bluuebunny/crossref_metadata_2025 huggingface dataset:
Porcine Circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice
Authors: Kiupel Matti , Stevenson Gregory W , Galbreath Elizabeth J , North Adam , HogenEsch Harm , Mittal Suresh K
Published: November 2005

Background

We have previously described microscopic and electron microscopic alterations in lymphoid organs of PCV2 inoculated mice as apoptosis. In this study we wanted to investigate the molecular pathogenetic mechanism of PCV2-induced apoptosis. Eight-week old BALB/c mice were either sham inoculated (control mice) or inoculated intraperitoneally (ip) and intranasally (in) with a single (sPCV mice) or multiple (mPCV mice) doses of PCV2. Four control mice and 4 sPCV mice were sacrificed 7, 14, 28 and 42 days post inoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. Following necropsy, immunohistochemistry for caspase 3 and in-situ TUNEL assay were performed on sections of spleen, lymph nodes, thymus and ileum from control, sPCV and mPCV mice. In addition, total RNA was extracted from spleens of control, sPCV and mPCV mice for simultaneous detection and semiquantitation of bcl-2 homologues and various caspase mRNAs using a multiprobe RNase protection assay system.

Results

PCV2 replicated and was associated with apoptosis in spleens, lymph nodes and Peyer's patches of infected BALB/c mice. Upregulation of caspase 1, 2, 3, 6, 7, 8, 11 and 12 and upregulation for the transcripts of apoptosis inhibitors bcl-2, bcl-w and bcl-X and apoptosis promoters' bax, bak and bad was detected in spleens of sPCV and mPCV mice, but not control mice. Apoptosis was further confirmed by light and electron microscopic morphology as well as by positive TUNEL assay and detection of activated caspase 3. PCV2 nucleic acid was detected by in-situ hybridization in the nuclei and cytoplasm of such apoptotic cells.

Conclusion

The data presented here support the hypothesis that PCV2 induces apoptosis mediated through the activation of caspases 8 and 3 in the spleens of infected mice.
Transcriptome analysis of antigenic variation in Plasmodium falciparum - var silencing is not dependent on antisense RNA
Authors: Ralph Stuart A , Bischoff Emmanuel , Mattei Denise , Sismeiro Odile , Dillies Marie-Agnès , Guigon Ghislaine , Coppee Jean-Yves , David Peter H , Scherf Artur
Published: November 2005

Background

Plasmodium falciparum, the causative agent of the most severe form of malaria, undergoes antigenic variation through successive presentation of a family of antigens on the surface of parasitized erythrocytes. These antigens, known as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins, are subject to a mutually exclusive expression system, and are encoded by the multigene var family. The mechanism whereby inactive var genes are silenced is poorly understood. To investigate transcriptional features of this mechanism, we conducted a microarray analysis of parasites that were selected to express different var genes by adhesion to chondroitin sulfate A (CSA) or CD36.

Results

In addition to oligonucleotides for all predicted protein-coding genes, oligonucleotide probes specific to each known var gene of the FCR3 background were designed and added to the microarray, as well as tiled sense and antisense probes for a subset of var genes. In parasites selected for adhesion to CSA, one full-length var gene (var2csa) was strongly upregulated, as were sense RNA molecules emanating from the 3' end of a limited subset of other var genes. No global relationship between sense and antisense production of var genes was observed, but notably, some var genes had coincident high levels of both antisense and sense transcript.

Conclusion

Mutually exclusive expression of PfEMP1 proteins results from transcriptional silencing of non-expressed var genes. The distribution of steady-state sense and antisense RNA at var loci are not consistent with a silencing mechanism based on antisense silencing of inactive var genes. Silencing of var loci is also associated with altered regulation of genes distal to var loci.
Glucose represses connexin36 in insulin-secreting cells
Authors: Allagnat Florent , Martin David , Condorelli Daniele F. , Waeber Gérard , Haefliger Jacques-Antoine
Published: November 2005

The gap-junction protein connexin36 (Cx36) contributes to control the functions of insulin-producing cells. In this study, we investigated whether the expression of Cx36 is regulated by glucose in insulin-producing cells. Glucose caused a significant reduction of Cx36 in insulin-secreting cell lines and freshly isolated pancreatic rat islets. This decrease appeared at the mRNA and the protein levels in a dose- and time-dependent manner. 2-Deoxyglucose partially reproduced the effect of glucose, whereas glucosamine, 3-O-methyl-D-glucose and leucine were ineffective. Moreover, KCl-induced depolarization of β-cells had no effect on Cx36 expression, indicating that glucose metabolism and ATP production are not mandatory for glucose-induced Cx36 downregulation. Forskolin mimicked the repression of Cx36 by glucose. Glucose or forskolin effects on Cx36 expression were not suppressed by the L-type Ca2+-channel blocker nifedipine but were fully blunted by the cAMP-dependent protein kinase (PKA) inhibitor H89. A 4 kb fragment of the human Cx36 promoter was identified and sequenced. Reporter-gene activity driven by various Cx36 promoter fragments indicated that Cx36 repression requires the presence of a highly conserved cAMP responsive element (CRE). Electrophoretic-mobility-shift assays revealed that, in the presence of a high glucose concentration, the binding activity of the repressor CRE-modulator 1 (CREM-1) is enhanced. Taken together, these data provide evidence that glucose represses the expression of Cx36 through the cAMP-PKA pathway, which activates a member of the CRE binding protein family.
Analyzing focal adhesion structure by atomic force microscopy
Authors: Franz Clemens M. , Müller Daniel J.
Published: November 2005

Atomic force microscopy (AFM) can produce high-resolution topographic images of biological samples in physiologically relevant environments and is therefore well suited for the imaging of cellular surfaces. In this work we have investigated focal adhesion complexes by combined fluorescence microscopy and AFM. To generate high-resolution AFM topographs of focal adhesions, REF52 (rat embryo fibroblast) cells expressing YFP-paxillin as a marker for focal adhesions were de-roofed and paxillin-positive focal adhesions subsequently imaged by AFM. The improved resolution of the AFM topographs complemented the optical images and offered ultrastructural insight into the architecture of focal adhesions. Focal adhesions had a corrugated dorsal surface formed by microfilament bundles spaced 127±50 nm (mean±s.d.) apart and protruding 118±26 nm over the substratum. Within focal adhesions microfilaments were sometimes branched and arranged in horizontal layers separated by 10 to 20 nm. From the AFM topographs focal adhesion volumes could be estimated and were found to range from 0.05 to 0.50 μm3. Furthermore, the AFM topographs show that focal adhesion height increases towards the stress-fiber-associated end at an angle of about 3°. Finally, by correlating AFM height information with fluorescence intensities of YFP-paxillin and F-actin staining, we show that the localization of paxillin is restricted to the ventral half of focal adhesions, whereas F-actin-containing microfilaments reside predominantly in the membrane-distal half.
Cost of Intravenous Immunoglobulin Therapy Versus Conventional Immunosuppressive Therapy in Patients with Mucous Membrane Pemphigoid: A Preliminary Study
Authors: Daoud Yassine , Amin Ketan G , Mohan Krishn , Ahmed A Razzaque
Published: November 2005

BACKGROUND

Intravenous immunoglobulin (IVIG) is an expensive biologic agent used to treat patients with mucous membrane pemphigoid (MMP) nonresponsive to conventional immunosuppressive therapy (CIST). The high cost of IVIG is of concern to healthcare providers and insurance companies.

OBJECTIVE

To compare the cost of IVIG with that of CIST in treating a cohort of 15 patients with severe and extensive MMP.

METHODS

Fifteen patients with biopsy-proven MMP nonresponsive to CIST were subsequently treated with IVIG and demonstrated a positive clinical response. This was a comparative, retrospective study; the mean total duration of the observation period was 8.4 years. A comparison of the cost of IVIG with that of CIST during the study period and the annual cost was performed. The cost of CIST was defined as the actual cost of the drug plus the cost of management of the multiple adverse effects, including hospitalizations, produced by CIST. In the same patient cohort, no significant adverse effects to IVIG were observed and no hospitalizations were required. Hence, the cost of IVIG therapy is simply the actual cost of the IVIG.

RESULTS

In this cohort of patients, CIST had significant adverse effects, many of which were hazardous and required prolonged and frequent hospitalizations. The mean total cost using IVIG therapy was significantly less than that of CIST during the entire course of the disease (p < 0.001) and on an annual basis (p < 0.05).

CONCLUSIONS

IVIG therapy is a safe, clinically beneficial, and less-expensive alternative treatment in patients with progressive MMP that is nonresponsive to CIST.
Optic Neuritis with Concurrent Etanercept and Isoniazid Therapy
Authors: Noguera-Pons Raul , Borrás-Blasco Joaquín , Romero-Crespo Isabel , Antón-Torres Rosa , Navarro-Ruiz Andrés , González-Ferrandez Jose Antonio
Published: November 2005

OBJECTIVE

To report a case of optic neuritis associated with concurrent etanercept and isoniazid therapy.

CASE SUMMARY

A 55-year-old man diagnosed as having rheumatoid arthritis had received treatment with nonsteroidal anti-inflammatory drugs, sulfasalazine, oral methotrexate, leflunomide, and deflazacort. Four months prior to admission, he had a Disease Activity Score of 6.06; treatment with etanercept was considered. Three months prior to admission, because of evidence of latent tuberculosis, isoniazid 300 mg once daily and pyridoxine 50 mg once daily were prescribed. Treatment with subcutaneous etanercept 25 mg twice weekly was started 5 days after isoniazid was initiated. Two weeks prior to admission, the patient developed blurred vision in his left eye. Ten days later, his vision worsened and he was hospitalized. The visual acuity in both eyes was 0.7, and a campimetric examination was compatible with optic neuritis. Magnetic resonance imaging of the brain revealed lesions suggesting demyelinating lesions. The clinical course was consistent with bilateral optic neuritis. Etanercept was stopped, and isoniazid was replaced with rifampin 600 mg once daily. The patient was treated with intravenous methylprednisolone hemisuccinate 1 g/day for 5 days followed by oral prednisolone, resulting in a minor subjective improvement in left eye visual acuity. He then received oral prednisone for 3 weeks, slowly tapering to discontinuation.

DISCUSSION

No physiologic factors could have predisposed this patient to develop optic neuritis. He was not diagnosed with a demyelinating disease or underlying systemic condition. The optic neuritis was unlikely to be an early manifestation of multiple sclerosis based on the clinical course and the negative results of the imaging tests. Furthermore, there was a close temporal correlation between the drug exposure and the onset of symptoms. After discontinuation of etanercept and isoniazid therapy, the patient's general condition improved. Use of the Naranjo probability scale indicated a possible relationship between optic neuritis and combined etanercept–isoniazid therapy.

CONCLUSIONS

Patients initiated on etanercept and isoniazid should be closely monitored for the development of adverse neurologic signs and effects. If optic neuritis is determined, etanercept and isoniazid should be discontinued immediately.
German Technique for Pressed Potassium Bromide Infrared Sampling
Authors: Schiedt U.
Published: November 2005

In the past two years a highly original infrared sampling technique has been developed. This is probably the most constructive method of solid state sampling yet devised. It has been found possible by making dilutions of organic solids in solid potassium bromide and with subsequent pressing to prepare disks of these materials which are visually clear and of known concentration of weight so that they can readily be placed into the spectrophotometer without the usual difficulties and interferences resulting from solvents or nujol mulls. This method was developed independently by Sister Miriam Michael Stimson of Siena Heights College in this country (2), and by Dr. U. Schiedt of the Max Planck Institute for Biochemistry in Tübingen, Germany (1). The latter has been able to investigate this method more in detail and to develop it to a greater extent. Some of these results and developments are the object of this report.
The Spectrographic Analysis of Antimony, Cadmium, and Tin in a Lead Base Alloy
Authors: Bergstrom Norman C. , Lucas Ernest H.
Published: November 2005

This method provides for the rapid analysis of a lead base alloy containing approximately 2% tin, 1% cadmium and 0.25 percent antimony. A high power, medium-high inductance, spark discharge excites the sample by the point to plane technique. A super-imposed spectrum is obtained consisting of 3 exposures along the cross-section of the sample. This achieves greater precision since any variation due to segregation is thereby reduced.
Modernization Increases Accuracy and Utility of Spectrographic Computer
Authors: Adams M. M.
Published: November 2005

This report is a brief description of the component changes and product engineering made in the Phillips 66 Spectro Computer since the earlier models were described in a paper by Morgan and Crawford.

The improvements described add greatly to the versatility of the Spectro Computer, as well as make possible approximately a tenfold increase in accuracy. At the same time, the instrument is unitized so as to minimize maintenance problems.
Semi-Quantitative Analysis of Elemental Selenium
Authors: Mellichamp J. W.
Published: November 2005

A spectrochemical method is given for the semi-quantitative analysis of 24 impurity elements that may appear in elemental selenium. The method is simple, rapid and adequate for the classification of selenium into various purity grades. Synthetic standards are used in place of chemically analyzed standards. A 50 milligram sample, in its “as received” form, is burned directly in the direct current arc. From the standard spectrograms, the line-to-background ratios of the impurity elements are established to obtain analytical working curves. The elements sought, their analytical spectral lines, and their minimum detectable amounts are given in table form.
Determination of Small Amounts of an Element in a Powder without the AID of Standard Samples
Authors: Gillis J. , Eeckhout J.
Published: November 2005

A new method of calibration for estimating an element in a powder sample without synthetic standard samples is described. Allowance is made for the possible effect of the state of combination of the element on relative line intensities, which might interfere with extrapolation from simple addition standards. The method has been tried on a sample of graphite from nodular cast iron, to estimate the Mg content, and has led to the construction of a working curve for the estimation of Mg in graphite in the range 0.1 to 1%.

Resume

A new spectrochemical method is described for the determination of an unknown element in a powder sample without the aid of standard samples. The method described compensates for possible influence of the form of chemical combination on the relative intensities of the lines measured. The method has been applied to the determination of the Mg content of a graphite sample from a cast iron treated with Mg. The analytical curve for Mg in graphite allowing the determination of Mg from 0.05% to 1.0% can be set up by means of the results obtained.
Positive Ion Counting for Mass Spectrometer Beam Currents of 10−14 TO 10−19 Ampere
Authors: White F. A. , Collins T. L.
Published: November 2005

A reliable method for detecting and recording very small ion beam currents is described. A twenty-stage electron multiplier is used in conjunction with sealers and other circuitry for counting individual positive ions. Advantages and limitations of this method, as applied to mass spectrometer problems, are discussed.
Developing creativity for the world of work: a case study
Authors: Massey Anne
Published: November 2005

Professional studies has traditionally been regarded as an add-on extra to the mainstream business of creative practice for design students. It has frequently been delivered in the final year of study and the content has normally been giving general advice on CV preparation plus appearances from successful practitioners and/or various funding bodies. This article shares the experiences of developing professional studies for students at the Arts Institute at Bournemouth as a funded ADC-LTSN project, with reference to creativity as it is perceived in the world of business and management. This revealed a dominance of the myth of the creative artist in the literature of art, design and management studies. The second part of the project involved professional trainers using psychological profiling tools and other activities with the students. This led to a consideration of the importance of teamworking for the process of creativity. The activities met with some resistance from the students. This could be explained by the prevalence of the myth of the creative artist and also the questioning culture of a higher education context.
How art, media and design students conceive of the relation between the dissertation and practice
Authors: Pritchard Tracy , Heatly Richard , Trigwell Keith
Published: November 2005

This study examined students' conceptions of the relationship between aspects of theory and practice in art, media and design undergraduate education. This was considered specifically in relation to the dissertation which most final-year arts practice undergraduates undertake. The study
was based on interviews conducted within one institution where theory and practice is normally delivered, supported and assessed by the tutors who teach the student both theory and practice. These practice/theory tutors also supervise and assess the dissertation. An analysis of interviews
of a varied sample of 24 students from the disciplines of fashion design, animation and photographic arts yield four qualitatively different ways of conceiving the relations between dissertation and practice. The semi-structured interviews looked at all facets of the students' experience of
how a dissertation may have an impact upon them, from considerations on how they perceived the notion of having to complete a written paper to how a dissertation may support their practice and to the simple practicalities of how they might achieve this piece of work. The categories range from
the conception that the dissertation and practice are inseparable, through to a conception that the dissertation is not necessary. These different conceptions appeared to be related to variations of students' views of the role they had undertaken in relation to their own involvement in preparing
and writing the dissertation. The implications of this study are discussed in terms of the relations between student conceptions of the rationale for the dissertation, and their understanding of the academic task at hand. The outcomes also suggest further avenues for research and exploration
in relation to the key issues raised.
Immigrants and a regional economy in Spain: the case of Murcia
Authors: Corkill David
Published: November 2005

This article examines some of the issues that arise from the integration of non-EU immigrant workers into the labour market in a region that boasts a successful agricultural sector. After establishing the characteristics of the regional economy in Murcia, one of Spain’s autonomous
communities, the focus is on the rapidly changing composition of the migrant community and the process of its incorporation into an increasingly complex regional economy. The premise is that immigration from abroad is closely linked to the ‘new’ forms of agricultural production
associated with the intensive, export-oriented agriculture and with the rapid growth of the tourism and construction sectors that has become such a characteristic feature of southern and eastern Spain. One outcome has been the emergence of a new ethnic hierarchy of older and newer immigrants
and of the increasing prevalence of labour displacement, no longer of Spaniards by immigrants, but of one immigrant group by another. A survey of immigrants in Murcia carried out in 2002 serves to demonstrate the rapidly changing dynamics in this sensitive area.
Cholinergic Deafferentation of the Entorhinal Cortex in Rats Impairs Encoding of Novel But Not Familiar Stimuli in a Delayed Nonmatch-to-Sample Task
Authors: McGaughy Jill , Koene Randal A. , Eichenbaum Howard , Hasselmo Michael E.
Published: November 2005

Acetylcholine may regulate working memory for novel stimuli by activating intrinsic mechanisms for sustained spiking in entorhinal cortical neurons, which have been demonstrated in slice preparations of the entorhinal cortex. Computational modeling demonstrates that loss of the cholinergic activation of intrinsic mechanisms for sustained activity could selectively impair working memory for novel stimuli, whereas working memory for familiar stimuli could be maintained because of previously modified synapses. Blockade of muscarinic cholinergic receptors and selective cholinergic lesions has been shown to impair encoding in delayed matching tasks. However, previous studies have not compared explicitly the role of cholinergic modulation in working memory for novel versus familiar stimuli. Here, we show that lesions of the cholinergic innervation of the entorhinal cortex selectively impair delayed nonmatch to sample performance for novel odors, whereas delayed nonmatch to sample for familiar odors is spared. This indicates an important role for cholinergic innervation of the entorhinal cortex in working memory for novel stimuli.
Rapid Eye Movement Sleep Is Reduced in Prolactin-Deficient Mice
Authors: Obál Ferenc , Garcia-Garcia Fabio , Kacsóh Balint , Taishi Ping , Bohnet Stewart , Horseman Nelson D. , Krueger James M.
Published: November 2005

Prolactin (PRL) is implicated in the modulation of spontaneous rapid eye movement sleep (REMS). Previous models of hypoprolactinemic animals were characterized by changes in REMS, although associated deficits made it difficult to ascribe changes in REMS to reduced PRL. In the current studies, male PRL knock-out (KO) mice were used; these mice lack functional PRL but have no known additional deficits. Spontaneous REMS was reduced in the PRL KO mice compared with wild-type or heterozygous littermates. Infusion of PRL for 11-12 d into PRL KO mice restored their REMS to that occurring in wild-type or heterozygous controls. Six hours of sleep deprivation induced a non-REMS and a REMS rebound in both PRL KO mice and heterozygous littermates, although the REMS rebound in the KOs was substantially less. Vasoactive intestinal peptide (VIP) induced REMS responses in heterozygous mice but not in KO mice. Similarly, an ether stressor failed to enhance REMS in the PRL KOs but did in heterozygous littermates. Finally, hypothalamic mRNA levels for PRL, VIP, neural nitric oxide synthase (NOS), inducible NOS, and the interferon type I receptor were similar in KO and heterozygous mice. In contrast, tyrosine hydroxylase mRNA was lower in the PRL KO mice than in heterozygous controls and was restored to control values by infusion of PRL, suggesting a functioning short-loop negative feedback regulation in PRL KO mice. Data support the notion that PRL is involved in REMS regulation.
Control of Spontaneous Firing Patterns by the Selective Coupling of Calcium Currents to Calcium-Activated Potassium Currents in Striatal Cholinergic Interneurons
Authors: Goldberg Joshua A. , Wilson Charles J.
Published: November 2005

The spontaneous firing patterns of striatal cholinergic interneurons are sculpted by potassium currents that give rise to prominent afterhyperpolarizations (AHPs). Large-conductance calcium-activated potassium (BK) channel currents contribute to action potential (AP) repolarization; small-conductance calcium-activated potassium channel currents generate an apamin-sensitive medium AHP (mAHP) after each AP; and bursts of APs generate long-lasting slow AHPs (sAHPs) attributable to apamin-insensitive currents. Because all these currents are calcium dependent, we conducted voltage- and current-clamp whole-cell recordings while pharmacologically manipulating calcium channels of the plasma membrane and intracellular stores to determine what sources of calcium activate the currents underlying AP repolarization and the AHPs. The Cav2.2 (N-type) blocker ω-conotoxin GVIA (1 μm) was the only blocker that significantly reduced the mAHP, and it induced a transition to rhythmic bursting in one-third of the cells tested. Cav1 (L-type) blockers (10 μmdihydropyridines) were the only ones that significantly reduced the sAHP. When applied to cells induced to burst with apamin, dihydropyridines reduced the sAHPs and abolished bursting. Depletion of intracellular stores with 10 mmcaffeine also significantly reduced the sAHP current and reversibly regularized firing. Application of 1 μmω-conotoxin MVIIC (a Cav2.1/2.2 blocker) broadened APs but had a negligible effect on APs in cells in which BK channels were already blocked by submillimolar tetraethylammonium chloride, indicating that Cav2.1 (Q-type) channels provide the calcium to activate BK channels that repolarize the AP. Thus, calcium currents are selectively coupled to the calcium-dependent potassium currents underlying the AHPs, thereby creating mechanisms for control of the spontaneous firing patterns of these neurons.
ADrosophilaKCNQ Channel Essential for Early Embryonic Development
Authors: Wen Hua , Weiger Thomas M. , Ferguson Tanya S. , Shahidullah Mohammad , Scott Samae S. , Levitan Irwin B.
Published: November 2005

The mammalian voltage-dependent KCNQ channels are responsible for distinct types of native potassium currents and are associated with several human diseases. We cloned a novelDrosophilaKCNQ channel (dKCNQ) based on its sequence homology to the mammalian genes. When expressed in Chinese hamster ovary cells, dKCNQ gives rise to a slowly activating and slowly deactivating current that activates in the subthreshold voltage range. Like the M-current produced by mammalian KCNQ channels, dKCNQ current is sensitive to the KCNQ-specific blocker linopirdine and is suppressed by activation of a muscarinic receptor. dKCNQ is also similar to the mammalian channels in that it binds calmodulin (CaM), and CaM binding is necessary to produce functional currents.In situhybridization analysis demonstrates thatdKCNQmRNA is present in brain cortical neurons, the cardia (proventriculus), and the nurse cells and oocytes of the ovary. We generated mutant flies with deletions in the genomic sequence ofdKCNQ. Embryos produced by homozygous deletion females exhibit disorganized nuclei and fail to hatch, suggesting strongly that a maternal contribution of dKCNQ protein and/or mRNA is essential for early embryonic development.
Glucagon-Expressing Neurons within the Retina Regulate the Proliferation of Neural Progenitors in the Circumferential Marginal Zone of the Avian Eye
Authors: Fischer Andy J. , Omar Ghezal , Walton Nathaniel A. , Verrill Thomas A. , Unson Cecilia G.
Published: November 2005

Glucagon-expressing retinal amacrine cells have been implicated in regulating postnatal ocular growth. Furthermore, experimentally accelerated rates of ocular growth increase the number of neurons added to the peripheral edge of the retina. Accordingly, we assayed whether glucagon-expressing neurons within the retina regulate the proliferation of progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken eye. We found that glucagon-containing neurites are heavily clustered within the CMZ at the peripheral edge of the retina. Many of these neurites originate from a cell type that is distinct from other types of retinal neurons, which we termed large glucagon-expressing neurons (LGENs). The LGENs are immunoreactive for glucagon and glucagon-like peptide 1 (GLP1), have a unipolar morphology, produce an axon that projects into the CMZ, and are found only in ventral regions of the retina. In dorsal regions of the retina, a smaller version of the LGENs densely ramifies neurites in the CMZ. Intraocular injections of glucagon or GLP1 suppressed the proliferation of progenitors in the CMZ, whereas a glucagon-receptor antagonist promoted proliferation. In addition, we found that glucagon, GLP1, and glucagon antagonist influenced the number of progenitors in the CMZ. We conclude that the LGENs may convey visual information to the CMZ to control the addition of new cells to the edge of the retina. We propose that glucagon/GLP1 released from LGENs acts in opposition to insulin (or insulin-like growth factor) to regulate precisely the proliferation of retinal progenitors in the CMZ.
Extensive Cortical Rewiring after Brain Injury
Authors: Dancause Numa , Barbay Scott , Frost Shawn B. , Plautz Erik J. , Chen Daofen , Zoubina Elena V. , Stowe Ann M. , Nudo Randolph J.
Published: November 2005

Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.
Input to V2 Thin Stripes Arises from V1 Cytochrome Oxidase Patches
Authors: Sincich Lawrence C. , Horton Jonathan C.
Published: November 2005

Parallel streams from the primary visual cortex (V1) to the second visual area (V2) are thought to mediate different aspects of visual perception in primates. One hypothesis is that the projection from cytochrome oxidase patches to thin stripes is responsible for color, whereas a separate pathway from interpatches to pale stripes mediates form. Recently, the notion of segregated pathways has been challenged by a report showing that patches and interpatches project equally to thin stripes. We made injections of a retrograde tracer, cholera toxin-B (CTB-Au), into macaque V2 thin stripes and counted the number of labeled cells in patches versus interpatches in layer 2/3. Analysis of eight thin-stripe injections showed that a mean of 81% of labeled cells were located in patches (defined as 33% of the surface area of V1). This result confirms that the projection to thin stripes arises predominately from patches. To assess the segregation of patch and interpatch projections, we injected CTB-Au in a pale stripe and horseradish peroxidase in an adjacent thin stripe. In both successful cases, interdigitated fields of labeled cells were present in V1. Less than 1% of cells were double-labeled, indicating that the populations of cells supplying thin stripes and pale stripes are quite independent. This finding means that different signals are likely conveyed by patches and interpatches to V2.
Molecular Control of Spinal Accessory Motor Neuron/Axon Development in the Mouse Spinal Cord
Authors: Dillon Allison K. , Fujita Shinobu C. , Matise Michael P. , Jarjour Andrew A. , Kennedy Timothy E. , Kollmus Heike , Arnold Hans-Henning , Weiner Joshua A. , Sanes Joshua R. , Kaprielian Zaven
Published: November 2005

Within the developing vertebrate spinal cord, motor neuron subtypes are distinguished by the settling positions of their cell bodies, patterns of gene expression, and the paths their axons follow to exit the CNS. The inclusive set of cues required to guide a given motor axon subtype from cell body to target has yet to be identified, in any species. This is attributable, in part, to the unavailability of markers that demarcate the complete trajectory followed by a specific class of spinal motor axons. Most spinal motor neurons extend axons out of the CNS through ventral exit points. In contrast, spinal accessory motor neurons (SACMNs) project dorsally directed axons through lateral exit points (LEPs), and these axons assemble into the spinal accessory nerve (SAN). Here we show that an antibody against BEN/ALCAM/SC1/DM-GRASP/MuSC selectively labels mouse SACMNs and can be used to trace the pathfinding of SACMN axons. We use this marker, together with a battery of transcription factor-deficient or guidance cue/receptor-deficient mice to identify molecules required for distinct stages of SACMN development. Specifically, we find thatGli2is required for the initial extension of axons from SACMN cell bodies, and thatnetrin-1and its receptorDccare required for the proper dorsal migration of these cells and the dorsally directed extension of SACMN axons toward the LEPs. Furthermore, in the absence of the transcription factorNkx2.9, SACMN axons fail to exit the CNS. Together, these findings suggest molecular mechanisms that are likely to regulate key steps in SACMN development.
cAMP Response Element-Binding Protein Regulates Differentiation and Survival of Newborn Neurons in the Olfactory Bulb
Authors: Giachino Claudio , De Marchis Silvia , Giampietro Costanza , Parlato Rosanna , Perroteau Isabelle , Schütz Günther , Fasolo Aldo , Peretto Paolo
Published: November 2005

The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases of adult neurogenesis in the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, cell transplants, and quantitative analyses, we show that although CREB is expressed by the SVZ neuroblasts throughout the neurogenic process, its phosphorylation is transient and parallels neuronal differentiation, increasing during the late phase of tangential migration and decreasing after dendrite elongation and spine formation.In vitro, inhibition of CREB function impairs morphological differentiation of SVZ-derived neuroblasts. Transgenic mice lacking CREB, in a null CREM genetic background, show reduced survival of newborn neurons in the OB. This finding is further supported by peripheral afferent denervation experiments resulting in downregulation of CREB phosphorylation in neuroblasts, the survival of which appears heavily impaired. Together, these findings provide evidence that CREB regulates differentiation and survival of newborn neurons in the OB.
N-Terminal Insertion and C-Terminal Ankyrin-Like Repeats of α-Latrotoxin Are Critical for Ca2+-Dependent Exocytosis
Authors: Li Gang , Lee David , Wang Li , Khvotchev Mikhail , Chiew Soon Kwang , Arunachalam Lakshmanan , Collins Tony , Feng Zhong-Ping , Sugita Shuzo
Published: November 2005

α-Latrotoxin, a potent stimulator of exocytosis from neurons and neuroendocrine cells, has been studied intensively, but the mechanisms of its actions are poorly understood. Here, we developed a new method to generate active recombinant α-latrotoxin and conducted a structure/function analysis of the toxin in stimulating Ca2+-dependent exocytosis. α-Latrotoxin consists of a conserved N-terminal domain and C-terminal ankyrin-like repeats. After cleavage of an N-terminally fused purification tag of glutathioneS-transferase (GST), the recombinant toxin strongly stimulated exocytosis, whereas the GST-fused toxin was much less potent. The GST-fused toxin bound to the receptors [neurexin 1α; CL1 (CIRL/latrophilin 1)] as efficiently as did the GST-cleaved toxin but was much less effective in inserting into the plasma membrane and inducing cation conductance. The toxin with deletion of the last two ankyrin-like repeats still bound the receptors but could neither stimulate exocytosis nor induce cation conductance efficiently. The abilities of the mutated toxins to stimulate exocytosis correlated well with their abilities to induce cation conductance, but not their binding to the receptors. Our results indicate that (1) C-terminal ankyrin-like repeats and a free (unfused) N terminus are both required for the toxin to form pores, which is essential for Ca2+-dependent exocytosis, and (2) receptor binding alone is not sufficient to stimulate Ca2+-dependent exocytosis.
Deletion of the Prostaglandin E2EP2 Receptor Reduces Oxidative Damage and Amyloid Burden in a Model of Alzheimer's Disease
Authors: Liang Xibin , Wang Qian , Hand Tracey , Wu Liejun , Breyer Richard M. , Montine Thomas J. , Andreasson Katrin
Published: November 2005

Epidemiological studies demonstrate that chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in normal aging populations reduces the risk of developing Alzheimer's disease (AD). NSAIDs inhibit the enzymatic activity of cyclooxygenase-1 (COX-1) and inducible COX-2, which catalyze the first committed step in the synthesis of prostaglandins. These studies implicate COX-mediated inflammation as an early and potentially reversible preclinical event; however, the mechanism by which COX activity promotes development of AD has not been determined. Recent studies implicate the prostaglandin E2(PGE2) E prostanoid subtype 2 (EP2) receptor in the development of the innate immune response in brain. Here, we report that deletion of the PGE2EP2 receptor in the APPSwe-PS1ΔE9 model of familial AD results in marked reductions in lipid peroxidation in aging mice. This reduction in oxidative stress is associated with significant decreases in levels of amyloid-β (Aβ) 40 and 42 peptides and amyloid deposition. Aged APPSwe-PS1ΔE9 mice lacking the EP2 receptor harbor lower levels of β C-terminal fragments, the product of β-site APP cleaving enzyme (BACE1) processing of amyloid precursor protein. Increases in BACE1 processing have been demonstrated in models of aging and AD and after oxidative stress. Our results indicate that PGE2signaling via the EP2 receptor promotes age-dependent oxidative damage and increased Aβ peptide burden in this model of AD, possibly via effects on BACE1 activity. Our findings identify EP2 receptor signaling as a novel proinflammatory and proamyloidogenic pathway in this model of AD, and suggest a rationale for development of therapeutics targeting the EP2 receptor in neuroinflammatory diseases such as AD.
Cerebral Lymphoma in an Adenosine Deaminase–Deficient Patient With Severe Combined Immunodeficiency Receiving Polyethylene Glycol–Conjugated Adenosine Deaminase
Authors: Kaufman David A. , Hershfield Michael S. , Bocchini Joseph A. , Moissidis I. John , Jeroudi Majed , Bahna Sami L.
Published: November 2005

Polyethylene glycol–conjugated adenosine deaminase (PEG-ADA) provides an alternate therapy to mismatched stem cell transplantation for patients with ADA-deficient severe combined immunodeficiency. Although replacement therapy with PEG-ADA is effective in preventing infections, immune function does not return to normal, and most patients remain lymphopenic. Information is limited regarding the prognosis of patients on long-term ADA-replacement therapy. Here we present a case of a 10-year-old child who was diagnosed with ADA-severe combined immunodeficiency at 4 weeks of age after contracting pneumonia. Treatment with PEG-ADA was begun, the biochemical markers of ADA deficiency normalized, and his clinical progress was very good without significant infections. At 10 years of age, after presenting with headaches and cranial nerve deficits, he was diagnosed with Epstein-Barr virus–positive malignant brain lymphoma. It did not respond to various regimens of aggressive chemotherapy, and the patient expired 5 months later. We speculate that in this patient the immunologic surveillance by T cells may have been defective with respect to elimination of Epstein-Barr virus–infected cells, hence the formation of neoplasm. The possible mechanisms underlying such pathology are reviewed.
Sociocultural Factors Affecting the Prevalence and Control of Lymphatic Filariasis in Lau Local Government Area, Taraba State
Authors: Ogbonnaya Lawrence Ulu , Okeibunor Joseph C.
Published: November 2005

The Health Belief Model (HBM) and the Structural Basis for Health Action theories were employed in assessing the factors associated with the prevalence of lymphatic filariasis (LF) and the feasibility of a control program using a mass chemotherapy approach, in Lau Local Government Area of Taraba State, Nigeria. Two communities with health facilities and one without a health facility were studied in 2003. A modified version of the WHO cluster sampling technique was used in the random selection of respondents. Clinical examination, questionnaire survey, focus group discussion and key informant interview techniques were used in collecting the data. LF, involving elephantiasis and hydrocoele, is perceived as a severe disease in the communities, being ranked the 2nd and 3rd most severe respectively among the ten most common diseases in the communities. However a low perception of personal susceptibility to LF was identified among the people. The study also found serious gaps in understanding between knowledge of the cause of the disease and the means of its transmission. Very few people associated LF with mosquito bites. The treatments available and used by the people are predominantly traditional (scarifications and application of herbal preparations). Effective alternatives provided by the health system were lacking, even though about 97% of the people indicated willingness to take part in a mass chemotherapy program for the control of the disease. The two theories were useful in explaining the widespread prevalence of LF in the community and in understanding the health behavior of the people faced with the challenge of such a debilitating and stigmatizing disease. The health system has failed to provide an effective program to eliminate the disease. In the absence of a control or elimination program for LF, the people make use of traditional treatments both because of limited knowledge with regard to LF and the lack of effective care for those already affected and not because of lack of belief in the efficacy of modern treatment.
Challenges to HIV Prevention in Young Adults in the English-Speaking Caribbean: The Case in Rural Eastern Jamaica
Authors: Morrison Sharon D. , Chen W. William
Published: November 2005

This article presents findings from qualitative interviews with persons involved with HIV/AIDS prevention and youth development initiatives in rural Eastern Jamaica. Key informants were asked to describe the HIV/AIDS prevention strategies being employed in the region. Informants were also asked to share perspectives on challenges to HIV prevention with young adults in this setting. HIV/AIDS prevention strategies included: peer education, HIV talks and condom use demonstrations at family planning centers and the local health clinic, information dissemination at community events, and guest lectures with follow-up discussions during youth meetings and social development programs. Preoccupation with economic survival versus personal protection, denial of risk, fatalistic attitude, and ongoing struggle with low self-esteem, particularly among young adult females, were identified as reasons the message of prevention and willingness to practice personal protection was often rejected.
Reactions of Mental Health Social Workers following a Client Suicide Completion: A Qualitative Investigation
Authors: Sanders Sara , Jacobson Jodi , Ting Laura
Published: November 2005

The impact of client suicidal behavior on mental health social workers is slowly receiving increased empirical attention. This qualitative study examined the impact of client suicide on social workers. Results indicate that social workers experience multiple personal and professional reactions immediately following a client suicide completion. Long-term effects, such as the continual experience of emotional reactions and permanent behavior changes, including changing practice strategies, are also reported. The results of this study have significant implications for the preparation of social workers and other mental health therapists for practice with suicidal clients.
What You Need to Know about the Global Gag Rule and U.S. HIV/AIDS Assistance: An Unofficial Guide
Authors:   Population Action International
Published: November 2005

The Mexico City Policy, also known as the Global Gag Rule, was reinstated in 2001. It is a complicated policy for which explanations are rarely brief. Consequently, it is widely misunderstood and often over-interpreted. Anecdotal evidence from the field strongly suggests that the Global Gag Rule restrictions on U.S. family planning assistance are being mistakenly applied to other U.S. Agency for International Development (USAID) accounts, especially U.S. assistance for HIV/AIDS prevention, treatment and care. The purpose of this guide is to clarify that the Global Gag Rule does not apply to HIV/AIDS assistance from the U.S. government. And further, foreign non-governmental organizations (NGOs) providing HIV/AIDS-related services are eligible to receive U.S. HIV/AIDS assistance, regardless of their eligibility to receive U.S. family planning assistance. This guide also seeks to help current and potential recipients better understand the restrictions governing U.S. HIV/AIDS assistance.
Ethylbenzene
Authors: Welch Vincent A. , Fallon Kevin J. , Gelbke Heinz‐Peter
Published: November 2005

The article contains sections titled:1.Introduction2.Physical Properties3.Chemical Properties4.Production4.1.Alkylation with Non‐Zeolite Lewis Acid Catalysts4.2.Vapor‐Phase Alkylation over Zeolites4.3.Liquid‐Phase Alkylation over Zeolites4.4.Mixed‐Phase Zeolite‐Based Process4.5.Separation from Mixed C8Streams5.Environmental Protection6.Quality Specifications7.Handling, Storage, and Transportation8.Uses9.Economic Aspects10.Toxicology
Membranes: Gas‐Separation Applications
Authors: Stookey Donald J.
Published: November 2005

The article contains sections titled:

1.Introduction2.Commercial Membrane Gas‐Separation Applications2.1.Hydrogen Separation2.2.Helium Separation2.3.Nitrogen Generation2.4.Acid‐Gas Separation2.5.Gas Dehydration3.Developing Membrane Applications3.1.Oxygen and Oxygen‐Enriched Air3.2.Nitrogen‐Enriched Air (NEA)3.3.Nitrogen Rejection from Natural Gas3.4.Carbon Dioxide Removal from Liquid Hydrocarbons3.5.Removal of Condensable and Volatile Organic Compounds (VOC)