bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: A strategy for prevention
Authors: Sowden Evin , Carmichael Andrew J
Published: October 2004

Background

Pneumocystis pneumonia (PCP) is an increasing problem amongst patients on immunosuppression with autoimmune inflammatory disorders (AID). The disease presents acutely and its diagnosis requires bronchoalveolar lavage in most cases. Despite treatment with intravenous antibiotics, PCP carries a worse prognosis in AID patients than HIV positive patients. The overall incidence of PCP in patients with AID remains low, although patients with Wegener's granulomatosis are at particular risk.

Discussion

In adults with AID, the risk of PCP is related to treatment with systemic steroid, ill-defined individual variation in steroid sensitivity and CD4+ lymphocyte count. Rather than opting for PCP prophylaxis on the basis of disease or treatment with cyclophosphamide, we argue the case for carrying out CD4+ lymphocyte counts on selected patients as a means of identifying individuals who are most likely to benefit from PCP prophylaxis.

Corticosteroids, lymphopenia and a low CD4+ count in particular, have been identified as risk factors for the development of PCP in adults with AID. Trimethoprim-sulfamethoxazole (co-trimoxazole) is an effective prophylactic agent, but indications for its use remain ill-defined. Further prospective trials are required to validate our proposed prevention strategy.
Effect of granulocyte colony-stimulating factor in experimental methicillin resistant Staphylococcus aureus sepsis
Authors: Alp Emine , Gozukucuk Suveyda , Canoz Ozlem , Kirmaci Beyhan , Doganay Mehmet
Published: October 2004

Background

Methicillin resistant Staphylococcus aureus (MRSA) is the leading pathogenic cause of nosocomial infections, especially in bacteraemia and sepsis. The essential therapy for MRSA infection is glycopeptides. Therapeutic failure can be seen with this therapy and the mortality is still high. The aim of this study was to evaluate the additional effect of G-CSF on the traditional antibiotic treatment in an experimental MRSA sepsis.

Methods

Experimental sepsis was performed in mice by intraperitoneal injection of MRSA isolate. Inoculum dose was estimated as 6 × 109/ml. Mice were randomised for the study into four group; control group (not receive any therapy), G-CSF group (1000 ng/daily, subcutaneously for 3 d), antibiotic group (vancomycin 25 or 50 mg/kg intraperitoneally every 12 hours for 7 d), and vancomycin+G-CSF group (at the same concentrations and duration). Autopsy was done within one hour after mice died. If mice was still alive at the end of seventh day, they were sacrificed, and autopsy was done. In all groups, the effect of G-CSF therapy on the survival, the number of the MRSA colonies in the lung, liver, heart, spleen, and peritoneal cultures, the histopathology of the lung, liver, heart and spleen was investigated.

Results

One hundred and six mice were used. There were no significant differences in survival rates and bacterial eradication in G-CSF group compared with control group, and also in antibiotic +G-CSF group compared with antibiotic alone group. These parameters were all significantly different in antibiotic alone group compared with control group. Histopathologically, inflammation of the lung and liver were significantly reduced in vancomycin (25 mg/kg)+G-CSF and vancomycin (50 mg/kg)+G-CSF subgroups, respectively (p < 0.01). The histopathological inflammation of the other organs was not significantly different in antibiotic+G-CSF group compared with antibiotic group and, also G-CSF group compared with control group.

Conclusion

G-CSF treatment had no additional effect on survival and bacterial eradication in MRSA sepsis in nonneutropenic mice; and only a little effect on histopathology. G-CSF treatment is very expensive, likewise glycopeptides. The more interest in infection control measures, and prevent the spread of MRSA infections is more rational.
Atherosclerotic renal artery stenosis: one year outcome of total and separate kidney function following stenting
Authors: Coen Giorgio , Moscaritolo Eleonora , Catalano Carlo , Lavini Raffaella , Nofroni Italo , Ronga Giuseppe , Sardella Daniela , Zaccaria Alvaro , Cianci Rosario
Published: October 2004

Background

Renal artery stenosis (RAS) is a known cause of hypertension and ischemic nephropathy. Stenting of the artery is a valid approach, in spite of cases of unexpected adverse evolution of renal function.

Methods

In this study, 27 patients with unilateral RAS were subjected to stenting and followed for a period of one year, while 19 patients were observed while on medical treatment only. The group of 27 patients, 67.33 ± 6.8 years of age, creatinine of 2.15 ± 0.9 mg/dl, following stenting, were followed at intervals with biochemical tests, renal scintigraphy and doppler ultrasonography. The control group (70.0 ± 6.1 years, creatinine 1.99 ± 0.7 mg/dl) was also followed for one year.

Result

One year after stenting mean creatinine clearance (Ccr) increased from 36.07 ± 17.2 to 40.4 ± 21.6 ml/min (NS). Arterial BP, decreased after 1,3,6, and 12 months (p < 0.05). The number of antihypertensive drugs also decreased (p < 0.05). A significant increase in proteinuria was also observed. In the control group both Ccr, BP and proteinuria did not show significant changes. Based on renal scintigraphy and Ccr at subsequent times, it was possibile to evaluate the timecourse of renal function in both kidneys of the stented patients. In the stented kidneys Ccr increased significantly. On the controlateral kidney a decrease of renal function (p < 0.05) was observed. Resistance index appeared to be a risk factor of the functional outcome.

Conclusions

Stenting of RAS due to atherosclerosis is followed by stabilization or improvement of Ccr, mainly at the stented kidney, while contralateral renal function showed a decrease.
Social Phobia in an Italian region: do Italian studies show lower frequencies than community surveys conducted in other European countries?
Authors: Carta Mauro Giovanni , Hardoy Maria Carolina , Cadeddu Mariangela , Carpiniello Bernardo , Dell'Osso Liliana , Reda Mario Antonio , Wittchen Hans-Ulrich
Published: October 2004

Background

The lifetime prevalence of Social Phobia (SP) in European countries other than Italy has been estimated to range from 3.5% to 16.0%. The aim of this study was to assess the frequency of SP in Sardinia (Italy) in order to verify the evidence of a lower frequency of SP in Italy observed in previous studies (from 1.0% to 3.1%).

Methods

A randomised cross sample of 1040 subjects, living in Cagliari, in rural areas, and in a mining district in Sardinia were interviewed using a Simplified version of the Composite International Diagnostic Interview (CIDIS). Diagnoses were made according to the 10th International Classification of Diseases (ICD-10).

Results

Lifetime prevalence of SP was 2.2% (males: 1.5%, females: 2.8%) whereas 6-month prevalence resulted in 1.5% (males: 0.9%, females: 2.1%). Mean age at onset was 16.2 ± 9.3 years. A statistically significant association was found with Depressive Episode, Dysthymia and Generalized Anxiety Disorder.

Conclusions

The study is consistent with findings reported in several previous studies of a lower prevalence of SP in Italy. Furthermore, the results confirm the fact that SP, due to its early onset, might constitute an ideal target for early treatment aimed at preventing both the accumulation of social disabilities and impairments caused by anxiety and avoidance behaviour, as well as the onset of more serious, associated complications in later stages of the illness.
Toxoplasma and coxiella infection and psychiatric morbidity: A retrospective cohort analysis
Authors: Thomas Hollie V , Thomas Daniel Rh , Salmon Roland L , Lewis Glyn , Smith Andy P
Published: October 2004

Background

It has been suggested that infection with Toxoplasma gondii is associated with slow reaction and poor concentration, whilst infection with Coxiella burnetii may lead to persistent symptoms of fatigue.

Methods

425 farmers completed the Revised Clinical Interview Schedule (CIS-R) by computer between March and July 1999 to assess psychiatric morbidity. Samples of venous blood had been previously collected and seroprevalence of T. gondii and C. burnetii was assessed.

Results

45% of the cohort were seropositive for T. gondii and 31% were positive for C. burnetii. Infection with either agent was not associated with symptoms reflecting clinically relevant levels of concentration difficulties, fatigue, depression, depressive ideas or overall psychiatric morbidity.

Conclusions

We do not provide any evidence that infection with Toxoplasma gondii or Coxiella burnetii is associated with neuropsychiatric morbidity, in particular with symptoms of poor concentration or fatigue. However, this is a relatively healthy cohort with few individuals reporting neuropsychiatric morbidity and therefore the statistical power to test the study hypotheses is limited.
Use of and attitudes to a hospital information system by medical secretaries, nurses and physicians deprived of the paper-based medical record: a case report
Authors: Lærum Hallvard , Karlsen Tom H , Faxvaag Arild
Published: October 2004

Background

Most hospitals keep and update their paper-based medical records after introducing an electronic medical record or a hospital information system (HIS). This case report describes a HIS in a hospital where the paper-based medical records are scanned and eliminated. To evaluate the HIS comprehensively, the perspectives of medical secretaries and nurses are described as well as that of physicians.

Methods

We have used questionnaires and interviews to assess and compare frequency of use of the HIS for essential tasks, task performance and user satisfaction among medical secretaries, nurses and physicians.

Results

The medical secretaries use the HIS much more than the nurses and the physicians, and they consider that the electronic HIS greatly has simplified their work. The work of nurses and physicians has also become simplified, but they find less satisfaction with the system, particularly with the use of scanned document images.

Conclusions

Although the basis for reference is limited, the results support the assertion that replacing the paper-based medical record primarily benefits the medical secretaries, and to a lesser degree the nurses and the physicians. The varying results in the different employee groups emphasize the need for a multidisciplinary approach when evaluating a HIS.
Physical restraint use among nursing home residents: A comparison of two data collection methods
Authors: Laurin Danielle , Voyer Philippe , Verreault René , Durand Pierre J
Published: October 2004

Background

In view of the issues surrounding physical restraint use, it is important to have a method of measurement as valid and reliable as possible. We determined the sensitivity and specificity of physical restraint use a) reported by nursing staff and b) reviewed from medical and nursing records in nursing home settings, by comparing these methods with direct observation.

Methods

We sampled eight care units in skilled nursing homes, seven care units in nursing homes and one long-term care unit in a hospital, from eight facilities which included 28 nurses and 377 residents. Physical restraint use was assessed the day following three periods of direct observation by two different means: interview with one or several members of the regular nursing staff, and review of medical and nursing records. Sensitivity and specificity values were calculated according to 2-by-2 contingency tables. Differences between the methods were assessed using the phi coefficient. Other information collected included: demographic characteristics, disruptive behaviors, body alignment problems, cognitive and functional skills.

Results

Compared to direct observation (gold standard), reported restraint use by nursing staff yielded a sensitivity of 87.4% at a specificity of 93.7% (phi = 0.84). When data was reviewed from subjects' medical and nursing records, sensitivity was reduced to 74.8%, and specificity to 86.3% (phi = 0.54). Justifications for restraint use including risk for falls, agitation, body alignment problems and aggressiveness were associated with the use of physical restraints.

Conclusions

The interview of nursing staff and the review of medical and nursing records are both valid and reliable techniques for measuring physical restraint use among nursing home residents. Higher sensitivity and specificity values were achieved when nursing staff was interviewed as compared to reviewing medical records. This study suggests that the interview of nursing staff is a more reliable method of data collection.
Melanoma-restricted genes
Authors: Wang Ena , Panelli Monica C , Zavaglia Katia , Mandruzzato Susanna , Hu Nan , Taylor Phil R , Seliger Barbara , Zanovello Paola , Freedman Ralph S , Marincola Francesco M
Published: October 2004

Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets.
Time and frequency domain methods for quantifying common modulation of motor unit firing patterns
Authors: Myers Lance J , Erim Zeynep , Lowery Madeleine M
Published: October 2004

Background

In investigations of the human motor system, two approaches are generally employed toward the identification of common modulating drives from motor unit recordings. One is a frequency domain method and uses the coherence function to determine the degree of linear correlation between each frequency component of the signals. The other is a time domain method that has been developed to determine the strength of low frequency common modulations between motor unit spike trains, often referred to in the literature as 'common drive'.

Methods

The relationships between these methods are systematically explored using both mathematical and experimental procedures. A mathematical derivation is presented that shows the theoretical relationship between both time and frequency domain techniques. Multiple recordings from concurrent activities of pairs of motor units are studied and linear regressions are performed between time and frequency domain estimates (for different time domain window sizes) to assess their equivalence.

Results

Analytically, it may be demonstrated that under the theoretical condition of a narrowband point frequency, the two relations are equivalent. However practical situations deviate from this ideal condition. The correlation between the two techniques varies with time domain moving average window length and for window lengths of 200 ms, 400 ms and 800 ms, the r2 regression statistics (p < 0.05) are 0.56, 0.81 and 0.80 respectively.

Conclusions

Although theoretically equivalent and experimentally well correlated there are a number of minor discrepancies between the two techniques that are explored. The time domain technique is preferred for short data segments and is better able to quantify the strength of a broad band drive into a single index. The frequency domain measures are more encompassing, providing a complete description of all oscillatory inputs and are better suited to quantifying narrow ranges of descending input into a single index. In general the physiological question at hand should dictate which technique is best suited.
Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis
Authors: Banerjee Kaustuv , Biswas Partha Sarathi , Rouse Barry T
Published: October 2004

Herpetic stromal keratitis (HSK) results in postinfection with Herpes simplex virus type 1 (HSV-1). The pathogenesis involves tissue damage by the host immune system, classifying HSK as an immunopathological disease. The crucial disease orchestrating cells is thought to be the T lymphocytes. The present study elucidates pathogenic and protective T cell subsets involved in the development of HSK using the gBT mice, which possess a monoclonal population of CD8+ T cells reactive to a HSV immunodominant epitope. Results show that HSV-reactive CD8+ T cells enter infected corneas during the acute but not the chronic phase of the disease during which the predominant population is CD4+ T cells. Adoptive transfer experiments in T and B cell-deficient recombination-activating gene knockout mice revealed that HSV-reactive CD8+ T cells are capable of ocular virs clearance, possibly through a combination of corneal and peripheral nervous system antiviral effects, but are not involved in lesion development. CD4+ T cells of the virus-specific or nonspecific species emerged as the pathogenic T cells capable of precipitating disease. These observations have the potential to yield important treatment strategies by targeting specific cell types in HSK.
Root infinitives in child second language English: an aspectual features account
Authors: Gavruseva Elena
Published: October 2004

This article examines the emergence of finiteness in early second language (L2) English of five consecutive bilinguals (ages 6 to 9). The departure point is Gavruseva’s (2002; 2003) proposal that nonfinite root predicates result from the underspecification of syntactic aspectual heads at the initial state S0. Gavruseva’s ‘underspecification of AspP’ account is developed further by examining the feature contents of aspectual projections in English from a crosslinguistic perspective. It is argued that English, in contrast to Russian and French, lacks the genuine imperfective and perfective morphemes and so makes use of a greater variety of aspectual features (e.g., intrinsic and compositional telicity features, inter alia). It is also proposed that an English verb’s telicity semantics defines its aspectual class and predicts its finiteness status in children’s early grammar. An advantage of the ‘aspectual features account’ is that it explains why statives (inherent atelics) and punctual eventives (inherent telics) show much higher finiteness rates than nonpunctual eventives (an aspectual class defined by a compositional telicity feature) in the child L2 data. Other approaches to the root infinitive phenomenon such as the Truncation Hypothesis (Rizzi 1993=94) and the Morphological Deficit Hypothesis (Haznedar and Schwartz, 1997; Lardiere, 1998; Prévost and White, 2000) cannot explain these finiteness patterns.
Resources on quantitative/statistical research for applied linguists
Authors: Brown James Dean
Published: October 2004

The purpose of this review article is to survey and evaluate existing books on quantitative/statistical research in applied linguistics. The article begins by explaining the types of texts that will not be reviewed, then it briefly describes nine books that address how to do quantitative/statistical applied linguistics research. The review then compares (in prose and tables) the general characteristics of these nine books, and their coverage of conceptual and statistical topics. Examining all nine books together provides answers to three questions: What is the range of conceptual/statistical topics in applied linguistics? What are the most important conceptual/statistical topics in applied linguistics? And, how has the coverage of topics changed over the years? This review article should help readers sort through current books on how to do quantitative/statistical research so that they can locate one or more texts that will best meet their needs.
Familial antiphospholipid antibodies and acquired circulating anticoagulants
Authors: ElHajj I , Uthman I , Chahel A , Khoury F , Arayssi T , Taher A
Published: October 2004

Familial clustering of elevated antiphospholipid antibody levels has been described, but the reports are heterogeneous with regard to the characterization of the antiphospholipid syndrome (APS), coexisting autoimmune diseases and clinical implications. We report a familial occurrence of APS in two patients, in the presence of SLE in the mother and absence of autoimmune diseases in the daughter along with acquired circulating inhibitors in both cases: platelet inhibitor and factor IX inhibitor, respectively.
Autoantibodies recognizing the 27 carboxy-terminal amino acids of calpastatin are associated with secondary Sjögren syndrome in systemic lupus erythematosus
Authors: Salle V , Vittecoq O , Jouen-Beades F , Ménard J F , Ducroix J P , Godin M , Le Loët X , Tron F
Published: October 2004

The objective of this study was to determine in systemic lupus erythematosus (SLE) the prevalence and clinical significance of anticalpastatin antibodies (ACAST), an autoantibody population previously detected in sera from patients with various connective tissue diseases. Eighty-four patients with SLE (mean age: 30 years at diagnosis, females 77) that fulfilled ACR criteria were included in the study retrospectively. Several clinical and biological data were collected. ACAST were detected by a solid-phase enzyme linked immunosorbent assay (ELISA) using as antigen a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27). The prevalence of ACAST-C27 was 13% (11/84) in SLE patients. No correlation was found between the presence of ACAST-C27 and clinical manifestations such as thrombosis and vasculitis. Furthermore, no correlation was observed with the presence of antiphospholipid antibodies (APL). However, we found a statistically significant association between the presence of ACAST-C27 and that of secondary Sjögren syndrome ( P = 0.01). The conclusion is ACAST-C27 are not associated with thrombosis in SLE patients. The association observed between ACAST-C27 and secondary Sjögren syndrome suggests that ACAST-C27 might be useful in discriminating a clinical subgroup of SLE patients.
Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach
Authors: Laustrup H , Heegaard N HH , Voss A , Green A , Lillevang S T , Junker P
Published: October 2004

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1: 40, 1: 80 and 1: 160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-β2 GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1: 160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1: 80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1: 40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1: 80 ( P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores ( P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.
Modulation of Erbb2 signaling during development: a threshold level of Erbb2 signaling is required for development
Authors: Chan Richard , Hardy W. Rod , Dankort David , Laing Michael A. , Muller William J.
Published: October 2004

We have generated a series of Erbb2 cDNA knock-in animals to explore the role of signaling pathways coupled to Erbb2 during development. Although this knock-in allele was hypomorphic, expressing tenfold less Erbb2 protein than wild type, the knock-in animals were healthy. However, a further twofold reduction in Erbb2 levels in hemizygous knock-in animals resulted in perinatal lethality with defects in the innervation of the diaphragm. Genetic rescue of this hypomorph was accomplished by expression of the Erbb2-Y1028F mutant in a comparable knock-in allele. Interestingly, hemizygous Y1028F animals were viable with normal innervation of the diaphragm. Molecular analyses revealed that the Y1028F allele expressed higher levels of Erbb2 and that Y1028 promoted the turnover of the receptor. In addition, ablation of the Shc-binding site in Erbb2 (Y1227) resulted in subtle defects in the sensory nerves not observed in the other mutant erbb2 strains. Thus, we have established how Erbb2 levels may be modulated through development and that a minimum threshold level of Erbb2 is required.
Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells
Authors: Joseph Nancy M. , Mukouyama Yoh-suke , Mosher Jack T. , Jaegle Martine , Crone Steven A. , Dormand Emma-Louise , Lee Kuo-Fen , Meijer Dies , Anderson David J. , Morrison Sean J.
Published: October 2004

Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest,but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived,whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo,consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation.
Eya1 and Six1 are essential for early steps of sensory neurogenesis in mammalian cranial placodes
Authors: Zou Dan , Silvius Derek , Fritzsch Bernd , Xu Pin-Xian
Published: October 2004

Eya1 encodes a transcriptional co-activator and is expressed in cranial sensory placodes. It interacts with and functions upstream of the homeobox gene Six1 during otic placodal development. Here, we have examined their role in cranial sensory neurogenesis. Our data show that the initial cell fate determination for the vestibuloacoustic neurons and their delamination appeared to be unaffected in the absence of Eya1 or Six1 as judged by the expression of the basic helix-loop-helix genes, Neurog1that specifies the neuroblast cell lineage, and Neurod that controls neuronal differentiation and survival. However, both genes are necessary for normal maintenance of neurogenesis. During the development of epibranchial placode-derived distal cranial sensory ganglia, while the phenotype appears less severe in Six1 than in Eya1 mutants, an early arrest of neurogenesis was observed in the mutants. The mutant epibranchial progenitor cells fail to express Neurog2 that is required for the determination of neuronal precursors, and other basic helix-loop-helix as well as the paired homeobox Phox2 genes that are essential for neural differentiation and maintenance. Failure to activate their normal differentiation program resulted in abnormal apoptosis of the progenitor cells. Furthermore, we show that disruption of viable ganglion formation leads to pathfinding errors of branchial motoneurons. Finally, our results suggest that the Eya-Six regulatory hierarchy also operates in the epibranchial placodal development. These findings uncover an essential function for Eya1 and Six1 as critical determination factors in acquiring both neuronal fate and neuronal subtype identity from epibranchial placodal progenitors. These analyses define a specific role for both genes in early differentiation and survival of the placodally derived cranial sensory neurons.
Spatial pattern of sonic hedgehog signaling throughGligenes during cerebellum development
Authors: Corrales JoMichelle D. , Rocco Gina L. , Blaess Sandra , Guo Qiuxia , Joyner Alexandra L.
Published: October 2004

The cerebellum consists of a highly organized set of folia that are largely generated postnatally during expansion of the granule cell precursor (GCP)pool. Since the secreted factor sonic hedgehog (Shh) is expressed in Purkinje cells and functions as a GCP mitogen in vitro, it is possible that Shh influences foliation during cerebellum development by regulating the position and/or size of lobes. We studied how Shh and its transcriptional mediators,the Gli proteins, regulate GCP proliferation in vivo, and tested whether they influence foliation. We demonstrate that Shh expression correlates spatially and temporally with foliation. Expression of the Shh target gene Gli1 is also highest in the anterior medial cerebellum, but is restricted to proliferating GCPs and Bergmann glia. By contrast, Gli2is expressed uniformly in all cells in the developing cerebellum except Purkinje cells and Gli3 is broadly expressed along the anteroposterior axis. Whereas Gli mutants have a normal cerebellum, Gli2 mutants have greatly reduced foliation at birth and a decrease in GCPs. In a complementary study using transgenic mice, we show that overexpressing Shh in the normal domain does not grossly alter the basic foliation pattern, but does lead to prolonged proliferation of GCPs and an increase in the overall size of the cerebellum. Taken together, these studies demonstrate that positive Shh signaling through Gli2 is required to generate a sufficient number of GCPs for proper lobe growth.
DrosophilaDeltex mediates Suppressor of Hairless-independent and late-endosomal activation of Notch signaling
Authors: Hori Kazuya , Fostier Maggy , Ito Mikiko , Fuwa Takashi J. , Go Masahiro J. , Okano Hideyuki , Baron Martin , Matsuno Kenji
Published: October 2004

Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling. However, the precise mechanism of Dx action is unknown. Here, we found that Dx was required and sufficient to activate the expression of gene targets of the canonical Su(H)-dependent N signaling pathway. Although Dx required N and a cis-acting element that overlaps with the Su(H)-binding site, Dx activated a target enhancer of N signaling, the dorsoventral compartment boundary enhancer of vestigial (vgBE), in a manner that was independent of the Delta (Dl)/Serrate (Ser) ligands- or Su(H). Dx caused N to be moved from the apical cell surface into the late-endosome, where it accumulated stably and co-localized with Dx. Consistent with this, the dx gene was required for the presence of N in the endocytic vesicles. Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)-independent N signaling.
Developmental plasticity of physiology and morphology in diet-restricted European shag nestlings (Phalacrocorax aristotelis)
Authors: Moe Børge , Brunvoll Siri , Mork Daniel , Brobakk Trond Einar , Bech Claus
Published: October 2004

Growing animals may exhibit developmental plasticity as an adaptation to variability in the environmental conditions during development. We examined physiological and morphological responses to short-term food shortage of 12–16-day-old European shag nestlings kept under laboratory conditions. After 4 days on a weight maintenance diet, the resting metabolic rate (RMR) of diet-restricted nestlings was 36.5% lower compared with control fed nestlings,after controlling for body mass. This response was accompanied by a reduction in body temperature (Tb) and by reductions in the size of several visceral organs, muscles and lipid stores, while the overall structural growth was maintained almost in line with the age-specific growth rate of controls. Hence, the pattern of energy allocation reflected a very high priority to structural growth at the expense of visceral organs, lipid deposits and muscles. The reduced Tb and size of the liver served as important physiological processes behind the observed reductions in RMR. We discuss the possible adaptive significance of this differential developmental plasticity during temporal food shortage. This is the first study of avian developmental plasticity to report substantial energy saving in combination with a high structural growth rate.
Kinematics of aquatic and terrestrial escape responses in mudskippers
Authors: Swanson Brook O. , Gibb Alice C.
Published: October 2004

Escape responses in fishes are rapid behaviors that are critical for survival. The barred mudskipper (Periophthalmus argentilineatus) is an amphibious fish that must avoid predators in two environments. We compared mudskipper terrestrial and aquatic escapes to address two questions. First,how does an amphibious fish perform an escape response in a terrestrial environment? Second, how similar is a terrestrial escape response to an aquatic escape response? Because a mudskipper on land does not have to contend with the high viscosity of water, we predicted that, if the same behavior is employed across environments, terrestrial escape responses should have`better' performance (higher velocity and more rapid completion of movements)when compared with aquatic escape responses. By contrast, we predicted that intervertebral bending would be similar across environments because previous studies of escape response behaviors in fishes have proposed that vertebral morphology constrains intervertebral bending. High-speed digital imaging was used to record mudskipper escapes in water and on land, and the resulting images were used to calculate intervertebral bending during the preparatory phase, peak velocity and acceleration of the center of mass during the propulsive phase, and relative timing of movements. Although similar maximum velocities are achieved across environments, terrestrial responses are distinct from aquatic responses. During terrestrial escapes, mudskippers produce greater axial bending in the preparatory phase, but only in the posterior region of the body and over a much longer time period. Mudskippers also occasionally produced the `wrong' behavior for a given environment. Thus,it appears that the same locomotor morphology is recruited differently by the central nervous system to produce a distinct behavior appropriate for each environment.
The role of drag in insect hovering
Authors: Wang Z. Jane
Published: October 2004

Studies of insect flight have focused on aerodynamic lift, both in quasi-steady and unsteady regimes. This is partly influenced by the choice of hovering motions along a horizontal stroke plane, where aerodynamic drag makes no contribution to the vertical force. In contrast, some of the best hoverers– dragonflies and hoverflies – employ inclined stroke planes,where the drag in the down- and upstrokes does not cancel each other. Here,computation of an idealized dragonfly wing motion shows that a dragonfly uses drag to support about three quarters of its weight. This can explain an anomalous factor of four in previous estimates of dragonfly lift coefficients,where drag was assumed to be small.

To investigate force generation and energy cost of hovering flight using different combination of lift and drag, I study a family of wing motion parameterized by the inclined angle of the stroke plane. The lift-to-drag ratio is no longer a measure of efficiency, except in the case of horizontal stroke plane. In addition, because the flow is highly stalled, lift and drag are of comparable magnitude, and the aerodynamic efficiency is roughly the same up to an inclined angle about 60°, which curiously agrees with the angle observed in dragonfly flight.

Finally, the lessons from this special family of wing motion suggests a strategy for improving efficiency of normal hovering, and a unifying view of different wing motions employed by insects.
Adjusting muscle function to demand: joint work during acceleration in wild turkeys
Authors: Roberts Thomas J. , Scales Jeffrey A.
Published: October 2004

We measured the net work performed at hind limb joints in running turkeys to determine the source of mechanical power for acceleration. We tested the hypothesis that net mechanical work per step increases in proportion to acceleration at all four major hind limb joints (hip, knee, ankle and tarsometatarsal–phalangeal joint). This hypothesis was based on the idea that all hind limb muscles should contribute mechanical work to maximize performance during accelerations, and a previous study that indicated the mechanical power output of the entire turkey hind limb musculature was remarkably high. We used high-speed video and force-plate measurements to measure joint moment, velocity and power output during single foot-contacts of running accelerations. By measuring steps in which the animals were relatively more or less motivated to accelerate, we obtained data for a range of accelerations, all at approximately the same running speed. Net joint work per step increased at the hip and ankle as a function of acceleration. Hip net work per unit body mass was 0.12±0.09 J kg-1 averaged over the five lowest accelerations (–0.22±0.08 m s-2), and 0.87±0.20 J kg-1 for the five highest accelerations(4.86±0.27 m s-2). Ankle work was –0.21±0.11 J kg-1 for the lowest accelerations and 0.71±0.28 J kg-1 for the highest. The high work output at the ankle is consistent with the idea that elastic mechanisms function to increase muscle work during acceleration. The work performed at the knee and tarsometatarsal–phalangeal joint was independent of acceleration in a step. These results support the idea that hip and ankle extensors contribute significantly to the work necessary to accelerate the body.

We also measured the change in joint moment and angular excursion with acceleration to determine whether the mechanism for increasing work output at a joint involved an increase in muscle force or muscle shortening. The increase in joint work at the hip and ankle resulted almost entirely from an increase in joint angular excursion during stance. Hip extension increased by more than threefold from the lowest to the highest accelerations, and the angular excursion of the ankle increased from –24.8±4.7° (net flexion) at the lowest accelerations to 33.0±12.8° (net extension)at the highest accelerations. Mean stance joint moment was unchanged with acceleration at the ankle and increased by approximately 35% at the hip across the range of accelerations. These patterns of joint moment and excursion indicate that turkeys increase mechanical work for acceleration primarily by increasing muscle shortening, rather than muscle force.
Inflation of the esophagus and vocal tract filtering in ring doves
Authors: Riede Tobias , Beckers Gabriël J. L. , Blevins William , Suthers Roderick A.
Published: October 2004

Ring doves vocalize with their beaks and nostrils closed, exhaling into inflatable chambers in the head and neck region. The source sound produced at the syrinx contains a fundamental frequency with prominent second and third harmonic overtones, but these harmonics are filtered out of the emitted signal. We show by cineradiography that the upper esophagus, oral and nasal cavities collect the expired air during vocalization and that the inflated esophagus becomes part of the suprasyringeal vocal tract. The level of the second and third harmonics, relative to the fundamental frequency(f0), is reduced in the esophagus and emitted vocalization compared with in the trachea, although these harmonics are still considerably higher in the esophagus than in the emitted signal. When the esophagus is prevented from fully inflating, there is a pronounced increase in the level of higher harmonics in the emitted vocalization. Our data suggest that the trachea and esophagus act in series as acoustically separate compartments attenuating harmonics by different mechanisms. We hypothesize that the trachea behaves as a tube closed at the syringeal end and with a variable, restricted opening at the glottal end that lowers the tracheal first resonance to match the f0 of the coo. The inflated esophagus may function as a Helmholtz resonator in which the elastic walls form the vibrating mass. Such a resonator could support the f0 over a range of inflated volumes.
Why do macaroni penguins choose shallow body angles that result in longer descent and ascent durations?
Authors: Sato Katsufumi , Charrassin Jean-Benol̂t , Bost Charles-André , Naito Yasuhiko
Published: October 2004

It is generally assumed that air-breathing aquatic animals always choose the shortest route to minimize duration for transit between the surface and foraging depth in order to maximize the proportion of time spent foraging. However, empirical data indicate that the body angles of some diving animals are rarely vertical during descent and ascent. Why do they choose shallower body angles that result in longer descent and ascent durations? To investigate this question, we attached acceleration data loggers to eight female macaroni penguins, breeding on the Kerguelen Islands(48°45′–50°00′S,68°45′–70°58′E; South Indian Ocean), to record depth, two-dimensional acceleration (stroke cycle frequency and body angle)and temperature. We investigated how they controlled body angle and allocated their submerged time. The instrumented females performed multiple dives(N=6952) with a mean dive depth for each bird ranging from 24.5±28.5 m to 56.4±75.1 m. Mean body angles during descent and ascent were not vertical. There was large variation in mean descent and ascent angles for a given dive depth, which, in turn, caused large variation in descent and ascent duration. Body angles were significantly correlated with time spent at the bottom-phase of the dive. Birds that spent long periods at the bottom exhibited steep body angles during ascent and subsequent descent. By contrast, they adopted shallow body angles after they had short or no bottom phases. Our results suggest that macaroni penguins stay at the bottom longer after encountering a good prey patch and then travel to the surface at steep body angles. If they do not encounter prey, they discontinue the dive,without staying at the bottom, ascend at shallow body angles and descend at shallow body angles in a subsequent dive. A shallow body angle can increase the horizontal distance covered during a dive, contributing to the move into a more profitable area in the following dive. During the ascent, in particular,macaroni penguins stopped beating their flippers. The buoyantly gliding penguins can move horizontally with minimum stroking effort before reaching the surface.
Palindromes in SARS and Other Coronaviruses
Authors: Chew David S. H. , Choi Kwok Pui , Heidner Hans , Leung Ming-Ying
Published: October 2004

With the identification of a novel coronavirus associated with the severe acute respiratory syndrome (SARS), computational analysis of its RNA genome sequence is expected to give useful clues to help elucidate the origin, evolution, and pathogenicity of the virus. In this paper, we study the collective counts of palindromes in the SARS genome along with all the completely sequenced coronaviruses. Based on a Markov-chain model for the genome sequence, the mean and standard deviation for the number of palindromes at or above a given length are derived. These theoretical results are complemented by extensive simulations to provide empirical estimates. Using a z score obtained from these mathematical and empirical means and standard deviations, we have observed that palindromes of length four are significantly underrepresented in all the coronaviruses in our data set. In contrast, length-six palindromes are significantly underrepresented only in the SARS coronavirus. Two other features are unique to the SARS sequence. First, there is a length-22 palindrome TCTTTAACAAGCTTGTTAAAGA spanning positions 25962–25983. Second, there are two repeating length-12 palindromes TTATAATTATAA spanning positions 22712–22723 and 22796–22807. Some further investigations into possible biological implications of these palindrome features are proposed.
Optimal Solutions for the Closest-String Problem via Integer Programming
Authors: Meneses Cláudio N. , Lu Zhaosong , Oliveira Carlos A. S. , Pardalos Panos M.
Published: October 2004

In this paper we study the closest-string problem (CSP), which can be defined as follows: Given a finite set 𝒮 = {s1, s2, …, sn} of strings, each string with length m, find a center string t of length m minimizing d, such that for every string si ∈ 𝒮, dH(t, si) ≤ d. By dH(t, si) we mean the Hamming distance between t and si. This is an NP-hard problem, with applications in molecular biology and coding theory. Even though there are good approximation algorithms for this problem, and exact algorithms for instances with d constant, there are no studies trying to solve it exactly for the general case. In this paper we propose three integer-programming (IP) formulations and a heuristic, which is used to provide upper bounds on the value of an optimal solution. We report computational results of a branch-and-bound algorithm based on one of the IP formulations, and of the heuristic, executed over randomly generated instances. These results show that it is possible to solve CSP instances of moderate size to optimality.
Searching for Multiple Words in a Markov Sequence
Authors: Park Yonil , Spouge John L.
Published: October 2004

The theory of the discrete-time Markovian arrival process (DMAP) can be applied to some statistical problems encountered when searching for multiple words in a Markov sequence. Such word searches are often emphasized in studies of the human genome. There are several advantages to the DMAP approach we present. Most notably, its derivations are transparent, and they readily unify disparate results about the exact distributions of overlapping and nonoverlapping word counts. We also present several examples and applications of our theory, including a numerical study using a random DNA dataset from the human genome.