Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT) samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP1 positive adipocytes in 10.3% of 87 lean children (aged 0.3 to 10.7 years) and in one overweight infant, whereas we did not find brown adipocytes in obese children or adults. In our samples, the brown-like adipocytes were interspersed within white AT of perirenal, visceral and also subcutaneous depots. Samples with brown-like adipocytes showed an increased expression of UCP1 (>200fold), PRDM16 (2.8fold), PGC1α and CIDEA while other brown/beige selective markers, such as PAT2, P2RX5, ZIC1, LHX8, TMEM26, HOXC9 and TBX1 were not significantly different between UCP1 positive and negative samples. We identified a positive correlation between UCP1 and PRDM16 within UCP1 positive samples, but not with any other brown/beige marker. In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults. Our data indicate that brown-like adipocytes are present well beyond infancy in subcutaneous depots of non-obese children. The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.

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Various acute and chronic brain diseases result in disturbed expression of the glial glutamate transporters, GLAST/EAAT-1 and GLT-1/EAAT-2, and subsequent secondary neuronal cell death. The idea that glutamate-induced brain damage can be prevented by restoring glutamate homeostasis in the injured brain, focussed previous efforts on identifying the network controlling astrocytic glutamate transport. Since most of this work was performed with rat astrocytes, we now sought to compare the transcriptional regulation of the GLAST/EAAT-1 gene in rat and man. Reporter gene assay demonstrated that the human GLAST/EAAT-1 promoter comprises the 2.3 kb region immediately flanking the 5'-end of the human GLAST/EAAT-1 gene. Cloning of the previously unknown promoter of rat GLAST/EAAT-1 gene demonstrated maximal reporter gene activity with a sequence comprising the 1.5 kb region flanking the 5'-end of the gene as well as non-coding exon 1, and intron 1-2. Although the promoter regions from both species lacked sequence homology, they contained numerous identical consensus motifs. In human promoter constructs, dbcAMP, PACAP, EGF, and TGFα, which represent potent stimulators of endogenous GLAST/EAAT-1 expression, only further increased reporter gene activity in the presence of the GLAST/EAAT-1 3'-UTR. By contrast, the rat GLAST/EAAT-1 3'-UTR only mediated the stimulatory increases of dbcAMP. Moreover, the GLAST/EAAT-1 3'-UTR repressed constitutive GLAST/EAAT-1 expression in man, but enhanced GLAST/EAAT-1 transcription in rat. Together, our findings suggest the existence of close functional similarities of the GLAST/EAAT-1 promoter regions in man and rat and further point to a species-specific function of the GLAST/EAAT-1 3'-UTR in constitutive and regulated GLAST/EAAT-1 expression.

Herein, we included 527 individuals from two Hospitals, Chemnitz and University-Hospital Leipzig. In total, 199 were negative for PCR and 328 were positive upon first admission. We used next generation sequencing for HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, and DPB1, and in some cases, HLA-E, F, G, and H. Furthermore, we molecularly defined 22 blood group systems comprising 26 genes and 5 platelet antigen genes. We observed a significant enrichment of homozygosity for DQA/DQB in the positive group. Within the negative subjects, HLA-B*57:01, HLA-B*55:01, DRB1*13:01, and DRB1*01:01 were enriched, and in the positive group, homozygosity for DQA/DQB, DRB1*09:01, and DRB1*15:01 was observed. DQA1*01:01, DQA1*02:01, and DQA1*01:03 were enriched in the negative group. HLA-DQB1*06:02 was enriched in the positive group, and HLA-DQB1*05:01 and HLA-DQB1*06:03 were enriched in the negative group. For the blood group systems MNS, RH, LE, FY, JK, YT, DO, and KN, enrichment was seen in both groups, depending on the antigen under observation. Homozygosity for D-positive RHD alleles, as well as the phenotypes M-N+ of the MNS blood group system and Yk(a-) of the KN system, were enriched in the positive group. All of these significances disappeared upon correction. Subjects who carried homozygous HPA-1a were more frequent in the negative group, contrasting with the finding that HPA-1ab was enriched in the positive group.