Evidence for the cerebral uptake in vivo from two pools of glucose and the role of glucose-6-phosphatase in removing excess substrate from brain

We propose the following scheme for cerebral uptake and overall metabolism of glucose in vivo: that brain selects from two pools of glucose anomers in arterial blood, that it takes up excess glucose, that glucose enters the brain tissue as glucose-6-phosphate through the actions of mutarotase and hexokinase, that some glucose-6-phosphate becomes metabolized to CO₂ and some becomes incorporated into brain carbon pools, and that excess glucose-6-phosphate leaves brain through glucose-6-phosphatase and mutarotase activities. This results from our observations in arterio-venous studies for the determination of cerebral metabolism in humans in vivo that the cerebral uptake of [¹⁴C]glucose often appeared to differ from that of unlabeled glucose. With rapidly falling arterial radioactivity, unlabeled glucose uptake was more than [¹⁴C]glucose. With rising arterial radioactivity, [¹⁴C]glucose extraction extraction exceeded unlabeled glucose. Studies with [¹⁴C]glucose-6-phosphate suggested that glucose-6-phosphatase in brain removes excess substrate by dephosphorylation. However, when arterial [¹⁴C]glucose increased slowly, [¹⁴C]glucose uptake varied considerably and the data resembled human cerebral metabolism of glucose anomers. An experiment employing [¹³C]glucose and NMR provided further support for our proposed scheme.     

Two cases of X/autosome translocation in females with incontinentia pigmenti

Summary We report two unrelated girls who present some clinical features of severe incontinentia pigmenti (IP), with characteristic skin pigmentation. Both have balanced de novo X/autosome translocations involving band Xp11. The coincidence of the probable de novo expression of an X-linked disorder in these two girls with translocations involving similar breakpoints on the X chromosome suggests that this band may be the site of the IP gene locus.     

Phasing out the bad—How SQSTM1/p62 sequesters ubiquitinated proteins for degradation by autophagy

The degradation of misfolded, ubiquitinated proteins is essential for cellular homeostasis. These proteins are primarily degraded by the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy serves as a backup mechanism when the UPS is overloaded. How autophagy and the UPS are coordinated is not fully understood. During the autophagy of misfolded, ubiquitinated proteins, referred to as aggrephagy, substrate proteins are clustered into larger structures in a SQSTM1/p62-dependent manner before they are sequestered by phagophores, the precursors to autophagosomes. We have recently shown that SQSTM1/p62 and ubiquitinated proteins spontaneously phase separate into micrometer-sized clusters in vitro. This enabled us to characterize the properties of the ubiquitin-positive substrates that are necessary for the SQSTM1/p62-mediated cluster formation. Our results suggest that aggrephagy is triggered by the accumulation of substrates with multiple ubiquitin chains and that the process can be inhibited by active proteasomes.     

Spheroids from adipose‐derived stem cells exhibit an miRNA profile of highly undifferentiated cells

Two‐dimensional (2D) cell cultures have been extensively used to investigate stem cell biology, but new insights show that the 2D model may not properly represent the potential of the tissue of origin. Conversely, three‐dimensional cultures exhibit protein expression patterns and intercellular junctions that are more representative of their in vivo condition. Multiclonal cells that grow in suspension are defined as “spheroids,” and we have previously demonstrated that spheroids from adipose‐derived stem cells (S‐ASCs) displayed enhanced regenerative capability. With the current study, we further characterized S‐ASCs to further understand the molecular mechanisms underlying their stemness properties. Recent studies have shown that microRNAs (miRNAs) are involved in many cellular mechanisms, including stemness maintenance and proliferation, and adipose stem cell differentiation. Most studies have been conducted to identify a specific miRNA profile on adherent adipose stem cells, although little is still known about S‐ASCs. In this study, we investigate for the first time the miRNA expression pattern in S‐ASCs compared to that of ASCs, demonstrating that cell lines cultured in suspension show a typical miRNA expression profile that is closer to the one reported in induced pluripotent stem cells. Moreover, we have analyzed miRNAs that are specifically involved in two distinct moments of each differentiation, namely early and late stages of osteogenic, adipogenic, and chondrogenic lineages during long‐term in vitro culture. The data reported in the current study suggest that S‐ASCs have superior stemness features than the ASCs and they represent the true upstream stem cell fraction present in adipose tissue, relegating their adherent counterparts.     

Infections Caused by <Emphasis Type="Italic">Fusarium</Emphasis> Species in Pediatric Cancer Patients and Review of Published Literature

Fusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment. Since there are few reports of invasive and disseminated fusariosis in children, the aim of this study was to report four cases of nosocomial infection caused by this microorganism in children with cancer hospitalized in a public children’s hospital located in Brazil. Two of these patients were female and two were male. All patients presented febrile neutropenia, while three patients had acute lymphocytic leukemia and one patient had Wilms’ tumor as underlying disease. In two cases, fungi were isolated from blood and identified as Fusarium oxysporum species complex after phenotypic and genotypic studies, while in two other cases fungi were isolated from skin biopsies and identified as Fusarium solani species complex. One patient died 12 days after the onset of cutaneous lesions. All isolates, after susceptibility testing, presented high levels of minimum inhibitory concentration for itraconazole, voriconazole and amphotericin B. Considering the emergence of filamentous fungi as etiologic agents of nosocomial infections, health professionals should be aware of the problems these infections, especially fungal ones, may cause to debilitated patients.