Description of lymphocyte and cytokine profiles in individuals with acute myeloid leukemia associated with FLT3-ITD and NPM1 mutation status.

The pathogenesis of acute myeloid leukemia (AML) involves mutations in genes such as FLT3 and NPM1, which are also associated with the prognosis of the disease. The immune system influences disease progression, but the mechanisms underlying the interaction between the immune system and AML are not clear. In this study, the profiles of lymphocytes and cytokines were described in individuals with AML stratified by molecular changes associated with prognosis. The participants included in this study were newly diagnosed AML patients (n = 43) who were about to undergo chemotherapy. Subtypes of lymphocytes in peripheral blood, including B cells, T cells, and natural killer cells, and serum concentrations of cytokines, including Th1, Th2, and Th17, were studied by flow cytometry assays (BD FACSCanto II). The correlations between lymphocyte subsets, cytokines, and genetic/prognostic risk stratification (based on the FLT3 and NPM1 genes) were analyzed. The differences in B lymphocytes (%), T lymphocytes (%), plasmablasts (%), leukocytes (cells/µl), and tumor necrosis factor (pg/ml) were determined between groups with FLT3-ITD+ and FLT3-ITD- mutations. The presence of mutations in NPM1 and FLT3-ITD and age suggested changes in the lymphocyte and cytokine profile in individuals with AML.

Enhancing diagnostic accuracy of multiple myeloma through ML-driven analysis of hematological slides: new dataset and identification model to support hematologists.

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals' expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies.

Immunophenotypic characterization of acute leukemias in Bahia, Brazil.

OBJECTIVE: To characterize the immunophenotypic profile of acute leukemias in the population of the state of Bahia, Brazil. METHODS: This is a descriptive, retrospective study. From 2014 to 2018, 796 new cases of acute leukemia were evaluated. The data were obtained from analysis of reports and records of tests performed by flow cytometry immunophenotyping. All individuals of all age groups diagnosed as acute lymphoblastic leukemia or acute myeloid leukemia were included in the study. Demographic variables and expression of leukemia antigens were evaluated. RESULTS: Most cases were diagnosed as acute myeloid leukemia and 42.7% as acute lymphoblastic leukemia. Significant differences were found in expression of markers in acute leukemias when age groups were compared, as well as in demographic characteristics. B-cell acute lymphoblastic leukemia was more prevalent than cases of T-cell origin. Assessing the aberrant markers in acute myeloid leukemias, the non-acute promyelocytic leukemia group presented expression of CD7 and CD56 as the most frequent ones. In B-cell acute lymphoblastic leukemia, the most frequent aberrant markers were CD66c, CD13 and CD33. CONCLUSION: Significant differences were found as to several antigens when comparing adults and children, and these findings may contribute to future studies correlating the phenotypic profile to genetic characteristics and therapeutic response, including specific antigen therapies, which may be better targeted.

Immunophenotypic characterization of acute leukemias in Bahia, Brazil

ABSTRACT Objective To characterize the immunophenotypic profile of acute leukemias in the population of the state of Bahia, Brazil. Methods This is a descriptive, retrospective study. From 2014 to 2018, 796 new cases of acute leukemia were evaluated. The data were obtained from analysis of reports and records of tests performed by flow cytometry immunophenotyping. All individuals of all age groups diagnosed as acute lymphoblastic leukemia or acute myeloid leukemia were included in the study. Demographic variables and expression of leukemia antigens were evaluated. Results Most cases were diagnosed as acute myeloid leukemia and 42.7% as acute lymphoblastic leukemia. Significant differences were found in expression of markers in acute leukemias when age groups were compared, as well as in demographic characteristics. B-cell acute lymphoblastic leukemia was more prevalent than cases of T-cell origin. Assessing the aberrant markers in acute myeloid leukemias, the non-acute promyelocytic leukemia group presented expression of CD7 and CD56 as the most frequent ones. In B-cell acute lymphoblastic leukemia, the most frequent aberrant markers were CD66c, CD13 and CD33. Conclusion Significant differences were found as to several antigens when comparing adults and children, and these findings may contribute to future studies correlating the phenotypic profile to genetic characteristics and therapeutic response, including specific antigen therapies, which may be better targeted.

Quality of life and psychological aspects in children with overactive bladder treated with parasacral transcutaneous electrical nerve stimulation - A prospective multicenter study.

OBJECTIVE: To assess the impact of parasacral transcutaneous electrical nerve stimulation (parasacral TENS) on quality of life (QoL) and psychological aspects in children treated for overactive bladder (OAB). METHODS: This international, multicenter, prospective cohort study involved individuals of 6-16 years of age under TENS treatment for OAB. The study was conducted between June 2016 and December 2019 in four participating centers: two in Australia, one in Germany and one in Brazil. Patients with anatomical and/or neurological abnormalities of the urinary tract were excluded. Questionnaires were applied before and after parasacral TENS treatment: the Dysfunctional Voiding Symptom Score (DVSS), used in Brazil, or the International Consultation on Incontinence Questionnaire - Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS), used in Germany and Australia, to analyze urinary symptoms; the Strengths and Difficulties Questionnaire (SDQ) to assess emotional and behavioral aspects; and the Pediatric Incontinence Questionnaire (PinQ) for bladder-specific Qol. RESULTS: Fifty-three patients (28 girls and 25 boys) with a mean age of 8.64 ± 2.63 years were included. Median DVSS was 11 (range 6-13.5) and 3 (range 0-7), (p < 0.001), and median ICIQ-CLUTS was 12 (range 9-14) and 9 (range 5.7-12), (p < 0.001), before and after treatment, respectively. Median PinQ score decreased from 47.8 (range 38.9-59.7) to 39 (range 29-53.15) following treatment (p = 0.04). Median total SDQ score before and after treatment was 17 (range 13.5-21) and 15 (range 12-21), respectively (p = 0.939). CONCLUSION: Parasacral TENS was associated with a significant improvement in urinary symptoms and QoL; however, there was no change in psychological symptoms, as measured using the SDQ.

Total corpora mobilization for penile reconstruction

ABSTRACT Purpose: Total corpora mobilization (TCM) is a novel technique that is used for penile reconstruction in cases of micropenis and penile amputation. Its principle is based on Kelly's procedure for bladder exstrophy (1). In contrast to the Kelly procedure, TCM is performed entirely through the perineum with the patient in the lithotomy position. Materials and Methods: TCM was performed on three patients. The first was a boy who suffered trauma from a dog bite at an age of eight months. At 23 years old he underwent TCM. The second patient had genital self-amputation induced by psychiatric disorder. After treatment, at 27 years old, he desired surgery for penile reconstruction. The third patient had partial androgen insensitivity syndrome (PAIS) with a micropenis and at 23 years old had TCM procedure. The patients were placed in the lithotomy position with a perineal incision in the midline. A subperiosteal incision was made and the corpora cavernosa were detached from the pubic arch and the ischial rami. The periosteum and the neurovascular bundles were preserved. Subsequently the corpora cavernosa was mobilized upward and the periosteum that was left attached to them was sutured to the pubis. Results: At twenty-four, nine, and six months, respectively, in the follow-up process, all patients expressed satisfaction with the final cosmetic appearance, penile length, and erectile function. Conclusion: TCM may prove to be an alternative for patients with a functional disturbance because of small penile length, though a higher number of cases and a more extended follow-up are needed to draw a more definitive conclusion.

Total corpora mobilization for penile reconstruction.

PURPOSE: Total corpora mobilization (TCM) is a novel technique that is used for penile reconstruction in cases of micropenis and penile amputation. Its principle is based on Kelly's procedure for bladder exstrophy (1). In contrast to the Kelly procedure, TCM is performed entirely through the perineum with the patient in the lithotomy position. MATERIALS AND METHODS: TCM was performed on three patients. The first was a boy who suffered trauma from a dog bite at an age of eight months. At 23 years old he underwent TCM. The second patient had genital self-amputation induced by psychiatric disorder. After treatment, at 27 years old, he desired surgery for penile reconstruction. The third patient had partial androgen insensitivity syndrome (PAIS) with a micropenis and at 23 years old had TCM procedure. The patients were placed in the lithotomy position with a perineal incision in the midline. A subperiosteal incision was made and the corpora cavernosa were detached from the pubic arch and the ischial rami. The periosteum and the neurovascular bundles were preserved. Subsequently the corpora cavernosa was mobilized upward and the periosteum that was left attached to them was sutured to the pubis. RESULTS: At twenty-four, nine, and six months, respectively, in the follow-up process, all patients expressed satisfaction with the final cosmetic appearance, penile length, and erectile function. CONCLUSION: TCM may prove to be an alternative for patients with a functional disturbance because of small penile length, though a higher number of cases and a more extended follow-up are needed to draw a more definitive conclusion.

The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion-related organelle.

The simplest class of mitochondrion-related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms. The identification of enzymes responsible for sulfate activation (AS, IPP, and APSK) and a number of lineage-specific proteins such as the outer membrane beta-barrel protein (MBOMP30), and transmembrane domain-containing proteins that bind to various organellar proteins (ETMP1, ETMP30, EHI_170120, and EHI_099350) showcased the remarkable divergence of this organelle compared to the other MROs of anaerobic protozoa. Here, we summarize the findings regarding the biology of the mitosomes in E. histolytica, from their discovery up to the present understanding of its roles and interactions. We also include current advances and future perspectives on the biology, biochemistry, and evolution of the mitosomes of E. histolytica.

Entamoeba histolytica EHD1 Is Involved in Mitosome-Endosome Contact.

Interorganellar cross talk is often mediated by membrane contact sites (MCSs), which are zones where participating membranes come within 30 nm of one another. MCSs have been found in organelles, including the endoplasmic reticulum, Golgi bodies, endosomes, and mitochondria. Despite its seeming ubiquity, reports of MCS involving mitochondrion-related organelles (MROs) present in a few anaerobic parasitic protozoa remain lacking. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called the mitosome. We previously discovered several Entamoeba-specific transmembrane mitosomal proteins (ETMPs) from in silico and cell-biological analyses. One of them, ETMP1 (EHI_175060), was predicted to have one transmembrane domain and two coiled-coil regions and was demonstrated to be mitosome membrane integrated based on carbonate fractionation and immunoelectron microscopy (IEM) data. Immunoprecipitation analysis detected a candidate interacting partner, EH domain-containing protein (EHD1; EHI_105270). We expressed hemagglutinin (HA)-tagged EHD1 in E. histolytica, and subsequent immunofluorescence and IEM data indicated an unprecedented MCS between the mitosome and the endosome. Live imaging of a green fluorescent protein (GFP)-EHD1-expressing strain demonstrated that EHD1 is involved in early endosome formation and is observed in MCS between endosomes of various sizes. In vitro assays using recombinant His-EHD1 demonstrated ATPase activity. MCSs are involved in lipid transfer, ion homeostasis, and organelle dynamics. The serendipitous discovery of the ETMP1-interacting partner EHD1 led to the observation of the mitosome-endosome contact site in E. histolytica. It opened a new view of how the relic mitochondria of Entamoeba may likewise be involved in organelle cross talk, a conserved feature of mitochondria and other organelles in general. IMPORTANCE Membrane contact sites (MCSs) are key regulators of interorganellar communication and have been widely demonstrated between various organelles. However, studies on MCSs involving mitochondrion-related organelles (MROs), present in some anaerobic parasitic protozoans, remain scarce. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called the mitosome. This organelle is crucial for cellular differentiation and disease transmission, thereby significantly contributing to the amoeba's parasitic lifestyle. Our recent discovery of the interaction between the Entamoeba-specific transmembrane mitosomal protein (ETMP1) and EH domain-containing protein (EHD1) showcases a newly found mitosome-endosome contact site in E. histolytica. This finding reflects the idea that despite their substantially divergent and reduced nature, MROs like mitosomes conserve mechanisms for interorganellar cross talk. We posit lipid and ion transport, mitosome fission, and quality control as potential processes that are mediated by the ETMP1-EHD1-tethered mitosome-endosome contact site in E. histolytica.

Transfer RNA-Derived Small RNAs in the Pathogenesis of Parasitic Protozoa.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are newly identified non-coding small RNAs that have recently attracted attention due to their functional significance in both prokaryotes and eukaryotes. tsRNAs originated from the cleavage of precursor or mature tRNAs by specific nucleases. According to the start and end sites, tsRNAs can be broadly divided into tRNA halves (31-40 nucleotides) and tRNA-derived fragments (tRFs, 14-30 nucleotides). tsRNAs have been reported in multiple organisms to be involved in gene expression regulation, protein synthesis, and signal transduction. As a novel regulator, tsRNAs have also been identified in various protozoan parasites. The conserved biogenesis of tsRNAs in early-branching eukaryotes strongly suggests the universality of this machinery, which requires future research on their shared and potentially disparate biological functions. Here, we reviewed the recent studies of tsRNAs in several representative protozoan parasites including their biogenesis and the roles in parasite biology and intercellular communication. Furthermore, we discussed the remaining questions and potential future works for tsRNAs in this group of organisms.

Interorganellar communication and membrane contact sites in protozoan parasites.

A key characteristic of eukaryotic cells is the presence of organelles with discrete boundaries and functions. Such subcellular compartmentalization into organelles necessitates platforms for communication and material exchange between each other which often involves vesicular trafficking and associated processes. Another way is via the close apposition between organellar membranes, called membrane contact sites (MCSs). Apart from lipid transfer, MCSs have been implicated to mediate in various cellular processes including ion transport, apoptosis, and organelle dynamics. In mammalian and yeast cells, contact sites have been reported between the membranes of the following: the endoplasmic reticulum (ER) and the plasma membrane (PM), ER and the Golgi apparatus, ER and endosomes (i.e., vacuoles, lysosomes), ER and lipid droplets (LD), the mitochondria and vacuoles, the nucleus and vacuoles, and the mitochondria and lipid droplets, whereas knowledge of MCSs in non-model organisms such as protozoan parasites is extremely limited. Growing evidence suggests that MCSs play more general and conserved roles in cell physiology. In this mini review, we summarize and discuss representative MCSs in divergent parasitic protozoa, and highlight the universality, diversity, and the contribution of MCSs to parasitism.

Characterization of Plasmodium falciparum Pantothenate Kinase and Identification of Its Inhibitors From Natural Products.

Coenzyme A (CoA) is a well-known cofactor that plays an essential role in many metabolic reactions in all organisms. In Plasmodium falciparum, the most deadly among Plasmodium species that cause malaria, CoA and its biosynthetic pathway have been proven to be indispensable. The first and rate-limiting reaction in the CoA biosynthetic pathway is catalyzed by two putative pantothenate kinases (PfPanK1 and 2) in this parasite. Here we produced, purified, and biochemically characterized recombinant PfPanK1 for the first time. PfPanK1 showed activity using pantetheine besides pantothenate, as the primary substrate, indicating that CoA biosynthesis in the blood stage of P. falciparum can bypass pantothenate. We further developed a robust and reliable screening system to identify inhibitors using recombinant PfPanK1 and identified four PfPanK inhibitors from natural compounds.

Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences.

Mitochondrial matrix proteins synthesized in the cytosol often contain amino (N)-terminal targeting sequences (NTSs), or alternately internal targeting sequences (ITSs), which enable them to be properly translocated to the organelle. Such sequences are also required for proteins targeted to mitochondrion-related organelles (MROs) that are present in a few species of anaerobic eukaryotes. Similar to other MROs, the mitosomes of the human intestinal parasite Entamoeba histolytica are highly degenerate, because a majority of the components involved in various processes occurring in the canonical mitochondria are either missing or modified. As of yet, sulfate activation continues to be the only identified role of the relic mitochondria of Entamoeba. Mitosomes influence the parasitic nature of E. histolytica, as the downstream cytosolic products of sulfate activation have been reported to be essential in proliferation and encystation. Here, we investigated the position of the targeting sequence of one of the mitosomal matrix enzymes involved in the sulfate activation pathway, ATP sulfurylase (AS). We confirmed by immunofluorescence assay and subcellular fractionation that hemagluttinin (HA)-tagged EhAS was targeted to mitosomes. However, its ortholog in the δ-proteobacterium Desulfovibrio vulgaris, expressed as DvAS-HA in amoebic trophozoites, indicated cytosolic localization, suggesting a lack of recognizable mitosome targeting sequence in this protein. By expressing chimeric proteins containing swapped sequences between EhAS and DvAS in amoebic cells, we identified the ITSs responsible for mitosome targeting of EhAS. This observation is similar to other parasitic protozoans that harbor MROs, suggesting a convergent feature among various MROs in favoring ITS for the recognition and translocation of targeted proteins.

Characterization of mitochondrial carrier proteins of malaria parasite Plasmodium falciparum based on in vitro translation and reconstitution.

Members of the mitochondrial carrier (MC) family of membrane transporters play important roles in cellular metabolism. We previously established an in vitro reconstitution system for membrane transporters based on wheat germ cell-free translation system. We have now applied this reconstitution system to the comparative analysis of MC proteins from the malaria parasite Plasmodium falciparum and Saccharomyces cerevisiae. We synthesized twelve putative P. falciparum MCs and determined the transport activities of four of these proteins including PF3D7_1037300 protein (ADP/ATP translocator), PF3D7_1004800 protein (ADP/ATP translocator), PF3D7_1202200 protein (phosphate carrier), and PF3D7_1241600 protein (S-adenosylmethionine transporter). In addition, we tested the effect of cardiolipin on the activity of MC proteins. The transport activities of the yeast MCs, ScAac2p, ScGgc1p, ScDic1p, ScPic1p, and ScSam5p, which localize to the mitochondrial inner membrane, were increased by cardiolipin supplementation, whereas that of ScAnt1p, which localizes to the peroxisome membrane, was not significantly affected. Together, this indicates that the functional properties of the reconstituted MCs reflect the lipid content of their native membranes. Except for PF3D7_1241600 protein, these P. falciparum proteins manifested cardiolipin-dependent transport activities. Immunofluorescence analysis showed that PF3D7_1241600 protein is not mainly localized to the mitochondria of P. falciparum cells. We thus revealed the functions of four MC proteins of the malaria parasite and the effects of cardiolipin on their activities.

Genome-Wide Analysis of Known and Potential Tetraspanins in Entamoeba histolytica.

Tetraspanins are membrane proteins involved in intra- and/or intercellular signaling, and membrane protein complex formation. In some organisms, their role is associated with virulence and pathogenesis. Here, we investigate known and potential tetraspanins in the human intestinal protozoan parasite Entamoeba histolytica. We conducted sequence similarity searches against the proteome data of E. histolytica and newly identified nine uncharacterized proteins as potential tetraspanins in E. histolytica. We found three subgroups within known and potential tetraspanins, as well as subgroup-associated features in both their amino acid and nucleotide sequences. We also examined the subcellular localization of a few representative tetraspanins that might be potentially related to pathogenicity. The results in this study could be useful resources for further understanding and downstream analyses of tetraspanins in Entamoeba.

Novel lineage-specific transmembrane ß-barrel proteins in the endoplasmic reticulum of Entamoeba histolytica.

ß-barrel outer membrane proteins (BOMPs) are essential components of outer membranes of Gram-negative bacteria and endosymbiotic organelles, usually involved in the transport of proteins and substrates across the membrane. Based on the analysis of our in silico BOMP predictor data for the Entamoeba histolytica genome, we detected a new transmembrane ß-barrel domain-containing protein, EHI_192610. Sequence analysis revealed that this protein is unique to Entamoeba species, and it exclusively clusters with a homolog, EHI_099780, which is similarly lineage specific. Both proteins possess an N-terminal signal peptide sequence as well as multiple repeats that contain dyad hydrophobic periodicities. Data from immunofluorescence assay of trophozoites expressing the respective candidates showed the absence of colocalization with mitosomal marker, and interestingly demonstrated partial colocalization with endoplasmic reticulum (ER) proteins instead. Integration to organellar membrane was supported by carbonate fractionation assay and immunoelectron microscopy. CD analysis of reconstituted proteoliposomes containing EHI_192610 showed a spectrum demonstrating a predominant ß-sheet structure, suggesting that this protein is ß-strand rich. Furthermore, the presence of repeat regions with predicted transmembrane ß-strand pairs in both EHI_192610 and EHI_099780, is consistent with the hypothesis that BOMPs originated from the amplification of ßß-hairpin modules, suggesting that the two Entamoeba-specific proteins are novel ß-barrels, intriguingly localized partially to the ER membrane.

An Entamoeba-Specific Mitosomal Membrane Protein with Potential Association to the Golgi Apparatus.

The aerobic mitochondrion had undergone evolutionary diversification, most notable among lineages of anaerobic protists. Entamoeba is one of the genera of parasitic protozoans that lack canonical mitochondria, and instead possess mitochondrion-related organelles (MROs), specifically mitosomes. Entamoeba mitosomes exhibit functional reduction and divergence, most exemplified by the organelle's inability to produce ATP and synthesize iron-sulfur cluster. Instead, this organelle is capable of sulfate activation, which has been linked to amoebic stage conversion. In order to understand other unique features and components of this MRO, we utilized an in silico prediction tool to screen transmembrane domain containing proteins in the mitosome proteome. Here, we characterize a novel lineage-specific mitosomal membrane protein, named Entamoeba transmembrane mitosomal protein of 30 kDa (ETMP30; EHI_172170), predicted to contain five transmembrane domains. Immunofluorescence analysis demonstrated colocalization of hemagglutinin (HA)-tagged ETMP30 with the mitosomal marker, adenosine-5'-phosphosulfate kinase. Mitosomal membrane localization was indicated by immunoelectron microscopy analysis, which was supported by carbonate fractionation assay. Transcriptional gene silencing successfully repressed RNA expression by 60%, and led to a defect in growth and partial elongation of mitosomes. Immunoprecipitation of ETMP30 from ETMP30-HA-expressing transformant using anti-HA antibody pulled down one interacting protein of 126 kDa. Protein sequencing by mass spectrometry revealed this protein as a cation-transporting P-type ATPase, previously reported to localize to vacuolar compartments/Golgi-like structures, hinting at a possible mitosome-vacuole/Golgi contact site.

Microsurgical Treatment of Posterior Cerebral Artery Aneurysm (P2P Segment): Case Report and Review of the Literature

Introduction Aneurysms of the posterior cerebral artery (PCA) represent 1% of all intracranial aneurysms and usually present with subarachnoid hemorrhage. Objective The aimof the present study is to describe the case of an adult man presenting a saccular aneurysm of the right PCA at the posterior half of the postcommunicating (P2P) segment, and to discuss the technical nuances of the approach and of the clipping process. Case Report An investigation of a chronic headache in a 55-year-old man found a saccular aneurysm located just posterior to the most lateral portion of the right cerebral peduncle. A digital subtraction arteriography revealed a 7.8 mm 5.6 mm 4.8 mm posterior-medial projecting aneurysm of the right PCA at the P2P segment. A subtemporal approach was performed with partial aspiration of the right parahippocampal gyrus for a better exposure of the vascular structures. A proximal temporary occlusion of the PCA was performed at the anterior half of the postcommunicating P2A segment. The aneurysm was clipped with two semi-curved clips. The patient presented an uneventful recovery and was discharged from the hospital on the third postoperative day without any additional neurological deficits. Conclusion Aneurysms of the PCA are an uncommon vascular disease that challenges the ability of the neurosurgeons due to their many anatomical nuances, to their vast number of perforators, and to the risk of bleeding. However, the operative management of aneurysms of the PCA is technically feasible, safe and effective when performed respecting microsurgical principles.

Reinventing an Organelle: The Reduced Mitochondrion in Parasitic Protists.

Mitochondria originated from the endosymbiotic event commencing from the engulfment of an ancestral α-proteobacterium by the first eukaryotic ancestor. Establishment of niches has led to various adaptations among eukaryotes. In anaerobic parasitic protists, the mitochondria have undergone modifications by combining features shared from the aerobic mitochondria with lineage-specific components and mechanisms; a diversified class of organelles emerged and are generally called mitochondrion-related organelles (MROs). In this review we summarize and discuss the recent advances in the knowledge of MROs from parasitic protists, particularly the themes such as metabolic functions, contribution to parasitism, dynamics, protein targeting, and novel lineage- specific proteins, with emphasis on the diversity among these organelles.

Hetero-oligomer of dynamin-related proteins participates in the fission of highly divergent mitochondria from Entamoeba histolytica.

Entamoeba histolytica is an anaerobic parasitic protist and possesses mitosomes, one of the most highly divergent mitochondrion-related organelles (MROs). Although unique metabolism and protein/metabolite transport machinery have been demonstrated in Entamoeba mitosomes, the mechanism of mitosomal fusion and fission remains to be elucidated. In this study, we demonstrate that two dynamin-related proteins (DRPs) are cooperatively involved in the fission of Entamoeba mitosomes. Expression of a dominant negative form of EhDrpA and EhDrpB, and alternatively, repression of gene expression of EhDrpA and EhDrpB genes, caused elongation of mitosomes, reflecting inhibition of mitosomal fission. Moreover, EhDrpA and EhDrpB formed an unprecedented hetero-oligomeric complex with an approximate 1:2 to 1:3 ratio, suggesting that the observed elongation of mitosomes is likely caused by the disruption and instability of the complex caused by an imbalance in the two DRPs. Altogether, this is the first report of a hetero-oligomeric DRP complex which participates in the fission of mitochondria and MROs.