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ObjectivesAlexander disease (AD) is a rare disorder of the CNS. Diagnosis is based on clinical symptoms, typical MRI findings, and mutations in the glial fibrillary acid protein (GFAP) gene. In this case study, we describe a new mutation (p.L58P) in GFAP that caused a phenotype of adult-onset AD (AOAD).MethodsIn our outpatient clinic, a patient presented with cerebellar and bulbar symptoms after brain concussion. We used MRI and performed next-generation exome sequencing (NGS) to find mutations in GFAP to diagnose AD. The mutation was then transfected into HeLa cell lines to prove its pathogenicity.ResultsThe brain MRI finding showed typical AD alterations. The NGS found a heterozygous variant of unknown significance in GFAP (c.173T>C; p.L58P). After transfecting HeLa cell lines with this mutation, we showed that GFAP-L58P formed pathogenic clusters of cytoplasmic aggregates.DiscussionWe have found a new mutation that causes AOAD. We recommend that AOAD is included in the diagnostic workup in adult patients with gait ataxia and cerebellar and bulbar symptoms in association with a traumatic head injury.

BackgroundMutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP), a neurodegenerative disease characterized by dysfunction and death of dopamine (DA) neurons in the substantia nigra pars compacta. Since a neuroprotective therapy for ARJP does not exist, research efforts aimed at discovering potential targets for neuroprotection are critically needed.A previous study demonstrated that loss of parkin function or expression of parkin mutants associated with ARJP causesan accumulation of glutamate kainate receptors (KARs) in human brain tissues and an increase of KAR-mediated currents in neuronsin vitro. MethodsBased on the hypothesisthat such KAR hyper-activation may contribute to the death of nigralDA neurons, we investigated the effect of KAR antagonism on the DA neuron dysfunction and death that occur in the parkinQ311X mouse, a model of human parkin-induced toxicity. ResultsWe found that early accumulation of KARs occurs in the DA neurons of the parkinQ311X mouse model and that chronic administration of the KAR antagonist UBP310 prevents DA neuron loss. This neuroprotective effect was associated with rescue of the abnormal firing rate of nigral DA neurons and downregulation of GluK2, the key KAR subunit. ConclusionsThis study provides novel evidence ofa causal role of glutamate KARs in the DA neuron dysfunction and loss occurring in a mouse model of human parkin-induced toxicity. Our results support KAR as a potential target in the development of a neuroprotective therapy for ARJP.

The characteristics of problematic biofilms (i.e., fouling and clogging layers) were studied with regards to the removal and fate of trace metals (contents well under 100 μg/L) during the long-term operation of a pilot-scale membrane bioreactor for the treatment of real wastewaters from a large industrial area. Results showed that clogging layer was more effective than suspended activated sludge in the biosorption of As > Zn > Ni > Cd > Sb > Fe > Se due to the synergic effects of extracellular polymeric compounds and metal-resistant bacteria. In fact the selective microbial speciation of the phylum of Bacteroidetes, which is highly resistant to heavy metals, was observed in the clogging sludge in spite of the very low concentration of dissolved metals in the bioreactor. Compared to the suspended activated sludge, the clogging layer enhanced the biosorption of very toxic substances such as As, Cd and Ni. In fact, the metal contents were respectively: 7.9–7.4 vs. 690–840 μgAs/kgTS; 1.5–2.2 vs. 149–219 μgCd/kgTS; 58.8–71.7 vs. 227–298 μgNi/kgTS. Then, the potential desorption of metals during the membrane acid cleanings was estimated as relevant as 10–15% of the metals associated to the clogging sludge. The combined effects of pH and the selected microbial community, and the minor effect of the redox potential, let us conclude on the major importance of bio-sorption/desorption mechanisms with respect to bio-precipitation/dissolution.

Real-time control of biological nitrogen removal is a major issue to advance the performances and the efficiencies of the wastewater treatment, especially when coupled to the processes via-nitrite pathway. Over the last three decades many researchers focused on indirect parameters (namely pH, DO, ORP, conductivity) to control the conventional nitrification and denitrification, up to several full scale applications. On the other hand, the real-time control to achieve and operate the processes via-nitrite is under investigation over the last years. This short review analyzes and discusses the main real-time control strategies and their most common and successful applications in sequencing batch reactors. In conclusion, the knowledge concerning the conventional processes will be outlined together with the next developments for short-cut nitrogen removal.

Antithrombin III (AT-III) deficiency may be due to quantitative or qualitative AT-III reduction. The diagnosis of qualitative disorder is suspected when a discrepancy is found between immunological and functional levels of AT-III. Heterogeneity has been hypothesized in both quantitative and qualitative deficiency of AT-III. A technique based on crossed immunoelectrofocusing (CIEF) was applied to investigate molecular variants of AT-III. 3 families with low functional and immunological levels of AT-III and 1 family with only a low functional AT-III level were investigated. An abnormal AT-III pattern was found with CIEF in the family with suspected qualitative disorder and in 1 of the families with quantitative disorder. The 2 abnormal patterns were different. Thus the use of CIEF AT-III patterns could help to define congenital AT-III deficiencies and could serve as a basis for classification of different forms of AT-III deficiency.