SMN and Gemins: ‘We are family’ … or are we?

Gemins 2-8 and Unr-interacting protein (UNRIP) are intimate partners of the survival motor neuron (SMN) protein, which is the determining factor for the neuromuscular disorder spinal muscular atrophy (SMA). The most documented role of SMN, Gemins and UNRIP occurs within the large macromolecular SMN complex and involves the cytoplasmic assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs), a housekeeping process critical in all cells. Several reports detailing alternative functions for SMN in either motor neurons or skeletal muscles may, however, hold the answer to the extreme neuromuscular tissue specificity observed in SMA. Recent discoveries indicate that collaboration between SMN and Gemins also extends to these non-canonical functions, hence raising the possibility that mutations in Gemin genes may be the cause of unlinked neuromuscular hereditary syndromes. This review evaluates the functions of Gemins and UNRIP inside the SMN complex and discusses whether these less notorious SMN complex members are capable of acting independently of SMN.     

SIRT1 longevity factor suppresses NF‐κB ‐driven immune responses: regulation of aging via NF‐κB acetylation?

The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.     

Do ‘we’ ‘do’ God? Linda Woodhead & Rebecca Catto (eds), Religion and change in modern Britain. London: Routledge.

What does it mean to talk of the religion ‘of’ a given country? I reflect on an edited volume dealing with religion in Britain and consider two related themes: the secular considered as ‘absence’ or ‘presence’, and the siting of religion not in conventional denominations or ritual practices but in spaces of encounter between religions, and between the so‐called ‘religious’ and ‘secular’.     

Who Is the King? The α‐Hydroxy‐β‐oxo‐α,β‐enone Moiety or the Catechol B Ring: Relationship between the Structure of Quercetin Derivatives and Their Pro‐Oxidative Abilities

Quercetin and other flavonoids have been reported to exhibit both antioxidant and pro‐oxidant properties. Most studies about the pro‐oxidative ability were conducted in the presence of metal ions, and the essential functional moiety of quercetin responsible for the pro‐oxidative effect is still unclear. In this study, we evaluated the pro‐oxidative abilities in the absence of metal ions of two quercetin derivatives, i.e., quercetin‐3′‐O‐β‐D ‐glucoside ( 1 ) and quercetin‐3‐O‐β‐D ‐glucoside ( 2 ), by assessing DNA cleavage and HO^.‐radical production. The binding mode between these compounds and DNA was studied by fluorescence and viscometric titrations. The results showed that 1 can efficiently induce oxidative damage to plasmid DNA, while 2 shows poor activity. Both 1 and 2 bind to DNA via groove‐binding. These results proved that the α‐hydroxy‐β‐oxo‐α,β‐enone moiety contributes to the pro‐oxidative activity of quercetin.     

Mitochondria and peroxisomes: Are the ‘Big Brother’ and the ‘Little Sister’ closer than assumed?

Mitochondria and peroxisomes are essential subcellular organelles in mammals. Despite obvious differences, both organelles display certain morphological and functional similarities. Recent studies have elucidated that these highly dynamic and plastic organelles share components of their division machinery. Mitochondria and peroxisomes are metabolically linked organelles, which are cooperating and cross-talking. This review addresses the dynamics and division of mitochondria and peroxisomes as well as their functional similarities to provide insight as to why these organelles share the fission machinery in evolutionary aspects.     

Étienne Geoffroy St.‐Hilaire: father of “evo‐devo”?

SUMMARY In the early decades of the nineteenth century, the most important disagreement among comparative anatomists was not evolution versus "special creation" but between advocates of "transcendental morphology" and those of teleological anatomy—form versus function. In France this dichotomy was represented by the 1830–1832 public debate between Geoffroy St.-Hilaire (form) and Cuvier (function). Geoffroy's aim was to establish links of homology (known to him as "analogies") between the four "embranchements" into which Cuvier had divided the animal kingdom. Despite the fanciful nature of some of his homologies, Geoffroy, who was guided by his " principe de connections ," set in motion a school of morphology, some of whose conclusions, notably the homology of the dorsal surface of segmented invertebrates with the ventral surface of vertebrates, has been corroborated by recent studies in developmental genetics.     

“Take My Bone Away?” Hypoxia and bone: A narrative review

To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic–angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic‐inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid–base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic‐induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.     

Erratum: Human Demography in the Pleistocene: Do Mitochondrial and Nuclear Genes Tell the Same Story? Evol. Anthropol. 8: 81–86.

Eugene E. Harris and Jody Hey (1999). Human Demography in the Pleistocene: Do Mitochondrial and Nuclear Genes Tell the Same Story? Evol. Anthropol. 8: 81–86. On page 84 at the end of 1st paragraph of the 2nd column should read “. . .intergenetic variation Xq 13.3 to about 535,000 years,³⁹. . .” On page 84 in the 2nd paragraph of the 3rd column should read “. . .and seem to indicate widespread or restricted gene flow among populations.”^19,48,49 On page 85 in the 2nd paragraph of the 1st column should read “. . .united by gene flow at zones of overlap.”⁵³     

β‐Amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?

The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting A,beta degradation may provide a novel approach to the therapy of Alzheimer's disease.     

Comment on ‘Birdstrikes and barcoding: can DNA methods help make the airways safer?’

GenBank is the database of record for public sequence data. Results reported in the scientific literature that are based on sequence data cannot be evaluated if the underlying data is not in the public record.     

How and why does β‐actin mRNA target?

beta-Actin mRNA is localized near the leading edge in several cell types where actin polymerization is actively promoting forward protrusion. The localization of the beta-actin mRNA near the leading edge is facilitated by a short sequence in the 3'UTR (untranslated region), the 'zipcode'. Localization of the mRNA at this region is important physiologically. Treatment of chicken embryo fibroblasts with antisense oligonucleotides complementary to the localization sequence (zipcode) in the 3'UTR leads to delocalization of beta-actin mRNA, alteration of cell phenotype and a decrease in cell motility. The dynamic image analysis system (DIAS) used to quantify movement of cells in the presence of sense and antisense oligonucleotides to the zipcode showed that net pathlength and average speed of antisense-treated cells were significantly lower than in sense-treated cells. This suggests that a decrease in persistence of direction of movement and not in velocity results from treatment of cells with zipcode-directed antisense oligonucleotides. We postulate that delocalization of beta-actin mRNA results in delocalization of nucleation sites and beta-actin protein from the leading edge followed by loss of cell polarity and directional movement. Hence the physiological consequences of beta-actin mRNA delocalization affect the stability of the cell phenotype.