Proteomic-based stratification of intermediate-risk prostate cancer patients

Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in the Gleason grade group (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or overtreatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign sample runs from 278 patients. Three proteins (F5, TMEM126B, and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomize prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management

Map of Port Hudson and vicinity

Scale ca. 1:,950.LC Civil War Maps (2nd ed.), 238Map indicates fortifications, drainage, hachures, vegetation, roads, and houses. Positions of Confederate batteries are shown with the number of guns in each. Inset contains a keyed list of the Union batteries giving the number and type of guns in each position, and the names of the battery commanders.Description derived from published bibliography

Military map no. 54, prepared as basis for additional surveys

Scale 1:380,160.LC Civil War Maps (2nd ed.), 102.8General map of southern Alabama and West Florida showing roads, railroads, towns, drainage, and a few names of residents along the Tensaw River.Description derived from published bibliography.Map is incomplete; the bottom border is missing. DL

Map of Anacostia River in the District of Columbia and Maryland /

Depths shown by contours and soundings."Area to be filled shaded in red."Oriented with north toward the upper right."To accompany report of Oct. 24, 1891, Peter C. Hains, Lieut. Colonel of Engineers."Includes "Cross section of proposed channel.""H Ex--30--52 1.

Heat shock of wheat during grain filling: characterisation of proteins associated with heat-tolerance using a proteome approach

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The ω-atracotoxins: Selective blockers of insect M-LVA and HVA calcium channels

The ω-atracotoxins (ω-ACTX) are a family of arthropod-selective peptide neurotoxins from Australian funnel-web spider venoms (Hexathelidae: Atracinae) that are candidates for development as biopesticides. We isolated a 37-residue insect-selective neurotoxin, ω-ACTX-Ar1a, from the venom of the Sydney funnel-web spider Atrax robustus, with high homology to several previously characterized members of the ω-ACTX-1 family. The peptide induced potent excitatory symptoms, followed by flaccid paralysis leading to death, in acute toxicity tests in house crickets. Using isolated smooth and skeletal nerve-muscle preparations, the toxin was shown to lack overt vertebrate toxicity at concentrations up to 1 μM. To further characterize the target of the ω-ACTXs, voltage-clamp analysis using the whole-cell patch-clamp technique was undertaken using cockroach dorsal unpaired median neurons. It is shown here for the first time that ω-ACTX-Ar1a, and its homolog ω-ACTX-Hv1a from Hadronyche versuta, reversibly block both mid–low- (M-LVA) and high-voltage-activated (HVA) insect calcium channel (Cav) currents. This block occurred in the absence of alterations in the voltage-dependence of Cav channel activation, and was voltage-independent, suggesting that ω-ACTX-1 family toxins are pore blockers rather than gating modifiers. At a concentration of 1 μM ω-ACTX-Ar1a failed to significantly affect global Kv channel currents. However, 1 μM ω-ACTX-Ar1a caused a modest 18% block of insect Nav channel currents, similar to the minor block of Nav channels reported for other insect Cav channel blockers such as ω-agatoxin IVA. These findings validate both M-LVA and HVA Cav channels as potential targets for insecticides

The American Engineers that Built the Panama Canal

When the United States took over title of the French canal franchise in Panama in 1903 they approached the project with vigor and confidence, treating it as an enormous railroad engineering project. A large part of the eventual success of the United States in building a canal at Panama came from avoiding the mistakes of the French, whose leadership had proven too inflexible. From the outset the Americans employed third party oversight and a knack for innovate solutions on a broad number of challenges which, like the French, they did not foresee. By 1907 the various excavation problems led American engineer John Frank Stevens to redesign the project, using a series of three locks at either end to lift ships 85 feet and transit across man-made Gatun Lake. In 1908 control of the project passed to four Army Corps of Engineers officers and a Navy civil engineer, who completed the project in August 1914, excavating 225 million cubic yards of material at a cost of $22 million below budget, despite battling landslides for the previous 10 months. The project was the jewel of an emerging American empire, and its contributions to world health and sea-born commerce were without precedent

Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids

The remarkable radiation of South American (SA) canids produced 10 extant species distributed across diverse habitats, including disparate forms such as the short-legged, hypercarnivorous bush dog and the long-legged, largely frugivorous maned wolf. Despite considerable research spanning nearly two centuries, many aspects of their evolutionary history remain unknown. Here, we analyzed 31 whole genomes encompassing all extant SA canid species to assess phylogenetic relationships, interspecific hybridization, historical demography, current genetic diversity, and the molecular bases of adaptations in the bush dog and maned wolf. We found that SA canids originated from a single ancestor that colonized South America 3.9 to 3.5 Mya, followed by diversification east of the Andes and then a single colonization event and radiation of Lycalopex species west of the Andes. We detected extensive historical gene flow between recently diverged lineages and observed distinct patterns of genomic diversity and demographic history in SA canids, likely induced by past climatic cycles compounded by human-induced population declines. Genome-wide scans of selection showed that disparate limb proportions in the bush dog and maned wolf may derive from mutations in genes regulating chondrocyte proliferation and enlargement. Further, frugivory in the maned wolf may have been enabled by variants in genes associated with energy intake from short-chain fatty acids. In contrast, unique genetic variants detected in the bush dog may underlie interdigital webbing and dental adaptations for hypercarnivory. Our analyses shed light on the evolution of a unique carnivoran radiation and how it was shaped by South American topography and climate change