Objective
Autosomal‐recessive mutations in TBCK cause intellectual disability of variable severity. Although the physiological function of TBCK remains unclear, loss‐of‐function mutations are ...associated with inhibition of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Given that mTORC1 signaling is known to regulate autophagy, we hypothesized that TBCK‐encephalopathy patients with a neurodegenerative course have defects in autophagic‐lysosomal dysfunction.
Methods
Children (n = 8) of Puerto Rican (Boricua) descent affected with homozygous TBCK p.R126X mutations underwent extensive neurological phenotyping and neurophysiological studies. We quantified autophagosome content in TBCK−/− patient‐derived fibroblasts by immunostaining and assayed autophagic markers by western assay. Free sialylated oligosaccharide profiles were assayed in patient's urine and fibroblasts.
Results
The neurological phenotype of children with TBCK p.R126X mutations, which we call TBCK‐encephaloneuronopathy (TBCKE), include congenital hypotonia, progressive motor neuronopathy, leukoencephalopathy, and epilepsy. Systemic features include coarse facies, dyslipidemia, and osteoporosis. TBCK−/− fibroblasts in vitro exhibit increased numbers of LC3+ autophagosomes and increased autophagic flux by immunoblots. Free oligosaccharide profiles in fibroblasts and urine of TBCKE patients differ from control fibroblasts and are ameliorated by treatment with the mTORC1 activator leucine.
Interpretation
TBCKE is a clinically distinguishable syndrome with progressive central and peripheral nervous system dysfunction, consistently observed in patients with the p.R126X mutation. We provide evidence that inappropriate autophagy in the absence of cellular stressors may play a role in this disorder, and that mTORC1 activation may ameliorate the autophagic‐lysosomal system dysfunction. Free oligosaccharide profiles could serve as a novel biomarker for this disorder as well as a tool to evaluate potential therapeutic interventions. Ann Neurol 2018;83:153–165
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•TiO2-rGO composite showed higher photocatalytic activity than TiO2-P25.•Reactive oxygen species produced under UV and visible irradiation were investigated.•Under UV–Vis irradiation ...TiO2-rGO produced hydroxyl radicals, hydrogen peroxide and singlet oxygen.•Under visible light singlet oxygen was detected from TiO2-rGO and TiO2-P25 catalysts.•A mechanism for the photocatalytic synthesis of singlet oxygen from H2O2 is discussed.
Photocatalysis has been shown to be effective for the disinfection of water contaminated with pathogenic microorganisms. In order to increase the solar efficiency of photocatalysis on titanium dioxide (TiO2) it is necessary to modify the TiO2 so that visible photons may be utilised in addition to the UV. TiO2 – reduced graphene oxide composites (TiO2-rGO) were prepared by the photocatalytic reduction of exfoliated graphene oxide (GO) using P25 (Evonik-Aeroxide) as the photocatalyst. The composites were tested for the inactivation of E. coli as the model microorganism under UV–Vis and visible only irradiation at relatively low light intensities to help elucidate the mechanism of disinfection. The results showed a 6log inactivation of E. coli after 120min of treatment with unmodified TiO2-P25 and the same level of inactivation was achieved after 90min with TiO2-rGO under UV–Vis irradiation. Under visible irradiation only, the TiO2-rGO gave a 5.3log inactivation of E. coli following 180min of treatment whereas the unmodified P25 gave only a 1.7log-reduction in the same time, similar to that observed in the light control. Using probes, the main reactive oxygen species involved in the disinfection process were determined to be hydrogen peroxide, hydroxyl radicals, and singlet oxygen under UV–Vis irradiation; and only singlet oxygen under visible only irradiation. Scavenger studies were also performed to further elucidate the mechanism of disinfection.
The anomalous Hall effect soars when Dirac quasiparticles meet frustrated magnetism.
The anomalous Hall effect (AHE) is one of the most fundamental phenomena in physics. In the highly conductive ...regime, ferromagnetic metals have been the focus of past research. Here, we report a giant extrinsic AHE in KV
3
Sb
5
, an exfoliable, highly conductive semimetal with Dirac quasiparticles and a vanadium Kagome net. Even without report of long range magnetic order, the anomalous Hall conductivity reaches 15,507 Ω
−1
cm
−1
with an anomalous Hall ratio of ≈ 1.8%; an order of magnitude larger than Fe. Defying theoretical expectations, KV
3
Sb
5
shows enhanced skew scattering that scales quadratically, not linearly, with the longitudinal conductivity, possibly arising from the combination of highly conductive Dirac quasiparticles with a frustrated magnetic sublattice. This allows the possibility of reaching an anomalous Hall angle of 90° in metals. This observation raises fundamental questions about AHEs and opens new frontiers for AHE and spin Hall effect exploration, particularly in metallic frustrated magnets.
Orion BN/KL is an example of a poorly understood phenomena in star-forming regions involving the close encounters of young stellar objects. The explosive structure, the great variety of molecules ...observed, the energy involved in the event, and the mass of the region suggest a contribution to the chemical diversity of the local interstellar medium. Nevertheless, the frequency and duration of other, similar events have not been determined. In this paper, we explore a recent analytic model that takes into account the interaction of a clump with its molecular environment. We show that the widespread kinematic ages of the Orion fingers-500 to 4000 yr-are a consequence of the interaction of the explosion debris with the surrounding medium. This model explains satisfactorily the age discrepancy of the Orion fingers, and infers the initial conditions together with the lifetime of the explosion. Moreover, our model can explain why some CO streamers do not have an associated H2 finger.
The Dichromatic Polynomial of a Digraph González-Moreno, D.; Hernández-Ortiz, R.; Llano, B. ...
Graphs and combinatorics,
06/2022, Letnik:
38, Številka:
3
Journal Article
Recenzirano
Let
λ
be a positive integer. An acyclic
λ
-coloring of a digraph
D
is a partition of the vertices of
D
into
λ
color clases such that the color classes induce acyclic subdigraphs in
D
. The minimum ...integer
λ
for which there exists an acyclic
λ
-coloring of
D
is the
dichromatic number
dc
(
D
) of
D
. Let
P
(
D
;
λ
)
be the dichromatic polynomial of
D
, which is the number of acyclic
λ
-colorings of
D
. In this paper, a recursive formula for
P
(
D
;
λ
)
is given. The coefficients of the polynomial
P
(
D
;
λ
)
are studied. The dichromatic polynomial of a digraph
D
is related to the structure of its underlying graph
UG
(
D
). Also, we study dichromatic equivalently and dichromatically unique digraphs.
► Phycobiliproteins and C-phycocyanin of Arthrospira (Spirulina) are nephroprotector. ► Phycobiliproteins and C-phycocyanin of Arthrospira are nutraceutics. ► Phycobiliproteins obtaining is cheaper ...and easier than C-phycocyanin production.
Our objective was to determine if the phycobiliproteins of Arthrospira (Spirulina) maxima protect renal cells against mercury-caused oxidative stress and cellular damage in the kidney. We used 40 male mice that were assigned into eight groups: (1) a control group that received 100mM phosphate buffer (PB) ig and 0.9% saline ip, (2) PB+HgCl2 (5mg/kg ip), (3) PB plus phycobiliproteins (100mg/kg ig), (4) PB plus C-phycocyanin (100mg/kg ig), and four groups receiving HgCl2+phycobiliproteins or C-phycocyanin (50, and 100mg/kg ig). The left kidneys were used to determine lipid peroxidation, quantification of reactive oxygen species, and reduced glutathione and oxidised content. The right kidneys were processed for histology. The HgCl2 caused oxidative stress and cellular damage. All doses of phycobiliproteins or C-phycocyanin prevented enhancement of oxidative markers and they protected against HgCl2-caused cellular damage.
LEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain.
This is an interim analysis evaluating the ...baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria.
161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed).
Unlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.
Intraventricular and extraventricular choroid plexuses are neuroepithelial folds which arise from the roof of the diencephalon. We describe the circumventricular structure of the diencephalon roof ...(paraphysis cerebri) during the various development stages of Ambystoma mexicanum. The parasagittal sections of the larvae epithalamus exhibit the presence, in addition to the epiphysis, of two dorsal primordia in nearby areas, which appear to be extraventricular saccular evaginations of different origin that give rise to two structures we define as the anterior extraventricular choroid plexus (AEP) and posterior extraventricular choroid plexus (PEP). During larvae development, the primordia arise perpendicular to each other, grow and show luminal folds and invaginations. Later, the two extraventricular evaginations, which are separate units, become interrelated. As the PEP grows, it covers the AEP dorsally, but it is difficult to define the borders of these organs. AEP is formed by alveolar-acinar epithelial aggregates with evidence of secretion-like content. PEP structure is like a choroid plexus, but its position is extraventricular and dorsal to the AEP. The PEP is always between the AEP and the meninges and can be small or large in size. This means that in A. mexicanum, the paraphysis cerebri is made up of two adjacent organs, which arise almost simultaneously from two different primordia (the AEP and the PEP) and as the posterior one grows, it overlaps the anterior one and masks itself. In conclusion, we suggest that AEP and PEP are homologous to paraphysis cerebri and the dorsal sac, respectively.
Lactate dehydrogenase (LDH) is key for anaerobic glycolysis. LDH is induced by the hypoxia inducible factor −1 (HIF-1). HIF-1 induces genes involved in glucose metabolism and regulates cellular ...oxygen homeostasis. HIF-1 is formed by a regulatory α-subunit (HIF-1α) and a constitutive β-subunit (HIF-1β). The white spot syndrome virus (WSSV) induces anaerobic glycolysis in shrimp hemocytes, associated with lactate accumulation. Although infection and lactate production are associated, the LDH role in WSSV-infected shrimp has not been examined. In this work, the effects of HIF-1 silencing on the expression of two LDH subunits (LDHvan-1 and LDHvan-2) in shrimp infected with the WSSV were studied. HIF-1α transcripts increased in gills, hepatopancreas, and muscle after WSSV infection, while HIF-1β remained constitutively expressed. The expression for both LDH subunits increased in each tissue evaluated during the WSSV infection, translating into increased enzyme activity. Glucose concentration increased in each tissue evaluated, while lactate increased in gills and hepatopancreas, but not in muscle. Silencing of HIF-1α blocked the increase of LDH expression and enzyme activity, along with glucose (all tissues) and lactate (gills and hepatopancreas) concentrations produced by WSSV infection. These results demonstrate that HIF-1 up regulates the expression of LDH subunits during WSSV infection, and that this induction contributes to substrate metabolism in energetically active tissues of infected shrimp.
•WSSV infection induces HIF-1α mRNA expression.•LDH mRNA expression and activity increased during WSSV infection.•Silencing of HIF-1α ameliorates the WSSV-induced on LDH expression and activity.•LDH is regulated by HIF-1 during WSSV infection.
Abstract
Objectives
To investigate the effects of applying dry needling into a trigger point (TrP) or non-TrP area in people who have suffered a stroke and to investigate if the effects of dry ...needling are maintained at six-week follow-up.
Methods
A controlled, repeated-measures, crossover, double-blinded randomized trial was conducted. Nineteen patients with hemiparetic shoulder pain after a stroke event were randomly assigned to receive a single multimodal treatment session combined with TrP dry needling or non-TrP dry needling. The neuro-rehabilitation session included modulatory interventions targeting the central nervous system. Spasticity (Modified Ashworth Scale), shoulder pain intensity (numerical pain rate scale, 0–10), and upper extremity function (Motor Evaluation Scale for Upper Extremity in Stroke MESUPES, Reaching Performance Scale RPS) were assessed before (baseline) and one, two, three, four, five, and six weeks after the treatment session by a blinded assessor. All participants received both sessions in a randomized order where they were followed up for six weeks before receiving the opposite treatment and then followed up for another six weeks.
Results
Changes in muscle tone (all P > 0.266) and upper extremity function (MESUPES: F = 0.544, P = 0.465; RPS close task: F = 0.820, P = 0.371; RPS far task: 0.830, P = 0.368) were similar after both interventions at all follow-up periods. The decrease in shoulder pain was higher within the TrP dry needling group as compared with the non-TrP dry needling group, particularly at two and four weeks (P = 0.01).
Conclusions
The effect of dry needling on muscle tone (spasticity) and upper extremity function is not related to its application in or outside of a TrP area. The effect of dry needling on shoulder pain was slightly superior when applied over a TrP in poststroke people. These effects were maintained six weeks after treatment.
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