumonia with significant physiological, anatomical, functional and quality of life improvement observed following. This directly goes against the natural history of both disease processes, demonstrating the benefit resulting from infective autobullectomy.

In-Depth Genomic and Transcriptomic Analysis of Five K+ Transporter Gene Families in Soybean Confirm Their Differential Expression for Nodulation.

Plants have evolved a sophisticated network of K+ transport systems to regulate growth and development. Limited K+ resources are now forcing us to investigate how plant demand can be satisfied. To answer this complex question, we must understand the genomic and transcriptomic portfolio of K+ transporters in plants. Here, we have identified 70 putative K+ transporter genes from soybean, including 29 HAK/KT/KUP genes, 16 genes encoding voltage-gated K+ channels, 9 TPK/KCO genes, 4 HKT genes, and 12 KEA genes. To clarify the molecular evolution of each family in soybean, we analyzed their phylogeny, mode of duplication, exon structures and splice sites, and paralogs. Additionally, ortholog clustering and syntenic analysis across five other dicots further explored the evolution of these gene families and indicated that the soybean data is suitable as a model for all other legumes. Available microarray data sets from Genevestigator about nodulation was evaluated and further confirmed with the RNA sequencing data available by a web server. For each family, expression models were designed based on Transcripts Per Kilobase Million (TPM) values; the outcomes indicated differential expression linked to nodulation and confirmed the genes' putative roles. In-depth studies such as ours provides the basis for understanding K+ inventories in all other plants.

Dual effectiveness of Flaxseed in constipation and diarrhea: Possible mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: This study was planned to assess pharmacological basis for the medicinal use of Flaxseed in constipation and diarrhea. MATERIALS AND METHODS: The oil and mucilage of Flaxseeds were studied for their laxative, and antidiarrheal activities in mice. The mechanisms of laxative and antidiarrheal activities were further studied using the isolated tissue preparations (rabbit jejunum and guinea-pig ileum) immersed in Tyrode׳s solution maintained at 37°C and aerated with carbogen gas. Isotonic responses were measured on spontaneously contracting isolated jejunum and guinea-pig ileum preparations. RESULTS: Oral administration of Flaxseed oil (30 and 70mg/kg, orally) and mucilage (1 and 2.5g/kg, orally) caused dose-dependent increase in wet feces in mice. The spasmogenic effect of Flaxseed oil was partially blocked by pyrilamine (p<0.05) and atropine (p<0.01) in isolated rabbit jejunum whereas atropine completely blocked the effect of Flaxseed mucilage on isolated guinea-pig ileum. When studied for its antidiarrheal effect, Flaxseed oil reduced the castor oil-induced diarrheal score by 49.35% and 84.41% and intestinal secretions by 19% and 33.62% at the oral doses of 100 and 300mg/kg respectively. In isolated rabbit jejunum preparations, Flaxseed oil produced a dose-dependent inhibition of both spontaneous and low K(+) (25mM) -induced contractions in rabbit jejunum. The inhibitory effect against low K(+) was most sensitive to tetra-ethylammonium chloride, a non-specific K(+) channel blocker, followed by glibenclamide, a partial ATP-dependent K(+) channels blocker and 4-Aminopyridine, a voltage gated K(+)-channel blocker. CONCLUSIONS: Our results indicate that Flaxseed oil and mucilage exhibit laxative activity, mediated primarily through cholinergic pathway with weak histaminergic effect component evident in Flaxseed oil, which also showed antidiarrheal activity, mediated possibly through K(+) channels activation. Thus this study rationalizes the medicinal use of Flaxseed in both the constipation and diarrhea with sound mechanistic basis.

Importancia de la corrección de la KCO informada computarizada en pacientes con volumen alveolar disminuído / Importance to adjust computerized informed KCO in patients with low alveolar volume

La disminución del factor de transferencia de monóxido de carbono (TLCO) y del Volumen Alveolar (VA) no es uniforme. Los informes de los equipos computadorizados entregan un valor de KCO que no toma en cuenta este detalle.Objetivo: Realizar el cálculo de KCO a través de la corrección de Stam (J Apply Physiol 1994) y compararlas con las informadas por el software de un equipo de laboratorio pulmonar computadorizado reconocido (Collins).Material y Método: Fueron incluídos pacientes consecutivos derivados al Laboratorio Pulmonar de la Unidad para realizar una prueba de TLCO por enfermedad intersticial pulmonar entre Enero y Junio de 2008. Se realizaron las pruebas según recomendacionesATS/ERS por el método de respiración única y con el método de toma de muestra de Ogilvie. Se analizó la KCO según lo informa el software del equipo Collins Plus/SQL System (1995Warren Collins), y luego se lo recalculó corregida según el cálculo de Stam (J Apply Physiol 1994). Se incluyó en este análisis si tenían <80% del volumen alveolar predicho. Resultados: Fueron evaluados 15 pacientes (media edad: 57.5 ± 12.9 años, sexo femenino 66.7%) con enfermedad intersticial.La media de VA fue 3.5±0.8 L(64.3±11.6%). La media de KCO informada a través del software fue 4.2± 1.3ml/min/mmHg/L. La media de KCO corregida fue 3.7 ± 1.2ml/min/mmHg/L (Δ 11.8±3.8, rango: 6.8%-21.1%). Se observó una relación lineal y negativa entre el %VA y el delta de KCO corregida/informada (r2= -0.99). La elección de diferentes tablas de valores normales de VA altera hasta 12% el valor de la misma, pero la KCO corregida se altera en grado mínimo (3%). Conclusiones: Cuando el VA está disminuído, se debe realizar la corrección del informe computadorizado de la KCO, porque se observa una diferencia promedio del 12%, sobreestimando la real KCO del paciente. Otros factores, como la tabla de valores predictivos de VA, influencia muy poco la corrección de KCO.

The decrease of the Transfer Factor of the Lung for Carbon Monoxide (TLCO) and the Alveolar Volume (VA) is not uniform. Software of lung computed machine informs the carbon monoxide transfer coefficient TLCO/VA (KCO) by calculating the ratio without adjusting for that assumption. Objectives: To calculate KCO using a correction by the Stam´s equation (J Apply Physiol1994), to compare the corrected KCO with the result informed by the software of Collins lung laboratory equipment, and to evaluate the impact of using different predictive tables of VA in the estimates of KCO. Materials: Consecutive patients with intersticial lung disease who attended the LungLaboratory to perform the TLCO between January and June 2008 were included in the study. TLCO was performed according to ATS/ERS recommendations by the single-breathand Ogilvie methods. KCO was calculated by the software of Collins Plus/SQL System (1995 Warren Collins), and then recalculated by Stam´s equation. Only patients withless than 80% of VA predictive value were included. Results: 15 patients with interstitial lung disease were evaluated (age: 57.53 ± 12.93 years old, female: 66.66%). The mean VA was 3.55 ±0.83 L (64.33 ±11.56%) and the mean KCO informed by software was 4.17 ±1.31 ml/min/mmHg/L. The corrected KCO was 3.76 ±1.33 ml/min/mmHg/L(Δ 11.84 ±3.84, range: 6.82%-21.1%). It was observed a negative and lineal relation between %VA and Δ KCO corrected/informed (R2= -0.99). The election of different tables of VA normal values distorts up to12% the individualvalues, but the corrected KCO is little modified (3%). Conclusion: When the VA is reduced, the correction of the KCO must be performed, to avoid on average a 12% overestimate. Other factors such as the election of VA predictive tables have little influence on the KCO correction.