Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects

Background

Eschericia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases.

Methods and Findings

In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1^−/− and heterozygous Alkbh1^+/− offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5–10% of the tubules in Alkbh1^−/− adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations.

Conclusions

Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice.     

Context dependency of infectious disease: the cyanobacterium Microcystis aeruginosa decreases white bacterial disease in Daphnia magna

相似文献   

Strong density-dependent competition and acquired immunity constrain parasite establishment: implications for parasite aggregation

The vast majority of parasites exhibit an aggregated frequency distribution within their host population, such that most hosts have few or no parasites while only a minority of hosts are heavily infected. One exception to this rule is the trophically transmitted parasite Pterygodermatites peromysci of the white-footed mouse (Peromyscus leucopus), which is randomly distributed within its host population. Here, we ask: what are the factors generating the random distribution of parasites in this system when the majority of macroparasites exhibit non-random patterns? We hypothesise that tight density-dependent processes constrain parasite establishment and survival, preventing the build-up of parasites within individual hosts, and preclude aggregation within the host population. We first conducted primary infections in a laboratory experiment using white-footed mice to test for density-dependent parasite establishment and survival of adult worms. Secondary or challenge infection experiments were then conducted to investigate underlying mechanisms, including intra-specific competition and host-mediated restrictions (i.e. acquired immunity). The results of our experimental infections show a dose-dependent constraint on within-host-parasite establishment, such that the proportion of mice infected rose initially with exposure, and then dropped off at the highest dose. Additional evidence of density-dependent competition comes from the decrease in worm length with increasing levels of exposure. In the challenge infection experiment, previous exposure to parasites resulted in a lower prevalence and intensity of infection compared with primary infection of naïve mice; the magnitude of this effect was also density-dependent. Host immune response (IgG levels) increased with the level of exposure, but decreased with the number of worms established. Our results suggest that strong intra-specific competition and acquired host immunity operate in a density-dependent manner to constrain parasite establishment, driving down aggregation and ultimately accounting for the observed random distribution of parasites.     

Fire ant-detecting canines: a complementary method in detecting red imported fire ants

In this investigation, detection dogs are trained and used in identifying red imported fire ants, Solenopsis invicta Buren, and their nests. The methodology could assist in reducing the frequency and scope of chemical treatments for red imported fire ant management and thus reduce labor costs and chemical use as well as improve control and quarantine efficiency. Three dogs previously trained for customs quarantine were retrained to detect the scents of red imported fire ants. After passing tests involving different numbers of live red imported fire ants and three other ant species--Crematogaster rogenhoferi Mayr, Paratrechina longicornis Latreille, and Pheidole megacephala F.--placed in containers, ajoint field survey for red imported fire ant nests by detection dogs and bait traps was conducted to demonstrate their use as a supplement to conventional detection methods. The most significant findings in this report are (1) with 10 or more red imported fire ants in scent containers, the dogs had >98% chance in tracing the red imported fire ant. Upon the introduction of other ant species, the dogs still achieved on average, a 93% correct red imported fire ant indication rate. Moreover, the dogs demonstrated great competence in pinpointing emerging and smaller red imported fire ant nests in red imported fire ant-infested areas that had been previously confirmed by bait trap stations. (2) Along with the bait trap method, we also discovered that approximately 90% of red imported fire ants foraged within a distance of 14 m away from their nests. The results prove detection dogs to be most effective for red imported fire ant control in areas that have been previously treated with pesticides and therefore containing a low density of remaining red imported fire ant nests. Furthermore, as a complement to other red imported fire ant monitoring methods, this strategy will significantly increase the efficacy of red imported fire ant control in cases of individual mount treatment.     

The L7Ae protein binds to two kink-turns in the Pyrococcus furiosus RNase P RNA

The RNA-binding protein L7Ae, known for its role in translation (as part of ribosomes) and RNA modification (as part of sn/oRNPs), has also been identified as a subunit of archaeal RNase P, a ribonucleoprotein complex that employs an RNA catalyst for the Mg²⁺-dependent 5′ maturation of tRNAs. To better understand the assembly and catalysis of archaeal RNase P, we used a site-specific hydroxyl radical-mediated footprinting strategy to pinpoint the binding sites of Pyrococcus furiosus (Pfu) L7Ae on its cognate RNase P RNA (RPR). L7Ae derivatives with single-Cys substitutions at residues in the predicted RNA-binding interface (K42C/C71V, R46C/C71V, V95C/C71V) were modified with an iron complex of EDTA-2-aminoethyl 2-pyridyl disulfide. Upon addition of hydrogen peroxide and ascorbate, these L7Ae-tethered nucleases were expected to cleave the RPR at nucleotides proximal to the EDTA-Fe–modified residues. Indeed, footprinting experiments with an enzyme assembled with the Pfu RPR and five protein cofactors (POP5, RPP21, RPP29, RPP30 and L7Ae–EDTA-Fe) revealed specific RNA cleavages, localizing the binding sites of L7Ae to the RPR''s catalytic and specificity domains. These results support the presence of two kink-turns, the structural motifs recognized by L7Ae, in distinct functional domains of the RPR and suggest testable mechanisms by which L7Ae contributes to RNase P catalysis.     

Spatial and environmental determinants of the distribution of Striped Marlin (Kajikia audax) in the western and central North Pacific Ocean

Striped Marlin is a highly migratory species distributed throughout tropical and temperate waters in the North Pacific Ocean. The habitat characteristics of Striped Marlin in the western and central North Pacific Ocean were examined using generalized additive models by modelling fishery catch-rates as a function of remotely-sensed environmental covariates, including sea surface temperature (SST), chlorophyll-a concentration (CHL), mixed layer depth (MLD) and sea height anomalies (SHA). SST explained the largest proportion of the deviance, and is therefore considered the best predictor for the habitat of Striped Marlin. Spatial distributions of the relative density of Striped Marlin indicated that there is a seasonal north–south migration, and that the highest densities occur in the central North Pacific Ocean. The preferred habitat characteristics of Striped Marlin in high density areas were identified as SST between 23 and 26 °C, MLD within 30 m depth, and CHL around 0.08 mg m^?3, while no preferred range was found for SHA. The results of this study could improve our understanding of Striped Marlin spatial distributions and habitat characteristics.     

Assessment of left ventricular function by two-dimensional speckle-tracking echocardiography in small breed dogs with hyperadrenocorticism

Background

Hyperadrenocorticism (HAC) is associated with an increased prevalence of hypertension. This study investigated the left ventricular function using two-dimensional speckle-tracking echocardiography (2D-STE) in small breed dogs affected with spontaneous HAC.Age-matched healthy controls (n?=?9), dogs with pituitary-dependent hyperadrenocorticism (PDH, n?=?10), and dogs with adrenal-dependent hyperadrenocorticism (ADH, n?=?9) were included in this study. Conventional echocardiography, global longitudinal and circumferential strain, and strain rate were assessed.

Results

On group-wise comparison, left ventricular free wall (LVFWd) and interventricular septal thickness in diastole (IVSd) were thickest in the ADH group, followed by the PDH and controls (P?=?0.014 and P?=?0.001, respectively). Neither LVFWd nor IVSd was correlated with systemic blood pressure (P?=?0.238 and P?=?0.113, respectively). The values of all variables derived from the global strain and strain rate in longitudinal and circumferential directions followed the same pattern: highest in the controls, followed by PDH and then ADH (all P?<?0.05, respectively). On multiple regression analyses, global longitudinal strain, global longitudinal strain rate in systole and early diastole, and global circumferential strain all decreased linearly with increased IVSd (all P?<?0.05).

Conclusions

Left ventricular hypertrophy (LVH) was more prevalent in the HAC group compared to the control group. Association between hypertension and development of LVH was not identified. Decreased global longitudinal and circumferential strains were associated with increased IVSd. 2D-STE revealed significant decreases in systolic functions that were undetected using conventional echocardiography in the ADH and PDH groups.

     

Expression of zebrafish anterior gradient 2 in the semicircular canals and supporting cells of otic vesicle sensory patches is regulated by Sox10

AGR2 is a member of the protein disulfide isomerase (PDI) family, which is implicated in cancer cell growth and metastasis, asthma, and inflammatory bowel disease. Despite the contributions of this protein to several biological processes, the regulatory mechanisms controlling expression of the AGR2 gene in different organs remain unclear. Zebrafish anterior gradient 2 (agr2) is expressed in several organs, including the otic vesicles that contain mucus-secreting cells. To elucidate the regulatory mechanisms controlling agr2 expression in otic vesicles, we generated a Tg(− 6.0 k agr2:EGFP) transgenic fish line that expressed EGFP in a pattern recapitulating that of agr2. Double immunofluorescence studies were used to demonstrate that Agr2 and GFP colocalize in the semicircular canals and supporting cells of all sensory patches in the otic vesicles of Tg(− 6.0 k agr2:EGFP) embryos. Transient/stable transgenic analyses coupled with 5′-end deletion revealed that a 100 bp sequence within the − 2.6 to − 2.5 kbp region upstream of agr2 directs EGFP expression specifically in the otic vesicles. Two HMG-binding motifs were detected in this region. Mutation of these motifs prevented EGFP expression. Furthermore, EGFP expression in the otic vesicles was prevented by knockdown of the sox10 gene. This corresponded with decreased agr2 expression in the otic vesicles of sox10 morphants during different developmental stages. Electrophoretic mobility shift assays were used to show that Sox10 binds to HMG-binding motifs located within the − 2.6 to − 2.5 kbp region upstream of agr2. These results demonstrate that agr2 expression in the otic vesicles of zebrafish embryos is regulated by Sox10.