Theoretical and experimental evaluation of high energy forming of hemispherical shapes in metals, Phase II Engineering report, May - Dec. 1963

Electrohydraulic, explosive, and other high energy rate forming processes compared to conventional methods denoting influence of strain rate on mechanical propertie

Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain

The mitochondrial presequence translocase transports preproteins to either matrix or inner membrane. Two different translocase forms have been identified: the matrix transport form, which binds the heat-shock protein 70 (Hsp70) motor, and the inner membrane–sorting form, which lacks the motor but contains translocase of inner mitochondrial membrane 21 (Tim21). The sorting form interacts with the respiratory chain in a Tim21-dependent manner. It is unknown whether the respiratory chain–bound translocase transports preproteins and how the switch between sorting form and motor form occurs. We report that the respiratory chain–bound translocase contains preproteins in transit and, surprisingly, not only sorted but also matrix-targeted preproteins. Presequence translocase-associated motor (Pam) 16 and 18, two regulatory components of the six-subunit motor, interact with the respiratory chain independently of Tim21. Thus, the respiratory chain–bound presequence translocase is not only active in preprotein sorting to the inner membrane but also in an early stage of matrix translocation. The motor does not assemble en bloc with the translocase but apparently in a step-wise manner with the Pam16/18 module before the Hsp70 core

Beyond effectiveness. The adversities of implementing a fortification program : a case study on the quality of iron fortification of fish and soy sauce in Cambodia

Fortification of fish and soy sauces is a cost-effective strategy to deliver and increase iron intake in the Cambodian diet, as both are widely consumed by the entire population. In order to qualify as fortified sauces recognized by international regulations, iron content must be between 230 and 460 mg/L, whilst nitrogen and salt should contain no less than 10 g/L and 200 g/L respectively. This survey aims to analyze the progress of the fortification program. Through a better understanding of its obstacles and successes, the paper will then consider approaches to strengthen the program. Two hundred and fifty two samples were collected from 186 plants and 66 markets in various provinces. They were then analyzed for iron, nitrogen and salt content. The study demonstrates that 74% of fortified fish and soy sauces comply with Cambodian regulations on iron content. 87% and 53.6% of the collected samples do not have adequate level of nitrogen and salt content, respectively. The paper will discuss additional efforts that need to be implemented to ensure the sustainability of the project, including the need to: (i) comply with International Codex; (ii) adopt mandatory legislation; and (iii) ensure enforcement

Biogenesis of mitochondrial porin

We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance

Grammatical comprehension in italian children with autism spectrum disorder

Language deficits represent one of the most relevant factors that determine the clinical phenotype of children with autism spectrum disorder (ASD). The main aim of the research was to study the grammatical comprehension of children with ASD. A sample of 70 well-diagnosed children (60 boys and 10 girls; aged 4.9–8 years) were prospectively recruited. The results showed that language comprehension is the most impaired language domain in ASD. These findings have important clinical implications, since the persistence of grammatical receptive deficits may have a negative impact on social, adaptive and learning achievements. As for the grammatical profiles, persistent difficulties were found during the school-age years in morphological and syntactic decoding in children with relatively preserved cognitive and expressive language skills. These data and the lack of a statistically significant correlation between the severity of ASD symptoms and language skills are in line with the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) perspective that considers the socio-communication disorder as a nuclear feature of ASD and the language disorder as a specifier of the diagnosis and not as a secondary symptom anymore. The presence of receptive difficulties in school-age ASD children with relatively preserved non-verbal cognitive abilities provides important hints to establish rehabilitative treatments

Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection