Evaluating the molecular events that underlie functional recovery of botulinum poisoned neurones in vitro and in vivo

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The Plasmodial Surface Anion Channel Is Functionally Conserved in Divergent Malaria Parasites

The plasmodial surface anion channel (PSAC), a novel ion channel induced on human erythrocytes infected with Plasmodium falciparum, mediates increased permeability to nutrients and presumably supports intracellular parasite growth. Isotope flux studies indicate that other malaria parasites also increase the permeability of their host erythrocytes, but the precise mechanisms are unknown. Channels similar to PSAC or alternative mechanisms, such as the upregulation of endogenous host transporters, might fulfill parasite nutrient demands. Here we evaluated these possibilities with rhesus monkey erythrocytes infected with Plasmodium knowlesi, a parasite phylogenetically distant from P. falciparum. Tracer flux and osmotic fragility studies revealed dramatically increased permeabilities paralleling changes seen after P. falciparum infection. Patch-clamp of P. knowlesi-infected rhesus erythrocytes revealed an anion channel with striking similarities to PSAC: its conductance, voltage-dependent gating, pharmacology, selectivity, and copy number per infected cell were nearly identical. Our findings implicate a family of unusual anion channels highly conserved on erythrocytes infected with various malaria parasites. Together with PSAC's exposed location on the host cell surface and its central role in transport changes after infection, this conservation supports development of antimalarial drugs against the PSAC family

Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation

Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery. (C) 2003 Elsevier Science (USA). All rights reserved

Changes in the Plasmodial Surface Anion Channel Reduce Leupeptin Uptake and Can Confer Drug Resistance in Plasmodium falciparum-Infected Erythrocytes▿

Cysteine protease inhibitors kill malaria parasites and are being pursued for development as antimalarial agents. Because they have multiple targets within bloodstream-stage parasites, workers have assumed that resistance to these inhibitors would not be acquired easily. In the present study, we used in vitro selection to generate a parasite resistant to growth inhibition by leupeptin, a broad-profile cysteine and serine protease inhibitor. Resistance was not associated with upregulation of cysteine protease activity, reduced leupeptin sensitivity of this activity, or expression level changes for putative cysteine or serine proteases in the parasite genome. Instead, it was associated with marked changes in the plasmodial surface anion channel (PSAC), an ion channel on infected erythrocytes that functions in nutrient and bulky organic solute uptake. Osmotic fragility measurements, electrophysiological recordings, and leupeptin uptake studies revealed selective reductions in organic solute permeability via PSAC, altered single-channel gating, and reduced inhibitor affinity. These changes yielded significantly reduced leupeptin uptake and could fully account for the acquired resistance. PSAC represents a novel route for the uptake of bulky hydrophilic compounds acting against intraerythrocytic parasite targets. Drug development based on such compounds should proceed cautiously in light of possible resistance development though the selection of PSAC mutants

تدخّل اللغة الإندونيسية في كتابة اللغة العربية لدى طلبة المدرسة الثانوية الإسلامية الحكومية باتو: دراسة وصفية تحليلية

مستخلص البحث إن تدخل اللغة عند متعلمي اللغة العربية في إندونيسيا هو من ظاهرة عادة. ولو تلك الظاهرة عادة ولكنها مشكلة لأن اللغة لكلها قواعد. وقد وجد تدخل اللغة الإندونيسية في كتابة اللغة العربية لدى طلبة المدرسة الثانوية الإسلامية الحكومية باتو. وأما أهداف هذا البحث لتحليل أشكال تدخل اللغة الإندونيسية في كتابة اللغة العربية لدى طلبة المدرسة الثانوية الإسلامية الحكومية باتو، وكشف أسباب وقوع تدخل اللغة الإندونيسية في كتابة اللغة العربية لديهم، وتحليل الحلول لمشكلات تدخل اللغة الإندونيسية في كتابة اللغة العربية لديهم. وأما مدخل هذا البحث المدخل الكيفي، وأما منهجه وصفي تحليلي. وأسلوب جمع البيانات في هذا البحث هي تحليل الوثائق والمقابلة. والمصادر البيانات هي وثائق كتابة طلبة المدرسة الثانوية الإسلامية الحكومية باتو ومدرسة اللغة العربية في تلك المدرسة. وفي هذا البحث وجدت الباحثة أشكال تدخل اللغة الإندونيسية في كتابة اللغة العربية في مستوى النحو والصرف والدلالي. وأسباب وقوع ذلك التدخل هناك أسباب داخلية وأسباب خارجية. والحلول لتلك المشكلة هو تحليل تقابلي وتدريبات كتابة كثيرة. ABSTRACT Language Interference to arabic language learners in Indonesia is a common phenomenon. Although the phenomenon is normal, but it is a problematic. Because each language has rules of each rule. It has been found forms of Indonesian interference into Arabic in the MAN Batu's students. The purpose of this study was to analyze the forms of interference Indonesian into Arabic in the students MAN Batu, uncover the causes of interference Languages Indonesisa into Arabic in the MAN Batu's students, and analyze solutions to the problem of interference Indonesian to Arabic in student writing MAN Batu. This study used a qualitative descriptive study, and the data collection with analysis of documentation and interviews. Source data is written documentation of students and teachers of Arabic. In this study, researchers found other forms of interference Indonesian into Arabic at the level of syntax, morphology and semantics. The causes interference Indonesian into Arabic in the MAN Batu's students that there is a cause intra linguistics and causes inter linguistics. The solution to the problem of interference is tahlil taqobuli and plenty of exercise in the writing ABSTRAK Interferensi bahasa bagi pelajar bahasa arab di Indonesia merupakan fenomena yang biasa. Meskipun fenomena itu biasa, tetapi hal itu merupakan problematika. Karena setiap bahasa memiliki kaidah aturan masing-masing. Telah ditemukan bentuk-bentuk interferensi Bahasa Indonesia dalam tulisan Bahasa Arab pada siswa MAN Batu. Adapun tujuan penelitian ini adalah untuk menganalisis bentuk-bentuk interferensi Bahasa Indonesia dalam tulisan Bahasa Arab pada siswa MAN Batu, menyingkap sebab-sebab terjadinya interferensi Bahasa Indonesisa dalam tulisan Bahasa Arab pada siswa MAN Batu, dan menganalisis solusi untuk masalah interferensi Bahasa Indonesia dalam tulisan Bahasa Arab pada siswa MAN Batu. Penelitian ini menggunakan penelitian deskriptif kualitatif, dan pengumpulan datanya dilakukan dengan analisis dokumentasi dan wawancara. Sumber datanya adalah dokumentasi tulisan siswa dan guru bahasa arab. Dalam penelitian ini, peneliti menemukan bentuk-bentuk interferensi Bahasa Indonesia dalam tulisan Bahasa Arab pada tataran sintaksis, morfologi dan semantik. Sebab-sebab interferensi Bahasa Indonesia dalam tulisan Bahasa Arab pada siswa MAN Batu yaitu ada sebab intralinguistik dan sebab interlinguistik. Solusi untuk masalah interferensi adalah tahlil taqobuli dan banyak latihan kitabah