Forest calcium depletion and biotic retention along a soil nitrogen gradient

High nitrogen (N) accumulation in terrestrial ecosystems can shift patterns of nutrient limitation and deficiency beyond N toward other nutrients, most notably phosphorus (P) and base cations (calcium [Ca], magnesium [Mg], and potassium [K]). We examined how naturally high N accumulation from a legacy of symbiotic N fixation shaped P and base cation cycling across a gradient of nine temperate conifer forests in the Oregon Coast Range. We were particularly interested in whether long-term legacies of symbiotic N fixation promoted coupled N and organic P accumulation in soils, and whether biotic demands by non-fixing vegetation could conserve ecosystem base cations as N accumulated. Total soil N (0–100 cm) pools increased nearly threefold across the N gradient, leading to increased nitrate leaching, declines in soil pH from 5.8 to 4.2, 10-fold declines in soil exchangeable Ca, Mg, and K, and increased mobilization of aluminum. These results suggest that long-term N enrichment had acidified soils and depleted much of the readily weatherable base cation pool. Soil organic P increased with both soil N and C across the gradient, but soil inorganic P, biomass P, and P leaching loss did not vary with N, implying that historic symbiotic N fixation promoted soil organic P accumulation and P sufficiency for non-fixers. Even though soil pools of Ca, Mg, and K all declined as soil N increased, only Ca declined in biomass pools, suggesting the emergence of Ca deficiency at high N. Biotic conservation and tight recycling of Ca increased in response to whole-ecosystem Ca depletion, as indicated by preferential accumulation of Ca in biomass and surface soil. Our findings support a hierarchical model of coupled N–Ca cycling under long-term soil N enrichment, whereby ecosystem-level N saturation and nitrate leaching deplete readily available soil Ca, stimulating biotic Ca conservation as overall supply diminishes. We conclude that a legacy of biological N fixation can increase N and P accumulation in soil organic matter to the point that neither nutrient is limiting to subsequent non-fixers, while also resulting in natural N saturation that intensifies base cation depletion and deficiency.Keywords: Potassium, Base cation depletion, Temperate forest, Calcium, Magnesium, Douglas-fir, Aluminum, Phosphorus, Nitrate leaching, Nitrogen saturatio

A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose.

We report the first genome-wide association study (GWAS) whose sample size (1,053 Swedish subjects) is sufficiently powered to detect genome-wide significance (p<1.5 x 10(-7)) for polymorphisms that modestly alter therapeutic warfarin dose. The anticoagulant drug warfarin is widely prescribed for reducing the risk of stroke, thrombosis, pulmonary embolism, and coronary malfunction. However, Caucasians vary widely (20-fold) in the dose needed for therapeutic anticoagulation, and hence prescribed doses may be too low (risking serious illness) or too high (risking severe bleeding). Prior work established that approximately 30% of the dose variance is explained by single nucleotide polymorphisms (SNPs) in the warfarin drug target VKORC1 and another approximately 12% by two non-synonymous SNPs (*2, *3) in the cytochrome P450 warfarin-metabolizing gene CYP2C9. We initially tested each of 325,997 GWAS SNPs for association with warfarin dose by univariate regression and found the strongest statistical signals (p<10(-78)) at SNPs clustering near VKORC1 and the second lowest p-values (p<10(-31)) emanating from CYP2C9. No other SNPs approached genome-wide significance. To enhance detection of weaker effects, we conducted multiple regression adjusting for known influences on warfarin dose (VKORC1, CYP2C9, age, gender) and identified a single SNP (rs2108622) with genome-wide significance (p = 8.3 x 10(-10)) that alters protein coding of the CYP4F2 gene. We confirmed this result in 588 additional Swedish patients (p<0.0029) and, during our investigation, a second group provided independent confirmation from a scan of warfarin-metabolizing genes. We also thoroughly investigated copy number variations, haplotypes, and imputed SNPs, but found no additional highly significant warfarin associations. We present power analysis of our GWAS that is generalizable to other studies, and conclude we had 80% power to detect genome-wide significance for common causative variants or markers explaining at least 1.5% of dose variance. These GWAS results provide further impetus for conducting large-scale trials assessing patient benefit from genotype-based forecasting of warfarin dose

Characterization of acDNA highly enriched in CNS

MUD 5 is one of several cDNAs isolated in a differential screen to identify messages induced during apoptosis in differentiated PC12 cells following removal of NGF. Although subsequent studies indicated that MUD 5 mRNA was not consistently modulated during apoptosis, its characterization was continued because it was expressed primarily or exclusively in the nervous system. Northern blots indicate a single 1.4 kb transcript in all brain regions with expression beginning around postnatal day 3 and increasing gradually until it reaches adult levels at postnatal day 25. In situ hybridization studies of adult rat brain localize MUD 5 mRNA to neurons in cortical and limbic structures as well as cerebellum and brain stem. The most heavily labeled neurons include Purkinje cells, and neurons in the hippocampus, dentate gyrus, deep cerebellar nuclei, and several brainstem nuclei. A full length MUD 5 was isolated from a PC12 cDNA library. The cDNA is 1299 bases, contains a strong Kozak sequence, and predicts an acidic protein of 308 amino acids. The transcript has a high GC content, 62% overall, with some areas as high as 71%. The protein has a predicted molecular weight of 35 kDa; however, following in vitro translation and gel electrophoresis it runs as a 40 kDa protein. The protein has no membrane spanning regions and is predicted to be a globular polypeptide. MUD 5 is highly homologous to OCP1, one of two major proteins in the organ of Corti. Mud 5 also contains a region of 140 amino acids that is similar to proteins in the ICE/ced-3 family of cell death proteases. This homology includes the active site cysteine and flanking amino acids (QACRG/L). The N terminal region of MUD 5 contains a glutamic acid rich PEST sequence which is known to decrease protein stability and an F box that is speculated to be involved in ubiquitin mediated proteolysis. MUD 5 mRNA is decreased following exposure of PC12 cells to metabolic stress induced by a proline analogue but is not modulated by heat shock or reactive oxygen species

Characterization of acDNA highly enriched in CNS

MUD 5 is one of several cDNAs isolated in a differential screen to identify messages induced during apoptosis in differentiated PC12 cells following removal of NGF. Although subsequent studies indicated that MUD 5 mRNA was not consistently modulated during apoptosis, its characterization was continued because it was expressed primarily or exclusively in the nervous system. Northern blots indicate a single 1.4 kb transcript in all brain regions with expression beginning around postnatal day 3 and increasing gradually until it reaches adult levels at postnatal day 25. In situ hybridization studies of adult rat brain localize MUD 5 mRNA to neurons in cortical and limbic structures as well as cerebellum and brain stem. The most heavily labeled neurons include Purkinje cells, and neurons in the hippocampus, dentate gyrus, deep cerebellar nuclei, and several brainstem nuclei. A full length MUD 5 was isolated from a PC12 cDNA library. The cDNA is 1299 bases, contains a strong Kozak sequence, and predicts an acidic protein of 308 amino acids. The transcript has a high GC content, 62% overall, with some areas as high as 71%. The protein has a predicted molecular weight of 35 kDa; however, following in vitro translation and gel electrophoresis it runs as a 40 kDa protein. The protein has no membrane spanning regions and is predicted to be a globular polypeptide. MUD 5 is highly homologous to OCP1, one of two major proteins in the organ of Corti. Mud 5 also contains a region of 140 amino acids that is similar to proteins in the ICE/ced-3 family of cell death proteases. This homology includes the active site cysteine and flanking amino acids (QACRG/L). The N terminal region of MUD 5 contains a glutamic acid rich PEST sequence which is known to decrease protein stability and an F box that is speculated to be involved in ubiquitin mediated proteolysis. MUD 5 mRNA is decreased following exposure of PC12 cells to metabolic stress induced by a proline analogue but is not modulated by heat shock or reactive oxygen species

Rudolph K. Hynicka letter to Warren G. Harding, February 11, 1920

In this letter dated February 11, 1920, Rudolph K. Hynicka, Cincinnati politician and the Ohio representative for the Republican National Committee, writes to Senator Warren G. Harding. Hynicka outlines his plans for ticket distribution and allotment, both for presidential candidates and the public, for the Republican National Convention. This letter is part of the Warren G. Harding Papers (MSS 345). This collection includes correspondence, business records, and other materials documenting Harding’s business career as owner and editor-in-chief of The Daily Marion Star, as well as the various stages of his political career. A significant portion of the collection, and what’s available on Ohio Memory, highlights his 1920 presidential campaign, spanning just before publicly announcing his candidacy to handily defeating Ohio Governor James M. Cox in the election. Correspondents include both Ohio and national businessmen, political figures, and ordinary citizens writing with questions, support, congratulatory notes, and campaign advice. Some of the most interesting insights into the tumultuous political climate in the U.S., the extreme factionalism within the Republican Party in Ohio, and Harding’s campaign strategies are described in letters between Harding and his campaign manager, Harry M. Daugherty. Some of the topics addressed include women’s suffrage, Prohibition, the League of Nations, African American representation and issues, and lingering peace negotiations following World War I.RUD. K. HYNICKA COLUMBIA THEATRE BUILDING 701 SEVENTH AVENUE NEW YORK February 11th 1920. Hon. Warren G. Harding, United States Senate, Washington, D.C. My dear Senator Harding:- At our meeting in Columbus last Friday, the 6th inst., I arranged with Mr. Clark and our Committee members that all appointments and distribution of tickets for the Chicago Republican National Convention should be made through State Headquarters, subject to approval and recommendation of the several Congressional Districts. It was my idea that this arrangement would give better satisfaction than any other and would probably relieve us all of the responsibility of discriminating in favor of or against somebody, or at least the charge of having so acted. I have filed with Mr. Clark all applications made to me, and will continue to do so. I expect to act and co-operate with Mr. Clark in making selections and distribution. Of course this arrangement has no reference to any tickets that may be alloted Presidential candidates. In my last talk with Mr. Hert, Chairman cf the Convention Arrangements Committee, he told me that the first proposition was an allotment of 25 admission tickets; each ticket covering the several sessions of the Convention. I suggested that this allotment ought to be at least 50 tickets, and I am inclined to think that this will probably be the public allotment. Confidentially, I have been promised additional tickets, conditioned of course that they are available. I will be pleased to turn over such tickets to you, retaining a small percentage for the accomodation of a few personal friends who seem to think that I can get whatever I ask for. If satisfactory to you I would be pleased to turn over such tickets as I may have for your personal use and distribution to Mr. Christian, whenever they are ready. A word from Mr. Christian in this matter will be sufficient as I know that you are too much occupied at present to give attention to matters of this sort. Sincerely, [written signature] Hynicka RKH.gh

Rudolph K. Hynicka letter to Warren G. Harding, May 17, 1920

In this letter dated May 17, 1920, Rudolph K. Hynicka, Cincinnati politician and the Ohio representative for the Republican National Committee, writes to Senator Warren G. Harding in regards to his upcoming meeting with Colonel William Procter, head of Procter & Gamble and an important political insider for the Republican Party. According to Hynicka, Procter would like to discuss how to foster harmony with Ohio Republicans, and would like to meet with Harding soon to discuss the situation. This letter is part of the Warren G. Harding Papers (MSS 345). This collection includes correspondence, business records, and other materials documenting Harding’s business career as owner and editor-in-chief of The Daily Marion Star, as well as the various stages of his political career. A significant portion of the collection, and what’s available on Ohio Memory, highlights his 1920 presidential campaign, spanning just before publicly announcing his candidacy to handily defeating Ohio Governor James M. Cox in the election. Correspondents include both Ohio and national businessmen, political figures, and ordinary citizens writing with questions, support, congratulatory notes, and campaign advice. Some of the most interesting insights into the tumultuous political climate in the U.S., the extreme factionalism within the Republican Party in Ohio, and Harding’s campaign strategies are described in letters between Harding and his campaign manager, Harry M. Daugherty. Some of the topics addressed include women’s suffrage, Prohibition, the League of Nations, African American representation and issues, and lingering peace negotiations following World War I.RUD. K. HYNICKA COLUMBIA THEATRE BUILDING 701 SEVENTH AVENUE New York May 17th 192Q. Hon. Warren G. Harding, United States Senate, Washington, D.C. My dear Senator:- I have just received word by wire from Colonel Procter that he will be in Hew York Friday of the present week. He asks for an appointment with me on that day. He indicates a willingness to "go the limit to secure harmony in the State"; however, says that he cannot agree to "go as far as your letter apparently does". Of course as you well-said on the train my letter is only to be taken as a "basis for discussion". I really feel that we ought to get together and frankly discuss the whole situation. I still feel as I wrote to Colonel Procter last Friday and, while it wouldn't be wise at this time to make public pronouncement of the views I entertain the more I think about the whole matter the more confirmed I become in the conviction that they are sound. When I see Colonel Procter Friday I will go into the whole situation and try to bring about a conference at which we can all definitely and frankly discuss this whole matter. Of course its up to the Delegation to determine on its organization, yet in all fairness you are entitled to consideration and consultation and I would regard Messrs. Herrick, Brown and Johnson as perfectly satisfactory for Delegation representation. Would you want me to mention these parties to Colonel Procter when I see him or should I defer reference to them until we might have a Washington conference, if it can be brought about? I will keep you advised as to further developments. Sincerely, [witten signature] Hynicka RKH.gh

Rudolph K. Hynicka letter to Warren G. Harding, May 6, 1920

In this letter dated May 6, 1920, Rudolph K. Hynicka, Cincinnati politician and the Ohio representative for the Republican National Committee, writes to Senator Warren G. Harding. Hynicka informs Harding that he will be embarking on a trip west soon, but would like to help Harding in any way he can. In recognizing the division and unease within the Republican Party, Hynicka offers to help to bring together opposing groups within the Ohio Republican Party to ensure its success. This letter is part of the Warren G. Harding Papers (MSS 345). This collection includes correspondence, business records, and other materials documenting Harding’s business career as owner and editor-in-chief of The Daily Marion Star, as well as the various stages of his political career. A significant portion of the collection, and what’s available on Ohio Memory, highlights his 1920 presidential campaign, spanning just before publicly announcing his candidacy to handily defeating Ohio Governor James M. Cox in the election. Correspondents include both Ohio and national businessmen, political figures, and ordinary citizens writing with questions, support, congratulatory notes, and campaign advice. Some of the most interesting insights into the tumultuous political climate in the U.S., the extreme factionalism within the Republican Party in Ohio, and Harding’s campaign strategies are described in letters between Harding and his campaign manager, Harry M. Daugherty. Some of the topics addressed include women’s suffrage, Prohibition, the League of Nations, African American representation and issues, and lingering peace negotiations following World War I

Rudolph K. Hynicka letter to Warren G. Harding, May 4, 1920

In this letter dated May 4, 1920, Rudolph K. Hynicka, Cincinnati politician and the Ohio representative for the Republican National Committee, writes to Senator Warren G. Harding in regards to a telegram from Will Hays, Chairman of the Republican National Committee, and suggests that the Ohio delegation to the Republican National Convention choose its member for the Chicago Resolutions Committee. This letter is part of the Warren G. Harding Papers (MSS 345). This collection includes correspondence, business records, and other materials documenting Harding’s business career as owner and editor-in-chief of The Daily Marion Star, as well as the various stages of his political career. A significant portion of the collection, and what’s available on Ohio Memory, highlights his 1920 presidential campaign, spanning just before publicly announcing his candidacy to handily defeating Ohio Governor James M. Cox in the election. Correspondents include both Ohio and national businessmen, political figures, and ordinary citizens writing with questions, support, congratulatory notes, and campaign advice. Some of the most interesting insights into the tumultuous political climate in the U.S., the extreme factionalism within the Republican Party in Ohio, and Harding’s campaign strategies are described in letters between Harding and his campaign manager, Harry M. Daugherty. Some of the topics addressed include women’s suffrage, Prohibition, the League of Nations, African American representation and issues, and lingering peace negotiations following World War I