Biology subjects

Farooq, U.

Publications and source records attributed to Farooq, U..

7 recordsLinked to original sources

bioRxiv2023

Geometric experience sculpts the development and dynamics of hippocampal sequential cell assemblies

Euclidean space is the fabric of the world we live in. Whether and how geometric experience shapes our spatial-temporal representations of the world remained unknown. We deprived rats of experience with crucial features of Euclidean geometry by rearing them inside translucent spheres, and compared activity of large hippocampal neuronal ensembles during navigation and sleep with that of cuboid cage-reared controls. Sphere-rearing from birth permitted emergence of accurate neuronal ensemble spatial codes and preconfigured and plastic time-compressed neuronal sequences. However, sphere-rearing led to diminished individual place cell tuning, similar neuronal mapping of different track ends/corners, and impaired neuronal pattern separation and plasticity of multiple linear track experiences, partly driven by reduced preconfigured network repertoires. Subsequent experience with multiple linear environments over four days largely reversed these effects, substantiating the role of geometric experience on hippocampal neural development. Thus, early-life experience with Euclidean geometry enriches the hippocampal repertoire of preconfigured neuronal patterns selected toward unique representation and discrimination of multiple linear environments.

neuroscience↗

bioRxiv2023

Diagnostic efficacy of hand-held digital refractometer for determining total serum protein in indigenous sheep of Pakistan

The study was designed to ascertain the diagnostic efficacy of hand-held digital refractometer in determining total protein. The Sipli sheep (n=141) were grouped as per gender (females=99, males=29) and age (G1=up till 1 year, G2=from 1 to 2 years, G3=above 2 years). The results regarding the overall mean ({+/-}SE) values and RIs for the TPs attained through serum chemistry analyzer (TP1) and hand-held digital refractometer (TP2) were non-significantly (P[≤]0.05) different (59.2{+/-}1.6g/L and 59.8{+/-}0.5g/L, respectively). However, the RIs were quite different between the two TPs being 45.1-95.7g/L and 57.0-67.0g/L for TP1 and TP2, respectively. Similar results were seen for gender-wise and group-wise results. On the contrary, the results regarding correlation coefficient and logilinear regression showed a negative correlation between the two TPs (r=-0.0244) with an adjusted r-square of 0.059 (5.9% probability). Furthermore, the results for Cronbach alpha and intraclass correlation coefficient between TP1 and TP2 showed that the values for single measure and average values were lower between TP1 and TP2 being - 0.135 and -0.313. Bland and Altman test between TP1 and TP2 also showed a weak level of agreement between the two methods of detecting TP. A proportional bias on the distribution of data around the mean difference line was noticed between TP1 and TP2 (Mean= 0.5; 95% CI= 39.8 to -40.9) with a standard deviation of biasness being 20.58. In a nutshell, the hand-held digital refractometer cannot be used as an on-farm POCT device for determining serum TP in sheep. However, certain other models of refractometers with higher sensitivity and specificity may be utilized in future studies to establish these conclusions for other species of livestock.

zoology↗

bioRxiv2023

Unravelling the anticancer and enzyme inhibition potential of different classes of compounds including a new steroid, isolated from Cassia mimosoïdes

The genus Cassia is a significant source of secondary metabolites that are physiologically active and come from several chemical classes. The current research deals with the isolation, spectroscopic elucidation (1D and 2D NMR spectroscopy) and enzymatic activity of fifteen known compounds as well as a new unidentified avenasterol derivative namely 21-methylene-24-ethylidene lophenol. The urease and {beta}-glucosidase inhibitory effects of these compounds were studied for the first time, and molecular docking studies were also performed to verify the structure-activity relationships. All the compounds evaluated towards urease showed higher inhibitory activity (1.224{+/-}0.43 < IC50 > 6.678{+/-}0.11 M) compared to standard thiourea (IC50 = 18.61{+/-}0.11 M). Molecular docking results revealed that compound 7 strongly inhibits urease due to the formation of a stable ligand-urease complex via hydrogen bonding, van der Waal and hydrophobic interactions. Formation of a favourable complex of 7 with the target enzyme gave a more negative docking score (-6.95 kcal/mol) than that of thiourea (-3.13 kcal/mol). Regarding the {beta}-glucosidase enzyme, all the compounds evaluated did not show activity except compound 1 which inhibited the latter with a percentage of inhibition of 82.6. These findings imply that this plant may be a contender for developing novel treatments for infectious disorders brought on by urease-producing bacteria.

biochemistry↗

bioRxiv2022

A study on packed cell volume for deducing hemoglobin: Cholistani camels in perspective

In human medical practice, a hematological rule of three has been validated for healthy human populations. One such formula is estimating hemoglobin (Hb) levels as 1/3rd of Packed Cell Volume (PCV). However, no such hematological formulae have been devised and validated for veterinary medical practice. The present study was devised with an aim to evaluate the relationship between hemoglobin (Hb) concentration and Packed Cell Volume (PCV) in camels (n=215) being reared under pastoralism, and to devise a simple pen-side hematological formula for estimation of Hb from PCV. The PCV was determined through microhematocrit method whereas Hb estimation by cyanmethaemoglobin method (HbD). The Hb was also calculated as 1/3rd of PCV and was dubbed as calculated Hb (HbC). Overall HbD and HbC were significantly (P[≥]0.05) different. Similar results were attained for all study groups i.e. males (n=94) and females (n=121), and young (n=85) and adult (n=130) camels. The corrected Hb (CHb) was deduced through regression prediction equation attained from linear regression model. Scatter-plots were drawn, linear regression was carried out, and Bland Altman chart was built for agreement of both methods of Hb estimation. A non-significant (P[≥]0.05) difference was noticed between HbD and CHb. Bland Altman chart revealed good agreement between HbD and CHb and there was no proportional bias on the distribution of data around the mean difference line (Mean= 0.1436, 95% CI= 3.00, -2.72). We accordingly recommend a simplified pen-side hematological formula for deducing Hb concentration from PCV viz. Hb concentration (g/dL)=0.18(PCV)+5.4 for all age and gender groups of camels instead of its calculation as one-third of PCV.

physiology↗

bioRxiv2021

Active enhancers strengthen TAD insulation by bRNA mediated CTCF enrichment at the TAD boundaries

Vertebrate genomes are partitioned into Topologically Associating Domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at TAD boundaries correlates with better insulation, however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant INK4a/ARF TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer:promoter interactions and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters we show that active TAD enhancers but not promoters induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.

genomics↗

bioRxiv2019

Ligand dependent gene regulation by transient ER clustered enhancers

Unliganded nuclear receptors have been implicated in ligand-dependent gene regulation. However, the underlying mechanisms are not fully understood. Here we demonstrate that unliganded ER binds to specific sites in the genome thereby pre-marking them as future functional enhancers. Upon ligand exposure, ER binds to several EREs relatively proximal to the pre-marked, or persistent, ER-bound sites. Interestingly, the persistent sites interact extensively, via chromatin looping, with the proximal transiently bound sites forming ER clustered enhancers in 3D. CRISPR-based deletion of TFF1 persistent site disrupts the formation of its clustered enhancer resulting in the loss of E2-dependent induced expression of TFF1 and its neighboring genes within the same cluster. The clustered enhancers overlap with nuclear ER puncta that coalesce in a ligand-dependent manner. Furthermore, formation of clustered enhancers, as well as puncta, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ER. Our results establish the role of persistent unliganded ER binding in priming enhancer clusters in 3D that drive transient, but robust, gene expression in a ligand-dependent fashion.

molecular biology↗

bioRxiv2018

AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL

Microtubule associated serine threonine like kinase (MASTL) has been recently identified as an important regulator of mitosis. By inhibiting protein phosphatase 2A, it plays a crucial role in activating one of the most important mitotic kinases known as cyclin dependent kinase1 (CDK1). MASTL has been seen to be up regulated in various types of cancers and is involved in tumor recurrence. It is activated by CDK1 through its auto regulatory loop but the complete mechanism of its activation is still unclear. In this study, we evaluated the regulation of MASTL via AKT during mitosis. Here we report that AKT phosphorylates MASTL at T299 which plays a critical role in its activation. Our results suggest that AKT increases CDK1 mediated phosphorylation and hence activity of MASTL which in turn promotes cell proliferation.. We also show that the oncogenic potential of AKT is augmented by MASTL activation as the AKT mediated oncogenesis in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT has an important role in the progression of mitosis in mammalian cells and it does so through the phosphorylation and activation of MASTL.

cancer biology↗