Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal CO2 and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in CO2 and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/min with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal CO2 and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 +/- 5.0% (P < 0.0001) and 24.4 +/- 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal CO2 and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders.     

Imaging of the cell surface interface using objective coupled widefield surface plasmon microscopy

We report on the development and on the first use of the widefield surface plasmon (WSPR) microscope in the examination of the cell surface interface at submicron lateral resolutions. The microscope is Kohler illuminated and uses either a 1.45 numerical aperture (NA) oil immersion lens, or a 1.65 NA oil immersion lens to excite surface plasmons at the interface between a thin gold layer and a glass or sapphire cover slip. Like all surface plasmon microscope systems the WSPR has been proven in previous studies to also be capable of nanometric z-scale resolutions. In this study we used the system to image the interface between HaCaT cells and the gold layer. Imaging was performed in air using fixed samples and the 1.45 NA objective based system and also using live cells in culture media using the 1.65 NA based system. Imaging in air enabled the visualisation of high resolution and high-contrast submicron features identified by vinculin immunostaining as component of focal contacts and focal adhesions. In comparison, imaging in fluid enabled cell surface interfacial interactions to be tracked by time-lapse video WSPR microscopy. Our results indicate that the cell surface interface and thus cell signalling mechanisms may be readily interrogated in live cells without the use of labelling techniques.     

Silicon Carbide Whisker-Mediated Embryogenic Callus Transformation of Cotton (<Emphasis Type="Italic">Gossypium hirsutum</Emphasis> L.) and Regeneration of Salt Tolerant Plants

A silicon carbide whisker-mediated gene transfer system with recovery of fertile and stable transformants was developed for cotton (Gossypium hirsutum L.) cv. Coker-312. Two-month-old hypocotyl-derived embryogenic/non-embryogenic calli at different days after subculture were treated with silicon carbide whiskers for 2 min in order to deliver pGreen0029 encoding GUS gene and pRG229 AVP1 gene, encoding Arabidopsis vacuolar pyrophosphatase, having neomycin phosphotransferaseII (nptII) genes as plant-selectable markers. Three crucial transformation parameters, i.e., callus type, days after subculture and selection marker concentration for transformation of cotton calli were evaluated for optimum efficiency of cotton embryogenic callus transformation giving upto 94% transformation efficiency. Within six weeks, emergence of kanamycin-resistant (km^r) callus colonies was noted on selection medium. GUS and Southern blot analysis showed expression of intact and multiple transgene copies in the transformed tissues. Kanamycin wiping of leaves from T₁, T₂, and T₃ progeny plants revealed that transgenes were inherited in a Mendelian fashion. Salt treatment of T₁ AVP1 transgenic cotton plants showed significant enhancement in salt tolerance as compared to control plants. Thus far, this is first viable physical procedure after particle bombardment available for cotton that successfully can be used to generate fertile cotton transformants.     

Extensive evolution analysis of the global chikungunya virus strains revealed the origination of CHIKV epidemics in Pakistan in 2016

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes epidemics widely in the world especially in the tropical and subtropical regions. Phylogenetic analysis has found that the CHIKV lineages were associated with the spatial and temporal distributions, which were related to the virus adaption to the major mosquito species and their distributions. In this study, we reported the complete genome sequences of eight CHIKV isolates from the outbreak in Pakistan last year. Then we reviewed the evolutionary history using extensive phylogenetic analysis, analyzed lineage-specific substitutions in viral proteins, and characterized the spreading pathway of CHIKV strains including the Pakistani strains. The results showed that the Pakistani stains belonged to the ECSA.IOL sub-lineage and derived from India. The genetic properties of the Pakistani strains including the adaptive substitution to vectors were further characterized, and the potential risks from the occurrence of CHIKV infection in Pakistan were discussed. These results provided better understanding of CHIKV evolution and transmission in the world and revealed the possible origination of the CHIKV outbreak and epidemic in Pakistan, which would promote the disease prevention and control in the identified countries and territories with the history of CHIKV infections as well as new regions with potential risk of CHIKV outbreaks.

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A PLETHORA/PIN-FORMED/auxin network mediates prehaustorium formation in the parasitic plant Striga hermonthica

The parasitic plant Striga (Striga hermonthica) invades the host root through the formation of a haustorium and has detrimental impacts on cereal crops. The haustorium results from the prehaustorium, which is derived directly from the differentiation of the Striga radicle. The molecular mechanisms leading to radicle differentiation shortly after germination remain unclear. In this study, we determined the developmental programs that regulate terminal prehaustorium formation in S. hermonthica at cellular resolution. We showed that shortly after germination, cells in the root meristem undergo multiplanar divisions. During growth, the meristematic activity declines and associates with reduced expression of the stem cell regulator PLETHORA1 and the cell cycle genes CYCLINB1 and HISTONE H4. We also observed a basal localization of the PIN-FORMED (PIN) proteins and a decrease in auxin levels in the meristem. Using the structural layout of the root meristem and the polarity of outer-membrane PIN proteins, we constructed a mathematical model of auxin transport that explains the auxin distribution patterns observed during S. hermonthica root growth. Our results reveal a fundamental molecular and cellular framework governing the switch of S. hermonthica roots to form the invasive prehaustoria.

The parasitic plant Striga hermonthica forms its invasive organ, the prehaustorium, by inducing differentiation of the radicle by arresting cell division.     

Response of Contrasting Rice Genotypes to Zinc Sources under Saline Conditions

Abiotic stresses are among the major limiting factors for plant growth and crop productivity. Among these, salinity is one of the major risk factors for plant growth and development in arid to semi-arid regions. Cultivation of salt tolerant crop genotypes is one of the imperative approaches to meet the food demand for increasing population. The current experiment was carried out to access the performance of different rice genotypes under salinity stress and Zinc (Zn) sources. Four rice genotypes were grown in a pot experiment and were exposed to salinity stress (7 dS m⁻¹), and Zn (15 mg kg⁻¹ soil) was applied from two sources, ZnSO₄ and Zn-EDTA. A control of both salinity and Zn was kept for comparison. Results showed that based on the biomass accumulation and K⁺/Na⁺ ratio, KSK-133 and BAS-198 emerged as salt tolerant and salt sensitive, respectively. Similarly, based on the Zn concentration, BAS-2000 was reported as Zn-in-efficient while IR-6 was a Zn-efficient genotype. Our results also revealed that plant growth, relative water content (RWC), physiological attributes including chlorophyll contents, ionic concentrations in straw and grains of all rice genotypes were decreased under salinity stress. However, salt tolerant and Zn-in-efficient rice genotypes showed significantly higher shoot K⁺ and Zn concentrations under saline conditions. Zinc application significantly alleviates the harmful effects of salinity by improving morpho-physiological attributes and enhancing antioxidant enzyme activities, and the uptake of K and Zn. The beneficial effect of Zn was more pronounced in salt-tolerant and Zn in-efficient rice genotypes as compared with salt-sensitive and Zn-efficient genotypes. In sum, our results confirmed that Zn application increased overall plant’s performance under saline conditions, particularly in Zn in-efficient and tolerant genotypes as compared with salt-sensitive and Zn efficient rice genotypes.     

Inhibition of Glutamate Uptake and Proton Pumping in Synaptic Vesicles by S-Nitrosylation

Abstract: Nitric oxide (NO; including NO^•, NO⁺, and NO⁻) was found to inhibit glutamate uptake by isolated synaptic vesicles of rat brain. This was observed when two unrelated NO donors, S -nitrosogluthathione and S -nitroso- N -acetylpenicillamine, were used. The primary target of NO is the H⁺-ATPase found in the synaptic vesicles, which leads to dissipation of the electrochemical proton gradient and inhibition of glutamate uptake. Oxyhemoglobin (12 µ M ) and, to a much lesser extent, methemoglobin protected the vacuolar H⁺-ATPase from inhibition. Inhibition of H⁺ pumping by NO was reversed by addition of 0.5 m M dithiothreitol. The results indicate that the vacuolar H⁺-ATPase from synaptic vesicles is inhibited by NO by a mechanism that involves S -nitrosylation of critical sulfhydryl groups in the enzyme. The interaction of NO with synaptic vesicles might be of importance for the understanding of the multiple effects of NO in neurotransmission.