Parthenogenetic Reproduction in Strumigenys Ants: An Update.

Parthenogenetic reproduction is a common feature for social Hymenoptera, as males typically develop from unfertilized eggs (arrhenotoky). Production of female offspring without the involvement of sperm (thelytoky) also exists but is rather exceptional as it has been reported for only 16 ant species so far. Three of these belong to the genus Strumigenys: S. hexamera, S. membranifera and S. rogeri. Our observations on the reproductive biology in various Oriental Strumigenys species extends this list of thelytokous ants with three more species: S. emmae, S. liukueiensis and S. solifontis. Of these six thelotykous species, S. emmae, S. membranifera and S. rogeri are known as tramp species. Reproduction without the need to fertilize eggs no doubt offers these species a considerable advantage when establishing colonies in new environments. Published histological data on S. hexamera and S. membranifera already showed that the queens possess a functional spermatheca. We now provide evidence that this is also the case for the four other thelytokous Strumigenys species. Retaining a functional spermatheca and reproductive system may keep the queens ready for the exceptional event of mating and hence increase genetic variability, as males do occur very rarely.

Japanese Tetramorium queens: identification key and species diagnoses (Hymenoptera, Formicidae, Myrmicinae).

In Japan, nine species have been known in the ant genus Tetramorium, of which five or more are considered tramps. A key to the queens of nine Tetramorium species found in Japan is presented. The tramp species T.tonganum Mayr, 1870 is excluded from the key because no queen was available for us, while T.pacificum Mayr, 1870 is included because it was once intercepted at a port in Japan and exotic queens were available. Diagnosis of the queen of each species is provided together with differences between the two female castes. Tetramoriumtanakai Bolton, 1977 is resurrected from synonymy with T.kraepelini Forel, 1905 based mainly on the queen characters.

Unusual uterine cervical polypoid mass presenting during pregnancy.

The authors encountered a case of uterine cervical adenosarcoma with sarcomatous overgrowth during pregnancy. Cytological images of atypical stromal cells in sarcoma components were obtained in this case.

The basitarsal sulcus gland, a novel exocrine structure in ants.

The basitarsus of the mid- and/or hindlegs of several Amblyoponinae ants shows a deep longitudinal groove or sulcus on its anterior face in workers and queens. Histological examination reveals this sulcus is associated with a conspicuous novel epithelial gland, which brings the number of exocrine glands in the legs of ants to 25. The ultrastructural characteristics of the gland show the presence of a well-developed smooth endoplasmic reticulum. This is indicative for the elaboration of a non-proteinaceous and thus possibly pheromonal secretion. Behavioural observations show that this secretion is collected by the tarsomeres and spread onto the brood and nest, suggesting a role in nestmate recognition. A similar basitarsal sulcus gland was also found in Nothomyrmecia, Paraponera and Tetraponera, which represents both a wide phylogenetic and ecological distribution, as it includes arboreal, ground-dwelling as well as subterranean taxa.

Geographic patterns in colonial reproductive strategy in Myrmecina nipponica: Links between biogeography and a key polymorphism in ants.

The ability to express different phenotypes can help define species distributions by allowing access to, and exploitation of, new environments. Social insects employ two markedly different reproductive strategies with contrasting cost/benefit characteristics: independent colony foundation (ICF), which is associated with high dispersal range and high risk, and dependent colony foundation (DCF), characterized by low risk but low dispersal. The ant Myrmecina nipponica employs both of these strategies, with the frequency of each apparently varying between populations. We combine molecular data with data on reproductive strategy from different populations of this species throughout Japan to explore how this polymorphism is linked to environmental factors and whether this relationship can help explain the current and historical biogeography of this species. Reproductive strategy exhibited a strong geographic pattern, with ICF predominant in southern populations and DCF more common in northern and southern highland populations. Molecular analyses clearly divided populations into broad geographic regions, with the southern lowland populations basal to (southern highland (+ northern)) populations. Intra-population polymorphism in colony-founding strategy was widespread, and polymorphism was reconstructed as the likely ancestral state. The frequency of different strategies was linked with climate, with DCF more common in colder areas. A recent inferred origin to the northern lineage suggests that colonization of northern Japan was a rapid event coincident with warming at the end of the Last Glacial Maxima, likely facilitated by the cold-adaptive advantages of DCF. We discuss how such polymorphisms could help explain the biogeography of this and other social insects.

Search for conditions to avoid parametrectomy during radical hysterectomy for cervical cancer.

AIM: This study aimed to assess adequate conditions for omitting parametrectomy for stage IB1-IIA2 cervical cancer with the aim of reducing postoperative complications during Type III radical hysterectomy (RH). METHODS: We investigated factors associated with parametrial invasion (PMI) in patients who underwent Type III RH for stage IB1, IB2, IIA1, IIA2 and IIB cervical cancer at two tertiary institutions from November 2006 to February 2018. Both clinicopathological and preoperatively estimated factors were assessed. RESULTS: One hundred fifty-six patients were preoperatively diagnosed with stage IB1 to IIB disease. Thirty-four patients (21.8%) showed PMI on histological analyses. In the multivariate analysis, an age older than 50 years, tumor size larger than 40 mm, common iliac lymph node metastasis and lymphovascular space invasion were identified as significant risk factors for PMI (P-values = 0.008, 0.003, 0.004 and 0.004, respectively). The preoperatively estimated risk factors for PMI were an older age, larger tumor size, and common iliac lymph node metastasis (P-values = 0.007, 0.002 and 0.001, respectively). A combination of these three factors was sufficient to estimate PMI with a high specificity (100%) and positive predictive value (100%) in patients with stage IB1 to IIA2 disease. CONCLUSION: During RH, resecting the posterior layer of the vesicouterine ligament and the paracolpium without removing the cardinal ligament (avoiding parametrectomy) might be feasible for stage IB1-IIA2 cervical cancer in patients younger than 50 years presenting with smaller tumors (<40 mm) and no common iliac lymph node metastasis.

Clinical significance of M2 macrophages expressing heme oxygenase-1 in malignant transformation of ovarian endometrioma.

Malignant transformation of endometriosis is a rare and still poorly understood event, but is associated with the distortion of the pro-oxidant and anti-oxidant balance. The aim of the present study was to quantify the numbers of macrophages polarized as M1 or M2 phenotypes and the expression of heme oxygenase (HO)-1 in tissue sections from patients with benign ovarian endometrioma (OE) and its malignant transformation (endometriosis-associated ovarian cancer, EAOC). We performed a retrospective study at the Department of Gynecology, Nara Medical University hospital from December 2012 to March 2015. This study included 53 patients with OE (n = 33) and EAOC (n = 20), and we evaluated polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c, CD163 and HO-1. The number of the M1 phenotype (CD11c+, p = 0.001) and the M2 phenotype (CD163+, p = 0.009) was significantly lower in EAOC patients than in OE patients. Analyzing the correlations between the studied markers, the expression of CD68, CD11c, and CD163 proteins significantly correlated with each other (p < 0.001). The number of M2 phenotypes expressing HO-1 was significantly decreased in the EAOC group, compared with the OE group (P < 0.001), demonstrating sustained downregulation of an antioxidant marker, HO-1, in EAOC. In conclusion, reduced number of M2 macrophages expressing HO-1 may have an important role in promoting malignant transformation of OE.

Comparison of redox parameters in ovarian endometrioma and its malignant transformation.

The present study aimed to evaluate the levels of oxidative stress and antioxidant markers in benign endometrioma (OE) and its malignant transformation [endometriosis-associated ovarian cancer (EAOC)] by measuring 8-hydroxy-2-deoxyguanosine (8-OHdG), heme oxygenase-1 (HO-1) and total antioxidant capacity (TAC/Heme-iron) alterations associated with disease progression. Cyst fluid samples from 44 patients with OE and 14 patients with EAOC were studied using an enzyme-linked immunosorbent assay. A χ2 test, t-test and Pearson correlation test were performed using SPSS version 22.0. The cut-off point, sensitivity and specificity of each marker for EAOC diagnosis were evaluated by receiver operating characteristic curve analysis. Cyst fluid 8-OHdG and HO-1 levels in the EAOC group were significantly decreased compared with the OE subjects (P=0.013 and P<0.001, respectively). The levels of TAC/Heme-iron in patients with EAOC were significantly higher compared with those in the OE subjects (P<0.001). The present study demonstrated a positive correlation between 8-OHdG and HO-1 levels (P=0.012). HO-1 exhibited the highest discriminant value for EAOC (Area Under the Curve=0.901). The optimal cut-off point of HO-1 for the diagnosis of EAOC was 2.314 ng/ml, with a sensitivity and specifity of 95.2 and 85.7%, respectively. The present study revealed a clear separation between the overall redox state in OE and EAOC. It was concluded that characteristic alterations in important factors in redox may be helpful for understanding the pathogenesis of the malignant transformation of endometriosis.

The HNF-1ß-USP28-Claspin pathway upregulates DNA damage-induced Chk1 activation in ovarian clear cell carcinoma.

Transcription factor hepatocyte nuclear factor 1-beta (HNF-1ß) enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. However, the underlying mechanism leading to checkpoint activation of HNF-1ß still remains largely unknown. To clarify the effects of HNF-1ß on cell cycle checkpoints, human CCC cell lines were transfected with siRNAs targeting HNF-1ß, Claspin, USP28, or a control vector. Ubiquitination and stabilization of Claspin protein by HNF-1ß was assessed by immunoprecipitation. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1ß facilitated the Claspin expression after treatment with a genotoxic agent bleomycin, resulting in accumulation of phosphorylated Chk1 (p-Chk1) and promotion of survival in CCC cell lines. This study showed for the first time that USP28, a de-ubiquitinase crucial for Claspin expression, is one target gene of HNF-1ß. Knockdown of endogenous USP28 suppressed the Claspin expression and p-Chk1 activation and cell viability. Our findings identify a novel pathway of the HNF-1ß-USP28-Claspin-Chk1 axis in checkpoint signal amplification in response to DNA damage. Targeting this pathway may represent a putative, novel, anticancer strategy in ovarian CCC.

Novel thoracic glands in the ant Myopias hollandi.

Besides the common labial and metapleural glands, four novel exocrine glands are described in the thorax of both workers and queens of the ponerine ant Myopias hollandi. From anterior to posterior, these glands were designated as the propleural pit gland, the posterolateral pronotal gland, the anterolateral propodeal gland and the metasternal process gland. They all correspond with class-3 glands, that are made up of bicellular units that each comprise a secretory cell and a duct cell. In the propleural pit gland, the ducts are characterized by a gradually widening diameter, while in the three other glands the ducts show a portion which displays a balloon-like expansion, that on semithin sections stains very dark. For none of these novel glands the function is known as yet, although ultrastructural examination indicates that they produce a non-proteinaceous and therefore possibly pheromonal secretion.

Adaptive phenotypic variation among clonal ant workers.

Phenotypic variations are observed in most organisms, but their significance is not always known. The phenotypic variations observed in social insects are exceptions. Genetically based response threshold variances have been identified among workers and are thought to play several important adaptive roles in social life, e.g. allocating tasks among workers according to demand, promoting the sustainability of the colony and forming the basis of rationality in collective decision-making. Several parthenogenetic ants produce clonal workers and new queens by asexual reproduction. It is not clearly known whether such genetically equivalent workers show phenotypic variations. Here, we demonstrate that clonal workers of the parthenogenetic ant Strumigenys membranifera show large threshold variances among clonal workers. A multi-locus genetic marker confirmed that colony members are genetic clones, but they showed variations in their sucrose response thresholds. We examined the changing pattern of the thresholds over time generating hypotheses regarding the mechanism underlying the observed phenotypic variations. The results support the hypothesis that epigenetic modifications that occur after eclosion into the adult form are the cause of the phenotypic variations in this asexual species.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis.

The purpose of this phase II trial was to assess the efficacy and toxicity of paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175 mg/m2 and nedaplatin at 80 mg/m2 were administered every 28-day cycle, of which there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled in the study from November 2011 to July 2015. Their median age was 48.5 years (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%) had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%), respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy with TN for cervical cancer with LNM was demonstrated to be an effective and feasible treatment. A phase III trial is warranted to compare this with concurrent chemoradiotherapy.

Discrimination of malignant transformation from benign endometriosis using a near-infrared approach.

The aim of the present single-center retrospective study was to investigate the discrimination of malignant transformation from ovarian endometrioma (OE) using a near-infrared approach ex vivo. Cystic fluid samples were collected from patients with OE (n=34) and endometriosis-associated ovarian cancer (EAOC) (n=12). The light reflected from each sample of cystic fluid [change in luminance, Δl (cd/m2) = background luminance-cystic fluid luminance at 800 nm] was spectrally measured by a near-infrared CCD camera with band-path filter (800 nm). The Δl in EAOC was significantly lower compared with that in OE. On regression analysis, a positive correlation was observed between the Δl and Hb level in the cystic fluid, and this association was exponential. The diagnostic sensitivity and specificity of Δl was 83.3 and 94.1% at the cutoff value of 21.5 cd/m2, with an area under the ROC curve of 0.897. The present ex vivo study potentially provides a powerful near-infrared approach for quantitative discrimination between EAOC and benign OE, with high sensitivity and specificity, which may have clinical applications.

A novel peptide blocking cancer cell invasion by structure-based drug design.

The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion. The molecular and functional mechanisms of H1 were determined by complementary biochemical and biological methods in the promyeloid U937 cell line as well as ovarian cancer cell lines, including serous carcinoma SKOV3 and clear cell carcinoma TOV21G. The effects of H1 treatment on cancer cell invasion were evaluated in vitro. H1 inhibited cancer cell invasion, without affecting cell viability, accompanied by the suppression of extracellular signal-regulated kinase (ERK)-1 phosphorylation and then matrix metalloproteinase (MMP)-9 expression. H1 failed to block the interaction of uPA-uPAR protein-protein interaction in cells, but antagonized the uPA function. H1 failed to disrupt the uPA-uPAR complex, but abolished the invasion of ovarian cancer cells at least through suppression of the ERK-MMP-9 signaling pathway. Further studies are needed to confirm our observations and to describe the underlying molecular mechanism.

Transcriptome profiling of the spermatheca identifies genes potentially involved in the long-term sperm storage of ant queens.

Females of social Hymenoptera only mate at the beginning of their adult lives and produce offspring until their death. In most ant species, queens live for over a decade, indicating that ant queens can store large numbers of spermatozoa throughout their long lives. To reveal the prolonged sperm storage mechanisms, we identified enriched genes in the sperm-storage organ (spermatheca) relative to those in body samples in Crematogaster osakensis queens using the RNA-sequencing method. The genes encoding antioxidant enzymes, proteases, and extracellular matrix-related genes, and novel genes that have no similar sequences in the public databases were identified. We also performed differential expression analyses between the virgin and mated spermathecae or between the spermathecae at 1-week and 1-year after mating, to identify genes altered by the mating status or by the sperm storage period, respectively. Gene Ontology enrichment analyses suggested that antioxidant function is enhanced in the spermatheca at 1-week after mating compared with the virgin spermatheca and the spermatheca at 1-year after mating. In situ hybridization analyses of 128 selected contigs revealed that 12 contigs were particular to the spermatheca. These genes have never been reported in the reproductive organs of insect females, suggesting specialized roles in ant spermatheca.

Worker reproduction of the invasive yellow crazy ant Anoplolepis gracilipes.

BACKGROUND: Reproductive division of labor is one of the key features of social insects. Queens are adapted for reproduction while workers are adapted for foraging and colony maintenance. In many species, however, workers retain functional ovaries and can lay unfertilized male eggs or trophic eggs. Here we report for the first time on the occurrence of physogastric workers and apparent worker reproduction in the invasive yellow crazy ant Anoplolepis gracilipes (Fr. Smith). We further examined the reproductive potential and nutritional role of physogastric workers through multidisciplinary approaches including morphological characterization, laboratory manipulation, genetic analysis and behavioral observation. RESULTS: Egg production with two types of eggs, namely reproductive and trophic eggs, by physogastric workers was found. The reproductive egg was confirmed to be haploid and male-destined, suggesting that the workers produced males via arrhenotokous parthenogenesis as no spermatheca was discovered. Detailed observations suggested that larvae were mainly fed with trophic eggs. Along with consumption of trophic eggs by queens and other castes as part of their diet, the vital role of physogastric workers as "trophic specialist" is confirmed. CONCLUSION: We propose that adaptive advantages derived from worker reproduction for A. gracilipes may include 1) trophic eggs provisioned by physogastric workers likely assist colonies of A. gracilipes in overcoming unfavorable conditions such as paucity of food during critical founding stage; 2) worker-produced males are fertile and thus might offer an inclusive fitness advantage for the doomed orphaned colony.

Skin-mucous membrane disorder and therapeutic effect of pegylated liposomal doxorubicin in recurrent ovarian cancer.

AIM: Hand-foot syndrome (HFS) induced by chemotherapy and molecule-targeting drugs is correlated with treatment efficacy. We conducted a retrospective analysis to evaluate the relationship between HFS and efficacy of pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer. METHODS: Patients were treated with PLD between July 2009 and May 2014. We evaluated patient characteristics, incidence of adverse events, clinical benefit (rate of complete response, partial response, and stable disease), progression-free survival, and overall survival. RESULTS: Twenty-seven patients were included in the study. Median age was 63 years (range, 41-77 years). The median number of cycles of PLD was 3 (range, 1-6). The clinical benefit rate was 33.3%, and progressive disease was noted in 18 patients (66.7%). Median overall survival was 6.7 months (range, 1.1-41 months). Compared with patients with grade 0/1 HFS and oral mucositis, patients with grade 2-4 toxicity (n = 9, 33.3%) had a significantly higher rate of clinical benefit (11.1% vs 77.7%; P < 0.001) and a longer median overall survival (3.7 months vs 20.8 months; P < 0.001). CONCLUSIONS: Severity of HFS and mucositis may be a predictive marker of PLD efficacy. The prevention and management of HFS and mucositis are important for continued treatment.

Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.

Effectiveness of antiemetic triplet therapy with aprepitant, palonosetron, and dexamethasone for gynecologic cancer patients receiving carboplatin and paclitaxel: a prospective single-arm study.

PURPOSE: There is no positive evidence for the efficacy of antiemetic triplet therapy with aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) for moderate emetogenic chemotherapy, especially for gynecologic malignancies. Thus, the present study evaluated the efficacy of this triplet therapy in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy. METHODS: Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2-3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate, i.e., no vomiting and no rescue, at 24-120 h after chemotherapy administration. RESULTS: Seventy patients were enrolled. The delayed CR rate was 97.1% (68/70). No serious adverse events were observed. Younger patient age (≤50 years) tended to be associated with a poor delayed CR rate. CONCLUSIONS: This study demonstrated a notable efficacy of antiemetic triplet therapy with APR, PALO, and DEX in female patients receiving CP. Further evaluation with a larger phase III trial is warranted.