The Hall-Petch effect as a manifestation of the general size effect

The experimental evidence for the Hall-Petch dependence of strength on the inverse square-root of grain size is reviewed critically. Both the classic data and more recent results are considered. While the data can be fitted to the inverse square-root dependence excellently (but using two free fitting parameters for each dataset), it is also consistent with a dependence on the simple inverse of grain size (with one free fitting parameter for each dataset). There have been difficulties, recognised for half-a-century, in explaining the inverse square-root expression. A Bayesian analysis shows that the data strongly supports the simple inverse expression proposed. Since this expression derives from underlying theory, it is also more readily explicable. It is concluded that the Hall-Petch effect is not to be explained by the variety of theories found in the literature, but is a manifestation of, or underlain by, the general size effect observed throughout micromechanics, due to the inverse relationship between the stress required and the space available for dislocation sources to operate.Comment: Paper presented at Plasticity 2014, The Bahama

Targeted Ablation of Oligodendrocytes Triggers Axonal Damage

Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage

Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP

Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain of CLPX. In contrast, the C-terminal (DUF525) domain forms an immunoglobin-like β-sandwich fold, which contains a highly conserved putative substrate binding pocket. Importantly, PDIP38 modulates the substrate specificity of CLPX and protects CLPX from LONM-mediated degradation, which stabilises the cellular levels of CLPX. Collectively, our findings shed new light on the mechanism and function of mitochondrial PDIP38, demonstrating that PDIP38 is a bona fide adaptor protein for the mitochondrial protease, CLPXP

Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells.

Statins have a neuroprotective effect in neurological diseases, a pleiotropic effect possibly related to blood-brain barrier (BBB) function. We investigated the effect of pitavastatin on barrier functions of an in vitro BBB model with primary cultures of rat brain capillary endothelial cells (RBEC). Pitavastatin increased the transendothelial electrical resistance (TEER), an index of barrier tightness of interendothelial tight junctions (TJs), at a concentration of 10(-8) M, and decreased the endothelial permeability for sodium fluorescein through the RBEC monolayer. The increase in TEER was significantly reduced in the presence of isoprenoid geranylgeranyl pyrophosphate, whereas farnesyl pyrophosphate had no effect on TEER. Our immunocytochemical and Western blot analyses revealed that treatment with pitavastatin enhanced the expression of claudin-5, a main functional protein of TJs. Our data indicate that pitavastatin strengthens the barrier integrity in primary cultures of RBEC. The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression

Oligodendrocytes: biology and pathology

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so

Considering Soil Potassium Pools with Dissimilar Plant Availability

Soil potassium (K) has traditionally been portrayed as residing in four functional pools: solution K, exchangeable K, interlayer (sometimes referred to as “fixed” or “nonexchangeable”) K, and structural K in primary minerals. However, this four-pool model and associated terminology have created confusion in understanding the dynamics of K supply to plants and the fate of K returned to the soil in fertilizers, residues, or waste products. This chapter presents an alternative framework to depict soil K pools. The framework distinguishes between micas and feldspars as K-bearing primary minerals, based on the presence of K in interlayer positions or three-dimensional framework structures, respectively; identifies a pool of K in neoformed secondary minerals that can include fertilizer reaction products; and replaces the “exchangeable” K pool with a pool defined as “surface-adsorbed” K, identifying where the K is located and the mechanism by which it is held rather than identification based on particular soil testing procedures. In this chapter, we discuss these K pools and their behavior in relation to plant K acquisition and soil K dynamics