bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Passive Mixing Behavior in a Poly(Dimethylsiloxane) Microfluidic Channel Using Confocal Fluorescence and Raman Microscopy
Authors: Park Taehan , Lee Moonkwon , Choo Jaebum , Kim Yang S. , Lee Eun Kyu , Kim Duck Joong , Lee Sang-Hoon
Published: October 2004

Confocal fluorescence microscopy (CFM) and confocal Raman microscopy (CRM) have been applied to monitor the laminar flow mixing behavior in a poly(dimethylsiloxane) (PDMS) microfluidic channel. Two passive PDMS micromixing devices were fabricated for this purpose: a two-dimensional round-wave channel and a three-dimensional serpentine channel. The microscale laminar flow mixing of ethanol and isopropanol was evaluated using the CFM and CRM at various flow rates. The mixing behavior of confluent streams in the microchannel was assessed by determining the degree of color change in Rhodamine 6G dye on mixing using the CFM. However, it was also possible to quantitatively evaluate the mixing process without employing a fluorescence label using the CRM. The results show a strong potential for CRM as a highly sensitive detection tool to measure fundamental fluid mixing processes and to provide detailed information on chemical changes of non-fluorescent reaction mixtures in a PDMS microfluidic channel.
Rhizomatic cyborgs: hypertextual considerations in a posthuman age
Authors: Calleja Gordon , Schwager Christian
Published: October 2004

Recent work in the theoretical humanities has given increasing importance to what has been termed posthumanism and hypertextuality. For many within the humanities, posthumanism and hypertextuality have become accessible as a result of studies which have interdisciplinarily explored
concerns that have evident implications for the humanities interest in aesthetics, ethics, politics, mind, cognition, identity, subjectivity and language. The work of Donna Haraway, N. Katherine Hayles, Elaine Graham, George P. Landow and others has been at the forefront of these initiatives.
What perhaps needs to be looked at now is the extent to which the interdisciplinary work that has been built up in this new field (which has been called new cultural theory) is a developing episteme, and how it might affect future ways of writing and thinking in the humanities. The paper proposed
attempts to explore how new cultural theory, and especially the digitalist strain in the theoretical humanities, might profitably explore ways of integrating certain key concepts and practices in posthumanism and hypertextuality. Familiarity with the literature of both discourses reveals that
while the two have obvious affinities, these have not always been approached in ways which would allow the conceptuality of one field to productively merge with those of the other. What seems to be particularly pressing is some speculation on how thought itself is reshaped through interaction
with the new modalities of writing and language, and through attunedness to the potentialities of new posthuman ways of being. For this reason, some reflections will be offered on the implications of present and futuristic practices involving Internet culture and cyborg studies.
The end of reading, the beginning of virtual fiction?
Authors: Page Adrian
Published: October 2004

Could it be that what we now call reading may eventually be superseded by virtual reality (VR)? This article asks whether the growing ability within new technologies to place the reader of literature in the position of the chief character in a literary narrative might give rise to an
experience which is more rewarding and informative. Brechtian dramatic theory suggests that a form of engagement with narrative which presents dilemmas directly to the ‘reader’ can lead to deeper insights. The issue of whether a narrative in a VR format might also enable one person
to share the consciousness of another and so transcend the reading experience altogether is explored. Nietzsche’s theory of consciousness is used to illustrate how it might be valid to assert that this new kind of reading from within the narrative might overcome objections to the idea
of the merging of consciousnesses. Intimations of this change in reading are illustrated by reference to the work of experimental theatre groups using new media.
Mapping Dopamine Function in Primates Using Pharmacologic Magnetic Resonance Imaging
Authors: Jenkins Bruce G. , Sanchez-Pernaute Rosario , Brownell Anna-Liisa , Chen Yin-Ching Iris , Isacson Ole
Published: October 2004

Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry in nonhuman primates with high sensitivity and spatial resolution. Seven control cynomolgous monkeys and 10 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied longitudinally using both positron emission tomography (PET) and phMRI. Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative cerebral blood volume (rCBV) in a number of brain regions not described previously, such as parafascicular thalamus, precentral gyrus, and dentate nucleus of the cerebellum. With the high spatial resolution, we were also able to readily identify changes in rCBV in the anterior cingulate, substantia nigra, ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens. Amphetamine induced decreases in rCBV in occipital and posterior parietal cortices. Parkinsonian primates had a prominent loss of response to amphetamine, with relative sparing of the nucleus accumbens and parafascicular thalamus. There was a significant correlation between rCBV loss in the substantia nigra and both PET imaging of dopamine transporters and behavioral measures. Monkeys with partial lesions as defined by 2β-carbomethoxy-3β-(4-fluorophenyl) tropane binding to dopamine transporters showed recruitment of premotor and motor cortex after amphetamine stimulus similar to what has been noted in Parkinson's patients during motor tasks. These data indicate that phMRI is a powerful tool for assessment of dynamic changes associated with normal and dysfunctional DA brain circuitry in primates.
Intrinsic Noise in Cultured Hippocampal Neurons: Experiment and Modeling
Authors: Diba Kamran , Lester Henry A. , Koch Christof
Published: October 2004

Ion channels open and close stochastically. The fluctuation of these channels represents an intrinsic source of noise that affects the input-output properties of the neuron. We combined whole-cell measurements with biophysical modeling to characterize the intrinsic stochastic and electrical properties of single neurons as observed at the soma. We measured current and voltage noise in 18 d postembryonic cultured neurons from the rat hippocampus, at various subthreshold and near-threshold holding potentials in the presence of synaptic blockers. The observed current noise increased with depolarization, as ion channels were activated, and its spectrum demonstrated generalized 1/fbehavior. Exposure to TTX removed a significant contribution from Na+channels to the noise spectrum, particularly at depolarized potentials, and the resulting spectrum was now dominated by a single Lorentzian (1/f2) component. By replacing the intracellular K+with Cs+, we demonstrated that a major portion of the observed noise was attributable to K+channels. We compared the measured power spectral densities to a 1-D cable model of channel fluctuations based on Markov kinetics. We found that a somatic compartment, in combination with a single equivalent cylinder, described the effective geometry from the viewpoint of the soma. Four distinct channel populations were distributed in the membrane and modeled as Lorentzian current noise sources. Using the NEURON simulation program, we summed up the contributions from the spatially distributed current noise sources and calculated the total voltage and current noise. Our quantitative model reproduces important voltage- and frequency-dependent features of the data, accounting for the 1/fbehavior, as well as the effects of various blockers.
TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation
Authors: Sugiuar Takeshi , Bielefeldt Klaus , Gebhart G. F.
Published: October 2004

Using whole-cell patch-clamp methods, we examined the hypothesis that serotonin [5-hydroxytryptamine (5-HT)] receptor activation enhances TRPV1 function in mouse colon sensory neurons in lumbosacral dorsal root ganglia, which were identified by retrograde labeling with DiI (1,1′-dioctadecyl-3,3,3′,3-tetramethlindocarbocyanine methanesulfonate) injected into multiple sites in the wall of the descending colon. 5-HT increased membrane excitability at a temperature below body temperature in response to thermal ramp stimuli in colon sensory neurons from wild-type mice, but not from TRPV1 knock-out mice. 5-HT significantly enhanced capsaicin-, heat-, and proton-evoked currents with an EC50value of 2.2 μm. 5-HT (1 μm) significantly increased capsaicin-evoked (100 nm) and proton-evoked (pH 5.5) currents 1.6- and 4.7-fold, respectively, and significantly decreased the threshold temperature for heat current activation from 42 to 38°C. The enhancement of TRPV1 by 5-HT was significantly attenuated by selective 5-HT2and 5-HT4receptor antagonists, but not by a 5-HT3receptor antagonist. In support, 5-HT2and 5-HT4receptor agonists mimicked the facilitating effects of 5-HT on TRPV1 function. Downstream signaling required G-protein activation and phosphorylation as intracellularly administered GDP-β-S [guanosine 5′-O-(2-thiodiphosphate], protein kinase A inhibitors, and an A-kinase anchoring protein inhibitor significantly blocked serotonergic facilitation of TRPV1 function; 5-HT2receptor-mediated facilitation was also inhibited by a PKC inhibitor. We conclude that the facilitation of TRPV1 by metabotropic 5-HT receptor activation may contribute to hypersensitivity of primary afferent neurons in irritable bowel syndrome patients.
The Effect of Motor Imagery on Spinal Segmental Excitability
Authors: Li Sheng , Kamper Derek G. , Stevens Jennifer A. , Rymer William Z.
Published: October 2004

The purpose of this study was to investigate the effect of motor imagery on spinal segmental excitability by recording the reflex responses to externally applied stretch of the extrinsic finger flexors and extensors during the performance of an imaginary task. Nine young healthy subjects performed a series of imagined flexion-extension movements of the fingers. Muscle stretch was imposed concurrently by applying rotations of the metacarpophalangeal joints at 100, 300, or 500°/sec. Three of the nine tested subjects also generated 0.2 Newton meter voluntary flexion torque in preloading tasks before stretch.

At 300°/sec stretch, electromyogram (EMG) and torque reflex responses, which were observed in the finger flexors in four of nine subjects during motor imagery, were activated at a short latency (38.6 ± 10.6 msec). This latency was similar to that recorded during a stretch of preactivated flexor muscles (34.4 ± 3.6 msec), in which motoneurons are already suprathreshold and in which monosynaptic effects of muscle afferents are likely to be discernable. In a similar manner, for stretches imposed at 500°/sec, responses to stretch of the flexors were observed in all five tested subjects in imaginary flexion tasks at very short latencies (26.4 ± 3.7 msec), again similar to those induced by tendon taps (22.8 ± 1.2 msec). No EMG response was observed at rest during stretches.

These observations support the view that effects must have been mediated by imagery-related subthreshold activation of spinal motoneurons and/or interneurons, rather than by long-latency transcortical reflex responses. We conclude that motor imagery has a potent effect on the excitability of spinal reflex pathways.
Monitoring Neural Activity and [Ca2+] with Genetically Encoded Ca2+Indicators
Authors: Pologruto Thomas A. , Yasuda Ryohei , Svoboda Karel
Published: October 2004

Genetically encoded Ca2+indicators (GECIs) based on fluorescent proteins (XFPs) and Ca2+-binding proteins [like calmodulin (CaM)] have great potential for the study of subcellular Ca2+signaling and for monitoring activity in populations of neurons. However, interpreting GECI fluorescence in terms of neural activity and cytoplasmic-free Ca2+concentration ([Ca2+]) is complicated by the nonlinear interactions between Ca2+binding and GECI fluorescence. We have characterized GECIs in pyramidal neurons in cultured hippocampal brain slices, focusing on indicators based on circularly permuted XFPs [GCaMP (Nakai et al., 2001), Camgaroo2 (Griesbeck et al., 2001), and Inverse Pericam (Nagai et al., 2001)]. Measurements of fluorescence changes evoked by trains of action potentials revealed that GECIs have little sensitivity at low action potential frequencies compared with synthetic [Ca2+] indicators with similar affinities for Ca2+. The sensitivity of GECIs improved for high-frequency trains of action potentials, indicating that GECIs are supralinear indicators of neural activity. Simultaneous measurement of GECI fluorescence and [Ca2+] revealed supralinear relationships. We compared GECI fluorescence saturation with CaM Ca2+-dependent structural transitions. Our data suggest that GCaMP and Camgaroo2 report CaM structural transitions in the presence and absence of CaM-binding peptide, respectively.
Dopamine Modulates Release from Corticostriatal Terminals
Authors: Bamford Nigel S. , Robinson Siobhan , Palmiter Richard D. , Joyce John A. , Moore Cynthia , Meshul Charles K.
Published: October 2004

Normal striatal function is dependent on the availability of synaptic dopamine to modulate neurotransmission. Within the striatum, excitatory inputs from cortical glutamatergic neurons and modulatory inputs from midbrain dopamine neurons converge onto dendritic spines of medium spiny neurons. In addition to dopamine receptors on medium spiny neurons, D2 receptors are also present on corticostriatal terminals, where they act to dampen striatal excitation. To determine the effect of dopamine depletion on corticostriatal activity, we used the styryl dye FM1-43 in combination with multiphoton confocal microscopy in slice preparations from dopamine-deficient (DD) and reserpine-treated mice. The activity-dependent release of FM1-43 out of corticostriatal terminals allows a measure of kinetics quantified by the halftime decay of fluorescence intensity. In DD, reserpine-treated, and control mice, exposure to the D2-like receptor agonist quinpirole revealed modulation of corticostriatal kinetics with depression of FM1-43 destaining. In DD and reserpine-treated mice, quinpirole decreased destaining to a greater extent, and at a lower dose, consistent with hypersensitive corticostriatal D2 receptors. Compared with controls, slices from DD mice did not react to amphetamine or to cocaine with dopamine-releasing striatal stimulation unless the animals were pretreated withl-3,4-dihydroxyphenylalanine (l-dopa). Electron microscopy and immunogold labeling for glutamate terminals within the striatum demonstrated that the observed differences in kinetics of corticostriatal terminals in DD mice were not attributable to aberrant cytoarchitecture or glutamate density. Microdialysis revealed that basal extracellular striatal glutamate was normal in DD mice. These data indicate that dopamine deficiency results in morphologically normal corticostriatal terminals with hypersensitive D2 receptors.
Regulation of Brain Proteolytic Activity Is Necessary for theIn VivoFunction of NMDA Receptors
Authors: Kvajo Mirna , Albrecht Hugo , Meins Marita , Hengst Ulrich , Troncoso Edgardo , Lefort Sandrine , Kiss Jozsef Z. , Petersen Carl C. H. , Monard Denis
Published: October 2004

Serine proteases are considered to be involved in plasticity-related events in the nervous system, but theirin vivotargets and the importance of their control by endogenous inhibitors are still not clarified. Here, we demonstrate the crucial role of a potent serine protease inhibitor, protease nexin-1 (PN-1), in the regulation of activity-dependent brain proteolytic activity and the functioning of sensory pathways. Neuronal activity regulates the expression of PN-1, which in turn controls brain proteolytic activity. In PN-1-/-mice, absence of PN-1 leads to increased brain proteolytic activity, which is correlated with an activity-dependent decrease in the NR1 subunit of the NMDA receptor. Correspondingly, reduced NMDA receptor signaling is detected in their barrel cortex. This is coupled to decreased sensory evoked potentials in the barrel cortex and impaired whisker-dependent sensory motor function. Thus, a tight control of serine protease activity is critical for thein vivofunction of the NMDA receptors and the proper function of sensory pathways.
Cyclin D Does Not Provide Essential Cdk4-Independent Functions in Drosophila
Authors: Emmerich Jan , Meyer Claas A , de la Cruz Aida Flor A , Edgar Bruce A , Lehner Christian F
Published: October 2004

The three mammalian D-type cyclins are thought to promote progression through the G1 phase of the cell cycle as regulatory subunits of cyclin-dependent kinase 4 and 6. In addition, they have been proposed to control the activity of various transcription factors without a partner kinase. Here we describe phenotypic consequences of null mutations in Cyclin D, the single D-type cyclin gene in Drosophila. As previously observed with null mutations in the single Drosophila Cdk4 gene, these mutations do not primarily affect progression through the G1 phase. Moreover, the apparently indistinguishable phenotypes of double (CycD and Cdk4) and single mutants (CycD or Cdk4) argue against major independent functions of Cyclin D and Cdk4. The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver.
Single-Locus Latitudinal Clines and Their Relationship to Temperate Adaptation in Metabolic Genes and Derived Alleles in Drosophila melanogaster
Authors: Sezgin Efe , Duvernell David D , Matzkin Luciano M , Duan Yihao , Zhu Chen-Tseh , Verrelli Brian C , Eanes Walter F
Published: October 2004

We report a study in Drosophila melanogaster of latitudinal clines for 23 SNPs embedded in 13 genes (Pgi, Gapdh1, UGPase, Pglym78, Pglym87, Eno, Men, Gdh, Sod, Pgk, Mdh1, TreS, Treh) representing various metabolic enzymes. Our samples are from 10 populations spanning latitude from southern Florida to northern Vermont. Three new clines with latitude were detected. These are the amino acid polymorphisms in the NAD-dependent glutamate dehydrogenase (Gdh) and trehalase (Treh) genes, and a silent site polymorphism in the UDP-glucose pyrophosphorylase gene (UGPase). The result, when combined with the overall incidence and pattern of reports for six other genes (Adh, Gpdh, Pgm, G6pd, 6Pgd, Hex-C), presents a picture of latitudinal clines in metabolic genes prevalent around the branch point of competing pathways. For six of the seven amino acid polymorphisms showing significant latitudinal clines in North America, the derived allele is the one increasing with latitude, suggesting temperate adaptation. This is consistent with a model of an Afrotropical ancestral species adapting to temperate climates through selection favoring new mutations.
Thiamine Pyrophosphate Biosynthesis and Transport in the Nematode Caenorhabditis elegansSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession no. AY513235.
Authors: de Jong Liesbeth , Meng Yan , Dent Joseph , Hekimi Siegfried
Published: October 2004

Thiamine (vitamin B1) is required in the diet of animals, and thiamine deficiency leads to diseases such as beri-beri and the Wernicke-Korsakoff syndrome. Dietary thiamine (vitamin B1) consists mainly of thiamine pyrophosphate (TPP), which is transformed into thiamine by gastrointestinal phosphatases before absorption. It is believed that TPP itself cannot be transported across plasma membranes in significant amounts. We have identified a partial loss-of-function mutation in the Caenorhabditis elegans gene (tpk-1) that encodes thiamine pyrophosphokinase, which forms TPP from thiamine at the expense of ATP inside cells. The mutation slows physiological rhythms and the phenotype it produces can be rescued by TPP but not thiamine supplementation. tpk-1 functions cell nonautonomously, as the expression of wild-type tpk-1 in one tissue can rescue the function of other tissues that express only mutant tpk-1. These observations indicate that, in contrast to expectation from previous evidence, TPP can be transported across cell membranes. We also find that thiamine supplementation partially rescues the phenotype of partial loss-of-function mutants of the Na/K ATPase, providing genetic evidence that thiamine absorption, and/or redistribution from the absorbing cells, requires the full activity of this enzyme.
ospC Diversity in Borrelia burgdorferi
Authors: Brisson Dustin , Dykhuizen Daniel E
Published: October 2004

The outer surface protein C (ospC) locus of the Lyme disease bacterium, Borrelia burgdorferi, is at least an order of magnitude more variable than other genes in the species. This variation is classified into 22 ospC major groups, 15 of which are found in the northeastern United States. The frequency distributions of ospC within populations suggest that this locus is under balancing selection. In multiple-niche polymorphism, a type of balancing selection, diversity within a population can be maintained when the environment is heterogeneous and no one genotype has the highest fitness in all environments. Genetically different individuals within vertebrate species and different vertebrate species constitute diverse environments for B. burgdorferi. We examined four important host species of B. burgdorferi and found that the strains that infected each species had different sets of ospC major groups. We found no variation among conspecific hosts in the ospC major groups of their infecting strains. These results suggest multiple niches create balancing selection at the ospC locus.
Caenorhabditis elegans atx-2 Promotes Germline Proliferation and the Oocyte FateSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession no. AY571963.
Authors: Maine Eleanor M , Hansen Dave , Springer Deborah , Vought Valarie E
Published: October 2004

In the Caenorhabditis elegans germline, proliferation is induced by Notch-type signaling. Entry of germ cells into meiosis is triggered by activity of the GLD-1 and GLD-2 pathways, which function redundantly to promote meiosis and/or inhibit proliferation. Activation of the germline Notch-type receptor, GLP-1, ultimately inhibits the activities of the GLD-1 and GLD-2 pathways. We previously identified several ego (enhancer of glp-1) genes that promote germline proliferation and interact genetically with the GLP-1 signaling pathway. Here, we show that atx-2 is an ego gene. Our data suggest that ATX-2 is not a positive regulator of the GLP-1 signaling pathway and GLP-1 signaling is not the sole positive regulator of ATX-2 activity. Moreover, our data indicate that GLP-1 must have an additional function, which may be to repress activity of a third meiotic entry pathway that would work in parallel with the GLD-1 and GLD-2 pathways. In addition to its role in proliferation, ATX-2 acts downstream of FOG-2 to promote the female germline fate.
Arabidopsis hapless Mutations Define Essential Gametophytic Functions
Authors: Johnson Mark A , von Besser Kiera , Zhou Qing , Smith Evadne , Aux George , Patton David , Levin Joshua Z , Preuss Daphne
Published: October 2004

In flowering plants, the egg develops within a haploid embryo sac (female gametophyte) that is encased within the pistil. The haploid pollen grain (male gametophyte) extends a pollen tube that carries two sperm cells within its cytoplasm to the embryo sac. This feat requires rapid, precisely guided, and highly polarized growth through, between, and on the surface of the cells of the stigma, style, and ovary. Pollen tube migration depends on a series of long-range signals from diploid female cells as well as a short-range attractant emitted by the embryo sac that guides the final stage of tube growth. We developed a genetic screen in Arabidopsis thaliana that tags mutant pollen with a cell-autonomous marker carried on an insertion element. We found 32 haploid-disrupting (hapless) mutations that define genes required for pollen grain development, pollen tube growth in the stigma and style, or pollen tube growth and guidance in the ovary. We also identified genomic DNA flanking the insertion element for eleven hap mutants and showed that hap1 disrupts AtMago, a gene whose ortholog is important for Drosophila cell polarity.
Mutations in SIN4 and RGR1 Cause Constitutive Expression of MAL Structural Genes in Saccharomyces cerevisiae
Authors: Wang Xin , Michels Corinne A
Published: October 2004

Transcription of the Saccharomyces MAL structural genes is induced 40-fold by maltose and requires the MAL-activator and maltose permease. To identify additional players involved in regulating MAL gene expression, we carried out a genetic selection for MAL constitutive mutants. Strain CMY4000 containing MAL1 and integrated copies of MAL61promoter-HIS3 and MAL61promoter-lacZ reporter genes was used to select constitutive mutants. The 29 recessive mutants fall into at least three complementation groups. Group 1 and group 2 mutants exhibit pleiotropic phenotypes and represent alleles of Mediator component genes RGR1 and SIN4, respectively. The rgr1 and sin4 constitutive phenotype does not require either the MAL-activator or maltose permease, indicating that Mediator represses MAL basal expression. Further genetic analysis demonstrates that RGR1 and SIN4 work in a common pathway and each component of the Mediator Sin4 module plays a distinct role in regulating MAL gene expression. Additionally, the Swi/Snf chromatin-remodeling complex is required for full induction, suggesting a role for chromatin remodeling in the regulation of MAL gene expression. A sin4Δ mutation is unable to suppress the defects in MAL gene expression resulting from loss of the Swi/Snf complex component Snf2p. The role of the Mediator in MAL gene regulation is discussed.
Epigenetic Control of CACTA Transposon Mobility in Arabidopsis thaliana
Authors: Kato Masaomi , Takashima Kazuya , Kakutani Tetsuji
Published: October 2004

Epigenetic mutation, heritable developmental variation not based on a change in nucleotide sequence, is widely reported in plants. However, the developmental and evolutionary significance of such mutations remains enigmatic. On the basis of our studies of the endogenous Arabidopsis transposon CACTA, we propose that the inheritance of epigenetic gene silencing over generations can function as a transgenerational genome defense mechanism against deleterious movement of transposons. We previously reported that silent CACTA1 is mobilized by the DNA hypomethylation mutation ddm1 (decrease in DNA methylation). In this study, we report that CACTA activated by the ddm1 mutation remains mobile in the presence of the wild-type DDM1 gene, suggesting that de novo silencing is not efficient for the defense of the genome against CACTA movement. The defense depends on maintenance of transposon silencing over generations. In addition, we show that the activated CACTA1 element transposes throughout the genome in DDM1 plants, as reported previously for ddm1 backgrounds. Furthermore, the CACTA1 element integrated into both the ddm1-derived and the DDM1-derived chromosomal regions in the DDM1 wild-type plants, demonstrating that this class of transposons does not exhibit targeted integration into heterochromatin, despite its accumulation in the pericentromeric regions in natural populations. The possible contribution of natural selection as a mechanism for the accumulation of transposons and evolution of heterochromatin is discussed.
Enolase and Glycolytic Flux Play a Role in the Regulation of the Glucose Permease Gene RAG1 of Kluyveromyces lactisSequence data from this article have been deposited with the EMBL Data Library under accession no. AJ586240.
Authors: Lemaire Marc , Wésolowski-Louvel Micheline
Published: October 2004

We isolated a mutant, rag17, which is impaired in glucose induction of expression of the major glucose transporter gene RAG1. The RAG17 gene encodes a protein 87% identical to S. cerevisiae enolases (Eno1 and Eno2). The Kleno null mutant showed no detectable enolase enzymatic activity and has severe growth defects on glucose and gluconeogenic carbon sources, indicating that K. lactis has a single enolase gene. In addition to RAG1, the transcription of several glycolytic genes was also strongly reduced in the ΔKleno mutant. Moreover, the defect in RAG1 expression was observed in other mutants of the glycolytic pathway (hexokinase and phosphoglycerate kinase). Therefore, it seems that the enolase and a functional glycolytic flux are necessary for induction of expression of the Rag1 glucose permease in K. lactis.
Multiple Quantitative Trait Loci Mapping With Cofactors and Application of Alternative Variants of the False Discovery Rate in an Enlarged Granddaughter Design
Authors: Bennewitz Jörn , Reinsch Norbert , Guiard Volker , Fritz Sebastien , Thomsen Hauke , Looft Christian , Kühn Christa , Schwerin Manfred , Weimann Christina , Erhardt Georg , Reinhardt Fritz , Reents Reinhard , Boichard Didier , Kalm Ernst
Published: October 2004

The experimental power of a granddaughter design to detect quantitative trait loci (QTL) in dairy cattle is often limited by the availability of progeny-tested sires, by the ignoring of already identified QTL in the statistical analysis, and by the application of stringent experimentwise significance levels. This study describes an experiment that addressed these points. A large granddaughter design was set up that included sires from two countries (Germany and France), resulting in almost 2000 sires. The animals were genotyped for markers on nine different chromosomes. The QTL analysis was done for six traits separately using a multimarker regression that included putative QTL on other chromosomes as cofactors in the model. Different variants of the false discovery rate (FDR) were applied. Two of them accounted for the proportion of truly null hypotheses, which were estimated to be 0.28 and 0.3, respectively, and were therefore tailored to the experiment. A total of 25 QTL could be mapped when cofactors were included in the model—7 more than without cofactors. Controlling the FDR at 0.05 revealed 31 QTL for the two FDR methods that accounted for the proportion of truly null hypotheses. The relatively high power of this study can be attributed to the size of the experiment, to the QTL analysis with cofactors, and to the application of an appropriate FDR.
The Gene Sex-lethal of the Sciaridae Family (Order Diptera, Suborder Nematocera) and Its Phylogeny in Dipteran InsectsSequence data from this article have been deposited with the EMBL/GenBank data libraries under accession nos. AY538250 for Sciara coprophila, AY538251 for Rhynchosciara americana, and AY538252 for Trichosia pubescens.
Authors: Serna Esther , Gorab Eduardo , Ruiz M Fernanda , Goday Clara , Eirín-López José M , Sánchez Lucas
Published: October 2004

This article reports the cloning and characterization of the gene homologous to Sex-lethal (Sxl) of Drosophila melanogaster from Sciara coprophila, Rhynchosciara americana, and Trichosia pubescens. This gene plays the key role in controlling sex determination and dosage compensation in D. melanogaster. The Sxl gene of the three species studied produces a single transcript encoding a single protein in both males and females. Comparison of the Sxl proteins of these Nematocera insects with those of the Brachycera showed their two RNA-binding domains (RBD) to be highly conserved, whereas significant variation was observed in both the N- and C-terminal domains. The great majority of nucleotide changes in the RBDs were synonymous, indicating that purifying selection is acting on them. In both sexes of the three Nematocera insects, the Sxl protein colocalized with transcription-active regions dependent on RNA polymerase II but not on RNA polymerase I. Together, these results indicate that Sxl does not appear to play a discriminatory role in the control of sex determination and dosage compensation in nematocerans. Thus, in the phylogenetic lineage that gave rise to the drosophilids, evolution coopted for the Sxl gene, modified it, and converted it into the key gene controlling sex determination and dosage compensation. At the same time, however, certain properties of the recruited ancestral Sxl gene were beneficial, and these are maintained in the evolved Sxl gene, allowing it to exert its sex-determining and dose compensation functions in Drosophila.
Development of an Expressed Sequence Tag (EST) Resource for Wheat (Triticum aestivum L.)
Authors: Lazo G R , Chao S , Hummel D D , Edwards H , Crossman C C , Lui N , Matthews D E , Carollo V L , Hane D L , You F M , Butler G E , Miller R E , Close T J , Peng J H , Lapitan N L V , Gustafson J P , Qi L L , Echalier B , Gill B S , Dilbirligi M , Randhawa H S , Gill K S , Greene R A , Sorrells M E , Akhunov E D , Dvořák J , Linkiewicz A M , Dubcovsky J , Hossain K G , Kalavacharla V , Kianian S F , Mahmoud A A ,   Miftahudin, Ma X-F , Conley E J , Anderson J A , Pathan M S , Nguyen H T , McGuire P E , Qualset C O , Anderson O D
Published: October 2004

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid (2n = 6x = 42) wheat genome (Triticum aestivum L.). Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags (ESTs) representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection (113,220 ESTs). Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of ESTs into contigs. These contigs plus singletons (unassembled ESTs) were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics.
Early Sepsis-Associated Acute Kidney Injury and Obesity
Authors: Ahn Yoon Hae , Yoon Si Mong , Lee Jinwoo , Lee Sang-Min , Oh Dong Kyu , Lee Su Yeon , Park Mi Hyeon , Lim Chae-Man , Lee Hong Yeul ,   Korean Sepsis Alliance Investigators, Heo Jeongwon , Lee Jae-myeong , Kim Kyung Chan , Lee Yeon Joo , Cho Young-Jae , Lim Sung Yoon , Chang Youjin , Jeon Kyeongman , Ko Ryoung-Eun , Suh Gee Young , Hong Suk-Kyung , Hong Sang-Bum , Cho Woo Hyun , Kwak Sang Hyun , Lee Heung Bum , Ahn Jong-Joon , Seong Gil Myeong , Lee Song-I , Park Sunghoon , Park Tai Sun , Lee Su Hwan , Choi Eun Young , Moon Jae Young , Kang Hyung Koo
Published: February 2024

Importance

The prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation.

Objective

To explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis.

Design, Setting, and Participants

This nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded.

Exposures

Sepsis and hospitalization in the ICU.

Main Outcomes and Measures

The primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable.

Results

Of the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI.

Conclusions and Relevance

In this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.
Die Meldepflicht als Grundlage der epidemiologischen Statistik: Die Auswirkungen der Meldepraxis und der Verwendung von paper technologies auf den Informationsgehalt von Morbiditätsstatistiken 1886–1921
Authors: Jochum Henrik
Published: February 2024

Dieser Artikel untersucht anhand einer Betrachtung der praktischen Umsetzung des schweizerischen Meldewesens für Infektionskrankheiten zwischen 1886 und 1921, welche Auswirkungen die Meldepraxis und die Verwendung vonpaper technologiesauf die Meldungen hatten, die daraufhin für Morbiditätsstatistiken verwendet wurden. Eine genaue Untersuchung der Herstellungsprozesse von Meldungen zeigt die Schwierigkeiten und Lösungsansätze bei der Umsetzung des gesetzlich vorgegebenen Meldeprozesses. Zwei Krankheitsausbrüche – ein Pockenausbruch in Schaffhausen und ein Typhusausbruch im Kanton Luzern – dienen dabei als Fallbeispiele. Es wird gezeigt, dass Meldungen mehr als nur objektive Repräsentationen von Erkrankungen sind, sondern auch die medizinisch-sozialen Interaktionen darstellen, die sie produzieren, gezeitigt durch administrative Werkzeuge wie Meldeformulare und den Akt des Meldens. Das problematisiert die Aussagekraft von historischen Statistiken und zeigt die Komplexität des historischen Quellenmaterials, da diese Interaktionen und ihre Auswirkungen auf die Meldungen mit in Betracht gezogen werden müssen. Diese Erkenntnisse werden mit der Betrachtung des schweizerischen Meldewesens während der Spanischen Grippe 1918 und dessen Scheitern bei der Erfassung der Influenzafälle verdeutlicht.
Guardians of precision: advancing radiation protection, safety, and quality systems in nuclear medicine
Authors: Giammarile Francesco , Knoll Peter , Kunikowska Jolanta , Paez Diana , Estrada Lobato Enrique , Mikhail-Lette Miriam , Wahl Richard , Holmberg Ola , Abdel-Wahab May , Scott Andrew M. , Delgado Bolton Roberto C.
Published: February 2024

Background

In the rapidly evolving field of nuclear medicine, the paramount importance of radiation protection, safety, and quality systems cannot be overstated. This document provides a comprehensive analysis of the intricate regulatory frameworks and guidelines, meticulously crafted and updated by national and international regulatory bodies to ensure the utmost safety and efficiency in the practice of nuclear medicine.

Methods

We explore the dynamic nature of these regulations, emphasizing their adaptability in accommodating technological advancements and the integration of nuclear medicine with other medical and scientific disciplines.

Results

Audits, both internal and external, are spotlighted for their pivotal role in assessing and ensuring compliance with established standards, promoting a culture of continuous improvement and excellence. We delve into the significant contributions of entities like the International Atomic Energy Agency (IAEA) and relevant professional societies in offering universally applicable guidelines that amalgamate the latest in scientific research, ethical considerations, and practical applicability.

Conclusions

The document underscores the essence of international collaborations in pooling expertise, resources, and insights, fostering a global community of practice where knowledge and innovations are shared. Readers will gain an in-depth understanding of the practical applications, challenges, and opportunities presented by these regulatory frameworks and audit processes. The ultimate goal is to inspire and inform ongoing efforts to enhance safety, quality, and effectiveness in nuclear medicine globally.
The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma
Authors: Olbrich Anne , Niemeyer Johannes , Seiffert Hendrik , Ebel Sebastian , Gros Olga , Lordick Florian , Forstmeyer Dirk , Seehofer Daniel , Rademacher Sebastian , Denecke Timm , Matz-Soja Madlen , Berg Thomas , van Bömmel Florian
Published: February 2024

Purpose

The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC.

Methods

A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria.

Results

The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001).

In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP.

Conclusion

The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.
Antimicrobial and antitumor properties of anuran peptide temporin-SHf induce apoptosis in A549 lung cancer cells
Authors: Antony Anet , Purayil Anupama Kizhakke , Olakkaran Shilpa , Dhannura Shweta , Shekh Shamasoddin , Gowd Konkallu Hanumae , Gurushankara Hunasanahally Puttaswamygowda
Published: February 2024

Temporin-SHf is a linear, ultra-short, hydrophobic, α-helix, and phe-rich cationic antimicrobial peptide. The antitumor activities and mechanism of temporin-SHf-induced cancer cell death are unknown. The temporin-SHf was synthesized by solid-phase Fmoc chemistry and antimicrobial and antitumor activities were investigated. Temporin-SHf was microbiocidal, non-hemolytic, and cytotoxic to human cancer cells but not to non-tumorigenic cells. It affected the cancer cells' lysosomal integrity and caused cell membrane damage. The temporin-SHf inhibited A549 cancer cell proliferation and migration. It is anti-angiogenic and causes cancer cell death through apoptosis. The molecular mechanism of action of temporin-SHf confirmed that it kills cancer cells by triggering caspase-dependent apoptosis through an intrinsic mitochondrial pathway. Owing to its short length and broad spectrum of antitumor activity, temporin-SHf is a promising candidate for developing a new class of anticancer drugs.
Amplification, Resistance, and Kinetics of the Jaw Stretching Device (ARK-JSD): analysis of the force variation and implications for trismus therapy
Authors: Charters Emma , Cheng Kai , Dunn Masako , Luo Aaron , Aung Y. M. , Lewin Will , Clark Jonathan R.
Published: February 2024

Purpose

Jaw-stretching devices, including the Amplification, Resistance, and Kinetics of the Jaw (ARK-JSD), are an effective option for treating trismus after head and neck cancer (HNC) treatment. The force, however, that is applied to the patient’s jaw is unknown.

Methods

Ten ARK-JSD devices were constructed for each of the levels of resistance (total of 30 samples). Each sample was tested using a Universal Testing Machine (UTM).

Results

The easy, medium, and hard ARK-JSD had a mean maximum force of 12.3, 21.0, and 32.7 Newtons (N) at a mean interincisal distance (IID) of 8.0 mm, 13.0 mm, and 16.0 mm, respectively. The force varied by 6.9 N for the easy and 24.1 N for the hard ARK-JSD. Fatigue analysis demonstrated up to 5.5 N loss of force over 10 weeks.

Conclusion

The ARK-JSD is a low-cost trismus device that can force between 12.3 and 32.7 N. The variation in resistance may impact efficacy. Understanding this variation will assist clinicians and patients using the ARK-JSD for trismus therapy.