73 research outputs found

    Predicting the seasonal evolution of southern African summer precipitation in the DePreSys3 prediction system

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    We assess the ability of the DePreSys3 prediction system to predict austral summer precipitation (DJF) over southern Africa, defined as the African continent south of 15°S. DePresys3 is a high resolution prediction system (at a horizontal resolution of ~ 60 km in the atmosphere in mid-latitudes and of the quarter degree in the Ocean) and spans the long period 1959–2016. We find skill in predicting interannual precipitation variability, relative to a long-term trend; the anomaly correlation skill score over southern Africa is greater than 0.45 for the first summer (i.e. lead month 2–4), and 0.37 over Mozambique, Zimbabwe and Zambia for the second summer (i.e. lead month 14–16). The skill is related to the successful prediction of the El-Nino Southern Oscillation (ENSO), and the successful simulation of ENSO teleconnections to southern Africa. However, overall skill is sensitive to the inclusion of strong La-Nina events and also appears to change with forecast epoch. For example, the skill in predicting precipitation over Mozambique is significantly larger for the first summer in the 1990–2016 period, compared to the 1959–1985 period. The difference in skill in predicting interannual precipitation variability over southern Africa in different epochs is consistent with a change in the strength of the observed teleconnections of ENSO. After 1990, and consistent with the increased skill, the observed impact of ENSO appears to strengthen over west Mozambique, in association with changes in ENSO related atmospheric convergence anomalies. However, these apparent changes in teleconnections are not captured by the ensemble-mean predictions using DePreSys3. The changes in the ENSO teleconnection are consistent with a warming over the Indian Ocean and modulation of ENSO properties between the different epochs, but may also be associated with unpredictable atmospheric variability

    Stabilization of dense Antarctic water supply to the Atlantic Ocean overturning circulation

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    The lower limb of the Atlantic overturning circulation is resupplied by the sinking of dense Antarctic Bottom Water (AABW) that forms via intense air–sea–ice interactions next to Antarctica, especially in the Weddell Sea. In the last three decades, AABW has warmed, freshened and declined in volume across the Atlantic Ocean and elsewhere, suggesting an ongoing major reorganization of oceanic overturning. However, the future contributions of AABW to the Atlantic overturning circulation are unclear. Here, using observations of AABW in the Scotia Sea, the most direct pathway from the Weddell Sea to the Atlantic Ocean, we show a recent cessation in the decline of the AABW supply to the Atlantic overturning circulation. The strongest decline was observed in the volume of the densest layers in the AABW throughflow from the early 1990s to 2014; since then, it has stabilized and partially recovered. We link these changes to variability in the densest classes of abyssal waters upstream. Our findings indicate that the previously observed decline in the supply of dense water to the Atlantic Ocean abyss may be stabilizing or reversing and thus call for a reassessment of Antarctic influences on overturning circulation, sea level, planetary-scale heat distribution and global climate

    Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

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    Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain

    A needs assessment for a minor eye condition service within Leeds, Bradford and Airedale, UK

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    YesBackground: There are a number of limitations to the present primary eye care system in the UK. Patients with minor eye conditions typically either have to present to their local hospital or GP, or face a charge when visiting eye care professionals (optometrists). Some areas of the UK have commissioned enhanced community services to alleviate this problem; however, many areas have not. The present study is a needs assessment of three areas (Leeds, Airedale and Bradford) without a Minor Eye Conditions Service (MECS), with the aim of determining whether such a service is clinically or economically viable. Method: A pro forma was developed for optometrists and practice staff to complete when a patient presented whose reason for attending was due to symptoms indicative of a problem that could not be optically corrected. This form captured the reason for visit, whether the patient was seen, the consultation funding, the outcome and where the patient would have presented to if the optometrists could not have seen them. Optometrists were invited to participate via Local Optical Committees. Results were submitted via a Google form or a Microsoft Excel document and were analysed in Microsoft Excel. Results: Seventy-five percent of patients were managed in optometric practice. Nine and 16% of patients required subsequent referral to their General Practitioner or hospital ophthalmology department, respectively. Should they not have been seen, 34% of patients would have presented to accident and emergency departments and 59% to their general practitioner. 53% of patients paid privately for the optometrist appointment, 28% of patients received a free examination either through use of General Ophthalmic Service sight tests (9%) or optometrist good will (19%) and 19% of patients did not receive a consultation and were redirected to other providers (e.g. pharmacy, accident and emergency or General Practitioner). 88% of patients were satisfied with the level of service. Cost-analyses revealed a theoretical cost saving of £3198 to the NHS across our sample for the study period, indicating cost effectiveness. Conclusions: This assessment demonstrates that a minor eye condition service in the local areas would be economically and clinically viable and well received by patients

    Excessive activation of the TLR9/TGF-β1/PDGF-B pathway in the peripheral blood of patients with systemic lupus erythematosus

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    Abstract Background Our aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN). Methods Protein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments. Results Compared to healthy controls (N Control = 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-β1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (N SLE = 112). Significant correlations between the levels of TLR9, TGF-β1, and PDGF-B were observed in both healthy controls and SLE patients. The levels of TGF-β1 and PDGF-B were greatly enhanced by TLR9 activation in primary cell cultures. The proliferation of mesangial cells induced by the plasma of SLE patients was significantly higher than that induced by healthy controls; PDGF-B was involved in this process. The protein levels of PDGF-B homodimer correlated with the levels of urine protein in SLE patients with LN (N LN =38). Conclusions The TLR9/TGF-β1/PDGF-B pathway exists in humans and can be excessively activated in SLE patients. High levels of PDGF-B may result in overproliferation of mesangial cells in the kidney that are involved in the development of glomerulonephritis and LN. Further studies are necessary to identify TLR9, TGF-β1, and PDGF-B as new therapeutic targets to prevent the development of glomerulonephritis and LN

    Cytokinin and auxin interaction in root stem-cell specification during early embryogenesis

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    Plant stem-cell pools, the source for all organs, are first established during embryogenesis. It has been known for decades that cytokinin and auxin interact to control organ regeneration in cultured tissue. Auxin has a critical role in root stem-cell specification in zygotic embryogenesis, but the early embryonic function of cytokinin is obscure. Here, we introduce a synthetic reporter to visualize universally cytokinin output in vivo. Notably, the first embryonic signal is detected in the hypophysis, the founder cell of the root stem-cell system. Its apical daughter cell, the precursor of the quiescent centre, maintains phosphorelay activity, whereas the basal daughter cell represses signalling output. Auxin activity levels, however, exhibit the inverse profile. Furthermore, we show that auxin antagonizes cytokinin output in the basal cell lineage by direct transcriptional activation of ARABIDOPSIS RESPONSE REGULATOR genes, ARR7 and ARR15, feedback repressors of cytokinin signalling. Loss of ARR7 and ARR15 function or ectopic cytokinin signalling in the basal cell during early embryogenesis results in a defective root stem-cell system. These results provide a molecular model of transient and antagonistic interaction between auxin and cytokinin critical for specifying the first root stem-cell niche
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