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Violência doméstica contra a mulher recebe esse nome porque ocorre nas dependências da residência, por ter ligação com familiares ou em uma relação íntima de afeto. As violências podem ir de lesões mais leves a transtornos psicológicos, entre outros. O objetivo deste estudo foi pesquisar e identificar a violência doméstica sofrida por mulheres; apontar os tipos de violência doméstica; identificar informações e dados de publicações a respeito das consequências psicológicas advindas da violência doméstica descritas na literatura. A metodologia consistiu em Revisão Bibliográfica entre os anos de 2010 a 2021 em bases de dados indexadas com periódicos e artigos científicos. Resultado: Identificou-se a relação dos tipos de violência doméstica e suas consequências psicológicas com foco no TEPT, ansiedade, depressão, vergonha, medo, culpa e outros não menos relevantes. Conclusão: Uma das possibilidades deste estudo foi identificar e propor novos dados para pesquisa quanto à violência doméstica e suas consequências psicológicas.

Orphan genes (OGs) are protein-coding genes that are restricted to particular clades or species and lack homology with genes from other organisms, making their biological function difficult to predict. OGs can rapidly originate and become functional; consequently, they may support rapid adaptation to environmental changes. Extensive spread of mobile elements, and whole genome duplication, occurred in the Saccharum group, which may have contributed to the origin and diversification of OGs in the sugarcane genome. Here, we identified and characterized OGs in sugarcane, examined their expression profiles across tissues and genotypes, and investigated their regulation under varying conditions. We identified 319 OGs in the Saccharum spontaneum genome without detected homology to protein-coding genes in green plants, except those belonging to Saccharinae. Transcriptomic analysis showed 288 sugarcane OGs with detectable expression levels in at least one tissue or genotype. We observed similar expression patterns of OGs in sugarcane genotypes originating from the closest geographical locations. We also observed tissue-specific expression of some OGs, possibly indicating a complex regulatory process for maintaining diverse functional activity of these genes across sugarcane tissues and genotypes. Sixty-six OGs were differentially expressed under stress conditions, especially cold and osmotic stresses. Gene co-expression network and functional enrichment analyses suggested that sugarcane OGs may be involved in several biological mechanisms, including stimulus response and defence mechanisms. These findings provide a valuable genomic resource for sugarcane researchers, especially those interested in selecting stress-responsive genes.

Background The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients’ antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46. Methods We treated several human myeloma cell lines and non-myeloma cell lines with BVDV to evaluate the expression of CD46 and to study the effect on cell viability by flow cytometry. The possible synergistic effect of bortezomib in combination with BVDV was also tested. Moreover, we infected the bone marrow mononuclear cells obtained from myeloma patients and we checked the BVDV effect on different cell populations, defined by CD138, CD14, CD3, CD19, and CD56 expression evaluated by flow cytometry. Finally, the in vivo BVDV effect was tested in NOD-SCID mice injected subcutaneously with myeloma cell lines. Results Human myeloma cells were selectively sensitive to BVDV treatment with an increase of cell death and, consequently, of apoptotic markers. Consistently, bone marrow mononuclear cells isolated from myeloma patients treated with BVDV, showed a significant selective decrease of the percentage of viable CD138+ cells. Interestingly, bortezomib pre-treatment significantly increased the cytotoxic effect of BVDV in myeloma cell lines with a synergistic effect. Finally, the in vitro data were confirmed in an in vivo myeloma mouse model showing that BVDV treatment significantly reduced the tumoral burden compared to the vehicle. Conclusions Overall, our data indicate, for the first time, a direct oncolytic effect of the BVDV in human myeloma cells suggesting its possible use as novel alternative anti-myeloma virotherapy strategy.

The protein kinase (PK) superfamily is one of the largest superfamilies in plants and the core regulator of cellular signaling. Despite this substantial importance, the kinomes of sugarcane and sorghum have not been profiled. Here, we identified and profiled the complete kinomes of the polyploid Saccharum spontaneum (Ssp) and Sorghum bicolor (Sbi), a close diploid relative. The Sbi kinome was composed of 1,210 PKs; for Ssp, we identified 2,919 PKs when disregarding duplications and allelic copies, and these were related to 1,345 representative gene models. The Ssp and Sbi PKs were grouped into 20 groups and 120 subfamilies and exhibited high compositional similarities and evolutionary divergences. By utilizing the collinearity between the species, this study offers insights into Sbi and Ssp speciation, PK differentiation and selection. We assessed the PK subfamily expression profiles via RNA-Seq and identified significant similarities between Sbi and Ssp. Moreover, coexpression networks allowed inference of a core structure of kinase interactions with specific key elements. This study provides the first categorization of the allelic specificity of a kinome and offers a wide reservoir of molecular and genetic information, thereby enhancing the understanding of Sbi and Ssp PK evolutionary history.

Simple Summary Osteolytic bone lesions represent an important clinical feature of multiple myeloma (MM). MM cells metabolize very high amounts of glutamine (Gln) and significantly lower Gln in the bone marrow. In this contribution we demonstrate that MM-dependent Gln depletion impairs the differentiation of bone marrow mesenchymal stromal cells into osteoblasts, the cells that form new bone tissue. We also found that osteoblast differentiation is associated with increased expression of glutaminase, the main enzyme that metabolizes Gln, SNAT2, a transporter able to accumulate Gln into the cells, and asparagine synthetase, the enzyme that uses Gln to obtain asparagine (Asn). Asn rescued osteoblast differentiation of Gln-starved mesenchymal stromal cells. These results demonstrate that MM cells impair osteoblast differentiation, hindering mesenchymal Asn synthesis through Gln depletion. Besides providing a metabolic mechanism underlying osteolytic lesions in MM, these results suggest that Asn supplementation may prevent bone disease in MM patients. Abstract Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentiation of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM.

The protein kinase (PK) superfamily is one of the largest superfamilies in plants and is the core regulator of cellular signaling. Even considering this substantial importance, the kinomes of sugarcane and sorghum have not been profiled. Here we identified and profiled the complete kinomes of the polyploidSaccharum spontaneum(Ssp) andSorghum bicolor(Sbi), a close diploid relative. The Sbi kinome was composed of 1,210 PKs; for Ssp, we identified 2,919 PKs when disregarding duplications and allelic copies, which were related to 1,345 representative gene models. The Ssp and Sbi PKs were grouped into 20 groups and 120 subfamilies and exhibited high compositional similarities and evolutionary divergences. By utilizing the collinearity between these species, this study offers insights about Sbi and Ssp speciation, PK differentiation and selection. We assessed the PK subfamily expression profiles via RNA-Seq, identifying significant similarities between Sbi and Ssp. Moreover, through coexpression networks, we inferred a core structure of kinase interactions with specific key elements. This study is the first to categorize the allele specificity of a kinome and provides a wide reservoir of molecular and genetic information, enhancing the understanding of the evolutionary history of Sbi and Ssp PKs.HighlightThis study describes the catalog of kinase gene family inSaccharum spontaneumandSorghum bicolor, providing a reservoir of molecular features and expression patterns based on RNA-Seq and co-expression networks.

Sugarcane is an economically important crop, but its genomic complexity has hindered advances in molecular approaches for genetic breeding. New cultivars are released based on the identification of interesting traits, and for sugarcane, brown rust resistance is a desirable characteristic due to the large economic impact of the disease. Although marker-assisted selection for rust resistance has been successful, the genes involved are still unknown, and the associated regions vary among cultivars, thus restricting methodological generalization. We used genotyping by sequencing of full-sib progeny to relate genomic regions with brown rust phenotypes. We established a pipeline to identify reliable SNPs in complex polyploid data, which were used for phenotypic prediction via machine learning. We identified 14,540 SNPs, which led to a mean prediction accuracy of 50% by using different models. We also tested feature selection algorithms to increase predictive accuracy, resulting in a reduced dataset with more explanatory power for rust phenotypes. Using different feature selection techniques, we achieved accuracy of up to 95% with a dataset of 131 SNPs related to brown rust QTL regions and auxiliary genes. Therefore, our novel strategy has the potential to assist studies of the genomic organization of brown rust resistance in sugarcane.

Periductal stromal tumor (PDST) is a rare biphasic tumor of the breast that exhibits low-grade malignancy and intermediate behavior. It is characterized by proliferation of atypical spindle cells surrounding benign mammary ducts and infiltrating adjacent adipose tissue. PDST is distinguished from phyllodes tumor by its lack of leaf-like architecture; however, it is still unclear whether PDST is a separate entity or a certain spectrum of phyllodes tumor. Phyllodes tumors constitute a group of rare epithelial lesions of the breast which mainly develops at around 40-50 years. The histologic characteristics to be considered are many and often heterogeneous in the same lesion which makes interpretation in needle biopsy material difficult. Most phyllodes tumors have a benign nature, with a high rate of postsurgical recurrence. In the malignant form, metastases are described by distant hematogenous route; its indolent behavior implies a tight surgical management with precise excision of the lesion even if there is not, however, a unanimous consent on the parameters of accuracy of the margins.

The four cemeteries of Cyrene were a living archaeological landscape whose life continued far beyond antiquity. The habit of using monumental tombs was a long-lasting one in Cyrene, starting in the Archaic period and continuing until Roman times. The concept of ‘reuse’ is in itself a problematic one since, from a semantic point of view, it implies the presence of a clear-cut division between an original ‘phase of use’ and of a later ‘phase of reuse’. This approach could have sense when a clear hiatus is present, for example when speaking of modern reuse of ancient Greek tombs. However, the main problem is the use of the term ‘reuse’ when describing two ancient phases, such as a Hellenistic phase and a Roman phase of the same tomb, implying a clear hiatus between them even if one often lacks the elements for identifying the existence of such a hiatus. In particular, the Southern and Northern Necropolises have been analysed here to investigate this subject, basing the hypotheses on data coming from field research and previous studies. However, the topic of reuse for the tombs of Cyrene would need far more space than this paper, so this work should be considered an introduction to a matter that needs a far deeper and a far wider analysis. Given these limits, an ‘anthological’ approach is here proposed, with a sequence of various subjects connected to the ‘reuse’ topic and some new data coming from recent research (such as the surveys in the Northern and Southern Necropolises and the excavation of Tomb S1 by the Chieti University team, and of a tomb in the Northern Necropolis by a team of colleagues from the local Department of Antiquities).

Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined. The reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes. Surprisingly, 80% of nucleotide binding site-encoding genes associated with disease resistance are located in 4 rearranged chromosomes and 51% of those in rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing selection in rearranged regions, maintaining their diversity. Introgressed S. spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441 genome, indicating random recombination among homologs in different S. spontaneum accessions. The allele-defined Saccharum genome offers new knowledge and resources to accelerate sugarcane improvement.

// Federica Costa 1, * , Denise Toscani 1, * , Antonella Chillemi 2 , Valeria Quarona 2 , Marina Bolzoni 1 , Valentina Marchica 1, 6 , Rosanna Vescovini 3 , Cristina Mancini 4 , Eugenia Martella 4 , Nicoletta Campanini 4 , Chiara Schifano 5 , Sabrina Bonomini 5 , Fabrizio Accardi 1, 5 , Alberto L. Horenstein 2 , Franco Aversa 1, 5 , Fabio Malavasi 2 and Nicola Giuliani 1, 5, 6 1 Department of Medicine and Surgery, University of Parma, Parma, Italy 2 Laboratory of Immunogenetics, Department of Medical Sciences and CeRMS, University of Torino, Torino, Italy 3 Clinical Medicine Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy 4 Pathology, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy 5 Hematology and BMT Center, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy 6 CoreLab, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy * These authors contributed equally to this work Correspondence to: Nicola Giuliani, email: nicola.giuliani@unipr.it Keywords: multiple myeloma, CD38, osteoclast, bone disease, immunotherapy Received: October 27, 2016 Accepted: April 29, 2017 Published: May 16, 2017 ABSTRACT It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies. Results indicate that only plasma cells expressed CD38 at high level within the bone niche. In addition, the flow cytometry analysis shows that CD38 was also expressed by monocytes and early osteoclast progenitors but not by osteoblasts and mature osteoclasts. Indeed, CD38 was lost during in vitro osteoclastogenesis. Consistently, we found that Daratumumab reacted with CD38 expressed on monocytes and its binding inhibited in vitro osteoclastogenesis and bone resorption activity from bone marrow total mononuclear cells of MM patients, targeting early osteoclast progenitors. The inhibitory effect was not observed from purified CD14 + cells, suggesting an indirect inhibitory effect of Daratumumab. Interestingly, all-trans retinoic acid treatment increased the inhibitory effect of Daratumumab on osteoclast formation. These observations provide a rationale for the use of an anti-CD38 antibody-based approach as treatment for multiple myeloma-induced osteoclastogenesis.

International audience; Sugarcane (Saccharum spp.) is highly polyploid and aneuploid. Modern cultivars are derived from hybridization between S. officinarum and S. spontaneum. This combination results in a genome exhibiting variable ploidy among different loci, a huge genome size (similar to 10 Gb) and a high content of repetitive regions. An approach using genomic, transcriptomic, and genetic mapping can improve our knowledge of the behavior of genetics in sugarcane. The hypothetical HP600 and Centromere Protein C (CENP-C) genes from sugarcane were used to elucidate the allelic expression and genomic and genetic behaviors of this complex polyploid. The physically linked side-by-side genes HP600 and CENP-C were found in two different homeologous chromosome groups with ploidies of eight and ten. The first region (Region01) was a Sorghum bicolor ortholog region with all haplotypes of HP600 and CENP-C expressed, but HP600 exhibited an unbalanced haplotype expression. The second region (Region02) was a scrambled sugarcane sequence formed from different noncollinear genes containing partial duplications of HP600 and CENP-C (paralogs). This duplication resulted in a non-expressed HP600 pseudogene and a recombined fusion version of CENP-C and the orthologous gene Sobic. 003G299500 with at least two chimeric gene haplotypes expressed. It was also determined that it occurred before Saccharum genus formation and after the separation of sorghum and sugarcane. A linkage map was constructed using markers from nonduplicated Region01 and for the duplication (Region01 and Region02). We compare the physical and linkage maps, demonstrating the possibility of mapping markers located in duplicated regions with markers in nonduplicated region. Our results contribute directly to the improvement of linkage mapping in complex polyploids and improve the integration of physical and genetic data for sugarcane breeding programs. Thus, we describe the complexity involved in sugarcane genetics and genomics and allelic dynamics, which can be useful for understanding complex polyploid genomes.

C-X3-C motif chemokine ligand 1 (CX3CL1)/fractalkine is a chemokine released after cleavage by two metalloproteases, ADAM metallopeptidase domain 10 (ADAM10) and ADAM metallopeptidase domain 17 (ADAM17), involved in inflammation and angiogenesis in the cancer microenvironment. The role of the CX3CL1/ C-X3-C motif chemokine receptor 1(CX3CR1) axis in the multiple myeloma (MM) microenvironment is still unknown. Firstly, we analyzed bone marrow (BM) plasma levels of CX3CL1 in 111 patients with plasma cell disorders including 70 with active MM, 25 with smoldering myeloma (SMM), and 16 with monoclonal gammopathy of undetermined significance (MGUS). We found that BM CX3CL1 levels were significantly increased in MM patients compared to SMM and MGUS and correlated with BM microvessel density. Secondly, we explored the source of CX3CL1 in MM and BM microenvironment cells. Primary CD138+ cells did not express CXC3L1 but up-regulated its production by endothelial cells (ECs) through the involvement of tumor necrosis factor alpha (TNF&alpha, ). Lastly, we demonstrated the presence of CX3CR1 on BM CD14+CD16+ monocytes of MM patients and on ECs, but not on MM cells. The role of CX3CL1 in MM-induced angiogenesis was finally demonstrated in both in vivo chick embryo chorioallantoic membrane and in vitro angiogenesis assays. Our data indicate that CX3CL1, present at a high level in the BM of MM patients, is a new player of the MM microenvironment involved in MM-induced angiogenesis.

The skin is a possible site of extramedullary localization in multiple myeloma (MM) patients; however, the mechanisms involved in this process are poorly understood. We describe the case of a refractory MM patient who developed a cutaneous localization under bortezomib treatment and we further expanded observations in other eight MM patients. We focused on the expression of genes involved in plasma cell skin homing, including CCR10, which was highly expressed. Moreover, we observed a lack of CXCR4 surface expression and the down-regulation of ICAM1/CD54 throughout the progression of the disease, suggesting a possible mechanism driving the escape of MM cells from the bone marrow into the skin.

The importance of glutamine (Gln) metabolism in multiple myeloma (MM) cells and its potential role as a therapeutic target are still unknown, although it has been reported that human myeloma cell lines (HMCLs) are highly sensitive to Gln depletion. In this study, we found that both HMCLs and primary bone marrow (BM) CD138(+) cells produced large amounts of ammonium in the presence of Gln. MM patients have lower BM plasma Gln with higher ammonium and glutamate than patients with indolent monoclonal gammopathies. Interestingly, HMCLs expressed glutaminase (GLS1) and were sensitive to its inhibition, whereas they exhibited negligible expression of glutamine synthetase (GS). High GLS1 and low GS expression were also observed in primary CD138(+) cells. Gln-free incubation or treatment with the glutaminolytic enzyme l-asparaginase depleted the cell contents of Gln, glutamate, and the anaplerotic substrate 2-oxoglutarate, inhibiting MM cell growth. Consistent with the dependence of MM cells on extracellular Gln, a gene expression profile analysis, on both proprietary and published datasets, showed an increased expression of the Gln transporters SNAT1, ASCT2, and LAT1 by CD138(+) cells across the progression of monoclonal gammopathies. Among these transporters, only ASCT2 inhibition in HMCLs caused a marked decrease in Gln uptake and a significant fall in cell growth. Consistently, stable ASCT2 downregulation by a lentiviral approach inhibited HMCL growth in vitro and in a murine model. In conclusion, MM cells strictly depend on extracellular Gln and show features of Gln addiction. Therefore, the inhibition of Gln uptake is a new attractive therapeutic strategy for MM.

Quantitative trait locus (QTL) mapping contributes to sugarcane (Saccharum spp.) breeding programs by providing information about the genetic effects, positioning and number of QTLs. Combined with marker-assisted selection, it can help breeders reduce the time required to develop new sugarcane varieties. We performed a QTL mapping study for important agronomic traits in sugarcane using the composite interval mapping method for outcrossed species. A new approach allowing the 1:2:1 segregation ratio and different ploidy levels for SNP markers was used to construct an integrated genetic linkage map that also includes AFLP and SSR markers. Were used 688 molecular markers with 1:1, 3:1 and 1:2:1 segregation ratios. A total of 187 individuals from a bi-parental cross (IACSP95-3018 and IACSP93-3046) were assayed across multiple harvests from two locations. The evaluated yield components included stalk diameter (SD), stalk weight (SW), stalk height (SH), fiber percentage (Fiber), sucrose content (Pol) and soluble solid content (Brix). The genetic linkage map covered 4512.6 cM and had 118 linkage groups corresponding to 16 putative homology groups. A total of 25 QTL were detected for SD (six QTL), SW (five QTL), SH (four QTL), Fiber (five QTL), Pol (two QTL) and Brix (three QTL). The percentage of phenotypic variation explained by each QTL ranged from 0.069 to 3.87 %, with a low individual effect because of the high ploidy level. The mapping model provided estimates of the segregation ratio of each mapped QTL (1:2:1, 3:1 or 1:1). Our results provide information about the genetic organization of the sugarcane genome and constitute the first step toward a better dissection of complex traits.

// Sabrina Rossi 1 , Marta Sbaraglia 1 , Marta Campo Dell’Orto 1 , Daniela Gasparotto 2 , Matilde Cacciatore 1 , Elena Boscato 1 , Valentina Carraro 1 , Luisa Toffolatti 1 , Giovanna Gallina 1 , Monia Niero 1 , Emanuela Pilozzi 3 , Alessandra Mandolesi 4 , Fausto Sessa 5 , Aurelio Sonzogni 6 , Cristina Mancini 7 , Guido Mazzoleni 8 , Salvatore Romeo 1 , Roberta Maestro 2,* and Angelo P. Dei Tos 1,* 1 Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso, Italy 2 Department of Experimental Oncology, CRO, Aviano, Italy 3 Department of Clinical and Molecular Medicine, University of Rome “La Sapienza”, Rome, Italy 4 Department of Pathology, University of Marche, Ancona School of Medicine, Ancona, Italy 5 Department of Pathology, Macchi Fondation, Varese, Italy 6 Department of Pathology, General Hospital, Bergamo, Italy 7 Department of Pathology, Azienda Ospedaliera-Universitaria, Parma, Italy 8 Department of Pathology, General Hospital, Bolzano, Italy * These authors have contributed equally to the work Correspondence to: Angelo P. Dei Tos, email: // Keywords : GIST, BRAF-mutated GIST, KIT/BRAF concomitant mutations, Imatinib resistance, BRAF VE1 antibody, Pathology Section Received : December 30, 2015 Accepted : April 04, 2016 Published : April 16, 2016 Abstract AIM: The BRAF mutation is a rare pathogenetic alternative to KIT/PDGFRA mutation in GIST and causes Imatinib resistance. A recent description of KIT and BRAF mutations co-occurring in an untreated GIST has challenged the concept of their being mutually exclusive and may account for ab initio resistance to Imatinib, even in the presence of Imatinib-sensitive KIT mutations. BRAF sequencing is generally limited to KIT/PDGFRA wild-type cases. Hence, the frequency of concomitant mutations may be underestimated. METHODS: We screened for KIT (exon 9, 11 ,13 ,17), PDGFRA (exon 12,14, 18) and BRAF (exon 15) mutations a series of 407 GIST. Additionally, we evaluated the BRAF V600E mutation-specific antibody, VE1, as a surrogate for V600E mutation, on a series of 313 GIST (24 on whole sections, 288 cases on tissue array), including 6 cases molecularly ascertained to carry the BRAF V600E mutation. RESULTS: No concomitant KIT / BRAF or PDGFRA / BRAF mutations were detected. BRAF mutation was detected only in one case, wild-type for KIT/PDGFRA. All the 6 BRAF -mutant cases stained positive with the VE1 antibody. A weak VE1 expression was observed in 14/287 (4.9%) BRAF wild-type cases, as observed also in 2/6 BRAF -mutant cases. Overall in our series, sensitivity and specificity of the VE1 antobody were 100% and 95.1%, respectively. CONCLUSION: The concomitance of BRAF mutation with either KIT or PDGFRA mutation is rare in GIST. In these tumors, moderate/strong VE1 immunoreactivity is a valuable surrogate for molecular analysis. Instead, genotyping is warranted in the presence of weak VE1 staining.

Background The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. Case presentation Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. Discussion and conclusion In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.

BackgroundSugarcane (Saccharum spp.) is highly polyploid and aneuploid. Modern cultivars are derived from hybridization betweenS. officinarumandS. spontaneum. This combination results in a genome exhibiting variable ploidy among different loci, a huge genome size (approximately 10 Gb) and a high content of repetitive regions. Gene expression mechanisms are poorly understood in these cultivars. An approach using genomic, transcriptomic and genetic mapping can improve our knowledge of the behavior of genetics in sugarcane.ResultsThe hypotheticalHP600and centromere protein C (CENP-C) genes from sugarcane were used to elucidate the allelic expression and genomic and genetic behavior of this complex polyploid. The genomically side-by-side genesHP600andCENP-Cwere found in two different homeologous chromosome groups with ploidies of eight and ten. The first region (Region01) was aSorghum bicolorortholog with all haplotypes ofHP600andCENP- Cexpressed, butHP600exhibited an unbalanced haplotype expression. The second region (Region02) was a scrambled sugarcane sequence formed from different noncollinear genes containing duplications ofHP600andCENP-C(paralogs). This duplication occurred before theSaccharumgenus formation and after the separation of sorghum and sugarcane, resulting in a nonexpressedHP600pseudogene and a recombined fusion version ofCENP-Cand orthologous gene Sobic.003G299500 with at least two chimerical gene haplotypes expressed. The genetic map construction supported the difficulty of mapping markers located in duplicated regions of complex polyploid genomes.ConclusionAll these findings describe a low synteny region in sugarcane, formed by events occurring in all members of theSaccharumgenus. Additionally, evidence of duplicated and truncate gene expression and the behavior of genetic markers in a duplicated region was found. Thus, we describe the complexity involved in sugarcane genetics and genomics and allelic dynamics, which can be useful for understanding the complex polyploid genome.

The association between Neurofibromatosis type I (NF1) and multiple myeloma (MM), a plasma cell, dyscrasia is very rare. Here we put to the attention of the scientific community two new cases. The first one is a patient with active MM whereas the second with smoldering MM. Both patients present typical features of NF1 but skeletal alterations were present only in the second case including dysplasia, marked scoliosis and osteoporosis. MM osteolytic lesions were absent in both patients. In addition to the clinical diagnosis of NF1, a molecular testing for NF1 gene mutations has been performed finding that patient one was heterozygous for the c.6855C>A (Tyr2285Ter) mutation, whilepatient two was heterozygous for thec.7838dupC (Lys2614GlufsTer20) mutation. The two mutations were diagnosed both in genomic DNA from peripheral blood and from MM cells. The potential link between NF1 mutation and the increased risk of MM is discussed in the report.

Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels. Transmission electron microscopy (TEM) confirmed amyloid fibrils around perimysial vessels associated with collagen fibrils. A stepwise approach to diagnosis and staging of this disorder is critical and involves confirmation of amyloid deposition, identification of the fibril type, assessment of underlying amyloidogenic disorder, and evaluation of the extent and severity of amyloidotic organ involvement.

Multiple myeloma (MM) is characterized by severely imbalanced bone remodeling. In this study, we investigated the potential effect of proteasome inhibitors (PIs), a class of drugs known to stimulate bone formation, on the mechanisms involved in osteocyte death induced by MM cells. First, we performed a histological analysis of osteocyte viability on bone biopsies on a cohort of 37 MM patients with symptomatic disease. A significantly higher number of viable osteocytes was detected in patients treated with a bortezomib (BOR)-based regimen compared with those treated without BOR. Interestingly, both osteocyte autophagy and apoptosis were affected in vivo by BOR treatment. Thereafter, we checked the in vitro effect of BOR to understand the mechanisms whereby BOR maintains osteocyte viability in bone from MM patients. We found that osteocyte and preosteocyte autophagic death was triggered during coculturing with MM cells. Our evaluation was conducted by analyzing either autophagy markers microtubule-associated protein light chain 3 beta (LC3B) and SQSTM1/sequestome 1 (p62) levels, or the cell ultrastructure by transmission electron microscopy. PIs were found to increase the basal levels of LC3 expression in the osteocytes while blunting the myeloma-induced osteocyte death. PIs also reduced the autophagic death of osteocytes induced by high-dose dexamethasone (DEX) and potentiated the anabolic effect of PTH(1-34). Our data identify osteocyte autophagy as a new potential target in MM bone disease and support the use of PIs to maintain osteocyte viability and improve bone integrity in MM patients.

Background Sugarcane (Saccharum spp.) is predominantly an autopolyploid plant with a variable ploidy level, frequent aneuploidy and a large genome that hampers investigation of its organization. Genetic architecture studies are important for identifying genomic regions associated with traits of interest. However, due to the genetic complexity of sugarcane, the practical applications of genomic tools have been notably delayed in this crop, in contrast to other crops that have already advanced to marker-assisted selection (MAS) and genomic selection. High-throughput next-generation sequencing (NGS) technologies have opened new opportunities for discovering molecular markers, especially single nucleotide polymorphisms (SNPs) and insertion-deletion (indels), at the genome-wide level. The objectives of this study were to (i) establish a pipeline for identifying variants from genotyping-by-sequencing (GBS) data in sugarcane, (ii) construct an integrated genetic map with GBS-based markers plus target region amplification polymorphisms and microsatellites, (iii) detect QTLs related to yield component traits, and (iv) perform annotation of the sequences that originated the associated markers with mapped QTLs to search putative candidate genes. Results We used four pseudo-references to align the GBS reads. Depending on the reference, from 3,433 to 15,906 high-quality markers were discovered, and half of them segregated as single-dose markers (SDMs) on average. In addition to 7,049 non-redundant SDMs from GBS, 629 gel-based markers were used in a subsequent linkage analysis. Of 7,678 SDMs, 993 were mapped. These markers were distributed throughout 223 linkage groups, which were clustered in 18 homo(eo)logous groups (HGs), with a cumulative map length of 3,682.04 cM and an average marker density of 3.70 cM. We performed QTL mapping of four traits and found seven QTLs. Our results suggest the presence of a stable QTL across locations. Furthermore, QTLs to soluble solid content (BRIX) and fiber content (FIB) traits had markers linked to putative candidate genes. Conclusions This study is the first to report the use of GBS for large-scale variant discovery and genotyping of a mapping population in sugarcane, providing several insights regarding the use of NGS data in a polyploid, non-model species. The use of GBS generated a large number of markers and still enabled ploidy and allelic dosage estimation. Moreover, we were able to identify seven QTLs, two of which had great potential for validation and future use for molecular breeding in sugarcane. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3383-x) contains supplementary material, which is available to authorized users.

Modern sugarcane cultivars (Saccharum spp.) are derived from an interspecific hybridization between Saccharum officinarum and Saccharum spontaneum and pose a significant challenge for both genotyping and data analysis. Due to their large (estimated at approximately 10 Gb) and complex genome, which can include variable ploidy levels and aneuploidy, studies involving molecular markers for genetic and quantitative trait locus (QTL) mapping are extremely laborious. Several advances in the genetics and genomics of sugarcane have recently become possible with the emergence of new sequencing technologies, the use of several types of marker systems, and the use of genotyping data analysis software. Molecular markers and comparative genomics are powerful resources that allow us to explore allelic variation and to thus understand the genome organization of sugarcane. This chapter provides an overview of what is known about the genetic structure and the genomics of sugarcane as well as the main genomics strategies developed for sugarcane. Among the strategies discussed are the use of single-nucleotide polymorphisms (SNPs) and bacterial artificial chromosome (BAC) libraries and the analysis of the syntenic relationships with related species (maize, sorghum, and rice).

In the last ten years the Archaeological Mission of Chieti University in Cyrenaica has investigated, through intensive field surveys and excavations, several contexts of the Cyrenaicanchora. Among the many recorded settlements, Lamluda is the most interesting because of its urban organisation, productivity and location at the intersection of the main road network. Our aim is to present the preliminary data from the mapping, survey and excavation of the site, including the results of the archaeometric analysis and the epigraphic study. Among the copious ceramic finds the Roman coarse wares and amphorae are particularly numerous, dating mainly to the Imperial, Late Roman and Byzantine periods. The pottery illustrates not only the longevity of the settlement, which lasted until the eighth or ninth century AD, but also helps to trace the evolution of agricultural wealth and trade. Through archaeometrical and archaeological research it is possible to identify the main local products and their circulation, as well as the imported or exported amphorae and hypothesise on the nature of their contents.

Sugarcane brown rust, caused by Puccinia melanocephala, is one of the major sugarcane diseases. The detection of molecular markers associated to brown rust resistance and also of its epistatic interactions were investigated in a mapping population obtained by crossing the brown rust susceptible clone IACSP953018 and the resistant cultivar IACSP933046. Resistance was evaluated in a field trial in plant cane and first ratoon under natural infection and scored using a diagrammatic scale from 1 (most resistance) to 9 (most susceptible). A total of 488 single dose markers (amplified fragment length polymorphism AFLP, genomic microsatellite gSSR and expressed sequence tag derived microsatellites EST-SSRs) were evaluated through a single marker trait association approach for brown rust resistance. Sixty one putative quantitative trait alleles (QTA) for brown rust (30 in plant cane, 31 in ratoon cane; 10 of them was common for both crop years) were detected of which several were related to resistance. Twenty one (34 %) of the markers associated to QTA derived from ESTs. Some of them have similarity to genes/proteins related to disease response pathways. The estimates of the proportion of the total phenotypic variation ( $$\hat{R}^{2}$$ ) explained by each significant main QTA effect ranged from 1.84 to 7.22 %, while the total explained variance estimates were 37.25 % (plant cane) and 43.26 % (ratoon cane) considering all main significant QTA effects. Fifty significant digenic epistatic interactions were suggested with the majority (68 %) contributing to increase brown rust resistance. Together, these probable epistatic effects explain 16.26 % (plant cane) and 17.22 % (ratoon cane) of the total phenotypic variance. Although evidence of epistasis was observed, linkage cannot be ruled out as the majority of the markers involved in the digenic interaction could not be addressed to any linkage group. The results suggest that epistasis may have an important contribution on sugarcane resistance to brown rust.

The bone marrow provides a protected environment for generating a vast array of cell types. Bones are thus a dynamic source of structural components and soluble factors used either locally or at a distance from their site of production. We discuss the role of ectoenzymes in the bone niche where human myeloma grows. Selected ectoenzymes have been tested for their ability to promote production of substrates involved in signaling, synthesis of growth factors and hormones, and modulation of the immune response. Because of the difficulty of simultaneously tracking all these activities, we narrow our focus to events potentially influencing synthesis of adenosine (ADO), an important regulator of multiple biological functions, including local immunological tolerance. Our working hypothesis, to be discussed and partially tested herein, is that CD38, and likely BST1/CD157--both NAD(+) -consuming enzymes, are active in the myeloma niche and lead a discontinuous chain of ectoenzymes whose final products are exploited by the neoplastic plasma cell as part of its local survival strategy. Coadjuvant ectoenzymes include PC-1/CD203a, CD39, and CD73, which control the production of ADO. Results discussed here and from ongoing experiments indicate that the myeloma niche hosts the canonical, as well as alternative, pathways of ADO generation. Other possibilities are presented and discussed.