Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex

Peroxisome biogenesis disorders (PBDs) are fatal autosomal recessive diseases and are caused by impaired peroxisome biogenesis. PBDs are genetically heterogeneous and classified into 13 complementation groups (CGs). CG8 is one of the most common groups and has three clinical phenotypes, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy, and infantile Refsum disease (IRD). We recently isolated PEX26 as the pathogenic gene for PBD of CG8. Pex26p functions in recruiting to peroxisomes the complexes of the AAA ATPase peroxins, Pex1p and Pex6p. In the present work, we identified four distinct mutations in PEX26 from five patients of CG8 PBD including 2 with ZS and 3 with IRD, in addition to 7 mutant alleles in 8 patients in the first report describing the pathogenic PEX26 gene for CG8 PBD. Phenotype-genotype analyses revealed that temperature-sensitive (ts) peroxisome assembly gave rise to a milder IRD in contrast to the non-ts phenotype of the cells from ZS patients. Furthermore, we present several lines of evidence that show that the instability, insufficient binding to Pex1p x Pex6p complexes, or mislocalization of patient-derived Pex26p mutants is most likely responsible for the CG8 PBDs.     

Antimicrobial resistance in Campylobacter isolated from food animals and humans in northern Thailand

A study was conducted to determine the prevalence of Campylobacter with antimicrobial resistance from chickens, pigs, dairy cows, healthy farm workers, and children hospitalized with diarrhea in northern Thailand. Resistance was highest in pig samples and lowest in healthy farm workers. Resistance to fluoroquinolones and tetracycline was high in all study populations. The increased prevalence of resistant isolates from meat samples collected at markets, compared to isolates collected from animals on the farm or the slaughterhouse, suggests that contamination after carcasses leave the slaughterhouse is an important factor in the spread of resistant bacteria into the human food chain.     

Salt soluble without jelly-like component from the oviducal gland induces chorionic expansion in the ova of the Japanese common squid Todarodes pacificus

Abstract

In vitro fertilization of squid requires the jelly substance found in the female oviducal gland; yet, the active component of this substance that facilitates fertilization remains unknown. Here, we used biochemical methods to separate the jelly substance of Todarodes pacificus (Oegopsida) and Sepioteuthis lessoniana (Myopsida family) into four fractions; specifically, two water soluble fractions (Molecular weight > 10,000 and < 10,000), one salt soluble fraction, and one insoluble fraction. The salt soluble fraction of T. pacificus induced chorionic expansion (perivitelline space formation), which precedes the normal embryonic development of ova. In contrast, the salt soluble fraction of S. lessoniana elicited insufficient expansion of the ova, only producing embryos with high abnormality rates. These results suggest that the salt soluble component(s) (not the jelly-like substances) in the oviducal gland induce chorionic expansion and hatching in Oegopsida, and that these components may be similar in Myopsida.     

Oxidative Cyclization of 2′,3′-O-Isopropylidene-Adenosines into 5′-O,8-Cycloadenosines with Lead Tetraacetate: Remarkable Effect of N6-Substituents on the Oxidation

Abstract

Oxidation of 2′,3′-O-isopropylideneadenosines (1) with lead tetraacetate (LTA) in dry benzene resulted in the formation of the corresponding 5′-O,8-cyclo-2′,3′-O-isopropylideneadenosines (2), which has a new methodological implication for the chemical modification of adenosines. The occurrence of the oxidative cyclization was remarkably affected by the nature of N⁶-substituents: N⁶-benzoyl substitution prominently accelerated the oxidative cyclization in comparison with none and dimethyl substitutions. In the oxidation of N⁶,N⁶-dimethyladenosine (1d), an intriguing oxidative demethylation was observed.     

Postnatal Changes in Activities of Acetylcholinesterase and Cholinesterase in the Brain of a Methylazoxymethanol-induced Microencephalic Rat

Activities of AChE and ChE per g wet weight of the cerebrum were higher in the cerebrum of the MAM-induced microencephalic rats that were the offspring of the mother rats injected on the 15th day of pregnancy with MAM-acetate than in the normal rats cerebrum. They increased for 30 days after birth and were maintained constant thereafter. The activity of AChE more increased in the cerebral subcortex than in other regions. With the increase in dose of the drug administered to mother rats, the cerebral weight of their offspring decreased gradually whereas AChE activity per g wet weight of their cerebrum increased. These findings support existence of plasticity in the cerebrum.     

Synthesis of carbocyclic pyrimidine nucleosides and their inhibitory activities against Plasmodium falciparum thymidylate kinase

Plasmodium falciparum thymidylate kinase (PfTMK) is a promising antimalarial target due to its unique substrate specificity. Recently, we reported that 2′,3′-dideoxycarbocyclic thymidine showed moderate inhibitory activity and reported the related structure–activity relationship for inhibitors against PfTMK. In this study, we have designed and synthesized enantioselective 2′,3′-dideoxycarbocyclic pyrimidine nucleosides based on our previous results and screened them for inhibitory activity against PfTMK. The most potent inhibitor showed K_i^TMP and K_i^dGMP values of 14 and 20 μM, respectively. The fluorinated dideoxy derivative (-)-7, exhibited lower K_i^TMP and higher K_i^dGMP compared with that of the parent compound (K_i^TMP, K_i^dGMP equals 20 and 7 μM, respectively). The modification of carbocyclic pyrimidine nucleosides is a promising strategy for developing powerful PfTMK inhibitors.     

Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function

Although the secreted phospholipase A(2) (sPLA(2)) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA(2) (sPLA(2)-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA(2)-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA(2)-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA(2)-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.     

Fungus fruit body lytic enzyme from a myxomycete,Badhamia utricularis

Chitinase,β-1,3-glucanase, cellulase, xylanase and protease activity were detected in a crude enzyme preparation obtained from a slime mold (Badhamia utricularis) which was grown on autoclaved mycelia ofPholiota nameko in a petri dish. The optimal pH of the enzyme preparation for lytic activity against fruit bodies ofLentinus edodes was 4.0, and those ofβ-1,3-glucanase and cellulase were the same. On the other hand, chitinase and protease showed optimal activity at pH 5.0 and 8.0, respectively. The lytic activity was stable below 40°C but completely inactivated at 70°C, and was most stable at pH 5.0. The studies of the optimal pH, thermal stability, and pH stability, and isoelectric focusing analysis of the enzyme preparation suggest that chitinase,β-1,3-glucanase and cellulase activities may be responsible for lysis of fruit bodies of some mushrooms. The crude enzyme preparation from the slime mold lysed fruit bodies of several mushrooms more efficiently than did commercial lytic enzymes preparations (Driselase and Usukizyme).