Uncovering Tropical Eiversity: Six Sympatric Cryptic Species of Blepharoneura (Diptera: Tephritidae) in Flowers of Gurania spinulosa (Cucurbitaceae) in Eastern Ecuador

Diversification of phytophagous insects is often associated with changes in the use of host taxa and host parts. We focus on a group of newly discovered Neotropical tephritids in the genus Blepharoneura, and report the discovery of an extraordinary number of sympatric, morphologically cryptic species, all feeding as larvae on calyces of flowers of a single functionally dioecious and highly sexually dimorphic host species (Gurania spinulosa) in eastern Ecuador. Molecular analyses of the mitochondrial cytochrome oxidase-I gene from flies reared from flowers of G. spinulosa reveal six distinct haplotype groups that differ by 7.2-10.1% bp (uncorrected pairwise distances; N = 624 bp). Haplotype groups correspond to six distinct and well-supported clades. Members of five clades specialize on the calyces of flowers of a particular sex: three clades comprise male flower specialists; two clades comprise female flower specialists; the sixth clade comprises generalists reared from male and female flowers. The six clades occupy significantly different morphological spaces defined by wing pigmentation patterns; however, diagnostic morphological characters were not discovered. Behavioural observations suggest specific courtship behaviours may play a role in maintaining reproductive isolation among sympatric species

The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer

Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE) and creation of an Exonic Splicing Silencer (ESS). We show that this vulnerability of HRAS exon 2 is caused by a weak 3' splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS- causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

Phylogenetics of Seed Plants: An Analysis of Nucleotide Sequences from the Plastid Gene rbcL

We present the results of two exploratory parsimony analyses of DNA sequences from 475 and 499 species of seed plants, respectively, representing all major taxonomic groups. The data are exclusively from the chloroplast gene rbcL, which codes for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO or RuBPCase). We used two different state-transformation assumptions resulting in two sets of cladograms: (i) equal-weighting for the 499-taxon analysis; and (ii) a procedure that differentially weights transversions over transitions within characters and codon positions among characters for the 475-taxon analysis. The degree of congruence between these results and other molecular, as well as morphological, cladistic studies indicates that rbcL sequence variation contains historical evidence appropriate for phylogenetic analysis at this taxonomic level of sampling. Because the topologies presented are necessarily approximate and cannot be evaluated adequately for internal support, these results should be assessed from the perspective of their predictive value and used to direct future studies, both molecular and morphological. In both analyses, the three genera of Gnetales are placed together as the sister group of the flowering plants, and the anomalous aquatic Ceratophyllum (Ceratophyllaceae) is sister to all other flowering plants. Several major lineages identified correspond well with at least some recent taxonomic schemes for angiosperms, particularly those of Dahlgren and Thorne. The basalmost clades within the angiosperms are orders of the apparently polyphyletic subclass Magnoliidae sensu Cronquist. The most conspicuous feature of the topology is that the major division is not monocot versus dicot, but rather one correlated with general pollen type: uniaperturate versus triaperturate. The Dilleniidae and Hamamelidae are the only subclasses that are grossly polyphyletic; an examination of the latter is presented as an example of the use of these broad analyses to focus more restricted studies. A broadly circumscribed Rosidae is paraphyletic to Asteridae and Dilleniidae. Subclass Caryophyllidae is monophyletic and derived from within Rosidae in the 475-taxon analysis but is sister to a group composed of broadly delineated Asteridae and Rosidae in the 499-taxon study

Phylogenetics of Seed Plants: An Analysis of Nucleotide Sequences from the Plastid Gene rbcL

We present the results of two exploratory parsimony analyses of DNA sequences from 475 and 499 species of seed plants, respectively, representing all major taxonomic groups. The data are exclusively from the chloroplast gene rbcL, which codes for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO or RuBPCase). We used two different state-transformation assumptions resulting in two sets of cladograms: (i) equal-weighting for the 499-taxon analysis; and (ii) a procedure that differentially weights transversions over transitions within characters and codon positions among characters for the 475-taxon analysis. The degree of congruence between these results and other molecular, as well as morphological, cladistic studies indicates that rbcL sequence variation contains historical evidence appropriate for phylogenetic analysis at this taxonomic level of sampling. Because the topologies presented are necessarily approximate and cannot be evaluated adequately for internal support, these results should be assessed from the perspective of their predictive value and used to direct future studies, both molecular and morphological. In both analyses, the three genera of Gnetales are placed together as the sister group of the flowering plants, and the anomalous aquatic Ceratophyllum (Ceratophyllaceae) is sister to all other flowering plants. Several major lineages identified correspond well with at least some recent taxonomic schemes for angiosperms, particularly those of Dahlgren and Thorne. The basalmost clades within the angiosperms are orders of the apparently polyphyletic subclass Magnoliidae sensu Cronquist. The most conspicuous feature of the topology is that the major division is not monocot versus dicot, but rather one correlated with general pollen type: uniaperturate versus triaperturate. The Dilleniidae and Hamamelidae are the only subclasses that are grossly polyphyletic; an examination of the latter is presented as an example of the use of these broad analyses to focus more restricted studies. A broadly circumscribed Rosidae is paraphyletic to Asteridae and Dilleniidae. Subclass Caryophyllidae is monophyletic and derived from within Rosidae in the 475-taxon analysis but is sister to a group composed of broadly delineated Asteridae and Rosidae in the 499-taxon study

Waterjet fracture-directed steerable needles

The focus of this proposal is on the new classes of steerable needles namely fracture-directed steerable needles, and two approaches to achieve this that are tube and stylet method, and water-jet method. Steerable needles hold the promise of improving the accuracy of both therapies and biopsies as they are able to steer to a target location around obstructions, correct for disturbances, and account for movement of internal organs. However, their ability to make late- insertion corrections has always been limited by the lower bound on the attainable radius of curvature. Stylet and tube fracture-directed steerable needles involve a new class of steerable needle insertion where the objective is to first control the direction of tissue fracture with an inner stylet and later follow with the hollow needle. This method is shown to be able to achieve radius of curvature as low as 6.9 mm across a range of tissue stiffnesses and the radius of curvature is controllable from the lower bound up to a near infinite radius of curvature based on the stylet/needle step size. The approach of ”fracture-directed” steerable needles indicates the promise of the technique for providing a tissue-agnostic method of achieving high steerability that can account for variability in tissues during a typical procedure and achieve radii of curvature unattainable through current bevel-tipped techniques. Water-jet technology has been used extensively for decades industrially for many applications including mining, plastic, metal, stone, wood, and produce cutting. The use of water-jet in medical applications has been developed more recently and it is used for different applications such as soft tissue resection, bone cutting, wound debridement, and surgery. Water-jet fracture-directed steerable needles is a new application of water-jet technology in the medical field that harnesses the advantages of water-jet technology and steerable needle technology into one. A needle insertion system is designed and built, which has a custom-designed water-jet nozzle attached to a Nitinol needle as its ”needle”. Insertions with and without water-jet into 10%, 15% and 20% Poly (styrene-b-ethylene-co-butylene-b-styrene) triblock copolymer (SEBS) tissue-mimicking simulants are performed and the associated force data are measured using a force sensor at the base of the needle. Preliminary results of force vs. displacement showed that the water-jet reduces the insertion force associated with traditional needles by eliminating tip forces. For preliminary results, custom-designed straight nozzle is used to show the feasibility of water-jet steerable needles, whereas research underway is focused on steerability using steerable nozzles to improve steerability compared to current steerable needle technologies. Depth of cut as a function of fluid velocity is also measured for different volumetric flow rates. Preliminary results show that depth of cut is a linear function of fluid velocity when the width of the water-jet nozzle is sufficiently small and smooth. Research is underway to understand the characteristics of water-jet - tissue interaction, which is an important aspect to be explored to design better devices as well as path planning and control algorithms. To do so, a physics-based model to predict cutting depth, crack dimensions and insertion load on the needle based on parameters such as tissue properties (constitutive response and toughness), nozzle diameter, tip shape of the needle, and volumetric flow rate is the other aim of this proposal that is lacking in the literature. Another aim of the current proposal is using current path planning methods and proposing a control method for the developed water-jet steerable needle. In order to direct steerable needles to specific targets and avoid anatomical obstacles, planning paths through the patient’s anatomy is needed. Path planning of steerable needles is beyond the intuition of human beings because of complex kinematics, effects of tissue deformation, effects of tissue inhomogeneities, and other causes of motion uncertainty. Efficient computational methods for path planning enables using the full potential of steerable needles. Due to nonlinearity of needle steering, estimation and control problems are coupled. Controller-observed pairs are needed to estimate needle orientation. For image-guided control of water-jet needle steering, needle steering models should be used for model-based feedback controllers to steer the needle inside the tissue. Therefore the other aim of this proposal will be developing a controller to control water-jet needle to reach to a specified target