Anterior Hippocampus and Goal-Directed Spatial Decision Making

Contains fulltext : 115487.pdf (publisher's version ) (Open Access

Investigation of the effect of PD-L1 blockade on triple negative breast cancer cells using fourier transform infrared spectroscopy

Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In this study, we investigated the biochemical changes in MDA-MB-231 cells following treatment with atezolizumab, a specific PD-L1 blocker. Our readouts were Fourier Transform Infrared (FTIR) spectroscopy and flow cytometric analyses. Chemometrical analysis, such as principal component analysis (PCA), was applied to delineate the spectral differences. We were able to identify the chemical alterations in both protein and lipid structure of the treated cells. We found that there was a shift from random coil and ?-helical structure to ?-sheet conformation of PD-L1 on tumor cells due to atezolizumab treatment, which could hinder binding with its receptors on immune cells, ensuring sustained T cell activation for potent immune responses. This work provides novel information about the effects of atezolizumab at molecular and cellular levels. FTIR bio-spectroscopy, in combination with chemometric analyses, may expedite research and offer new approaches for cancer immunology. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Department of Chemistry and Earth Sciences, Qatar University (QU), P.O. Box 2713 Doha, Qatar Qatar Computing Research Institute, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Qatar Environment & Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box 34110 Doha, Qatar Correspondence: [email protected] (M.H.M.A.); [email protected] (E.E.

Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism

BACKGROUND: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. METHODS: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. RESULTS: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. CONCLUSION: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype

Cloning, purification and preliminary X-ray data analysis of the human ID2 homodimer

10.1107/S174430911203895XActa Crystallographica Section F: Structural Biology and Crystallization Communications68111354-135

Androgen receptor mutations causing human androgen insensitivity syndromes show a key role of residue M807 in helix 8-helix 10 interactions and in receptor ligand-binding domain stability

Molecular Human Reproduction82101-108MHRE

Crystallization and preliminary crystallographic study of stonustoxin, a protein lethal factor isolated from the stonefish (Synanceja horrida) venom

10.1006/jsbi.1999.4193Journal of Structural Biology1282216-218JSBI

Nonrandom Intragenic Variations in Patterns of Codon Bias Implicate a Sequential Interplay between Transitional Genetic Drift and Functional Amino Acid Selection

10.1007/s00239-003-2507-5Journal of Molecular Evolution575538-545JMEV

Towards the MHC-peptide combinatorics

10.1016/S0198-8859(01)00219-1Human Immunology625539-556HUIM

A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators

10.1371/journal.pone.0048591PLoS ONE710

Purpureotin: A novel di-dimeric C-type lectin-like protein from Trimeresurus purpureomaculatus venom is stabilized by noncovalent interactions

10.1016/j.abb.2004.01.015Archives of Biochemistry and Biophysics424153-62ABBI