Dopamine depletion and subsequent treatment with L-DOPA, but not the long-lived dopamine agonist pergolide, enhances activity of the Akt pathway in the rat striatum

Dysregulation of signaling pathways is believed to contribute to Parkinson's disease pathology and l-DOPA-induced motor complications. Long-lived dopamine (DA) agonists are less likely to cause motor complications by virtue of continuous stimulation of DA receptors. In this study, we compared the effects of the unilateral 6-hydroxydopamine lesion and subsequent treatment with l-DOPA and DA agonist pergolide on signaling pathways in rats. Pergolide caused less pronounced behavioral sensitization than l-DOPA (25 mg/kg, i.p., 10 days), particularly at lower dose (0.5 and 0.25 mg/kg, i.p.). Pergolide, but not l-DOPA, reversed lesion-induced up-regulation of preproenkephalin and did not up-regulate preprodynorphine or DA D3 receptor in the lesioned hemisphere. Pergolide was as effective as l-DOPA in reversing the lesion-induced elevation of ERK2 phosphorylation in response to acute apomorphine administration (0.05 mg/kg, s.c.). Chronic l-DOPA significantly elevated the level of Akt phosphorylation at both Thr(308) and Ser(473) and concentration of phosphorylated GSK3alpha, whereas pergolide suppressed the lesion- and/or challenge-induced supersensitive Akt responses. The data indicate that l-DOPA, unlike pergolide, exacerbates imbalances in the Akt pathway caused by the loss of DA. The results support the hypothesis that the Akt pathway is involved in long-term actions of l-DOPA and may be linked to l-DOPA-induced dyskinesia.     

Phytogeographical significance of Wadi Wateer (Sinai), Egypt, with special reference to Cocculus hirsutus (L.) W.Theob.

The botanical survey of Wadi Wateer, located in the southeastern Sinai, revealed the presence of a plant that provides an important new record to the Flora of Egypt: Cocculus hirsutus (L.) Theob. This plant has not been recorded previously as existing in its wild form in the Flora of Egypt. The plant cover in Wadi Wateer is dominated by plant taxa belonging to the Saharo-Sindian phytogeographical element. However, many plants in the wadi have been attributed to the Sudanian chorotype, such as Acacia tortilis (Forssk.) Hayne subsp. raddiana (Savi) Brenan, Chrozophora brocchiana Vis., Lycium shawii Roem & Schult., Moricandia sinaica (Boiss.) Boiss., Cocculus hirsutus (L.) Theob. and Cocculus pendulus (J.R. & G. Forst.) Diels. The presence of Sudanian chorotype plant taxa [including the newly recorded Cocculus hirsutus (L.) Theob.] provides evidence that Wadi Wateer and Aqaba Gulf functioned as migratory tracks for these African plants, assisting their penetration into the Saharo-Sindian, Mediterranean and Irano-Turanian phytogeographical regions in the Sinai and Asia. This study suggests that Wadi Wateer should be declared a protected area for its habitat and climatic diversity as well as for its phytogeographical significance.     

The redevelopment of Indo-Aryan case systems from a lexical semantic perspective

The original case system found in Sanskrit (Old Indo-Aryan) was lost in Middle Indo-Aryan and then reinvented in most of the modern New Indo-Aryan (NIA) languages. This paper suggests that: (1) a large factor in the redevelopment of the NIA case systems is the expression of systematic semantic contrasts; (2) the precise distribution of the newly innovated case markers can only be understood by taking their original spatial semantics into account and how this originally spatial semantics came to be used primarily for marking the core participants of a sentence (e.g., agents, patients, experiencers, recipients). Furthermore, given that case markers were not innovated all at once, but successively, we suggest a model in which already existing case markers block or compete with newer ones, thus giving rise to differing particular instantiations of one and the same originally spatial postposition across closely related languages.     

Transactivation of the epidermal growth factor receptor mediates parathyroid hormone and prostaglandin F2 alpha-stimulated mitogen-activated protein kinase activation in cultured transgenic murine osteoblasts

Recent data suggest that G protein-coupled receptors (GPCRs), including those for PTH and prostaglandins (PGs), contribute to the proliferation and differentiation of osteoblasts in vivo. To understand how these signals are transduced, we studied activation of the ERK1/2 MAPK cascade in cultures of differentiating TMOb murine osteoblasts. In TMOb cells, stimulation of endogenous Gs/Gq-coupled PTH receptors, Gq-coupled PGF2 alpha receptors, and Gi/Gq-coupled lysophosphatidic acid receptors, but not Gs-coupled PGE2 receptors, caused a rapid 5- to 10-fold increase in ERK1/2 phosphorylation. GPCR-stimulated ERK1/2 activation coincided with increased tyrosine phosphorylation of epidermal growth factor (EGF) receptors and was blocked by the EGF receptor inhibitor, tyrphostin AG1478, and the metalloprotease inhibitor, batimastat, suggesting that the response involved transactivation of EGF receptors through the proteolytic release of an EGF receptor ligand. To further examine the mechanism of PTH-stimulated EGF receptor transactivation, we employed COS-7 cells expressing the rat PTH receptor. Here, stimulation with PTH(1-34) caused proteolysis of hemagglutinin epitope-tagged heparin binding-EGF, increased tyrosine autophosphorylation of EGF receptors, and AG1478-sensitive ERK1/2 activation. When PTH receptor-expressing COS-7 cells were placed in a mixed culture with cells lacking the PTH receptor but expressing a green fluorescent protein-tagged ERK2, stimulation with PTH(1-34) induced phosphorylation of green fluorescent protein-ERK2 that was abolished by either batimastat or tyrphostin AG1478. These data suggest that autocrine/paracrine cross-talk between EGF receptors and Gi- or Gq/11-coupled GPCRs represents the predominant mechanism of GPCR-mediated activation of ERK1/2 in cultured TMOb osteoblasts.     

Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20 mg/kg bwt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3 mg/kg bwt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1β levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type (SDAT).     

Effect of vegetation on density thresholds of adult desert locust gregarization from survey data in Mauritania

In the desert locust, Schistocerca gregaria (Forskål) (Orthoptera: Acrididae), the threshold density inducing the gregarization phenomenon has never been determined under natural conditions. The influence of environmental factors on this phenomenon has been studied mostly in controlled environments. Based on data collected during several years by the survey teams of the National Center for Locust Control in Mauritania, we analyzed the influence of locust density, vegetation cover, and vegetation status on the probability of observing gregarious locusts. We assumed that a probability to observe gregarious locusts of 0.5 corresponded to the density threshold of gregarization. The results showed in detail the change in the threshold of gregarization according to the cover and status of the vegetation. Low cover and dry vegetation led to a low density threshold of gregarization probably due to high probability of individuals to touch each other. Dense and green vegetation favored a high threshold of gregarization probably due to a dispersion of the individuals and a low probability of individual encounters. These findings should help the management of locusts and decision making during control operations.     

Epidemiology and Management of Candidiasis in Solid Organ Transplant Recipients

Purpose of Review

Invasive candidiasis (IC) is the leading cause of fungal infections in solid organ transplant recipients (SOT). In this article, we aim to review the epidemiology, risk factors, presentation, and management of IC in this population.

Recent Findings

Certain risk factors have been associated with IC in SOT recipients. Targeted antifungal prophylaxis for SOT recipients at the highest risk of infection is currently recommended although the choice and duration of antifungal agents remain controversial. Early diagnosis and monitoring of IC in SOT recipients are critical to achieve better outcomes and prevent serious complications. Non-culture-based diagnostic modalities have been introduced to aid in earlier and more accurate diagnosis.

Summary

The use of azoles for prophylaxis or treatment in SOT recipients allowed for selection of resistance and increased the incidence of non-albicans Candida. Drug–drug interactions, cost, and risk of resistance are to be considered when using more potent or newer antifungal agents.

     

Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization

Background  

Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization.