A search for solar related changes in tropospheric weather

The possibility that solar variations associated with the 11-year solar cycle may be the cause of the changes in tropospheric weather and climate has been the subject to scientific investigation for several decades. Meteorologists are greatly concerned with the changes in tropospheric phenomena. An attempt was made to find solar activity related changes in tropospheric weather, by the modulation of the quasi-biennial oscillation (QBO) of zonal wind at 50 mb. Rainfall and surface temperature data for a period of about three solar cycles, 1953 to 1988, from various stations in the Indian subcontinent were utilized. By extension, a possible teleconnection was looked for between the temperature changes in middle atmospheric levels and surface temperature when the data are stratified according to east or west phase of the QBO. The temperature data were averaged for January and February to represent the winter temperature and for July and August to represent the summer temperature

Influence of solar activity on middle atmosphere associated with phases of equatorial quasi-biennial oscillation

Earlier studies on the influence of solar activity variations within a 11-year solar cycle on temperature changes in the middle atmosphere revealed that while the temperature in the mesosphere showed strong responses to changes in solar activity, the stratosphere remained almost unaffected. Recent studies showed that when the temperature data were grouped into east or west phase of the equatorial quasi-biennial oscillation (QBO) in stratospheric zonal wind, significant relationships of temperature in the lower stratosphere and troposphere could be obtained with 10.7 cm solar radio flux. Positive correlations in high latitude regions and negative correlations in mid-latitude and tropical regions were obtained during winter when the QBO was in its west phase. During the east phase, converse relationships were indicated. These results inspired this study on the response of solar activity in 11-year cycle on the temperature structure of the middle atmosphere in the two phases of equatorial QBO of zonal wind at 50 mb, in tropics, mid-latitude and antarctic regions

L-deprenyl attenuates the rotenone-induced dopaminergic neurotoxicity: experimental evidences in rats

Parkinson disease (PD) is progressive neurological disorder because of massive degeneration of nigrostriatal dopaminergic neurons. The pathogenesis of PD is unknown, but considerable evidence suggests multifactorial factors including genetic, mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium cytotoxicity, environmental factors and apoptosis. We investigated the role of oxidative damage produced by intranigral infusion of a potent mitochondrial complex-I inhibitor, rotenone and studied the neuroprotective effects with a well-known antiparkinsonian drug L-deprenyl in rats. Unilateral stereotaxic intranigral infusion of rotenone 6 lg caused significant decrease in dopamine levels. L-deprenyl (10 mg/kg) treatment significantly attenuated the DA depletion caused by rotenone. Parallely, a significant decrease in the concentration of GSH was also observed in the SN was reverted by L-deprenyl treatment. L-deprenyl significantly attenuated the rotenone-induced decrease in tyrosine hydroxylase immunoreactivity in striatum. The results suggest that L-deprenyl can rescue the dopaminergic neurons from the rotenone mediated neurodegeneration in this experimental animal model

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

Neuro-nutraceuticals: Further insights into their promise for brain health

In this Special Issue on “Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain”, the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules from natural products can beneficially affect brain function at the molecular level. Other contributions address key emergent issues such as bioavailability, neuronal health, inflammation and the holistic benefit of multi-targeted actions that impact upon how nutraceuticals ultimately leverage the brain to function better. In terms of the benefit of nutraceuticals it is clear that some naturally occurring molecules can be advantageous to both the young and aged brain, and that they have actions that ultimately can be directed to aid either in the improvement of cognition or in the management of debilitating neurodegenerative and neuropsychiatric condition

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4 + T cells and donor-derived antigen presenting cells. DNAse-1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen-specific CD4 + T cell proliferation through activating toll-like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil-specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse-1 administration to wild-type recipients promotes the recognition of allo- and self-antigens and prevents immunosuppression-mediated lung allograft acceptance through a MyD88-dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeon

Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor