Structural basis for the nuclear export activity of Importin13

Importin13 (Imp13) is a bidirectional karyopherin that can mediate both import and export of cargoes. Imp13 recognizes several import cargoes, which include the exon junction complex components Mago‐Y14 and the E2 SUMO‐conjugating enzyme Ubc9, and one known export cargo, the translation initiation factor 1A (eIF1A). To understand how Imp13 can perform double duty, we determined the 3.6‐Å crystal structure of Imp13 in complex with RanGTP and with eIF1A. eIF1A binds at the inner surface of the Imp13 C‐terminal arch adjacent and concomitantly to RanGTP illustrating how eIF1A can be exported by Imp13. Moreover, the 3.0‐Å structure of Imp13 in its unbound state reveals the existence of an open conformation in the cytoplasm that explains export cargo release and completes the export branch of the Imp13 pathway. Finally, we demonstrate that Imp13 is able to bind and export eIF1A in vivo and that its function is essential.     

Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: Prevalence of a novel mutation

We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers. The diagnosis of 5-α-reductase-2 deficiency syndrome was first hypothesized on clinical grounds and then confirmed by molecular analysis. Direct sequencing analysis of the SRD5A2 gene revealed in five patients a novel homozygous frame-shift mutation (c.453delC) and in two related patients a previous reported missense mutation. The presence of the same mutation in unrelated patients of the same population suggests a possible founder effect. This report brings the 5-α-reductase-2 deficiency syndrome to the attention of clinical geneticists and child surgeons and discusses the appropriate clinical and surgical strategies for treating these patients.     

Population distribution and density of Pentalonia nigronervosa (Hemiptera: Aphididae) within banana mats: influence of plant age and height on sampling and management

The banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae), is the most economically important pest of banana (Musa spp.) fields in Hawaii. Recently, there has been a concerted effort in Hawaii to learn more about the biology and ecology of this pest. However, limited work has been directed at determining the distribution of P. nigronervosa in banana fields and developing an integrated pest management plan. Therefore, a survey was conducted in banana fields throughout the Hawaiian Islands to determine the distribution and density of P. nigronervosa within banana mats from plants of different stages. Another aim was to determine whether the presence of ants on banana plants could be used as a reliable indicator of aphid infestations. Results of the survey showed that plants < or = 1.5 m (small sucker) in height contain the highest aphid populations per meter in plant height and that mother plants (> or = 2.5 m) had the lowest aphid counts and rate of infestation compared with small and intermediate suckers (> 1.5 < 2.5 m). More specifically, aphid population was reduced by approximately 12 aphids for every meter increase in plant height and that aphids are rarely found > or = 2.5 m within the plant canopy. Although there was an increase likelihood of finding ants on banana plants with higher aphid densities, results suggest that ants would be present on plants in the absence of aphids. Implications of these and other findings with respect to sampling and managing P. nigronervosa and associated Banana bunchy top virus are discussed.     

Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish

The extracellular matrix is crucial for organogenesis. It is a complex and dynamic component that regulates cell behavior by modulating the activity, bioavailability and presentation of growth factors to cell surface receptors. Here, we determined the role of the extracellular matrix protein Nephronectin (Npnt) in heart development using the zebrafish model system. The vertebrate heart is formed as a linear tube in which myocardium and endocardium are separated by a layer of extracellular matrix termed the cardiac jelly. During heart development, the cardiac jelly swells at the atrioventricular (AV) canal, which precedes valve formation. Here, we show that Npnt expression correlates with this process. Morpholino-mediated knockdown of Npnt prevents proper valve leaflet formation and trabeculation and results in greater than 85% lethality at 7 days post-fertilization. The earliest observed phenotype is an extended tube-like structure at the AV boundary. In addition, the expression of myocardial genes involved in cardiac valve formation (cspg2, fibulin 1, tbx2b, bmp4) is expanded and endocardial cells along the extended tube-like structure exhibit characteristics of AV cells (has2, notch1b and Alcam expression, cuboidal cell shape). Inhibition of has2 in npnt morphants rescues the endocardial, but not the myocardial, expansion. By contrast, reduction of BMP signaling in npnt morphants reduces the ectopic expression of myocardial and endocardial AV markers. Taken together, our results identify Npnt as a novel upstream regulator of Bmp4-Has2 signaling that plays a crucial role in AV canal differentiation.     

Plasmodium falciparum: limited genetic diversity of MSP-2 in isolates circulating in Brazilian endemic areas

The genetic polymorphism of the surface merozoite protein 2 (MSP-2) was evaluated in Plasmodium falciparum isolates from individuals with uncomplicated malaria living in a Brazilian endemic area of Peixoto de Azevedo. The frequency of MSP-2 alleles and the survival of genetically different populations clones in 104 isolates were verified by Southern blot and SSCP-PCR. Single and mixed infections were observed in similar frequencies and the rate of detection of FC27 and 3D7 allelic families was equivalent. Eight alleles were identified and among them, the sequence polymorphism was mainly attributed to variations in the repetitive region. Interestingly, in three alleles nucleotide polymorphism was identical to that detected in a previous study, conducted in 1992, in a near Brazilian endemic area. This finding demonstrated the genetic similarity between two isolate groups, besides the certain temporal stability in the allelic patterns. The implications of these data for studies on the genetic diversity are also discussed.     

Transforming growth factor β 869C/T and interleukin 6 -174G/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis

Introduction  

Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA.     

Excitability of jcBNST Neurons Is Reduced in Alcohol-Dependent Animals during Protracted Alcohol Withdrawal

Alcohol dependence and withdrawal has been shown to cause neuroadaptive changes at multiple levels of the nervous system. At the neuron level, adaptations of synaptic connections have been extensively studied in a number of brain areas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrative properties of neurons. To address these problems, here, we analyze physiological properties of neurons in the bed nucleus of stria terminalis (jcBNST) in animals with a history of alcohol dependence. As a comprehensive approach, first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyze their firing responses under the action of simulated synaptic bombardment via dynamic clamp. We find that most physiological properties as measured by DC current injection are barely affected during protracted withdrawal. However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedly reduced in all 3 types of jcBNST neurons. These results support the importance of studying the effects of alcohol and drugs of abuse on the firing properties of neurons with dynamic clamp protocols designed to bring the neurons into a high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputs from the infralimbic and the insular cortices and in turn is believed to contribute to the inhibitory input to the central nucleus of the amygdala (CeA) the reduced excitability of the jcBNST during protracted withdrawal in alcohol-dependent animals will likely affect ability of the jcBNST to shape the activity and output of the CeA.     

Effects of the Integration of Sunn Hemp and Soil Solarization on Plant-Parasitic and Free-Living Nematodes

Sunn hemp (SH), Crotolaria juncea, is known to suppress Rotylenchulus reniformis and weeds while enhancing free-living nematodes involved in nutrient cycling. Field trials were conducted in 2009 (Trial I) and 2010 (Trial II) to examine if SH cover cropping could suppress R. reniformis and weeds while enhancing free-living nematodes if integrated with soil solarization (SOL). Cover cropping of SH, soil solarization, and SH followed by SOL (SHSOL) were compared to weedy fallow control (C). Rotylenchulus reniformis population was suppressed by SHSOL at the end of cover cropping or solarization period (Pi) in Trial I, but not in Trial II. However, SOL and SHSOL did not suppress R. reniformis compared to SH in either trial. SH enhanced abundance of bacterivores and suppressed the % herbivores only at Pi in Trial II. At termination of the experiment, SH resulted in a higher enrichment index indicating greater soil nutrient availability, and a higher structure index indicating a less disturbed nematode community compared to C. SOL suppressed bacterivores and fungivores only in Trial II but not in Trial I. On the other hand, SHSOL enhanced bacterivores and fungivores only at Pi in Trial I. Weeds were suppressed by SH, SOL and SHSOL throughout the experiment. SHSOL suppressed R. reniformis and enhanced free-living nematodes better than SOL, and suppressed weeds better than SH.