In situ morphometric survey elucidates the evolutionary systematics of the Eurasian Himantoglossum clade (Orchidaceae: Orchidinae)

Background and Aims The charismatic Himantoglossum s.l. clade of Eurasian orchids contains an unusually large proportion of taxa that are of controversial circumscriptions and considerable conservation concern. Whereas our previously published study addressed the molecular phylogenetics and phylogeography of every named taxon within the clade, here we use detailed morphometric data obtained from the same populations to compare genotypes with associated phenotypes, in order to better explore taxonomic circumscription and character evolution within the clade. Methods Between one and 12 plants found in 25 populations that encompassed the entire distribution of the Himantoglossum s.l. clade were measured in situ for 51 morphological characters. Results for 45 of those characters were subjected to detailed multivariate and univariate analyses. Key Results Multivariate analyses readily separate subgenus Barlia and subgenus Comperia from subgenus Himantoglossum, and also the early-divergent H. formosum from the less divergent remainder of subgenus Himantoglossum. The sequence of divergence of these four lineages is confidently resolved. Our experimental approach to morphometric character analysis demonstrates clearly that phenotypic evolution within Himantoglossum is unusually multi-dimensional. Conclusions Degrees of divergence between taxa shown by morphological analyses approximate those previously shown using molecular analyses. Himantoglossum s.l. is readily divisible into three subgenera. The three sections of subgenus Himantoglossum—hircinum, caprinum and formosum—are arrayed from west to east with only limited geographical overlap. At this taxonomic level, their juxtaposition combines with conflict between contrasting datasets to complicate attempts to distinguish between clinal variation and the discontinuities that by definition separate bona fide species. All taxa achieve allogamy via food deceit and have only weak pollinator specificity. Artificial crossing demonstrates that intrinsic sterility barriers are weak. Although we have found evidence of gene flow among and within the three sections of subgenus Himantoglossum, reports of natural hybrids are surprisingly rare, probably because putative parents are sufficiently similar to questionably warrant the status of species. Phenological separation and increased xeromorphy characterise the origin of subgenus Barlia. Several individual morphological characters show evidence of parallel acquisition, and loss of features is especially frequent in floral markings among members of section caprinum. Detailed patterns of gain and loss demonstrate that several different categories of flower markings are inherited independently. Along with the dimensions of labellar lobes, these pigmentation characters have been over-emphasised in previous taxonomic treatments. Increased plant vigour was a crucial element of the origin of the genus, but vegetative characters underwent remarkably little subsequent evolution. Attempts to reconstruct hypothetical ancestors at internal nodes of the phylogeny are weakened by (a) uncertain placement of Steveniella as sister to Himantoglossum s.l. and (b) uncertain relationships among subtly different putative species within section caprinum. Nonetheless, heterochronic/allometric trends, ultimately limited by functional constraints, clearly dictate transitions between contrasting flower sizes and complex labellum shapes

On the supersymmetric nonlinear evolution equations

Supersymmetrization of a nonlinear evolution equation in which the bosonic equation is independent of the fermionic variable and the system is linear in fermionic field goes by the name B-supersymmetrization. This special type of supersymmetrization plays a role in superstring theory. We provide B-supersymmetric extension of a number of quasilinear and fully nonlinear evolution equations and find that the supersymmetric system follows from the usual action principle while the bosonic and fermionic equations are individually non Lagrangian in the field variable. We point out that B-supersymmetrization can also be realized using a generalized Noetherian symmetry such that the resulting set of Lagrangian symmetries coincides with symmetries of the bosonic field equations. This observation provides a basis to associate the bosonic and fermionic fields with the terms of bright and dark solitons. The interpretation sought by us has its origin in the classic work of Bateman who introduced a reverse-time system with negative friction to bring the linear dissipative systems within the framework of variational principle.Comment: 12 pages, no figure

Oncolytic Viruses: Do They Have a Role in Anti-Cancer Therapy?

Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a ‘dangerous’ context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage

Himantoglossum jankae (Orchidaceae: Orchideae), a new name for a long-misnamed lizard orchid

A new name, Himantoglossum jankae, is given to the widely recognised lizard orchid species that is distributed primarily in the Balkan Peninsula and the northwestern region of Asia Minor and has been erroneously named H. caprinum in most previous literature. The new species differs from its closest relatives in having the combination of relatively large, reddish-purple coloured flowers and labella that bear red papillate spots and comparatively long spurs. We present a morphological description of H. jankae, together with illustrations, distribution information and diagnostic comparisons with H. calcaratum, H. adriaticum and H. caprinum

Disentangling late quaternary fluvial and climatic drivers of palaeohydrological change in the Najaf Sea basin, Western Iraq

The water resource provided by lake basins in the western desert of Iraq is important for human occupation of areas outside the Tigris-Euphrates floodplain, both in the past and into the future. This paper presents the first geomorphological and geochronological study of the date of formation of the Najaf Sea and the only such study of any lake basin to the west of Mesopotamia. Geomorphological shoreline features and a palaeochannel linking to the Euphrates were studied and dated using optically stimulated luminescence (OSL) and radiocarbon dating. Provenance was determined using heavy mineral analysis. Past environments in the Najaf Sea were reconstructed by molluscan analysis. The earliest OSL ages date from c. 30 000 and 22 000 years ago and seem to predate lake formation. Younger OSL ages date the highest lake level at c. 19 m asl to between 1620–1760 AD (base) to 1906–1974 AD (near surface). The radiocarbon ages are affected by a freshwater reservoir effect, but the maximum ages recorded for either of the c. 15 m and c. 17 m asl shorelines are c. 800 cal. BC. This predates the first archaeological sites in the Najaf basin and is similar to maximum ages of c. 850 and c. 1100 cal. BC from the associated palaeochannel. This timing does not seem to be linked to a humid climate event. We therefore conclude that the establishment of the Najaf Sea in the Najaf basin occurred as a result of an avulsion event within the Euphrates system that diverted flow to the basin. The trigger for this avulsion event likely related to rapid sediment accumulation and may have been either autogenic or driven by human activity. This study therefore suggests that Najaf Sea formation facilitated human expansion beyond the Tigris- Euphrates floodplain and occurred due to avulsion of the Euphrates

Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity

Radiotherapy-induced gut toxicity (RIGT) is a debilitating effect of radiotherapy for cancer, often resulting in significant diarrhoea and pain. Previous studies have highlighted roles of the intestinal microvasculature and matrix metalloproteinases (MMPs) in the development of RIGT. We hypothesized vascular mediators would be significantly altered in a dark agouti (DA) rat model of RIGT. Additionally, we aimed to assess the effect of MMP-2 and -9 inhibition on the response of tumour-associated microvascular endothelial cells (TAMECs) to radiation.Dark Agouti (DA) rats were administered 2.5 Gy abdominal irradiation (3 times/week over 6 weeks). Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), von Willebrand factor (VWF), angiostatin, and endostatin expression was assessed at 3, 6 and 15 weeks. Additionally, DA rat mammary adenocarcinoma tumour-associated microvascular endothelial cells (TAMECs) were used to assess the effects of radiation (12 Gy) and the MMP inhibitor SB-3CT on MMP, VEGF, and TGFβ expression, and cell viability.VEGF mRNA expression was significantly increased in the colon at week 15 (p = 0.0012), and TGFβ mRNA expression was significantly increased in both the jejunum and colon at week 3 (p = 0.0280, and p = 0.0310, respectively). Endostatin immunostaining was significantly increased at week 3 (p = 0.0046), and angiostatin at 3 and 6 weeks (p = 0.0022, and p = 0.0135, respectively). MMP-2 and -9 mRNA and total protein levels were significantly increased following irradiation of TAMECs. Although this increase was significantly attenuated by SB-3CT, it did not significantly alter endothelial cell viability or VEGF and TGFβ mRNA expression.Findings of this study support the involvement of VEGF, TGFβ, angiostatin, endostatin, and MMP-2 in the pathobiology of RIGT. However, the relationship between these mediators is complex and needs further investigation to improve understanding of their therapeutic potential in RIGT.Romany L. Stansborough, Emma H. Bateman, Noor Al-Dasooqi, Joanne M. Bowen, Anthony Wignall, Dorothy M. Keefe, Ann S. Yeoh, Richard M. Logan, Eric E. K. Yeoh, Andrea M. Stringer and Rachel J. Gibso

Calculation of the Flux of Atmospheric Neutrinos

Atmospheric neutrino-fluxes are calculated over the wide energy range from 30 MeV to 3,000 GeV for the study of neutrino-physics using the data from underground neutrino-detectors. The atmospheric muon-flux at high altitude and at sea level is studied to calibrate the neutrino-fluxes at low energies and high energies respectively. The agreement of our calculation with observations is satisfactory. The uncertainty of atmospheric neutrino-fluxes is also studied.Comment: 51 page

Associations Among 25-Hydroxyvitamin D Levels, Lung Function, and Exacerbation Outcomes in COPD: An Analysis of the SPIROMICS Cohort

Background: The relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations. Methods: Serum 25-OH-vitamin D level was measured in stored samples from 1,609 SPIROMICS participants with COPD. 25-OH-vitamin D levels were modeled continuously and dichotomized as deficient (< 20 ng/mL) vs not deficient (≥ 20 ng/mL). Outcomes of interest included % predicted FEV1 (current and 1-year longitudinal decline) and COPD exacerbations (separately any and severe, occurring in prior year and first year of follow-up). Results: Vitamin D deficiency was present in 21% of the cohort and was more prevalent in the younger, active smokers, and blacks. Vitamin D deficiency was independently associated with lower % predicted FEV1 (by 4.11%) at enrollment (95% CI, –6.90% to –1.34% predicted FEV1; P =.004), 1.27% predicted greater rate of FEV1 decline after 1 year (95% CI, –2.32% to –0.22% predicted/y; P =.02), and higher odds of any COPD exacerbation in the prior year (OR, 1.32; 95% CI, 1.00-1.74; P =.049). Each 10-ng/mL decrease in 25-OH-vitamin D was associated with lower baseline lung function (–1.04% predicted; 95% CI, –1.96% to –0.12% predicted; P =.03) and increased odds of any exacerbation in the year before enrollment (OR, 1.11; 95% CI, 1.01-1.22; P =.04). Conclusions: Vitamin D deficiency is associated with worse cross-sectional and longitudinal lung function and increased odds of prior COPD exacerbations. These findings identify 25-OH-vitamin D levels as a potentially useful marker of adverse COPD-related outcomes