bluuebunny/crossref_metadata_2025 huggingface dataset:
The Political Art of Jacques‐Louis David and his Modern Day American Successors
Authors: Carrier David
Published: December 2003

Until relatively recently, Jacques‐Louis David was a famous, relatively well‐understood painter. Thanks to Thomas Crow, and a number of recent historians, his art now has come to seem much more complex. According to these writers, David's pre‐Revolutionary paintings make subtle comments on French politics of the Revolutionary period. I demonstrate that this way of thinking cannot be understood without acknowledging the intense desire of recent American critics that there be art which is aesthetically significant and politically critical. Crow's account of David, so I argue, projects back into the 1780s important concerns of American art writers in the 1980s.
Modelling phylogenetic relationships using reticulated networks
Authors: Makarenkov Vladimir , Legendre Pierre , Desdevises Yves
Published: December 2003

Makarenkov, V., Legendre, P. & Desdevises, Y. (2004). Modelling phylogenetic relationships using reticulated networks. — Zoologica Scripta, 33, 89–96.

Most traditional methods of phylogenetic analysis assume that species evolution can be represented by means of a bifurcating tree model. In many phylogenetic situations, however, some of the evolutionary links between species are due to reticulate evolution. For instance, reticulate models can adequately describe such complicated mechanisms as lateral gene transfer in bacteria or species hybridization. The theoretical concepts of reticulate evolution developed in the 1980s and 1990s need to be supported by appropriate analytical tools and software. In this paper, we present the main features of a new distance‐based method for modelling phylogenetic relationships among species by means of reticulated networks (RNs). The method uses the least‐squares model to build a RN by gradually improving upon the solution provided by a phylogenetic tree. A computer program facilitating the reconstruction and visualization of reticulate phylogenies is made available to researchers. In the application section, we illustrate the usefulness of the method by studying the evolution of honeybees (genus Apis). The method for reconstructing RNs has been included in the T‐Rex (Tree and Reticulogram Reconstruction) package recently developed by the first‐named author.
Factors secreted by Schwann cells stimulate the regeneration of neonatal retinal ganglion cells
Authors: Taylor Jeremy S. H. , Bampton Edward T. W.
Published: December 2003

The adult mammalian central nervous system (CNS) does not repair after injury. However, we and others have shown in earlier work that the neonatal CNS is capable of repair and importantly of allowing regenerating axons to re‐navigate through the same pathways as they did during development. This phase of neonatal repair is restricted by the fragility of neurons after injury and a lack of trophic factors that enable their survival. Our aim is to define better the factors that sustain neurons after injury and allow regeneration to occur. We describe some of our work using Schwann cells to promote the regeneration of neurons from young postnatal rodents. We have established rapid methods for purifying Schwann cells without the use of either anti‐mitotic agents to suppress contaminating fibroblasts or mitotic stimulation to generate large numbers of Schwann cells. The rapidly purified Schwann cells have been used to generate conditioned medium that we have shown stimulates axon regeneration in cultured retinal ganglion cell neurons. We also show that the positive effects of Schwann cells are still present after pharmacological blockade of the neurotrophin receptors, suggesting that novel factors mediate these effects.
Oral microbial flora and oral malodour of the institutionalised elderly in Japan
Authors: Honda Eiki
Published: December 2003

Objectives: To determine the oral health status, especially the level of oral microbial flora and oral malodour, of institutionalised elderly people compared with non‐institutionalised elderly people.

Setting: Three institutions and numerous private homes.

Subjects: 56 institutionalised and 56 non‐institutionalised elderly people.

Main Outcome Measures: Institutionalised elderly people had higher levels of Candida, staphylococci, and oral malodour.

Results: Institutionalised elderly people had a higher level of Candida in denture wearers, and a higher level of staphylococci and oral malodour compared with the non‐institutionalised elderly.

Conclusion: The institutionalised elderly have a higher risk of opportunistic infections and oral health care should be improved to protect them from these infections and to reduce oral malodour.
Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change
Authors: Williams DW , Bartie KL , Potts AJC , Wilson MJ , Fardy MJ , Lewis MAO
Published: December 2003

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC).

Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination.

Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates.

Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.
Clinical and behavioural risk indicators for root caries in older people
Authors: Steele James G , Sheiham Aubrey , Marcenes Wagner , Fay Nick , Walls Angus W G
Published: December 2003

Objective: To investigate the clinical and behavioural factors indicating root caries risk among older people.

Desing: Cross sectional clinical and interview data from the National Diet and Nutrition Survey (aged 65 years and over) in Great Britain. Logistic regression models of the prevalence of root caries and linear regression models of the extent of root caries were constructed to quantify the role of a range of clinical and behavioural risk indicators, including sugars intake.

Setting: A national sample of older British adults, free‐living and institutionalised. Participants: 462 dentate adults aged 65 years or over.

Results: Nine or more intakes of sugars per day more than doubled the odds of root caries being present (OR 2.2–2.4). Other clinical and behavioural factors affecting root caries included wearing a partial denture in the presence of heavy plaque deposits (OR 2.1–2.6) and infrequent tooth brushing (OR 2.8 – 4.1). Linear regression models showed that, amongst those that had root caries, sucking sweets in the presence of a dry mouth, poor hygiene, partial dentures and living in an institution contributed to the extent of root caries, as measured by the RCI(d).

Conclusions: Of the factors open to possible clinical or behavioural intervention, frequent sugars intake, poor hygiene and partial dentures were all associated with large increases in risk.
Food choices and eating difficulty among elderly edentate patients in Greece
Authors: Anastassiadou Vassiliki , Heath M. Robin
Published: December 2003

Aims: To evaluate food choice and eating difficulty experienced by older Greek edentate patients.

Subjects: Three samples of patients seeking provision of replacement dentures were studied. A primary study of urban mainland U1 (n=54) and island rural R1 samples (n=84) was followed by a mainland urban U2 sample (n=119) in the Secondary study.

Setting: Greek dental clinics.

Intervention: Semi‐structured interviews (SSI) were employed, using both open and closed questions.

Design: The primary study used SSI to identify eating difficulty experienced by two culturally different Greek groups. The secondary study established patterns of difficulty for comparisons between an urban Greek population and northern European urban studies.

Main Outcome Measures: The prevalence of eating difficulty, the degree of difficulty eating specified foods and the exclusion of foods because difficult.

Results: Most patients expressed difficulty eating at least one type of food, a high percentage of these patients were willing to eat foods found difficult, while others use particular methods of food preparation that make food easier to eat. Chicken illustrated the importance of specifying the method of cooking when questioning eating difficulties. Roast meats provided insight into the more difficult end of the food range. Raw vegetables were rated difficult. Apples and oranges were also food of particular interest.

Conclusions: The semi‐structured interview method provides a succesful method to identify eating difficulty and food choices by older Greek complete denture wearers. Differences, probably largely cultural, were identified between Greek island rural and mainland urban communities. Greek food choices differed favourably from an English sample, strikingly in that Greek patients report continuing to eat difficult foods despite difficulty eating them. This may be relevant to health data on Greek populations that show better mortality statistics despite adverse factors such as high prevalence of smoking.
Colonization of denture plaque by respiratory pathogens in dependent elderly
Authors: Sumi Y , Miura H , Sunakawa M , Michiwaki Y , Sakagami N
Published: December 2003

Objectives: Recently, there has been a resurgence of interest in the interactions between oral conditions and a number of prevalent systemic diseases. The morbidity and mortality of the dependent elderly that result from aspiration pneumonia have been recognized as a major geriatric health problem. The purpose of this study was to gain more information on the microflora of plaque on dentures and to assess the existence of oral infectious pathogens potentially causing the respiratory disease in the dependent elderly.

Subjects and Methods: The denture bacterial flora of 50 dependent elderly were examined to identify microorganisms by the culture method.

Results: 18 species of microorganisms were detected in denture plaque in this study. A variety of pathogens with the potential to cause respiratory infection pathogens colonized on the dentures of dependent elderly.

Conclusion: The results of the present study revealed that bacteria that commonly cause respiratory infection colonized on the dentures of dependent elderly, suggesting that denture plaque may function as a reservoir of potential respiratory pathogens to facilitate colonization on the oropharynx.
The causes and consequences of maxillofacial injuries in elderly people
Authors: Rehman K. , Edmondson H
Published: December 2003

Objective: The occurrence of trauma in older people is well‐documented; however the incidence of maxillofacial trauma is scarcely reported. Therefore, the objective of this study is to determine the causes and consequences of maxillofacial trauma in older people. Design: A five‐year (March 95 ‐ March 2000) retrospective study was earned out of all patients over the age of 65 years with facial trauma presenting to Accident and Emergency Department (A&E). The information was collected using the medical notes and discharge summaries.

Setting: The Departments of A&E and Maxillofacial Surgery.

Subjects: A total of 42 patients' records were examined for study related data.

Results: A total of 42 patients were seen during the study period. Thirty‐six gave a history of a fall, of which 15 had tripped, 5 had slipped, 3 resulted from a Transient Ischaemic Attack (TIA), 1 as a result of alcohol abuse, in 1 a prosthetic knee gave way and 11 gave no cause for the fall. Of the remaining 6 patients. 5 were assaulted and 1 had a wardrobe fall on top of him. The majority of the falls occurred during the winter months. Maxillofacial injuries were noted in 27 of the 42 patients. Sixteen patients had cheekbone fractures, 8 mandibular fractures, 2 midface and 1 orbital complex fracture. Twenty‐five percent of cheekbone fractures and 50% of mandibular fractures were treated surgically. Medical history was noted in 27 patients.

Conclusions: This study clearly demonstrates the majority of the facial trauma in the older people can be treated conservatively unless the patients complain of functional problems.
Oral health behind bars: A study of oral disease and its impact on the life quality of an older prison population
Authors: McGrath Colman
Published: December 2003

Objective: The principal aims of this study were to report on the prevalence of oral disease and its impact on the life quality of older (aged 60 and above) prisoners at Hong Kong SAR's elderly detention centre, China.

Design: A cross‐sectional epidemiological survey involving clinical oral examinations and face‐to‐face interviews with 64 older prisoners at the centre. Clinical oral examinations were carried out following WHO criteria. The impact of oral health on life quality was assessed using the 14‐item Oral Health Impact Profile measure, OHIP‐14

Results: The prevalence of oral disease was high, the mean DMFT was 22.5 (SD 10.6) and 40% (18) of the dentate prisoners had shallow or deep periodontal pockets. Most (75%, 48) were in need of prosthetic treatment. Over half the prisoners experienced one or more oral health impacts on life quality during the previous year. This was associated with socio‐demographic factors: employment status prior to incarceration (P<0.01), oral health behaviour: smoking habits (P<0.01) and clinical oral health status: DMFT (P<0.05) and prosthetic need (P<0.05).

Conclusion: Among inmates at Hong Kong's elderly detention centre, the prevalence of oral disease was high and the impact of oral health on their life quality was substantial. The impact of oral health on the life quality of the older prisoners was associated with prisoners socio‐demographic background, oral health behaviour and oral health status.
Influence of age and dental status on chewing behaviour studied by EMG recordings during consumption of various food samples
Authors: Kohyama K. , Mioche L. , Bourdio P.
Published: December 2003

Objective: To evaluate the effects of age and dental status on chewing performance in humans. Design: Electromyography recordings (EMG) were made during chewing of six foods (rice, beef, cheese, crispy bread, apple, and peanuts) to compare the masticatory patterns of four subject groups with different ages and dental status. Subjects: Nineteen elders (mean age 67.2 years) classified into three categories according to their number of opposing post‐canine teeth pairs (i.e. functional units) and a control group of 10 young adults (mean age 26.5 years) with a high number of functional units. Main outcome measures: Number of chewing cycles, chewing time, total muscle activity and muscle activity per chew, burst and inter‐burst durations, maximum and mean voltages from EMG recordings. Results: Time‐related EMG parameters increased from young subjects to elderly subjects with high, middle and low dental status. Parameters related to EMG voltages per chew decreased in the same order among the different groups of subjects. These tendencies were observed for all the studied products. Subjects with weak muscle contraction may compensate for their poor chewing performance by lengthening both chewing cycle and sequence duration. Additional alterations in the chewing patterns were observed when age effect was associated with a dental status degradation in terms of number of functional units. Conclusion: Impairment in mastication for the elderly is due to both ageing and decreasing number of functional pairs of post‐canine teeth.
Factors influencing eating ability of old in‐patients in a rehabilitation hospital in Japan
Authors: Ono Takahiro , Hori Kazuhiro , Ikebe Kazunori , Nokubi Takashi , Nago Shotaro , Kumakura Isami
Published: December 2003

Objectives: This study was designed to determine the factors influencing eating ability of old in‐patients in a rehabilitation hospital. Design: Cross‐sectional investigation. Setting: Forty‐six in‐patients in the rehabilitation ward of Hashimoto Hospital in Kagawa Prefecture in Japan were investigated using a multi‐disciplinary approach. Main outcome measures: Age, gender, state of dentition, muscle activity of lip, cheek and tongue, biting force, salivary flow rate per a minute (SFR), masticatory ability for gummy jelly, swallowing ability, texture of meal, independency of walking (Functional Independence Measure=FIM) and ability to communicate. Results: Bivariate analysis for the relationship between surveyed items and masticatory ability (chi‐square test) identified that better masticatory ability for gummy jelly was associated with age (<85 years), gender (male), state of dentition (dentate), SFR (high), activity of lip (good), biting force (high), swallowing ability (good) and activity of communication (high). Among these items, SFR (p=0.001), gender (p=0.004), ability to communicate (p=0.005) and age (p=0.012) were found having an influence on the masticatory ability (logistic regression analysis). On the other hand, age (<85years), gender (male), SFR (high), activity of lip (good), activity of cheek (good), biting force (high), masticatory ability (good) and swallowing ability (good) had a relationship with normal texture of meal. In regression analysis, only two items, activity of lip (p=0.003) and swallowing ability (p=0.024) emerged as factors on texture of meal. Conclusions: Masticatory ability for gummy jelly was influenced by cognitive function and was excluded from the factors on the state of meal. These results suggested the limitation of evaluation using test food, so dentists should observe eating behaviour of in‐patients. In addition, dentists should pay attention to the activity of the lip and swallowing ability as well as dentition and prostheses in the rehabilitation of eating ability. As SFR was the most significant factor on masticatory ability, this emphasizes the necessity of care for dry mouth caused by side effects of multi‐medication
Contemporary Models of Youth Development and Problem Prevention: Toward an Integration of Terms, Concepts, and Models
Authors: Small Stephen , Memmo Marina
Published: December 2003

Over the past several years, increased interest in preventing youth problems and promoting healthy youth development has led youth and family practitioners, policy makers, and researchers to develop a wide range of approaches based on various theoretical frameworks. Although the growth in guiding frameworks has led to more complex models and a greater diversity in the options available to scholars and practitioners, the lack of an integrative conceptual scheme and consistent terminology has led to some confusion in the field. Here, we provide an overview of three approaches to youth development and problem prevention, critically examine their strengths and weaknesses, and offer some elaborations to help clarify, extend, and integrate the models. We conclude by discussing some general implications for researchers, practitioners, and policy makers.
Key Issues in the Practice of Youth Development
Authors: Silliman Benjamin
Published: December 2003

Three significant trends in youth development practice are discussed: movement toward consensus in models guiding practice, movement toward science‐based practice, and increasing resources available to practitioners. Consensus on an ecological framework for risk reduction and competence building among advocates for prevention, resilience, and developmental paradigms improves selection of appropriate strategies for all youth audiences, as does research‐based evidence on effective programs. Practitioners enjoy an increasing number of print and Internet resources for information, curriculum, program evaluation and improvement, and professional training. Continued improvements in programming and research can significantly enhance existing programs and related areas, but cuts in funding for program sustainability and expansion to all cultural groups represent a major threat to youth development.
Caregivers of Older Adults: Advantages and Disadvantages of Internet‐based Social Support*
Authors: Colvin Jan , Chenoweth Lillian , Bold Mary , Harding Cheryl
Published: December 2003

We explored the perceptions of caregivers of older adults using Internet‐based social support networks regarding the unique advantages and disadvantages of online social support. Participants were recruited with permission of Web owners through 15 Web sites that offered social networks, and responses from 63 electronically submitted surveys were analyzed qualitatively. Two major advantages of online social support were attributes of computer‐mediated communication (CMC)(anonymity, asynchrony, and ability to personalize use) and connectivity (connecting with other caregivers). Disadvantages included limitations of CMC and complaints with CMC. Findings suggest that Internet use may be a potential resource for caregivers in expanding their status‐similar social support networks.
Family Advocates’ Perspectives on the Early Academic Success of Children Born to Low‐Income Adolescent Mothers*
Authors: Luster Tom , Bates Laura , Vandenbelt Marcia , Angela Nievar M.
Published: December 2003

Qualitative analyses were conducted to examine family factors related to individual differences in the early school success of children born to low‐income adolescent mothers from the perspective of paraprofessional family advocates. These families were participants in a 5‐year family support program. Achievement test scores and teacher ratings were used to identify the most successful and least successful students in first grade. Interviews with the advocates about the life experiences of children in each of these groups revealed differences between them in the areas of caregiving practices, maternal characteristics, child characteristics, and contextual sources of stress and support. Given that family service providers are rarely used as informants in this way, the possible strengths and limitations of this approach are discussed.
“I was more her Mom than she was mine:” Role Reversal in a Community Sample*
Authors: Mayseless Ofra , Bartholomew Kim , Henderson Antonia , Trinke Shanna
Published: December 2003

Family processes associated with childhood role reversal and related adult outcomes were examined in a community sample (128 adults) using a semistructured interview exploring family, friend, and romantic relationships. Women showed stronger role reversal than men, and role reversal was stronger with mothers than with fathers. Role reversal of women with mothers was associated with parental divorce, neglect, and rejection. Only parental divorce was consistently associated with men's role reversal. Role reversal was not associated with current symptoms for either men or women, nor with attachment orientations for women. Three patterns with distinct family dynamics and outcomes—guardians/protectors, pleasers/compliants, and spousified—emerged from qualitative analyses of 16 women who experienced high levels of childhood role reversal.
Early Adolescence Talking Points: Questions that Middle School Students Want To Ask Their Parents*
Authors: Richardson Rhonda A.
Published: December 2003

In early adolescence, young people need caring parents to guide them through numerous changes and decisions. Little is known about what particular issues middle school students want to discuss with their parents. This study provides a basis for promoting parent–child communication by identifying topics that young adolescents would like to talk about with parents, using responses from 1,124 students age 10 to 15. Findings were that the largest percentage of questions pertained to family issues, whereas only 1 in 4 dealt with sensitive subjects such as drugs and sex. Implications for practice are included.
Isoform specificity of human Na+,K+‐ATPase localization and aldosterone regulation in mouse kidney cells
Authors: Summa Vanessa , Camargo Simone M. R. , Bauch Christian , Zecevic Marija , Verrey François
Published: December 2003

Short‐term aldosterone coordinately regulates the cell‐surface expression of luminal epithelial sodium channels (ENaC) and of basolateral Na+ pumps (Na+,K+‐ATPase α1–β1) in aldosterone‐sensitive distal nephron (ASDN) cells. To address the question of whether the subcellular localization of the Na+,K+‐ATPase and its regulation by aldosterone depend on subunit isoform‐specific structures, we expressed the cardiotonic steroid‐sensitive human α isoforms 1–3 by retroviral transduction in mouse collecting duct mpkCCDc14 cells. Each of the three exogenous human isoforms could be detected by Western blotting. Immunofluorescence indicated that the exogenous α1 subunit to a large extent localizes to the basolateral membrane or close to it, whereas much of the α2 subunit remains intracellular. An ouabain‐sensitive current carried by exogenous pumps could be detected in apically amphotericin B‐permeabilized epithelia expressing human α1 and α2 subunits, but not the α3 subunit. This current displayed a higher apparent Na+ affinity in pumps containing human α2 subunits (10 mm) than in pumps containing human α1 (33.2 mm) or endogenous (cardiotonic steroid‐resistant) mouse α1 subunits (mean: 16.3 mm). A very low mRNA level of the Na+,K+‐ATPase γ subunit (FXYD2) in mpkCCDc14 cells suggested that this ancillary gene product is not responsible for the relatively low apparent Na+ affinity measured for a1 subunit‐containing pumps. Aldosterone increased the pump current carried by endogenous pumps and by pumps containing the human α1 subunit. In contrast, the current carried by pumps with a human α2 subunit was not stimulated by the same treatment. In summary, quantitative basolateral localization of the Na+,K+‐ATPase and its responsiveness to aldosterone require α1 subunit‐specific sequences that differentiate this isoform from the α2 and α3 subunit isoforms.
Effects of inflation on the coupling between the ribs and the lung in dogs
Authors: Troyer André De , Leduc Dimitri
Published: December 2003

The coupling between the ribs and the lung in dogs increases with increasing rib number in the cranial part of the rib cage and then decreases markedly in the caudal part. The hypothesis was raised that this non‐uniformity is primarily related to differences between the areas of the lung subtended by the different ribs, and in the current study we tested this idea by assessing the effects of passive lung inflation. Thus, by causing a descent of the diaphragm, inflation would expand the area of the lung subtended by the caudal ribs and improve the coupling between these ribs and the lung. The axial displacements of the ribs and the changes in airway opening pressure (ΔPao) were measured in anaesthetized, pancuronium‐treated, supine dogs while loads were applied in the cranial direction to individual rib pairs at functional residual capacity (FRC) and after passive inflation to 10 and 20 cmH2O transrespiratory pressure. In agreement with the hypothesis, inflation caused an increase in ΔPao for ribs 9 and 10. The most prominent alteration, however, was a marked decrease in ΔPao for ribs 2–8; at 20 cmH2O, ΔPao for these ribs was only 30% of the value at FRC. Additional measurements indicated that this decrease in ΔPao results partly from the increase in diaphragmatic compliance but mostly from the reduction in outward rib displacement. This alteration in the pattern of rib motion should add to the decrease in muscle length to reduce the lung expanding action of the external intercostal muscles at high lung volumes.
Reducing Integrins Improves the Quality of Fly Life
Authors: Torgler Catherine N. , Brown Nicholas H.
Published: December 2003

Integrins are cell surface receptors that mediate adhesion to the extracellular matrix. In this Perspective, we focus on the recent finding that a decrease in the levels of integrins yields fruit flies that retain youthful mobility as they age and display an increased mean life span. We discuss how the reduction of integrin activity might lead to the observed changes.
Common Denominator
Authors: Beckman Mary
Published: December 2003

Like a beaver dam that backs up a river into its tributaries, a crippled metabolic enzyme causes overflows upstream that spur cardiovascular disease in diabetics, new research shows. The results suggest that breaching the dam might be a new approach for preventing diabetes-related heart disease.
Huntington's Disease
Authors: Groves Mark , Vonsattel Jean-Paul , Mazzoni Pietro , Marder Karen
Published: December 2003

In this case study, we describe the symptoms, neurological exam, neuropsychological test results, and brain pathology of a man who died with Huntington's disease (HD). HD is a rare neurodegenerative disease. Like other movement disorders involving the basal ganglia, HD affects motor, cognitive, and psychiatric functioning. The disease follows an autosomal dominant pattern of inheritance, with onset of symptoms most commonly occurring in the late 30s or early 40s, as in this patient. HD is caused by an unstable expansion of the trinucleotide CAG, coding for glutamine, on chromosome 4. Despite knowledge of the gene mutation responsible for HD, no definitive treatment is currently available to slow or halt progression of the disease. However, symptomatic treatment can significantly improve the quality of life for patients with HD.
The "Fly Die" Diet
Authors: Beckman Mary
Published: December 2003

Like the fine print in a late-night infomercial for a miracle supplement, new work suggests that with a life-extending diet, "results may vary." Rations that lengthen worm life span hasten fruit fly demise, new research shows. The victuals lack a component of mitochondria, the cell's power plants. The diet quickened the pace of mitochondrial decay, a problem that exists in human disease, suggesting that fruit flies might mimic age-related decline of human mitochondrial function better than worms do.
Visceral Reaction
Authors: Leslie Mitch
Published: December 2003

When it comes to aging, nematodes listen to their gut as well as their head, according to new work. The study indicates that the intestine helps determine how fast the animal grows old, adding a new twist to previous work that implicated the worm's neurons.
Consequence, Not Cause
Authors: Davenport R. John
Published: December 2003

NEW ORLEANS, LOUISIANA
--Overloading a microphone can turn a sweet sax solo into a high-pitched squall. Similarly, a flood of the neurotransmitter glutamate--from stroke, brain injury, or neurodegenerative disease--provokes excess neuron firing and causes cells to die (see
Nicholls Perspective
). Previous studies hinted that reactive oxygen species (ROS) spurred this slaughter, but new research shows that ROS are a byproduct of the process, according to work presented here on 10 November 2003 at the Society for Neuroscience Annual Meeting. The study helps place ROS in the order of events that lead to neuron death.
Eat Less, Nurture Neurons
Authors: Davenport R. John
Published: December 2003

NEW ORLEANS, LOUISIANA
--A diet that extends life also repels brain plaques associated with Alzheimer's disease, according to research presented here 10 November 2003 at the Society for Neuroscience Annual Meeting. The feeding plan also reduces amounts of a brain protein that apparently impairs the ability of neurons to make new connections.
Coronary Artery Disease and the MEF2A Transcription Factor
Authors: Olson Eric N.
Published: December 2003

Coronary artery disease (CAD) that results from lesions of the vascular wall is a major cause of myocardial infarction (MI) and stroke. A human pedigree with a predisposition to CAD and MI has been shown to harbor a mutation in the MEF2A transcription factor. These findings reveal a new function for this regulator of cardiovascular development and raise intriguing questions about the underlying mechanisms of CAD.
What's That Smell?
Authors: Davenport R. John
Published: December 2003

Elderly flies lose the capacity to identify evil odors, but memories don't flee immediately after the insects take a sniff, according to new research. The work reveals that old age impairs a middle stage of memory storage, and it links the deficit to a known memory-control gene. The connection provides a starting point for deciphering why brain retention falters with age.
Cyclin-Dependent Kinase 5--A Neuronal Killer?
Authors: Guo Qing
Published: December 2003

In dividing cells, cyclin-dependent kinases (Cdks) are cell cycle-associated protein kinases that regulate proliferation, differentiation, senescence, and apoptosis. In neurons that no longer divide, deregulation of Cdks, especially Cdk5, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Cdk5 is a unique member of the Cdk family because it does not play a critical role in cell cycle progression, and it is not activated by a cyclin. Instead, Cdk5 normally is activated by the regulatory protein p35. This Cdk5/p35 activity has emerged as an important regulator of proper development of the mammalian central nervous system. In vitro studies suggest that aberrant activation of Cdk5 by an endogenous truncated version (p25) of p35 might be a key event in the process of neurodegeneration. One enzyme responsible for cleavage of p35 to form p25 is calpain, a calcium-activated protease that has been shown to be involved in neuronal cell death. Recent studies provided important in vivo evidence that hyperactivation and redistribution of Cdk5 by p25 plays an essential role in the phosphorylation of "pathological" substrates (such as tau) and the cell death of neurons in experimental models of AD and PD. Because amyloid β peptide, the primary neurotoxic component of amyloid plaques in AD, has been shown to increase the conversion of p35 to p25, aberrant activation of Cdk5 by p25 might be a pathway connecting amyloid β toxicity to tau hyperphosphorylation in AD.
Transformation of Olfactory Representations in the
Drosophila
Antennal Lobe
Authors: Wilson Rachel I. , Turner Glenn C. , Laurent Gilles
Published: December 2003

Molecular genetics has revealed a precise stereotypy in the projection of primary olfactory sensory neurons onto secondary neurons. A major challenge is to understand how this mapping translates into odor responses in these second-order neurons. We investigated this question in
Drosophila
using whole-cell recordings in vivo. We observe that monomolecular odors generally elicit responses in large ensembles of antennal lobe neurons. Comparison of odor-evoked activity from afferents and postsynaptic neurons in the same glomerulus revealed that second-order neurons display broader tuning and more complex responses than their primary afferents. This indicates a major transformation of odor representations, implicating lateral interactions within the antennal lobe.
TOR Signaling
Authors: Harris Thurl E. , Lawrence John C.
Published: December 2003

The mammalian target of rapamycin, mTOR, is a protein Ser-Thr kinase that functions as a central element in a signaling pathway involved in the control of cell growth and proliferation. The activity of mTOR is controlled not only by amino acids, but also by hormones and growth factors that activate the protein kinase Akt. The signaling pathway downstream of Akt leading to mTOR involves the protein products of the genes mutated in tuberous sclerosis, TSC1 and TSC2, and the small guanosine triphosphatase, Rheb. In cells, mTOR is found in a complex with two other proteins, raptor and mLST8. In this review, we describe recent progress in understanding the control of the mTOR signaling pathway and the role of mTOR-interacting proteins.
Meeting Report: Cellular Dependence--Old Concept, New MechanismsA review of the meeting Dependence Receptors, Fondation des Treilles, France, 3 to 7 July 2003.
Authors: Mehlen Patrick , Bredesen Dale E.
Published: December 2003

Programmed cell death occurs in response to both the presence of various extracellular factors and the lack of specific factors. Receptors that can mediate cell death in the absence of ligand binding are called dependence receptors, and they were the topic of the meeting held during the summer of 2003 in Fondation des Treilles, France. Not only is progress being made in the identification of new dependence receptors, but the partners that carry out this "negative" signal are also coming to light. With several of the receptors implicated in various human developmental disorders or disease states, gaining an understanding of the molecular mechanisms controlling dependence receptor-mediated cell death has clear clinical relevance.
Membrane Recognition and Targeting by Lipid-Binding Domains
Authors: DiNitto Jonathan P. , Cronin Thomas C. , Lambright David G.
Published: December 2003

Modular domains that recognize and target intracellular membranes play a critical role in the assembly, localization, and function of signaling and trafficking complexes in eukaryotic cells. Large domain families, including PH, FYVE, PX, PHD, and C2 domains, combine specific, nonspecific, and multivalent interactions to achieve selective membrane targeting. Despite structural and functional diversity, general features of lipid recognition are evident in the various membrane-targeting mechanisms.
Sialylation of Lipooligosaccharides Promotes Biofilm Formation by Nontypeable
Haemophilus influenzae
Authors: Swords W. Edward , Moore Miranda L. , Godzicki Luciana , Bukofzer Gail , Mitten Michael J. , VonCannon Jessica
Published: December 2003

Nontypeable
Haemophilus influenzae
(NTHi) is a major cause of opportunistic respiratory tract infections, including otitis media and bronchitis. The persistence of NTHi in vivo is thought to involve bacterial persistence in a biofilm community. Therefore, there is a need for further definition of bacterial factors contributing to biofilm formation by NTHi. Like other bacteria inhabiting host mucosal surfaces, NTHi has on its surface a diverse array of lipooligosaccharides (LOS) that influence host-bacterial interactions. In this study, we show that LOS containing sialic (
N
-acetyl-neuraminic) acid promotes biofilm formation by NTHi in vitro and bacterial persistence within the middle ear or lung in vivo. LOS from NTHi in biofilms was sialylated, as determined by comparison of electrophoretic mobilities and immunochemical reactivities before and after neuraminidase treatment. Biofilm formation was significantly reduced in media lacking sialic acid, and a
siaB
(CMP-sialic acid synthetase) mutant was deficient in biofilm formation in three different in vitro model systems. The persistence of an asialylated
siaB
mutant was attenuated in a gerbil middle ear infection model system, as well as in a rat pulmonary challenge model system. These data show that sialylated LOS glycoforms promote biofilm formation by NTHi and persistence in vivo.
Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface
Authors: Ren Bing , Szalai Alexander J. , Hollingshead Susan K. , Briles David E.
Published: December 2003

Streptococcus pneumoniaeinfection is a frequent cause of pneumonia, otitis media, meningitis, and septicemia. Pneumococcal surface protein A (PspA) is an important virulence factor on the pathogen surface, and it is known to interfere with complement activation. In this study, flow cytometry was used to study the effects of PspA and antibodies to PspA on the deposition of complement C3 on the surface of a capsular type 3 strain, WU2, and its PspA−mutant, JY1119. Using naive mouse serum as a complement source, measurable deposition of C3 was observed within 4 min on PspA−pneumococci, and the amount of surface-bound C3 accumulated rapidly as the amount of serum was increased. In contrast, very little C3 was deposited on the PspA+strain. In nonimmune mouse serum, the classical pathway was the dominant activation pathway triggered by PspA−pneumococci. Accordingly, EGTA blocked almost all of the complement activation. Moreover, a significant amount of C3 was still deposited on the PspA−strain when serum from factor B-deficient mice was used. This deposition was not observed on the PspA+pneumococci, indicating that PspA may inhibit complement deposition via the classical pathway. Furthermore, under the conditions we tested, PspA also inhibited C3 deposition when the classical pathway was initiated by antibodies to capsular polysaccharide. Antibodies to PspA could overcome the anticomplementary effect of PspA, allowing for increased complement activation and C3 deposition onto PspA+bacteria.
Analysis of
Mycobacterium
Species for the Presence of a Macrolide Toxin, Mycolactone
Authors: Daniel Alexa K. , Lee Richard E. , Portaels Francoise , Small P. L. C.
Published: December 2003

Mycobacterium ulcerans
is an environmental organism which is responsible for the disease Buruli ulcer, a necrotizing skin disease emerging in west Africa.
M. ulcerans
produces the polyketide-derived macrolide mycolactone, which is required for the immunosuppression and tissue damage which characterizes Buruli ulcer. We have extracted lipids from the cell envelope and culture filtrate from 52 isolates of
Mycobacterium
species, analyzed them with thin-layer chromatography, and tested them in a murine fibroblast cell line (L929) cytotoxicity assay to investigate whether these mycobacterial species produce mycolactone. For these studies chloroform-methanol (2:1, vol/vol) extracts were prepared from representative fast- and slow-growing mycobacterial species. Isolates tested included 16 uncharacterized, slow-growing, environmental mycobacterial species isolated from areas in which
M. ulcerans
infection is endemic. Although several strains of mycobacteria studied produced cytopathic lipids, none of these produced a phenotype on cultured cells consistent with that produced by mycolactone. Two mycobacterial species,
M. scrofulaceum
and
M. kansasii
, and eight of the environmental mycobacterial isolates contained cell-associated lipids cytopathic to fibroblasts at concentrations of 33 to 1,000 μg/ml. In contrast, mycolactone produces cytotoxicity at less than 2 ng/ml. Analysis of 16S rRNA sequences from the eight environmental isolates suggests that these are novel mycobacterial species. Results from these studies suggest that, although production of cytopathic lipids is relatively common among mycobacterial species, the production of mycolactone as a cell-associated or secreted molecule appears so far to be restricted to
M. ulcerans
.
Further Characterization of Immunomodulation by a Monoclonal Antibody againstStreptococcus mutansAntigen P1
Authors: Rhodin Nikki R. , Van Tilburg Marloes L. J. A. , Oli Monika W. , McArthur William P. , Brady L. Jeannine
Published: December 2003

We demonstrated previously that mucosal immunization of mice withStreptococcus mutanscoated with the monoclonal antibody (MAb) 6-11A directed against the major surface adhesin protein P1 results in changes in the amount, isotype distribution, and specificity of serum antibodies compared with animals immunized with bacteria only. We now show that the specificity of the mucosal secretory IgA response was also influenced by this MAb. Changes in antibody specificity were associated with changes in biological activity. Serum samples which differed in antibody reactivity with P1 polypeptides generated by partial digestion withN-chlorosuccinimide but not in isotype distribution or overall reactivity withS. mutansor intact P1 demonstrated a statistically significant difference in the ability to inhibit bacterial adherence to salivary-agglutinin-coated hydroxyapatite beads. Serum IgG antibodies against P1 from mice immunized with eitherS. mutansalone orS. mutanscoated with 6-11A were shown to recognize antigenic determinants dependent on the presence of the central proline-rich repeat domain, a segment necessary for the structural integrity of the molecule. However, no statistically significant differences were observed in antibody reactivity with a panel of six partial P1 polypeptides encoded by overlappingspaPsubclones, suggesting that the targets of biologically relevant antibodies involve complex epitopes not reconstituted by the recombinant products tested. Lastly, we show that binding of MAb 6-11A to P1 on the surface ofS. mutansalters P1's susceptibility to proteolytic digestion. Hence, changes in antigen processing and presentation may contribute to the immunomodulatory effects of this MAb.
Cross-Sectional Analysis of Clinical and Environmental Isolates of
Pseudomonas aeruginosa
: Biofilm Formation, Virulence, and Genome Diversity
Authors: Head Nathan E. , Yu Hongwei
Published: December 2003

Chronic lung infections with
Pseudomonas aeruginosa
biofilms are associated with refractory and fatal pneumonia in cystic fibrosis (CF). In this study, a group of genomically diverse
P. aeruginosa
isolates were compared with the reference strain PAO1 to assess the roles of motility, twitching, growth rate, and overproduction of a capsular polysaccharide (alginate) in biofilm formation. In an in vitro biofilm assay system,
P. aeruginosa
displayed strain-specific biofilm formation that was not solely dependent on these parameters. Compared with non-CF isolates, CF isolates expressed two opposing growth modes: reduced planktonic growth versus efficient biofilm formation. Planktonic cells of CF isolates showed elevated sensitivity to hydrogen peroxide, a reactive oxygen intermediate, and decreased lung colonization in an aerosol infection mouse model. Despite having identical genomic profiles, CF sequential isolates produced different amounts of biofilm. While
P. aeruginosa
isolates exhibited genomic diversity, the genome size of these isolates was estimated to be 0.4 to 19% (27 to 1,184 kb) larger than that of PAO1. To identify these extra genetic materials, random amplification of polymorphic DNA was coupled with PAO1-subtractive hybridization. Three loci were found within the genomes of two CF isolates encoding one novel homolog involved in retaining a
Shigella
virulence plasmid (
mvpTA
) and two divergent genes that function in removing negative supercoiling (
topA
) and biosynthesis of pyoverdine (PA2402). Together,
P. aeruginosa
biodiversity could provide one cause for the variation of morbidity and mortality in CF.
P. aeruginosa
may possess undefined biofilm adhesins that are important to the development of an antibiofilm therapeutic target.