From the Cover: Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance

Mitochondria cannot form de novo but require mechanisms allowing their inheritance to daughter cells. In contrast to most other eukaryotes Trypanosoma brucei has a single mitochondrion whose single-unit genome is physically connected to the flagellum. Here we identify a β-barrel mitochondrial outer membrane protein, termed tripartite attachment complex 40 (TAC40), that localizes to this connection. TAC40 is essential for mitochondrial DNA inheritance and belongs to the mitochondrial porin protein family. However, it is not specifically related to any of the three subclasses of mitochondrial porins represented by the metabolite transporter voltage-dependent anion channel (VDAC), the protein translocator of the outer membrane 40 (TOM40), or the fungi-specific MDM10, a component of the endoplasmic reticulum–mitochondria encounter structure (ERMES). MDM10 and TAC40 mediate cellular architecture and participate in transmembrane complexes that are essential for mitochondrial DNA inheritance. In yeast MDM10, in the context of the ERMES, is postulated to connect the mitochondrial genomes to actin filaments, whereas in trypanosomes TAC40 mediates the linkage of the mitochondrial DNA to the basal body of the flagellum. However, TAC40 does not colocalize with trypanosomal orthologs of ERMES components and, unlike MDM10, it regulates neither mitochondrial morphology nor the assembly of the protein translocase. TAC40 therefore defines a novel subclass of mitochondrial porins that is distinct from VDAC, TOM40, and MDM10. However, whereas the architecture of the TAC40-containing complex in trypanosomes and the MDM10-containing ERMES in yeast is very different, both are organized around a β-barrel protein of the mitochondrial porin family that mediates a DNA–cytoskeleton linkage that is essential for mitochondrial DNA inheritance.Mitochondria are a hallmark of all eukaroytic cells. They derive from an endosymbiontic event between a free-living bacterium and a presumably prokaryotic host cell. More than 1.5 billion years of evolution resulted in a great diversification of mitochondria. As a consequence, the shape and number of organelles per cell as well as size, content, copy number, and organization of their genomes vary greatly between different taxons (1). However, all eukaryotes must be able to faithfully transmit mitochondria to their offspring (2, 3).Unlike most other eukaryotes, the parasitic protozoa Trypanosoma brucei has a single mitochondrion throughout its life and its cell cycle. Due to the single-unit nature of the mitochondrion, its duplication must be coordinated with the duplication of the nucleus (4). The mitochondrial genome of T. brucei, termed kinetoplast DNA (kDNA), is essential for growth of both the procyclic insect stage and the bloodstream form of the parasite (5). It consists of a disk-shaped single-unit kDNA network that localizes to a distinct region within the mitochondrial matrix (6). The kDNA is physically connected with the cytosolic basal body, the organizing center of the eukaryotic flagellum, via a high-order transmembrane structure termed tripartite attachment complex (TAC) (7) of which only few components have been identified (8–10). Replication of the kDNA network occurs at a defined stage of the cell cycle shortly before the onset of the nuclear S phase. After replication, the kDNA networks need to be correctly positioned so that during cell and mitochondrial division each daughter cell receives a single organelle with a single kDNA network. This process requires an intact TAC and is mediated by the movement of the basal body: one kDNA network remains connected to the basal body of the old flagellum whereas the other one segregates with the basal body of the new flagellum (7, 11).Unlike trypanosomes, Saccharomyces cerevisiae propagates by budding and contains highly dynamic mitochondria that constantly divide and fuse (12, 13). Mitochondrial inheritance in budding yeast therefore requires a mechanism to move mitochondria and their genomes from the mother cell into the growing bud. The protein-associated mitochondrial genomes of S. cerevisiae, termed nucleoids, localize to dozens of globular foci that are distributed all over the organelles. Most actively replicating nucleoids are associated with a protein complex that includes the outer membrane (OM) protein MDM10 as a central unit, as well as the proteins MDM12, MDM34, and MMM1 (14–16). The protein complex forms the endoplasmic reticulum (ER)–mitochondria encounter structure (ERMES) tethering the ER to the mitochondrion (17). The ERMES has also been suggested to connect to cytosolic actin fibers that mediate the movement of mitochondria to the bud of dividing yeast cells (14, 18, 19). Besides its role in mitochondrial inheritance, the ERMES has been implicated in maintenance of mitochondrial morphology and in phospholipid and calcium exchange as well as in the assembly of the protein translocase of the mitochondrial OM (TOM) (20, 21). Some of the proposed ERMES functions are controversial and there is evidence that some of them might be due to secondary effects caused by the drastically altered mitochondrial morphology (22).The central ERMES subunit, the β-barrel protein MDM10 belongs to the mitochondrial porin superfamily, which comprises the three members voltage-dependent anion channel (VDAC), Tom40, and MDM10. Whereas VDAC and Tom40 have so far been found in all eukaryotes, including T. brucei (23, 24), MDM10 is specific to the fungal clade.In this study we identify a mitochondrial OM protein of T. brucei as a novel component of the TAC. We show that the protein defines a novel subclass of the mitochondrial porin superfamily that is specialized in mitochondrial DNA inheritance.     

Intraosseous angioleiomyoma the tibia: A case report

Angioleiomyoma (vascular leiomyoma/angiomyoma) is a morphologically distinctive tumor characterized by proliferating smooth muscle cells admixed with prominent vascular elements. The majority of angioleiomyomas involve the superficial soft tissues. Examples of this lesion originating in bone, particularly in the appendicular skeleton, are extremely rare. The present report details the clinicopathologic features of an unusual case of an intraosseous angioleiomyoma arising in the distal tibia. The skeletal tumor exhibited the typical histologic appearance and immunophenotypic features of this entity. Due to its rarity, angioleiomyoma of bone can pose problems in diagnosis. Awareness that angioleiomyoma can present as a primary intraosseous lesion is important so as not to confuse this neoplasm with more commonly encountered bone tumors.     

Pulmonary benign metastasizing leiomyoma: a case report

Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity usually occurring in females with history of uterine leiomyoma, and it is preferential to metastasize to the lung and appears as a histopathologic benign tumor of smooth muscle origin. In this article, the clinical and pathological data from 1 patient with PBML were analyzed. Chest CT scan showed that multiple well-defined nodules in the both lobes of the lungs. The tumor cells in the lung were well differentiated, and the pattern of tumor was similar to the original tumor. IHC identified it originated from smooth muscle cells, consistent with the diagnosis of PBML. Positive staining of estrogen and progestogen receptors was detected in both the leiomyoma and the metastasizing lesions. During two years of observation, pulmonary function parameters were within normal limits and there was no evidence of tumor recurrence.     

经支气管镜介入技术治疗气道平滑肌瘤的临床研究

目的 探讨经支气管镜下联合荧光、氩离子束凝固术（APC）、二氧化碳冷冻术介入治疗气道平滑肌瘤的可行性及安全性,观察临床疗效。方法 回顾性分析2014年6月－2019年12月该院8例确诊为气道平滑肌瘤所致的气道阻塞患者,在支气管镜下联合荧光进行圈套、电切、APC和二氧化碳冷冻术治疗,观察气道打通程度、临床症状改善情况、并发症的发生率及复发情况,术中监测患者心率、血压、呼吸和血氧饱和度,比较治疗前后患者的气道狭窄分级情况、气促分级和Karnofsky评分（KPS）。评估此技术的疗效和安全性。结果 在8例平滑肌瘤中,行支气管镜下APC、电切和冷冻术共计21次,肿瘤切除后气道完全打通,临床症状完全缓解;无纵隔气肿、呼吸道穿孔及大出血等严重并发症;经随访,无复发。结论 经支气管镜下联合荧光进行APC、高频电刀和二氧化碳冷冻术在治疗气道平滑肌瘤导致的气道阻塞中疗效显著,可达到临床根治,避免了开胸手术创伤,适合临床推广。     

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm. © 1996 Wiley-Liss, Inc.     

贲门部平滑肌瘤的诊断与外科治疗

目的探讨贲门部平滑肌瘤诊断和外科治疗特点.方法回顾性分析经外科手术及病理证实的18例贲门部平滑肌瘤的临床资料.结果吞咽困难、胸及上腹部疼痛和消化道出血是本病的主要症状,平均病程9个月.手术前2例被误诊为贲门癌.17例行胃部分切除术,1例行近端胃大部切除术.全组无手术死亡及严重手术并发症.结论贲门平滑肌瘤是一种少见的良性肿瘤,因其可被误诊为贲门部恶性肿瘤,应特别重视鉴别诊断.手术是治疗本病的最有效方法.     

胃肠造影、胃镜及胃部CT对胃平滑肌瘤诊断的对比研究

目的 提高对胃平滑肌瘤临床及影像学表现的认识及诊断水平.方法 回顾性分析14例经胃镜及胃肠造影初步诊断为胃平滑肌瘤患者的一般资料、临床表现、胃镜表现、胃肠造影表现;并分析其CT表现,其中12例经手术证实.结果 胃肠造影表现:14例在胃底或胃体可见半圆形或边界光整的充盈缺损,胃壁蠕动正常,胃粘膜皱襞展平,3例在充盈缺损表面可见小龛影.胃镜:14例在胃体或胃底部可见粘膜隆起、质韧、边界清晰,其中3例可见胃粘膜表面有小溃疡.CT表现:12例可见在胃体或胃底部软组织肿块影,边界清晰,位于胃壁,与周围组织关系分界清晰;2例胃壁未见明显异常.结论 胃肠造影、胃镜及胃部CT对诊断胃平滑肌瘤各有优缺点,胃镜或胃肠造影与胃部CT结合检查,对胃平滑肌瘤的诊断更准确.     

Nutritional status and intestinal parasites among young children from pastoralist communities of the Ethiopian Somali region

Pastoralist children in the Ethiopian Somali Regional State (ESRS) are at high risk for undernutrition and intestinal parasitic infections (IPIs). We assessed the nutritional status and its association with IPIs in 500 children <5 years of age in a clustered cross‐sectional study in Adadle district, ESRS. Stool samples were microscopically examined for IPIs and biomarkers for iron and vitamin A status, anthropometry, and food variety score (FVS) were assessed. Median (interquartile range [IQR]) FVS was 2.0 (2.0, 4.0), and 35% of children were exclusively breastfed up to age 6 months. Prevalence of stunting, wasting, underweight and mid‐upper arm circumference (MUAC) <12.5 cm was 30, 34, 40, and 16%, respectively. Median (IQR) haemoglobin, ferritin, and retinol‐binding protein concentrations were 9.5 g dL^‐1 (8.2, 10.9), 6.2 μg L^‐1 (4.0, 10.2), and 0.8 μmol L^?1 (0.67, 0.91), respectively. Prevalence of anaemia, iron, and vitamin A deficiency was 75, 91, and 30%, respectively. IPIs' prevalence was 47%; the most prevalent IPIs were Giardia lamblia (22%) and Ascaris lumbricoides (15%). Giardial infections but not A. lumbricoides increased the risk for MUAC <12.5 cm (adjusted odds ratio [aOR]: 3.50, 95% confidence interval [CI] [2.21, 5.54]). The odds for anaemia were 97% (aOR: 0.03, 95% CI [0.03, 0.07]) and 89% (aOR: 0.11, 95% CI [0.11, 0.23]) less for children with FVS >2 or with exclusive breastfeeding up to 6 months, respectively. Undernutrition and IPIs are alarmingly high in <5 years of age children in ESRS. Giardial infections and low nutritional adequacy of the diet seem to be major contributing factors to the precarious nutritional status and should be addressed by appropriate interventions.     

Imaging benign gynaecological conditions

Radiology plays an essential role in the management of benign gynaecological conditions and includes: ultrasound; computed tomography and magnetic resonance imaging. Each modality has a different role in diagnosis, treatment selection and follow-up. This review discusses the different imaging modalities, their recommended roles in the imaging and imaging findings of common female pelvic pathology.