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We have examined the process by which cell diversity is generated in neuroblast (NB) lineages in the central nervous system of Drosophila melanogaster. Thoracic NB6-4 (NB6-4t) generates both neurons and glial cells, whereas NB6-4a generates only glial cells in abdominal segments. This is attributed to an asymmetric first division of NB6-4t, localizing prospero (pros) and glial cell missing (gcm) only to the glial precursor cell, and a symmetric division of NB6-4a, where both daughter cells express pros and gcm. Here we show that the NB6-4t lineage represents the ground state, which does not require the input of any homeotic gene, whereas the NB6-4a lineage is specified by the homeotic genes abd-A and Abd-B. They specify the NB6-4a lineage by down-regulating levels of the G1 cyclin, DmCycE (CycE). CycE, which is asymmetrically expressed after the first division of NB6-4t, functions upstream of pros and gcm to specify the neuronal sublineage. Loss of CycE function causes homeotic transformation of NB6-4t to NB6-4a, whereas ectopic CycE induces reverse transformations. However, other components of the cell cycle seem to have a minor role in this process, suggesting a critical role for CycE in regulating cell fate in segment-specific neural lineages. 相似文献
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Korhan Buyukturkoglu Hans Roettgers Jens Sommer Mohit Rana Leonie Dietzsch Ezgi Belkis Arikan Ralf Veit Rahim Malekshahi Tilo Kircher Niels Birbaumer Ranganatha Sitaram Sergio Ruiz 《PloS one》2015,10(8)
Introduction
Obsessive-compulsive disorder (OCD) is a common and chronic condition that can have disabling effects throughout the patient''s lifespan. Frequent symptoms among OCD patients include fear of contamination and washing compulsions. Several studies have shown a link between contamination fears, disgust over-reactivity, and insula activation in OCD. In concordance with the role of insula in disgust processing, new neural models based on neuroimaging studies suggest that abnormally high activations of insula could be implicated in OCD psychopathology, at least in the subgroup of patients with contamination fears and washing compulsions.Methods
In the current study, we used a Brain Computer Interface (BCI) based on real-time functional magnetic resonance imaging (rtfMRI) to aid OCD patients to achieve down-regulation of the Blood Oxygenation Level Dependent (BOLD) signal in anterior insula. Our first aim was to investigate whether patients with contamination obsessions and washing compulsions can learn to volitionally decrease (down-regulate) activity in the insula in the presence of disgust/anxiety provoking stimuli. Our second aim was to evaluate the effect of down-regulation on clinical, behavioural and physiological changes pertaining to OCD symptoms. Hence, several pre- and post-training measures were performed, i.e., confronting the patient with a disgust/anxiety inducing real-world object (Ecological Disgust Test), and subjective rating and physiological responses (heart rate, skin conductance level) of disgust towards provoking pictures.Results
Results of this pilot study, performed in 3 patients (2 females), show that OCD patients can gain self-control of the BOLD activity of insula, albeit to different degrees. In two patients positive changes in behaviour in the EDT were observed following the rtfMRI trainings. Behavioural changes were also confirmed by reductions in the negative valence and in the subjective perception of disgust towards symptom provoking images.Conclusion
Although preliminary, results of this study confirmed that insula down-regulation is possible in patients suffering from OCD, and that volitional decreases of insula activation could be used for symptom alleviation in this disorder. 相似文献65.
David A. X. Nayagam Richard A. Williams Penelope J. Allen Mohit N. Shivdasani Chi D. Luu Cesar M. Salinas-LaRosa Sue Finch Lauren N. Ayton Alexia L. Saunders Michelle McPhedran Ceara McGowan Joel Villalobos James B. Fallon Andrew K. Wise Jonathan Yeoh Jin Xu Helen Feng Rodney Millard Melanie McWade Patrick C. Thien Chris E. Williams Robert K. Shepherd 《PloS one》2014,9(5)
Purpose
To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.Methods
Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.Results
All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.Conclusions
Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents. 相似文献66.
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Ahmadzadeh Maryam Farshdari Farzaneh Behdani Mahdi Nematollahi Leila Mohit Elham 《International journal of peptide research and therapeutics》2021,27(1):433-446
International Journal of Peptide Research and Therapeutics - Breast cancer is the most common cancer in women, worldwide. The correlation between breast cancer malignancy and human epidermal growth... 相似文献
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Mohit Kumar Ashutosh Singh Sonam Kumari Praveen Kumar Mohd. Wasi Alok K. Mondal Shivaprakash M. Rudramurthy Arunaloke Chakrabarti Naseem A. Gaur Neil A.R. Gow Rajendra Prasad 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2021,1866(1):158815
Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLCR) or amphotericin B (AmBR) or both drugs. Relative to Candida glabrata and Candida albicans strains, these C. auris isolates were susceptible to SL pathway inhibitors such as myriocin and aureobasidin A, suggesting that SL content may influence azole and AmB susceptibilities. Our analysis of SLs confirmed the presence of 140 SL species within nine major SL classes, namely the sphingoid bases, Cer, αOH-Cer, dhCer, PCer, αOH-PCer, αOH-GlcCer, GlcCer, and IPC. Other than for αOH-GlcCer, most of the SLs were found at higher concentrations in FLCR isolates as compared to the AmBR isolates. SLs were at intermediate levels in FLCR + AmBR isolates. The observed diversity of molecular species of SL classes based on fatty acyl composition was further reflected in their distinct specific imprint, suggesting their influence in drug resistance. Together, the presented data improves our understanding of the dynamics of SL structures, their synthesis, and link to the drug resistance in C. auris. 相似文献
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Sukrit Srivastava Mohit Kamthania Rajesh Kumar Pandey Ajay Kumar Saxena Vaishali Saxena Santosh Kumar Singh 《Journal of biomolecular structure & dynamics》2013,31(16):4345-4360
AbstractSevere acute respiratory syndrome (SARS) is endemic in South China and is continuing to spread worldwide since the 2003 outbreak, affecting human population of 37 countries till present. SARS is caused by the severe acute respiratory syndrome Coronavirus (SARS-CoV). In the present study, we have designed two multi-epitope vaccines (MEVs) composed of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell epitopes overlap, bearing the potential to elicit cellular as well as humoral immune response. We have used truncated (residues 10–153) Onchocerca volvulus activation-associated secreted protein-1 as molecular adjuvants at N-terminal of both the MEVs. Selected overlapping epitopes of both the MEVs were further validated for stable molecular interactions with their respective human leukocyte antigen class I and II allele binders. Moreover, CTL epitopes were further studied for their molecular interaction with transporter associated with antigen processing. Furthermore, after tertiary structure modelling, both the MEVs were validated for their stable molecular interaction with Toll-like receptors 2 and 4. Codon-optimized cDNA of both the MEVs was analysed for their potential high level of expression in the mammalian cell line (Human) needed for their further in vivo testing. Overall, the present study proposes in silico validated design of two MEVs against SARS composed of specific epitopes with the potential to cause a high level of SARS-CoV specific cellular as well as humoral immune response.Communicated by Ramaswamy H. Sarma 相似文献
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Nicolas Toupoint Vani Mohit Isabelle Linossier Nathalie Bourgougnon Bruno Myrand Frédéric Olivier 《Biofouling》2013,29(9):985-1001
Biofilm ageing is commonly assumed to improve mussel settlement on artificial substrata, but the structure and taxonomic composition of biofilms remains unclear. In the present study, multi-species biofilms were characterized at different ages (1, 2, and 3 weeks) and their influence on settlement of the blue mussel, Mytilus edulis, was tested in the field. As biofilms can constitute a consistent food resource for larvae, the lipid quality, defined as the proportion of related essential fatty acids, may be a selection criterion for settlement. Overall mussel settlement increased on biofilms older than 1 week, and the enhanced settlement corresponded to the abundance and composition of the biofilm community, rather than to essential fatty acid levels. However, during a pulse of phytoplankton, the positive influence of biofilm was not detected, suggesting that pelagic cues overwhelmed those associated with biofilms. The influence of biofilms on mussel settlement could be more crucial when planktonic resources are limited. 相似文献