Characteristics of Kepler Planetary Candidates Based on the First Data Set: The Majority are Found to be Neptune-Size and Smaller

In the spring of 2009, the Kepler Mission commenced high-precision photometry on nearly 156,000 stars to determine the frequency and characteristics of small exoplanets, conduct a guest observer program, and obtain asteroseismic data on a wide variety of stars. On 15 June 2010 the Kepler Mission released data from the first quarter of observations. At the time of this publication, 706 stars from this first data set have exoplanet candidates with sizes from as small as that of the Earth to larger than that of Jupiter. Here we give the identity and characteristics of 306 released stars with planetary candidates. Data for the remaining 400 stars with planetary candidates will be released in February 2011. Over half the candidates on the released list have radii less than half that of Jupiter. The released stars include five possible multi-planet systems. One of these has two Neptune-size (2.3 and 2.5 Earth-radius) candidates with near-resonant periods.Comment: Paper to accompany Kepler's June 15, 2010 data release; submitted to Astrophysical Journal Figures 1,2,& 3 revised. Improved labeling on all figures. Slight changes to planet frequencies in result

MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion

One of the most interesting challenges facing paleobiologists is explaining the Cambrian explosion, the dramatic appearance of most metazoan animal phyla in the Early Cambrian, and the subsequent stability of these body plans over the ensuing 530 million years. We propose that because phenotypic variation decreases through geologic time, because microRNAs (miRNAs) increase genic precision, by turning an imprecise number of mRNA transcripts into a more precise number of protein molecules, and because miRNAs are continuously being added to metazoan genomes through geologic time, miRNAs might be instrumental in the canalization of development. Further, miRNAs ultimately allow for natural selection to elaborate morphological complexity, because by reducing gene expression variability, miRNAs increase heritability, allowing selection to change characters more effectively. Hence, miRNAs might play an important role in shaping metazoan macroevolution, and might be part of the solution to the Cambrian conundrum

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Acute neurological signs as the predominant clinical manifestation in four dogs with Angiostrongylus vasorum infections in Denmark

Four dogs with acute neurological signs caused by haemorrhages in the central nervous system were diagnosed with Angiostrongylus vasorum infection as the underlying aetiology. Two dogs presented with brain lesions, one dog with spinal cord lesions and one with lesions in both the brain and spinal cord. Only one dog presented with concurrent signs of classical pulmonary angiostrongylosis (respiratory distress, cough), and only two dogs displayed overt clinical signs of haemorrhages. Results of coagulation assays were inconsistent. Neurological signs reflected the site of pathology and included seizures, various cranial nerve deficits, vestibular signs, proprioceptive deficits, ataxia and paraplegia. One dog died and three were euthanised due to lack of improvement despite medical treatment. This emphasises canine angiostrongylosis as a potential cause of fatal lesions of the central nervous system and the importance of including A. vasorum as a differential diagnosis in young dogs with acute neurological signs in Denmark

Kuhnian revolutions in neuroscience: the role of tool development.

The terms "paradigm" and "paradigm shift" originated in "The Structure of Scientific Revolutions" by Thomas Kuhn. A paradigm can be defined as the generally accepted concepts and practices of a field, and a paradigm shift its replacement in a scientific revolution. A paradigm shift results from a crisis caused by anomalies in a paradigm that reduce its usefulness to a field. Claims of paradigm shifts and revolutions are made frequently in the neurosciences. In this article I will consider neuroscience paradigms, and the claim that new tools and techniques rather than crises have driven paradigm shifts. I will argue that tool development has played a minor role in neuroscience revolutions.The work received no fundin

Conditioning Individual Mosquitoes to an Odor: Sex, Source, and Time

Olfactory conditioning of mosquitoes may have important implications for vector-pathogen-host dynamics. If mosquitoes learn about specific host attributes associated with pathogen infection, it may help to explain the heterogeneity of biting and disease patterns observed in the field. Sugar-feeding is a requirement for survival in both male and female mosquitoes. It provides a starting point for learning research in mosquitoes that avoids the confounding factors associated with the observer being a potential blood-host and has the capability to address certain areas of close-range mosquito learning behavior that have not previously been described. This study was designed to investigate the ability of the southern house mosquito, Culex quinquefasciatus Say to associate odor with a sugar-meal with emphasis on important experimental considerations of mosquito age (1.2 d old and 3–5 d old), sex (male and female), source (laboratory and wild), and the time between conditioning and testing (<5 min, 1 hr, 2.5 hr, 5 hr, 10 hr, and 24 hr). Mosquitoes were individually conditioned to an odor across these different experimental conditions. Details of the conditioning protocol are presented as well as the use of binary logistic regression to analyze the complex dataset generated from this experimental design. The results suggest that each of the experimental factors may be important in different ways. Both the source of the mosquitoes and sex of the mosquitoes had significant effects on conditioned responses. The largest effect on conditioning was observed in the lack of positive response following conditioning for females aged 3–5 d derived from a long established colony. Overall, this study provides a method for conditioning experiments involving individual mosquitoes at close range and provides for future discussion of the relevance and broader questions that can be asked of olfactory conditioning in mosquitoes

Grand challenges in evolutionary developmental biology

EVO-DEVO'S IDENTITY There is a widespread consensus on the view that evolutionary developmental biology (evo-devo) is the discipline eventually borne to fill the gap between evolutionary biology and developmental biology, following a divorce between these two fields that extended over more than half a century (Amundson, 2005). On closer inspection, however, this broadly acceptable perspective discloses a wealth of questions, if looked at retrospectively, and of potentially divergent possibilities, if looked at prospectively. The slow pace of integration between the different threads that were converging into evo-devo was well expressed by Raff (2000) in a survey of the main issues in this field. Some 15 years ago Raff, one of the discipline's founding fathers, remarked that "What constitutes the fundamental problems for a science of evolutionary developmental biology (evo-devo) depends on whether the scientist is a developmental biologist, a paleontologist or an evolutionary biologist" and drafted a list of at the time hot issues. Evo-devo has answered these questions only in part. However, this discipline is now mature for addressing a number of more precise, and more challenging questions, as I will argue in this article. To date, two sets of problems have been primarily floated in discussions about the identity and research targets of evo-devo. On the one hand are those centered around the (controversial) notions of evolvability, robustness and constraint in connection with the increasing appreciation of the intricacies of the genotype→phenotype map (Alberch, 1991; Altenberg, 1995; West-Eberhard, 2003; Pigliucci, 2010; Wagner and Zhang, 2011). On the other hand are those centered around the notions of origination, innovation, and novelty, the so-called "innovation triad." To Hendrikse et al. (2007), for example, evolvability is the key issue that justifies recognizing evo-devo as an autonomous discipline. Others, e.g., Muller and Newman (2005), focus instead on the innovation triad. Unfortunately, for all these candidates to core concept of evo-devo, too many alternative definitions have been proposed (or, more dangerously, implicitly assumed), thus adding new items to the dramatically increasing series of biological terms on whose definition there seem to be more and more disagreement. Eventually, we should probably learn to accept that multiple notions associated with each of these terms deserve to be retained and perhaps recognized by adjectival specifications. Similar terminological refinement is applied to other biological terms such as species (e.g., Claridge et al., 1997), homology (e.g., Minelli and Fusco, 2013a), and gene (e.g., Beurton et al., 2000). In discussing the concept of gene in historical perspective, Muller-Wille and Rheinberger (2009) have sensibly recalled Friedrich Nietzsche's (1887; second essay, para. 13) dictum, that "all concepts in which an entire process is semiotically concentrated elude definition; only that which has no history is definable." In addition to terminological ambiguity, there is an another problem with the "innovation triad"—the problem that these terms are all framed in terms of "origins." Framing definitions in terms of origin requires splitting the evolutionary sequence in two contiguous segments, "before" and "after" the origination of a new feature. This splitting is a natural consequence if origination indeed "refers to the specific causality of the generative conditions that underlie both the first origins and the later innovations of phenotypes" and especially "the very first beginnings of phenotypes, e.g., the origin of multicellular assemblies, of complex tissues, and of the generic forms that result from the self-organizational and physical principles of cell interaction (Newman, 1992, 1994). In contrast, innovation [evolutionary modes and mechanisms] and novelty [their phenotypic outcome] designate the processes and results of introducing new characters into already existing phenotypic themes of a certain architecture (bodyplans)" (Muller and Newman, 2005, p. 490). This separation, however, is artificial. The better we know a process, the less we are able to identify its exact origins, these instead being determined by arbitrary choice. In science, and especially in biological disciplines with a strong historical dimension such as evolutionary biology and developmental biology, we should frame questions in terms of transitions rather than origins

Characteristics of planetary candidates observed by Kepler. II. Analysis of the first four months of data

On 2011 February 1 the Kepler mission released data for 156,453 stars observed from the beginning of the science observations on 2009 May 2 through September 16. There are 1235 planetary candidates with transit-like signatures detected in this period. These are associated with 997 host stars. Distributions of the characteristics of the planetary candidates are separated into five class sizes: 68 candidates of approximately Earth-size (Rp &lt; 1.25 R⊕), 288 super-Earth-size (1.25 R⊕ ≤ R p &lt; 2 R⊕), 662 Neptune-size (2 R ⊕ ≤ Rp &lt; 6 R⊕), 165 Jupiter-size (6 R⊕ ≤ Rp &lt; 15 R ⊕), and 19 up to twice the size of Jupiter (15 R ⊕ ≤ Rp &lt; 22 R⊕). In the temperature range appropriate for the habitable zone, 54 candidates are found with sizes ranging from Earth-size to larger than that of Jupiter. Six are less than twice the size of the Earth. Over 74% of the planetary candidates are smaller than Neptune. The observed number versus size distribution of planetary candidates increases to a peak at two to three times the Earth-size and then declines inversely proportional to the area of the candidate. Our current best estimates of the intrinsic frequencies of planetary candidates, after correcting for geometric and sensitivity biases, are 5% for Earth-size candidates, 8% for super-Earth-size candidates, 18% for Neptune-size candidates, 2% for Jupiter-size candidates, and 0.1% for very large candidates; a total of 0.34 candidates per star. Multi-candidate, transiting systems are frequent; 17% of the host stars have multi-candidate systems, and 34% of all the candidates are part of multi-candidate systems