Recombination and RNA processing: a common strand?

Genetic recombination is a basic cellular process required for altering genome structure. The RecA protein of Escherichia coli has a central role in homologous recombination, and a eukaryotic protein with similar properties has been discovered in the yeast Saccharomyces cerevisiae. Unexpectedly, this RecA-like protein has additional biochemical activities, and its function may not be restricted to recombination.     

Phylloxera and the grapevine: a sense of common purpose?

The purpose of life is its continuation: survival is the reason things live. Here we explore this 'basic' of biology, by reference to the extraordinary life-cycle of the aphid-like pest phylloxera, and the complexity of its relationship with its host the grapevine. The effort and ingenuity that phylloxera employs to continue itself leads to a doubt that survival alone is sufficient reason. It has frequently been suggested that the reduction of life to a catalogue of facts (by science) creates this doubt, because it robs existence of its essence (which is something other than its mechanics). The part that science is said to steal is what Robert Pirsig calls Quality-the harmonious balance of things. Pirsig seems to imply that this is something inherent in things-and independent from us. A more mundane explanation is that the difference between facts and the complete reality is us-the tendency of mind to connect freely between different kinds of information. This possibility is briefly illustrated here by a myth based on the facts of phylloxera.     

Native language background and academic achievement: Is socioemotional well-being a mediator?

This study examined the extent to which socioemotional well-being mediated the relationship between language status and achievement, while exploring variability in this relationship based on informant (student versus teacher reports of socioemotional problems) and native language background (Spanish-speaking English language learners [ELLs] versus ELLs from Asian-language backgrounds). Participants included 9,046 fifth-grade students from the Early Childhood Longitudinal Study-Kindergarten Cohort of 1998. Results from structural equation modeling showed that Spanish-speaking ELLs reported more social-emotional problems as compared to English-monolingual (EM) and Asian-language ELL classmates in third grade, which partially explained their lower achievement levels in fifth grade. The model accounted for approximately 34% of the variance in students’ academic achievement in fifth grade (R² = .343, p < .001). When comparing ELL and EM students, results differed when using teachers’ versus students’ reports of socioemotional well-being. For both Spanish-speaking and Asian-language ELLs, teachers perceived fewer social and emotional difficulties than the students themselves reported in comparison to their EM classmates.     

Aurora kinases and spindle assembly: Variations on a common theme?

The Aurora A (AurA) serine/threonine kinase controls multiple aspects of cell division and plays a key role in centrosome maturation and bipolar spindle assembly. The pleiotropic functions of AurA depend on its interaction with several cofactors, the best known of which is TPX2. TPX2 targets AurA to spindle microtubules (MTs) and activates it, both allosterically and by protecting the activation loop (T-loop) of the kinase domain from dephosphorylation. Although several factors have been implicated in the regulation of AurA at centrosomes, the underlying mechanism has remained elusive, and the existence of a distinct centrosome-specific AurA activator has been proposed. Our recent study has identified this activator as Cep192/Spd-2, one of the key factors in centrosome biogenesis. Cep192 targets AurA to centrosomes, where it promotes its activation by a novel, oligomerization-dependent mechanism characterized by extensive T-loop phosphorylation and high kinase activity. This process is key to the function of centrosomes as microtubule-organizing centers. Here, our findings are discussed in the context of other recent studies on the Aurora kinases, with an emphasis on their role in spindle assembly. The collected evidence suggests that the ‘hot spots’ of MT nucleation, centrosomes and kinetochores, rely on the oligomerization-mediated mechanism of activation of AurA and AurB, respectively.     

Pathophysiology of heart failure and frailty: a common inflammatory origin?

Frailty, a clinical syndrome that typically occurs in older adults, implies a reduced ability to tolerate biological stressors. Frailty accompanies many age‐related diseases but can also occur without overt evidence of end‐organ disease. The condition is associated with circulating inflammatory cytokines and sarcopenia, features that are shared with heart failure (HF). However, the biological underpinnings of frailty remain unclear and the interaction with HF is complex. Here, we describe the inflammatory pathophysiology that is associated with frailty and speculate that the inflammation that occurs with frailty shares common origins with HF. We discuss the limitations in investigating the pathophysiology of frailty due to few relevant experimental models. Leveraging current therapies for advanced HF and current known therapies to address frailty in humans may enable translational studies to better understand the inflammatory interactions between frailty and HF.     

Wilson's disease: a common liver disorder?

In two sibships 7 of 24 siblings were homozygous for Wilson''s disease. In family A, the largest kindred of this recessively inherited disease thus far reported, the proband presented with chronic active hepatitis, one sibling died of cirrhosis, a second had clinical evidence of chronic liver disease and two others had biochemical and histologic changes in liver biopsy specimens. In family B the proband had cirrhosis and portal hypertension and one sibling had biochemical and histologic evidence of liver disease. All six living patients had low serum concentrations of ceruloplasmin and copper and a high 24-hour urinary excretion of copper, which was greatly increased by administration of D-penicillamine. None showed neurologic abnormalities and only one had Kayser-Fleischer rings (detectable only by slit-lamp examination). Each patient had an erythrocyte sedimentation rate (ESR) of 8 mm/h or less. After 3 and 2 years, respectively, of D-penicillamine therapy the conditions of the two probands had improved. Liver function became normal in three siblings, and no abnormalities developed in the remaining one. Thus, since Wilson''s disease may present with chronic active hepatitis or cirrhosis with a normal ESR and without ocular or neurologic signs, it may be a more common cause of liver disease in young people than has been appreciated.     

The Mauthner cell half a century later: a neurobiological model for decision-making?

The Mauthner (M) cell is a critical element in a vital escape "reflex" triggered by abrupt or threatening events. Its properties at the molecular and synaptic levels, their various forms of plasticity, and the design of its networks, are all well adapted for this survival function. They guarantee that this behavior is appropriately unilateral, variable, and unpredictable. The M cell sets the behavioral threshold, and, acting in concert with other elements of the brainstem escape network, determines when, where, and how the escape is executed.     

Staufen: a common component of mRNA transport in oocytes and neurons?

Mammalian homologues of Staufen, a protein involved in localizing mRNAs during oogenesis and early central nervous system development in Drosophila, have been identified recently. The mammalian staufen gene encodes a protein containing several conserved double-stranded mRNA-binding domains and is expressed in hippocampal neurons. The mammalian Staufen protein forms granules that are transported to the distal dendrite during neuronal maturation. The Staufen granules colocalize with ribonuclear particles that transport mRNA to the dendrites. These findings might provide clues to a mechanism of mRNA transport conserved in mammalian neurons and Drosophila oogenesis.     

Canonical and non-canonical autophagy: variations on a common theme of self-eating?

The autophagosome is the central organelle in macroautophagy, a vacuolar lysosomal catabolic pathway that degrades cytoplasmic material to fuel starving cells and eliminates intracellular pathogens. Macroautophagy has important physiological roles during development, ageing and the immune response, and its cytoprotective function is compromised in various diseases. A set of autophagy-related (ATG) proteins is hierarchically recruited to the phagophore, the initial membrane template in the construction of the autophagosome. However, recent findings suggest that macroautophagy can also occur in the absence of some of these key autophagy proteins, through the unconventional biogenesis of canonical autophagosomes. Such alternatives to the evolutionarily conserved scheme might provide additional therapeutic opportunities.     

Thiol proteases and aldehyde dehydrogenases: Evolution from a common thiolesterase precursor?

The C-terminal 222 residues of human liver aldehyde dehydrogenase can be aligned with the C-terminal 226 residues of a thiol protease from Dictyostelium discoideum to yield 47 residue identities, including matching active site cysteine residues. A multiple alignment with three more aldehyde dehydrogenases and three more thiol proteases yields three regions with clustered residue similarities. In the tertiary structure of papain, these three regions are in close proximity although widely separated in primary structure, and many conserved residues are located in the active site groove. The three-dimensional relationships, the common thiol ester mechanisms of the enzymes, the locations of exon boundaries in the dehydrogenase and protease genes, and the conservation of internal salt-bridging and disulfide-paired residues in papain, all appear compatible with the hypothesis of an ancestral relationship between thiol proteases and aldehyde dehydrogenases.     

LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?

The presence of alpha-synuclein Lewy body pathology is used to distinguish Parkinson's disease from parkinsonism, for which a broader spectrum of neuropathologies, including tau-immunopositive neurofibrillary tangles and ubiquitin inclusions, might accompany nigral neuronal loss. These neuropathologies define the endpoint of many neurodegenerative disorders but might be symptomatic rather than causative. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) were recently discovered in late-onset parkinsonism, the phenotype of which can be clinically and pathologically indistinguishable from Parkinson's disease. However, in some kindreds with LRRK2- associated disease, pathologically distinct forms of parkinsonism, including nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary tangles, were discovered. Understanding the molecular function of the LRRK2 protein and its associated pathways might elucidate the switch between Lewy body pathology and neurofibrillary tangles, and holds promise for prospective therapeutics that might slow or halt progression of many forms of parkinsonism.     

Shading and texture: separate information channels with a common adaptation mechanism?

We outline a scheme for the way in which early vision may handle information about shading (luminance modulation, LM) and texture (contrast modulation, CM). Previous work on the detection of gratings has found no sub-threshold summation, and no cross-adaptation, between LM and CM patterns. This strongly implied separate channels for the detection of LM and CM structure. However, we now report experiments in which adapting to LM (or CM) gratings creates tilt aftereffects of similar magnitude on both LM and CM test gratings, and reduces the perceived strength (modulation depth) of LM and CM gratings to a similar extent. This transfer of aftereffects between LM and CM might suggest a second stage of processing at which LM and CM information is integrated. The nature of this integration, however, is unclear and several simple predictions are not fulfilled. Firstly, one might expect the integration stage to lose identity information about whether the pattern was LM or CM. We show instead that the identity of barely detectable LM and CM patterns is not lost. Secondly, when LM and CM gratings are combined in-phase or out-of-phase we find no evidence for cancellation, nor for 'phase-blindness'. These results suggest that information about LM and CM is not pooled or merged--shading is not confused with texture variation. We suggest that LM and CM signals are carried by separate channels, but they share a common adaptation mechanism that accounts for the almost complete transfer of perceptual aftereffects.     

Do plant and human pathogens have a common pathogenicity strategy?

Recently, a novel 'two-step' model of pathogenicity has been described that suggests host-cell-derived vasculoproliferative factors play a crucial role in the pathogenesis of bacillary angiomatosis, a disease caused by the human pathogenic bacterium Bartonella henselae. The resulting proliferation of endothelial cells could be interpreted as bacterial pathogens triggering the promotion of their own habitat: the host cell. Similar disease mechanisms are well known in the plant pathogen Agrobacterium tumefaciens, which causes crown gall disease. There are notable similarities between the pathogenicity of A. tumefaciens leading to tumourous disease in plants and to the B. henselae-triggered proliferation of endothelial cells in humans. Here, we hypothesize that this pathogenicity strategy might be common to several bacterial species in different hosts owing to shared pathogenicity factors.     

Maternal steroids and contaminants in common tern eggs: a mechanism of endocrine disruption?

We looked for evidence for the hypothesis that exposure of female birds to polychlorinated biphenyls (PCBs) results in alteration of blood steroid hormone concentrations and alters subsequent hormone transfer of steroids to eggs. Eggs of three-egg clutches were collected from a PCB-exposed common tern (Sterna hirundo) colony (Ram Island, Buzzards Bay, MA, USA) and from a relatively clean colony (Bodkin Island, Chesapeake Bay, MD, USA), and were analyzed for concentrations of organochlorine contaminants and steroid hormones (17beta-estradiol, 5alpha-dihydrotestosterone, testosterone and androstenedione). There was no relationship between total PCBs and steroid concentrations considering all eggs together, considering eggs of different laying order or considering differences between sequentially laid eggs in a clutch. Similarly, concentrations of di- and tri-chlorinated biphenyls and steroids in eggs were not related. The concentrations of PCBs, mercury and selenium were below estimated thresholds for toxicity to embryos. Maternal steroids, except estradiol, were present in yolk of all eggs, with increasing concentrations in the second and third eggs laid. Our data provided no evidence for a maternal toxicological event that might alter the amount of maternal steroid hormone transferred to eggs.     

Opinion: Cell entry machines: a common theme in nature?

Molecular machines orchestrate the translocation and entry of pathogens through host cell membranes, in addition to the uptake and release of molecules during endocytosis and exocytosis. Viral cell entry requires a family of glycoproteins, and the structural organization and function of these viral glycoproteins are similar to the SNARE proteins, which are known to be involved in intracellular vesicle fusion, endocytosis and exocytosis. Here, we propose that a family of bacterial membrane proteins that are responsible for cell-mediated adherence and entry resembles the structural architecture of both viral fusion proteins and eukaryotic SNAREs and might therefore share similar, but distinct, mechanisms of cell membrane translocation. Furthermore, we propose that the recurrence of these molecular machines across species indicates that these architectural motifs were evolutionarily selected because they provided the best solution to ensure the survival of pathogens within a particular environment.