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1.
Nat Commun ; 15(1): 801, 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38280873

ABSTRACT

Arbuscular mycorrhizal (AM) fungi associate with the roots of many plant species, enhancing their hosts access to soil nutrients whilst obtaining their carbon supply directly as photosynthates. AM fungi often face competition for plant carbon from other organisms. The mechanisms by which plants prioritise carbon allocation to mutualistic AM fungi over parasitic symbionts remain poorly understood. Here, we show that host potato plants (Solanum tuberosum cv. Désirée) selectively allocate carbon resources to tissues interacting with AM fungi rather than those interacting with phytophagous parasites (the nematode Globodera pallida). We found that plants reduce the supply of hexoses but maintain the flow of plant-derived fatty acids to AM fungi when concurrently interacting with parasites. Transcriptomic analysis suggest that plants prioritise carbon transfer to AM fungi by maintaining expression of fatty acid biosynthesis and transportation pathways, whilst decreasing the expression of mycorrhizal-induced hexose transporters. We also report similar findings from a different plant host species (Medicago truncatula) and phytophagous pest (the aphid Myzus persicae). These findings suggest a general mechanism of plant-driven resource allocation in scenarios involving multiple symbionts.


Subject(s)
Mycorrhizae , Mycorrhizae/metabolism , Carbon/metabolism , Symbiosis , Fungi/metabolism , Plant Roots/metabolism , Plants/metabolism
2.
Chem Commun (Camb) ; 58(57): 7912-7915, 2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35726903

ABSTRACT

Pre-targeting of bispecific antibodies is probed to enhance tumour retention while limiting clearance of administered multifunctional branched PEGylated nanomedicines. The temporal influence of pre-targeting on polymer interaction with tumour cells and tissue is explored using in vitro assays through to preclinical validation.


Subject(s)
Antibodies, Bispecific , Nanostructures , Neoplasms , Humans , Nanomedicine , Neoplasms/drug therapy , Polymers
3.
Mol Biol Cell ; 11(10): 3589-99, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11029057

ABSTRACT

Ligand binding to receptor tyrosine kinases (RTKs) regulates receptor dimerization and activation of the kinase domain. To examine the role of the transmembrane domain in regulation of RTK activation, we have exploited a simplified transmembrane motif, [VVVEVVV](n), previously shown to activate the Neu receptor. Here we demonstrate rotational linkage of the transmembrane domain with the kinase domain, as evidenced by a periodic activation of Neu as the dimerization motif is shifted across the transmembrane domain. These results indicate that activation requires a specific orientation of the kinase domains with respect to each other. Results obtained with platelet-derived growth factor receptor-beta suggest that this rotational linkage of the transmembrane domain to the kinase domain may be a general feature of RTKs. These observations suggest that activating mutations in RTK transmembrane and juxtamembrane domains will be limited to those residues that position the kinase domains in an allowed rotational conformation.


Subject(s)
Receptor Protein-Tyrosine Kinases/genetics , Receptor, ErbB-2/chemistry , Receptor, ErbB-2/genetics , 3T3 Cells , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Chlorocebus aethiops , Dimerization , Ligands , Mice , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/metabolism , Protein Conformation , Receptor Protein-Tyrosine Kinases/chemistry , Receptor Protein-Tyrosine Kinases/metabolism , Receptor, ErbB-2/metabolism , Receptor, Platelet-Derived Growth Factor beta/chemistry , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolism , Transcription, Genetic
4.
Biochim Biophys Acta ; 411(2): 263-81, 1975 Dec 05.
Article in English | MEDLINE | ID: mdl-1201280

ABSTRACT

The polyamine content of Escherichia coli is inversely related to the osmolality of the growth medium. The experiments described here demonstrate that a similar phenomenon occurs in mammalian cells. When grown in media of low NaCl concentration, HeLa cells and human fibroblasts were found to contain high levels of putrescine, spermidine, and spermine. The putrescine content of HeLa cells was a function of the osmolality of the medium, as shown by growing cells in media containing mannitol or additional glucose. External osmolality per se had no effect on the contents of spermidine and spermine. For all media, the total cellular polyamine content could be correlated with the activity of ornithine decarboxylase, the first enzyme in polyamine biosynthesis. Different levels of enzyme activity appear to result solely from variations in the rate of enzyme degradation. A sudden increase in a NaCl concentration produced rapid loss of ornithine decarboxylase activity and a gradual loss of putrescine and spermidine. A sudden decrease in NaCl concentration led to rapid and substantial increases in ornithine decarboxylase activity and putrescine.


Subject(s)
HeLa Cells/metabolism , Polyamines/metabolism , Culture Media , DNA/metabolism , HeLa Cells/drug effects , HeLa Cells/ultrastructure , Ornithine Decarboxylase/metabolism , Osmolar Concentration , Protein Biosynthesis/drug effects , Putrescine/metabolism , Sodium Chloride/pharmacology , Spermidine/metabolism , Spermine/metabolism , Transcription, Genetic/drug effects
5.
J Am Coll Cardiol ; 22(2): 449-58, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8335814

ABSTRACT

OBJECTIVES: The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND: Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS: Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS: Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS: These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.


Subject(s)
Blood Flow Velocity , Coronary Circulation/physiology , Coronary Disease/physiopathology , Coronary Vessels/physiopathology , Adult , Aged , Blood Pressure , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Female , Humans , Male , Middle Aged , Ultrasonography
6.
Biochem Pharmacol ; 31(9): 1723-8, 1982 May 01.
Article in English | MEDLINE | ID: mdl-6809009

ABSTRACT

Four C(2')-substituted 2'-deoxyadenosines were examined as substrates for human erythrocytic adenosine deaminase and for formation of intracellular nucleotide analogs in human erythrocytes, lymphocytes and murine Sarcoma 180 cells: 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)adenine, 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine, 9-(2'-azido-2'-deoxy-beta-D-ribofuranosyl)adenine (2'-N3-riboA) and 9-(2-azido-2'-deoxy-beta-D-arabinofuranosyl)adenine. All four adenosine analogs were substrates of human erythrocytic adenosine deaminase, but the corresponding inosine analogs (synthesized by the adenosine deaminase reaction) were highly resistant to cleavage by human erythrocytic purine nucleoside phosphorylase. Only 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)hypoxanthine underwent very slow phosphorolysis, and no inhibition of inosine phosphorolysis was detected when a 30 microM concentration of any studied inosine analog was added to a reaction mixture containing 30 microM inosine (the Km concentration). Kinetic parameters were determined for the deamination of the adenosine analogs. The greatest affinity for adenosine deaminase was found with 2'-N3-ribo A (Ki = 2 microM), but the reaction velocity was highest with the F-substituted analogs. All four adenosine analogs formed triphosphate nucleotides after incubation with human erythrocytes, murine Sarcoma 180 cells, or human lymphocytes (tested only with the F analogs) in the presence of deoxycoformycin.


Subject(s)
Adenosine Deaminase/pharmacology , Antineoplastic Agents/metabolism , Nucleoside Deaminases/pharmacology , Pentosyltransferases/pharmacology , Purine Nucleosides/biosynthesis , Purine Nucleosides/metabolism , Purine-Nucleoside Phosphorylase/pharmacology , Chromatography, High Pressure Liquid , Humans , Kinetics , Structure-Activity Relationship
7.
Accid Anal Prev ; 30(1): 61-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9542545

ABSTRACT

This paper summarizes a two-phase project that reviewed the Commercial Vehicle Safety Alliance's out-of-service criteria for vehicles. The first phase examined relevant background information and conducted a questionnaire survey of CVSA inspectors and industry representatives. The second phase of the project involved extensive collection and evaluation of accident data. The results of both phases show a high level of support, in terms of contribution to vehicle accidents, for four of the vehicle criteria (regarding brakes, load securement, tires, and wheels and rims). There was some support for coupling devices, fuel systems, lighting devices, steering and suspension. The support for the remaining vehicle criteria (exhaust systems, frames, van and open top trailer bodies, and windshield wipers) was little to none. Further research continuing the study of accident data is recommended to confirm these findings. However, the data must be collected in a consistent and detailed manner if accurate information on the relationship of accidents and vehicle criteria is to be established.


Subject(s)
Motor Vehicles , Safety , Equipment Design , Humans , Oregon
9.
Child Welfare ; 62(2): 167-73, 1983.
Article in English | MEDLINE | ID: mdl-6831978

ABSTRACT

The increase in teen-age pregnancy creates a growing population of young mothers unable to care adequately for themselves or their children. Responding to budget cuts in Utah, the authors report on a program that combines the resources of an agency and a university program to teach mothers child care and self-sufficiency, promotes the healthy development of their children, and gives field training to social work students.


PIP: This article reports on a program that combines the resources of an agency and a university program to teach mothers child care and self sufficiency, promotes the healthy development of their children, and gives field training to social work students. The program was a response to budget cuts in Utah and awareness that the increase in teengage pregnancy creates a growing population of young mothers unable to care adequately for themselves or their children. The increase is attributed to a drop in the age of menarche and a steady increase in the number of sexually active young people. In Utah, where conservative mores concerning sexuality predominate, teenage unmarried mothers frequently perceive themselves as alienated from the mainstream of society and human service agencies have been unable to deal adequately with the increased demands for service. The Single Parent Project combines the resources of the Children's Aid Society and the Early Childhood Research Program at Utah State University to help pregnant adolescents and their at risk preschool children. In 1980-81, a core group of 15 mothers and 29 children were serviced. Mothers had to meet 4 criteria from a list that included health problems, economic privation, substance abuse, age factors, deficient parenting, negative or no support network and previous victim of abuse. Children had to meet two or more criteria including birth problems, nutrition, developmental and behavioral problems or reported victim of abuse or neglect. The program included weekly group sessions with mothers, and home intervention using individualized plans for each child. Activities and resources used are described. Success is measured in a comparison with non program users. A significantly higher percentage of program graduates found employment, went on to college, had less dependence on welfare and fewer referrals for child abuse. The programs next phase calls for an experimental design to test the program's effectiveness.


Subject(s)
Child Welfare , Maternal Welfare , Pregnancy in Adolescence , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Parents/education , Pregnancy , Social Work , Utah
10.
Neuroscience ; 254: 61-9, 2013 Dec 19.
Article in English | MEDLINE | ID: mdl-24045100

ABSTRACT

Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood-brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit - effects that are also seen in patients with Alzheimer's disease.


Subject(s)
Alzheimer Disease/pathology , Cerebral Arteries/pathology , Cerebral Ventricles/pathology , Cholesterol, Dietary/adverse effects , Disease Models, Animal , Alzheimer Disease/etiology , Animals , Cerebrovascular Circulation/physiology , Cholesterol, Dietary/administration & dosage , Male , Rabbits
11.
Int J Tuberc Lung Dis ; 16(8): 1086-91, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22687275

ABSTRACT

SETTING: Since 2005, private pharmacies linked to the National Tuberculosis Programme (NTP) and the Municipal Health Department in Phnom Penh have referred tuberculosis (TB) symptomatic patients to public sector TB clinics. OBJECTIVE: To investigate the attitudes and practices of pharmacy-initiated referral service providers in Phnom Penh from 2005 to 2010. METHODS: In a qualitative study, participants were purposively selected from the register of pharmacy owners providing referral services. Discussions were conducted in Khmer by trained facilitators. Participants discussed topics relating to their experiences and participation in the referral programme. RESULTS: In January 2011, 54 pharmacy owners participated in six focus group discussions held in Phnom Penh. Interpreted data showed consistency of message across all topics. The emergent themes-altruism, pragmatism and professionalism-underpinned owner commitment to programme goals. Issues associated with patient counselling, fear of infection and quality of care in public sector clinics were of concern to participants. Owners believed ongoing professional support, improved public sector patient care and media campaigns would strengthen their role. CONCLUSION: Pharmacy outlets provide further options for NTPs engaging with private sector providers. Recognising private provider needs and aspirations may be an essential component of public/private mix programmes to meet public health goals.


Subject(s)
Antitubercular Agents/therapeutic use , Attitude of Health Personnel , Community Pharmacy Services , Health Knowledge, Attitudes, Practice , Perception , Pharmacists/psychology , Referral and Consultation , Tuberculosis/drug therapy , Adult , Aged , Altruism , Cambodia/epidemiology , Female , Focus Groups , Health Care Surveys , Health Services Research , Humans , Male , Middle Aged , National Health Programs , Private Sector , Professional Role , Program Evaluation , Public Sector , Quality of Health Care , Registries , Time Factors , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Young Adult
12.
Int J Tuberc Lung Dis ; 15(8): 1005-17, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21669027

ABSTRACT

SETTING: The past decade has seen a significant increase in private sector provision of tuberculosis (TB)care. While patients often seek and select treatment from private providers at significant out-of-pocket expense,treatment outcomes remain largely unknown. OBJECTIVE: To investigate the knowledge, attitudes and practices of private sector TB care providers in high burden countries. METHODS: Medline, PubMed, Embase, International Pharmaceutical Abstracts and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched using Medical Subject Headings terms,Emtree terms and key words. Searches were limited to the English language and published between 1998 and week 2 of November 2009. Studies were included if they reported the knowledge, attitudes or practice behaviours of private health care providers working in one of 22 high-TB-burden countries. Each included study was critically assessed using a structured data extraction tool. Data extracted included the study setting, objective, design, sample, response rate, outcomes and limitations. RESULTS: The 34 studies that met review inclusion criteriaen compassed diverse study methods and designs.All categories of TB care providers lacked comprehensive knowledge of national treatment guidelines. Procedures for referral, treatment monitoring, record keeping and case holding were not systematically implemented.However, there was a high degree of willingness to collaborate with national TB programmes. CONCLUSION: Research using standardised data collection methods may assist in identifying gaps in knowledge and practice among all providers of TB care. Further studies in developing and evaluating needs-based interventions should be undertaken; systematic reviews of such studies may then assist in strategic decision making in public-private mix DOTS expansion.


Subject(s)
Antitubercular Agents/therapeutic use , Developing Countries , Health Knowledge, Attitudes, Practice , Outcome and Process Assessment, Health Care , Practice Patterns, Physicians' , Private Sector , Quality of Health Care , Tuberculosis/drug therapy , Directly Observed Therapy , Guideline Adherence , Humans , Medical Records , Outcome and Process Assessment, Health Care/statistics & numerical data , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Private Sector/statistics & numerical data , Quality of Health Care/statistics & numerical data , Referral and Consultation , Treatment Outcome , Tuberculosis/diagnosis
17.
Parasitol Today ; 4(4): 90, 1988 Apr.
Article in English | MEDLINE | ID: mdl-15463053

ABSTRACT

Seldom if ever have parasitological insights been found in the great works of literature. Important observations on the transmammary transmission o f hookworm, however, may be found in a literary manuscript recently discovered in a Parisian archive. The concept of transmammary transmission is now well established, and while canine hookworm species are generally considered incapable of reaching maturity in man, they may well be capable of producing transient patent infections in neonates. The manuscript, to judge by its literary style, is clearly a fragment written by Marcel Proust (1871-1922) for his great seven-part masterpiece A la Recherche du Temps Perdu (Remembrance of Things Past) and perhaps it will appear in future editions. The manuscript was discovered by Professor C.A.M. Bell, who has kindly provided the following translation.

18.
Parasitol Today ; 2(4): 117-9, 1986 Apr.
Article in English | MEDLINE | ID: mdl-15462792

ABSTRACT

Among the uncertainties surrounding the life of Mozart, few have been the subject of as much speculation as the matter of the composer's final illness and death. The debate has often seemed somewhat pointless, because direct medical evidence has been lacking and, since the body was buried in an unmarked gravesite, is likely to remain lacking. Indirect or circumstantial evidence, however, can contribute to an understanding of the matter, and it is the purpose of this communication to call attention to the discovery of an unexpected piece of circumstantial evidence which throws an entirely new light on the subject.

19.
Am J Public Health ; 81(6): 729-32, 1991 Jun.
Article in English | MEDLINE | ID: mdl-2029041

ABSTRACT

BACKGROUND: Women, while noted for low occupational injury mortality rates, are more likely to die as victims of assault than from any other manner of injury at work. METHODS: From the National Traumatic Occupational Fatality surveillance data, 950 women were identified who were fatally assaulted at work. Homicide rates were calculated for the demographic and employment characteristics of these women. Risk ratios among types of lethal injuries were examined. RESULTS: During 1980-1985, the crude six-year workplace homicide rate was 4.0 deaths per million working women: one twentieth the homicide rate of the US female population. Decedents ranged from 16 years (the lowest age included in the data base) to 93 years of age. Working women older than 65 years had the highest age-specific homicide rate, 11.3 per million. Women younger than 20 had the lowest, 2.5 per million per year. Homicide rates for women of races other than White were nearly twice as high as those of Whites. The leading causes of death were gunshot wounds (64 percent), stabbings (19 percent), asphyxiations (7 percent), and blunt force trauma (6 percent). Nearly 43 percent of the deceased women had been employed in retail trade: 8.7 per million employed women annually. CONCLUSIONS: During 1980-1985, only 6 percent of the nation's victims of work-related injury deaths were female: 41 percent of those women were murdered. Homicide is currently the leading manner of traumatic workplace death among women in the United States.


Subject(s)
Accidents, Occupational/mortality , Homicide/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , Databases, Factual , Death Certificates , Female , Homicide/classification , Humans , Industry , Middle Aged , Occupations , Population Surveillance , Risk Factors , Sex Factors , United States/epidemiology , United States Occupational Safety and Health Administration
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