Increased parasite resistance and recurrent airway obstruction in horses of a high-prevalence family

BACKGROUND: Equine recurrent airway obstruction (RAO) shares many characteristics with human asthma. In humans, an inverse relationship between susceptibility to asthma and resistance to parasites is suspected. HYPOTHESIS/OBJECTIVES: Members of a high-incidence RAO half-sibling family (F) shed fewer strongylid eggs compared with RAO-unaffected pasture mates (PM) and that RAO-affected horses shed fewer eggs than RAO-unaffected half-siblings. ANIMALS: Seventy-three F and 73 unrelated, age matched PM. METHODS: Cases and controls kept under the same management and deworming regime were examined. Each individual was classified as RAO affected or RAO unaffected and fecal samples were collected before and 1-3 weeks and 3 months after deworming. Samples were analyzed by combined sedimentation-flotation and modified McMaster methods and classified into 3 categories of 0 eggs per gram of feces (EpG), 1-100 EpG, and > 100 EpG, respectively. RESULTS: PM compared with RAO-affected F had a 16.7 (95% confidence interval [CI]: 2.0-136.3) times higher risk for shedding > 100 EpG compared with 0 EpG and a 5.3 (95% CI: 1.0-27.4) times higher risk for shedding > 100 EpG compared with 0 EpG. There was no significant effect when RAO-unaffected F were compared with their PM. RAO-unaffected compared with RAO-affected offspring had a 5.8 (95% CI: 0.0-1.0) times higher risk for shedding 1-100 EpG. Age, sex, breed, and sharing pastures with other species had no significant confounding effects. CONCLUSION AND CLINICAL IMPORTANCE: RAO is associated with resistance against strongylid parasites in a high-prevalence family.

Five-year results of cervical disc prostheses in the SWISSspine registry

BACKGROUND: The Swiss Federal Office of Public Health demanded a nationwide HTA-registry for cervical total disc arthroplasty (TDA), to decide about its reimbursement. The goal of the SWISSspine registry is to generate evidence about the safety and efficiency of cervical TDA. MATERIALS AND METHODS: Three hundred thirty-two cases treated between 3.2005 and 6.2006 who were eligible for 5 years follow-ups were included in the study. Follow-up rates for 3-6 months, 1, 2 and 5 years were 84.6, 74.4, 50.6 and 64.8 %, respectively. Outcome measures were neck and arm pain, medication, quality of life, intraoperative and postoperative complication and revision rates. In addition, segmental mobility, ossification, adjacent and distant segment degeneration were analyzed at the 5-year follow-up. RESULTS: There was significant, clinically relevant and lasting reduction of neck (preop/postop 60/21 VAS points) and arm pain (preop/postop VAS 67/17) and a consequently decreased analgesics consumption and quality of life improvement (preop/postop 0.39/0.82 EQ-5D points) until the 5-year follow-up. The rates for intraoperative and early postoperative complications were 0.6 and 7.2 %, respectively. In 0.6 % an early and in 3.9 % a late revision surgery was performed. At the 5-year follow-up, the average range of motion of the mobile segments (88.2 %) was 10.2°. In 40.7 % of the patients osteophytes at least potentially affecting range of motion were seen. CONCLUSIONS: Cervical TDA appeared as safe and efficient in long-term pain alleviation, consequent reduction of pain killer consumption and in improvement of quality of life. The improvement is stable over the 5 years postoperative period. The vast majority of treated segments remained mobile after 5 years, although 40.7 % of patients showed osteophytes.

The Unintended Consequences of Requiring a Licence to Help

Comments that current proposals for licensure, accreditation, and 3rd-party reimbursement may have several unintended consequences. Until now discussion has focused on the effects of the proposed regulations on the development of psychology as a profession. Recent proposals, however, may have unexpected adverse consequences on 3 other areas as well: the education of professionals within psychology, the delivery of psychological and other helping services, and the self-definition of the consumer of psychological services. Any changes in licensure, accreditation, and reimbursement require compromises of concerns for the profession, for the consumer, and for psychologists' livelihood.

Periodic breathing during ascent to extreme altitude quantified by spectral analysis of the respiratory volume signal

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Extent and structure of health insurance expenditures for complementary and alternative medicine in Swiss primary care

BACKGROUND: The study is part of a nationwide evaluation of complementary and alternative medicine (CAM) in primary care in Switzerland. The goal was to evaluate the extent and structure of basic health insurance expenditures for complementary and alternative medicine in Swiss primary care. METHODS: The study was designed as a cross-sectional evaluation of Swiss primary care providers and included 262 certified CAM physicians, 151 noncertified CAM physicians and 172 conventional physicians. The study was based on data from a mailed questionnaire and on reimbursement information obtained from health insurers. It was therefore purely observational, without interference into diagnostic and therapeutic procedures applied or prescribed by physicians. Main outcome measures included average reimbursed costs per patient, structured into consultation- and medication-related costs, and referred costs. RESULTS: Total average reimbursed cost per patient did not differ between CAM physicians and conventional practitioners, but considerable differences were observed in cost structure. The proportions of reimbursed costs for consultation time were 56% for certified CAM, 41% for noncertified CAM physicians and 40% for conventional physicians; medication costs--including expenditures for prescriptions and directly dispensed drugs--respectively accounted for 35%, 18%, and 51% of costs. CONCLUSION: The results indicate no significant difference for overall treatment cost per patient between CAM and COM primary care in Switzerland. However, CAM physicians treat lower numbers of patients and a more cost-favourable patient population than conventional physicians. Differences in cost structure reflect more patient-centred and individualized treatment modalities of CAM physicians.

Molecular characterisation of BSR4, a novel bradyzoite-specific gene from Neospora caninum

Here we present the identification and cloning of the NcBSR4 gene, the putative Neospora caninum orthologue to the Toxoplasma gondii TgBSR4 gene. To isolate NcBSR4, genome walking PCR was performed on N. caninum genomic DNA using the expressed sequence tag NcEST3c28h02.y1 sequence, which shares a 44% identity with the TgBSR4 gene, as a framework. Nucleotide sequencing of amplified DNA fragments revealed a single uninterrupted 1227 bp open reading frame that encodes a protein of 408 amino acids with 66% similarity to the TgBSR4 antigen. A putative 39-residue signal peptide was found at the NH2-terminus, followed by a hydrophilic region. At the COOH-terminus, a potential site for a glycosylphosphatidylinositol anchor was identified at amino acid 379. A polyclonal serum against recombinant NcBSR4 protein was raised in rabbits, and immunolabelling demonstrated stage-specific expression of the NcBSR4 antigen in N. caninum bradyzoites produced in vitro and in vivo. Furthermore, RT-PCR analysis showed a slight increase of NcBSR4 transcripts in bradyzoites generated during in vitro tachyzoite-to-bradyzoite stage-conversion, suggesting that this gene is specifically expressed at the bradyzoite stage and that its transcription relies on the switch to this stage.

Antibiotic-dependent correlation between drug-induced killing and loss of luminescence in Streptococcus gordonii expressing luciferase

Measuring antibiotic-induced killing relies on time-consuming biological tests. The firefly luciferase gene (luc) was successfully used as a reporter gene to assess antibiotic efficacy rapidly in slow-growing Mycobacterium tuberculosis. We tested whether luc expression could also provide a rapid evaluation of bactericidal drugs in Streptococcus gordonii. The suicide vectors pFW5luc and a modified version of pJDC9 carrying a promoterless luc gene were used to construct transcriptional-fusion mutants. One mutant susceptible to penicillin-induced killing (LMI2) and three penicillin-tolerant derivatives (LMI103, LMI104, and LMI105) producing luciferase under independent streptococcal promoters were tested. The correlation between antibiotic-induced killing and luminescence was determined with mechanistically unrelated drugs. Chloramphenicol (20 times the MIC) inhibited bacterial growth. In parallel, luciferase stopped increasing and remained stable, as determined by luminescence and Western blots. Ciprofloxacin (200 times the MIC) rapidly killed 1.5 log10 CFU/ml in 2-4 hr. Luminescence decreased simultaneously by 10-fold. In contrast, penicillin (200 times the MIC) gave discordant results. Although killing was slow (< or = 0.5 log10 CFU/ml in 2 hr), luminescence dropped abruptly by 50-100-times in the same time. Inactivating penicillin with penicillinase restored luminescence, irrespective of viable counts. This was not due to altered luciferase expression or stability, suggesting some kind of post-translational modification. Luciferase shares homology with aminoacyl-tRNA synthetase and acyl-CoA ligase, which might be regulated by macromolecule synthesis and hence affected in penicillin-inhibited cells. Because of resemblance, luciferase might be down-regulated simultaneously. Luminescence cannot be universally used to predict antibiotic-induced killing. Thus, introducing reporter enzymes sharing mechanistic similarities with normal metabolic reactions might reveal other effects than those expected.

Looking at the effectiveness of an earth science unit designed using the Understanding by Design process

This report shares my efforts in developing a solid unit of instruction that has a clear focus on student outcomes. I have been a teacher for 20 years and have been writing and revising curricula for much of that time. However, most has been developed without the benefit of current research on how students learn and did not focus on what and how students are learning. My journey as a teacher has involved a lot of trial and error. My traditional method of teaching is to look at the benchmarks (now content expectations) to see what needs to be covered. My unit consists of having students read the appropriate sections in the textbook, complete work sheets, watch a video, and take some notes. I try to include at least one hands-on activity, one or more quizzes, and the traditional end-of-unit test consisting mostly of multiple choice questions I find in the textbook. I try to be engaging, make the lessons fun, and hope that at the end of the unit my students get whatever concepts I‘ve presented so that we can move on to the next topic. I want to increase students‘ understanding of science concepts and their ability to connect understanding to the real-world. However, sometimes I feel that my lessons are missing something. For a long time I have wanted to develop a unit of instruction that I know is an effective tool for the teaching and learning of science. In this report, I describe my efforts to reform my curricula using the “Understanding by Design” process. I want to see if this style of curriculum design will help me be a more effective teacher and if it will lead to an increase in student learning. My hypothesis is that this new (for me) approach to teaching will lead to increased understanding of science concepts among students because it is based on purposefully thinking about learning targets based on “big ideas” in science. For my reformed curricula I incorporate lessons from several outstanding programs I‘ve been involved with including EpiCenter (Purdue University), Incorporated Research Institutions for Seismology (IRIS), the Master of Science Program in Applied Science Education at Michigan Technological University, and the Michigan Association for Computer Users in Learning (MACUL). In this report, I present the methodology on how I developed a new unit of instruction based on the Understanding by Design process. I present several lessons and learning plans I‘ve developed for the unit that follow the 5E Learning Cycle as appendices at the end of this report. I also include the results of pilot testing of one of lessons. Although the lesson I pilot-tested was not as successful in increasing student learning outcomes as I had anticipated, the development process I followed was helpful in that it required me to focus on important concepts. Conducting the pilot test was also helpful to me because it led me to identify ways in which I could improve upon the lesson in the future.

The Problematic of Privacy in the Namespace

In the twenty-first century, the issue of privacy--particularly the privacy of individuals with regard to their personal information and effects--has become highly contested terrain, producing a crisis that affects both national and global social formations. This crisis, or problematic, characterizes a particular historical conjuncture I term the namespace. Using cultural studies and the theory of articulation, I map the emergent ways that the namespace articulates economic, juridical, political, cultural, and technological forces, materials, practices and protocols. The cohesive articulation of the namespace requires that privacy be reframed in ways that make its diminution seem natural and inevitable. In the popular media, privacy is often depicted as the price we pay as citizens and consumers for security and convenience, respectively. This discursive ideological shift supports and underwrites the interests of state and corporate actors who leverage the ubiquitous network of digitally connected devices to engender a new regime of informational surveillance, or dataveillance. The widespread practice of dataveillance represents a strengthening of the hegemonic relations between these actors--each shares an interest in promoting an emerging surveillance society, a burgeoning security politics, and a growing information economy--that further empowers them to capture and store the personal information of citizens/consumers. In characterizing these shifts and the resulting crisis, I also identify points of articulation vulnerable to rearticulation and suggest strategies for transforming the namespace in ways that might empower stronger protections for privacy and related civil rights.

Razor Thin Win: The 1972 Constitution Ballot, Campaign, Ratification & the Courts -- Mae Nan (Robinson) Ellingson & Mick McKeon “In the Crucible of Change”

Beyond the challenge of crafting a new state Constitution that empowered the people and modernized and opened up state and local government in Montana, the Constitutional Convention delegates, as they signed the final document, looked forward to the arduous task of getting it ratified by the electorate in a short ten week period between the end of the convention on March 24 and the ratification election of June 6, 1972. While all 100 delegates signed the draft Constitution, not all supported its adoption. But the planning about how to get it adopted went back to the actions of the Convention itself, which carefully crafted a ballot that kept “hot political issues” from potentially killing the entire document at the polls. As a result, three side issues were presented to the electorate on the ballot. People could vote for or against those side issues and still vote to ratify the entire document. Thus, the questions of legalizing gambling, having a unicameral legislature and retaining the death penalty were placed separately on the ballot (gambling passed, as did the retention of the death penalty, but the concept of a one-house legislature was defeated). Once the ballot structure was set, delegates who supported the new Constitution organized a grassroots, locally focused effort to secure ratification – thought hampered by a MT Supreme Court decision on April 28 that they could not expend $45,000 in public monies that they had set aside for voter education. They cobbled together about $10,000 of private money and did battle with the established political forces, led by the MT Farm Bureau, MT Stockgrowers’ Assn. and MT Contractors Assn., on the question of passage. Narrow passage of the main document led to an issue over certification and a Montana Supreme Court case challenging the ratification vote. After a 3-2 State Supreme Court victory, supporters of the Constitution then had to defend the election results again before the federal courts, also a successful effort. Montana finally had a new progressive State Constitution that empowered the people, but the path to it was not clear and simple and the win was razor thin. The story of that razor thin win is discussed in this chapter by the two youngest delegates to the 1972 Constitutional Convention, Mae Nan Ellingson of Missoula and Mick McKeon, then of Anaconda. Both recognized “Super Lawyers in their later professional practices were also significant players in the Constitutional Convention itself and actively participated in its campaign for ratification. As such, their recollections of the effort provide an insider’s perspective of the struggle to change Montana for the better through the creation and adoption of a new progressive state Constitution “In the Crucible of Change.” Mae Nan (Robinson) Ellingson was born Mae Nan Windham in Mineral Wells, TX and graduated from Mineral Wells High School in 1965 and Weatherford College in Weatherford, TX in 1967. Mae Nan was the youngest delegate at the 1972 Convention from Missoula. She moved to Missoula in 1967 and received her BA in Political Science with Honors from the University of MT in 1970. She was a young widow known by her late husband’s surname of Robinson while attending UM graduate school under the tutelage of noted Professor Ellis Waldron when he persuaded her to run for the Constitutional Convention. Coming in a surprising second in the delegate competition in Missoula County she was named one of the Convention’s “Ten Outstanding Constitutional Convention Delegates,” an impressive feat at such a young age. She was 24 at the time, the youngest person to serve at the ConCon, and one of 19 women out of 100 delegates. In the decade before the Convention, there were never more than three women Legislators in any session, usually one or two. She was a member of the American Association of University Women, a Pi Sigma Alpha political science honorary, and a Phi Alpha Theta historical honorary. At the Convention, she led proposals for the state's bill of rights, particularly related to equal rights for women. For years, Ellingson kept a copy of the preamble to the Constitution hanging in her office; while all the delegates had a chance to vote on the wording, she and delegate Bob Campbell are credited with the language in the preamble. During the convention, she had an opportunity that opened the door to her later career as an attorney. A convention delegate suggested to her that she should go to law school. Several offered to help, but at the time she couldn't go to school. Her mom had died in Texas, and she ended up with a younger brother and sister to raise in Missoula. She got a job teaching, but about a year later, intrigued with the idea of pursuing the law as a career, she called the man back to ask about the offer. Eventually another delegate, Dave Drum of Billings, sponsored her tuition at the UM School of Law. After receiving her JD with Honors (including the Law Review and Moot Court) from the UM Law School Ellingson worked for the Missoula city attorney's office for six years (1977-83), and she took on landmark projects. During her tenure, Missoula became the first city to issue open space bonds, a project that introduced her to Dorsey & Whitney. The city secured its first easement on Mount Sentinel, and it created the trail along the riverfront with a mix of playing fields and natural vegetation. She also helped develop a sign ordinance for the city of Missoula. She ended up working as bond counsel for Dorsey & Whitney, and she opened up the firm's full-fledged Missoula office after commuting a couple of years to its Great Falls office. She was a partner at Dorsey Whitney, working there from 1983 until her retirement in 2012. The area of law she practiced there is a narrow specialty - it requires knowledge of constitutional law, state and local government law, and a slice of federal tax law - but for Ellingson it meant working on great public projects – schools, sewer systems, libraries, swimming pools, ire trucks. At the state level, she helped form the Montana Municipal Insurance Authority, a pooled insurance group for cities. She's shaped MT’s tax increment law, and she was a fixture in the MT Legislature when they were debating equal rights. As a bond lawyer, though, Ellingson considers her most important work for the state to be setting up the Intercap Program that allowed local governments to borrow money from the state at a low interest rate. She has been a frequent speaker at the League of Cities and Towns, the Montana Association of Counties, and the Rural Water Users Association workshops on topics related to municipal finance, as well as workshops sponsored by the DNRC, the Water and Sewer Agencies Coordination Team, and the Montana State University Local Government Center. In 2002, she received an outstanding service award from the Montana Rural Water Users Association. In addition to being considered an expert on Montana state and constitutional law, local government law and local government finance, she is a frequent teacher at the National Association of Bond Lawyers (NABL) Fundamentals of Municipal Bond Law Seminar and the NABL Bond Attorney’s Workshop. For over 30 years Mae Nan has participated in the drafting of legislation in Montana for state and local finance matters. She has served on the Board of Directors of NABL, as Chairman of its Education Committee, was elected as an initial fellow in 1995 to the American College of Bond Counsel, and was recognized as a Super Lawyer in the Rocky Mountain West. Mae Nan was admitted to practice before the MT and US Supreme Courts, was named one of “America’s Leading Business Lawyers” by Chambers USA (Rank 1), a Mountain States Super Lawyer in 2007 and is listed in Best Lawyers in America; she is a member and former Board Member of NABL, a Fellow of the American College of Bond Counsel and a member of the Board of Visitors of the UM Law School. Mae Nan is also a philanthropist who serves on boards and applies her intelligence to many organizations, such as the Missoula Art Museum. [Much of this biography was drawn from a retirement story in the Missoulian and the Dorsey Whitney web site.] Mick McKeon, born in Anaconda in 1946, is a 4th generation Montanan whose family roots in this state go back to the 1870’s. In 1968 he graduated from Notre Dame with a BA in Communications and received a Juris Doctorate degree from the University of Montana Law School in 1971. Right after graduating from law school, Mick was persuaded by his father, longtime State Senator Luke McKeon, and his uncle, Phillips County Attorney Willis McKeon, to run for delegate to Montana’s Constitutional Convention and was elected to represent Deer Lodge, Philipsburg, Powell, and part of Missoula Counties. Along with a coalition of delegates from Butte and Anaconda, he fought through the new Constitution to eliminate the legal strangle hold, often called “the copper collar,” that corporate interests -- the Anaconda Company and its business & political allies -- had over state government for nearly 100 years. The New York Times called Montana’s Constitutional Convention a “prairie revolution.” After helping secure the ratification of the new Constitution, Mick began his practice of law in Anaconda where he engaged in general practice for nearly 20 years. Moving to Butte in 1991, Mick focused has practice in personal injury law, representing victims of negligence and corporate wrongdoing in both Montana district courts and federal court. As such, he participated in some of the largest cases in the history of the state. In 1992 he and his then law partner Rick Anderson obtained a federal court verdict of $11.5 million -- the largest verdict in MT for many years. Mick’s efforts on behalf of injured victims have been recognized by many legal organizations and societies. Recently, Mick was invited to become a member of the International Academy of Trial Lawyers - 600 of the top lawyers in the world. Rated as an American Super Lawyer, he has continuously been named one of the Best Lawyers in America, and an International Assn. of Trial Lawyers top 100 Trial Lawyer. In 2005, he was placed as one of Montana’s top 4 Plaintiff’s lawyers by Law Dragon. Mick is certified as a civil trial specialist by the National Board of Trial Advocacy and has the highest rating possible from Martindale-Hubble. Mick was awarded the Montana Trial Lawyers Public Service Award and provided pro bono assistance to needy clients for his entire career. Mick’s law practice, which he now shares with his son Michael, is limited to representing individuals who have been injured in accidents, concentrating on cases against insurance companies, corporations, medical providers and hospitals. Mick resides in Butte with his wife Carol, a Butte native. Mick, Carol, Michael and another son, Matthew, who graduated from Dartmouth College and was recently admitted to the Montana bar, enjoy as much of their time together in Butte and at their place on Flathead Lake.

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

The CopA copper ATPase of Enterococcus hirae belongs to the family of heavy metal pumping CPx-type ATPases and shares 43% sequence similarity with the human Menkes and Wilson copper ATPases. Due to a lack of suitable protein crystals, only partial three-dimensional structures have so far been obtained for this family of ion pumps. We present a structural model of CopA derived by combining topological information obtained by intramolecular cross-linking with molecular modeling. Purified CopA was cross-linked with different bivalent reagents, followed by tryptic digestion and identification of cross-linked peptides by mass spectrometry. The structural proximity of tryptic fragments provided information about the structural arrangement of the hydrophilic protein domains, which was integrated into a three-dimensional model of CopA. Comparative modeling of CopA was guided by the sequence similarity to the calcium ATPase of the sarcoplasmic reticulum, Serca1, for which detailed structures are available. In addition, known partial structures of CPx-ATPase homologous to CopA were used as modeling templates. A docking approach was used to predict the orientation of the heavy metal binding domain of CopA relative to the core structure, which was verified by distance constraints derived from cross-links. The overall structural model of CopA resembles the Serca1 structure, but reveals distinctive features of CPx-type ATPases. A prominent feature is the positioning of the heavy metal binding domain. It features an orientation of the Cu binding ligands which is appropriate for the interaction with Cu-loaded metallochaperones in solution. Moreover, a novel model of the architecture of the intramembranous Cu binding sites could be derived.

Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain

BACKGROUND: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006). RESULTS: We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1. CONCLUSION: The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

An economic assessment of drought effects on three grassland systems in Switzerland

This paper analyzes the economic impacts of summer drought on Swiss grassland production. We combine field trial data from drought experiments in three different grasslands in Switzerland with site-specific information on economic costs and benefits. The analysis focuses on the economic implications of drought effects on grassland yields as well as grassland composition. In agreement with earlier studies, we found rather heterogeneous yield effects of drought on Swiss grassland systems, with significantly reduced yields as a response to drought at the lowland and sub-alpine sites, but increased yields at the wetter pre-alpine site. Relative yield losses were highest at the sub-alpine site (with annual yield losses of up to 37 %). However, because income from grassland production at extensive sites relies to a large extent on ecological direct payments, even large yield losses had only limited implications in terms of relative profit reductions. In contrast, negative drought impacts at the most productive, intensively managed lowland site were dominant, with average annual drought-induced profit margin reductions of about 28 %. This is furthermore emphasized if analyzing the farm level perspective of drought impacts. Combining site-specific effects at the farm level, we found that in particular farms with high shares of lowland grassland sites suffer from summer droughts in terms of farm-level fodder production and profit margins. Moreover, our results showed that the higher competitiveness of weeds (broad-leaved dock) under drought conditions will require increasing attention on weed control measures in future grassland production systems. Taking into account that the risk of drought occurrence is expected to increase in the coming years, additional instruments to cope with drought risks in fodder production and finally farmers’ income have to be developed.

Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma

BACKGROUND Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data. METHODS Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. RESULTS Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05). CONCLUSIONS Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.