bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential proteins and microRNAs in Multiple Sclerosis and Huntington’s diseases using in silico methods
Authors: Maiti Tarasankar , Chakraborty Souvik 
Published: September 2021

AbstractNeurogenerative diseases like multiple sclerosis, Huntington’s disease are the major roadblocks in the way towards a healthy brain. Neurodegenerative diseases like multiple sclerosis and Huntington’s disease are affected by several factors such as environmental, immunological, genetics, and the worse scenario we can think of is that they are on the rise worldwide. Degenerative diseases specifically target a limited group of neurons at first resulting in the loss of specific functions associated with the specific part of the brain. The early diagnosis of these neurodegenerative diseases is important so that treatments can start from the early stages of these diseases. In this study, we have established a link between Multiple sclerosis and Huntington’s disease, and also we were able to establish the possible microRNAs that were connected to the expression of genes associated with these two diseases. In this present study, we analyzed the microarray datasets obtained from Gene Expression Omnibus and we identified 266 differentially expressed genes tried to identify using in silico methods the Hub genes involved in Multiple sclerosis and Huntington’s disease. After identifying the genes and proteins we tried to identify the microRNAs that are interacting with the Hub genes. In our study, we identified that the protein network has PTPRC, CXCL8, RBM25 proteins that have maximum connectivity. The top Hub genes are then subjected to a database that contains information concerning the microRNAs that are interacting with the Hub proteins as well as with each other. According to our study, the hsa-mir-155-5p has one of the highest degrees in the microRNA network. Our study will be useful in the future for the development of new drug targets for these neurodegenerative diseases.
Efference information flow during skill acquisition mediate its interaction with medical simulation technology
Authors: Kamat Anil , Makled Basiel , Norfleet Jack , Schwaitzberg Steven D. , Intes Xavier , De Suvranu , Dutta Anirban 
Published: September 2021

AbstractDespite substantial progress towards establishing virtual reality (VR) simulators as a replacement for physical ones for skill training, its effect on the brain network during skill acquisition has not been well addressed. In this study, we employed portable optical neuroimaging technology and Granger causality approach to uncover the impact of the two medical simulation technologies on the directed functional brain network of the subjects with two different skill levels. The mobile brain-behavior relantionship was evaluated using functional near-infrared spectroscopy (fNIRS) while right-handed subjects performed well-established fundamentals of laparoscopic surgery (FLS) pattern cutting task. A multiple regression path analysis found that the cognitive-action information flow from the right prefrontal cortex to the supplementary motor area statistically significantly predicted the FLS task performance. Here, the skill level (expert vs novice) affected the cognitive-action information flow from the right prefrontal cortex and the efference copy information flow from the left primary motor cortex via supplementary motor area as hub to the cognitive-perception at the left prefrontal cortex, i.e., the action-preception link. The simulation technology (physical vs VR simulator) affected solely the cognitive-action information flow from the right prefrontal cortex to the left primary motor cortex; however, the interaction between the medical simulation technology) and the skill level affected the efference information flow from the left primary motor cortex to the right prefrontal cortex and from the supplementary motor area to the left prefrontal cortex. These discriminative findings are crucial since our VR simulator had face and construct validity. Therefore, our study highlighted the importance of efference information flow within the framework of the perception-action cycle when comparing medical simulation technology for visuomotor skill acquisition.
The therapeutic and diagnostic potential of amyloid β oligomers (AβOs) selective antibodies to treat Alzheimer’s disease
Authors: Viola Kirsten L. , Bicca Maira A. , Bebenek Adrian M. , Kranz Daniel L. , Nandwana Vikas , Waters Emily A. , Haney Chad R. , Lee Maxwell , Gupta Abhay , Brahmbhatt Zach , Huang Weijian , Chang Ting-Tung , Peck Anderson , Valdez Clarissa , Dravid Vinayak P. , Klein William L. 
Published: September 2021

AbstractImprovements have been made in the diagnosis of Alzheimer’s disease (AD), manifesting mostly in the development of in vivo imaging methods that allow for the detection of pathological changes in AD by MRI and PET scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques - species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression. Here we report evidence further supporting the role of AβOs as pathological instigators of AD and introduce promising anti-AβO diagnostic probes capable of distinguishing the 5xFAD mouse model from wild type mice by PET and MRI. In a developmental study, Aβ oligomers in 5xFAD mice were found to appear at 3 months of age, just prior to the onset of memory dysfunction, and spread as memory worsened. The increase of AβOs is prominent in the subiculum and correlates with concomitant development of reactive astrocytosis. The impact of these AβOs on memory is in harmony with findings that intraventricular injection of synthetic AβOs into wild type mice induced hippocampal dependent memory dysfunction within 24 hours. Compelling support for the conclusion that endogenous AβOs cause memory loss was found in experiments showing that intranasal inoculation of AβO-selective antibodies into 5xFAD mice completely restored memory function, measured 30-40 days post-inoculation. These antibodies, which were modified to give MRI and PET imaging probes, were able to distinguish 5xFAD mice from wild type littermates. These results provide strong support for the role of AβOs in instigating memory loss and salient AD neuropathology, and they demonstrate that AβO selective antibodies have potential both for therapeutics and for diagnostics.
RNA polymerase II dynamics and mRNA stability feedback scale mRNA in proportion to cell size
Authors: Swaffer Matthew P. , Marinov Georgi K. , Zheng Huan , Tsui Crystal Yee , Jones Andrew W. , Greenwood Jessica , Kundaje Anshul , Greenleaf William J. , Reyes-Lamothe Rodrigo , Skotheim Jan M. 
Published: September 2021

AbstractA fundamental feature of cellular growth is that protein and RNA amounts scale with cell size so that concentrations remain constant. A key component to this is that global transcription rates increase in larger cells, but the underlying mechanism has remained unknown. Here, we identify RNAPII as the major limiting factor increasing transcription with cell size in budding yeast as transcription is highly sensitive to the dosage of RNAPII but not to other components of the general transcriptional machinery. Our experiments support a dynamic equilibrium model where global transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII, and DNA content. This drives a sub-linear increase in transcription with size, which is precisely compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to ensure mRNA concentration homeostasis in growing cells.
Mechanistic Insights into the Effects of Key Mutations on SARS-CoV-2 RBD-ACE2 Binding
Authors: Aggarwal Abhishek , Naskar Supriyo , Maroli Nikhil , Gorai Biswajit , Dixit Narendra M. , Maiti Prabal K. 
Published: September 2021

AbstractSome recent SARS-CoV-2 variants appear to have increased transmissibility than the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on target cells and infect them. In this study, we provide atomic-level insight into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities of the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.
Comparison of two injectable anaesthetic protocols in Egyptian fruit bats(Rousettus aegyptiacus)undergoing gonadectomy
Authors: Amari Martina , Brioschi Federica A. , Rabbogliatti Vanessa , Di Cesare Federica , Pecile Alessandro , Giordano Alessia , Moretti Pierangelo , Magnone William , Bonato Francesco , Ravasio Giuliano 
Published: September 2021

AbstractEgyptian fruit bats are experimental animals of increasing interest because they have been identified as a natural reservoir for several emerging zoonotic viruses. For this reason, bats could undergo different experimental procedures that require sedation or anaesthesia. Our aim was to compare the effects of two balanced anaesthetic protocols on sedation, cardiopulmonary variables and recovery in bats undergoing gonadectomy. Twenty bats were randomized into two groups; patients in group DK received intramuscular injection of dexmedetomidine (40 μg kg-1) and ketamine (7 mg kg-1), whereas those in group DBM were anaesthetized with intramuscular dexmedetomidine (40 μg kg-1), butorphanol (0.3 mg kg-1) and midazolam (0.3 mg kg-1). Time of induction, cardiopulmonary parameters and anaesthetic depth were measured. If anaesthesia plan was considered inadequate, fraction of inspired isoflurane was titrate-to-effect to achieve immobility. At the end of the surgery venous blood gas analysis was performed and intramuscular atipamezole (200 μg kg-1) or atipamezole (200 μg kg-1) and flumazenil (0.03 mg kg-1) was administered for timed and scored recovery phase. A significantly higher heart rate and peripheral oxygen saturation were recorded in DBM group (p= 0.001;p= 0.003 respectively), while respiratory rate was significantly lower than DK group (p= 0.001). All bats required isoflurane supplementation during surgery with no significant difference. No differences were observed in rectal temperature, induction and recovery times. Sodium and chlorine where significantly higher in DBM group (p= 0.001;p= 0.002 respectively). Recovery scores in group DK were significantly better than in group DBM (p= 0.034). Both protocols induced anaesthesia in Egyptian fruit bats with comparable sedative and cardiorespiratory effect. These drug combinations may be useful for minor procedures in bats, and they could be associated with inhalation anaesthesia in determining and maintaining a surgical anaesthetic plan.
Distinct ground state and activated state modes of firing in forebrain neurons
Authors: Levenstein Daniel , Gornet Jonathan , Huszár Roman , Girardeau Gabrielle , Grosmark Andres , Peyrache Adrien , Senzai Yuta , Watson Brendon O. , Mizuseki Kenji , Rinzel John , Buzsáki György 
Published: September 2021

ABSTRACTNeuronal firing patterns have significant spatiotemporal variability with no agreed upon theoretical framework. Using a combined experimental and modeling approach, we found that spike interval statistics can be described by discrete modes of activity. Of these, a “ground state” (GS) mode of low-rate spiking is universal among forebrain excitatory neurons and characterized by irregular spiking at neuron-specific rates. In contrast, “activated state” (AS) modes consist of spiking at characteristic timescales and regularity that are specific to neuron populations in a given region and brain state. The majority of spiking is contributed by GS mode, while neurons can transiently switch to AS spiking in response to stimuli or in coordination with population activity patterns. We hypothesize that GS spiking serves to maintain a persistent backbone of neuronal activity while AS modes support communication functions.
Slow-oscillatory tACS does not modulate human motor cortical response to repeated plasticity paradigms
Authors: Bradley Claire , Elliott Jessica , Dudley Samuel , Kieseker Genevieve A. , Mattingley Jason B. , Sale Martin V. 
Published: September 2021

AbstractPrevious history of activity and learning modulates synaptic plasticity and can lead to saturation of synaptic connections. According to the synaptic homeostasis hypothesis, neural oscillations during slow-wave sleep play an important role in restoring plasticity within a functional range. However, it is not known whether slow-wave oscillations – without the concomitant requirement of sleep – play a causal role in human synaptic homeostasis. Here, slow-oscillatory transcranial alternating current stimulation (tACS, 1Hz, 1mA, 18 minutes) was interleaved between two plasticity-inducing interventions: motor learning, and a paradigm known to induce long-term-potentiation-like plasticity in human motor cortex (paired associative stimulation; PAS). The hypothesis tested was that slow-oscillatory tACS would abolish the expected interference between motor learning and PAS, and facilitate plasticity from successive interventions. Thirty-six participants received sham and active fronto-motor tACS in two separate sessions, along with electroencephalography (EEG) recordings. A further 38 participants received tACS through a control (posterior midline) montage. Using neuro-navigated transcranial magnetic stimulation (TMS) over the left motor cortex, motor evoked potentials (MEPs) were recorded throughout the session. Bayesian statistics were used to quantify evidence for or against the hypothesis of an effect of each intervention on MEP amplitude. As expected, there was converging evidence that motor training increased MEPs. Importantly, we found moderate evidence against an effect of active tACS in restoring PAS plasticity, and no evidence of lasting entrainment of slow-oscillations in the EEG. This suggests that, under the conditions tested here, slow-oscillatory tACS does not modulate synaptic homeostasis in the motor system of awake humans.
PCDH7 Promotes Cell Migration by Regulating Myosin Activity
Authors: Qureshi Mohammad Haroon , Bayraktar Halil , Cinko M. Talha , Akkaya Cansu , Kamacioglu Altug , Uretmen-Kagiali Z. Cansu , Bozluolcay Erdem , Ozlu Nurhan 
Published: September 2021

AbstractCell migration requires spatiotemporally coordinated activities of multicomponent structures including the actomyosin cortex, plasma membrane, adhesion complexes and the polarity proteins. How they function together to drive this complex dynamic process remains an outstanding question. Here, we show that a member of the protocadherin family, PCDH7 displays a polarized localization in migratory cells with a dynamic enrichment at the leading and rear edges. Perturbation of PCDH7 interferes with the migration of nontransformed retinal pigment epithelial cells and the invasion of cancer cells. The overexpression of PCDH7 enhances the migration capability of cortical neurons in vivo. PCDH7 interacts with the myosin phosphatase subunits MYPT1 and PP1cβ. Ectopic expression of PCDH7 enhances the MYPT1 inhibitory phosphorylation levels and the phosphorylation of the myosin regulatory light chain and ERM at the polarized cortex. The chemical inhibition of phosphatase activity recovers migration phenotypes of PCDH7 knockout cells. We propose that PCDH7 regulates phosphorylation thus the activity of myosin and ERM at the polarized cortex through its interaction with myosin phosphatase. Collectively, our study suggests a new component for the spatial coordination of the plasma membrane and the cortex during cell migration.
Hippocampal representations switch from errors to predictions during acquisition of predictive associations
Authors: Aitken Fraser , Kok Peter 
Published: September 2021

AbstractWe constantly exploit the statistical regularities in our environment to help guide our perception. The hippocampus has been suggested to play a pivotal role in both learning environmental statistics, as well as exploiting them to generate perceptual predictions. However, it is unclear how the hippocampus balances encoding new predictive associations with the retrieval of existing ones. Here, we present the results of two high resolution human fMRI studies (N=24 for both experiments) directly investigating this. Participants were exposed to auditory cues that predicted the identity of an upcoming visual shape (with 75% validity). Using multivoxel decoding analysis, we found that the hippocampus initially preferentially represented unexpected shapes (i.e., those that violated the cue regularities), but later switched to representing the cue-predicted shape regardless of which was actually presented. These findings demonstrate that the hippocampus in involved both acquiring and exploiting predictive associations, and switches between these modes depending on whether learning is ongoing or complete.
Articulated dissent and immediacy: a cross-national analysis of the effects of COVID-19 lockdowns
Authors: Croucher Stephen Michael , Kelly Stephanie , Hui Chen , Rocker Kenneth J. , Cullinane Joanna , Homsey Dini , Ding George Guoyu , Nguyen Thao , Anderson Kirsty Jane , Green Malcolm , Ashwell Doug , Wright Malcolm , Palakshappa Nitha 
Published: September 2021

PurposeIn the midst of the COVID-19 pandemic, this study aims to explore how working remotely might impact the superior–subordinate relationship. Specifically, this study examines how immediacy explains articulated dissent, considers how an individual’s attitudes toward online communication predicts immediacy and articulated dissent and compares these relationships in England, Australia and the USA.Design/methodology/approachThree nations were examined: Australia, England and the USA (n= 1,776). Surveys included demographic questions and the following measures: organizational dissent scale, perceived immediacy measure, computer-mediated immediate behaviors measure and measure of online communication attitude.FindingsThe results reveal supervisors’ computer-mediated immediate behaviors and perceived immediacy both positively predict dissent. Some aspects of online communication attitudes positively predict computer-mediated immediate behaviors and perceived immediacy. In addition, attitudes toward online communication positively predict dissent. National culture influences some of these relationships; in each case the effects were substantively larger for the USA when compared to the other nations.Originality/valueThis study is the first to cross-culturally analyze dissent and immediacy. In addition, this study considers the extent to which the COVID-19 pandemic influences the superior–subordinate relationship.
The digital transformation of microfinance institutions: an empirical analysis
Authors: Dorfleitner Gregor , Forcella Davide , Nguyen Quynh Anh 
Published: September 2021

PurposeThis study seeks to identify the factors that are associated with the digital transformation of microfinance institutions (MFIs).Design/methodology/approachThe study employs probit models to investigate the likelihood of integrating digital solutions by MFIs and Heckman models for robustness checks.FindingsThe findings reveal that the adoption of these tools is consistent with the social performance of MFIs. Furthermore, the profitability of the institutions and their home country development are associated with a larger application of digital support solutions.Research limitations/implicationsSince the survey data collected is not longitudinal and does not cover many MFIs, it may encounter the absence of comprehensive results. Moreover, the study is limited to supply-side incentive factors, thus lacks of investigations under supply-demand interaction schemes. Therefore, future studies are encouraged to fill up these knowledge gaps.Practical implicationsThe results imply that the adoption of digital solutions does not necessarily harm the social performance of MFIs. In addition, the findings may imply that financial sustainability can serve as being a preliminary condition but must not lead to the mission drift of MFIs. Findings of the study have implications for policymakers, donors and investors who wish to accelerate the digital transformation within the microfinance industry and to significantly boost financial inclusion. A focus on more social-oriented MFIs can be an appropriate solution. Furthermore, the pathway to digital financial inclusion through microfinance can be made more efficient if improved and supportive facilities as well as systems for digital technology are available.Originality/valueThis paper is the first one which highlights the relationship between the MFI's social performance and the application of digital solutions by MFIs. Furthermore, we discuss this link while considering cost aspects.