The secret of Eta Black by Ananya Sharma

The secret of Eta Black by Ananya Sharma 

A man sitting behind the bars named Eta black has no clue what is happening with him. He was searching for questions like, why he has been put inside jail? Why everyone is hating him? Why everyone is abusing him with non- patriotic slogans. He was taken by Hercules Soldiers.

Eta black was born in Orion constellation and his parents left him in front of an orphanage where he grew with his friend Canopus, Rigel and Polaris , though Rigal was his best friend. On a fine day all five friends went for walk in the forest. Unfortunately there came a leopard and they ran away in different directions to save themselves and got separated but Regal and Eta black were together fall down and got fainted.

Rigal was picked up by a family who donot have children and has been taken to the Hercules constellation. Rigal inquired about his friend Eta black and they informed that he has been taken by  King’s Soldiers and would be hanged the next day.

Rigal got worried and started thinking how to save his friend and start seeking guidance from the family to give him some clue how he can save his friend.

Mr. Vega, the head of the family offered wine amphora along with roasted sorghum to Rigal and started thinking along Rigal for the solution for the saving Eta black life.

While thinking, Mr, Vega said, I know how to come out from Jail, but I donot know how to go inside the jai?

Rigal asked with surprise, what do you mean by that?

Vega said, I mean my ancestors had made this Palace and my grandfather was a great architect, he was put inside the jail after finishing this beautiful king’s palace since the king don’t want him to make similar palace for any other king. Hence my grandfather, know that so he had made a tunnel from the palace to the sea. He used that tunnel and came out and settle in the other constellation.

But that was palace this is jail, asked Rigal?

Now that palace has been converted into Jail, answered Mr. Vega

While Rigal was thinking and they heard a noise outside, both came out and saw that the Kings ride was passing from their street. Rigal started walking aggressively and hit on  a Kings Solder on his face saying that “O kings Solder, am your father and hit the face with aggressive slap” The Soldier came and started hitting him to almost death, Vega tried to save him but all vain. The king ordered the soldiers to put both of them in the jail as he was getting late for Dawat

In the jail, whatever they have left with energy, they started looking for Eta black and could not found him, then they started shouting with a different type of voice which only Eta black can understand.

When Eta black heard the voice, he woke up from his unconsciousness and started walking towards Rigal. Both friends met and started crying like anything and now everyone start abusing both friends with non-patriotic slogans.

Rigal asked why they are abusing us, Eta said, I am also looking the answer of this question?

At the same time, Mr. Vega came towards them and asked not to make any noise we will leave this jail tonight.

But Eta said, that I will not leave this jail until I get the answers, why they are abusing us without any reasons.

Vega and Rigal try to convince Eta but all in vain and hence they thought how to get answers of Eta’s question.

Vega suggested let’s talk to the prisoners, who is abusing to understand the reasons, but the moment they went to ask the prisoners, the prisoners started beating them. Now they have no energy left and fall sleep.

Eta dreamed that he is being hanged by the Kings Soldiers and woke up suddenly in the night. He was very frightened and cried, at the same time both Vega and Rigal also woke up by hearing his voice. Finally they decided to go out through the tunnel and later they will find the answers for Eta’s questions.

Suddenly they realize that the door of their barrack has been locked from outside. Regal said that I can open the door if I got a small pin since I know how to open locks. Trio started looking for Pin but could not found inside the barrack. Vega saw a wood stick and picked up the wood stick, sharpen with his teeth and handed over to Regal for opening the lock.

After multiple efforts, they were finally able to open the lock, they came out with stifled steps and started crossing the corridor. Now it is Mr. Vega  turn to lead them and take them out from Jail. He said lets us look for a “Ficus bengalensis” tree but it was extremely dark night, they were worried for any noise.

Suddenly the king came back from Dawat and asked the Soldiers to bring them in the court to be hanged in the night itself.

The Soldiers ran towards the jail barrack and to their surprise, they could not found them inside that, all these is being observed by Eta black, Regal and Vega. The solders whispered themselves lets search them otherwise King will kill us. To search them they turn on the lights inside and outside the Jail. THe moment light turns ups, Eta saw the Ficus bengalensis tree and they started running towards the tree, while running, Vega saw another Ficus bengalensis tree, he stopped them and said, lets us take pause and decided which one is right tree. By this time, they have noticed by the King Soldiers and they started celebrating saying that, ohoo hurray they are inside the Jail and become slow. Eta Black got an intuition and said the old one would be the right tree and they started running with full energy toward the old tree. The Soldier were still in dilemma that where they will go they will remain inside the Jail, so they decided not to chase them since they thought that when they will get tired they, we will catch them.

Trio went near the Ficus bengalensis tree and Vega started looking for clue, they found a bunch of large stones and started putting them away. The Solider thought that they are making an arrangement for sleeping. They have lifted all the stones but one and could not found any clue for exit, but the moment Eta black take out the last stone, the saw lot of water through the bark, everyone without wasting time jumped in the water and started swimming in the dark night and reached the sour and boundary of the kingdom.

 

To be continued   

 Short story by Ananya Sharma Jind Haryana 

 

 

 

Beta Amyloid Peptide: Research Paper : SQSTM1 variant in disorders of the frontotemporal dementia-amyotrophic lateral sclerosis spectrum: identification of a novel heterozygous variant and a review of the literature

SQSTM1 variant in disorders of the frontotemporal dementia-amyotrophic lateral sclerosis spectrum: identification of a novel heterozygous variant and a review of the literature

Abstract

Introduction: Accumulating evidence shows that SQSTM1 plays a vital role in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which represent a neurodegenerative disease continuum. Here, we report a novel SQSTM1 variant in a patient presenting with progressive nonfluent aphasia (PNFA) and progressive bulbar palsy (PBP). Relevant literature about FTD and FTD-ALS caused by SQSTM1 mutation was reviewed to better understand its clinical features.

Methods: We collected data from a 66-year-old male patient with a novel heterozygous variant (c.995C > G, p.S332X) in the SQSTM1 gene who was diagnosed with PNFA and PBP and performed a PubMed literature search using the advanced research criteria: [("frontotemporal lobar degeneration") OR ("frontotemporal dementia") OR ("amyotrophic lateral sclerosis") OR ("motor neuron disease")] AND ("SQSTM1"). The clinical features of FTD and FTD-ALS related to SQSTM1 mutation were summarized based on previous cases and our new case.

Results: The initial symptom of the current patient was progressive verb finding difficulties and effortful speech output, which developed into dysarthria and dysphagia in subsequent months. The results, including tongue atrophy, fasciculations, neurogenic changes, and mild left dominant hypometabolism of 18F-fluorodeoxyglucose PET in the frontal cortex, suggest the possibility of PNFA and PBP. A novel likely pathogenic heterozygous variant (c.995C > G, p.S332X) in the SQSTM1 gene was identified. The literature search revealed a total of 33 FTD and FTD-ALS cases related to the SQSTM1 mutation with detailed clinical information. The mean age of onset (including our patient) was 63.5 ± 9.7 years. bvFTD was the most common clinical phenotype. The missense mutation in the SQSTM1 gene coding region and the UBA domain involvement are its main genetic characteristics.

Conclusion: Although rare, mutations in SQSTM1 can lead to various clinical subtypes of FTD and FTD-ALS, including the rare combination of PNFA and PBP. Exon missense mutation is the main type of mutation, which is common in the UBA domain.

Keywords: Frontotemporal dementia; Progressive bulbar palsy; Progressive nonfluent aphasia; SQSTM1.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33125541/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons

Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons

Abstract

Background: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria-derived vesicles. The p.D620N mutation of VPS35 causes an autosomal-dominant form of Parkinson's disease (PD), clinically representing typical PD.

Objective: Most of the studies on p.D620N VPS35 were performed on human tumor cell lines, rodent models overexpressing mutant VPS35, or in patient-derived fibroblasts. Here, based on identified target proteins, we investigated the implication of mutant VPS35 in autophagy, lysosomal degradation, and mitochondrial function in induced pluripotent stem cell-derived neurons from a patient harboring the p.D620N mutation.

Methods: We reprogrammed fibroblasts from a PD patient carrying the p.D620N mutation in the VPS35 gene and from two healthy donors in induced pluripotent stem cells. These were subsequently differentiated into neuronal precursor cells to finally generate midbrain dopaminergic neurons.

Results: We observed a decreased autophagic flux and lysosomal mass associated with an accumulation of α-synuclein in patient-derived neurons compared to controls. Moreover, patient-derived neurons presented a mitochondrial dysfunction with decreased membrane potential, impaired mitochondrial respiration, and increased production of reactive oxygen species associated with a defect in mitochondrial quality control via mitophagy.

Conclusion: We describe for the first time the impact of the p.D620N VPS35 mutation on autophago-lysosome pathway and mitochondrial function in stem cell-derived neurons from an affected p.D620N carrier and define neuronal phenotypes for future pharmacological interventions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; VPS35; induced pluripotent stem cells; mitochondrial impairment; α-synuclein.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33142012/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Quercetin-3-O-Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ 1-42 -Induced AD-Like Mice and SH-SY5Y Cells

Quercetin-3-O-Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ 1-42 -Induced AD-Like Mice and SH-SY5Y Cells

Abstract

Scope: Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) related imbalance, Tau-hyperphosphorylation, and neuroinflammation, in which Aβ and neuroinflammation can induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD. As of yet, there are no effective treatments clinically. Thus, it is focused on the potential benefit of quercetin-3-O-glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome.

Methods and results: AD mice model built through intracerebroventricular injection of Aβ1-42 and AD cell model developed through the SH-SY5Y cell line and Aβ1-42 are used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high-throughput pyrosequencing of 16S rRNA are assessed. Data show that Q3G attenuates neuroinflammation and brain IR in Aβ1-42 -injected mice and relieves apoptosis in Aβ1-42 -treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates Aβ accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses Aβ1-42 -induced cognitive impairment. Besides, Q3G restores Aβ1-42 -induced reduction of short-chain fatty acids (SCFAs) and gut microbiota dysbiosis.

Conclusion: Q3G can alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve Aβ1-42 -induced cognitive dysfunction.

Keywords: Alzheimer's disease; brain insulin resistance; gut microbiota; inflammation; quercetin-3-O-glucuronide.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33141510/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : L-3-n-Butylphthalide improves synaptic and dendritic spine plasticity and ameliorates neurite pathology in Alzheimer's disease mouse model and cultured hippocampal neurons

L-3-n-Butylphthalide improves synaptic and dendritic spine plasticity and ameliorates neurite pathology in Alzheimer's disease mouse model and cultured hippocampal neurons

Abstract

Alzheimer's disease (AD) is the most common cause of dementia among elderly people. Despite enormous efforts, the pathogenesis of AD still remains unclear and no drug has yet been proved to be disease-modifying. As the basis of learning and memory, the plasticity of synapse and dendritic spine has been impaired during AD progression. Previous studies have showed a protective effect of L-3-n-butylphthalide (L-NBP) on cognitive deficits in AD, we wonder whether this protective effect is associated with positive alterations on synapse and dendritic spines. In this study, we first of all confirmed the anti-dementia effect of L-NBP in 13-month-old APP/PS1 mice, and then investigated the alterations in synaptic and dendritic spine plasticity due to L-NBP treatment both in vivo and in vitro. We also conducted preliminary studies and found the possible mechanisms related to the inhibition of over-activated complement cascade and the remodeling of actin cytoskeleton. Besides, we also found extra benefits of L-NBP on presynaptic dystrophic neurites and attempted to give explanations from the view of autophagy regulation. Taken together, our study added some new evidence to the application of L-NBP in AD treatment and provided deeper insight into the relevant mechanisms for future study.

Keywords: Alzheimer's disease; Cognition; Dendritic spine; L-3-n-Butylphthalide (L-NBP); Synapse.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33146400/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Isoform-specific upregulation of FynT kinase expression is associated with tauopathy and glial activation in Alzheimer's disease and Lewy body dementias

Isoform-specific upregulation of FynT kinase expression is associated with tauopathy and glial activation in Alzheimer's disease and Lewy body dementias

Abstract

Cumulative data suggest the involvement of Fyn tyrosine kinase in Alzheimer's disease (AD). Previously, our group has shown increased immunoreactivities of the FynT isoform in AD neocortex (with no change in the alternatively spliced FynB isoform) which associated with neurofibrillary degeneration and reactive astrogliosis. Since both the aforementioned neuropathological features are also variably found in Lewy Body dementias (LBD), we investigated potential perturbations of Fyn expression in the post-mortem neocortex of patients with AD, as well as those diagnosed as having one of the two main subgroups of LBD: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). We found selective upregulation of FynT expression in AD, PDD, and DLB which also correlated with cognitive impairment. Furthermore, increased FynT expression correlated with hallmark neuropathological lesions, soluble β-amyloid, and phosphorylated tau, as well as markers of microglia and astrocyte activation. In line with the human post-mortem studies, cortical FynT expression in aged mice transgenic for human P301S tau was upregulated and further correlated with accumulation of aggregated phosphorylated tau as well as with microglial and astrocytic markers. Our findings provide further evidence for the involvement of FynT in neurodegenerative dementias, likely via effects on tauopathy and neuroinflammation.

Keywords: Alzheimer's disease; Fyn kinase; Lewy body dementia; alternative splicing; glial activation; tauopathy.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33128789/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Primary age-related tauopathy (PART) in the general autopsy setting: Not just a disease of the elderly

Primary age-related tauopathy (PART) in the general autopsy setting: Not just a disease of the elderly

Abstract

Primary age-related tauopathy (PART) is generally considered a diagnosis of the elderly. In this letter, the authors present data showing that the pathologic changes of PART can occur in the general autopsy population significantly earlier than largely reported in the recent literature, particularly in woman.

Keywords: Alzheimer; PART; Tau; dementia; neurodegenerative.

© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33147361/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Yuan‑zhi‑san inhibits tau protein aggregation in an Aβ 1‑40‑induced Alzheimer's disease rat model via the ubiquitin‑proteasome system

Yuan‑zhi‑san inhibits tau protein aggregation in an Aβ 1‑40‑induced Alzheimer's disease rat model via the ubiquitin‑proteasome system

Abstract

Yuan‑zhi‑san (YZS) is a classic type of Traditional Chinese Medicine, which has been reported to aid in the treatment of Alzheimer's disease (AD). The present study aimed to investigate the effects of YZS on tau protein aggregation, a hallmark of AD pathology, and its possible mechanisms. The results demonstrated that YZS improved learning and memory abilities, and decreased the severity of AD pathology in β‑amyloid (Aβ1‑40)‑induced AD rats. Moreover, YZS administration inhibited the hyperphosphorylation of tau protein at Ser199 and Thr231 sites. Several vital enzymes in the ubiquitin‑proteasome system (UPS), including ubiquitin‑activating enzyme E1a/b, ubiquitin‑conjugating enzyme E2a, carboxyl terminus of Hsc70‑interacting protein, ubiquitin C‑236 terminal hydrolase L1 and 26S proteasome, were all significantly downregulated in AD rats, which indicated an impaired enzymatic cascade in the UPS. In addition, it was identified that YZS treatment partly increased the expression levels of these enzymes in the brains of AD rats. In conclusion, the present results suggested that YZS could effectively suppress the hyperphosphorylation of tau proteins, which may be partially associated with its beneficial role in restoring functionality of the UPS.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33604685/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

Abstract

Alzheimer's disease (AD) is the most common form of dementia that is primarily characterized by progressive cognitive deficits. The toxicity of amyloid β‑protein (Aβ) serves an important role in the progression of AD, resulting in neuronal loss via a number of possible mechanisms, including oxidative stress, mitochondrial dysfunction, energy depletion, apoptosis and neuroinflammation. Previous studies have reported that cocaine amphetamine regulated transcript (CART) treatment improves memory and synaptic structure in APP/PS1 mice. Therefore, the present study aimed to investigate whether CART served a protective role against memory deficits in AD. APP/PS1 mice were treated with CART or PBS. Spatial memory was assessed using the Morris water maze. Oxidative stress and DNA damage were compared among wild‑type, APP/PS1 and CART‑treated APP/PS1 mice. The mRNA and protein expression levels of Aβ metabolism‑associated enzymes, including neprilysin (NEP), insulin‑degrading enzyme (IDE), receptor for advanced glycation end products (RAGE) and low‑density lipoprotein receptor‑related protein 1 (LRP‑1), in the hippocampus were measured via reverse transcription‑quantitative PCR and western blotting, respectively. CART improved the memory impairment of APP/PS1 mice by reducing oxidative stress, inhibiting DNA damage and protecting against mitochondrial dysfunction in the cerebral cortex and hippocampus. CART also reduced cell senescence and oxidative stress in Aβ1‑42‑exposed primary cortical neurons in APP/PS1 mice. Moreover, CART promoted Aβ degradation via modulating Aβ metabolism‑associated enzymes, including IDE, NEP, LRP‑1 and RAGE. Collectively, the present study indicated that CART improved the learning and memory capacity of APP/PS mice, thus may have potential to serve as a novel therapeutic agent for AD.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33604684/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis

Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis

Abstract

Intronic hexanucleotide repeat expansions (HREs) in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis, a devastating, incurable motoneuron (MN) disease. The mechanism by which HREs trigger pathogenesis remains elusive. The discovery of repeat-associated non-ATG (RAN) translation of dipeptide repeat proteins (DPRs) from HREs along with reduced exonic C9ORF72 expression suggests gain of toxic functions (GOFs) through DPRs versus loss of C9ORF72 functions (LOFs). Through multiparametric high-content (HC) live profiling in spinal MNs from induced pluripotent stem cells and comparison to mutant FUS and TDP43, we show that HRE C9ORF72 caused a distinct, later spatiotemporal appearance of mainly proximal axonal organelle motility deficits concomitant to augmented DNA double-strand breaks (DSBs), RNA foci, DPRs, and apoptosis. We show that both GOFs and LOFs were necessary to yield the overall C9ORF72 pathology. Increased RNA foci and DPRs concurred with onset of axon trafficking defects, DSBs, and cell death, although DSB induction itself did not phenocopy C9ORF72 mutants. Interestingly, the majority of LOF-specific DEGs were shared with HRE-mediated GOF DEGs. Finally, C9ORF72 LOF was sufficient-albeit to a smaller extent-to induce premature distal axonal trafficking deficits and increased DSBs.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33619157/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.