bluuebunny/crossref_metadata_2025 huggingface dataset:
Fifth Metatarsal Jones Fracture Fixation with a 4.5-mm Cannulated Stainless Steel Screw in the Competitive and Recreational Athlete
Authors: Porter David A. , Duncan Melissa , Meyer Susan J. F.
Published: February 2005

Background

Fifth metatarsal Jones fractures are common in the athletic population. Optimal screw selection for operative treatment has not been determined.

Hypothesis

A 4.5-mm cannulated screw used for fixation of the fifth metatarsal Jones fractures in athletes is an effective treatment approach.

Study Design

Case series; Level of evidence, 4.

Methods

The authors studied 23 consecutive athletes (24 feet) who were treated surgically with a 4.5-mm cannulated screw for fifth metatarsal fractures (Jones fracture) with clinical and radiographic assessments.

Results

There have been no refractures to date. Clinical healing was 100%. The mean percentage healing as shown on radiographs was 98.9%, with a range of 90% to 100%. All athletes returned to sport at a mean time of 7.5 weeks (range, 10 days to 12 weeks). Two athletes experienced a “reinjury” without need for operative treatment. All athletes were recommended to wear orthoses until their competitive careers were completed.

Conclusion

Fixation with a stainless steel 4.5-mm cannulated screw gives 100% clinical healing and near-100% healing as shown on radiographs.

Clinical Relevance

The 4.5-mm cannulated screws can yield reliable and effective healing as evidenced by clinical assessment and radiographs of fifth metatarsal Jones fractures in athletes.
Varying Femoral Tunnels between the Anatomical Footprint and Isometric Positions
Authors: Musahl Volker , Plakseychuk Anton , Vanscyoc Andrew , Sasaki Tomoyuki , Debski Richard E. , Mcmahon Patrick J. , Fu Freddie H.
Published: February 2005

Background

Knee kinematics and in situ forces resulting from anterior cruciate ligament reconstructions with 2 femoral tunnel positions were evaluated.

Hypothesis

A graft placed inside the anatomical footprint of the anterior cruciate ligament will restore knee function better than a graft placed at a position for best graft isometry.

Study Design

Controlled laboratory study.

Methods

Ten cadaveric knees were tested in response to a 134-N anterior load and a combined 10-N·m valgus and 5-N·m internal rotation load. A robotic universal force-moment sensor testing system was used to apply loads, and resulting kinematics were recorded. An active surgical robot system was used for positioning tunnels in 2 locations in the femoral notch: inside the anatomical footprint of the anterior cruciate ligament and a position for best graft isometry. The same quadrupled hamstring tendon graft was used for both tunnel positions. The 2 loading conditions were applied.

Results

At 30° of knee flexion, anterior tibial translation in response to the anterior load for the intact knee was 9.8 ± 3.1 mm. Both femoral tunnel positions resulted in significantly higher anterior tibial translation (position 1: 13.8 ± 4.6 mm; position 2: 16.6 ± 3.7 mm; P <. 05). There was a significant difference between the 2 tunnel positions. At the same flexion angle, the anterior tibial translation in response to the combined load for the intact knee was 7.7 ± 4.0 mm. Both femoral tunnel positions resulted in significantly higher anterior tibial translation (position 1: 10.4 ± 5.5 mm; position 2: 12.0 ± 5.2 mm; P <. 05), with a significant difference between the tunnel positions.

Conclusion

Neither femoral tunnel position restores normal kinematics of the intact knee. A femoral tunnel position inside the anatomical footprint of the anterior cruciate ligament results in knee kinematics closer to the intact knee than does a tunnel position located for best graft isometry.

Clinical Relevance

Anatomical femoral tunnel position is important in reproducing function of the anterior cruciate ligament.
Assessment of Environmental Kuznets Curves and Socioeconomic Drivers in IPCC’s SRES Scenarios
Authors: Fonkych Kateryna , Lempert Robert
Published: February 2005

The Special Report on Emissions Scenarios (SRES) produced families of 21st century greenhouse gas (GHG) emissions trajectories that aim to be consistent with current knowledge and span a wide range of plausible futures. This study performs a standard econometric analysis on the simulation model outputs from six SRES scenarios to assess the extent to which the projected CO2 and NOx emissions reflect Environmental Kuznets Curve (EKC) behavior. Consistent with the empirical literature, which offers little consensus on the predictive value of the EKC hypothesis, our analysis finds that some SRES scenarios exhibit EKC behavior while others do not. Those showing EKC behavior have turning points—per captia income levels separating rising and falling emissions—similar to those found in empirical studies. Overall, this analysis supports the SRES scenarios as generally consistent with and spanning a wide range of different interpretations found in the EKC literature.
An Environmental Kuznets Curve Analysis of U.S. State-Level Carbon Dioxide Emissions
Authors: Aldy Joseph E.
Published: February 2005

Most environmental Kuznets curve (EKC) theories do not apply to carbon dioxide (CO2 )—an unregulated, invisible, odorless gas with no direct human health effects. This analysis addresses the hypothesis that the income-CO2 relationship reflects changes in the composition of an economy as it develops and the associated role of trade in an emissions-intensive good (e.g., electricity). To test this hypothesis, I use a novel data set of 1960 to 1999 state-level CO2 emissions to estimate pretrade (production-based) CO2 EKCs and posttrade (consumption-based) CO2 EKCs. Based on the first EKC analysis of CO2 emissions in the United States, I find that consumption-based EKCs peak at significantly higher incomes than production-based EKCs, suggesting that emissions-intensive trade drives, at least in part, the income-emissions relationship. I have also investigated the robustness of the estimated income-CO2 relationship through a variety of specifications. Estimated EKCs appear to vary by state, and the estimated income-emissions relationships could be spurious for some states with nonstationary income and emissions data. Finally, I find that cold winters, warm summers, and historic coal endowments are positively associated with states’ CO2 emissions.
Probabilistic Modeling of Sulfur and Nitrogen Pollution Controls and Their Relations With Income
Authors: Pepper W. , Sankovski A. , Leggett J.
Published: February 2005

The objective of this article is to evaluate (via modeling) the impact of different pollution control scenarios on the shape of the income-emissions relationship. The simulation of emissions and emission controls was conducted using the Climate Change Risk Assessment Framework, which projects SO2 and NOx emissions from energy consumption and conversion and non-energy sources. The analysis of resulting scenario-, region-, and gas-specific income-emission curves suggests that income alone as a model driver of future emissions cannot adequately capture all plausible future SO2 or NOx emission pathways, or important differences among regions in those trajectories. Future social choices regarding the degree and strategy for environmental protection introduce large uncertainties in future projections and result in differing relationships between income and emissions. The analysis also suggests that the inverted-U shape (hypothesized Environmental Kuznets Curve) is only one of several plausible forms of the future relationship between income and emissions.
Faster, Sooner, and More Simultaneously: How Recent Road and Air Transportation CO₂ Emission Trends in Developing Countries Differ From Historic Trends in the United States
Authors: Marcotullio Peter J. , Williams Eric , Marshall Julian D.
Published: February 2005

This article explores historic carbon dioxide (CO2 ) emission trends from road and air transportation of the United States and 26 developing and industrializing nations. It is argued that environmental trends in the newest industrializing countries do not follow the more sequential and long-term shifts experienced by the United States. The empirical analysis demonstrates that all rapidly developing countries analyzed exhibit comparable transportation CO2 emissions per capita levels at lower levels of income per capita, or sooner, than the United States. For some developing countries (the most rapidly growing), these emissions also grow faster over time. Last, there is clear evidence that emissions from road and air sources are occurring more simultaneously compared to the United States. This pattern of changes is in contrast with the common interpretation of environmental Kuznets curves, which suggest that countries follow similar patterns of environmental impacts over time as they develop economically.
Deforestation and Forest-Induced Carbon Dioxide Emissions in Tropical Countries: How Do Governance and Trade Openness Affect the Forest-Income Relationship?
Authors: López Ramón , Galinato Gregmar I.
Published: February 2005

The objective of this article is to study the implications of changes in land use induced by economic growth, economy-wide policies, and governance on deforestation and forest-induced atmospheric carbon dioxide emissions. Economic growth, democracy, and trade policy explain an important share of the variation in two key determinants of deforestation: agricultural expansion and road building. The resulting shape of the Environmental Kuznets Curve for forests is influenced by governance as well as trade openness. Trade shifts the forest-income curve up (down) for countries that have a comparative disadvantage (advantage) in the production of crops encroaching on forest areas, such as Brazil and the Philippines (Indonesia and Malaysia). Amore democratic country will have a farther turning point than a less democratic country, but whether the Environmental Kuznets Curve shifts up or down is country specific.
Ovol1regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression
Authors: Li Baoan , Nair Mahalakshmi , Mackay Douglas R. , Bilanchone Virginia , Hu Ming , Fallahi Magid , Song Hanqiu , Dai Qian , Cohen Paula E. , Dai Xing
Published: February 2005

Previous studies have shown that a targeted deletion of Ovol1(previously known as movo1), encoding a member of the Ovo family of zinc-finger transcription factors, leads to germ cell degeneration and defective sperm production in adult mice. To explore the cellular and molecular mechanism of Ovol1 function, we have examined the mutant testis phenotype during the first wave of spermatogenesis in juvenile mice. Consistent with the detection of Ovol1 transcripts in pachytene spermatocytes of the meiotic prophase, Ovol1-deficient germ cells were defective in progressing through the pachytene stage. The pachytene arrest was accompanied by an inefficient exit from proliferation, increased apoptosis and an abnormal nuclear localization of the G2-M cell cycle regulator cyclin B1, but was not associated with apparent chromosomal or recombination defects. Transcriptional profiling and northern blot analysis revealed reduced expression of pachytene markers in the mutant, providing molecular evidence that pachytene differentiation was defective. In addition,the expression of Id2 (inhibitor of differentiation 2), a known regulator of spermatogenesis, was upregulated in Ovol1-deficient pachytene spermatocytes and repressed by Ovol1 in reporter assays. Taken together, our studies demonstrate a role for Ovol1 in regulating pachytene progression of male germ cells, and identify Id2 as a Ovol1target.
Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut
Authors: Essner Jeffrey J. , Amack Jeffrey D. , Nyholm Molly K. , Harris Erin B. , Yost H. Joseph
Published: February 2005

Monocilia have been proposed to establish the left-right (LR) body axis in vertebrate embryos by creating a directional fluid flow that triggers asymmetric gene expression. In zebrafish, dorsal forerunner cells (DFCs)express a conserved ciliary dynein gene (left-right dynein-related1, lrdr1) and form a ciliated epithelium inside a fluid-filled organ called Kupffer's vesicle (KV). Here, videomicroscopy demonstrates that cilia inside KV are motile and create a directional fluid flow just prior to the onset of asymmetric gene expression in lateral cells. Laser ablation of DFCs and surgical disruption of KV provide direct evidence that ciliated KV cells are required during early somitogenesis for subsequent LR patterning in the brain, heart and gut. Antisense morpholinos against lrdr1 disrupt KV fluid flow and perturb LR development. Furthermore, lrdr1 morpholinos targeted to DFC/KV cells demonstrate that Lrdr1 functions in these ciliated cells to control LR patterning. This provides the first direct evidence, in any vertebrate, that impairing cilia function in derivatives of the dorsal organizer, and not in other cells that express ciliogenic genes, alters LR development. Finally, genetic analysis reveals novel roles for the T-box transcription factor no tail and the Nodal signaling pathway as upstream regulators of lrdr1 expression and KV morphogenesis. We propose that KV is a transient embryonic `organ of asymmetry' that directs LR development by establishing a directional fluid flow. These results suggest that cilia are an essential component of a conserved mechanism that controls the transition from bilateral symmetry to LR asymmetry in vertebrates.
thick tassel dwarf1encodes a putative maize ortholog of theArabidopsis CLAVATA1leucine-rich repeat receptor-like kinase
Authors: Bommert Peter , Lunde China , Nardmann Judith , Vollbrecht Erik , Running Mark , Jackson David , Hake Sarah , Werr Wolfgang
Published: February 2005

Development in higher plants depends on the activity of meristems,formative regions that continuously initiate new organs at their flanks. Meristems must maintain a balance between stem cell renewal and organ initiation. In fasciated mutants, organ initiation fails to keep pace with meristem proliferation. The thick tassel dwarf1 (td1)mutation of maize affects both male and female inflorescence development. The female inflorescence, which results in the ear, is fasciated, with extra rows of kernels. The male inflorescence, or tassel, shows an increase in spikelet density. Floral meristems are also affected in td1 mutants; for example, male florets have an increase in stamen number. These results suggest that td1 functions in the inflorescence to limit meristem size. In addition, td1 mutants are slightly shorter than normal siblings,indicating that td1 also plays a role in vegetative development. td1 encodes a leucine-rich repeat receptor-like kinase (LRR-RLK) that is a putative ortholog of the Arabidopsis CLAVATA1 protein. These results complement previous work showing that fasciated ear2 encodes a CLAVATA2-like protein, and suggest that the CLAVATA signaling pathway is conserved in monocots. td1 maps in the vicinity of quantitative trait loci that affect seed row number, spikelet density and plant height. We discuss the possible selection pressures on td1 during maize domestication.
Distinct functions for Bmp signaling in lip and palate fusion in mice
Authors: Liu Wei , Sun Xiaoxia , Braut Alen , Mishina Yuji , Behringer Richard R. , Mina Mina , Martin James F.
Published: February 2005

Previous work suggested that cleft lip with or without cleft palate (CL/P)is genetically distinct from isolated cleft secondary palate (CP). Mutations in the Bmp target gene Msx1 in families with both forms of orofacial clefting has implicated Bmp signaling in both pathways. To dissect the function of Bmp signaling in orofacial clefting, we conditionally inactivated the type 1 Bmp receptor Bmpr1a in the facial primordia, using the Nestin cre transgenic line. Nestin cre; Bmpr1amutants had completely penetrant, bilateral CL/P with arrested tooth formation. The cleft secondary palate of Nestin cre; Bmpr1amutant embryos was associated with diminished cell proliferation in maxillary process mesenchyme and defective anterior posterior patterning. By contrast,we observed elevated apoptosis in the fusing region of the Nestin cre; Bmpr1a mutant medial nasal process. Moreover, conditional inactivation of the Bmp4 gene using the Nestin cretransgenic line resulted in isolated cleft lip. Our data uncover a Bmp4-Bmpr1a genetic pathway that functions in lip fusion, and reveal that Bmp signaling has distinct roles in lip and palate fusion.
Nmycplays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation
Authors: Okubo Tadashi , Knoepfler Paul S. , Eisenman Robert N. , Hogan Brigid L. M.
Published: February 2005

Understanding how lung progenitor cells balance proliferation against differentiation is relevant to clinical disorders such as bronchopulmonary dysplasia of premature babies and lung cancer. Previous studies have established that lung development is severely disrupted in mouse mutants with reduced levels of the proto-oncogene Nmyc, but the precise mechanisms involved have not been explored. We show here that Nmyc expression in the embryonic lung is normally restricted to a distal population of undifferentiated epithelial cells, a high proportion of which are in the S phase of the cell cycle. Overexpression of NmycEGFP in the epithelium under the control of surfactant protein C (Sftpc) regulatory elements expands the domain of S phase cells and upregulates numerous genes associated with growth and metabolism, as shown by transcriptional microarray. In addition, there is marked inhibition of differentiation, coupled with an expanded domain of expression of Sox9 protein, which is also normally restricted to the distal epithelial compartment. By contrast, conditional deletion of Nmyc leads to reduced proliferation, epithelial differentiation and high levels of apoptosis in both epithelium and mesenchyme. Unexpectedly, about 50% of embryos in which only one copy of Nmyc is deleted die perinatally, with similarly abnormal lungs. We propose a model in which Nmyc is essential in the developing lung for maintaining a distal population of undifferentiated, proliferating progenitor cells.
FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis
Authors: Steinberg Zachary , Myers Christopher , Heim Vernon M. , Lathrop Colin A. , Rebustini Ivan T. , Stewart Julian S. , Larsen Melinda , Hoffman Matthew P.
Published: February 2005

Branching morphogenesis of mouse submandibular glands is regulated by multiple growth factors. Here, we report that ex vivo branching of intact submandibular glands decreases when either FGFR2 expression is downregulated or soluble recombinant FGFR2b competes out the endogenous growth factors. However, a combination of neutralizing antibodies to FGF1, FGF7 and FGF10 is required to inhibit branching in the intact gland, suggesting that multiple FGF isoforms are required for branching. Exogenous FGFs added to submandibular epithelial rudiments cultured without mesenchyme induce distinct morphologies. FGF7 induces epithelial budding, whereas FGF10 induces duct elongation, and both are inhibited by FGFR or ERK1/2 signaling inhibitors. However, a PI3-kinase inhibitor also decreases FGF7-mediated epithelial budding, suggesting that multiple signaling pathways exist. We immunolocalized FGF receptors and analyzed changes in FGFR, FGF and MMP gene expression to identify the mechanisms of FGF-mediated morphogenesis. FGFR1b and FGFR2b are present throughout the epithelium,although FGFR1b is more highly expressed around the periphery of the buds and the duct tips. FGF7 signaling increases FGFR1b and FGF1expression, and MMP2 activity, when compared with FGF10, resulting in increased cell proliferation and expansion of the epithelial bud, whereas FGF10 stimulates localized proliferation at the tip of the duct. FGF7- and FGF10-mediated morphogenesis is inhibited by an MMP inhibitor and a neutralizing antibody to FGF1, suggesting that both FGF1 and MMPs are essential downstream mediators of epithelial morphogenesis. Taken together,our data suggests that FGFR2b signaling involves a regulatory network of FGFR1b/FGF1/MMP2 expression that mediates budding and duct elongation during branching morphogenesis.
Vulva morphogenesis involves attraction of plexin 1-expressing primordial vulva cells to semaphorin 1a sequentially expressed at the vulva midline
Authors: Dalpé Gratien , Brown Louise , Culotti Joseph G.
Published: February 2005

Vulva development in C. elegans involves cell fate specification followed by a morphogenesis phase in which homologous mirror image pairs within a linear array of primordial vulva cells form a crescent shape as they move sequentially towards a midline position within the array. The homologous pairs from opposite half vulvae in fixed sequence fuse with one another at their leading tips to form ring-shaped (toroidal) cells stacked in precise alignment one atop the other. Here, we show that the semaphorin 1a SMP-1, and its plexin receptor PLX-1, are required for the movement of homologous pairs of vulva cells towards this midline position. SMP-1 is upregulated on the lumen membrane of each primordial vulva cell as it enters the forming vulva and apparently attracts the next flanking homologous PLX-1-expressing vulva cells towards the lumen surface of the ring. Consequently, a new ring-shaped cell forms immediately ventral to the previously formed ring. This smp-1- and plx-1-dependent process repeats until seven rings are stacked along the dorsoventral axis, creating a common vulva lumen. Ectopic expression of SMP-1 suggests it has an instructive role in vulva cell migration. At least two parallel acting pathways are required for vulva formation: one requires SMP-1, PLX-1 and CED-10; and another requires the MIG-2 Rac GTPase and its putative activator UNC-73.
Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system
Authors: Miyasaka Nobuhiko , Sato Yuki , Yeo Sang-Yeob , Hutson Lara D. , Chien Chi-Bin , Okamoto Hitoshi , Yoshihara Yoshihiro
Published: February 2005

Olfactory sensory neurons (OSNs) expressing a given odorant receptor project their axons to specific glomeruli, creating a topographic odor map in the olfactory bulb (OB). The mechanisms underlying axonal pathfinding of OSNs to their precise targets are not fully understood. Here, we demonstrate that Robo2/Slit signaling functions to guide nascent olfactory axons to the OB primordium in zebrafish. robo2 is transiently expressed in the olfactory placode during the initial phase of olfactory axon pathfinding. In the robo2 mutant, astray (ast), early growing olfactory axons misroute ventromedially or posteriorly, and often penetrate into the diencephalon without reaching the OB primordium. Four zebrafish Slit homologs are expressed in regions adjacent to the olfactory axon trajectory,consistent with their role as repulsive ligands for Robo2. Masking of endogenous Slit gradients by ubiquitous misexpression of Slit2 in transgenic fish causes posterior pathfinding errors that resemble the astphenotype. We also found that the spatial arrangement of glomeruli in OB is perturbed in ast adults, suggesting an essential role for the initial olfactory axon scaffold in determining a topographic glomerular map. These data provide functional evidence for Robo2/Slit signaling in the establishment of olfactory neural circuitry in zebrafish.
Patterning of proneuronal and inter-proneuronal domains byhairy- andenhancer of split-related genes in zebrafish neuroectoderm
Authors: Bae Young-Ki , Shimizu Takashi , Hibi Masahiko
Published: February 2005

In teleosts and amphibians, the proneuronal domains, which give rise to primary-motor, primary-inter and Rohon-Beard (RB) neurons, are established at the beginning of neurogenesis as three longitudinal stripes along the anteroposterior axis in the dorsal ectoderm. The proneuronal domains are prefigured by the expression of basic helix-loop-helix (bHLH) proneural genes,and separated by domains (inter-proneuronal domains) that do not express the proneural genes. Little is known about how the formation of these domains is spatially regulated. We have found that the zebrafish hairy- and enhancer of split-related (Her) genes her3 and her9are expressed in the inter-proneuronal domains, and are required for their formation. her3 and her9 expression was not regulated by Notch signaling, but rather controlled by positional cues, in which Bmp signaling is involved. Inhibition of Her3 or Her9 by antisense morpholino oligonucleotides led to ectopic expression of the proneural genes in part of the inter-proneuronal domains. Combined inhibition of Her3 and Her9 induced ubiquitous expression of proneural and neuronal genes in the neural plate, and abolished the formation of the inter-proneuronal domains. Furthermore,inhibition of Her3/Her9 and Notch signaling led to ubiquitous and homogeneous expression of proneural and neuronal genes in the neural plate, revealing that Her3/Her9 and Notch signaling have distinct roles in neurogenesis. These data indicate that her3 and her9 function as prepattern genes that link the positional dorsoventral polarity information in the posterior neuroectoderm to the spatial regulation of neurogenesis.
High Density Lipoproteins (HDL) and the Oxidative Hypothesis of Atherosclerosis
Authors: Bonnefont-Rousselot Dominique , Thérond Patrice , Beaudeux Jean-Louis , Peynet Jacqueline , Le-grand Alain , Delattre Jacques
Published: February 2005

The oxidative hypothesis of atherosclerosis classically implies a central role for low density lipoprotein (LDL) oxidation. However, new antiatherogenic properties have been recognized for high density lipoproteins (HDL), apart from their ability to reverse cholesterol transport. Indeed, native HDL could protect LDL from oxidation, thereby minimizing the deleterious consequences of this process. Several mechanisms have been suggested to explain this protective role. Two HDL-associated enzymes, paraoxonase and PAF-acetylhydrolase, detoxify oxidized phospholipids produced by lipid peroxidation. In addition, HDL could reduce hydroperoxides to their corresponding hydroxides. It has also been suggested that HDL could inhibit oxidized LDL-induced transduction signals. However, in vivo HDL oxidation in the subendothelial space would favor the atherosclerotic process. Indeed, atherogenic properties of these oxidized HDL partly result from some loss of their cholesterol effluxing capacity and from an inactivation of the lecithin-cholesterol acyltransferase, which is a HDL-associated enzyme involved in reverse cholesterol transport. Finally, oxidized HDL could induce cholesterol accumulation in macrophages. Further in-depth investigation is needed to assess these antagonistic effects and their consequences for the atherosclerotic process.
Magnesium in Disease: a Review with Special Emphasis on the Serum Ionized Magnesium
Authors: Sanders Gerard T. , Huijgen Henk J. , Sanders Renata
Published: February 2005

This review deals with the six main clinical situations related to magnesium or one of its fractions, including ionized magnesium: renal disease, hypertension, preeclampsia, diabetes mellitus, cardiac disease, and the administration of therapeutic drugs. Issues addressed are the physiological role of magnesium, eventual changes in its levels, and how these best can be monitored.

In renal disease mostly moderate hypermagnesemia is seen; measuring ionized magnesium offers minimal advantage. In hypertension magnesium might be lowered but its measurement does not seem relevant. In the prediction of severe pre-eclampsia, elevated ionized magnesium concentration may play a role, but no unequivocal picture emerges. Low magnesium in blood may be cause for, or consequence of, diabetes mellitus. No special fraction clearly indicates magnesium deficiency leading to insulin resistance. Cardiac diseases are related to diminished magnesium levels. During myocardial infarction, serum magnesium drops. Total magnesium concentration in cardiac cells can be predicted from levels in sublingual or skeletal muscle cells. Most therapeutic drugs (diuretics, chemotherapeutics, immunosuppressive agents, antibiotics) cause hypomagnesemia due to increased urinary loss.

It is concluded that most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease. Keeping in mind that only 1% of the total body magnesium pool is extracellular, no simple measurement of the real intracellular situation has emerged; measuring ionized magnesium in serum has little added value at present.
Das NPU-System (IFCC, IUPAC) der Messgrößen und Einheiten in der Laboratoriumsmedizin. The NPU coding system (IFCC, IUPAC) for properties and units in the clinical laboratory sciences
Authors: R. Külpmann Wolf
Published: February 2005

Abstract IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) and IUPAC (International Union of Pure and Applied Chemistry) have developed an elaborate system named NPU system (N: nomenclature; P: properties; U: units) to standardize reports of findings in laboratory sciences. The use of the system allows to provide results that are unambiguous, easily understandable and comparable all over the world. For data transfer, all items with regard to system, component, kind of property and unit of a quantity are represented by one number, the NPU code number. The value of the quantity expressed by the NPU code renders unequivocal information on the measured quantity. Currently, the NPU system is available for measurements e.g. in clinical chemistry, haemostaseology, immunohaematology, allergology, toxicology, microbiology, and molecular biology and is steadily being updated. The adoption of the NPU system does not require a change of the conventional individual way by which results of measurements are presented locally.
Kommerzielle Systeme zur Genotypisierung von humanen Immundefizienzviren Typ 1: Vergleich von ViroSeq (Abbott) und TruGene (Bayer). Commercially available assays for genotyping of human immunodeficiency virus type 1: Comparison of ViroSeq (Abbott) and TruGene (Bayer)
Authors: Stürmer Martin , Berger Annemarie , Preiser Wolfgang , Doerr Hans Wilhelm
Published: February 2005

Abstract HIV-1 resistance testing has become an increasingly important feature in antiretroviral treatment and is commonly performed by genotyping. Currently, two different systems are being marketed, and despite being far from easy to use, they have achieved a high degree of quality. Modifications of the standard kit protocols may be advantageous in certain situations. Although resistance reports issued by these systems are based on decision rules, they nevertheless require considerable knowledge and skills by the user to draw useful clinical data out of detected resistance patterns. Both systems described here in detail have their advantages and disadvantages; a decision in favor of one or the other needs to be based on individual requirements. In the future, Microarray systems may achieve a leading position on the market.
A Second-Generation Genetic Linkage Map of Tilapia (Oreochromis spp.)Sequence data from this article have been deposited with the EMBL/GenBank data libraries under accession nos. G68180, G68324 and BV005269, BV005594.
Authors: Lee Bo-Young , Lee Woo-Jai , Streelman J Todd , Carleton Karen L , Howe Aimee E , Hulata Gideon , Slettan Audun , Stern Justin E , Terai Yohey , Kocher Thomas D
Published: February 2005

We constructed a second-generation linkage map of tilapia from the F2 progeny of an interspecific cross between Oreochromis niloticus and Oreochromis aureus. The map reported here contains 525 microsatellite and 21 gene-based markers. It spans 1311 cM in 24 linkage groups, for an average marker spacing of 2.4 cM. We detected associations of sex and red color with markers on linkage group 3. This map will enable mapping and selective breeding of quantitative traits important to the economic culture of tilapia as a food fish and will contribute to the study of closely related cichlids that have undergone explosive adaptive radiation in the lakes of East Africa.
The Zebrafish pob Gene Encodes a Novel Protein Required for Survival of Red Cone Photoreceptor CellsSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession no. AY745978.
Authors: Taylor Michael R , Kikkawa Satoshi , Diez-Juan Antonio , Ramamurthy Visvanathan , Kawakami Koichi , Carmeliet Peter , Brockerhoff Susan E
Published: February 2005

The zebrafish mutant, partial optokinetic response b (pob), was isolated using an N-ethyl N-nitrosourea (ENU)-based screening strategy designed to identify larvae with defective optokinetic responses in red but not white light. Previous studies showed that red-light blindness in pob is due to the specific loss of long-wavelength photoreceptor cells via an apoptotic mechanism. Here, we used positional cloning to identify the mutated pob gene. We find that pob encodes a highly conserved 30-kDa protein of unknown function. To demonstrate that the correct gene was isolated, we used the Tol2 transposon system to generate transgenic animals and rescue the mutant phenotype. The Pob protein contains putative transmembrane regions and protein-sorting signals. It is localized to the inner segment and synapse in photoreceptor cells, and when expressed in COS-7 cells it localizes to intracellular compartments. We also show that the degeneration of red cone photoreceptors in the mutants occurs independently of light. On the basis of our findings, we propose that Pob is not involved in phototransduction but rather plays an essential role in protein sorting and/or trafficking.
Slit-Roundabout Signaling Neutralizes Netrin-Frazzled-Mediated Attractant Cue to Specify the Lateral Positioning of Longitudinal Axon Pathways
Authors: Bhat Krishna Moorthi
Published: February 2005

An extending axon growth cone is subjected to attractant and repellent cues. It is not clear how these growth cones discriminate the two opposing forces and select their projection paths. Here, we report that in the Drosophila nerve cord the growth cones of longitudinal tracts are subjected to attraction by the Netrin-Frazzled pathway. However, the midline Slit neutralizes this pathway in a Robo-dependent manner and prevents Netrin-Frazzled-mediated attraction of longitudinal tracts. Our results suggest that the loss of a neutralizing effect on the Netrin-mediated attraction is responsible for the longitudinal tracts entering the midline in slit mutants as opposed to a loss of repulsion as is currently believed. This effect is not via a direct inhibition of Frazzled by Robo; instead, it is at a level downstream of Frazzled. Thus, the growth cones of longitudinal tracts subjected to two opposing forces are able to block one with the other and specify their correct lateral positioning along the midline.
Mechanisms of Haploinsufficiency Revealed by Genome-Wide Profiling in Yeast
Authors: Deutschbauer Adam M , Jaramillo Daniel F , Proctor Michael , Kumm Jochen , Hillenmeyer Maureen E , Davis Ronald W , Nislow Corey , Giaever Guri
Published: February 2005

Haploinsufficiency is defined as a dominant phenotype in diploid organisms that are heterozygous for a loss-of-function allele. Despite its relevance to human disease, neither the extent of haploinsufficiency nor its precise molecular mechanisms are well understood. We used the complete set of Saccharomyces cerevisiae heterozygous deletion strains to survey the genome for haploinsufficiency via fitness profiling in rich (YPD) and minimal media to identify all genes that confer a haploinsufficient growth defect. This assay revealed that ∼3% of all ∼5900 genes tested are haploinsufficient for growth in YPD. This class of genes is functionally enriched for metabolic processes carried out by molecular complexes such as the ribosome. Much of the haploinsufficiency in YPD is alleviated by slowing the growth rate of each strain in minimal media, suggesting that certain gene products are rate limiting for growth only in YPD. Overall, our results suggest that the primary mechanism of haploinsufficiency in yeast is due to insufficient protein production. We discuss the relevance of our findings in yeast to human haploinsufficiency disorders.
The Snf1 Protein Kinase and Sit4 Protein Phosphatase Have Opposing Functions in Regulating TATA-Binding Protein Association With the Saccharomyces cerevisiae INO1 Promoter
Authors: Shirra Margaret K , Rogers Sarah E , Alexander Diane E , Arndt Karen M
Published: February 2005

To identify the mechanisms by which multiple signaling pathways coordinately affect gene expression, we investigated regulation of the S. cerevisiae INO1 gene. Full activation of INO1 transcription occurs in the absence of inositol and requires the Snf1 protein kinase in addition to other signaling molecules and transcription factors. Here, we present evidence that the Sit4 protein phosphatase negatively regulates INO1 transcription. A mutation in SIT4 was uncovered as a suppressor of the inositol auxotrophy of snf1Δ strains. We found that sit4 mutant strains exhibit an Spt− phenotype, suggesting a more general role for Sit4 in transcription. In fact, like the gene-specific regulators of INO1 transcription, Opi1, Ino2, and Ino4, both Snf1 and Sit4 regulate binding of TBP to the INO1 promoter, as determined by chromatin immunoprecipitation analysis. Experiments involving double-mutant strains indicate that the negative effect of Sit4 on INO1 transcription is unlikely to occur through dephosphorylation of histone H3 or Opi1. Sit4 is a known component of the target of rapamycin (TOR) signaling pathway, and treatment of cells with rapamycin reduces INO1 activation. However, analysis of rapamycin-treated cells suggests that Sit4 represses INO1 transcription through multiple mechanisms, only one of which may involve inhibition of TOR signaling.
Optimizing the Nucleotide Sequence of a Meiotic Recombination Hotspot in Schizosaccharomyces pombe
Authors: Steiner Walter W , Smith Gerald R
Published: February 2005

The ade6-M26 mutation of Schizosaccharomyces pombe created a meiotic recombination hotspot. Previous analyses indicated that the heptamer 5′-ATGACGT-3′ was necessary and sufficient for hotspot activity; the Atf1-Pcr1 transcription factor binds to this sequence and activates M26. After finding cases in which the M26 heptamer in ade6 was, surprisingly, not active as a hotspot, we used an in vitro selection method (SELEX) that revealed an 18-bp consensus sequence for Atf1-Pcr1 binding, 5′-GNVTATGACGTCATNBNC-3′, containing the M26 heptamer at its core. Using this consensus sequence as a guide, we made mutations on each side of the heptamer at two separate sites in ade6. These mutations increased the intracellular hotspot activity of the heptamer, in some cases by >15-fold. These results show that M26, the eukaryotic recombination hotspot with the most precisely defined nucleotide sequence, is larger than previously thought, and they provide valuable information for clarifying the role of M26, and perhaps other hotspots, in meiotic recombination.
Identification of Zebrafish Insertional Mutants With Defects in Visual System Development and Function
Authors: Gross Jeffrey M , Perkins Brian D , Amsterdam Adam , Egaña Ana , Darland Tristan , Matsui Jonathan I , Sciascia Salvatore , Hopkins Nancy , Dowling John E
Published: February 2005

Genetic analysis in zebrafish has been instrumental in identifying genes necessary for visual system development and function. Recently, a large-scale retroviral insertional mutagenesis screen, in which 315 different genes were mutated, that resulted in obvious phenotypic defects by 5 days postfertilization was completed. That the disrupted gene has been identified in each of these mutants provides unique resource through which the formation, function, or physiology of individual organ systems can be studied. To that end, a screen for visual system mutants was performed on 250 of the mutants in this collection, examining each of them histologically for morphological defects in the eye and behaviorally for overall visual system function. Forty loci whose disruption resulted in defects in eye development and/or visual function were identified. The mutants have been divided into the following phenotypic classes that show defects in: (1) morphogenesis, (2) growth and central retinal development, (3) the peripheral marginal zone, (4) retinal lamination, (5) the photoreceptor cell layer, (6) the retinal pigment epithelium, (7) the lens, (8) retinal containment, and (9) behavior. The affected genes in these mutants highlight a diverse set of proteins necessary for the development, maintenance, and function of the vertebrate visual system.
Drosophila Signal Peptide Peptidase Is an Essential Protease for Larval Development
Authors: Casso David J , Tanda Soichi , Biehs Brian , Martoglio Bruno , Kornberg Thomas B
Published: February 2005

We identified the Drosophila melanogaster Signal peptide peptidase gene (Spp) that encodes a multipass transmembrane aspartyl protease. Drosophila SPP is homologous to the human signal peptide peptidase (SPP) and is distantly related to the presenilins. We show that, like human SPP, Drosophila SPP can proteolyze a model signal peptide and is sensitive to an SPP protease inhibitor and that it localizes to the endoplasmic reticulum. Expression of Drosophila SPP was first apparent at germ band extension, and in late embryos it was robust in the salivary glands, proventriculus, and tracheae. Flies bearing mutations in conserved residues or carrying deficiencies for the Spp gene had defective tracheae and died as larvae.
Effect of Recombinant Human Bone Morphogenetic Protein‐4 Dose on Bone Formation in a Rat Calvarial Defect Model
Authors: Pang Eun‐Kyoung , Im Se‐Ung , Kim Chang‐Sung , Choi Seong‐Ho , Chai Jung‐Kiu , Kim Chong‐Kwan , Han Soo‐Boo , Cho Kyoo‐Sung
Published: February 2005

Background: Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein‐4 (rhBMP‐4) dose on local bone formation in a rat calvaria defect model.

Methods: Calvarial, 8 mm diameter, critical‐size osteotomy defects were created in 140 male Sprague‐Dawley rats. Seven groups of 20 animals each received either 1) rhBMP‐4 (2.5 µg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP‐4 (5 µg)/ACS, 3) rhBMP‐4 (2.5 µg) in a β‐tricalcium phosphate (β‐TCP) carrier, 4) rhBMP‐4 (5 µg)/β‐TCP, 5) ACS or 6) β‐TCP carrier controls, or 7) a sham‐surgery control, and were evaluated by histologic and histometric parameters following a 2‐ or 8‐week healing interval (10 animals/group/healing interval).

Results: Surgical implantation of rhBMP‐4/ACS and rhBMP‐ 4/β‐TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP‐4 did not exhibit an appreciable dose‐dependent response. Defect closure was not significantly different between the rhBMP‐4/ACS and rhBMP‐4/β‐TCP groups. New bone area of the rhBMP‐4/ β‐TCP group was significantly greater than that of the rhBMP‐4/ ACS group; however, bone density in the rhBMP‐4/ACS group was significantly greater than that in the rhBMP‐4/β‐TCP group at 8 weeks (P <0.05).

Conclusions: rhBMP‐4 combined with ACS or β‐TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP‐4 dose range and observation interval, there appeared to be no meaningful differences in bone formation. J Periodontol 2004;75:1364‐1370.
Patients' Experience of Pain and Discomfort During Instrumentation in the Diagnosis and Non‐Surgical Treatment of Periodontitis
Authors: van Steenberghe Daniel , Garmyn Peter , Geers Lut , Hendrickx Elke , Maréchal Marina , Huizar Karin , Kristofferson Ann , Meyer‐Rosberg Karin , Vandenhoven Guy
Published: February 2005

Background: The present multicenter study aimed to survey the patients' experiences in relation to the diagnosis and nonsurgical treatment of periodontitis according to current treatment routine.

Methods: Patients (N = 268) treated for plaque‐related periodontitis were enrolled in two groups: group 1 received primary probing of pocket depths (PD 1) and/or primary scaling and root planing (SRP 1); group 2 consisted of patients who were scheduled in the different centers for recall PD/scaling/subgingival instrumentation. Data collection included a full periodontal status, anesthesia employed, procedure time, and patient self‐completed questionnaires to assess their previous and current experience of pain and discomfort during anesthesia and periodontal treatment.

Results: Ninety percent of the patients received infiltration anesthesia during primary SRP, compared to only 2% during recall scaling/instrumentation and none during PD. Many patients (40% in SRP group 1 and 52% in the recall scaling/instrumentation group) were most bothered by the scaling procedure, while others (35% in the primary SRP patients) by the anesthetic injection. Painful experiences during previous primary PD and present SRP were highly correlated (r = 0.6).

Conclusions: From these results, it is evident that subgingival instrumentation causes pain and discomfort, an aspect that should be considered in periodontal therapy. Unfortunately, the use of local infiltration anesthesia to reduce pain is in itself a cause of discomfort. Attractive alternatives for anesthetic applications are much needed. J Periodontol 2004;75:1465‐1470.
Association Between Human Herpesviruses and the Severity of Periodontitis
Authors: Ling Li‐Jane , Ho Chuan‐Chen , Wu Ching‐Yi , Chen Yen‐Ting , Hung Shan‐Ling
Published: February 2005

Background: Herpesviruses may play roles in the development of periodontal diseases. The present study evaluated the relationships between herpesviruses and the severity of periodontitis.

Methods: Periodontal status in terms of gingival inflammation, bleeding on probing, probing depth, and clinical attachment loss of 20 participants was evaluated. The presence of herpes simplex virus (HSV), human cytomegalovirus (HCMV), or Epstein‐Barr virus type 1 (EBV‐1) in six subgingival plaques from each participant was examined by nested‐polymerase chain reaction techniques.

Results: Among the 120 sites examined, the prevalence of HCMV (51.7%) was higher than HSV (30.8%) followed by EBV‐1 (4.2%). The prevalence of HSV or HCMV was significantly higher in the subgroups that had lower plaque index (<1). However, the prevalence of HSV was significantly higher in the subgroup that had higher gingival index (≥2), positive bleeding on probing, deeper probing depth (≥4 mm), or higher clinical attachment loss (≥4 mm). Moreover, the prevalence of EBV‐1 was significantly higher in the subgroup that had higher probing depth (≥4 mm). Coinfection of HSV and HCMV was significantly associated with the sites that had higher gingival index (≥2) or positive bleeding on probing. Coinfection of any two herpesviruses was also associated with higher probing depth (≥4 mm) or higher clinical attachment loss (≥4 mm).

Conclusions: This study demonstrated that HSV is related to the severity of periodontal diseases in terms of clinical attachment loss. Coinfection of any two herpesviruses may also play roles. J Periodontol 2004;75:1479‐1485.