Phosphorylation has been shown to have a significant impact on expanded huntingtin-mediated cellular toxicity. Several phosphorylation sites have been identified on the huntingtin (Htt) protein. To ...find new potential therapeutic targets for Huntington's Disease (HD), we used mass spectrometry to identify novel phosphorylation sites on N-terminal Htt, expressed in HEK293 cells. Using site-directed mutagenesis we introduced alterations of phosphorylation sites in a N586 Htt construct containing 82 polyglutamine repeats. The effects of these alterations on expanded Htt toxicity were evaluated in primary neurons using a nuclear condensation assay and a direct time-lapse imaging of neuronal death. As a result of these studies, we identified several novel phosphorylation sites, validated several known sites, and discovered one phospho-null alteration, S116A, that had a protective effect against expanded polyglutamine-mediated cellular toxicity. The results suggest that S116 is a potential therapeutic target, and indicate that our screening method is useful for identifying candidate phosphorylation sites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Selective enrichments enabled the recovery of moderately thermophilic isolates with copper bioleaching ability from a spent copper sulfide heap. Phylogenetic and physiological characterization ...revealed that the isolates were closely related to Sulfobacillus thermosulfidooxidans, Acidithiobacillus caldus and Acidimicrobium ferrooxidans. While isolates exhibited similar physiological characteristics to their corresponding type strains, in general they displayed similar or greater tolerance of high copper, zinc, nickel and cobalt concentrations. Considerable variation was found between species and between several strains related to S. thermosulfidooxidans. It is concluded that adaptation to metals present in the bioleaching heap from which they were isolated contributed to but did not entirely explain high metals tolerances. Higher metals tolerance did not confer stronger bioleaching performance, suggesting that a physical, mineralogical or chemical process is rate limiting for a specific ore or concentrate.
Abstract
The formation of multi-species biofilms on marine infrastructure costs the global economy US $ billions annually, resulting in biofouling and microbiologically influenced corrosion. It is ...well documented that complex biofilms form on almost any submerged surface, yet there are still no truly effective and environmentally friendly treatment or prevention options available. An incomplete fundamental understanding of natural biofilm development remains a key limitation for biofilm control measures. The purpose of this review is to compile the current literature and knowledge gaps surrounding the development of multi-species biofilms in marine conditions on metals.
In this paper, a brief outline is presented on acidic ferric ion oxidation of mineral sulphides for the extraction of metals in both stirred tank reactors for mineral concentrates and heaps for ...low-grade ores. The identities and capabilities of the relatively few acidophiles that assist the oxidative processes are summarized and their responses to selected extremes in their growth environments described. Individually, the organisms adapt to the presence of high concentrations of heavy metals and other elements in the bioleaching environment, tolerate a wide range of acidities and can recover from prolonged exposure to temperatures significantly above their preferred temperatures for growth. However, the presence of chloride in their acidic environment presents a significant physiological challenge. Species that exhibit a chemotactic response and attachment to sulphide surfaces, where they can create their own micro-environments, would be favoured in both heap bioreactors with low availability of energy substrates and physically aggressive, agitated continuous stirred-tank reactor environments treating concentrates.
Electronic waste (e-waste) contains a wide range of elements, many of which are highly toxic to environmental and human health. On the other hand e-waste represents a significant potential source of ...valuable metals. This study used microbial oxidation of pyrite to generate a biolixiviant. Its efficiency in the dissolution of metals from printed circuit boards (PCBs) was evaluated as well as the effects of metals and PCB concentrations on microbial activity. The addition of elemental metals (Cu, Cr, Ni, Sn, Zn) had an immediate inhibitory effect on pyrite oxidation, though leaching recovered after a period of adaptation. Bioleaching was inhibited initially by the addition of 1 % (w/v) ground PCB, but recovered rapidly, whereas pulp densities of ≥5 % had sustained negative impacts on culture activity and viability. The loss of culture viability meant that only abiotic copper dissolution occurred at ≥5 % PCB. Final copper recoveries declined with increasing PCB pulp density. The relatively high content of elemental iron caused a lag period in copper solubilisation possibly due to displacement reactions. Leptospirillum ferriphilum was primarily responsible for pyrite oxidation, and most affected by both the pure metals (particularly Ni and Cu) and PCB.
•Pyrite was a suitable substrate for biolixiviant generation during leaching of PCBs.•Bioleaching of pyrite was inhibited by PCBs in a similar way to elemental metals.•L. ferriphilum was the principal bioleaching organism and was most easily inhibited.•PCB leaching was enhanced by the presence of microorganisms at <5 % PCB.•≥5 % PCB resulted in total loss of cell viability; any leaching observed was abiotic.
•Some patients request the removal of their Essure implants due to adverse effects.•All patients have had the same common anatomopathological study protocol.•Uterine biopsies were analyzed by ...scanning electron microscopy.•Tin particles were found in all the biopsies analyzed.•The symptoms could be for a great part linked to the wear of the tin weld.
To examine associations between local and systemic symptoms and the wear of the tin weld of Essure implants.
study of a series of cases.
Two French hospitals.
Eighteen patients explanted by hysterectomy and salpingectomy for removal of their Essure implants between September 2019 and July 2020, have had a common anatomopathological process.
anatomopathological examination by optical microscopy and mineralogical analysis of the fallopian tube or uterine horn with scanning electron microscopy coupled with energy dispersive X-ray (SEM-EDX). Evaluation of local and systemic symptoms with a questionnaire. Examination of blood metal assays (nickel, chromium, and tin).
anatomopathological examination highlights foreign body granulomas, fibrosis, adenomyosis, nonspecific inflammation, cysts and myomas in the Fallopian tubes, uterine horns, or both and mentions the presence of foreign bodies in seven cases. SEM-EDX analyses showed, systematically, the presence of tin particles integrated in the wall near the weld, generally in clusters, and with a size ranging from about one micron to several dozen microns. The questionnaire shows that the most frequent local symptoms were pelvic pain, urinary disorders, bleeding, and pains during intercourse. The most common systemic symptoms were: asthenia, visual disturbances, amnesia, giddiness, dorsal pains, headaches, and joint pains. The majority of local and systemic symptoms decreased after explantation, but sometimes incompletely. Before explantation, high levels of nickel, tin and chromium were observed in 11/17, 1/7 and 2/17 patients. After explantation, tin levels were high in 3/11 patients.
our new anatomopathological process systematically demonstrates the presence of tin particles in tissue near the weld. These particles could be responsible for granulomatous inflammations as well as local symptoms. Many of the systemic symptoms are consistent with chronic organotin poisoning but further studies are needed to find out whether tin from the solder can be converted to organotin in the patients' bodies.
•Distinct microbial communities dominate solids and liquids from heap.•Cell numbers decline rapidly when Fe3+ and (SO4)2− exceed 25 and 75gL−1 respectively.•Leptospirillum – the primary iron(II) ...oxidiser in solution and residue samples from the heap.
Three largely-independent studies were undertaken on the same heap leach system during the period of transition from processing oxidised ores to sulfide ores: monitoring of heap solutions for microorganisms, analysis of samples from a spent heap, and column tests. Microbial cell numbers and diversity were monitored in process water samples from the transition heap over a four-year period. Cell numbers remained low throughout, 1–30×104cells mL−1, possibly reflecting growth inhibition by the high element concentrations in process water. High iron, magnesium and aluminium concentrations in spent heap pregnant leach solution (PLS) are attributed to siderite and clinochlore dissolution and would be expected to impact on microbial growth. Planktonic cell numbers in a column leachate declined rapidly by two orders of magnitude when concentrations of ferric ion and sulfate exceeded 30 and 75gL−1, respectively. Nevertheless, a variety of bacterial strains closely related to Acidithiobacillus (At.) ferrooxidans, At. caldus, Leptospirillum (L.) ferriphilum, Acidimicrobium (Am.) ferrooxidans, Acidiphilium (Ap.) cryptum, an Alicyclobacillus-related strain and Sulfobacillus (S.) thermosulfidooxidans, and the archaeon Ferroplasma (F.) acidiphilum were isolated, mainly from the more acidic intermediate leach solutions (ILS). Overall, the results obtained from the use of culture-dependent and culture-independent methods of community analysis were complementary and consistent. The majority of identified genera and species were present in both the process water samples from the operating heap and the solutions and ore samples from the spent heap. In the spent heap, distinct populations dominated different sample types. Leptospirillum- and Acidithiobacillus-like strains dominated PLS samples and Leptospirillum also dominated seven of eight spent ore samples and all of the heap sediment samples, making it the primary iron(II) oxidising species.
This study investigates the effect of temperature on the population dynamics of microorganisms in bioleaching columns charged with a low-grade chalcopyrite ore. A mixed culture containing ten known ...bioleaching microorganisms was used to inoculate four bioleaching columns operated at 60, 50, 40 or 30
°C. Subsequently, Terminal Restriction Fragment Length Polymorphism (T-RFLP) was used to examine the diversity of bacterial and archaeal populations in the leachates and ores of the four columns. Similar results from samples collected from different locations in the columns give confidence in the reproducibility of the methods used.
Of the 10 microbial inoculants, only
Acidithiobacillus caldus,
Leptospirillum ferriphilum and
Ferroplasma acidiphilum were identified from the leachate and the column solids. However, adventitious growth of a number of other species resulted in different microbial populations in the leachate and on the ore. The results bring into question the effectiveness of heap inoculation, a strategy proposed to overcome the paucity of thermophilic organisms occurring naturally, even in very long-term sulfide-leaching operations. The anticipated impact of temperature on the leachate population was ameliorated by the solution management regime used for the columns, which was chosen to imitate heap leach practice.
►Different microbial populations observed in leachate and column solids.
►Only three of ten inoculant strains were observed in either leachate or column solids.
►Adventitious growth of a number of non inoculant species was observed.
Transcriptional dysregulation by mutant huntingtin (Htt) protein has been implicated in the pathogenesis of Huntington's disease (HD). We find that cultured cells expressing mutant Htt and striatal ...cells from HD transgenic mice have elevated nuclear factor-κB (NF-κB) activity. Furthermore, NF-κB is concentrated in the nucleus of neurons in the brains of HD transgenic mice. In inducible PC12 cells and in HD transgenic mice, mutant Htt activates the IκB kinase complex (IKK), a key regulator of NF-κB. Activation of IKK is likely mediated by direct interaction with mutant Htt, because the expanded polyglutamine stretch and adjacent proline-rich motifs in mutant Htt interact with IKKγ, a regulatory subunit of IKK. Activation of IKK may also influence the toxicity of mutant Htt, because expression of IKKγ promotes aggregation and nuclear localization of mutant Htt exon-1. Moreover, in acute striatal slice cultures, inhibition of IKK activity with an N-terminally truncated form of IKKγ blocks mutant Htt-induced toxicity in medium-sized spiny neurons (MSNs). In addition, blocking degradation of NF-κB inhibitors with a dominant-negative ubiquitin ligase β-transducin repeat-containing protein also reduces the toxicity of mutant Htt in MSNs. Therefore, aberrant NF-κB activation may contribute to the neurodegeneration induced by mutant Htt.
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