Targeted Disruption of Toxoplasma gondii Serine Protease Inhibitor 1 Increases Bradyzoite Cyst Formation In Vitro and Parasite Tissue Burden in Mice

As an intracellular protozoan parasite, Toxoplasma gondii is likely to exploit proteases for host cell invasion, acquisition of nutrients, avoidance of host protective responses, escape from the parasitophorous vacuole, differentiation, and other activities. T. gondii serine protease inhibitor 1 (TgPI1) is the most abundantly expressed protease inhibitor in parasite tachyzoites. We show here that alternative splicing produces two TgPI1 isoforms, both of which are secreted via dense granules into the parasitophorous vacuole shortly after invasion, become progressively more abundant over the course of the infectious cycle, and can be detected in the infected host cell cytoplasm. To investigate TgPI1 function, the endogenous genomic locus was disrupted in the RH strain background. ΔTgPI1 parasites replicate normally as tachyzoites but exhibit increased bradyzoite gene transcription and labeling of vacuoles with Dolichos biflorus lectin under conditions promoting in vitro differentiation. The differentiation phenotype can be partially complemented by either TgPI1 isoform. Mice infected with the ΔTgPI1 mutant display ∼3-fold-increased parasite burden in the spleen and liver, and this in vivo phenotype is also complemented by either TgPI1 isoform. These results demonstrate that TgPI1 influences both parasite virulence and bradyzoite differentiation, presumably by inhibiting parasite and/or host serine proteases

Elastic, inelastic, and 1 n transfer cross sections for the 10 B + 120 Sn reaction

The 10 B + 120 Sn reaction has been investigated at E Lab = 37.5 MeV. The cross sections for different channels, such as the elastic scattering, the excitation of the 2 + and 3 − 120 Sn states, the excitation of the 1 + state of 10 B , and the 1 n pick-up transfer, have been measured. One-step distorted-wave Born approximation and coupled-reaction-channels calculations have been performed in the context of the double-folding São Paulo potential. The effect of coupling the inelastic and transfer states on the angular distributions is discussed in the paper. In general, the theoretical calculations within the coupled-reaction-channels formalism yield a satisfactory agreement with the corresponding experimental angular distributions.Instituto Nacional de Ciência e Tecnologia-Física Nuclear e Aplicações de Brasil (INCT-FNA) 464898/2014-

Understanding the mechanisms of nuclear collisions: A complete study of the 10 B + 120 Sn reaction

Background: Reactions involving exotic and stable weakly bound nuclei have been extensively studied in recent years. Although several models have been successfully used to explain particular reaction outcomes, the answers to many questions remain elusive. In previous works, we presented elastic, inelastic, and transfer angular distributions for the 10B + 120Sn system measured at ELab = 31.5, 33.0, 35.0, and 37.5 MeV. The data set was analyzed through coupled reaction channels calculations in the context of the double-folding São Paulo potential. Purpose: We investigate nuclear reaction mechanisms for systems involving weakly bound projectiles. Method: Angular distributions for several nuclear reaction processes were measured for the 10B + 120Sn system at ELab = 39.70 MeV. Results: The new data set involves angular distributions for elastic scattering, projectile and target inelastic excitations, one-neutron pickup transfer, one-proton stripping transfer, deuteron pickup transfer, and 3,4 He stripping transfer. We have also observed 10Be nuclei. The effect of the couplings to some nonelastic states on the angular distributions is discussed. Conclusion: The theoretical calculations within the coupled reaction channels formalism provide an overall good agreement with the corresponding inelastic, one-neutron stripping, one-proton pickup, one-deuteron pickup, and 3 He stripping transfer data. However, to improve the description of the elastic scattering angular distribution, the inclusion of additional channels in the coupling scheme might be necessary.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2018/09998-8, 2019/07767-1, 2019/05769-7 y 2017/05660-0;Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 304056/2019-7, 302160/2018-3 y 306433/2017- 6Instituto Nacional de Ciência e Tecnologia-Física Nuclear e Aplicações (INCT-FNA) 464898/2014-5Ministerio de Ciencia, Innovación y Universidades de España. PGC2018-096994-B-C21Ministerio de Economía de España y Competitividad y fondos FEDER. FIS2017-88410-

Information development and flow : a study of the communication behavior of social scientists in a U.S. Land Grant and two Taiwan universities

Includes bibliographical references (pages 197-204)

A preliminary study on the formation of land legislation and cadastre system in Sarawak, Malaysia

Recent decades have witnessed a perceptible impact of land policy and cadastre on the urbanisation around the globe. Land legislation and cadastre system are the tools and mechanisms in order to achieve the objectives of land policy in delivering sustainable development. According to the Federal Constitution of Malaysia, article 74 empowers the State Legislative Assemblies to enact laws for the matters under the state list while land matters are one of the subjects under the list. Land matters in Sarawak are governed by Sarawak state government, resulting in different land legislation and cadastre system as compared to Peninsular Malaysia. Therefore, this paper aims to give an overview on the land legislation and cadastre system in Sarawak. The chronological evolutions of land legislation from the past to present are discussed. The cadastre system in Sarawak is also presented. On top of that, this paper attempts to review the literature concerning the subject matter of land legislation and cadastre from various countries, which in turn provides valuable lessons for Sarawak. A total of eight recent publications were chosen for review. Each of the publications is analysed based on the title, subject matter, research question, methodology, results and lessons for Sarawak. Towards the end of this paper, the key lessons from the review are presented

Hyperspectral remote sensing of foliar nitrogen content

http://www.pnas.orgPeer reviewe

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

3,4-Diaminopyridine Base Effectively Treats the Weakness of Lambert-Eaton Myasthenia

Introduction: 3,4-diaminopyridine has been used to treat Lambert Eaton myasthenia (LEM) for thirty years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in LEM patients who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in Triple Timed Up-and-Go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM–related weakness (W-SAS). Results: 32 participants were randomized to continuous 3,4-DAP or placebo. None of the 14 receiving continuous 3,4-DAP had >30% deterioration in 3TUG time vs 72% of the 18 who tapered to placebo (p<0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (p<0.0001). Need for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM

Validation of the triple timed up‐and‐go test in Lambert‐Eaton myasthenia

Introduction There are no validated, practical, and quantitative measures of disease severity in Lambert‐Eaton myasthenia (LEM). Methods Data from the Effectiveness of 3,4‐Diaminopyridine in Lambert‐Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up‐and‐go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. Results The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4‐diaminopyridine free base. Worsening patient‐reported Weakness Self‐Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. Discussion The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM