Parathyroid-Specific Deletion of Klotho Unravels a Novel Calcineurin-Dependent FGF23 Signaling Pathway That Regulates PTH Secretion

Klotho acts as a co-receptor for and dictates tissue specificity of circulating FGF23. FGF23 inhibits PTH secretion, and reduced Klotho abundance is considered a pathogenic factor in renal secondary hyperparathyroidism. To dissect the role of parathyroid gland resident Klotho in health and disease, we generated mice with a parathyroid-specific Klotho deletion (PTH-KL^−/−). PTH-KL^−/− mice had a normal gross phenotype and survival; normal serum PTH and calcium; unaltered expression of the PTH gene in parathyroid tissue; and preserved PTH response and sensitivity to acute changes in serum calcium. Their PTH response to intravenous FGF23 delivery or renal failure did not differ compared to their wild-type littermates despite disrupted FGF23-induced activation of the MAPK/ERK pathway. Importantly, calcineurin-NFAT signaling, defined by increased MCIP1 level and nuclear localization of NFATC2, was constitutively activated in PTH-KL^−/− mice. Treatment with the calcineurin-inhibitor cyclosporine A abolished FGF23-mediated PTH suppression in PTH-KL^−/− mice whereas wild-type mice remained responsive. Similar results were observed in thyro-parathyroid explants ex vivo. Collectively, we present genetic and functional evidence for a novel, Klotho-independent, calcineurin-mediated FGF23 signaling pathway in parathyroid glands that mediates suppression of PTH. The presence of Klotho-independent FGF23 effects in a Klotho-expressing target organ represents a paradigm shift in the conceptualization of FGF23 endocrine action.     

Morphological and molecular identification of medically important questing Dermacentor species collected from some recreational areas of Peninsular Malaysia

Systematic Parasitology - Questing is a situation when a tick is seeking to get closer or ambush its potential host. However, information on questing tick species in Malaysia is still lacking, thus...     

Distribution of detritivores in tropical forest streams of peninsular Malaysia: role of temperature,canopy cover and altitude variability

The diversity and abundance of macroinvertebrate shredders were investigated in 52 forested streams (local scale) from nine catchments (regional scale) covering a large area of peninsular Malaysia. A total of 10,642 individuals of aquatic macroinvertebrates were collected, of which 18.22 % were shredders. Biodiversity of shredders was described by alpha (α_average ), beta (β) and gamma diversity (γ) measures. We found high diversity and abundance of shredders in all catchments, represented by 1,939 individuals (range 6–115 and average per site of 37.29?±?3.48 SE) from 31 taxa with 2–13 taxa per site (α_average?=?6.98?±?0.33 SE) and 10–15 taxa per catchment (γ?=?13.33?±?0.55 SE). At the local scale, water temperature, stream width, depth and altitude were correlated significantly with diversity (Adj-R ²?=?0.205). Meanwhile, dissolved oxygen, stream velocity, water temperature, stream width and altitude were correlated to shredder abundance (Adj-R ²?=?0.242). At regional scale, however, water temperature was correlated negatively with β and γ diversity (r ²?=?0.161 and 0.237, respectively) as well as abundance of shredders (r ²?=?0.235). Canopy cover was correlated positively with β diversity (r ²?=?0.378) and abundance (r ²?=?0.266), meanwhile altitude was correlated positively with β (quadratic: r ²?=?0.175), γ diversity (quadratic: r ²?=?0.848) as well as abundance (quadratic: r ²?=?0.299). The present study is considered as the first report describing the biodiversity and abundance of shredders in forested headwater streams across a large spatial scale in peninsular Malaysia. We concluded that water temperature has a negative effect while altitude showed a positive relationship with diversity and abundance of shredders. However, it was difficult to detect an influence of canopy cover on shredder diversity.     

Multiple pterygium syndrome in five Arab sibs

This report describes an Arab family in which the parents are first cousins and with 5 siblings having multiple pterygium syndrome. The last pregnancy which produced an affected sib was prenatally diagnosed by ultrasonography. Intrafamilial variability of clinical features is discussed. The report stresses the importance of the differentiation between various genetic entities with multiple pterygium.     

Colonic Perforation after Exchange Transfusion

Four patients are reported in whom perforation of the colon followed exchange transfusion for haemolytic disease of the newborn. This association seems to be more than coincidental, and possibly the perforation is due to a vascular accident occurring as a mechanical result of the exchange transfusion. The insidious onset of colonic perforation may be recognized early by the passage of blood per rectum. There is no place for conservative treatment, and once the diagnosis has been made treatment must include broad-spectrum antibiotics and laparotomy.     

Asp-376-Glu substitution endows target-site resistance to AHAS inhibitors in Limnocharis flava,an invasive weed in tropical rice fields

Limnocharis flava (L.) Buchenau is a problematic weed in rice fields and water canals of Southeast Asia, and in Malaysia this invasive aquatic weed species has evolved multiple resistance to synthetic auxin herbicide and acetohydroxyacid synthase (AHAS) inhibitors. In this study, it was revealed that, a single nucleotide polymorphism (SNP) at amino acid position 376, where C was substituted to G at the third base of the same codon (GAC to GAG), resulting in Aspartate (Asp) substitution by Glutamate (Glu) was the contributing resistance mechanism in the L. flava population to AHAS inhibitors. In vitro assay further proved that, all the L. flava individuals carrying AHAS resistance mutation exhibited decreased-sensitivity to AHAS inhibitors at the enzyme level. In the bensulfuron-methyl whole-plant bioassay, high resistance indices (RI) of 328- and 437-fold were recorded in the absence and presence of malathion (the P450 inhibitor), respectively. Similarly, translocation and absorption of bensulfuron-methyl in both resistant and susceptible L. flava populations showed no remarkable differences, hence eliminated the possible co-existence of non-target-site resistance mechanism in the resistant L. flava. This study has confirmed another new case of a target-site resistant weed species to AHAS-inhibitors.     

Oviposition preference of swallowtail butterfly,Papilio polytes (Lepidoptera: Papilionidae) on four Rutaceae (Sapindales) host plant species

Abstract Oviposition preference and egg deposition site selection by the butterfly, Papilio polytes L. (Lepidoptera: Papilionidae) on four rutaceous host plants, Citrus aurantofolia (Christm.) Swing., Citrus hystrix DC., Citrus reticulata Blanco, and Murraya koenigii (L.) Sprengel, were assessed in field cages measuring 2 × 2 × 2 m. Simultaneous two-choice and four-choice oviposition tests of whole host plants were conducted. The mean total number of eggs laid per plant on C. reticulata in the two-choice test was significantly higher (P < 0.01) than those on C. aurantifolia, C. hystrix, and M. koenigii. Among the three other host plants, C. aurantifolia was preferred over C. hystrix, and M. koenigii (P < 0.01) and C. hystrix was preferred over M. koenigii (P < 0.01). In the four-choice test, C. reticulata was highly preferred and significantly different from C. hystrix and M. koenigii. However, no oviposition preference was detected with C. aurantifolia. Among the various plant parts in the two- and four-choice tests, eggs on leaves of each plant were the highest, followed by numbers on stems, and negligible numbers on pots. These numbers on leaves of C. reticulata and C. aurantifolia were not significantly different (P > 0.05), but differed significantly (P < 0.01) from those on leaves of C. hystrix and M. koenigii. The quantitative trend of egg-laying on stems was very similar to that observed for the leaves. Papilio polytes showed strong preference to lay eggs on the underside of leaves of all host plants than on the upper side or on the petiole. More eggs were laid on the upper side of each host plant than on its petiole. The four host plants in descending order of preference were C. reticulata≥C. aurantifolia > C. hystrix > M. koenigii. Although M. koenigii was the least preferred, it has the potential to serve as an alternative host plant for P. polytes which can be manipulated when necessary, to alleviate the infestation of this pest to the citrus industry.     

Molecular identification of blood meal sources of ticks (Acari,Ixodidae) using cytochrome b gene as a genetic marker

Blood meal analysis (BMA) from ticks allows for the identification of natural hosts of ticks (Acari: Ixodidae). The aim of this study is to identify the blood meal sources of field collected on-host ticks using PCR analysis. DNA of four genera of ticks was isolated and their cytochrome b (Cyt b) gene was amplified to identify host blood meals. A phylogenetic tree was constructed based on data of Cyt b sequences using Neighbor Joining (NJ) and Maximum Parsimony (MP) analysis using MEGA 5.05 for the clustering of hosts of tick species. Twenty out of 27 samples showed maximum similarity (99%) with GenBank sequences through a Basic Local Alignment Search Tool (BLAST) while 7 samples only showed a similarity range of between 91–98%. The phylogenetic trees showed that the blood meal samples were derived from small rodents (Leopoldamys sabanus, Rattus tiomanicus and Sundamys muelleri), shrews (Tupaia glis) and mammals (Tapirus indicus and Prionailurus bengalensis), supported by 82–88% bootstrap values. In this study, Cyt b gene as a molecular target produced reliable results and was very significant for the effective identification of ticks’ blood meal. The assay can be used as a tool for identifying unknown blood meals of field collected on-host ticks.