Selection, growth and form. Turing's two biological paths towards intelligent machinery.

We inquire into the role of Turing's biological thought in the development of his concept of intelligent machinery. We trace the possible relations between his proto-connectionist notion of 'organising' machines in Turing (1948) on the one hand and his mathematical theory of morphogenesis in developmental biology (1952) on the other. These works were concerned with distinct fields of inquiry and followed distinct paradigms of biological theory, respectively postulating analogues of Darwinian selection in learning and mathematical laws of form in organic pattern formation.

Assessment of PABPN1 nuclear inclusions on a large cohort of patients and in a human xenograft model of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) protein leading to the formation of intranuclear inclusions or aggregates in the muscle of OPMD patients. Despite numerous studies stressing the deleterious role of nuclear inclusions in cellular and animal OPMD models, their exact contribution to human disease is still unclear.

Adaptation and its analogues: Biological categories for biosemantics.

"Teleosemantic" or "biosemantic" theories form a strong naturalistic programme in the philosophy of mind and language. They seek to explain the nature of mind and language by recourse to a natural history of "proper functions" as selected-for effects of language- and thought-producing mechanisms. However, they remain vague with respect to the nature of the proposed analogy between selected-for effects on the biological level and phenomena that are not strictly biological, such as reproducible linguistic and cultural forms.

Trehalose alleviates the phenotype of Machado-Joseph disease mouse models.

Background: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model.

Low level of exosomal long non-coding RNA is a prognostic biomarker in colorectal cancer.

Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs ( and ) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more and transcripts in comparison to CRC patients.

Expression of Glypican 3 is an Independent Prognostic Biomarker in Primary Gastro-Esophageal Adenocarcinoma and Corresponding Serum Exosomes.

Exosomes are nano-sized membranous vesicles of endosomal origin that carry nucleic acids, lipids and proteins. The cargo of exosomes is cell origin specific and the release of these exosomes and uptake by an acceptor cell is seen as a vital element of cell-cell communication. Here, we sought to investigate the diagnostic and prognostic value of the expression of glypican 3 () on primary gastro-esophageal adenocarcinoma (GEA) tissue () and corresponding serum exosomes ().

TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.

Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of the mitochondrial enzyme, methylmalonyl-CoA mutase (MCM). The main treatments for MMA patients are dietary restriction of propiogenic amino acids and carnitine supplementation. Liver or combined liver/kidney transplantation has been used to treat those with the most severe clinical manifestations.

What is the extension of the extended mind?

Two aspects of cognitive coupling, as brought forward in the Extended Mind Hypothesis, are discussed in this paper: (1) how shall the functional coupling between the organism and some entity in his environment be spelled out in detail? (2) What are the paradigmatic external entities to enter into that coupling? These two related questions are best answered in the light of an aetiological variety of functionalist argument that adds historical depth to the "active externalism" promoted by Clark and Chalmers and helps to counter some of the core criticisms levelled against this view. Under additional reference to conceptual parallels between the Extended Mind Hypothesis and a set of heterodox theories in biology-environmental constructivism, niche construction, developmental systems theory-an argument for the grounding of environmentally extended cognitive traits in evolved biological functions is developed. In a spirit that seeks to integrate extended functionalism with views from cognitive integration and complementarity, it is argued (ad 1) that instances of environmental coupling should be understood as being constitutive to cognitive functions in either of two distinct ways.

Frataxin-deficient neurons and mice models of Friedreich ataxia are improved by TAT-MTScs-FXN treatment.

Friedreich ataxia (FA) is a rare disease caused by deficiency of frataxin, a mitochondrial protein. As there is no cure available for this disease, many strategies have been developed to reduce the deleterious effects of such deficiency. One of these approaches is based on delivering frataxin to the tissues by coupling the protein to trans-activator of transcription (TAT) peptides, which enables cell membranes crossing.

Analysis of Azithromycin Monohydrate as a Single or a Combinatorial Therapy in a Mouse Model of Severe Spinal Muscular Atrophy.

Background: Spinal muscular atrophy (SMA) is a neurodegenerative autosomal recessive disorder characterized by the loss of α-motor neurons. A variety of molecular pathways are being investigated to elevate SMN protein expression in SMA models and in the clinic. One of these approaches involves stabilizing the SMNΔ7 protein by inducing translational read-through.

Heterologous mitochondrial targeting sequences can deliver functional proteins into mitochondria.

Mitochondrial Targeting Sequences (MTSs) are responsible for trafficking nuclear-encoded proteins into mitochondria. Once entering the mitochondria, the MTS is recognized and cleaved off. Some MTSs are long and undergo two-step processing, as in the case of the human frataxin (FXN) protein (80aa), implicated in Friedreich's ataxia (FA).

A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.

Unlabelled: A large number of human diseases are caused by nonsense mutations. These mutations result in premature protein termination and the expression of truncated, usually nonfunctional products. A promising therapeutic strategy for patients suffering from premature termination codon (PTC)-mediated disorders is to suppress the nonsense mutation and restore the expression of the affected protein.

The Darwinian tension: Romantic science and the causal laws of nature.

There have been attempts to subsume Charles Darwin's theory of evolution under either one of two distinct intellectual traditions: early Victorian natural science and its descendants in political economy (as exemplified by Herschel, Lyell, or Malthus) and the romantic approach to art and science emanating from Germany (as exemplified by Humboldt and Goethe). In this paper, it will be shown how these traditions may have jointly contributed to the design of Darwin's theory. The hypothesis is that their encounter created a particular tension in the conception of his theory which first opened up its characteristic field and mode of explanation.

Cell transformation induced by hepatitis C virus NS3 serine protease.

Persistent infection with hepatitis C virus (HCV) may lead to hepatocellular carcinoma (HCC). It has been suggested that HCV-encoded proteins are directly involved in the tumorigenic process. The HCV nonstructural protein NS3 has been identified as a virus-encoded serine protease.

Mutations at vicinity of catalytic sites of hepatitis C virus NS3 serine protease gene isolated from hepatocellular carcinoma tissue.

The mechanism of hepatitis C virus (HCV) -induced hepatotocellular carcinoma (HCC) is still unknown, but in vitro studies clearly suggest that HCV proteins exert a direct effect on liver carcinogenesis. HCV NS3 serine protease is known to play a key role in the life cycle of the virus and may interact with the host cellular regulatory proteins. The aim of the present study was to conduct a genetic analysis of the HCV NS3 gene coding for the serine protease isolated from serum, tumor, and nontumor tissue of HCC patients.

The effects of short-term exercise on the cognitive orientation for health and adjustment in myocardial infarction patients.

Previous studies have shown that cardiovascular patients benefit from exercise. The explanations are partly physical and partly psychological, yet evidence for the latter is contradictory, possibly because only selected samples start and maintain prolonged exercising. The authors examined psychological effects of short-term exercise started as soon as possible after myocardial infarction, focusing on the motivation for health of 62 male and female patients who had had a myocardial infarction 7 to 10 days earlier.

The protein kinase C-related PKC-L(eta) gene product is localized in the cell nucleus.

The tumor promoters phorbol esters are thought to induce changes in cell growth and gene expression by direct activation of protein kinase C (PKC). However, the molecular mechanisms by which PKC molecules transduce signals into the cell nucleus are unknown. In this study, we provide evidence for a direct target for phorbol esters in the nucleus.