In a Model of Batten Disease,Palmitoyl Protein Thioesterase-1 Deficiency Is Associated with Brown Adipose Tissue and Thermoregulation Abnormalities

Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets) compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of neurodegenerative diseases that are linked to alterations in peripheral metabolic processes. In addition, extrapolating these findings clinically, impaired thermoregulation and hypothermia are potential risks in patients with INCL.     

Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities

Molecular and Cellular Biochemistry - Uterine leiomyoma is the most common tumor of the female reproductive system and originates from a single transformed myometrial smooth muscle cell. Despite...     

A study of some genetic characteristics of the Fur and Baggara tribes of the Sudan

The average inbreeding coefficients of the highly consanguineous Fur and Baggara tribes of Western Sudan were 0.04167 and 0.04450, respectively. Two hundred ninety-eight subjects from the two tribes were tested for polymorphism of hemoglobins, seven red cell enzymes, and four serum proteins. The Baggara showed a higher gene frequency of HbS and TfD and lower gene frequency of GdA and PC compared to the Fur. Both tribes showed a low gene frequency of PGM1 and high frequency of G6PD deficiency when compared to other Sudanese tribes. In spite of the high degree of inbreeding, no significant deviation from the Hardy-Weinburg equilibrium was observed in either tribe. The effects of inbreeding seem to be offset by mixing between the two tribes on Gabal Marra Plateau. The flow of the sickle gene from the Baggara into the Fur and other Sudanese tribes is discussed.     

Wave propagation across a bony discontinuity simulating a healing fracture

Stress wave propagation in a long bone with a progressively increasing defect in the bony cortex, simulating a healing fracture, was studied by recording the outputs of bonded semiconductor strain gages, proximal and distal to the defect. Statistically significant relations were found between the relative size of the discontinuity and the transmission coefficient, dispersion and transit time across the fracture. We also showed that the stress wave in a bone could be monitored from the vibration response of a traction pin, placed in a magnetic field. The results may be helpful for the development of new methods to measure the rate of fracture healing, as well as aiding our understanding of the dynamic loading of bone.     

Transferrin subtypes and spontaneous abortion in a Chinese population

A series of Chinese newborns of consecutive normal vaginal deliveries were investigated for the distribution of serum transferrin subtypes by polyacrylamide gel iso-electric focusing at pH 3.5-9.5. Newborns whose mothers had a history of previous spontaneous abortion (n = 189) had a significantly higher frequency of the C2 variant and the C2 gene compared to those (n = 864) without a history of spontaneous abortion. There was no significant difference in the frequency of transferrin alleles between newborns with normal and low birth weight (n = 147).     

On Neodiaptomus schmackeri (Poppe & Richard, 1892) (Crustacea,Copepoda)

Neodiaptomus schmackeri and related species are redescribed. The synonymy of this species with N. strigilipes and N. handeli is discussed.     

Genetic heterogeneity among the Negroid and Arab tribes of the Sudan

Genetic distance analysis was carried out among seven tribes of the Sudan comprising three Negroid (Nuba, Fur, and Nilotes) and four Arab tribes (Beja, Gaalin, Hawazma, and Messeria) on the basis of six polymorphic loci (ABO and Rhesus blood groups; haemoglobin and red cell glucose-6-phosphate dehydrogenase; serum haptoglobin and transferrin polymorphisms) controlling 21 alleles and compared with the Arab and Negroid populations in neighbouring countries. The Nuba and Nilotes have been found to have Negroid genetic characteristics, while the Fur are intermediate between the Arabs and Negroids. The Beja and Gaalin tribes have more pronounced Arab genetic characteristics than the Hawazma and Messeria, who have a great deal of Negroid admixture.     

Distribution of red cell phosphoglucomutase-1 subtypes in several Mongoloid populations of East Asia

The distribution of red cell phosphoglucomutase (PGM) subtypes was determined by starch-gel electrophoresis and isoelectric focusing in a group of 2,484 unrelated individuals from ten Mongoloid populations of East Asia. The sample comprised 998 Chinese from various localities--Singapore, 325; Malaysia, 270; Taiwan, 276; Hong Kong, 67; Fouzhou, 60--as well as 342 Koreans; 252 Filipinos; 529 Thais; 336 Malays, and 27 Indonesians. Altogether 15 phenotypes controlled by four common and five rare alleles at the PGM1 locus were observed in these populations. The frequency of the most frequent allele (PGM1+) varied from 0.56 to 0.74, with the highest frequency observed in the Singapore Chinese and the lowest in the Malays. Within the Chinese from different localities a significant degree of heterogeneity was observed at the PGM1 locus. The rare allele (PGM17)6 was observed only among the Chinese, Thais, and Malays, while the PGM1 was lacking in the Filipinos. A new allele with ahigh pI (6.5) was observed in a low frequency in all the populations but the Malays.