Objective
In prior open‐label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to ...skipping exon 51. The present study used a double‐blind placebo‐controlled protocol to test eteplirsen's ability to induce dystrophin production and improve distance walked on the 6‐minute walk test (6MWT).
Methods
DMD boys aged 7 to 13 years, with confirmed deletions correctable by skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 weeks (n = 4/group). Placebo patients switched to 30 or 50 mg/kg eteplirsen (n = 2/group) at week 25; treatment was open label thereafter. All patients had muscle biopsies at baseline and week 48. Efficacy included dystrophin‐positive fibers and distance walked on the 6MWT.
Results
At week 24, the 30 mg/kg eteplirsen patients were biopsied, and percentage of dystrophin‐positive fibers was increased to 23% of normal; no increases were detected in placebo‐treated patients (p ≤ 0.002). Even greater increases occurred at week 48 (52% and 43% in the 30 and 50 mg/kg cohorts, respectively), suggesting that dystrophin increases with longer treatment. Restoration of functional dystrophin was confirmed by detection of sarcoglycans and neuronal nitric oxide synthase at the sarcolemma. Ambulation‐evaluable eteplirsen‐treated patients experienced a 67.3 m benefit compared to placebo/delayed patients (p ≤ 0.001).
Interpretation
Eteplirsen restored dystrophin in the 30 and 50 mg/kg/wk cohorts, and in subsequently treated, placebo‐controlled subjects. Duration, more than dose, accounted for dystrophin production, also resulting in ambulation stability. No severe adverse events were encountered. Ann Neurol 2013;74:637–647
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND AND AIMS: The genus Salvia has traditionally included any member of the tribe Mentheae (Lamiaceae) with only two stamens and with each stamen expressing an elongate connective. The recent ...demonstration of the non-monophyly of the genus presents interesting implications for staminal evolution in the tribe Mentheae. In the context of a molecular phylogeny, the staminal morphology of the various lineages of Salvia and related genera is characterized and an evolutionary interpretation of staminal variation within the tribe Mentheae is presented. METHODS: Two molecular analyses are presented in order to investigate phylogenetic relationships in the tribe Mentheae and the genus Salvia. The first presents a tribal survey of the Mentheae and the second concentrates on Salvia and related genera. Schematic sketches are presented for the staminal morphology of each major lineage of Salvia and related genera. KEY RESULTS: These analyses suggest an independent origin of the staminal elongate connective on at least three different occasions within the tribe Mentheae, each time with a distinct morphology. Each independent origin of the lever mechanism shows a similar progression of staminal change from slight elongation of the connective tissue separating two fertile thecae to abortion of the posterior thecae and fusion of adjacent posterior thecae. A monophyletic lineage within the Mentheae is characterized consisting of the genera Lepechinia, Melissa, Salvia, Dorystaechas, Meriandra, Zhumeria, Perovskia and Rosmarinus. CONCLUSIONS: Based on these results the following are characterized: (1) the independent origin of the staminal lever mechanism on at least three different occasions in Salvia, (2) that Salvia is clearly polyphyletic, with five other genera intercalated within it, and (3) staminal evolution has proceeded in different ways in each of the three lineages of Salvia but has resulted in remarkably similar staminal morphologies.
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BFBNIB, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Premise of the Study
A key question in evolutionary biology is why some clades are more successful by being widespread geographically, biome diverse, or species‐rich. To extend understanding of how ...shifts in area, biomes, and pollinators impact diversification in plants, we examined the relationships of these shifts to diversification across the mega‐genus Salvia.
Methods
A chronogram was developed from a supermatrix of anchored hybrid enrichment genomic data and targeted sequence data for over 500 of the nearly 1000 Salvia species. Ancestral areas and biomes were reconstructed using BioGeoBEARS. Pollinator guilds were scored, ancestral pollinators determined, shifts in pollinator guilds identified, and rates of pollinator switches compared.
Key Results
A well‐resolved phylogenetic backbone of Salvia and updated subgeneric designations are presented. Salvia originated in Southwest Asia in the Oligocene and subsequently dispersed worldwide. Biome shifts are frequent from a likely ancestral lineage utilizing broadleaf and/or coniferous forests and/or arid shrublands. None of the four species diversification shifts are correlated to shifts in biomes. Shifts in pollination system are not correlated to species diversification shifts, except for one hummingbird shift that precedes a major shift in diversification near the crown of New World subgen. Calosphace. Multiple reversals back to bee pollination occurred within this hummingbird clade.
Conclusions
Salvia diversified extensively in different continents, biomes, and with both bee and bird pollinators. The lack of tight correlation of area, biome, and most pollinator shifts to the four documented species diversification shifts points to other important drivers of speciation in Salvia.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Salvia united Drew, Bryan T.; González-Gallegos, Jesús Guadalupe; Xiang, Chun-Lei ...
Taxon,
02/2017, Volume:
66, Issue:
1
Journal Article
Peer reviewed
Previous molecular phylogenetic research, based on chloroplast and nuclear ribosomal DNA data, has demonstrated that the large genus Salvia (Lamiaceae) is paraphyletic as traditionally circumscribed. ...However, neither relationships within Salvia s.l. nor within subtribe Salviinae have been evaluated using low-copy nuclear gene regions. Here, we use two low-copy nuclear gene regions (PPR-AT3G09060, GBSSI) to further assess relationships of Salvia and related genera within Salviinae. Our results largely confirm results from previous studies based on chloroplast and nuclear ribosomal DNA. Based upon the phylogenetic results presented here, previous phylogenetic studies, and taxonomic, morphological, and practical considerations, we conclude that the botanical community would be best served by maintaining a broadly defined Salvia, including the five small embedded genera Dorystaechas, Meriandra, Perovskia, Rosmarinus, and Zhumeria as Salvia species. We subsequently present an updated circumscription of Salvia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Salvia, with over 900 species from both the Old and New World, is the largest genus in the Lamiaceae. Unlike most members of the subfamily Nepetoideae to which it belongs, only two stamens are ...expressed in Salvia. Although the structure of these stamens is remarkably variable across the genus, generally each stamen has an elongate connective and divergent anther thecae, which form a lever mechanism important in pollination. In a preliminary investigation of infrageneric relationships within Salvia, the monophyly of the genus and its relationship to other members of the tribe Mentheae were investigated using the chloroplast DNA regions rbcL and trnL-F. Significant conclusions drawn from the data include: Salvia is not monophyletic, Rosmarinus and Perovskia together are sister to an Old World clade of Salvia, the section Audibertia is sister to subgenus Calosphace or the monotypic Asian genus Dorystaechas, and the New World members of section Heterosphace are sister to section Salviastrum. Owing to the non-monophyly of Salvia, relationships at the next clearly monophyletic level, tribe Mentheae, were investigated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Salvia
subgenus
Calosphace
(Lamiaceae) is economically and ethnomedicinally significant and comprised of more than 500 species. Although strongly supported as monophyletic, it has received no ...comprehensive systematic research since the initial establishment of 91 taxonomic sections in 1939. Representative taxa of 73 sections of
Calosphace
were sampled to investigate the phylogenetic relationships and identify major lineages using chloroplast (intergenic spacer
psb
A-
trn
H) and nuclear ribosomal DNA (internal transcribed spacer). Phylogenetic analysis of the combined data sets established monophyly of seven sections (
Blakea, Corrugatae, Erythrostachys, Hastatae, Incarnatae, Microsphace,
and
Sigmoideae
) and four major lineages (
S. axillaris, “Hastatae
clade”, “
Uliginosae
clade”, and “core
Calosphace
”). Sections spanning two or more centers of diversity are not supported by our results; rather, supported relationships exhibit significant geographic structure. Mexico is supported as the geographic origin of
Calosphace
, and no more than seven dispersal events to South America are required to account for current disjunct distributions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged ...detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.
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In the California Floristic Province (CA-FP) and nearby deserts, 19 species of Salvia (Lamiaceae, Mentheae) form a small radiation but an important component of the chaparral and desert communities. ...Traditionally, two groups within these Californian Salvia have been recognized (usually treated as sections), but relationships within each, to each other, and to other Salvia are unclear. Phylogenetic relationships of all species, with multiple accessions for most, were obtained using chloroplast DNA (cpDNA) and nuclear ribosomal DNA (nrDNA) markers. Ancestral character state reconstruction of both vegetative and floral features was done on the resulting nrDNA tree. Biogeographical analysis of the groups within the CA-FP and adjacent floristic provinces was done in BioGeoBEARS and species diversification assessed with BAMM. Significant conclusions drawn from the study include: 1) California Salvia should be classified into two monophyletic sections, Audibertia (15 species) and Echinosphace, (four species) in the new subgenus Audibertia; 2) subg. Audibertia and the Neotropical subg. Calosphace are sister clades, most closely related to Asian groups, and are likely Asian in origin; 3) nrDNA provides a fairly resolved tree for subg. Audibertia with all species monophyletic; 4) cpDNA and nrDNA trees are strongly incongruent and provide evidence that hybridization and chloroplast capture have played an important role in the evolution of subg. Audibertia; 5) ancestral character reconstruction of states in habit, possession of spines, calyx lobing, and staminal features highlights a complex (sometimes convergent) evolutionary history of this iconic CA-FP lineage; 6) subg. Audibertia arose in desert areas and more recently diversified into the southwestern California region and adjacent regions with the formation of the Mediterranean-like climate; and 7) this diversification exhibits a slight decrease in speciation and an increase in extinction rates over the group's 11 million year history.
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Salvia divinorum
Epl. & Játiva-M. (
Lamiaceae
) is a potent hallucinogenic plant that is classified within
Salvia
subgenus
Calosphace
, section
Dusenostachys
, and hypothesized to be an interspecific ...hybrid. It is of ethnobotanical significance due to its employment in traditional healing ceremonies by the Mazatecs of Oaxaca, Mexico, and due to its unique pharmacology—a highly selective, non-nitrogenous, κ-opioid receptor agonist. In order to test its phylogenetic position and putative hybridity, we sequenced multiple DNA regions (ITS,
trn
L-
trn
F, and
psb
A-
trn
H) of 52 species—representing the major lineages of subgenus
Calosphace
—and six accessions of
S. divinorum
. Our molecular phylogenetic results suggest that
S. divinorum
should not be classified within
Dusenostachys
and that it is not a hybrid. Additionally, we determine that the closest known relative of this psychoactive Mexican sage is
S. venulosa
, a rare endemic of Colombia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.
From 2014 to 2016, 4 ...patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.
All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.
No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.
Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
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