A Photoactivated Protein Degrader for Optical Control of Synaptic Function.

Hundreds of proteins determine the function of synapses, and synapses define the neuronal circuits that subserve myriad brain, cognitive, and behavioral functions. It is thus necessary to precisely manipulate specific proteins at specific sub-cellular locations and times to elucidate the roles of particular proteins and synapses in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy to optically degrade specific proteins with high spatial and temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze ubiquitylation and degradation of target proteins through endogenous proteasomes. Here we describe the design and chemical properties of a PHOTAC that targets Ca 2+ /calmodulin-dependent protein kinase II alpha (CaMKIIα), which is abundant and crucial for baseline synaptic function of excitatory neurons. We validate the PHOTAC strategy, showing that the CaMKIIα-PHOTAC is effective in mouse brain tissue. Light activation of CaMKIIα-PHOTAC removed CaMKIIα from regions of the mouse hippocampus only within 25 µm of the illuminated brain surface. The optically-controlled degradation decreases synaptic function within minutes of light activation, measured by the light-initiated attenuation of evoked field excitatory postsynaptic potential (fEPSP) responses to physiological stimulation. The PHOTACs methodology should be broadly applicable to other key proteins implicated in synaptic function, especially for evaluating their precise roles in the maintenance of long-term potentiation and memory within subcellular dendritic domains.

Gliomatosis cerebri and Rasmussen's encephalitis: Two different entities causing refractory epilepsy. Comparison through two clinical cases.

BACKGROUND AND IMPORTANCE: Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. CLINICAL PRESENTATION: We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. CONCLUSION: The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

[X-linked adrenoleukodystrophy with an atypical radiological pattern]. / Adrenoleucodistrofia ligada al X con patron radiologico atipico.

INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It is due to a mutation in the ABCD1 gene. The loss of functioning of ABCD1 triggers ineffective beta oxidation of very long-chain fatty acids, which gives rise to an accumulation of these fatty acids. The typical alteration revealed in neuroimaging scans in the cerebral form is symmetrical periventricular demyelination with posterior location. CASE REPORT: We report the case of a 10-year-old boy with right spastic hemiparesis and subacute cognitive impairment. Magnetic resonance imaging of the brain showed symmetrical involvement of the white matter in the left frontoparietotemporal region, and calcifications were observed in the computerised axial tomography scan. X-ALD was confirmed by means of the elevated levels of very long-chain fatty acids, and a pathogenic variant was found in the ABCD1 gene. CONCLUSIONS: Symmetrical demyelination with calcifications has rarely been reported in X-ALD, and these findings could delay diagnosis. This exceptional presentation should always be taken into consideration in children with subacute onset of motor symptoms and cognitive or behavioural regression.

TITLE: Adrenoleucodistrofia ligada al X con patron radiologico atipico.Introduccion. La adrenoleucodistrofia ligada al X (ALD-X) es la enfermedad peroxisomica mas frecuente. Se debe a una mutacion en el gen ABCD1. La perdida de la funcion de ABCD1 provoca una betaoxidacion inefectiva de los acidos grasos de cadena muy larga, lo que provoca la acumulacion de estos acidos grasos. La alteracion tipica en la neuroimagen en la forma cerebral es la desmielinizacion periventricular simetrica y de localizacion posterior. Caso clinico. Niño de 10 anos, con hemiparesia espastica derecha y deterioro cognitivo subagudo. La resonancia magnetica cerebral mostro afectacion asimetrica de la sustancia blanca en la region frontoparietotemporal izquierda, y en la tomografia axial computarizada se visualizaban calcificaciones. Se confirmo ALD-X mediante la elevacion de los niveles de acidos grasos de cadena muy larga, y se encontro una variante patogenica en el gen ABCD1. Conclusiones. La desmielinizacion asimetrica con calcificaciones raramente se ha descrito en la ALD-X, y estos hallazgos podrian retrasar el diagnostico. Esta presentacion excepcional se deberia considerar siempre en niños con inicio subagudo de sintomas motores y regresion cognitiva o del comportamiento.

A propósito de un caso de miopatía inflamatoria. Cuantificación de la inflamación muscular mediante PET/TC con 18F-FDG en la evaluación inicial y la respuesta terapéutica / Quantification of muscular inflammation by 18F-FDG PET/CT for initial evaluation and treatment response on inflammatory myopathy: a case report

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Lithium recovery with LiTi2O4 ion-sieves.

A feasibility study for the recovery of lithium from salt water with the protonated lithium titanium oxide ion-sieves was carried out in this work. Lithium ions (Li+) in LiTi2O4 having a similar ion density with H+ allow repeated exchanges and regeneration with high selectivity. By Li7 magic angle spinning solid-state magnetic resonance, it is apparent that chemical structure of lithium in the ion-sieves is not perturbed during the repeated Li+/H+ exchange processes. As the dissolution of titanium is negligible (<0.1%), the secondary contamination during the capture process can be minimized. The ion-sieves exhibit lithium capture capacities of up to 9.5mg/g during the repeated Li+/H+ exchanges with H0.23Li0.77Ti2O4/LiTi2O4 for 24h, and the captured Li+ may be recovered in the form of Li2CO3. Accordingly, the lithium capture method developed in this work could be integrated with current desalination processes for valuable lithium recovery.

KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors.

Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G>C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.

A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers for mitochondrial respiratory chain enzyme activities.

Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.

Capacitive deionization of seawater effected by nano Ag and Ag@C on graphene.

Drinking water shortage has become worse in recent decades. A new capacitive deionization (CDI) method for increasing water supplies through the effective desalination of seawater has been developed. Silver as nano Ag and Ag@C which was prepared by carbonization of the Ag(+)-ß-cyclodextrin complex at 573 K for 30 min can add the antimicrobial function into the CDI process. The Ag@C and Ag nanoparticles dispersed on reduced graphene oxide (Ag@C/rGO and nano Ag/rGO) were used as the CDI electrodes. The nano Ag/rGO and Ag@C/rGO electrodes can reduce the charging resistant, and enhance the electrosorption capability. Better CDI efficiencies with the nano Ag/rGO and Ag@C/rGO electrodes can therefore be obtained. When reversed the voltage, the electrodes can be recovered up to 90% within 5 min. This work presents the feasibility for the nano Ag and Ag@C on rGO electrodes applied in CDI process to produce drinking water from seawater or saline water.

Photocatalytic splitting of seawater effected by (Ni-ZnO)@C nanoreactors.

Novel photocatalysts i.e., metallic nickel and zinc oxide nanoparticles embedded in the carbon-shell ((Ni-ZnO)@C) have been used for photocatalytic splitting of seawater to generate H2. The (Ni-ZnO)@C core-shell nanoparticles having the Zn/Ni ratios of 0-3 were prepared by carbonization of Ni(2+)- and Zn(2+)-ß-cyclodextrin at 673 K for 2 h. To increase the collision frequency of water and photoactive sites within the carbon-shell, Ni and ZnO are partially etched from the (Ni-ZnO)@C core-shell to form yolk-shell nanoparticles with a H2SO4 solution (2N). By X-ray diffraction spectroscopy, mainly Ni and ZnO crystallites are observed in the core- and yolk-shell nanoparticles. The sizes of the Ni and ZnO in the (Ni-ZnO)@C nanoreactors are between 7 and 23 nm in diameters determined by TEM and small angel scattering spectroscopy. Under a 5-h UV-Vis light irradiation, 5.01 µmol/hgcat of H2 are yielded from photocatalytic splitting of seawater effected by (Ni-ZnO)@C nanoreactors.

Importancia de la biopsia muscular en el diagnóstico de dermatomiositis juvenil / Importance of muscle biopsy in the diagnosis of juvenile dermatomyositis

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Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency.

Pyruvate carboxylase deficiency is a rare metabolic disorder, with three different phenotypes. We aim to report the case of a newborn presenting the severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia and rigidity being the main features) and the results of the study of classic neurotransmitters involved in movement control. Hyperdopaminergic transmission (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic transmission (in the substantia nigra) were found. Both gamma-aminobutyric acid and dopamine markers were found coexisting in individual neurons of the substantia nigra. This is the first time this phenomenon has been reported in the literature. We discuss the possible role of GABAergic deficiency, its interaction with other neurotransmitters and its implication in neurotransmitter homeostasis. A better comprehension of that field would increase understanding of the pathophysiology of neurological symptoms and neurotransmitter plasticity.

Preliminary identification of watershed management strategies for the Houjing river in Taiwan.

The Houjing River watershed is one of the three major river watersheds in the Kaohsiung City, Taiwan. Based on the recent water quality analysis, the Houjing River is heavily polluted. Both point and non-point source (NPS) pollutants are the major causes of the poor water quality in the Houjing River. Investigation results demonstrate that the main point pollution sources included municipal, agricultural, and industrial wastewaters. In this study, land use identification in the Houjing River watershed was performed by integrating the skills of geographic information system (GIS) and global positioning system (GPS). Results show that the major land-use patterns in the upper catchment of the Houjing River watershed were farmlands, and land-use patterns in the mid to lower catchment were residential and industrial areas. An integrated watershed management model (IWMM) and Enhanced Stream Water Quality Model (QUAL2K) were applied for the hydrology and water quality modeling, watershed management, and carrying capacity calculation. Modeling results show that the calculated NH3-N carrying capacity of the Houjing River was only 31 kg/day. Thus, more than 10,518 kg/day of NH3-N needs to be reduced to meet the proposed water quality standard (0.3 mg/L). To improve the river water quality, the following remedial strategies have been developed to minimize the impacts of NPS and point source pollution on the river water quality: (1) application of BMPs [e.g. source (fertilizer) reduction, construction of grassy buffer zone, and land use management] for NPS pollution control; (2) application of river management scenarios (e.g. construction of the intercepting and sewer systems) for point source pollution control; (3) institutional control (enforcement of the industrial wastewater discharge standards), and (4) application of on-site wastewater treatment systems for the polishment of treated wastewater for water reuse.

Protein adsorption, fibroblast activity and antibacterial properties of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) grafted with chitosan and chitooligosaccharide after immobilized with hyaluronic acid.

Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) membrane was treated with ozone and grafted with acrylic acid. The resulting membranes were further grafted with chitosan (CS) or chitooligosaccharide (COS) via esterification. Afterward hyaluronic acid (HA) was immobilized onto CS- or COS-grafting membranes. The antibacterial activity of CS and COS against Staphylococus aureus, Escherichia coli, and Pseudomonas aeruginosa was preserved after HA immobilization. Among them, CS-grafted PHBV membrane showed higher antibacterial activity than COS-grafted PHBV membrane. In addition, after CS- or COS-grafting, the L929 fibroblasts attachment and protein adsorption were improved, while the cell number was decrease. After immobilizing HA, the cell proliferation was promoted, the protein adsorption was decreased, and the cell attachment was slightly lower than CS- or COS-grafting PHBV.

Convergent pathways for cardiac- and esophageal-somatic motor reflexes in rats.

Chest pain of esophageal and cardiac origin is often difficult to distinguish due to similar sensations and localization. We have shown that spasm-like contractions of the spinotrapezius muscles evoked by noxious cardiac stimulation could potentially sensitize muscle afferent fibers and produce angina-like referred pain. In this study, we proposed that a similar type of spinotrapezius contraction evoked by esophageal stimulation could produce nociceptive responses with similar quality and localization as evoked by cardiac stimulation. An objective of this study was to show convergence of pathways to the spinotrapezius muscles by measuring electromyographic (EMG) activity between the cardiac- and esophageal-motor reflexes. We also investigated afferent pathways of esophageal-motor reflexes by disrupting or activating the left sympathetic chain and vagus nerves; these pathways form the afferent limbs of the cardiac-motor reflexes. Results showed that more than 95% of animals responding to noxious cardiac stimulation also responded to esophageal distension. Transection of the left sympathetic chain to reduce upper thoracic visceral afferent innervation significantly decreased cardiac-evoked EMG activity or total motor unit potentials (t-MUP). In contrast, however, the transection did not significantly decrease t-MUP evoked by esophageal distension. Bilateral vagotomy and vagal afferent stimulation increased and decreased the cardiac-evoked t-MUP, respectively. However, the same vagal manipulations did not influence t-MUP evoked by esophageal distension. This study demonstrated that the spinotrapezius muscle could be activated by noxious stimulation of two different visceral organs. The spinotrapezius muscle contractions evoked by esophageal distension are produced in part by activation of esophageal afferent fibers found in upper thoracic sympathetic nerves, but not by activation of the vagus nerves.

Speciation of copper in the incineration fly ash of a municipal solid waste.

The speciation of copper and zinc in the incineration fly ash of a municipal solid waste in Taiwan was investigated in the present work. By the least-squares fitted X-ray absorption near edge structural (XANES) spectroscopy, we found that CuCO3, CuOH2, and CuO (fractions of 0.09, 0.39 and 0.51, respectively) were the main copper species in the fly ash. Quantitative analysis of the extended X-ray absorption fine structural (EXAFS) spectra indicated that the bond distance of Cu-O in the fly ash was 1.96 A with a coordination number (CN) of 3.9 in the first shell of copper. In the second shell, the bond distance and CN of Cu-(O)-Cu were 2.91 A and 2.7, respectively. In addition, speciation of Zn was also examined in the same X-ray absorption energy (8780-9970 eV). The bond distance of Zn-O and Zn-O-Zn were 1.97 and 2.94 A, respectively. However, the Zn-O-Cu structure was not found because of the physically unreasonable sigma(2) (Debye-Waller factor) values in the EXAFS data fitting process.

Afferent pathways for cardiac-somatic motor reflexes in rats.

The present study used a rat model in which algogenic chemicals were infused into the pericardial sac to evoke spasmlike contractions in paraspinal muscles. The following techniques were used to study the roles of sympathetic (SCA) and vagal cardiac afferents (VCA) in electromyographic (EMG) responses to pericardial algogenic chemicals: chemical stimulation, electrical stimulation, and nerve transection. Activation with bradykinin (n = 46) produced a significantly higher peak response than infusion of an algogenic mixture (n = 53) containing chemicals that also activate VCA. Electrical stimulation of SCA produced bilateral EMG activities (7 of 7). Electrical stimulation of VCA did not evoke EMG activity but inhibited the chemically evoked EMG response (12 of 12). The chemically evoked response was decreased after transection of the left sympathetic chain (n = 22) and was increased after bilateral vagotomy (n = 19). These results suggest an excitatory and inhibitory role for SCA and VCA, respectively. Therefore, in addition to spinothalamic convergence of somatic and visceral afferents, activation of SCA to generate spasmlike muscle contractions could account in part for anginal pain, and VCA activation could attenuate this effect.