A Splicing Mutation in the Novel Mitochondrial Protein DNAJC11 Causes Motor Neuron Pathology Associated with Cristae Disorganization, and Lymphoid Abnormalities in Mice

Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases

Structural modification of bacterial cellulose fibrils under ultrasonic irradiation

Ιn the present study we investigated ultrasounds as a pretreatment process for bacterial cellulose (BC) aqueous suspensions. BC suspensions (0.1–1% wt) subjected to an ultrasonic treatment for different time intervals. Untreated BC presented an extensively entangled fibril network. When a sonication time of 1 min was applied BC fibrils appeared less bundled and dropped in width from 110 nm to 60 nm. For a longer treatment (3–5 min) the width of the fibrils increased again to 100 nm attributed to an entanglement of their structure. The water holding capacity (WHC) and ζ-potnential of the suspensions was proportional to the sonication time. Their viscosity and stability were also affected; an increase could be seen at short treatments, while a decrease was obvious at longer ones. Concluding, a long ultrasonic irradiation led to similar BC characteristics as the untreated, but a short treatment may be a pre-handling method for improving BC properties

Carnosine:can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide's influence on cellular ATP concentrations. Carnosine's ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine's mode of action on human cells. © 2013 Hipkiss et al.; licensee Chemistry Central Ltd

Leaf structure and histochemistry of Ecballium elaterium (L.) A. Rich. (squirting cucumber)

Light, scanning and transmission electron microscopy as well as histochemical reactions were employed to study the leaf structure and secretory activity of Ecballium elaterium, a hairy pharmaceutical perennial common in the Mediterranean region. The amphistomatic leaf has a peculiar structure due to special cells supporting the conductive bundles, a remarkable shortage of mechanical tissue, and the existence of pectin strands between mesophyll cells. The secreting activity is limited mostly to secretary hairs. These attributes of the Ecballium leaf fine structures do not resemble the common structure of leaves from Mediterranean plants and point to a peculiar strategy of this species coping with stress conditions of its habitat. © 2010 Elsevier GmbH

Leaf structure and histochemical investigation in Papaver Rhoeas L. (Corn poppy, field poppy)

The anatomy of the dorsiventral, amphistomatic leaf of Papaver rhoeas was investigated. It was a simple structure possessing large epidermal cells having their vacuole impregnated with glycoproteins which varied in texture, forming a dense, hard core in the middle of the vacuole. Slender rays of cisternae radiated from the dense central core to the cell wall. Thin-walled palisade cells presented a unique, lobed shape probably creating larger surfaces for gas exchange. Mesophyll cells secreted phenolics, condensed tannins, alkaloids, terpene containing steroids and sesquiterpenes. P. rhoeas although being a therophyte, has adopted some structural features common in mediterranean phanerophytes. © 2013 Taylor & Francis Group, LLC

Leaf structure of Cistus creticus L. (rock rose), a medicinal plant widely used in folk remedies since ancient times

The dorsiventral, amphistomatic, hairy, summer and winter leaves of Cistuscreticus had a secretory apparatus in which the secreted resinous material was not preserved in a cutinous wrap, as common during excretion in xerophytes, but was directly spread all over the protective trichomes and the leaf surface. Summer and winter leaves differed in trichome function and density, mesophyll structure, and compactness and secondary metabolite accumulation, mainly phenolics, secreted in excess in the mesophyll cells of the summer leaves. In vitro cell cultures may be used for the production of novel compounds from low-cost precursors. © 2014 Copyright Taylor & Francis Group, LLC

Leaf structural peculiarities in Sarcopoterium spinosum, a seasonally dimorphic subshrub

Extensive investigations on the anatomy of the two leaf types in a seasonally dimorphic subshrub revealed interesting variations between summer and winter leaves. Summer leaves of Sarcopoterium spinosum possess a thick epidermis composed of tannin-containing cells and large amounts of mucilage secreted through the inner periclinal walls towards the mesophyll. A thick cuticle is also present on the surface of the leaf. In winter leaves the epidermal cells produce no mucilage while phenolics are accumulated in granular form only. Besides these, some other variations between summer and winter leaves are also discussed in respect of the ability of the plant to withstand the unfavourable Mediterranean conditions. © 1990 Annals of Botany Company

Leaf structural peculiarities in Sarcopoterium spinosum, a seasonally dimorphic subshrub

Extensive investigations on the anatomy of the two leaf types in a seasonally dimorphic subshrub revealed interesting variations between summer and winter leaves. Summer leaves of Sarcopoterium spinosum possess a thick epidermis composed of tannin-containing cells and large amounts of mucilage secreted through the inner periclinal walls towards the mesophyll. A thick cuticle is also present on the surface of the leaf. In winter leaves the epidermal cells produce no mucilage while phenolics are accumulated in granular form only. Besides these, some other variations between summer and winter leaves are also discussed in respect of the ability of the plant to withstand the unfavourable Mediterranean conditions. © 1990 Annals of Botany Company