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The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein–protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a “mix and match” model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.

DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown. DDX3 localized to the mitochondria and DDX3 inhibition with RK-33 reduced mitochondrial translation. As a consequence, oxygen consumption rates and intracellular ATP concentrations decreased and reactive oxygen species (ROS) increased. RK-33 antagonized the increase in oxygen consumption and ATP production observed after exposure to ionizing radiation and reduced DNA repair. Overall, we conclude that DDX3 inhibition with RK-33 causes radiosensitization in breast cancer through inhibition of mitochondrial translation, which results in reduced oxidative phosphorylation capacity and increased ROS levels, culminating in a bioenergetic catastrophe.

Characterization of prior austenite grain size is important for understanding the microstructure–property relationships in steels. The prior austenite grain size plays an important role in defining the microstructural scale of low-temperature phases and the mechanical properties (e.g., strength, ductility, fracture toughness, etc.) of steels in the final product form. Moreover, in several failure analyses, the cracks are observed to propagate along the prior austenite grain boundaries (PAGBs). The delineation of PAGBs in steels of new composition can be quite challenging, as the response to a particular etching protocol is very sensitive to the chemical composition of steel. The objective of this study was to establish a methodology to delineate PAGBs in AF9628, a newly developed low-alloy high-performance steel. Several different etchants and etching techniques from the literature were evaluated. These methods were unsuccessful or had limited success in revealing PAGBs in AF9628. However, swab etching with a solution of 100 ml saturated aqueous picric acid and 0.5 g sodium dodecyl benzene sulfonate worked remarkably well for delineating the PAGBs in this steel. This etchant was found to have high selectivity, revealing PAGBs preferentially over packet, block, and sub-block boundaries.

A comprehensive review of the unique anatomy and vascular supply of the talus and patterns of talar fractures and dislocations is meant to provide radiologists with a high-yield resource for identifying and differentiating between different types of talar injuries to facilitate proper management.

Previous studies have shown that day-long hill walking exercise results in significant sodium and water retention, followed during a recovery/rest period by natriuresis and diuresis. The purpose of this study was to assess the role of atrial natriuretic peptide (ANP) during the post-exercise natriuretic phase.Five subjects ate a fixed diet for 13 days. A period of 4 rest days preceded 5 days of strenuous hill walking, followed by a 4-day recovery period. Daily measurement of aldosterone, ANP and haematocrit, and sodium and water balances were performed. Exercise was associated with sodium retention and a positive cumulative balance, mean 268 mmol (SD 17) after 5 days. There was a mean cumulative positive water balance of 700 ml (sd34). Haematocrit was reduced from 44.6% to 39.3%, indicating an increase in plasma volume of 22%. Plasma aldosterone concentration during exercise was elevated. Plasma ANP concentrations were raised significantly throughout the exercise period (mean 20.3 pmol I−1[sd6.4], control 9.4 pmol I−1[sd5.4], P< 0.001). There was a fall (non-significant) during the recovery period (mean 17.2 pmol I−1[sd9.1]) but levels were significantly higher than control (P< 0.02). It is suggested that the natriuresis during recovery is mediated by elevated ANP levels, probably due to increased blood volume distending the atria.

The Political Economy of Mountain Java: An Interpretive History, by Robert W. Hefner. Berkeley, CA: University of California Press, 1990. Pp.xx + 278. US $34.95. ISBN 0 520 06933 1Arguing with the Crocodile: Gender and Class in Bangladesh, by Sarah C. White. London: Zed Books, 1992. Pp.192. £10.95 (paperback). ISBN 1 85649 086 6When Jesus Came, the Corn Mothers Went Away: Marriage, Sexuality, and Power in New Mexico, 1500-1846, by Ramon A. Gutierrez. Stanford, CA: Stanford University Press, 1991. Pp.xxxi + 424. $49.50 (hardback); $16.95 (paperback). ISBN 0 8047 1816 4 and 1832 6Child Labour in the Indian Sub-continent: Dimensions and Implications, edited by Ramesh Kanbargi. New Delhi Sage Publications, 1991. Pp.184. £25 (hardback). ISBN 0 8039 9693 4 (US)The White Lotus Teachings in Chinese Religious History, by B.J. ter Harr (Sinica Leidensia, 26). Leiden: E.J. Brill, 1992. Pp.xiii + 343. DF1.170/ $97.25. ISBN 90 04 094148Talolliset ja Torpparit: Vuosisadan vaihteen maatalouskysymys Suomessa (Landowners and Crofters: The Peasant Question in Finland and at the Turn of the Century), by Matti Peltonen. Helsinki: Societas Historica Finlandiae. 1992. Pp.429; maps, tables and photographs; Finnish text and English summary. NP (paperback). ISBN 951 8915 555The Corncribs of Buzet: Modernizing Agriculture in the French Southwest, by Peter H. Amann. Princeton: NJ, Princeton University Press, 1990. Pp.xiv + 292. $39.50 (hardback). ISBN 0 691 05563 7Les agriculteurs et la République, by Isabel Boussard (Collection -économie agricole & agro-alimentaire). Paris: Economica, 1990. Pp.160. Ffr.125 (paperback). ISBN 2 7178 1903 7

At a time when the markets are flooded with new remedies, each one backed by innumerable clinical observations, it would indeed seem reckless presumption to speak about one laden with age. But, while in the wide range of applicability the drug for which I propose to take up the cudgels this evening falls far below many of the recent ones, yet in effectiveness, circumstances and conditions remaining the same, it outdoes all the latest rivals and arrivals.My object here is to speak about nitrate of silver, its value in the local treatment of diseases of the skin.The physiologic action of nitrate of silver as applied locally, depends upon the strength of the salt employed. It may be caustic, escharotic, astringent and alterative, each condition resulting from the use of the mitigated, pure, saturated or very weak solution. A quality of silver nitrate passed unmentioned by writers on materia

Send your letters to the Editor, British Dental Journal, 64 Wimpole Street, London, W1G 8YS. bdj@bda.org.Priority will be given to letters less than 500 words long. Authors must sign the letter, which may be edited for reasons of space.Readers may now comment on letters via the BDJwebsite (www.bdj.co.uk). A 'Readers' Comments' section appears at the end of the full text of each letter online.

La qualité de vie (QDV) est un paramètre important à considérer dans la BPCO. Cependant, la QDV est rarement un critère principal des études cliniques dans la BPCO. L’objectif de cette étude est d’étudier l’effet de la combinaison fixe du tiotropium (T) et de l’olodatérol (O) versus T seul et placebo, chez des patients BPCO.

Les études jumelles ANHELTO 1 et 2 de 12 semaines, randomisées en double insu ont montré que l’association de d’olodaterol (O) 5μg (Respimat®) au tiotropium (T) 18μg (HandiHaler®) procurait un effet bronchodilatateur supérieur au tiotropium seul chez des patients BPCO. Il existe peu de données sur cette combinaison libre. L’objectif de cette analyse combinée prévue aux protocoles des études ANHELTO était d’évaluer l’effet bronchodilatateur de cette association par rapport au tiotropium et au placebo chez des patients BPCO selon leurs caractéristiques initiales.

There is much mystique surrounding the acquisition by a young practitioner of his or her first dental practice, arising largely from his fear of the unknown. In fact, provided that he or she obtains sound legal and commercial advice, he or she can purchase a dental practice almost exclusively out of borrowed capital. Whilst repaying capital (and interest) over a 10-year period, it is possible to earn more from day one than as a relatively experienced associate on the usual commission arrangement

New York City, June 25, 1898.Mrs. G., 26 years old, was delivered last January of an anacephelous male child. Labor was short and natural. Two days after, to prevent the secretion of milk with the consequent painful distention of the breasts, a belladonna plaster was applied to each gland in addition to the usual bandage compression. The nipples were not covered by the plasters. In about twelve hours I was hurriedly called to my patient and found her condition as follows: Flushed face, pulse 100 and good; temperature 100.5 degrees and quite actively delirious. She sang, whistled, laughed, cried and made futile attempts to get out of bed and house. Finding no appreciable cause for the combined disturbance of body and mind, puerperal insanity suggested itself as the most probable diagnosis.The second visit was made sixteen hours after the first; the woman's condition was found to be much

Since William Withering, a Birmingham practitioner, gave his "Account of Foxglove" in 1785, digitalis has been the favorite remedy in diseases of the heart. The great popularity of the drug, however, rendered it subject to abuse as well as to use. It suffered all through these many years and decades and still suffers to-day from misapplianee and insufficient appliance in the very dominion it rules. For example, if precordial pain, palpitation or a murmur is made the basis for prescribing digitalis it is a misapplication of a valuable agent constituting a serious abuse. Or, if digitalis is ordered merely because the patient has "heart disease," the drug, no less than the patient, is grievously abused.Another form of abuse of digitalis, even though the condition of the heart calls for it, is the withdrawal or discontinuance of the drug as soon as its therapeutic effects become manifest. Let it be