A closer look at the taxonomic and genetic diversity of endemic South African Marphysa Quatrefages, 1865.

The current study investigates the final unresolved cosmopolitan species of Marphysa in South Africa, Marphysa corallina, collected from KwaZulu Natal, Eastern and Western Cape provinces, together with another species collected from northern KwaZulu Natal. Morphological and genetic data prove that M. corallina, originally described from Hawaii, does not occur in South Africa. The curvature of the inner base on maxilla I, the elevated inner base of maxilla II, and the ventral cirrus as a transverse welt with a rounded tip allow us to identify it as a new species of Treadwellphysa, T. izinqa sp. nov. (common name: brown wonderworm). Characteristic traits include the basal reddish and distal golden colour of the subacicular hook, the ear-shaped postchaetal lobe, and tridentate falcigers which is reported for the first time for the genus. This species is harvested as bait on the south coast of SA, although less frequently than the more common blood wonderworm, Marphysa haemasona Quatrefages, 1866, and can be distinguished by its more uniform brown colouration and white-tipped antennae. A second species, Marphysa mzingazia sp. nov., is characterized by red eyes, six branchial filaments extending to the posterior end, the golden aciculae in posterior chaetigers, weakly bidentate yellow/brown subacicular hooks, and the presence of similar sized spinigers along the body. A molecular analysis based on cytochrome oxidase I fragments confirm both taxa as different species. A key for all South African species of Marphysa is included.

Morphometric approach supports distinction among three species of Paucibranchia Molina-Acevedo, 2018 (Annelida: Eunicidae).

In this study, we performed a morphometric approach of 23 quantitative features of Paucibranchia bellii (Audouin Milne-Edwards, 1833), P. disjuncta (Hartman, 1961), and P. carrerai Molina-Acevedo, 2018 in order to evaluate their importance in interspecific discrimination. We found that eight of the 23 features measured were correlated with the organisms size, in particular, branchiae, parapodia, and chaetae. The features that were not size-dependent presented a low range of variation related to the maxillary apparatus (as the maxillary formula) or the prostomial appendages and could be used as taxonomically informative characters. The multivariate analysis selected six characteristics that best contributed to the three species discrimination. At least four of these features were related to the start of the branchiae and subacicular hooks, the maximum number of chaetigers with branchiae, and the maximum number of branchial filaments, all of them considered size-dependent. However, two other features, teeth in maxilla III and the length of the opening cavity in the maxillary apparatus, were not size-dependent. The results allowed us to demonstrate that both sized- and non-sized depending on characters are helpful and necessary to improve species discrimination within the genus Paucibranchia. Finally, we provide a detailed analysis of the ontogenetic changes of P. carrerai with additional material found on the east coast of Peninsular Malaysia.

Morphological and molecular systematic review of Marphysa Quatrefages, 1865 (Annelida: Eunicidae) species from South Africa.

A vast polychaete fauna is hidden behind complexes of cryptic and pseudo-cryptic species, which has greatly hindered our understanding of species diversity in several regions worldwide. Among the eunicids, Marphysa sanguinea Montagu, 1813 is a typical example, recorded in three oceans and with various species considered its junior synonyms. In South Africa, specimens previously misidentified as M. sanguinea are now known as Marphysa elityeni Lewis & Karageorgopoulos, 2008. Of the six Marphysa Quatrefages, 1865a species recorded from the same region, three have their distributions restricted to South Africa while the others are considered to have worldwide distributions. Here, we evaluated the taxonomic status of the indigenous M. elityeni and investigated the presence of the widespread species Marphysa macintoshi Crossland, 1903 and Marphysa depressa Schmarda, 1861 in South Africa using morphological and molecular data. Our results reveal that M. elityeni is a junior synonym of Marphysa haemasoma, a species previously described from South Africa which is herein reinstated as a valid species. Both M. macintoshi and M. depressa are not present in South Africa and their status as being distributed worldwide deserves further investigation. Marphysa durbanensis Day, 1934 and the new species described here, M. sherlockae n. sp., had been misidentified as M. macintoshi and M. depressa respectively. Thus, the number of Marphysa species with distributions restricted to South Africa increased from three to five. This study reiterates the importance of implementing an integrated taxonomic framework to unravel local biodiversity.

Reinstatement of species belonging Marphysa sanguinea complex (Annelida: Eunicidae) and description of new species from the mid-Pacific Ocean and the Adriatic Sea.

Marphysa sanguinea Montagu, 1813, the type species of genus Marphysa, was described with few characteristics and subsequently reported in tropical and temperate waters as a cosmopolitan species. Recent comparative studies have shown that M. sanguinea has a limited distribution to the Northeast Atlantic. As a result, species from the tropical and subtropical zones are now being redescribed as new species. However, this issue is not completely resolved because of the taxonomic status of seven nominal species, considered as junior synonymies of M. sanguinea. Herein, we examined the type and additional materials from five species in synonymy M. sanguinea and performed a compared analysis with the neotype of M. sanguinea. Additionally, we reviewed specimens from two localities in the mid-Pacific Ocean and the Adriatic Sea, where M. sanguinea was previously reported. As a result of this study, three species were reinstated (M. californica Moore, 1909, M. leidii de Quatrefages, 1866, and M. parishii Baird, 1869) and two subspecies, are now raised to species level (M. americana n. status and M. brevibranchiata n. status). In addition, two new species from Hawaii and Croatia are described: M. baileybrockae n. sp. and M. birgeri n. sp., respectively. Morphological comparisons with most species currently assigned to the M. sanguinea complex are presented. This work provides more support for rejecting the hypothesis that M. sanguinea is a cosmopolitan species and we encourage the use of novel and traditional morphological characters to differentiate species within the complex.

IsCT-based analogs intending better biological activity.

IsCT1-NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an α-helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)-based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]3 -IsCT1-NH2 , [K]3 -IsCT1-NH2 , or [F]5 -IsCT1-NH2 ) showed no significant change in an activity relative to IsCT1-NH2 . The addition of a proline residue at position 8 ([P]8 -IsCT1-NH2 ) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13-50 µmol L-1 ), and the addition of a tryptophan residue at position 1 ([W]1 -IsCT1-NH2 ) increased the hemolytic activity (MHC = 1.56 µmol L-1 ) without an improvement in antimicrobial activity. The analog [A]1 [F]5 [K]8 -IsCT1-NH2 , which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 µmol L-1 ) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.

IsCT-based analogs intending better biological activity

IsCT1-NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an a-helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)-based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]3-IsCT1-NH2, [K]3-IsCT1-NH2, or [F]5-IsCT1-NH2) showed no significant change in an activity relative to IsCT1-NH2. The addition of a proline residue at position 8 ([P]8-IsCT1-NH2) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13-50 µmol L-1), and the addition of a tryptophan residue at position 1 ([W]1-IsCT1-NH2) increased the hemolytic activity (MHC = 1.56 µmol L-1) without an improvement in antimicrobial activity. The analog [A]1[F]5[K]8-IsCT1-NH2, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 µmol L-1) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.

IsCT-based analogs intending better biological activity

IsCT1-NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an a-helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)-based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]3-IsCT1-NH2, [K]3-IsCT1-NH2, or [F]5-IsCT1-NH2) showed no significant change in an activity relative to IsCT1-NH2. The addition of a proline residue at position 8 ([P]8-IsCT1-NH2) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13-50 µmol L-1), and the addition of a tryptophan residue at position 1 ([W]1-IsCT1-NH2) increased the hemolytic activity (MHC = 1.56 µmol L-1) without an improvement in antimicrobial activity. The analog [A]1[F]5[K]8-IsCT1-NH2, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 µmol L-1) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.

Morphological revision of the Subgroup 1 Fauchald, 1970 of Marphysa de Quatrefages, 1865 (Eunicidae: Polychaeta).

Fifteen species of Marphysa classified in the Subgroup 1 Fauchald (1970) were reviewed and evaluated in a morphological analysis of the subgroup. It was found that 13 of these have a characteristic morphological pattern distinct from that of Marphysa sensu stricto; as a consequence, a new genus is proposed, Paucibranchia n. gen. This new genus includes the species that have branchiae restricted to a few chaetigers in the anterior region, maxillae I with a rounded falcal arch and outer edge with a straight base plus a curvature in the basal inner edge, dorsal cirri longer in the branchial region and in media-posterior region as long or longer than pre-branchial chaetigers, and the postchaetal lobe in the branchial region well developed, elongated. Paucibranchia n. gen. includes six new species (P. andresi n. sp., P. carrerai n. sp., P. gathofi n. sp., P. gilberti n. sp., P. miroi n. sp. and P. patriciae n. sp.), two species not formally named, and other 13 species previously included in Marphysa (P. adenensis (Gravier, 1900) n. comb., P. bellii (Audouin Milne-Edwards, 1833) n. comb., P. cinari (Kurt-Sahin, 2014) n. comb., P. conferta (Moore, 1911) n. comb., P. disjuncta (Hartman, 1961) n. comb., P. fallax (Marion Bobretzky, 1875) n. comb., P. gemmata (Mohammad, 1973) n. comb., P. kinbergi (McIntosh, 1910) n. comb., P. oculata (Treadwell, 1921) n. comb., P. purcellana (Willey, 1904) n. comb., P. sinensis (Monro, 1934) n. comb., P. stragula (Grube, 1878) n. comb., P. totospinata (Lu Fauchald, 1998) n. comb.). One species previously classified in the subgroup, Marphysa striata (Kinberg, 1865), was considered indeterminate. Finally, some statistical analyses on size dependent features and an identification key for species of the new genus were included.

Revision of Marphysa de Quatrefages, 1865 and some species of Nicidion Kinberg, 1865 with the erection of a new genus (Polychaeta: Eunicidae) from the Grand Caribbean.

Nine species of Marphysa from the Grand Caribbean Region are recognized and described based on the type and non-type specimens. One species is formally described as new: M. emiliae n. sp., and one is re-established as a valid species: M. fragilis Treadwell, 1911. The diagnosis of Nicidion Kinberg, 1865 is restricted based on novel features of the maxillary apparatus. Nicidion angeli (Carrera-Parra & Salazar-Vallejo, 1998) is redescribed, and two species that previously belonged to Marphysa, are transferred to Nicidion: N. longula (Ehlers, 1887) n. comb. and N. obtusa (Verrill, 1900) n. comb.. A new genus Treadwellphysa n. gen. is proposed to include those species having a newly described type of chaetae named spinifalcigers (exhibiting a mixture of falciger and spiniger blades), the base of maxillae II with a small elevation, and the ventral cirri with swollen base as transverse welt with short digitiform tip. Treadwellphysa n. gen. includes a new species, T. yucatanensis n. sp. and three other species previously included in Marphysa: T. amadae (Fauchald, 1977) n. comb., T. languida (Treadwell, 1921) n. comb., and T. veracruzensis (de León-González & Díaz-Castañeda, 2006) n. comb. Some morphological features are evaluated to clarify their variability with respect to specimen size. A key to Eunicidae genera, and keys to species of Marphysa and Treadwellphysa n. gen. from the Grand Caribbean region are given.

Reinstatement of three species of the Marphysa sanguinea complex (Polychaeta: Eunicidae) from the Grand Caribbean Region.

As part of a study on Marphysa de Quatrefages, 1865 from the Grand Caribbean, three species regarded as junior synonyms of M. sanguinea (Montagu, 1913) were studied to clarify their taxonomic status. The examination of type and additional materials collected in the southern Gulf of Mexico and the Mexican Caribbean regions, allowed us to clarify that M. acicularum Webster, 1884, M. nobilis Treadwell, 1917 and M. viridis Treadwell, 1917 are distinct species. Therefore, the three species were redescribed and some important morphological features such as maxillary apparatus, shape of parapodial lobes, shape of ventral cirri and pectinate chaetae, among others, were described and evaluated. Furthermore, we consider that previous records of M. sanguinea for the Grand Caribbean are doubtful and it is necessary to reassess those specimens to clarify their taxonomic identity.

Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth.

Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis are poorly understood. Moreover, current therapies, particularly those for malignant lesions, have little beneficial effect on clinical outcomes. In this study, we show that endothelial activation of the Akt1 kinase is sufficient to drive de novo tumor formation. Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor endothelial cell growth and migration by inhibiting activation of the translation regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in turn acted through a negative feedback loop to restrain Akt3 expression. Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was silenced, and the growth of these tumor cells was inhibited by a novel S6K inhibitor. Overall, our findings offer a preclinical proof of concept for the therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K inhibitors.

Unusual presentation of myeloid sarcoma in a case of acute promyelocytic leukemia with a cryptic PML-RARA rearrangement involving multiple sites including the atrium.

Myeloid sarcoma is an extramedullary tumor mass composed of immature myeloid cells. Myeloid sarcoma may develop de novo, concurrently with acute myeloid leukemia (AML), or at relapse. Although myeloid sarcoma can occur at any site, myeloid sarcoma involving the heart is extremely rare. Reported here is the case of a 30-year-old man, initially diagnosed with acute promyelocytic leukemia (APL) in bone marrow, who presented later with myeloid sarcoma at multiple anatomical sites (left scapula, thoracic vertebra, right atrium, and supraclavicular mass) in multiple relapses. Conventional cytogenetic studies performed on the atrial sample revealed a karyotype with additional material on the short arm of chromosome 7, at 7p22. Fluorescence in situ hybridization studies confirmed a cryptic PML-RARA fusion on the short arm of chromosome 7, as well as a second fusion on one copy of chromosome 15. With the fourth and latest relapse, molecular cytogenetic studies performed on interphase nuclei of the myeloid sarcoma specimen (a supraclavicular mass) showed evidence of six related abnormal clones with a PML-RARA fusion, suggesting clonal evolution. This represents a rare case of APL with a cryptic PML-RARA rearrangement presenting as myeloid sarcoma at multiple relapses and involving multiple anatomical sites, including cardiac atrium.