Understanding intercellular interactions and cell adhesion: lessons from studies on protein-metal interactions

To understand cell-cell interactions and the interactions of cells to non-biological materials, studies on binding forces between cellular proteins and between proteins and non-biological material such as metal surfaces are essential. The adsorption of proteins to solid-water interfaces is a multifactorial and a multistep process. First steps are determined by long-range interactions where surface properties such as hydrophobicity, distribution of charged groups, ion concentrations and pH play important roles. In later steps structural rearrangements in the protein molecule and dehydration effects become more important making the adsorption process often irreversible. In the following we demonstrate that protein A and tubulin have a specific type of interaction to metal surfaces probably as an intermediate step in the adsorption process. The proteins were attached to the tip of a microfabricated cantilever in such a way that only one molecule interacts with the surface. By recording force-distance curves with an atomic force microscope the adhesion forces of single molecules binding to gold, titanium and indium-tinoxid surfaces were measured.     

T-cell receptor peptide-MHC interactions: biological lessons from structural studies

We have constructed a zebrafish genetic linkage map consisting of 705 simple sequence-length polymorphism markers (SSLPs). The map covers 2350 centimorgans (cM) of the zebrafish genome with an average resolution of 3.3 cM. It is a complete map in genetic mapping terms (there is one linkage group for each of the 25 chromosomes), and it has been confirmed by somatic-cell hybrids and centromere-mapping using half-tetrad analysis. The markers are highly polymorphic in the zebrafish strains used for genetic crosses and provide a means to compare genetic segregation of developmental mutations between laboratories. These markers will provide an initial infrastructure for the positional cloning of the nearly 600 zebrafish genes identified as crucial to vertebrate development,and will become the anchor for the physical map of the zebrafish genome.     

Some salient lessons from research and practice.

Discusses the therapist's indispensable abilities to listen and to resonate to his or her own inner world and the patient's inner world, and to manage his or her own emotional reactions. In short, transference and countertransference are the key to a successful working alliance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning lessons from sunk costs.

Study participants rated the quality of several arguments for continuing an original plan in sunk cost situations in order to (a) avoid wasting resources, (b) learn to make better decisions, (c) punish poor decision making, and (d) appear consistent. The lesson-learning argument was perceived as most appropriate when adult teachers taught lessons to others, the original decision was carelessly made, or if it consumed comparatively more resources. Ratings of the lesson-learning argument were higher for teacher-learner than for adult-alone situations, regardless of whether the learner was a child or an adult. The implications for improving decision making and judging whether the sunk cost effect is a bias are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involving patients: lessons from PACE

In the fourth part of our PACE series, based on the King's Fund Promoting Action on Clinical Effectiveness programme, the first article reviews the experiences of 16 PACE projects that offer tips for involving patients in programmes to implement evidence-based practice, quality initiatives and clinical governance arrangements. The second article provides a more detailed example of one project.     

Immunoconjugates: lessons from animal models

Monoclonal antibody-mediated cancer therapy has evolved through a challenging chain of problems and solutions. The very limited therapeutic success obtained with unarmed monoclonal antibodies has increased the interest in different antibody-based targeting strategies, and numerous preclinical and even clinical studies with immunoconjugates have now been conducted. We comment here on the messages implicit in a recent report on a doxorubicin-anti-carcinoma antibody conjugate and from several other studies.     

Memorable lessons from a multifaceted career.

Summarizes some of the major lessons of the author's experience consulting with thousands of patients, trainees, and supervisees in several dozen countries and hundreds of cities. The need for versatility in treatment style and approach is stressed, as well as the need of therapists to nurture and to know themselves. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arterial hypertension: lessons from patient education

The face of hypertension has been changing rapidly over the last few decades, from a serious disease to a cardiovascular risk factor. Patient education has been instrumental in bringing about tremendous improvements in hypertension-related mortality, morbidity, life expectancy, and life quality. Patient education has evolved from an adjunct to medical therapy to an intervention in its own right. In this process patient education tasks and techniques themselves have undergone remarkable developments, driven by evolving patient needs due to medical progress. The same is true for the roles of patients and health care providers. Dealing with hypertension is a behavior change process which demands serious learning efforts from all parties involved, patients, health practitioners and health care administrators alike. This paper focuses therefore on patient education for preventive behavior change and risk factor management. Special emphasis will be placed on processes and tools for effective patient education.     

Health sector reform: lessons from China

As a result of China's transition to a socialist market economy, its rural health services have undergone many of the changes commonly associated with health sector reform. These have included a decreased reliance on state funding, decentralisation of public health services, increased autonomy of health facilities, increased freedom of movement of health workers, and decreased political control. These changes have been associated with growing inequality in access to health services, increases in the cost of medical care, and the deterioration of preventive programmes in some poor areas. This paper argues that the government's strategy for addressing these problems has overemphasised the identification of new sources of revenue and has paid inadequate attention to factors that influence provider behaviour. The strategy also does not address contextual issues such as public sector employment practices and systems of local government finance. Other countries can learn from China's experience by taking a systematic approach to the formulation and implementation of strategies for health sector reform.     

Promoting choice: lessons from managed Medicaid

Drawing on the education, enrollment, and assignment experiences of seven states with mandatory Medicaid managed care programs, this paper finds that the vast majority of enrollees will choose their own health plan if the system is explicitly designed with this in mind (as in Minnesota and Oregon). These experiences provide lessons on ways to 1) align program design with state priorities; (2) increase the level of choice (by coordinating enrollment and eligibility processes, broad-based educational strategies, and personalized attention); (3) improve the quality of choice; and (4) design state contracting processes to support choice and continuity of care.     

Primary structure and crystallization of orotate phosphoribosyltransferase from Salmonella typhimurium

Orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10) catalyzes phosphoribosyl group transfer between alpha-D-5-phosphoribosyl-1-pyrophosphate and orotate to form orotidine-5'-monophosphate and pyrophosphate, the nucleotide-forming step in pyrimidine biosynthesis. It is one of ten PRTases that perform vital roles in de novo and salvage pathways for purine, pyrimidine and pyridine nucleotides. Although the PRTases are important drug targets, they are poorly understood mechanistically, and no three-dimensional structures exist. Here, we report the complete sequence of the Salmonella typhimurium pyrE gene and the deduced sequence of the OPRTase gene product. OPRTase forms tetragonal crystals from polyethylene glycol solutions; these crystals diffract to better than 2 A resolution, and are stable to radiation damage. The space group is P4(1)2(1)2 (or P4(3)2(1)2) with unit cell dimensions of a = b = 48.5 A, c = 210.5 A, and alpha = beta = gamma = 90 degrees. A crystalline form of the selenomethionine derivative of the protein is also reported.     

Control of coccidiosis: lessons from other sporozoa

Coccidiosis is the most important parasitic infection in poultry worldwide and also causes problems in cattle, sheep and goats. Control is largely limited to good husbandry and prophylactic chemotherapy using a range of drugs against which resistance is rapidly acquired. Attempts at vaccination using conventional vaccines have been disappointing and there is now a need for a new approach. Research into the immunology of coccidiosis has lagged behind that of other sporozoans and there are useful lessons that might be learned from studies on toxoplasmosis, cryptosporidiosis, theileriosis and malaria. In these infections the emphasis has turned to the cytokine network that drives the response towards protection. Central to these studies are the roles of interferon-gamma, interleukin-12 and activated macrophages with the involvement of nitric oxide in parasite killing. Cytotoxic T cells have also increasingly been implicated. Research has shown that different immune responses can be elicited by manipulating the cytokine system and these new concepts can be applied to the design of peptide or recombinant vaccines, and the possibilities of developing such vaccines against coccidiosis will be discussed.     

Clinical-experimental interactions in the development of neuroscience: A primer for nonspecialists and lessons for young scientists.

In the article, the author gives examples of some aspects of the development of neuroscience that may be of particular interest to the nonspecialist. In addition to the scientific discoveries involved, the examples illustrate how astute observations in the clinic can draw the attention of workers in the laboratory to significant new problems and how experiments in the laboratory can provide foundations for new clinical applications. These examples also illustrate general lessons that young investigators may find useful and point to the importance of facilitating communications among psychology's fragmenting specialties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transcriptional repression: lessons from thyroid hormone action and promyelocytic leukaemia

We report seemingly unique craniofacial malformations and deglutition dysfunction in a sib pair. The boy had right maxillomandibular alveolar synechae, ankylosis of right temporomandibular joint, hypoplasia of the zygomatico-maxillary region, nasal deviation to the left, choanal stenosis, and exophthalmos due to shallow orbita. His ears were apparently low-set with prominent lobules. He had severe gastroesophageal reflux and increasing respiratory problems and died at age 11 months. Psychomotor development was normal. His 10-year-old sister had similar craniofacial malformations and a cleft soft palate. She also had a severe deglutition dysfunction and developed a thoracolumbar kyphoscoliosis. Psychomotor development was normal. The parents were healthy and non-consanguineous. The malformations in the sibs do not fit any reported craniofacial malformation syndrome and may represent a previously unrecognized monogenic disorder. This may be an autosomal recessive or dominant trait with gonadal mosaicism in one of the parents.     

Regulation of megakaryocytopoiesis and platelet production: lessons from animal models

We showed differential expression of HSP70 during oral tumorigenesis. The precise functional role of HSP70 overexpression in the pathogenesis of betel and tobacco related oral cancer remains to be determined. To evaluate the utility of HSP70 as an indicator of the biological stress experienced by tumour cells or the malignant potential of oral epithelial lesions and predicting clinical outcome, its expression was assessed in different stages of oral carcinogenesis by immunohistochemical analysis and correlated with clinicopathological parameters. Overexpression of HSP70 protein was observed in 38 of 64 (59%) dysplastic lesions and 92 of 125 (74%) oral squamous cell carcinomas (SCCs) which included 76 of 105 cases (72%) of primary oral SCCs and 16 of 20 (80%) of recurrent oral SCCs. A significant correlation of HSP70 expression was observed with severity of dysplasia (P = 0.0006767), poor histological differentiation of primary tumours (P = 0.0184348), increase primary tumour size (P = 0.0221103) and consumption of betel and tobacco (P < 0.01). Follow-up studies showed that in patients with premalignant lesions the median transition time (premalignancy to malignancy) was significantly shorter in HSP70 overexpressing cases than those showing basal level of HSP70 (P = 0.012). Oral cancer patients with elevated levels of HSP70 showed decreased median disease-free survival time (no recurrence/metastasis) than those showing basal HSP70 immunoreactivity (P = 0.0246). The results suggest that HSP70 expression may not be a mere marker of biological stress but may also be implicated in the pathogenesis of oral cancer.