Huber T

References (3)

Title : Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors - Cheng_2016_Nat.Commun_7_13396
Author(s) : Cheng H , Ang HY , C AEF , Li P , Fang HT , Liu TM , Kong SL , Chin ML , Ling WY , Lim EK , Li H , Huber T , Loh KM , Loh YH , Lim B
Ref : Nat Commun , 7 :13396 , 2016
Abstract : Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase+ megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo. Molecularly, iHPs transcriptionally resemble native Kit+ hematopoietic progenitors. Mechanistically, reprogramming factor Lmo2 implements a hematopoietic programme in fibroblasts by rapidly binding to and upregulating the Hhex and Gfi1 genes within days. Moreover the reprogramming transcription factors also require extracellular BMP and MEK signalling to cooperatively effectuate reprogramming. Thus, the transcription factors that orchestrate embryonic hematopoiesis can artificially reconstitute this programme in developmentally distant fibroblasts, converting them into engraftable blood progenitors.
ESTHER : Cheng_2016_Nat.Commun_7_13396
PubMedSearch : Cheng_2016_Nat.Commun_7_13396
PubMedID: 27869129

Title : Directed evolution of new and improved enzyme functions using an evolutionary intermediate and multidirectional search - Porter_2015_ACS.Chem.Biol_10_611
Author(s) : Porter JL , Boon PL , Murray TP , Huber T , Collyer CA , Ollis DL
Ref : ACS Chemical Biology , 10 :611 , 2015
Abstract : The ease with which enzymes can be adapted from their native roles and engineered to function specifically for industrial or commercial applications is crucial to enabling enzyme technology to advance beyond its current state. Directed evolution is a powerful tool for engineering enzymes with improved physical and catalytic properties and can be used to evolve enzymes where lack of structural information may thwart the use of rational design. In this study, we take the versatile and diverse alpha/beta hydrolase fold framework, in the form of dienelactone hydrolase, and evolve it over three unique sequential evolutions with a total of 14 rounds of screening to generate a series of enzyme variants. The native enzyme has a low level of promiscuous activity toward p-nitrophenyl acetate but almost undetectable activity toward larger p-nitrophenyl esters. Using p-nitrophenyl acetate as an evolutionary intermediate, we have generated variants with altered specificity and catalytic activity up to 3 orders of magnitude higher than the native enzyme toward the larger nonphysiological p-nitrophenyl ester substrates. Several variants also possess increased stability resulting from the multidimensional approach to screening. Crystal structure analysis and substrate docking show how the enzyme active site changes over the course of the evolutions as either a direct or an indirect result of mutations.
ESTHER : Porter_2015_ACS.Chem.Biol_10_611
PubMedSearch : Porter_2015_ACS.Chem.Biol_10_611
PubMedID: 25419863
Gene_locus related to this paper: psepu-clcd1

Title : Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study - Hasler_2004_Psychopharmacology.(Berl)_172_145
Author(s) : Hasler F , Grimberg U , Benz MA , Huber T , Vollenweider FX
Ref : Psychopharmacology (Berl) , 172 :145 , 2004
Abstract : RATIONALE: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A) agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. OBJECTIVE: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.
METHODS: Eight subjects received placebo (PL), and 45 ("very low dose, VLD"), 115 ("low dose, LD"), 215 ("medium dose, MD"), and 315 ("high dose, HD") microg/kg body weight PY. The "Altered States of Consciousness Rating Scale" (5D-ASC), the "Frankfurt Attention Inventory" (FAIR), and the "Adjective Mood Rating Scale" (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined.
RESULTS: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation", "emotional excitability", and "dreaminess" were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60 min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. CONCLUSION: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health.
ESTHER : Hasler_2004_Psychopharmacology.(Berl)_172_145
PubMedSearch : Hasler_2004_Psychopharmacology.(Berl)_172_145
PubMedID: 14615876