A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. During a replicative cycle, CRK5 stably interacts with a single Plasmodium-specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. Our results provide evidence that during Plasmodium male gametogony, this divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication.

Giant cell tumor of soft tissue originating from the thyroid: a case report and literature review

Background: Giant cell tumor of soft tissues (GCT-ST) is a low malignant uncommon neoplasm, with is histological and immunophenotype similar to that of GCT of bone. Primary giant cell tumor of soft tissue arising in the thyroid is exceedingly rare. Case presentation: We reported a new case of GCT-ST originating from the thyroid occurring in 69-year-old woman. Histologically, the tumor was composed of two morphological components, mononuclear cells admixed with multinucleated osteoclast-like giant cells. Tumor is devoid of atypia, pleomorphism, and atypical mitosis. Immunohistochemically, the tumor cells showed strongly positivity with antibodies to CD68, but were negative for AE1/AE3, EMA and additional muscle markers. Conclusions: Due to its rare occurrence, we analyzed the clinical features of patients with primary thyroid GCT-ST to summarize some of our experiences and conduct a literature. The interest of this case lies in the rarity of this entity, the difficulty in preoperative diagnosis, and the confusion with other malignancies.

A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

SummaryCell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. During a replicative cycle, CRK5 stably interacts with a single Plasmodium-specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. Our results provide evidence that during Plasmodium male gametogony, this divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication.

Plasmodium condensin core subunits (SMC2/SMC4) mediate atypical mitosis and are essential for parasite proliferation and transmission

SummaryCondensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and ChIP-seq analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and II complexes form at these stages. Knockdown of smc2 and smc4 gene expression revealed essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle.

Useful histological findings in incisional biopsies of oral squamous cell carcinoma

Introduction. Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. Objective. The aim of this study was to investigate the histopathological features of OSCC specimens obtained from incisional biopsies and to alert clinicians to the importance of more representative biopsies. Methods.. Forty-eight OSCC samples were obtained from incisional biopsies and classified by Bryne?s score. The following morphological features were analyzed: invasive front, invasiveness, apoptotic cells, atypical mitosis, giant cells, acantholysis, ulceration, necrosis, calcification, surface epithelium, granulation tissue, desmoplasia, tissue invasions, inflammatory infiltrate and tumor thickness. Results. Ten (21%) cases were classified as high grade malignancies and 38 (79%) as low grade. Apoptotic cells (n = 26), atypical mitosis (1-2/20?; n = 38), giant cells (n = 8), acantholysis (n = 5), necrosis (n = 5), calcification (n = 1), granulation tissue (n = 32), desmoplasia (n = 4), perineural invasion (n = 2), muscular invasion (n = 8), invasion of salivary gland tissue (n = 3), vascular invasion (n = 10), and chronic inflammation (n = 33) were observed. Vascular invasion (p = 0.04, Pearson?s ?2 test) and necrosis (p = 0.04, Pearson?s ?2 test) were significantly associated with cases of high-grade malignant tumors. Atypical mitosis was associated with a greatest tumor thickness (p = 0.04, Fischer?s exact test). Conclusion. This study suggests that incisional biopsies may be useful and significant as they can show histopathological variables that are important to classify oral squamous cell carcinomas into low grade and high grade according to Bryne?s score, which was used in this study. Thus, more representative biopsies might be useful to achieve this and allow a more accurate planning.

Problems of Differential Diagnosis in Melanoma Arising from Blue Naevus

Melanoma arising from blue naevus is an exceedingly rare variant of melanoma. Most of the cases are located in head and neck area, with scalp the most affected site. This type of melanoma develops on blue naevus or resembles blue naevus, most frequently cellular blue naevus. We present the case of a 52 years old female diagnosed with a pigmented melanoma of the scalp, with maximum tumoral thickness of 6.8 mm and invasion of the hypodermis, highly resembling cellular blue naevus. All criteria of malignancy were present: prominent nuclear pleomorphism, infiltrative pattern, tumoral necrosis, high mitotic rate (11 mitoses/mm2) with atypical mitosis and high Ki67 index. No lymph node or distant metastases were identified at presentation. Because of the rarity of cases, histopathological diagnosis can be difficult, differential diagnosis with blue naevi, atypical blue naevi or metastatic melanoma being the most challenging problems. Prognosis is given by tumoral thickness, frequently being more than 4 mm.