Late Reversal Research Articles

Late reversal reaction 6 months after completion of WHO standard treatment for multibacillary leprosy

Late reversal reaction 6 months after completion of WHO standard treatment for multibacillary leprosy

Variability of Horizontal Magnetic Field Intensity Over Nigeria During Low Solar Activity

Magnetic field intensity of the horizontal component (H) data measured from Magnetic Data Acquisition System (MAGDAS) at Ilorin (geographic latitude: 8.47°N, geographic longitude: 4.68°E, geomagnetic latitude: 1.82°S, geomagnetic longitude: 78.6°S), Nigeria in the year 2009 (a low activity year) was used to study the diurnal, monthly-median and standard deviation of the solar quiet of the horizontal component (S q H). The diurnal variation of S q H and its corresponding monthly median variation (MS q H) shows minima values at pre-sunrise hours between 0500 and 0600 LT. The S q H value shows a daytime maximum variation range between 20 and 91 nT and a nighttime minimum variation range from 1 to 4 nT. The occurrences of daytime maxima of the S q H values that were observed in all the months are between the hours of 1000 and 1200 LT. The daytime maximum of the MS q H values from the entire months were seen at 1100 LT with exceptions of January and December. The month of October has the highest value (61 nT) and the lowest value was observed in December (35 nT). It is clearer that the range in maximums of S q H and MS q H variations during the daytime period in all the months is greater than the range in minimums observed at nighttime period (post-sunset and pre-sunrise). The monthly standard deviation (STD) depicts the index of variability of all the day-to-day variations in each month. Counter electrojet (CEJ) events were observed in the morning and as well during the evening hours. The magnitudes and frequencies of CEJ events during the evening hours are greater than that of the morning hours. CEJ seen during the morning period around 0500–0600 LT is the consequence of late reversals of nighttime westward currents to daytime eastward currents. A semi-annual variation with peak values during March, April, September and October was observed. Seasonal variation that was characterized with CEJ was also investigated.

A diatom-inferred record of reduced effective precipitation during the Last Glacial Coldest Phase (28.8–18.0 cal kyr BP) and increasing Holocene seasonality at Lake Pupuke, Auckland, New Zealand

A continuous, 1,420-cm sediment record from Lake Pupuke, Auckland, New Zealand (37°S) was analysed for diatom taxonomy, concentration and flux. A New Zealand freshwater diatom transfer function was applied to infer past pH, electrical conductivity, dissolved reactive phosphorus and chlorophyll a. A precise, mixed-effect regression model of age versus depth was constructed from 11 tephra and 13 radiocarbon dates, with a basal age of 48.2 cal kyr BP. Diatom-inferred changes in paleolimnology and climate corroborate earlier inferences from geochemical analyses (Stephens et al. 2012), with respect to the timing of marked climate changes in the Last Glacial Coldest Phase (LGCP; 28.8–18.0 cal kyr BP), the Last Glacial Interglacial Transition (LGIT; 18.0 to ca. 12–10 cal kyr BP) and the Holocene, the onset of which is difficult to discern from LGIT amelioration, but which includes an early climatic optimum (10.2–8.0 cal kyr BP). The LGCP is readily defined by a reduction in lake level and effective precipitation, whereas the LGIT represents a period of rising lake level, with greater biomass during the Holocene. There was limited change in diatom assemblage structure, influx or inferred water quality during a Late Glacial Reversal (LGR; 14.5–13.8 cal kyr BP), associated with heightened erosional influx. In contrast, an LGIT peak in paleoproductivity is recorded by increased diatom influx from 13.8 to 12.8 cal kyr BP. Changes in sediment influx and biomass record complex millennial-scale events attuned to the Antarctic Cold Reversal (ACR; 14.5–12.8 cal kyr BP). Additional millennial-scale environmental change is apparent in the Holocene, with marked changes in lake circulation beginning at 7.6 cal kyr BP, including the onset of seasonal thermal stratification and rapid species turnover at 5.7 cal kyr BP. The most rapid diatom community turnover accompanied widely varying nutrient availability and greater seasonality during the last 3.3 cal kyr. Rising seasonality appears to have been linked to strengthened Southern Westerlies at their northern margins during the middle and late Holocene.

The river it goes right on: Post-glacial landscape evolution in the upper Waipaoa River basin, eastern North Island, New Zealand

Post-glacial incision created 50 to 120m of relief in the headwaters of the Waipaoa River basin, but it is not known how the signal of incision propagated along the trunk streams. We addressed this issue by imposing previously determined long-term rates of rock uplift, that vary between 0.6 and 4mmyear−1, on the preaggradation longitudinal profile. Acting over the past 27.1±2cal.kaBP, these rates are sufficient to passively elevate the Waipaoa-1 terrace to its present level. But during the Last Glacial Maximum, rates of vertical incision failed to match those of the uplifting rocks. Thus, by the time favorable conditions for incision were reestablished after the Antarctic Cold/New Zealand Late Glacial reversal we estimate that the channel would have been elevated ≤55m above the datum the river should otherwise have maintained. The channel incised rapidly after the transition from glacial to interglacial conditions and reacquired its steady-state form in the mid-Holocene (5.5±2cal.kaBP). Thereafter, we suggest rates of incision matched rates of uplift. No knickpoints are found on the upper Waipaoa and Mangatu Rivers because incision commenced simultaneously along the entire length of the trunk streams, and the pattern of incision is consistent with the downstream decline in the rate of rock uplift. We also used hypsometric analysis to show how post-glacial incision affected the surface morphology of low order (0.1–4.3km2) drainages in the headwaters of the Waipaoa River basin. Values of the hypsometric integral are higher for proximal basins, which the incision signal did not permeate, than for low-order basins bordering the upper Waipaoa River and the lower reaches of tributaries that possessed enough erosive capacity to keep pace with incision along the mainstem. Hillslope adjustments were focused on the lower and mid-sections of these basins so that the most pronounced changes to the hypsometric curve occur in the vicinity of the toe, whereas the entire form of the hypsometric curve changes once mass wasting processes encroach onto hillslopes in the middle and upper sections of a basin.

Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems.

Slow phasic and tonic activity of ventral pallidal neurons during cocaine self‐administration

Ventral pallidal (VP) neurons exhibit rapid phasic firing patterns within seconds of cocaine-reinforced responses. The present investigation examined whether VP neurons exhibited firing rate changes: (1) over minutes during the inter-infusion interval (slow phasic patterns) and/or (2) over the course of the several-hour self-administration session (tonic firing patterns) relative to pre-session firing. Approximately three-quarters (43/54) of VP neurons exhibited slow phasic firing patterns. The most common pattern was a post-infusion decrease in firing followed by a progressive reversal of firing over minutes (51.16%; 22/43). Early reversals were predominantly observed anteriorly whereas progressive and late reversals were observed more posteriorly. Approximately half (51.85%; 28/54) of the neurons exhibited tonic firing patterns consisting of at least a two-fold change in firing. Most cells decreased firing during drug loading, remained low over self-administration maintenance, and reversed following lever removal. Over a whole experiment (tonic) timescale, the majority of neurons exhibited an inverse relationship between calculated drug level and firing rates during loading and post-self-administration behaviors. Fewer neurons exhibited an inverse relationship of calculated drug level and tonic firing rate during self-administration maintenance but, among those that did, nearly all were progressive reversal neurons. The present results show that, similar to its main afferent the nucleus accumbens, VP exhibits both slow phasic and tonic firing patterns during cocaine self-administration. Given that VP neurons are principally GABAergic, the predominant slow phasic decrease and tonic decrease firing patterns within the VP may indicate a disinhibitory influence upon its thalamocortical, mesolimbic, and nigrostriatal targets during cocaine self-administration.

Role of Perfusion Imaging in Differentiating Multifocal Vasospasm–related Ischemia versus Thromboembolic Stroke in a Setting of Cocaine Abuse

Cerebrovascular complications related to cocaine abuse are reaching epidemic proportions. Contemporary treatments for acute stroke have made it essential to gather all possible diagnostic information before proceeding with intervention. We describe a cocaine abuser who presented with acute right sided neurological deficits and deteriorating mental status. An MRI demonstrated right sided acute and chronic infarcts in the border zones of the right anterior cerebral arteries (ACA) and middle cerebral arteries (MCAs). Subsequent CT angiography (CTA)/CT perfusion (CTP) identified multifocal cerebral vasospasm of the bilateral ACAs and MCAs, preserved cerebral blood volume (CBV) and decreased cerebral blood flow (CBF) in bilateral frontoparietal regions. Early diagnosis of multifocal vasospasm related ischemia directed appropriate therapy and excluded thrombolytic intervention. After 3 weeks, patient's presenting symptoms gradually resolved. We report a unique case of cocaine induced multifocal vasospasm exhibiting late (>3 weeks) reversibility of focal neurological deficits. Furthermore, we illustrate the benefits of CTA/CTP imaging in the setting of cocaine abuse, differentiating multifocal vasospasm induced hypoperfusion/ischemia from focal thromboembolic ischemia/infarct and allowing for appropriate medical management in the crucial hyperacute setting.

P.1.c.014 MBDB, a recreational drug similar to MDMA, exhibits anxiogenic-like effects in mice tested in the elevated plus-maze

The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (<50% correct in one session) and late (>50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreen-based operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

Age frequency distribution and revised stable isotope curves for New Zealand speleothems: palaeoclimatic implications

The occurrence of speleothems in New Zealand with reversed magnetism indicates that secondary calcite deposition in caves has occurred for more than 780 thousand years (ka). 394 uranium-series dates on 148 speleothems show that such deposition has taken place somewhere in the country with little interruption for more than 500 ka. A relative probability distribution of speleothem ages indicates that most growth occurred in mild, moist interglacial and interstadial intervals, a conclusion reinforced by comparing peaks and troughs in the distribution with time series curves of speleothem δ18O and δ13C values. The stable isotope time series were constructed using data from 15 speleothems from two different regions of the country. The greater the number of overlapping speleothem series (i.e. the greater the sample depth) for any one region, the more confidence is justified in considering the stacked record to be representative of the region. Revising and extending earlier work, composite records are produced for central-west North Island (CWNI) and north-west South Island (NWSI). Both demonstrate that over the last 15 ka the regions responded similarly to global climatic events, but that the North Island site was also influenced by the waxing and waning of regional subtropical marine influences that penetrated from the north but did not reach the higher latitudes of the South Island. Cooling marking the commencement of the last glacial maximum (LGM) was evident from about 28 ka. There was a mid-LGM interstadial at 23-21.7 ka and Termination 1 occurred around 18.1 ka. The glacial-interglacial transition was marked by a series of negative excursions in δ18O that coincide with dated recessional moraines in South Island glaciers. A late glacial cooling event, the NZ Late Glacial Reversal, occurred from 13.4-11.2 ka and this was followed by an early Holocene optimum at 10.8 ka. Comparison of δ18O records from NWSI and EPICA DML ice-core shows climatic events in New Zealand to lag those in Antarctica by several centuries to a thousand years. Waxing and waning of subantarctic and subtropical oceanic influences in the Tasman Sea are considered the immediate drivers of palaeoclimatic change.

The neural correlates of attentional bias in blood phobia as revealed by the N2pc.

In the literature, a lack of attentional bias in blood phobia has been reported, using both behavioral and ERP measures. However, in the tasks employed so far, attentional resources to single stimuli, rather than attentional selection, were evaluated. The present study investigated whether in blood phobics disorder-relevant pictures can capture visuo-spatial attention when paired with neutral or non-specific unpleasant pictures (attack), and participants have to focus on a visual detection task. The N2pc component of the ERPs was measured as an index of spatial attentional selection. Results showed that in blood phobics, but not in controls, injuries elicited a larger early N2pc than attack pictures when paired with neutral material. Moreover, only in blood phobics a reliable N2pc to injury-attack pairs was found. The late N2pc reversal to injury pictures suggests that early orienting to phobic cues was followed by cognitive avoidance.

The long-term apoptotic effects of progesterone-only contraceptives on endometrium and ovary in rats

OBJECTIVE: Apoptosis is necessary for the balance between cell proliferation and cell loss. Various pathologies are related with excessive or deficient apoptosis. We evaluated apoptotic effect of widely used enjectable and implantable progestines on ovarian and uterine tissues via rat study design. DESIGN: Prospective randomise experimental study MATERIALS AND METHODS: Sixtysix Wistar-Albino rats were used. Etonogestrel(IMP) was implanted in 30 rats. Medroksiprogesterone-acetate(MPA) was enjected in another 30 rats. After application of drugs, 6 rats were sacrificed at the each 10th,20th,30th,40th and 50th days. Six rats served as controls. Ovarian and uterine tissues were evaluated for apoptotic index(AI) and caspase-3 immunoreactivity(HSCORE). RESULTS: In both IMP and MPA groups, AI and HScore values in stroma and glandular epithelium of uterus increased with the longer progesterone exposure time. AI and HScore values did not change in endometrium. AI and HScore values also increased with the longer progesterone exposure time in both granulosa and teca-lutein cells of the ovary in IMP and MPA groups. Particularly, increase in AI and HScore values were more prominent after 30 days of progestine exposure for teca-lutein cells of ovary. CONCLUSIONS: Progestine increased apoptosis in ovaries and uterus by the longer exposure time. This effect on uterus is consistent with literature. Apoptotic effect is more prominent by the longer exposure time. Apoptosis increased in ovaries by chronic progesterone exposure which is in contrast with some studies in literature. This effect might be related with chronic supression of gonadotropins and elevation of androgens due to decreased SHBG levels which are indirect effects of progestines. Late reversal of fertility with depot and implant forms of progestines when combined with their apoptotic effects it could be considered that longer duration of progestin usage can cause a shorter period of fertile life.

Superchron at the Mesoproterozoic-Neoproterozoic transition

The search for old superchrons represents an important direction in the study of geomagnetic field evolution. According to recent terminology, the superchron is a time interval (and corresponding state of the geomagnetic field), during which the process of reversal of the geomagnetic field polarity that is characteristic of any other period of geological history seems to become frozen and the field remains in one of two possible stationary states for many millions to tens of millions of years. It may confidently be postulated that the superchrons are the most remarkable and, probably, the most enigmatic events in the history of the geomagnetic field. Until recently, only two such superchrons had been reliably established: Cretaceous normal polarity and Carboniferous‐Permian (Kiama Superchron) reversed polarity. Recent studies revealed a third Phanerozoic superchron in the Early‐Middle Ordovician [1‐3]. In this communication, we present evidence for a new geomagnetic superchron at the Mesoproterozoic‐Neoproterozoic transition with outlining its boundaries and duration. The statistical analysis of the duration of magnetic polarity intervals [4] demonstrates that superchrons are most likely characterized by their own distribution mode, which is different from that typical of all other magnetic polarity intervals. This inference may be considered as pointing to the relation of superchrons to some basic changes in the Earth’s dynamo work. These changes might be induced by different factors: (1) layer D' evolution and formation of plumes; (2) mantle avalanches; (3) redistribution of “cryptocontinents” at the core surface; (4) transformation of the outer core shape; or (5) lateral variations in the heat flux across the core‐ mantle boundary regardless of the above-mentioned factors [5‐10 and others]. Some researchers are pessimistic believing that superchrons reflect the complex nonlinear nature of the Earth’s dynamo, which is completely independent from any external impact and, consequently, bears no information on changeable environments in the core and at the core‐mantle boundary [11]. At the same time, the discovery of the third Phanerozoic superchron supports the earlier assumption [12] that there is a certain characteristic period existing in the frequency variation of geomagnetic field reversals and that this period is 150‐200 Ma long. Our data [3] indicate that this inference is true, at least, of the Phanerozoic, i.e., the last 550 Ma. It is understandable that the characteristic period of superchron development favors the assumption that this process is controlled by some mechanism located in the Earth’s interior. It is clear, however, that the existence of a characteristic period favorable for the superchron appearance itself needs additional evidence. Such data may be obtained only for the Precambrian by studying the frequency of Late Precambrian geomagnetic reversals. In order to understand the nature of superchrons and the mechanisms responsible for them as well as to prove the reality of these mechanisms, we should find out whether superchrons existed in the Late Precambrian and what their age is if there were any of them. When studying the Late Mesoproterozoic Malgina Formation in the Uchur‐Maya Riphean hypostratototype section of the southeastern Siberian Platform, we established that frequent variations in the magnetic field polarity at the beginning of the Malgina time (1043 ± 14 Ma) were followed by a relatively long period when it remained unchanged [13]. The existence of the interval with stable magnetic polarity was confirmed by a limited number of samples taken at several stratigraphic levels from four remote sections of the Malgina Formation. In total, not more than one-fourth of the Malgina Formation thickness was previously studied with respect to its magnetostratigraphy. In the course of this work, we carried out detailed magnetostratigraphic study of the entire Malgina Formation and

Equatorial F-region vertical ion drifts during quiet solar maximum

Median values of ionosonde h′ F data acquired at Ibadan (Geographic:7.4°N, 3.9°E, Magnetic: dip 6°S, and magnetic declination, 3°W), Nigeria, West Africa, have been used to determine vertical ion drift (electric field) characteristics in the postsunset ionosphere in the African region during a time of high solar activity (average F 10.7 −208). The database spans from January and December 1958 during the era of International Geophysical Year (IGY) for geomagnetic quiet conditions. Bimonthly averaged diurnal variations patterns are very similar, but differ significantly in magnitude and in the evening reversal times. Also, monthly variations of F-region vertical ion drift reversal times inferred from the time of h′ F maximum indicates early reversal during equinoxes and December solstice months except for the month of April. Late reversal is observed during the June solstice months. The equatorial evening prereversal enhancement in vertical ion drift ( V zp ) occurs largely near 1900 LT with typical values ∼20–45 m/s. Comparison of Ibadan ionosonde V zp with the values of prereversal peak velocity reported for Jicamarca (South America), Kodaikanal (India), and Scherliess and Fejer global model show considerable disparity. The changes of postsunset peak in virtual height of F-layer ( h′ F P ) with prereversal velocity peak V zp are anti-correlated. Investigation of solar effects on monthly values of V zp and h′ F P revealed that these parameters are independent of monthly averaged solar flux intensity during quiet-time sunspot maximum conditions.

Intravascular large B-cell lymphoma as a cause of hypopituitarism: gradual and late reversal of hypopituitarism after long-term remission of lymphoma with immunochemotherapy

Intravascular large B-cell lymphoma (IVL) is a rare generally fatal disease characterized by massive proliferation of lymphoid cells within the small and medium blood vessels. Hypopituitarism has been reported only in a few fatal cases. We describe the clinical course of hypopituitarism as a complication of IVL, successfully treated with immunochemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone-CHOP) plus Rituximab anti-CD20 humanized antibody). Before immunochemotherapy, basal hormonal analysis and dynamic test for pituitary function were performed in a 67-year-old female with IVL. Endocrinological evaluation of the pituitary function was repeated after complete hematological remission and during the 2 years of follow-up. Multiple pituitary hormone deficiencies were diagnosed before therapy for IVL. Magnetic resonance imaging (MRI) of the pituitary gland showed partially empty sella. The patient was replaced with thyroxine 50 microg/day and prednisone 5 mg/day between the cycles of chemotherapy. After complete hematological remission (6 months after initial diagnosis) reversal of cortisol and gonadotropin deficiency occurred. After 18 months of hematological remission there was further improvement in growth hormone (GH) response to provocative testings (partial GH deficiency), with normalization of somatotropic and thyreotropic axis after 2 years of follow-up. This is the first case of IVL complicated with hypopituitarism, treated with immunochemotherapy which resulted in complete hematological remission and gradual and late reversal of hypopituitarism.

Necrotic cell death: From reversible mitochondrial uncoupling to irreversible lysosomal permeabilization

Dictyostelium atg1− mutant cells provide an experimentally and genetically favorable model to study necrotic cell death (NCD) with no interference from apoptosis or autophagy. In such cells subjected to starvation and cAMP, induction by the differentiation-inducing factor DIF or by classical uncouplers led within minutes to mitochondrial uncoupling, which causally initiated NCD. We now report that (1) in this model, NCD included a mitochondrial-lysosomal cascade of events, (2) mitochondrial uncoupling and therefore initial stages of death showed reversibility for a surprisingly long time, (3) subsequent lysosomal permeabilization could be demonstrated using Lysosensor blue, acridin orange, Texas red-dextran and cathepsin B substrate, (4) this lysosomal permeabilization was irreversible, and (5) the presence of the uncoupler was required to maintain mitochondrial lesions but also to induce lysosomal lesions, suggesting that signaling from mitochondria to lysosomes must be sustained by the continuous presence of the uncoupler. These results further characterized the NCD pathway in this priviledged model, contributed to a definition of NCD at the lysosomal level, and suggested that in mammalian NCD even late reversibility attempts by removal of the inducer may be of therapeutic interest.

Characteristics of the equatorial electrojet current in the central region of South America

Abstract We describe here for the first time the morphology of the equatorial electrojet (EEJ) in the Central American Sector based on an analysis of the geomagnetic field components from six stations distributed on both sides of the dip equator along the 60°W geographic longitude sector. Diurnal and latitudinal variations in the horizontal and vertical components are shown to follow the Chapman model of EEJ. The horizontal component vector due to the ionospheric current aligned itself close to magnetic north, with a mean Declination of 10°W (ranging from 9°W to 14°W). There was a significant counter-electrojet effect before sunrise at stations close to the dip equator, suggesting late reversal of solar-quiet (S q) electric field in the morning hours. The observed variations in the magnetic meridional current did not seem to be associated with EEJ currents. The centre of the electrojet was around 0.25°S of the dip equator in the morning hours and shifted gradually to 1.5°S by the evening hours. Magnetic storms occurring during the midday hours produced an exceptionally large decrease in the H (horizontal component) field at stations close to the dip equator.

Authoritarian Reversals and Democratic Consolidation

I present a new empirical approach to the study of democratic consolidation. This approach leads to new insights into the determinants of democratic consolidation that cannot be obtained with existing techniques. I distinguish between democracies that survive because they areconsolidatedand those democracies that arenot consolidatedbut survive because of some favorable circumstances. As a result, I can identify the determinants of two related yet distinct processes: the likelihood that a democracy consolidates, and the timing of authoritarian reversals in democracies that are not consolidated. I find that the level of economic development, type of democratic executive, and type of authoritarian past determine whether a democracy consolidates, but have no effect on the timing of reversals in democracies that are not consolidated. That risk is only associated with economic recessions. I also find that existing studies greatly underestimate the risk of early reversals while simultaneously overestimating the risk of late reversals, and that a large number of existing democracies are in fact consolidated.

Reversal of an immunity associated plant cell death program by the growth regulator auxin

BackgroundOne form of plant immunity against pathogens involves a rapid host programmed cell death at the site of infection accompanied by the activation of local and systemic resistance to pathogens, termed the hypersensitive response (HR). In this work it was tested (i) if the plant growth regulator auxin can inhibit the cell death elicited by a purified proteinaceous HR elicitor, (ii) how far down the process this inhibition can be achieved, and (iii) if the inhibition affects reporters of immune response. The effect of constitutive modulation of endogenous auxin levels in transgenic plants on this cell death program was also evaluated.ResultsThe HR programmed cell death initiated by a bacterial type III secretion system dependent proteinaceous elicitor harpin (from Erwinia amylovora) can be reversed till very late in the process by the plant growth regulator auxin. Early inhibition or late reversal of this cell death program does not affect marker genes correlated with local and systemic resistance. Transgenic plants constitutively modulated in endogenous levels of auxin are not affected in ability or timing of cell death initiated by harpin.ConclusionThese data indicate that the cell death program initiated by harpin can be reversed till late in the process without effect on markers strongly correlated with local and systemic immunity. The constitutive modulation of endogenous auxin does not affect equivalent signaling processes affecting cell death or buffers these signals. The concept and its further study has utility in choosing better strategies for treating mammalian and agricultural diseases.

Reversal of an immunity associated plant cell death program by the growth regulator auxin

AbstractOne form of plant immunity against pathogens involves a rapid host programmed cell death at the site of infection accompanied by resistance, termed the hypersensitive response (HR). Here it is shown that the HR programmed cell death program initiated by the bacterial type III secretion system dependent proteinaceous elicitor harpin from Erwinia amylovora can be reversed till very late in the process by the plant growth regulator auxin. Early inhibition or late reversal of this cell death program does not affect marker genes tightly correlated with local and systemic resistance. Cross-regulation between cell death programs and growth regulators is prevalent in different kingdoms. Thus, the concept that cell death program can be reversed till late provides a framework for further investigation of such phenomena, in addition to having utility in choosing better targets and strategies for treating mammalian and agricultural diseases.

Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells

AbstractLittle is known about age-related changes in red blood cell (RBC) membrane transport and homeostasis. We investigated first whether the known large variation in plasma membrane Ca2+ (PMCA) pump activity was correlated with RBC age. Glycated hemoglobin, Hb A1c, was used as a reliable age marker for normal RBCs. We found an inverse correlation between PMCA strength and Hb A1c content, indicating that PMCA activity declines monotonically with RBC age. The previously described subpopulation of high-Na+, low-density RBCs had the highest Hb A1c levels, suggesting it represents a late homeostatic condition of senescent RBCs. Thus, the normal densification process of RBCs with age must undergo late reversal, requiring a membrane permeability increase with net NaCl gain exceeding KCl loss. Activation of a nonselective cation channel, Pcat, was considered the key link in this density reversal. Investigation of Pcat properties showed that its most powerful activator was increased intracellular Ca2+. Pcat was comparably selective to Na+, K+, choline, and N-methyl-D-glucamine, indicating a fairly large, poorly selective cation permeability pathway. Based on these observations, a working hypothesis is proposed to explain the mechanism of progressive RBC densification with age and of the late reversal to a low-density condition with altered ionic gradients.