Tropicality and abjection: What do we really mean by “Neglected Tropical Diseases”?

Neglected tropical diseases are defined operationally as diseases that prevail in “tropical” regions and are under‐researched, under‐funded, and under‐treated compared with their disease burden. By analysing the adjectives “tropical” and “neglected,” I expose and interrogate the discourses within which the term “neglected tropical disease” derives its meaning. First, I argue that the term “tropical” conjures the notion of “tropicality,” a form of Othering which erroneously explains the disease‐prevalence of “tropical” regions by reference to environmental determinism, rather than colonialism and neocolonialism. Second, I examine the way in which this Othering enables the abjection of tropical regions and their peoples, leading to neglect. I recommend that the term “neglected tropical diseases” be more carefully contextualised within health scholarship, education, and policy.     

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)‐associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR‐7 expression was down‐regulated in lung tissue of PM group than control group, and NETs further decreased miR‐7 expression. TLR9 and Smad2 were up‐regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA‐treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR‐7 and Smad2 in LF. Finally, miR‐7‐Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM‐related ILD, and TLR9‐miR‐7‐Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.     

油田野外作业工人慢性疾病调查及职业紧张与神经递质的相关性研究

目的:调查油田野外作业工人慢性疾病患病情况,分析职业紧张与神经递质的相关性。方法:通过整群抽样的方式选取油田野外作业工人2000例作为研究对象,采用自制的慢性非传染性疾病调查量表对所有工人的慢性疾病情况予以调查,采用职业紧张量表对所有工人的职业紧张情况予以调查。采用酶联免疫吸附法检测所有工人血清五羟色胺、去甲肾上腺素以及神经肽Y水平,并采用偏相关分析油田野外作业工人职业紧张与神经递质的相关性。结果:2000例油田野外作业工人慢性疾病发病率最高的前三种疾病分别为颈腰部疾病、高血压、高血脂,占比分别为20.60%、15.35%、11.20%。油田野外作业工人中男性职业任务、个体应对资源评分高于女性,而锻炼工人的个体紧张反应评分低于不锻炼工人(P0.05)。油田野外作业工人中饮酒工人神经肽Y水平低于不饮酒工人,锻炼工人的去甲肾上腺素水平高于不锻炼工人(P0.05)。经偏相关分析可得:油田野外作业工人的职业任务评分与五羟色胺、去甲肾上腺素水平呈正相关(P0.05),个体紧张反应评分与神经肽Y水平呈负相关(P0.05)。结论:油田野外作业工人慢性疾病患病情况不容乐观,且其职业紧张与神经递质存在密切相关,在临床工作中可通过改善油田野外作业工人的职业紧张,从而达到改善其神经递质水平的目的。     

八种常见儿童感染性疾病相关指标差异性研究

摘要 目的：探讨异型淋巴细胞、白细胞、中性粒细胞、淋巴细胞、单核细胞、C-反应蛋白及血沉等在儿童感染性相关疾病不同疾病种类、不同年龄段及性别的差异情况,并进行分析,从而为疾病的诊断、鉴别诊断及治疗提供依据。方法：选取2017年1月-2018年12月266例患感染性疾病的儿童,根据疾病类型分为八组,分别为传染性单核细胞增多症（41例）、EB病毒感染（18例）、支气管肺炎（43例）、支气管炎（42例）、急性上呼吸道感染（48例）、急性化脓性扁桃体炎（18例）、肺炎（19例）、粒细胞减少（37例）等,应用检验相关手段,对患儿异型淋巴细胞、白细胞、中性粒细胞、淋巴细胞、单核细胞、C-反应蛋白及血沉等进行检测,采用SPSS17.0统计学分析软件,计算各检验结果的平均值与标准差,进行相关t检验,进而对不同疾病的检验项目进行统计学分析。结果：在八种疾病相关检验的比较中,传染性单核细胞增多症与其余七种感染性疾病在异型淋巴细胞、中性粒细胞、淋巴细胞及血沉的数据进行比较,其之间比较差异有统计学意义（P<0.05）,其余各组疾病相关指标没有统计学差异。在年龄段的分组比较中,异型淋巴细胞在各年龄段之间比较差异有统计学意义（P<0.05）。在性别分组比较中,白细胞在性别与各年龄段之间比较差异有统计学意义（P<0.05）。结论：不同种类感染性疾病及不同年龄、性别相关细胞检查存在差异,各类检测结果的综合对比分析,更有利于疾病的诊断及鉴别诊断。     

Discriminant haplotypes of avirulence genes of Phytophthora sojae lead to a molecular assay to predict phenotypes

The soybean–Phytophthora sojae interaction operates on a gene-for-gene relationship, where the product of a resistance gene (Rps) in the host recognizes that of an avirulence gene (Avr) in the pathogen to generate an incompatible reaction. To exploit this form of resistance, one must match with precision the appropriate Rps gene with the corresponding Avr gene. Currently, this association is evaluated by phenotyping assays that are labour-intensive and often imprecise. To circumvent this limitation, we sought to develop a molecular assay that would reveal the avirulence allele of the seven main Avr genes (Avr1a, Avr1b, Avr1c, Avr1d, Avr1k, Avr3a, and Avr6) in order to diagnose with precision the pathotypes of P. sojae isolates. For this purpose, we analysed the genomic regions of these Avr genes in 31 recently sequenced isolates with different virulence profiles and identified discriminant mutations between avirulence and virulence alleles. Specific primers were designed to generate amplicons of a distinct size, and polymerase chain reaction conditions were optimized in a final assay of two parallel runs. When tested on the 31 isolates of known virulence, the assay accurately revealed all avirulence alleles. The test was further assessed and compared to a phenotyping assay on 25 isolates of unknown virulence. The two assays matched in 97% (170/175) of the interactions studied. Interestingly, the sole cases of discrepancy were obtained with Avr3a, which suggests a possible imperfect interaction with Rps3a. This molecular assay offers a powerful and reliable tool to exploit and study with greater precision soybean resistance against P. sojae.     

Dependence of PINK1 accumulation on mitochondrial redox system

Accumulation of PINK1 on the outer mitochondrial membrane (OMM) is necessary for PINK‐mediated mitophagy. The proton ionophores, like carbonyl cyanide m‐chlorophenylhydrazone (CCCP) and carbonyl cyanide‐4‐(trifluoromethoxy)phenylhydrazone (FCCP), inhibit PINK1 import into mitochondrial matrix and induce PINK1 OMM accumulation. Here, we show that the CHCHD4/GFER disulfide relay system in the mitochondrial intermembrane space (IMS) is required for PINK1 stabilization when mitochondrial membrane potential is lost. Activation of CHCHD4/GFER system by mitochondrial oxidative stress or inhibition of CHCHD4/GFER system with antioxidants can promote or suppress PINK1 accumulation, respectively. Thus data suggest a pivotal role of CHCHD4/GFER system in PINK1 accumulation. The amyotrophic lateral sclerosis‐related superoxide dismutase 1 mutants dysregulated redox state and CHCHD4/GFER system in the IMS, leading to inhibitions of PINK1 accumulation and mitophagy. Thus, the redox system in the IMS is involved in PINK1 accumulation and damaged mitochondrial clearance, which may play roles in mitochondrial dysfunction‐related neurodegenerative diseases.     

Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models

Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLP^APT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLP^APT mice.