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After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapyresistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy., IntroductionDNA double-strand breaks (DSBs) are believed to be the most critical lesions induced by many cancer therapies, including chemotherapy and ionizing radiation (IR). Homology-directed repair (HDR), or homologous recombination repair, [...]

An improved reference genome for maize, using single-molecule sequencing and high-resolution optical mapping, enables characterization of structural variation and repetitive regions, and identifies lineage expansions of transposable elements that are unique to maize. A better map of the maize genome The maize genome was initially reported in 2009 but with some accuracy limitations. Doreen Ware and colleagues report a new reference genome for maize using single-molecule sequencing and high-resolution optical mapping. The technique shows improvements in the gene space including resolution of gaps and misassemblies and correction of order and orientation of genes. The authors characterize structural variation and repetitive regions, and identify transposable element lineage expansions unique to maize. Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation.sup.1. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions.sup.2. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome.sup.3, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing.sup.4. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes., Author(s): Yinping Jiao [sup.1] , Paul Peluso [sup.2] , Jinghua Shi [sup.3] , Tiffany Liang [sup.3] , Michelle C. Stitzer [sup.4] , Bo Wang [sup.1] , Michael S. Campbell [sup.1] [...]

During the breeding season, male white-tailed deer (Odocoileus virginianus) have been reported to take excursions outside of their normal home ranges, likely in search of receptive females. However, we documented additional excursive movements by males during spring in north central Pennsylvania. From December 2011--April 2012, we equipped 13 mature ([greater than or equal to] 2.5 y old) male white-tailed deer with global positioning system (GPS) collars programmed to record locations hourly. We defined an excursion as any occasion where a male traveled ≥ 1.6 km outside of its 95% home range boundaries for [greater than or equal to] 12 h. Between 6 April and 6 June 2012, nine males (69.2%) made excursions with six making ≥ 2 excursions. Mean total path distance and duration of excursions was 4.0 km (range = 1.7-8.0 km) and 22 h (range = 12-40 h), respectively. Although the reason for spring excursions is obscure, hypotheses such as increased doe aggression before parturition, males returning to natal home ranges, or visitation to mineral sites do not appear tenable based on current observations., INTRODUCTION Understanding how animals utilize landscapes is necessary to identify ecological processes influencing population dynamics, gene flow, and disease transmission. Long and short duration excursive behaviors undoubtedly influence these processes. [...]

Zinc telluride films doped with gadolinium (ZnTe:Gd)--made by laser ablation and deposition--have been characterized by X-ray photoelectron spectroscopy (XPS) to determine the molecular species of the elements in the material [...]

Nitrogen is an essential macronutrient for plant growth and basic metabolic processes. The application of nitrogen-containing fertilizer increases yield, which has been a substantial factor in the green revolution.sup.1. Ecologically, however, excessive application of fertilizer has disastrous effects such as eutrophication.sup.2. A better understanding of how plants regulate nitrogen metabolism is critical to increase plant yield and reduce fertilizer overuse. Here we present a transcriptional regulatory network and twenty-one transcription factors that regulate the architecture of root and shoot systems in response to changes in nitrogen availability. Genetic perturbation of a subset of these transcription factors revealed coordinate transcriptional regulation of enzymes involved in nitrogen metabolism. Transcriptional regulators in the network are transcriptionally modified by feedback via genetic perturbation of nitrogen metabolism. The network, genes and gene-regulatory modules identified here will prove critical to increasing agricultural productivity.The yeast one-hybrid network for nitrogen-associated metabolism in Arabidopsis reveals the transcription factors that regulate the architecture of root and shoot systems under conditions of changing nitrogen availability., Author(s): Allison Gaudinier [sup.1] , Joel Rodriguez-Medina [sup.1] , Lifang Zhang [sup.2] , Andrew Olson [sup.2] , Christophe Liseron-Monfils [sup.2] , Anne-Maarit Bågman [sup.1] , Jessica Foret [sup.1] , Shane [...]

Water-based drilling mud (WBM) systems are used by the petroleum industry during drilling of oil and natural gas wells. Provincial regulations in western Canada allow disposal of spent WBM on cropland and sometimes native prairie at low rates. There is concern, however, that application of drilling waste on native prairie in semiarid climates may alter soil properties, which may adversely affect soil biophysical processes and overall ecosystem productivity. This study was initiated to examine the effects of single and multiple applications of differential rates (0, 40, and 80 [m.sup.3] [ha.sup.-1]) of summer-applied WBM on hydraulic conductivity ([K.sub.[psi]]) and macropore indices. Results from unconfined, steady-state infiltration measurements taken at -0.03- and -0.01-m supply pressure potentials ([psi]) at the soil surface provide evidence of a significant alteration of these hydraulic parameters with excessive (80 [m.sup.3] [ha.sup.-1]) drilling mud application. Across the [psi] range investigated, [K.sub.[psi]] measured 5 to 7 wk after a single mud application and the effective water-transmission macroporosity ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) calculated using the [K.sub.[psi]] decreased by 54 and 61%, respectively, at 80 [m.sup.3] [ha.sup.-1] compared with the control (0) and 40 [m.sup.3] [ha.sup.-1] rates. Corresponding decreases 5 to 8 wk after a third annual mud application were 62 and 72%. While the rate effect had disappeared 1 yr after the single application, the effect of three annual applications persisted into the following summer. By modifying soil hydrophysical properties, excessive drilling mud applications may adversely affect the soil water balance and alter the plant community structure in this sensitive ecosystem, with important implications on overall biological productivity. Abbreviations: LWD, land spraying while drilling; WBM, water-based drilling mud.

Drilling mud systems are used by the petroleum industry to facilitate and expedite the drilling of oil and natural gas wells. In western Canada, spent water-based muds (WBM) are often applied to cropland and native prairie at low application rates as a disposal option. We speculate that application of drilling waste on native prairie in semiarid climates will alter the soil surface energy balance and adversely affect soil biophysical processes and subsequently ecosystem productivity. This study was initiated to examine the effect of application rate (0, 40, and 80 [m.sup.3] [ha.sup.-1]) of summer-applied WBM on surface albedo ([alpha]), soil temperature, and soil heat flux at the 0.05-m depth ([G.sub.0.05]) and at the surface (G) over 42 d following application. Our results provide evidence of a significant alteration of these micrometeorological parameters with WBM application. Surface albedo decreased by 15% (relative to the control) with the application of 40 [m.sup.3] [ha.sup.-1] mud and by an additional 3% when this mud rate was doubled. The lower [alpha] meant that a greater proportion of incoming shortwave solar radiation ([R.sub.si]) was available for partitioning into components of the surface energy balance, including G. This coincides with observed increases in [G.sub.0.05], G, and soil temperature at the 0.025-m depth, with higher WBM. By modifying heat flow and temperature in the root zone, WBM application may alter critical ecosystem biophysical and physiological processes, with important implications for overall biological productivity. The direction and magnitude of such changes, in conjunction with all the other ecological effects of WBM, will ultimately define the sustainability of the practice in this fragile ecosystem. Abbreviations: DOY, day of year; LWD, landspraying while drilling; SZA, solar zenith angle; TOC, total organic C; WBM, water-based mud.

Author(s): Yinping Jiao [1]; Paul Peluso [2]; Jinghua Shi [3]; Tiffany Liang [3]; Michelle C. Stitzer [4]; Bo Wang [1]; Michael S. Campbell [1]; Joshua C. Stein [1]; Xuehong Wei [...]

Organic amendments have been used to restore productivity to disturbed soils such as those on abandoned oil and natural gas wellsites. A study was conducted on three abandoned wellsites in southern Alberta, Canada to examine the effects of one-time applications of alfalfa (Medicago sativa L.) hay or beef cattle (Bos taurus) feedlot manure compost on soil properties under continuous wheat (Triticum aestivum L.). The base amendment rate (lx) [dry wt.] was 5.3 Mg [ha.sup.-1] for compost and 3.1 Mg [ha.sup.-1] for alfalfa. The five amendment rates of 0, 1 x, 2x, 4x, and 8x were soil-incorporated at the wellsites. Although approximately twice as much C was applied with alfalfa than with compost, final SOC content was similar for the two amendment treatments, indicating the greater stability of compost-derived C. Nitrate N content in the 0- to 60-cm depth was not affected by compost rate (mean 213 kg [ha.sup.-1]) but increased by 7.78 kg [ha.sup.-1] for each Mg [ha.sup.-1] increase in alfalfa rate. This result reflects the greater stability of compost-N compared with alfalfa-N and suggests a lower risk of N[O.sub.3]-N leaching with compost application. Compost rates >20 Mg [ha.sup.-1] resulted in excessive extractable P build-up in the topsoil (up to 95.7 mg [kg.sup.-1]), which may pose environmental risk to surface water. We recommend amending wellsites with up to 12 Mg [ha.sup.-1] of alfalfa or Abbreviations: MKP, modified Kelowna-extractable P; SOC, soil organic carbon.

Syllable structure influences hearing students' reading and spelling (e.g., Badecker, 1996; Caramazza & Miceli, 1990; Prinzmetal, Treiman, & Rho, 1986; Rapp, 1992; Treiman & Zukowski, 1988). This may seem unsurprising since hearers closely associate written and spoken words. We analysed a corpus of spelling errors made by deaf students. They would have learned English orthography with an attenuated experience of speech. We found that the majority of their errors were phonologically implausible but orthographically legal. A tendency to replace uncommon letter sequences with common sequences could not account for this pattern, nor could residual influence from speech. Since syllabically defined constraints are required to keep sequences orthographically legal, the deaf data are marked by an influence of syllable structure. Two main conclusions follow: (1) Our results contribute to evidence that abstract constraints, not derived from peripheral speech or hearing mechanisms, govern the organization of linguistic knowledge; and (2) statistical redundancy could not explain the deaf results. It does not offer a general alternative to suprasegmental structure.

We separated effects of contour summation and orthographic similarity under masking conditions, by comparing identification with simultaneous and sequentially presented letter strings, which either did or did not overlap spatially. With overlapping simultaneous stimuli, performance was better for strings with similar contours than for strings with the same letters (the orthographic similarity condition). This suggests that contour summation effects were strongest in the condition where stimuli had similar contours. With sequential presentations, performance in the similar contour and the orthographically similar conditions was equated when the stimuli were overlapping. However, effects of contour summation decreased when prime and target letters were spatially displaced, whereas performance in the orthographically similar condition was maintained. We conclude that effects of orthographic similarity can be distinguished from effects of contour summation, under masking conditions.

This article examines how deaf individuals structure orthographic information while reading. Findings indicate that deaf individuals who are skilled readers organize orthographic information based on syllable structure, not letter frequency, despite their lack of familiarity with spoken language.

This article describes research that suggests people with the ability to read well but spell poorly couple a good configurational memory with poor encoding of serial order. Experimental design to test the causes of agraphia, or dysgraphia, and a hypothesis for how reading strategy can exist with encoding order problems, are discussed.

MiXeD-cAsE stimuli have long been used to test whether word recognition is based on holistic visual information or preliminary letter identification. However, without knowing which properties of mixed-case stimuli disrupt processing, it is not possible to determine which visual units mediate word recognition. The present studies examined the effects of case mixing on word and nonword naming as a function of (a) whether spaces were inserted between letters and (b) whether letter size was alternated independent of letter case. The results suggest that case-mixing disruption effects are due to at least 2 factors: the introduction of inappropriate grouping between letters with the same size and case, and the disruption of transletter features. The data support a model of visual lexical access based on the input from multiple visually based units.

A study of selection mechanisms in two patients with lesions in the parietal lobe revealed that removal of the stimulus need not only be spatial in nature and that it can also be non-spatial or object-leased. In the two patients, pictures were selected in preference to words while closed shapes were selected instead of open shapes. The biases related to non-spatial extinction were independent of spatial extinction.

A study was conducted to gain insight into the role of the influenza RNA-dependent RNA polymerase (RdRp) virus in regulation of the relative amounts of mRNA transcription and replication of flu RNA genome. The data obtained provides insight into the regulation of RdRp throughout the viral life cycle and its role in synthesizing the appropriate concentration amounts of viral mRNA and replication products (vRNA and cRNA).

The characterization of changes to the dynamical state of the arginine side chains in phosphomevalonate kinase (PMK) due to binding of its highly charged substrates, adenosine triphosphate (ATP) and mevalonate 5-phosphate (M5P) is described. The global rigidification of arginine side chains is unprecedented and has shown that there are long-range electrostatic interactions of enough strength to restrict the motion of arginine side chains on the picosecond-to-nanosecond time scale.

Optimized methods are described for the design and synthesis of hairpin caged morpholino (cMO) incorporating a dimethoxynitrobenzyl (DMNB)-based functional linker that permits cMO assembly in only three steps from commercially available reagents. These methodologies have helped in preparing a next-generation cMO that contains a bromohydroxyquinoline (BHQ)-based linker for two-photon uncaging.

The characterization of binding synergy and cooperativity for ligand binding to Escherichia coli dihydrodipicolinate reductase (DHPR): NADH or catechol rhodanine acetic acid (CRRA) and pyridine dicarboxylate (PDC) (stable analog of DHP) is reported. The results interpreted based on steady-state data showed that DHPR activity requires NADH binding at only one of the four monomers.

Influential models of short-term memory have attributed the fact that short words are recalled well than longer words in serial recall to articulatory rehearsal. Under suppression, the length effect is abolished or reversed for real words but remains robust for nonwords.

A variety of impairments in visual attention can follow damage to the brain. The authors develop systematic methods for analyzing such impairments in terms of C. Bundesen's (1990) Theory of Visual Attention and apply these in a group of 9 patients with parietal lobe lesions and variable spatial neglect. In whole report, patients report letters from brief, vertical arrays in left or right visual field. The results show substantial, largely bilateral impairments in processing capacity, implying a major nonlateralized aspect to neglect. In partial report, arrays contain 1 or 2 letters in red and/or green. The task is to report only those letters in a specified target colon In addition to the expected bias against left-sided letters, patients show striking, bilateral preservation of top-down control, or attentional priority for targets. The results show how differentiation of attentional impairments can be informed by a theory of normal function.