Caenorhabditis elegans behavioral genetics: where are the knobs?

Thousands of behavioral mutants of Caenorhabditis elegans have been studied. I suggest a set of criteria by which some genes important in the evolution of behavior might be recognized, and identify neuropeptide signaling pathways as candidates

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Effects of denervation on 3 H-fucose incorporation by odontoblasts in the mouse incisor

The present study was designed to determine the effects of denervation on glycoprotein synthesis in the predentinal matrix of the mouse incisor. The inferior alveolar nerve (IAN), superior cervical ganglion (SCG) or both (IAN+SCG) were unilaterally resected in adult mice with the contralateral side remaining intact as a control. Fourteen days after surgery and 4 h prior to killing, 0.2 mCi of 3 H-fucose was injected intravenously and mandibles were processed for standard histological and autoradiographic techniques. Silver halide grains were counted over the predentin matrix for 2000 μm per tooth. The results showed that the IAN and SCG resection affected 3 H-fucose incorporation into the predentinal matrix; however, the highest absolute mean grain counts occurred after IAN+SCG resection. SCG resection increased the amount of 3 H-fucose incorporated into the predentinal matrix by 48%, that of IAN by 24% and that of IAN+SCG by 14% as compared to contralateral controls. These data indicate a regulatory role for the nervous system and a possible interaction of neural components in the control of glycoprotein synthesis by odontoblasts in the mouse incisor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47677/1/441_2004_Article_BF00216039.pd

Subduction initiation and ophiolite crust: new insights from IODP drilling

International Ocean Discovery Program (IODP) Expedition 352 recovered a high-fidelity record of volcanism related to subduction initiation in the Bonin fore-arc. Two sites (U1440 and U1441) located in deep water nearer to the trench recovered basalts and related rocks; two sites (U1439 and U1442) located in shallower water further from the trench recovered boninites and related rocks. Drilling in both areas ended in dolerites inferred to be sheeted intrusive rocks. The basalts apparently erupted immediately after subduction initiation and have compositions similar to those of the most depleted basalts generated by rapid sea-floor spreading at mid-ocean ridges, with little or no slab input. Subsequent melting to generate boninites involved more depleted mantle and hotter and deeper subducted components as subduction progressed and volcanism migrated away from the trench. This volcanic sequence is akin to that recorded by many ophiolites, supporting a direct link between subduction initiation, fore-arc spreading, and ophiolite genesis

Mercury flux to sediments of Lake Tahoe, California-Nevada

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Water, Air, & Soil Pollution 210 (2010): 399-407, doi:10.1007/s11270-009-0262-y.We report estimates of mercury (Hg) flux to the sediments of Lake Tahoe, California-Nevada: 2 and 15-20 µg/m2/yr in preindustrial and modern sediments, respectively. These values result in a modern to preindustrial flux ratio of 7.5-10, which is similar to flux ratios recently reported for other alpine lakes in California, and greater than the value of 3 typically seen worldwide. We offer plausible hypotheses to explain the high flux ratios, including (1) proportionally less photoreduction and evasion of Hg with the onset of cultural eutrophication and (2) a combination of enhanced regional oxidation of gaseous elemental Hg and transport of the resulting reactive gaseous Hg to the surface with nightly downslope flows of air. If either of these mechanisms is correct, it could lead to local/regional solutions to lessen the impact of globally increasing anthropogenic emissions of Hg on Lake Tahoe and other alpine ecosystems.Funding was provided by Miami University, EPA-STAR, the Postdoctoral Scholar Program at Woods Hole Oceanographic Institution, and the USGS

The effects of involving a nurse practitioner in primary care for adult patients with urinary incontinence: The PromoCon study (Promoting Continence)

Contains fulltext : 70765.pdf ( ) (Open Access)BACKGROUND: Urinary incontinence affects approximately 5% (800.000) of the Dutch population. Guidelines recommend pelvic floor muscle/bladder training for most patients. Unfortunately, general practitioners use this training only incidentally, but prescribe incontinence pads. Over 50% of patients get such pads, costing 160 million euros each year. Due to ageing of the population a further increase of expenses is expected. Several national reports recommend to involve nurse specialists to support general practitioners and improve patient care. The main objective of our study is to investigate the effectiveness and cost-effectiveness of involving nurse specialists in primary care for urinary incontinence. This paper describes the study protocol. METHODS/DESIGN: In a pragmatic prospective multi centre two-armed randomized controlled trial in the Netherlands the availability and involvement for the general practitioners of a nurse specialist will be compared with usual care. All consecutive patients consulting their general practitioner within 1 year for urinary incontinence and patients already diagnosed with urinary incontinence are eligible. Included patients will be followed for 12 months.Primary outcome is severity of urinary incontinence (measured with the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI SF)). Based on ICIQ-UI SF outcome data the number of patients needed to include is 350. For the economic evaluation quality of life and costs will be measured alongside the clinical trial. For the longer term extrapolation of the economic evaluation a Markov modelling approach will be used. DISCUSSION/CONCLUSION: This is, to our knowledge, the first trial on care for patients with urinary incontinence in primary care that includes a full economic evaluation and cost-effectiveness modelling exercise from the societal perspective. If this intervention proves to be effective and cost-effective, implementation of this intervention is considered and anticipated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN62722772

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

Measurement of the Relative Branching Fraction of Υ(4S)\Upsilon(4S) to Charged and Neutral B-Meson Pairs

We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ -> J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) -> B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- = 0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Y(4S) resonance.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

First Observation of the Decays B0→D∗−ppˉπ+B^{0}\to D^{*-}p\bar{p}\pi^{+} and B^{0}\to D^{*-}p\bar{n}$

We report the first observation of exclusive decays of the type B to D^* N anti-N X, where N is a nucleon. Using a sample of 9.7 times 10^{6} B-Bbar pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B^0 \to D^{*-} proton antiproton \pi^+) = ({6.5}^{+1.3}_{-1.2} +- 1.0) \times 10^{-4} and B(B^0 \to D^{*-} proton antineutron) = ({14.5}^{+3.4}_{-3.0} +- 2.7) times 10^{-4}. Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Seemingly Unrelated Regressions with Spatial Error Components

This paper considers various estimators using panel data seemingly unrelated regressions (SUR) with spatial error correlation. The true data generating process is assumed to be SUR with spatial error of the autoregressive or moving average type. Moreover, the remainder term of the spatial process is assumed to follow an error component structure. Both maximum likelihood and generalized moments (GM) methods of estimation are used. Using Monte Carlo experiments, we check the performance of these estimators and their forecasts under misspecification of the spatial error process, various spatial weight matrices, and heterogeneous versus homogeneous panel data models