1,720,984 research outputs found
Investigating the effect of PAX6 haploinsufficiency on neuronal projections using human cerebral assembloids
No full textInter- and intra-hemispheric communication in the cerebral cortex relies on axons. PAX6 is a crucial transcription factor for axon development, and its haploinsufficiency leads to defects in inter-hemispheric structures like the corpus callosum. This structure forms from SATB2-expressing cells, with Pax6 influencing their specification in mice.
We investigated the impact of PAX6 haploinsufficiency on human iPS cell-derived cerebral assembloids. Using a 3D-printed device, we established a method to generate these assembloids, optimised the RatDISCO protocol for assembloid imaging using 3D light sheet microscopy, and used AAV-hSyn-EGFP to visualise projections.
In our comparison, PAX6⁺/⁻ organoids showed a transient increase in SATB2- expressing cells at day 90, returning to control levels by day 120, indicating a role for PAX6 in age-dependent SATB2 specification. Tracing projections revealed only local extensions, with preliminary data indicating no morphological differences between genotypes. These findings suggested that PAX6 has a role in SATB2 specification, but a partial loss of PAX6 likely did not affect the morphology of neuronal projections
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Removal of Pax6 from cortical progenitors renders them abnormally likely to switch fate in response to Sonic Hedgehog activity
Get PDFThe paired-box protein PAX6 is a transcription factor that acts as a master regulator during neurodevelopment. In mice, it is expressed by neural progenitors in the cortical ventricular zone (VZ) where it regulates neurogenesis and fate specification. The complex processes of neurodevelopment are also regulated by morphogens such as Sonic Hedgehog (Shh) that promotes ventralization of the ventral telencephalon (vTel), through diffusion to form a concentration gradient.
Strikingly, when Pax6 is deleted, a subset of cortical progenitor cells that would normally become glutamatergic commit into a GABAergic fate, expressing ventral markers such as Gad67, Gsx2 and Dlx1. Previous studies have shown that when wild-type cortical cells are treated with substances that activates Shh signalling, they can be made to express genes such as Gsx2 which are associated with the generation of interneurons. Based on these findings, we asked what makes cortical progenitor cells change their fate when Pax6 is deleted? This study aimed to investigate the sensitivity of cortical progenitor cells in Pax6 mutant mice to Shh signalling.
In the present study, we used Pax6-floxed (Pax6fl/fl) mutant mice expressing a tamoxifen-inducible form of Cre recombinase under the control of the Emx1 locus (Emx1-CreERT2) and an EGFP reporter construct. Cultured cortical progenitors were exposed to increasing concentrations of Shh agonist, developed for the protein Smoothened (SAG), which is a key part of the activation of Hedgehog signalling pathway. Results showed significant increases of Gsx2+, Dlx1+ Olig2+ cells in parallel with the increase of Shh agonist concentrations. We also investigated the possibility that these cells matured into interneurons (INs) after exposure to SAG, if they do have electrical properties akin to specific type of INs.
Our finding suggests that morphogens such as Shh exert a ventralizing effect on cortical progenitors, and Pax6 is required to resist such an effect in order to safeguard glutamatergic fate. These cells also have the potential to develop into a subtype of IN when exposed to SAG
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Parametric Study On The Effectiveness Of A Novel Flat Truss Shape Punching Shear Reinforcement Using Finite Element Model
Get PDFThis research aims to gain understanding of the behaviour of a slab-column model in terms of deformation and stress in the steel reinforcement when subjected to force at
the top column surface. The intention is to simulate the punching shear failure of a flat slab in a building using ANSYS Static Structure R14 software. The context of this study is the prevention of punching failure by addition of novel flat truss shaped punching shear reinforcement (FTSPSR) and the effect of varying the number of segments in a truss to the punching behaviour of the slab. A total of five models were constructed for this study.
A validation work using ANSYS model (M1) with slab dimension 1050 mm x 1050 mm x 100 mm against past experimental data exhibited good agreement and the overall percentage difference was calculated to be less than 20 %. In order to accommodate the FTSPSR, the thickness of the slab was increased to 150 mm (model M2). The slab-column model having FTSPSR with four segments (model M3) reduced the maximum
deflection by approximately 6.02 % compared to model M2. Moreover, the maximum rebar stress at highest applied load was 2.81 % lesser than that of M2. It was also noted
that incorporating more truss segment FTSPSR increased the stiffness of the model. This phenomenon is particularly true for model M4 (five segments) and model M5 (six segments) because the maximum deflection was reduced by 5.33 % and 10.57 % respectively for model M4 and M5 compared to model M3. Meanwhile, the maximum rebar stress reduced by 8.19 % and further to 13.01 % for model M4 and M5 respectively
when compared to model M3. It can be concluded that the novel FTSPSR has the potential to be used in flat slab construction
Zeolite membrane reactor for treating endocrine disrupting compounds in water
No full textAn advanced ozone membrane reactor was employed for treating endocrine disrupting compounds (EDCs) in water as they survived in state of the art water treatment processes. A reactor which combined ozone oxidation and membrane separation is designed for treating EDCs. Potassium hydrogen phthalate (KHP) was selected as the model pollutant since it is refractory and has a small molecular size. 1.5 μm thick ZSM-5 zeolite membrane was used because of its high chemical tolerance, good water permeability and excellent selectivity. The reactor removed 100 % of KHP and 83 % of TOC at 7.5 minutes residence time by feeding 250 ppmC KHP. The TOC removal enhancement was 64 % higher for ozonation alone and permeated clean water (TOC < 2 ppmC) continuously. Similar performances were observed for diclofenac sodium, carbamazepine and caffeine in which 100 % EDCs removal could be achieved within 2 minutes of treatment. In additions, powder activated carbon and hydrotalcite (Mg/Al =3) were successfully coated on the α-alumina support, serving as the contactor for catalytic ozone treatment. However, those adsorbents did not have observable catalytic effect on KHP but influence of the performance of the reactor. Hydrotalcite-coated ZSM-5 membrane showed a strong adsorption of organic acids within the support and enhanced the development of concentration polarization which lowered the permeate flux. Even the hydrotalcite coating has negative influence on treating KHP, it is thought to be capable of enhancing performance when treating positively charged carrying species.</p
Role of differential heparan sulphate sulphation in Fgf/Erk signalling during mouse telencephalic development
Get PDFHeparan sulphate proteoglycans (HSPGs) are cell surface/secreted molecules
expressed by all cells. HSPGs consist of carbohydrate side-chains attached to a core
protein and are involved in regulating key signalling pathways in the developing
mammalian brain via sugar-protein interactions. It has been hypothesized, in the
‘heparan sulphate (HS) code hypothesis’, that the specificity for the interaction
between the HSPGs and particular signalling pathways is encoded by its HS side-chain.
HS has an enormous variety of structures due to postsynthetic modification.
Hs2st and Hs6st1 are enzymes involved in generating different HS structures by
sulphating the 2-carbon or 6-carbon molecule of the sugar backbone respectively.
Fibroblast growth factors (Fgfs) are a family of signalling molecules crucial for
forebrain development. Some of its members such as Fgf8 are morphogens which
pattern the forebrain via regulated gradient formation while others such as Fgf2 drive
neurogenesis and cell proliferation. One of the main molecular consequences of Fgf
signalling is activation of extracellular signal-regulated kinase (Erk) where the
activation of Erk then drives developmental events such as neurogenesis or cell
migration.
Based on previous studies on the HS code hypothesis, we hypothesized that
differential sulphation regulates Fgf signalling in a specific manner depending on the
HS sulphation pattern. We performed binding assays on Hs2st-/- mice to ascertain the
molecular mechanism behind the role of differential sulphation in Erk signalling
through Fgf2 in the forebrain. We found that differential sulphation also has an
important role to play in regionally targeting Fgf2/Erk signalling through regulating
the formation of active signalling complexes.
Studying the Fgf8/Erk signalling axis at E14.5 developing mouse corticoseptal
boundary (CSB) revealed increased Fgf8 levels and Erk hyperactivation in both
Hs2st and Hs6st1 null mutants. The dysregulation of Fgf8/Erk signalling at the CSB
also highly correlates with the high expression of Hs2st and Hs6st1 at the CSB. A
closer look into the molecular phenotypes of Hs2st-/- and Hs6st1-/- CSB revealed
differences between them in which Hs6st1-/- CSB has higher Fgf8 levels compared to
Hs2st-/- CSB.
To elucidate the mechanisms underlying Hs2st and Hs6st1 role at the CSB, we
investigated the formation and interpretation of Fgf8/Erk signalling gradient using
Fgf8 bead assays in mice with Hs2st and Hs6st1 loss of function throughout
development. We found that differential sulphation has a complex effect on Fgf8
gradient formation and interpretation in the forebrain in which Hs2st acts to stabilise
the Fgf8 distribution through regulating Fgf8 levels through time while Hs6st1 acts
to stabilise the Fgf8 distribution by maintaining the shape of the Fgf8 gradient
through restricting Fgf8 levels during the formation of the Fgf8 distribution. In
addition, we found Hs2st and Hs6st1 both function to increase the sensitivity of the
CSB to Fgf8 for an Erk response although through different modes of action.
Therefore, we conclude that differential HS sulphation plays a specific role in
Fgf/Erk signalling depending on the HS sulphation pattern
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