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Selective targeting of phosphodiesterases to develop potent antiparasitic drugs. 选择性靶向磷酸二酯酶,开发强效抗寄生虫药物。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-15 DOI: 10.1016/j.pt.2024.11.001
Shahbaz M Khan, Md Mukthar Mia, William H Witola

Regulation of intracellular cyclic nucleotides to avoid homeostatic imbalances is achieved through catabolic activity of phosphodiesterases (PDEs). Recently, Ajiboye et al. reported validation of Cryptosporidium PDE1 (CpPDE1) as a viable drug target and identified optimized pyrazolopyrimidines with selective activity against CpPDE1 over human PDEs and with potent anticryptosporidial efficacy.

细胞内环核苷酸的调节是通过磷酸二酯酶(PDEs)的分解活动来实现的,以避免体内平衡失调。最近,Ajiboye 等人报告了将隐孢子虫 PDE1(CpPDE1)作为可行药物靶点的验证结果,并确定了优化的吡唑嘧啶类药物,它们对 CpPDE1 的选择性活性优于人类 PDEs,并具有强大的抗隐孢子虫功效。
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引用次数: 0
Multiomic interrogation of an endomembrane disrupting antimalarial. 内膜干扰抗疟药物的多组学研究。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-20 DOI: 10.1016/j.pt.2024.11.002
Sophie L Collier, Stuart A Ralph

Challenges in adapting natural products as antimalarials include their cryptic mechanism of action (and by extension resistance), as well as their complex and expensive synthesis without an abundant natural source. Recently, Chahine et al. presented plausible means to address these challenges in the case of the kalihinol family of isocyanoterpenes.

将天然产品用作抗疟药物所面临的挑战包括其隐秘的作用机制(进而产生抗药性),以及在没有丰富天然来源的情况下进行复杂而昂贵的合成。最近,Chahine 等人以异氰基橙皮烯的卡利桧醇家族为例,提出了应对这些挑战的可行方法。
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引用次数: 0
Neoliberalism and managerialism in academia - a parasitologist's take. 学术界的新自由主义和管理主义--寄生虫学家的观点。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-22 DOI: 10.1016/j.pt.2024.10.003
Robin B Gasser

This brief article examines how neoliberalism and managerialism have transformed higher education in some countries, affecting academics in parasitology and other disciplines. It highlights the impact of reduced academic freedom, increased performance metrics and administrative burdens, calling for awareness and protection of core academic values amidst these systemic changes.

这篇短文探讨了新自由主义和管理主义如何改变了一些国家的高等教育,影响了寄生虫学和其他学科的学者。文章强调了学术自由减少、绩效指标增加和行政负担加重所带来的影响,呼吁在这些系统性变革中提高对核心学术价值观的认识并加以保护。
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引用次数: 0
Metabarcoding in gut protozoology. 肠道原生动物学中的元条码。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1016/j.pt.2024.10.015
Christen Rune Stensvold

Next-generation sequencing (NGS) methods include whole-genome sequencing, metagenomic analysis, and amplicon-based NGS, all of which are gaining territory in parasitology. A modality of particular interest within the field of gut protozoology is exhaustive metabarcoding of ribosomal genes in a complex matrix such as faeces, by which method, amplicon-based NGS enables the detection and differentiation of both eukaryotic and prokaryotic organisms, circumventing Sanger sequencing-based limitations and representing a one-fits-most approach. Apart from being a tool to break the code of intracellular genetic variation and tell mixed species infections apart, metabarcoding can produce data that can serve to augment our understanding of the interplay between the organisms within the gut.

下一代测序(NGS)方法包括全基因组测序、元基因组分析和基于扩增子的 NGS,这些方法在寄生虫学领域的应用日益广泛。肠道原生动物学领域特别感兴趣的一种模式是对粪便等复杂基质中的核糖体基因进行详尽的代谢编码,通过这种方法,基于扩增子的 NGS 可以检测和区分真核生物和原核生物,规避了基于桑格测序的局限性,是一种 "一刀切 "的方法。除了作为破解细胞内遗传变异密码和区分混合物种感染的工具外,代谢编码还能产生数据,有助于加深我们对肠道内生物之间相互作用的了解。
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引用次数: 0
Bric-à-brac, an 'umbilical cord' and trypanosome kinetoplast segregation. 砖块、"脐带 "和锥虫的内质体分离。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-18 DOI: 10.1016/j.pt.2024.10.021
Megan L Povelones, Michael L Ginger

Cadena et al. recently discovered a conserved trypanosomatid 'nabelschnur' protein TbNAB70 from a search through the protein localization resource TrypTag, providing new insight into kinetoplast origin and evolution.

Cadena 等人最近通过搜索蛋白质定位资源 TrypTag 发现了一种保守的锥虫 "nabelschnur "蛋白质 TbNAB70,为了解动粒起源和进化提供了新的视角。
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引用次数: 0
Sec14 proteins in the apicomplexan parasites Plasmodium and Toxoplasma. 疟原虫和弓形虫中的 Sec14 蛋白。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1016/j.pt.2024.10.018
Florian Lauruol, Dave Richard

Sec14 domain proteins are broadly conserved in eukaryotes and play essential roles in numerous cellular processes. Limited data on Sec14 proteins of apicomplexan parasites suggest that they could be important for their survival. The development of fungi-specific Sec14 inhibitors raises the tantalizing possibility that their apicomplexan counterparts might also be targeted.

Sec14 结构域蛋白在真核生物中广泛保守,在许多细胞过程中发挥着重要作用。有关类囊体寄生虫 Sec14 蛋白的有限数据表明,它们对寄生虫的生存可能很重要。真菌特异性 Sec14 抑制剂的开发,使我们看到了一种诱人的可能性,即它们也有可能成为 apicomplexan 寄生虫的靶标。
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引用次数: 0
Eimeria falciformis. 镰刀形艾美耳菌
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI: 10.1016/j.pt.2024.09.008
Özlem Günay-Esiyok, Nishith Gupta
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引用次数: 0
The apicoplast biogenesis and metabolism: current progress and questions. apicoplast 的生物发生和新陈代谢:当前的进展和问题。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI: 10.1016/j.pt.2024.10.019
Xiaowei Chen, Xun Suo, Guan Zhu, Bang Shen

Many apicomplexan parasites have a chloroplast-derived apicoplast containing several metabolic pathways. Recent studies have greatly expanded our understanding of apicoplast biogenesis and metabolism while also raising new questions. Here, we review recent progress on the biological roles of individual metabolic pathways, focusing on two medically important parasites, Plasmodium spp. and Toxoplasma gondii. We highlight the similarities and differences in how similar apicoplast metabolic pathways are utilized to adapt to different parasitic lifestyles. The execution of apicoplast metabolic functions requires extensive interactions with other subcellular compartments, but the underlying mechanisms remain largely unknown. Apicoplast metabolic functions have historically been considered attractive drug targets, and a comprehensive understanding of their metabolic capacities and interactions with other organelles is essential to fully realize their potential.

许多 apicomplexan 寄生虫都有一个源自叶绿体的 apicoplast,其中包含多种代谢途径。最近的研究大大扩展了我们对细胞质生物发生和代谢的了解,同时也提出了新的问题。在此,我们回顾了有关单个代谢途径的生物学作用的最新进展,重点是两种具有重要医学价值的寄生虫--疟原虫和弓形虫。我们强调了类似的细胞外代谢途径在适应不同寄生虫生活方式方面的异同。执行呼吸器代谢功能需要与其他亚细胞区室进行广泛的相互作用,但其基本机制在很大程度上仍不为人所知。表皮细胞代谢功能历来被认为是有吸引力的药物靶点,而全面了解其代谢能力以及与其他细胞器的相互作用对于充分发挥其潜力至关重要。
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引用次数: 0
Teratogenic parasites: disease mechanisms and emerging study models. 致畸寄生虫:疾病机制和新出现的研究模型。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-20 DOI: 10.1016/j.pt.2024.10.016
Rafaela Jose da Silva, Leah F Cabo, Jon P Boyle

Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission - Trypanosoma cruzi, Plasmodium spp., and Toxoplasma gondii - and the state of research into their transplacental transmission strategies. We highlight technological advancements in placental modeling that offer opportunities to reveal how parasites cause gestational pathology. Additionally, we discuss the likelihood that selective adaptation contributed to the evolution of mechanisms that facilitate placental infection. These insights provide a foundation for understanding the progression and pathology of congenital parasitic diseases and identifying future research directions.

先天性感染是影响母亲和胎儿的妊娠并发症的主要可预防原因。尽管人们对各种先天性感染的认识已经取得了进步,但对孕期寄生虫感染的机制仍然知之甚少。这篇综述涵盖了三种可进行先天性传播的寄生虫--克氏锥虫、疟原虫和弓形虫--的全球发病率,以及对其经胎盘传播策略的研究现状。我们重点介绍了胎盘建模方面的技术进步,这些技术为揭示寄生虫如何导致妊娠病理提供了机会。此外,我们还讨论了选择性适应促进胎盘感染机制进化的可能性。这些见解为了解先天性寄生虫病的进展和病理以及确定未来的研究方向奠定了基础。
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引用次数: 0
Young investigators in parasitology meeting: building foundations and supporting early-career researchers. 寄生虫学青年研究人员会议:奠定基础和支持早期职业研究人员。
IF 7 1区 医学 Q1 PARASITOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.pt.2024.10.004
Filipa Rijo-Ferreira, Chi-Min Ho, Alex Rosenberg
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引用次数: 0
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Trends in parasitology
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