Fold and flexibility: what can proteins' mechanical properties tell us about their folding nucleus?

The determination of a protein''s folding nucleus, i.e. a set of native contacts playing an important role during its folding process, remains an elusive yet essential problem in biochemistry. In this work, we investigate the mechanical properties of 70 protein structures belonging to 14 protein families presenting various folds using coarse-grain Brownian dynamics simulations. The resulting rigidity profiles combined with multiple sequence alignments show that a limited set of rigid residues, which we call the consensus nucleus, occupy conserved positions along the protein sequence. These residues'' side chains form a tight interaction network within the protein''s core, thus making our consensus nuclei potential folding nuclei. A review of experimental and theoretical literature shows that most (above 80%) of these residues were indeed identified as folding nucleus member in earlier studies.     

Transgenerational effects of the holocaust: Externalization of aggression in second generation of holocaust survivors.

Examined the psychological characteristics of the children of holocaust survivors. 38 males and females in their late 20's were interviewed; the parents of 19 Ss were holocaust survivors, and the parents of the other 19 Ss were in Israel during World War II and did not suffer directly. It was hypothesized that reactions of the children of the holocaust survivors would include guilt rather than external aggression and a tendency not to externalize aggressive impulses in reaction to frustrating events. The Ss' reactions to a projective test were analyzed, and the responses provide support for the major hypothesis. Results show that sons and daughters of holocaust survivors were less likely to externalize aggression than were those in a control group. This finding is supported by the content analysis of the structured interview conducted with the Ss in both groups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identifiability of nonlinear systems with application to HIV/AIDS models

In this note, we investigate different concepts of nonlinear identifiability in the generic sense. We work in the linear algebraic framework. Necessary and sufficient conditions are found for geometrical identifiability, algebraic identifiability and identifiability with known initial conditions. Relationships between different concepts are characterized. Constructive procedures are worked out for both generic geometrical and algebraic identifiability of nonlinear systems. As an application of the theory developed, we study the identifiability properties of a four dimensional model of HIV/AIDS. The questions answered in this study include the minimal number of measurement of the variables for a complete determination of all parameters and the best period of time to make such measurements. This information will be useful in formulating guidelines for clinical practice.     

Input-output feedback linearization of time-delay systems

In this note, the input-output linearization problem (IOLP) for a class of single-input-single-output nonlinear systems with multiple delays in the input, the output, and the state is studied. The problem is solved by means of various static or dynamic compensators, including state and output feedback. The mathematical setting is based on some noncommutative algebraic tools and the introduction of a nonlinear version of the so-called Roesser models for this class of systems. These are claimed to be the cornerstones for studying nonlinear time-delay systems. Necessary and sufficient conditions are given for the existence of a static or pure shift output feedback which solves the IOLP. Sufficient conditions for the existence of a dynamic state feedback solution are included as well.     

Water absorption properties of phosphate glass fiber‐reinforced poly‐ϵ‐caprolactone composites for craniofacial bone repair

The moisture uptake of polymers and composites has increasing significance where these materials are specified for invasive, long‐term medical applications. Here we analyze mass gain and the ensuing degradation mechanisms in phosphate glass fiber reinforced poly‐?‐caprolactone laminates. Specimens were manufactured using in situ polymerization of ?‐caprolactone around a bed of phosphate glass fibers. The latter were sized with 3‐aminopropyltriethoxysilane to control the rate of modulus degradation. Fiber content was the main variable in the study, and it was found that the moisture diffusion coefficient increased significantly with increasing fiber volume fraction. Diffusion, plasticization, and leaching of constituents appear to be the dominant aspects of the process over these short‐term tests. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin's disease

BACKGROUND: Staging of Hodgkin's disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. PATIENTS AND METHODS: Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up. PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. RESULTS: The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be downstaged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. CONCLUSIONS: Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.