Reduced immunoglobulin A transcytosis associated with immunoglobulin A nephropathy and nasopharyngeal carcinoma

Polymeric IgA (pIgA) is transcytosed by the pIgA receptor (pIgR) across mucosal epithelial cells. After transcytosis to the apical surface, the extracellular, ligand-binding portion of the pIgR is proteolytically cleaved. A missense mutation in human pIgR, A580V, is associated with IgA nephropathy and nasopharyngeal carcinoma. We report that this mutation reduces the rate of transcytosis of pIgR and pIgA, and seemingly the rate of pIgR cleavage. We propose that the defects in pIgR trafficking caused by the A580V mutation may underlie the pathogenesis of both diseases.     

Effects of recent warm and cold spells on European plant phenology

Climate change is already altering the magnitude and/or frequency of extreme events which will in turn affect plant fitness more than any change in the average. Although the fingerprint of anthropogenic warming in recent phenological records is well understood, the impacts of extreme events have been largely neglected. Thus, the temperature response of European phenological records to warm and cold spells was studied using the COST725 database. We restricted our analysis to the period 1951–2004 due to better spatial coverage. Warm and cold spells were identified using monthly mean ENSEMBLES temperature data on a 0.5° grid for Europe. Their phenological impact was assessed as anomalies from maps displaying mean onsets for 1930–1939. Our results clearly exhibit continental cold spells predominating in the period 1951–1988, especially during the growing season, whereas the period from 1989 onwards was mainly characterised by warm spells in all seasons. The impacts of these warm/cold spells on the onset of phenological seasons differed strongly depending on species, phase and timing. “False” phases such as the sowing of winter cereals hardly reacted to summer warm/cold spells; only the sowing of summer cereals mirrored spring temperature warm/cold spells. The heading dates of winter cereals did not reveal any consistent results probably due to fewer warm/cold spells identified in the relevant late spring months. Apple flowering and the harvest of winter cereals were the best indicators of warm/cold spells in early spring and summer, also being spatially coherent with the patterns of warm/cold spells.     

Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities

The annexins, a family of Ca(2+)- and lipid-binding proteins, are involved in a range of intracellular processes. Recent findings have implicated annexin A1 in the resealing of plasmalemmal injuries. Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin O. An injury-induced elevation in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) triggers plasmalemmal repair. The highly Ca(2+)-sensitive annexin A6 responds faster than annexin A1 to [Ca(2+)](i) elevation. Correspondingly, a limited plasmalemmal injury can be promptly countered by annexin A6 even without the participation of annexin A1. However, its high Ca(2+) sensitivity makes annexin A6 highly amenable to an unproductive binding to the uninjured plasmalemma; during an extensive injury accompanied by a massive elevation in [Ca(2+)](i), its active pool is severely depleted. In contrast, annexin A1 with a much lower Ca(2+) sensitivity is ineffective at the early stages of injury; however, it remains available for the repair even at high [Ca(2+)](i). Our findings highlight the role of the annexins in the process of plasmalemmal repair; a number of annexins with different Ca(2+)-sensitivities provide a cell with the means to react promptly to a limited injury in its early stages and, at the same time, to withstand a sustained injury accompanied by the continuous formation of plasmalemmal lesions.     

Population structure and comparative phylogeography of jack species (Caranx ignobilis and C. melampygus) in the high Hawaiian Islands

Members of the family Carangidae are top-level predators and highly prized food and sport fishes. Although ecologically and economically important, little is known about the biology of numerous species in the family. This is particularly true of the jacks Caranx ignobilis and C. melampygus, which have experienced recent population reductions around the high Hawaiian Islands due to overfishing. Previous studies have documented territorial tendencies as well as cases of long-distance excursions in both species, suggesting populations may exhibit a range of structure at the genetic level. To explore this possibility, mitochondrial DNA ATPase6 and ATPase8 gene sequence variation was assessed from 91 individuals (33 C. ignobilis and 58 C. melampygus) spanning the islands of Kaua'i, O'ahu, Moloka'i, Maui, and Hawai'i. Although a total of 20 distinct haplotypes (8 for C. ignobilis; 12 for C. melampygus) were recovered, no evidence of population structure was found for either species across the examined geographic range. However, distinct demographic patterns were identified, implying differing evolutionary histories and/or population dynamics. Additionally, ～ 6% of the examined C. ignobilis were C. ignobilis × C. melampygus hybrids because they harbored mitochondrial haplotypes typical of C. melampygus. These hybrids contribute to measurable gene flow between the species and may play a significant role in the evolution of the genus.     

A NEW SPECIES OF VOLVOX SECT. MERRILLOSPHAERA (VOLVOCACEAE,CHLOROPHYCEAE) FROM TEXAS1

Smith (1944) divided the familiar genus Volvox L. into four sections, placing seven species that lacked cytoplasmic bridges between adult cells in the section Merrillosphaera. Herein, we describe a new member of the section Merrillosphaera originating from Texas (USA): Volvox ovalis Pocock ex Nozaki et A. W. Coleman sp. nov. Asexual spheroids of V. ovalis are ovoid or elliptical, with a monolayer of 1,000–2,000 somatic cells that are not linked by cytoplasmic bridges, an expanded anterior region, and 8–12 gonidia in the posterior region. Visibly asymmetric cleavage divisions do not occur in V. ovalis embryos as they do Volvox carteri F. Stein, Volvox obversus (W. Shaw) Printz, and Volvox africanus G. S. West, so the gonidia of the next generation are not yet recognizable in V. ovalis embryos prior to inversion. Molecular phylogenetic analyses of the five chloroplast genes and the internal transcribed spacer (ITS) regions of nuclear rDNA indicated that V. ovalis is closely related to Volvox spermatosphaera Powers ( Powers 1908 , as “spermatosphara”) and/or Volvox tertius Art. Mey.; however, V. ovalis can be distinguished from V. spermatosphaera by its larger gonidia, and from V. tertius by visible differences in gonidial chloroplast morphology.     

A novel flow cytometry-based technique to measure adult neurogenesis in the brain

The stimulation of neurogenesis is an exciting novel therapeutic option for diseases of the central nervous system, ranging from depression to neurodegeneration. One major bottleneck in screening approaches for neurogenesis-inducing compounds is the very demanding in vivo quantification of newborn neurons based on stereological techniques. To effectively develop compounds in this area, novel fast and reliable techniques for quantification of in vivo neurogenesis are needed. In this study, we introduce a flow cytometry-based method for quantifying newly generated neurons in the brain based on the counting of cell nuclei from dissected brain regions. Important steps involve density sedimentation of the cell nuclei, and staining for the proliferation marker bromodeoxy uridine and nuclear cell type markers such as NeuN. We demonstrate the ability of the technique to detect increased neurogenesis in the hippocampus of animals which underwent physical exercise and received fluoxetine treatment.     

Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit its phosphatase activity

Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation of insulin and leptin signaling and is an established therapeutic target for diabetes and obesity. PTP1B is regulated by reactive oxygen species (ROS) produced in response to various stimuli, including insulin. The reversibly oxidized form of the enzyme (PTP1B-OX) is inactive and undergoes profound conformational changes at the active site. We generated conformation-sensor antibodies, in the form of single-chain variable fragments (scFvs), that stabilize PTP1B-OX and thereby inhibit its phosphatase function. Expression of conformation-sensor scFvs as intracellular antibodies (intrabodies) enhanced insulin-induced tyrosyl phosphorylation of the β subunit of the insulin receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of PKB/AKT. Our data suggest that stabilization of the oxidized, inactive form of PTP1B with appropriate therapeutic molecules may offer a paradigm for phosphatase drug development.     

Cellular pathways for viral transport through plasmodesmata

Plant viruses use plasmodesmata (PD) to spread infection between cells and systemically. Dependent on viral species, movement through PD can occur in virion or non-virion form, and requires different mechanisms for targeting and modification of the pore. These mechanisms are supported by viral movement proteins and by other virus-encoded factors that interact among themselves and with plant cellular components to facilitate virus movement in a coordinated and regulated fashion.     

Comparison of cytotoxic T lymphocyte efficacy in acute and persistent lymphocytic choriomeningitis virus infection

Immune responses mediated by cytotoxic T lymphocytes (CTLs) have often been found to be functionally impaired in persistent infections. It is assumed that this impairment contributes to persistence of the infection. In this study, we compare the killing efficacy of CD8(+) T-cell responses in mice acutely and persistently infected with the lymphocytic choriomeningitis virus, using an in vivo CTL killing assay. To infer the killing efficacy of CTLs, we developed a new mathematical model describing the disappearance of peptide-pulsed cells from the blood of the mice over time. We estimate a lower half-life for peptide-pulsed cells in acute infection than in persistent infection, which indicates a higher killing efficacy of the CD8(+) T-cell response in acute infection. However, by controlling for the different levels of CTLs in acutely and persistently infected mice, we find that CTLs in persistent infection are only two times less efficacious than CTLs in acute infections. These results strongly suggest that the in vivo cytotoxicity of CD8(+) T-cell responses in persistent infection is modulated via the number of CTLs rather than their individual functionality.