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The source rupture process of the M7.0 Lushan earthquake was here evaluated using 40 long-period P waveforms with even azimuth coverage of stations. Results reveal that the rupture process of the Lushan M7.0 event to be simpler than that of the Wenchuan earthquake and also showed significant differences between the two rupture processes. The whole rupture process lasted 36 s and most of the moment was released within the first 13 s. The total released moment is 1.9×10N m with M=6.8. Rupture propagated upwards and bilaterally to both sides from the initial point, resulting in a large slip region of 40 km×30 km, with the maximum slip of 1.8 m, located above the initial point. No surface displacement was estimated around the epicenter, but displacement was observed about 20 km NE and SW directions of the epicenter. Both showed slips of less than 40 cm. The rupture suddenly stopped at 20 km NE of the initial point. This was consistent with the aftershock activity. This phenomenon indicates the existence of significant variation of the medium or tectonic structure, which may prevent the propagation of the rupture and aftershock activity. The earthquake risk of the left segment of Qianshan fault is worthy of attention. [ABSTRACT FROM AUTHOR]

High luminescent bis(salicylaldehyde)o-phenylenediimine(salophen)microtubes with rectangular cross sections were successfully synthesizedby a self-assembly method. Accompanied by the formation of microtubes,a remarkable enhanced emission was observed. Crystal structure analysisand theoretical studies were both investigated in detail. It was foundthat a conformation change induced by multiple C–H···πinteractions between adjacent molecules was responsible for the formationof microtubes. The edge-to-face C–H···πinteractions also resulted in molecular structural rigidification,which made salophen a stronger emitter in microtubes. [ABSTRACT FROM AUTHOR]

High-resolution three-dimensional V and V/ V images in the Longtan reservoir area were obtained from local earthquake data by using 3,178 events with total 24,153 P-wave and 23,987 S-wave arrivals collected from 23 seismic stations. The tomographic images show that significant V heterogeneities can be seen at layers of different depth in the Longtan reservoir area. Low- V anomalies both beneath and around the main rivers in the reservoir area may be related to the composition of rocks which are mainly deposit carbonate and arenaceous shale, which contributes to water saturation. We deduced that the high porosity rocks beneath the main rivers may be fully saturated with water. The phenomenon that V is relatively high in the area which is 10-20 km away from the rivers indicates that horizontal saturation of water is limited within a small range of area that is about 10-20 km from the main rivers. The characteristic is significant that seismicity in the Longtan reservoir area is coincident with the distribution of the low- V area. V/ V tomographic images show that V/ V ranges from 1.8 to 2.05 in shallow layers above 4 km depth beneath the Longtan reservoir, suggesting the properties of the rocks are limestone and shale. At the depth of 7 km, the distribution of V/ V image varies quite remarkably, especially in the dam area. This demonstrates that the range of influence by the saturation of water in the media below the reservoir surface can reach 4-7 km depth in the dam area. [ABSTRACT FROM AUTHOR]

The functional connectivity of the cerebral cortex is shaped by experience during development, especially during a critical period early in life. In the prenatal and neonatal cortex, transient neuronal circuits are formed by a population of subplate neurons (SPNs). However, SPNs are absent in the adult cortex. While SPNs are crucial for normal development of the cerebral cortex and of thalamocortical synapses, little is known about how they are integrated in the developing thalamocortical circuit. We therefore investigated SPNs in vitro in thalamocortical slices of A1 and medial geniculate nucleus (MGN) in mouse from postnatal day 1 (P1) to P13. We found that SPNs can fire action potentials at P1 and that their intrinsic membrane properties are mature after P5. We find that SPNs receive functional excitatory inputs from theMGNas early as P2. TheMGNprojections to SPNs strengthen between P2 and P13 and are capable of inducing action potentials in SPNs. Selective activation of SPNs by photostimulation produced EPSCs in layer 4 neurons, demonstrating a functional excitatory connection. Thus, SPNs are tightly integrated into the developing thalamocortical circuit and would be a reliable relay of early spontaneous and sound-evoked activity. The role of SPNs in development likely results from their strong excitatory projection to layer 4, which might function to regulate activity-dependent processes that enable mechanisms required for the functional maturation and plasticity of the developing cortex and thereby contribute to the development of normal cortical organization. [ABSTRACT FROM AUTHOR]

Background: Limbic structures have recently garnered increased attention in Parkinson's disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD., Methods: Between December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1-weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD., Results: In patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores ( r  = -0.423, p  = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III ( r  = -0.435, p  = 0.006). Topological parameters, including characteristic path length ( L p ), global efficiency ( E g ), normalised shortest path length ( λ ) and nodal local efficiency ( N le ), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively., Conclusion: DTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Zhao, Yu, Xu, Liu, Zhang, Sun, Jiang, Zhao and Meng.)

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Background: Type 2 diabetes mellitus (T2DM) and osteoporosis are two age-associated diseases. Body mass index (BMI) is positively associated with osteoporosis or osteopenia in T2DM population. Bone mineral density does not necessarily reflect the alterations in bone microarchitecture. Our aims were to investigate the relationship between BMI and femoral neck strength in males with T2DM and normal range of bone mineral density (BMD)., Methods: This study enrolled 115 males (median age 53.3 years) with T2DM and normal BMD. Femoral neck strength indexes, including compression strength index (CSI), bending strength index (BSI), impact strength index (ISI), were calculated by parameters generated from Dual-energy X-ray absorptiometry software. Pearson correlation analysis was performed to evaluate the relationships between BMI and femoral neck strength variables., Results: Compared with T2DM-normal weight group, T2DM-overweight group and T2DM-obesity group had a higher femur neck and total femur BMDs. Cross sectional moment of inertia (CSMI), cross sectional area (CSA), section modulus (SM) were significantly higher (all p<0.05), and buckling ratio (BR) (6.35±2.08 vs 7.18±1.71) was lower in T2DM-obesity group than in T2DM-normal weight group. Compared with T2DM-normal weight group, CSI (all p<0.001), BSI (all p<0.001), ISI (all p<0.001) were significantly reduced in T2DM-obesity and T2DM-overweight groups. Pearson correlation analysis indicated that BMI was negatively correlated with CSI (r= - 0.457, p<0.001), BSI(r = -0.397, p<0.001), ISI (r = - 0.414, p<0.001)., Conclusions: Higher BMI is associated with lower femoral neck strength in males with T2DM and normal BMD. It implies that femoral neck fracture risk increases in obese and diabetic males, despite their high bone density., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We report a case of a pregnant woman who presented posterior reversible encephalopathy syndrome (PRES) without pre-eclampsia, eclampsia, or any other common causes of PRES., Methods: A 32-year-old primigravida at 25 weeks and 4 days of gestation was admitted to neurology department because of suffering intermittent headache, hearing loss, memory loss with mental and behavioral disorder, and blurred vision for 1 month. She was healthy before without hypertension, migraine, or other medical or family history. Brain magnetic resonance imaging (MRI) revealed diffuse symmetrical high-signal intensity lesions in the white matter, medulla oblongata, without enhancement. After completely multidisciplinary discussion and with the family of the patient, she accepted termination of pregnancy., Results: After the operation, the patient improved symptomatically. The follow-up MRI showed a decrease of the white matter lesion after 3 months and complete recovery at postoperative 6 months. The patient returned to work without any neurological sequelae., Conclusion: It might widen the cause spectrum of PRES that pregnancy itself without pre-eclampsia, eclampsia, or any other known risk factors could cause PRES. Pregnancy with acute or subacute leukoencephalopathy should be screened related causes and risk factors carefully. Hormonal fluctuations during the pregnancy might account for pregnancy-related PRES., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: We previously established a radiological protocol to discriminate multiple system atrophy-parkinsonian subtype (MSA-P) from Parkinson's disease (PD). However, we do not know if it can differentiate early stage disease. This study aimed to investigate whether the morphological and intensity changes in susceptibility weighted imaging (SWI) of the lentiform nucleus (LN) could discriminate MSA-P from PD at early stages., Methods: We retrospectively enrolled patients with MSA-P, PD and sex- and age-matched controls whose brain MRI included SWI, between January 2015 and July 2020 at the Movement Disorder Center. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI analysis, based on a defined and revised protocol for conducting morphological measurements of the LN and signal intensity., Results: Nineteen patients with MSA-P and 19 patients with PD, with less than 2 years of disease duration, and 19 control individuals were enrolled in this study. We found that patients with MSA- P presented significantly decreased size in the short line (SL) and corrected short line (cSL), ratio of the SL to the long line (SLLr) and corrected SLLr (cSLLr) of the LN, increased standard deviation of signal intensity (SIsd&#95;LN, cSIsd&#95;LN) compared to patients with PD and controls ( P < 0.05). With receiver operating characteristic (ROC) analysis, this finding had a sensitivity of 89.5% and a specificity of 73.7% to distinguish MSA- P from PD., Conclusion: Compared to PD and controls, patients with MSA-P are characterized by a narrowing morphology of the posterior region of the LN. Quantitative morphological changes provide a reference for clinical auxiliary diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Wang, Xia, Zhang, Zhao and Meng.)

Background: The absolute change in the severity score between the baseline and pre-specified time frame (absolute criterion) was recommended as a criterion for myasthenia gravis (MG) treatment response. But heterogeneity of disease severity might dilute major changes in individual patients. The rationality of relative criterion (improvement percentage) had not been evaluated in treatment response in patients with MG., Objectives: To investigate the consistency between an absolute criterion and a relative criterion in the evaluation of treatment response in patients with MG., Methods: We retrospectively analyzed the treatment response to a 3-month standardized treatment protocol with only glucocorticoid in 257 MG patients native to immunological treatments. With the commonly used absolute criterion, cut-offs of relative criteria were generated with the receiver operating characteristic (ROC) curve in the whole cohort and in patients with different degrees of baseline severity stratified by pre-treatment quantitative myasthenia gravis score (QMGS). The consistency between absolute and relative criteria was examined with Cohen's Kappa test and Venn diagrams., Results: The absolute and relative criteria had an overall substantial consistency (Kappa value, 0.639, p < 0.001) in the cohort. The Kappa values were substantial to almost perfect in mild and moderate groups and moderate in severe groups between the absolute and relative criteria (all p ≤ 0.001). More patients were classified as responsive with an absolute criterion while as unresponsive with a relative criterion in the moderate and severe groups., Conclusions: The overall consistency between absolute and relative criteria was substantial in the whole cohort. The inconsistency between the two criteria was mainly from the moderate or severe patients at the baseline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiang, Xie, Liang, Li, Zhao, Yue and Li.)

Background and Objectives: Sporadic late-onset nemaline myopathy (SLONM) is a treatable or otherwise fatal myopathy. Diagnosis of SLONM is still challenging, and no therapeutic consensus has been achieved. Here, we reported the clinicopathologic features and long-term follow-up data of SLONM in a Chinese cohort., Methods: We performed a retrospective evaluation of clinical, pathologic, and treatment outcomes of 17 patients with SLONM diagnosed between March 1986 and April 2021 at our neuromuscular center. Immunohistochemistry (IHC) with antibodies against 5 Z-disc-associated proteins was performed in the muscle biopsies of SLONM to identify a potential pathologic marker in aid of diagnosis. In comparison, we also performed muscle IHC in patients with selective type II fiber atrophy (n = 22), neurogenic atrophy (n = 22), mitochondrial myopathy (n = 5), immune-mediated necrotizing myopathy (n = 5), and normal controls (n = 5)., Results: Most of the patients exhibited asymmetric limb muscles weakness (71%, 12/17) and neck extensor weakness (53%, 9/17). Immunofixation electrophoresis was performed in 11 patients, and 4 of them were identified with monoclonal gammopathy of undetermined significance (MGUS). EMG from 16 patients demonstrated a myopathic pattern with spontaneous activities in 69% (11/16) of them. Muscle MRI showed preferential involvement of paraspinal, gluteus minimus and medius, semimembranosus, and soleus muscles. Suspected nemaline bodies on modified Gomori trichrome were confirmed by IHC using anti-α-actinin antibody (100%, 17/17), anti-myotilin antibody (94%, 16/17), anti-desmin antibody (94%, 16/17), anti-α-B crystallin antibody (65%, 11/17), and anti-telethonin antibody (18%, 3/17) with various positive rates. Notably, anti-α-actinin IHC showed the highest percentage of strongly positive staining (77%, 13/17), being the only one without negative results. Moderate improvement following autologous stem cell transplantation (ASCT) was noted in 3/4 patients with MGUS; favorable outcomes were also achieved in 6/7 patients without MGUS, including 3 patients with complete recovery who were given a combined treatment of prednisone and another immunosuppressant., Discussion: SLONM is a treatable myopathy with ASCT or traditional immunotherapy, especially when combined with steroids and immunosuppressants. Anti-α-actinin immunostaining is the most reliable pathologic marker to identify rod-bearing fibers, and it should be performed routinely in adult patients with undiagnosed nonnecrotic myopathies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the γδ IEL compartment under homeostatic conditions has yet to be determined. We identified a novel γδ IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple Vγ subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal γδ IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in γδ IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with γδ IEL expansion. Using intravital microscopy, we find that hyperproliferative γδ IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate γδ IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Iron-sulfur clusters are essential cofactors found in all kingdoms of life and play essential roles in fundamental processes, including but not limited to respiration, photosynthesis, and nitrogen fixation. The chemistry of iron-sulfur clusters makes them ideal for sensing various redox environmental signals, while the physics of iron-sulfur clusters and its host proteins have been long overlooked. One such protein, MagR, has been proposed as a putative animal magnetoreceptor. It forms a rod-like complex with cryptochromes (Cry) and possesses intrinsic magnetic moment. However, the magnetism modulation of MagR remains unknown. Here in this study, iron-sulfur cluster binding in MagR has been characterized. Three conserved cysteines of MagR play different roles in iron-sulfur cluster binding. Two forms of iron-sulfur clusters binding have been identified in pigeon MagR and showed different magnetic properties: [3Fe-4S]-MagR appears to be superparamagnetic and has saturation magnetization at 5 K but [2Fe-2S]-MagR is paramagnetic. While at 300 K, [2Fe-2S]-MagR is diamagnetic but [3Fe-4S]-MagR is paramagnetic. Together, the different types of iron-sulfur cluster binding in MagR attribute distinguished magnetic properties, which may provide a fascinating mechanism for animals to modulate the sensitivity in magnetic sensing., (© 2021. The Author(s).)

Aims: To detect abnormal eye movements in Parkinson's disease and explore its correlation with clinical characteristics and their value for diagnosis., Methods: We recruited forty-nine Parkinson's disease patients, including 35 early Parkinson's disease patients (Hoehn-Yahr: 1 to 2 stage) and 14 advanced Parkinson's disease patients (Hoehn-Yahr: 3 to 5 stage) and 23 healthy controls. Clinical manifestations in Parkinson's disease patients were recorded. Oculomotor performances including fixation, gaze, saccade in horizontal and vertical direction, and smooth pursuit in horizontal and vertical direction were measured by video-oculography., Results: We found that five oculomotor parameters, namely square wave jerk frequency, latency of downward saccade, latency of upward saccade, accuracy of upward saccade, and gain of horizontal smooth pursuit were significantly different in Parkinson's disease patients and controls. When combining all these five parameters, we got the diagnostic sensitivity of 78.3% and specificity of 95.2%. More deficits in upward saccade than in other directions were associated with disease duration and progression of Parkinson's disease., Conclusion: Our primary study suggests that oculomotor examination might serve as an aid in the clinical assessment of Parkinson's disease patients and differentiating between early Parkinson's disease and normal controls.

Iron-sulfur (Fe-S) clusters are among the oldest and most versatile cofactors present in all domains of life. Many bacterial and eukaryotic Fe-S proteins have been well-characterized, whereas the archaeal ones are less studied. Fe-S proteins are particularly abundant and play essential roles in methanogenic archaea. Methanococcus maripaludis is a model methanogen with available genetic tools. Here, we describe the techniques for anaerobic cultivation of M. maripaludis with formate, liposome-mediated transformation, expression and anoxic affinity purification of Fe-S proteins, Fe-S cluster reconstitution, and analysis of Fe-S proteins by UV-visible absorption spectroscopy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: It remains challenging to make a differential diagnosis between atypical parkinsonism and Parkinson's disease (PD) from routine neuroimaging. This case-control study aimed to quantitatively investigate both morphological and signal intensity changes in susceptibility weighted imaging (SWI) of the lentiform nucleus (LN) for discriminating parkinsonism-predominant multiple system atrophy (MSA-P) from PD., Methods: We retrospectively enrolled patients with MSA-P, PD, and sex- and age-matched controls between January 2016 and November 2019 at the Movement Disorder Center who underwent 3T MR imaging of brain with SWI sequence. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI image analysis based on a defined radiological protocol to conduct the ROI-based morphological measurements of the LN and the signal intensity., Results: A total of 19 patients with MSA-P, 19 patients with PD and 19 controls were enrolled in this study. We found that patients with MSA-P had significant decreases size in the short line (SL) and the ratio of the SL and the long line (SLLr) and increased value in the signal intensity standard deviation of the LN (SIsd&#95;LN) compared with the patients with PD and with the controls (P < 0.05). Combining these three indexes, this finding had a sensitivity of 94.7% and a specificity of 63.2% to distinguish MSA-P from PD., Conclusion: As compared to PD and control subjects, the SA-P patients are characterized by narrowing morphology and the inhomogeneous signal intensity of the posterior region of LN. The quantitative morphological change is a possible potential marker to differentiate MSA-P from PD on SWI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Catechol-O-methyltransferase (COMT) is one of the main enzymes in dopamine metabolism and is reported to be associated with susceptibility to Parkinson's disease (PD) and pharmacotherapy. However, researchers mostly focus on the most common polymorphism, rs4680. In this case-control study, we investigated the association of SNPs other than rs4680 with the levodopa (L-dopa) response and other clinical features in Chinese PD patients. Eleven single nucleotide polymorphisms (SNPs) in the COMT gene were genotyped, and clinical data were collected. Patients with the TT genotype of rs165728 or rs174699 had larger daily levodopa equivalent doses (LEDs) than the patients with CC and CT genotypes under the dominant model (p = 0.01421 for rs165728 and p = 0.02302 for rs174699). Under the dominant model, the patients with GG at rs4680 G > A had a lower occurrence of dyskinesia than those with AA and AG (p = 0.0196). Patients with CC at rs4633 had a lower occurrence of dyskinesia than those with TT and TC (p = 0.0429) under the dominant model. The frequencies of the rs174675 T and rs933271 C alleles were higher in PD patients than in the controls (p < 0.05). Our primary results showed the possible association of SNPs other than the most common functional rs4680 in COMT with interindividual variance in the L-dopa daily dose and susceptibility to dyskinesia in Chinese patients, although this was an exploratory study based on a small sample size. Larger and more randomized samples are necessary for further investigation.

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset, X-linked genetic, neurodegenerative disorder caused by a "premutation (PM)" in the fragile X mental retardation 1 (FMR1) gene. Here we report a case of FXTAS from mainland of China who presented with rare orthostatic tremor. A review of tremor of FXTAS in the literature is also included., Case Presentation: A 67-year-old right-handed farmer started with tremor of both legs 8 years ago which was present while standing but absent when sitting or lying and progressed with unsteady gait one and a half years ago. The brain MRI showed high intensity signal in the bilateral middle cerebellar peduncles (MCP) in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images and gene test for premutation for FMR1 was positive with 101 CGG repeats. The patient met the the diagnosis of definite FXTAS. Clonazepam and topiramate were administered to control tremor. We reviewed the literature and identified 64 cases with detailed clinical and genetic information. Orthostatic tremor associated with FXTAS is very rare. We found 85.2% patients reported tremor,42.6% with intention tremor,36.1% with kinetic tremor,32.8% with rest tremor and 29.5% with posture tremor. 37.7% of patients who have tremor showed at least two types of tremor. There were 6 patients with isolated rest tremor. There was 2 patient with voice tremor and 6 with head tremor. We also found that 74.6% FXTAS patients had family history of FMR1 gene associated diseases including Fragile X syndrome (FXS), FXTAS or fragile X-associated primary ovarian insufficiency (FXPOI)., Conclusions: Adding our data to the available literature suggests that orthostatic tremor could be a rare initial manifestation of FXTAS and the review will increasing our understanding the phenotype of tremor in FXTAS. Family history of FMR1 gene associated diseases might be an important clue to the diagnosis.

Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production (F SA ), whereas the jump muscle produces only minimal F SA We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher F SA , we substituted the IFM MHC isoform (IFI) into the jump muscle. Surprisingly, we found that IFI only caused a 1.7-fold increase in F SA , less than half the increase previously observed with EMB, and only at a high Pi concentration, 16 mM. This IFI-induced F SA is much less than what occurs in IFM, relative to isometric tension, and did not enable positive cyclical power generation by the jump muscle. Both isometric tension and F SA of control fibers decreased with increasing Pi concentration. However, for IFI-expressing fibers, only isometric tension decreased. The rate of F SA generation was ~1.5-fold faster for IFI fibers than control fibers, and both rates were Pi dependent. We conclude that MHC isoforms can alter F SA and hence cyclical power generation but that isoforms can only endow a muscle type with moderate F SA Highly SA muscle types, such as IFM, likely use a different or additional mechanism., (Copyright © 2017 the American Physiological Society.)

Alzheimer's disease (AD) is characterized by Amyloid-β (Aβ) deposition in senile plaques in specific areas of the brain and by intraneuronal p-tau accumulation in neurofibrillary tangles. Cumulative evidence supports that oxidative stress is an important factor in the pathogenesis of AD and contributes to Aβ generation. However, there is no effective treatment for AD. Human umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value for the treatment of neurological disease. However, the therapeutic impact of systemic administration of HUMSCs and their mechanism of action in AD have not yet been determined. Here, we found that intravenous infusion of HUMSCs significantly improved spatial learning and alleviated memory decline in an AβPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH) activity and ratio of GSH to oxidative glutathione as well as superoxide dismutase activity, while decreasing malondialdehyde activity and protein carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in AβPP/PS1 mice. In addition, HUMSC infusion reduced β-secretase 1 and CTFβ, thus reducing Aβ deposition in mice. HUMSCs may have beneficial effects in the prevention and treatment of AD.

Introduction: Cell therapy is a potential therapeutic approach for neurodegenerative disorders, such as Alzheimer disease (AD). Neuronal differentiation of stem cells before transplantation is a promising procedure for cell therapy. However, the therapeutic impact and mechanisms of action of neuron-like cells differentiated from human umbilical cord mesenchymal stem cells in AD have not been determined., Methods: In this study, we used tricyclodecan-9-yl-xanthogenate (D609) to induce human mesenchymal stem cells isolated from Wharton jelly of the umbilical cord (HUMSCs) to differentiate into neuron-like cells (HUMSC-NCs), and transplanted the HUMSC-NCs into an AβPP/PS1 transgenic AD mouse model. The effects of HUMSC-NC transplantation on the cognitive function, synapsin I level, amyloid β-peptides (Aβ) deposition, and microglial function of the mice were investigated., Results: We found that transplantation of HUMSC-NCs into AβPP/PS1 mice improved the cognitive function, increased synapsin I level, and significantly reduced Aβ deposition in the mice. The beneficial effects were associated with "alternatively activated" microglia (M2-like microglia). In the mice transplanted with HUMSC-NCs, M2-like microglial activation was significantly increased, and the expression of antiinflammatory cytokine associated with M2-like microglia, interleukin-4 (IL-4), was also increased, whereas the expression of proinflammatory cytokines associated with classic microglia (M1-like microglia), including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was significantly reduced. Moreover, the expression of Aβ-degrading factors, insulin-degrading enzyme (IDE) and neprilysin (NEP), was increased substantially in the mice treated with HUMSC-NCs., Conclusions: HUMSC-NC transplantation decreased Aβ deposition and improved memory in AβPP/PS1 mice by a mechanism associated with activating M2-like microglia and modulating neuroinflammation. Transplantation of neuron-like cells differentiated from mesenchymal stem cells might be a promising cell therapy for Alzheimer disease.

The mechanism behind stretch activation (SA), a mechanical property that increases muscle force and oscillatory power generation, is not known. We used Drosophila transgenic techniques and our new muscle preparation, the jump muscle, to determine if myosin heavy chain isoforms influence the magnitude and rate of SA force generation. We found that Drosophila jump muscles show very low SA force and cannot produce positive power under oscillatory conditions at pCa 5.0. However, we transformed the jump muscle to be moderately stretch-activatable by replacing its myosin isoform with an embryonic isoform (EMB). Expressing EMB, jump muscle SA force increased by 163% and it generated net positive power. The rate of SA force development decreased by 58% with EMB expression. Power generation is Pi dependent as >4 mM Pi was required for positive power from EMB. Pi increased EMB SA force, but not wild-type SA force. Our data suggest that when muscle expressing EMB is stretched, EMB is more easily driven backward to a weakly bound state than wild-type jump muscle. This increases the number of myosin heads available to rapidly bind to actin and contribute to SA force generation. We conclude that myosin heavy chain isoforms influence both SA kinetics and SA force, which can determine if a muscle is capable of generating oscillatory power at a fixed calcium concentration., (Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Many animals regulate power generation for locomotion by varying the number of muscle fibers used for movement. However, insects with asynchronous flight muscles may regulate the power required for flight by varying the calcium concentration ([Ca(2+)]). In vivo myoplasmic calcium levels in Drosophila flight muscle have been found to vary twofold during flight and to correlate with aerodynamic power generation and wing beat frequency. This mechanism can only be possible if [Ca(2+)] also modulates the flight muscle power output and muscle kinetics to match the aerodynamic requirements. We found that the in vitro power produced by skinned Drosophila asynchronous flight muscle fibers increased with increasing [Ca(2+)]. Positive muscle power generation started at pCa = 5.8 and reached its maximum at pCa = 5.25. A twofold variation in [Ca(2+)] over the steepest portion of this curve resulted in a two- to threefold variation in power generation and a 1.2-fold variation in speed, matching the aerodynamic requirements. To determine the mechanism behind the variation in power, we analyzed the tension response to muscle fiber-lengthening steps at varying levels of [Ca(2+)]. Both calcium-activated and stretch-activated tensions increased with increasing [Ca(2+)]. However, calcium tension saturated at slightly lower [Ca(2+)] than stretch-activated tension, such that as [Ca(2+)] increased from pCa = 5.7 to pCa = 5.4 (the range likely used during flight), stretch- and calcium-activated tension contributed 80% and 20%, respectively, to the total tension increase. This suggests that the response of stretch activation to [Ca(2+)] is the main mechanism by which power is varied during flight., (Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Muscle LIM protein (MLP) can be found at the Z-disk of sarcomeres where it is hypothesized to be involved in sensing muscle stretch. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function. Loss of MLP in Drosophila (mlp84B) also leads to muscle dysfunction, providing a model system to examine MLP's mechanism of action. Mlp84B-null flies that survive to adulthood are not able to fly or beat their wings. Transgenic expression of the mlp84B gene in the Mlp84B-null background rescues flight ability and restores wing beating ability. Mechanical analysis of skinned flight muscle fibers showed a 30% decrease in oscillatory power production and a slight increase in the frequency at which maximum power is generated for fibers lacking Mlp84B compared with rescued fibers. Mlp84B-null muscle fibers displayed a 25% decrease in passive, active, and rigor stiffness compared with rescued fibers, but no significant decrease in isometric tension generation was observed. Muscle ultrastructure of Mlp84B-null muscle fibers is grossly normal; however, the null fibers have a slight decrease, 11%, in thick filament number per unit cross-sectional area. Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation.

NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) plays pivotal roles in antioxidation and reductive biosynthesis. However, the effect of NADPH treatment on cell survival is unknown. In this study, we determined the effect of NADPH treatment on the survival of glioma cells. Treatment of C6 glioma cells with as low as 1 μM NADPH for 24 hrs induced a significant decrease in the survival of the glioma cells, while NADPH treatment had no effect on the survival of primary astrocyte cultures. We also found that NADPH treatment increased intracellular oxidative stress. Three antioxidants and the NADPH oxidase inhibitor, apocynin, attenuated the effect of NADPH. Poly(ADP-ribose) polymerase (PARP) activation appears to be a downstream effector of the oxidative stress, since PARP inhibitors reduced the effect of NADPH. Calcium chelator, BAPTA-AM, also attenuated the effect of NADPH. Collectively, these data indicate a novel property of NADPH: NADPH decreases glioma cell survival by inducing the NADPH oxidase-dependent increase in oxidative stress and by PARP activation. These results also suggest a potential therapeutic effect of NADPH on gliomas.

NAD+ plays important roles in various biological processes. It has been shown that NAD+ treatment can decrease genotoxic agent-induced death of primary neuronal and astrocyte cultures, and NAD+ administration can reduce ischemic brain damage. However, the effects of NAD+ treatment on tumor cell survival are unknown. In this study we found that treatment of NAD+ at concentrations from 10 micromolar to 1 mM can significantly decrease the survival of various types of tumor cells such as C6 glioma cells. In contrast, NAD+ treatment did not impair the survival of primary astrocyte cultures. Our study has also indicated that oxidative stress mediates the effects of NAD+ on the survival of tumor cells, and P2X7 receptors and altered calcium homeostasis are involved in the effects of NAD+ on the cell survival. Collectively, our study has provided the first evidence that NAD+ treatment can decrease the survival of tumor cells by such mechanisms as inducing oxidative stress. Because NAD+ treatment can selectively decrease the survival of tumor cells, NAD+ may become a novel agent for treating cancer.

Background Aims: Mesenchymal stromal cells (MSC) have been thought to be attractive candidates for the treatment of Duchenne muscular dystrophy (DMD), but the rate of MSC myogenesis is very low. Thus MSC treatment for DMD is restricted. Myostatin (Mstn), a negative regulator of myogenesis, is known to be responsible for limiting skeletal muscle regeneration. We hypothesized that inhibition of Mstn by using anti-Mstn antibody (Ab) would ameliorate the myogenic differentiation of MSC in vitro and in vivo., Methods: MSC were isolated from rat bone marrow. Induced rat MSC (rMSC) were treated with various concentrations of anti-Mstn Ab. The expression of myogenic differentiation antigen (MyoD), myogenin and myosin heavy chain-type alpha (MHC-alpha) were estimated by immunofluorescence analysis and reverse transcription-polymerase chain reaction (RT-PCR). Adipogenic differentiation of rMSC inhibited by anti-Mstn Ab was evaluated by Oil Red O staining. The expression of dystrophin was detected 16 weeks after anti-Mstn Ab injection and rMSC transplantation by immunofluorescence staining, RT-PCR and Western blot. Motor function, serum creatine kinase (CK) and histologic changes were also evaluated., Results: Five-azacytidine-mediated myogenic differentiation induced significant endogenous Mstn expression. Anti-Mstn Ab improved the expression of MyoD, myogenin and MHC-alpha and inhibited adipocyte formation. Sixteen weeks after transplantation, the inhibition of Mstn had improved motor function and muscle mass. In accordance with the increased motor function and muscle mass, dystrophin expression had increased. Furthermore, serum CK and centrally nucleated fiber (CNF) levels decreased slightly, suggesting specific pathologic features of the dystrophic muscle were partially restored., Conclusions: Using anti-Mstn Ab, we found that inhibition of Mstn improved myogenic differentiation of rMSC in vitro and in vivo. A combination of Mstn blockade and MSC transplantation may provide a pharmacologic and cell-based strategy for the treatment of DMD.

Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.