Recruitment limitation constrains local species richness and productivity in dry grassland

Species coexistence and local-scale species richness are limited by the availability of seeds and microsites for germination and establishment. We conducted a seed addition experiment in seminatural grassland at three sites in southern Switzerland and repeated the experiment in two successive years to evaluate various circumstances under which seed limitation and establishment success affect community functioning. A collection of 144000 seeds of 22 meadow species including grasses and forbs of local provenance was gathered, and seeds were individually sown in a density that resembled natural seed rain. The three communities were seed limited. Three years after sowing, single species varied in emergence (0–50%), survival (0–69%), and establishment rates (0–27%). One annual and 13 perennial species reached reproductive stage. Low establishment at one site and reduced growth at another site indicated stronger microsite limitation compared to the third site. Recruitment was influenced by differences in abiotic environmental conditions between sites (water availability, soil minerals) and by within-site differences in biotic interaction (competition). At the least water-limited site, sowing resulted in an increase in phytomass due to establishment of short-lived perennials in the second and third years after sowing. This increase persisted over the following two years due to establishment of longer-lived perennials. After sowing in a wetter year with higher phytomass, however, productivity did not increase, because higher intensity of competition in an early phase of establishment resulted in less vigorous plants later on. Due to the generally favorable weather conditions during this study, sowing year had a small effect on numbers of established individuals over all species. Recruitment limitation can thus constrain local-scale species richness and productivity, either by a lack of seeds or by reduced seedling growth, likely due to competition from the established vegetation.

closo-borane conjugated regulatory peptides retain high biological affinity: synthesis of closo-borane conjugated Tyr(3)-octreotate derivatives for BNCT

Despite the improvements in cancer therapy during the past years, high-grade gliomas and many other types of cancer are still extremely resistant to current forms of therapy. Boron neutron capture therapy (BNCT) provides a promising way to destroy cancer cells without damaging healthy tissue. However, BNCT in practice is still limited due to the lack of boron-containing compounds that selectively deliver boron to cancer cells. Since many neuroendocrine tumors show an overexpression of the somatostatin receptor, it was our aim to synthesize compounds that contain a large number of boron atoms and still show high affinity toward this transmembrane receptor. The synthetic peptide Tyr (3)-octreotate (TATE) was chosen as a high-affinity and internalizing tumor targeting vector (TTV). Novel boron cluster compounds, containing 10 or 20 boron atoms, were coupled to the N-terminus of TATE. The obtained affinity data demonstrate that the use of a spacer between TATE and the closo-borane moiety is the option to avoid a loss of biological affinity of closo-borane conjugated TATE. For the first time, it was shown that closo-borane conjugated regulatory peptides retain high biological affinity and selectivity toward their transmembrane tumor receptors. The results obtained and the improvement of spacer and boron building block chemistry may stimulate new directions for BNCT.

IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

The contribution of basophils in allergic disease and other Th2-type immune responses depends on their persistence at sites of inflammation, but the ligands and molecular pathways supporting basophil survival are largely unknown. The comparison of rates of apoptosis and of the expression of antiapoptotic proteins in different human granulocyte types revealed that basophils have a considerably longer spontaneous life span than neutrophils and eosinophils consistent with high levels of constitutive Bcl-2 expression. Interleukin-3 (IL-3) is the only ligand that efficiently protects basophils from apoptosis as evidenced by screening a large number of stimuli. IL-3 up-regulates the expression of the antiapoptotic proteins cIAP2, Mcl-1, and Bcl-X(L) and induces a rapid and sustained de novo expression of the serine/threonine kinase Pim1 that closely correlates with cytokine-enhanced survival. Inhibitor studies and protein transduction of primary basophils using wild-type and kinase-dead Pim1-Tat fusion-proteins demonstrate the functional importance of Pim1 induction in the IL-3-enhanced survival. Our data further indicate that the antiapoptotic Pim1-mediated pathway operates independently of PI3-kinase but involves the activation of p38 MAPK. The induction of Pim1 leading to PI3-kinase-independent survival as described here for basophils may also be a relevant antiapoptotic mechanism in other terminally differentiated leukocyte types.

Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA

The mRNA stabilizing factor HuR is involved in the posttranscriptional regulation of many genes, including that coding for cyclooxygenase 2 (COX-2). Employing RNA interference technology and actinomycin D experiments, we demonstrate that in human mesangial cells (hMC) the amplification of cytokine-induced COX-2 by angiotensin II (AngII) occurs via a HuR-mediated increase of mRNA stability. Using COX-2 promoter constructs with different portions of the 3' untranslated region of COX-2, we found that the increase in COX-2 mRNA stability is attributable to a distal class III type of AU-rich element (ARE). Likewise, the RNA immunoprecipitation assay showed AngII-induced binding of HuR to this ARE. Using the RNA pulldown assay, we demonstrate that the AngII-caused HuR assembly with COX-2 mRNA is found in free and cytoskeleton-bound polysomes indicative of an active RNP complex. Mechanistically, the increased HuR binding to COX-2-ARE by AngII is accompanied by increased nucleocytoplasmic HuR shuttling and depends on protein kinase Cdelta (PKCdelta), which physically interacts with nuclear HuR, thereby promoting its phosphorylation. Mapping of phosphorylation sites identified serines 221 and 318 as critical target sites for PKCdelta-triggered HuR phosphorylation and AngII-induced HuR export to the cytoplasm. Posttranslational modification of HuR by PKCdelta represents an important novel mode of HuR activation implied in renal COX-2 regulation.

Mechano-regulated tenascin-C orchestrates muscle repair

Tenascin-C (TNC) is a mechano-regulated, morphogenic, extracellular matrix protein that is associated with tissue remodeling. The physiological role of TNC remains unclear because transgenic mice engineered for a TNC deficiency, via a defect in TNC secretion, show no major pathologies. We hypothesized that TNC-deficient mice would demonstrate defects in the repair of damaged leg muscles, which would be of functional significance because this tissue is subjected to frequent cycles of mechanical damage and regeneration. TNC-deficient mice demonstrated a blunted expression of the large TNC isoform and a selective atrophy of fast-muscle fibers associated with a defective, fast myogenic expression response to a damaging mechanical challenge. Transcript profiling mapped a set of de-adhesion, angiogenesis, and wound healing regulators as TNC expression targets in striated muscle. Expression of these regulators correlated with the residual expression of a damage-related 200-kDa protein, which resembled the small TNC isoform. Somatic knockin of TNC in fast-muscle fibers confirmed the activation of a complex expression program of interstitial and slow myofiber repair by myofiber-derived TNC. The results presented here show that a TNC-orchestrated molecular pathway integrates muscle repair into the load-dependent control of the striated muscle phenotype.

The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure

Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom. It is a potent activator of platelets, resulting in a collagen-like response by binding and clustering platelet receptor CLEC-2. We present here the crystal structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary structure. The two alphabeta heterodimers are arranged through 2-fold rotational symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus presents two ligand binding sites on one surface and can therefore cluster ligands in a manner reminiscent of convulxin and flavocetin. To examine the molecular basis of the interaction with CLEC-2, we used a molecular modeling approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal domain (CLEC-2N). This model positions the CLEC-2N structure face down in the "saddle"-shaped binding site which lies between the aggretin alpha and beta lectin-like domains. A 2-fold rotation of this complex to generate the aggretin tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini into the proximity of each other, and a series of contacts involving two interlocking beta-strands close to the N-terminus are described. A comparison with homologous lectin-like domains from the immunoreceptor family reveals a similar but not identical dimerization mode, suggesting this structure may represent the clustered form of CLEC-2 capable of signaling across the platelet membrane.

Past is Prologue: Montana’s Historic Women’s Movement Re-emerges in the Progressive 1970s -- Dorothy Bradley, Marilyn Wessel & Jane Jelinski “In the Crucible of Change”

One-hundred years ago, in 1914, male voters in Montana (MT) extended suffrage (voting rights) to women six years before the 19th Amendment to the US Constitution was ratified and provided that right to women in all states. The long struggle for women’s suffrage was energized in the progressive era and Jeanette Rankin of Missoula emerged as a leader of the campaign; in 1912 both major MT political party platforms supported women suffrage. In the 1914 election, 41,000 male voters supported woman suffrage while nearly 38,000 opposed it. MT was not only ahead of the curve on women suffrage, but just two years later in 1916 elected Jeanette Rankin as the first woman ever elected to the United States Congress. Rankin became a national leader for women's equality. In her commitment to equality, she opposed US entry into World War I, partially because she said she could not support men being made to go to war if women were not allowed to serve alongside them. During MT’s initial progressive era, women in MT not only pursued equality for themselves (the MT Legislature passed an equal pay act in 1919), but pursued other social improvements, such as temperance/prohibition. Well-known national women leaders such as Carrie Nation and others found a welcome in MT during the period. Women's role in the trade union movement was evidenced in MT by the creation of the Women's Protective Union in Butte, the first union in America dedicated solely to women workers. But Rankin’s defeat following her vote against World War I was used as a way for opponents to advocate a conservative, traditionalist perspective on women's rights in MT. Just as we then entered a period in MT where the “copper collar” was tightened around MT economically and politically by the Anaconda Company and its allies, we also found a different kind of conservative, traditionalist collar tightened around the necks of MT women. The recognition of women's role during World War II, represented by “Rosie the Riveter,” made it more difficult for that conservative, traditionalist approach to be forever maintained. In addition, women's role in MT agriculture – family farms and ranches -- spoke strongly to the concept of equality, as farm wives were clearly active partners in the agricultural enterprises. But rural MT was, by and large, the bastion of conservative values relative to the position of women in society. As the period of “In the Crucible of Change” began, the 1965 MT Legislature included only three women. In 1967 and 1969 only one woman legislator served. In 1971 the number went up to two, including one of our guests, Dorothy Bradley. It was only after the Constitutional Convention, which featured 19 women delegates, that the barrier was broken. The 1973 Legislature saw 9 women elected. The 1975 and 1977 sessions had 14 women legislators; 15 were elected for the 1979 session. At that time progressive women and men in the Legislature helped implement the equality provisions of the new MT Constitution, ratified the federal Equal Rights Amendment in 1974, and held back national and local conservatives forces which sought in later Legislatures to repeal that ratification. As with the national movement at the time, MT women sought and often succeeded in adopting legal mechanisms that protected women’s equality, while full equality in the external world remained (and remains) a treasured objective. The story of the re-emergence of Montana’s women’s movement in the 1970s is discussed in this chapter by three very successful and prominent women who were directly involved in the effort: Dorothy Bradley, Marilyn Wessel, and Jane Jelinski. Their recollections of the political, sociological and cultural path Montana women pursued in the 1970s and the challenges and opposition they faced provide an insider’s perspective of the battle for equality for women under the Big Sky “In the Crucible of Change.” Dorothy Bradley grew up in Bozeman, Montana; received her Bachelor of Arts Phi Beta Kappa from Colorado College, Colorado Springs, in 1969 with a Distinction in Anthropology; and her Juris Doctor from American University in Washington, D.C., in 1983. In 1970, at the age of 22, following the first Earth Day and running on an environmental platform, Ms. Bradley won a seat in the 1971 Montana House of Representatives where she served as the youngest member and only woman. Bradley established a record of achievement on environmental & progressive legislation for four terms, before giving up the seat to run a strong second to Pat Williams for the Democratic nomination for an open seat in Montana’s Western Congressional District. After becoming an attorney and an expert on water law, she returned to the Legislature for 4 more terms in the mid-to-late 1980s. Serving a total of eight terms, Dorothy was known for her leadership on natural resources, tax reform, economic development, and other difficult issues during which time she gained recognition for her consensus-building approach. Campaigning by riding her horse across the state, Dorothy was the Democratic nominee for Governor in 1992, losing the race by less than a percentage point. In 1993 she briefly taught at a small rural school next to the Northern Cheyenne Indian Reservation. She was then hired as the Director of the Montana University System Water Center, an education and research arm of Montana State University. From 2000 - 2008 she served as the first Gallatin County Court Administrator with the task of collaboratively redesigning the criminal justice system. She currently serves on One Montana’s Board, is a National Advisor for the American Prairie Foundation, and is on NorthWestern Energy’s Board of Directors. Dorothy was recognized with an Honorary Doctorate from her alma mater, Colorado College, was named Business Woman of the Year by the Bozeman Chamber of Commerce and MSU Alumni Association, and was Montana Business and Professional Women’s Montana Woman of Achievement. Marilyn Wessel was born in Iowa, lived and worked in Los Angeles, California, and Washington, D.C. before moving to Bozeman in 1972. She has an undergraduate degree in journalism from Iowa State University, graduate degree in public administration from Montana State University, certification from the Harvard University Institute for Education Management, and served a senior internship with the U.S. Congress, Montana delegation. In Montana Marilyn has served in a number of professional positions, including part-time editor for the Montana Cooperative Extension Service, News Director for KBMN Radio, Special Assistant to the President and Director of Communications at Montana State University, Director of University Relations at Montana State University and Dean and Director of the Museum of the Rockies at MSU. Marilyn retired from MSU as Dean Emeritus in 2003. Her past Board Service includes Montana State Merit System Council, Montana Ambassadors, Vigilante Theater Company, Montana State Commission on Practice, Museum of the Rockies, Helena Branch of the Ninth District Federal Reserve Bank, Burton K. Wheeler Center for Public Policy, Bozeman Chamber of Commerce, and Friends of KUSM Public Television. Marilyn’s past publications and productions include several articles on communications and public administration issues as well as research, script preparation and presentation of several radio documentaries and several public television programs. She is co-author of one book, 4-H An American Idea: A History of 4-H. Marilyn’s other past volunteer activities and organizations include Business and Professional Women, Women's Political Caucus, League of Women Voters, and numerous political campaigns. She is currently engaged professionally in museum-related consulting and part-time teaching at Montana State University as well as serving on the Editorial Board of the Bozeman Daily Chronicle and a member of Pilgrim Congregational Church and Family Promise. Marilyn and her husband Tom, a retired MSU professor, live in Bozeman. She enjoys time with her children and grandchildren, hiking, golf, Italian studies, cooking, gardening and travel. Jane Jelinski is a Wisconsin native, with a BA from Fontbonne College in St. Louis, MO who taught fifth and seventh grades prior to moving to Bozeman in 1973. A stay-at-home mom with a five year old daughter and an infant son, she was promptly recruited by the Gallatin Women’s Political Caucus to conduct a study of Sex-Role Stereotyping in K Through 6 Reading Text Books in the Bozeman School District. Sociologist Dr. Louise Hale designed the study and did the statistical analysis and Jane read all the texts, entered the data and wrote the report. It was widely disseminated across Montana and received attention of the press. Her next venture into community activism was to lead the successful effort to downzone her neighborhood which was under threat of encroaching business development. Today the neighborhood enjoys the protections of a Historic Preservation District. During this time she earned her MPA from Montana State University. Subsequently Jane founded the Gallatin Advocacy Program for Developmentally Disabled Adults in 1978 and served as its Executive Director until her appointment to the Gallatin County Commission in 1984, a controversial appointment which she chronicled in the Fall issue of the Gallatin History Museum Quarterly. Copies of the issue can be ordered through: http://gallatinhistorymuseum.org/the-museum-bookstore/shop/. Jane was re-elected three times as County Commissioner, serving fourteen years. She was active in the Montana Association of Counties (MACO) and was elected its President in 1994. She was also active in the National Association of Counties, serving on numerous policy committees. In 1998 Jane resigned from the County Commission 6 months before the end of her final term to accept the position of Assistant Director of MACO, from where she lobbied for counties, provided training and research for county officials, and published a monthly newsletter. In 2001 she became Director of the MSU Local Government Center where she continued to provide training and research for county and municipal officials across MT. There she initiated the Montana Mayors Academy in partnership with MMIA. She taught State and Local Government, Montana Politics and Public Administration in the MSU Political Science Department before retiring in 2008. Jane has been married to Jack for 46 years, has two grown children and three grandchildren.

The NF-{kappa}B negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas

Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL). Inactivating mutations encoding truncated A20 proteins were identified in 6 (19%) of 32 MZLs, including 2 (18%) of 11 EMZLs, 3 (33%) of 9 NMZLs, and 1 (8%) of 12 SMZLs. Two additional unmutated nonsplenic MZLs also showed monoallelic or biallelic A20 deletions by fluorescent in situ hybridization (FISH) and/or SNP-arrays. Thus, A20 inactivation by either somatic mutation and/or deletion represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappaB activation.

Genetic diversity and ecological success of Staphylococcus aureus strains colonizing humans

The genetic determinants and phenotypic traits which make a Staphylococcus aureus strain a successful colonizer are largely unknown. The genetic diversity and population structure of 133 S. aureus isolates from healthy, generally risk-free adult carriers were investigated using four different typing methods: multilocus sequence typing (MLST), amplified fragment length polymorphism analysis (AFLP), double-locus sequence typing (DLST), and spa typing were compared. Carriage isolates displayed great genetic diversity which could only be revealed fully by DLST. Results of AFLP and MLST were highly concordant in the delineation of genotypic clusters of closely related isolates, roughly equivalent to clonal complexes. spa typing and DLST provided considerably less phylogenetic information. The resolution of spa typing was similar to that of AFLP and inferior to that of DLST. AFLP proved to be the most universal method, combining a phylogeny-building capacity similar to that of MLST with a much higher resolution. However, it had a lower reproducibility than sequencing-based MLST, DLST, and spa typing. We found two cases of methicillin-resistant S. aureus colonization, both of which were most likely associated with employment at a health service. Of 21 genotypic clusters detected, 2 were most prevalent: cluster 45 and cluster 30 each colonized 24% of the carrier population. The number of bacteria found in nasal samples varied significantly among the clusters, but the most prevalent clusters were not particularly numerous in the nasal samples. We did not find much evidence that genotypic clusters were associated with different carrier characteristics, such as age, sex, medical conditions, or antibiotic use. This may provide empirical support for the idea that genetic clusters in bacteria are maintained in the absence of adaptation to different niches. Alternatively, carrier characteristics other than those evaluated here or factors other than human hosts may exert selective pressure maintaining genotypic clusters.

Determinants of plant establishment success in a multispecies introduction experiment with native and alien species

Determinants of plant establishment and invasion are a key issue in ecology and evolution. Although establishment success varies substantially among species, the importance of species traits and extrinsic factors as determinants of establishment in existing communities has remained difficult to prove in observational studies because they can be confounded and mask each other. Therefore, we conducted a large multispecies field experiment to disentangle the relative importance of extrinsic factors vs. species characteristics for the establishment success of plants in grasslands. We introduced 48 alien and 45 native plant species at different seed numbers into multiple grassland sites with or without experimental soil disturbance and related their establishment success to species traits assessed in five independent multispecies greenhouse experiments. High propagule pressure and high seed mass were the most important factors increasing establishment success in the very beginning of the experiment. However, after 3 y, propagule pressure became less important, and species traits related to biotic interactions (including herbivore resistance and responses to shading and competition) became the most important drivers of success or failure. The relative importance of different traits was environment-dependent and changed over time. Our approach of combining a multispecies introduction experiment in the field with trait data from independent multispecies experiments in the greenhouse allowed us to detect the relative importance of species traits for early establishment and provided evidence that species traits—fine-tuned by environmental factors—determine success or failure of alien and native plants in temperate grasslands.

Functionalized Adamantane Tectons Used in the Design of Mixed-Ligand Copper(II) 1,2,4-Triazolyl/Carboxylate Metal–Organic Frameworks

Bistriazoles, 1,3-bis(1,2,4-triazol-4-yl)propane (tr2pr) and 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad), were examined in combination with the rigid tetratopic 1,3,5,7-adamantanetetracarboxylic acid (H4-adtc) platform for the construction of neutral heteroleptic copper(II) metal−organic frameworks. Two coordination polymers, [{Cu4(OH)2(H2O)2}{Cu4(OH)2}(tr2pr)2(H-adtc)4]·2H2O (1) and [Cu4(OH)2(tr2ad)2(H-adtc)2(H2O)2]·3H2O (2), were synthesized and structurally characterized. In complexes 1 and 2, the N1,N2-1,2,4-triazolyl (tr) and μ3-OH− groups serve as complementary bridges between adjacent metal centers supporting the tetranuclear dihydroxo clusters. The structure of 1 represents a unique association of two different kinds of centrosymmetrical {Cu4(OH)2} units in a tight 3D framework, while in compound 2, another configuration type of acentric tetranuclear metal clusters is organized in a layered 3,6-hexagonal motif. In both cases, the {Cu4(OH)2} secondary building block and trideprotonated carboxylate H-adtc3− can be viewed as covalently bound six- and three-connected nodes that define the net topology. The tr ligands, showing μ3- or μ4-binding patterns, introduce additional integrating links between the neighboring {Cu4(OH)2} fragments. A variable-temperature magnetic susceptibility study of 2 demonstrates strong antiferromagnetic intracluster coupling (J1 = −109 cm−1 and J2 = −21 cm−1), which combines for the bulk phase with a weak antiferromagnetic intercluster interaction (zj = −2.5 cm−1).