Biology subjects

Aziz, A.

Publications and source records attributed to Aziz, A..

25 records · Page 2Linked to original sources

bioRxiv2020

Development of intra-oral automated landmark recognition (ALR) for dental and occlusal outcome measurements

Previous studies embracing digital technology and automated methods of scoring dental arch relationships have shown that such technology is valid and accurate. To date, however there is no published literature on artificial intelligence and machine learning to completely automate the process of dental landmark recognition. This study aimed to develop and evaluate a fully automated system and software tool for the identification of landmarks on human teeth using geometric computing, image segmenting and machine learning technology. 239 digital models were used in the automated landmark recognition (ALR) validation phase, 161 of which were digital models from cleft palate subjects aged 5 years. These were manually annotated to facilitate qualitative validation. Additionally, landmarks were placed on 20 adult digital models manually by three independent observers. The same models were subjected to scoring using the ALR software and the differences (in mm) were calculated. All the teeth from the 239 models were evaluated for correct recognition by the ALR with a breakdown to find which stages of the process caused the errors. The results revealed that 1526 out of 1915 teeth (79.7%) were correctly identified, and the accuracy validation gave 95% confidence intervals for the geometric mean error of [0.285, 0.317] for the humans and [0.269, 0.325] for ALR - a negligible difference. It is anticipated that ALR software tool will have applications throughout Dentistry and anthropology and in research will constitute an objective tool for handling large datasets without the need for time intensive employment of experts to place landmarks manually.

bioinformatics↗

bioRxiv2020

In vivo imaging of swimming micromotors using hybrid high-frequency ultrasound and photoacoustic imaging

The fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic (PA) tomography has shown to be promising for the imaging of microrobots in deep-tissue (ex vivo and in vivo), as it possesses the molecular specificity of optical techniques and the penetration depth of ultrasound imaging. However, the precise maneuvering and function control of microrobots, in particular in living organisms, demand the combination of both anatomical and functional imaging methods. Therefore, herein, we report the use of a hybrid High-Frequency Ultrasound (HFUS) and PA imaging system for the real-time tracking of magnetically driven micromotors (single and swarms) in phantoms, ex vivo, and in vivo (in mice bladder and uterus), envisioning their application for targeted drug-delivery.

bioengineering↗

bioRxiv2020

The gamma-Protocadherins regulate the survival of GABAergic interneurons during developmentally-regulated cell death.

Inhibitory interneurons integrate into developing circuits in specific ratios and distributions. In the cortex, the formation of inhibitory networks occurs concurrently with the apoptotic elimination of a third of GABAergic interneurons. The molecular mechanisms that select GABAergic interneurons to survive or die are unknown. Here we report that the clustered Protocadherins regulate GABAergic cell survival in the developing brain. Deletion of the Pcdh-gamma genes (Pcdhgs) from GABAergic neurons in mice causes a severe loss of inhibitory neurons in multiple brain regions and results in motor deficits and seizure activities. By focusing on the neocortex and cerebellar cortex, we demonstrate that GABAergic interneuron loss results from elevated apoptosis during the postnatal wave of Bax-dependent programmed cell death. Pro-survival AKT signals are reduced in Pcdhg-deficient interneurons, diminishing the intrinsic capacity of interneurons to compete and incorporate into developing networks. We propose that the Pcdhgs mediate selective GABAergic interneuron survival to contribute to the formation of balanced inhibitory networks.

neuroscience↗

bioRxiv2019

Bacteriophages can be used as infection control agents: A proof-of concept study involving anti-Acinetobacter baumannii phage

Hospital acquired infections are responsible for morbidity and mortality worldwide. Acinetobacter spp. infections are particularly notorious for complicating patient management in ICU settings. Extremely high mortality rates are associated with Acinetobacter infections because of their resistance to first- and second-line drugs. There is imminent need to develop infections control systems that are specific and environment friendly. Here, we report a proof-of-concept anti-Acinetobacter spp. bacteriophage-based infection control assay that is very target specific as well as innocuous to environment. extensively drug resistant (XDR) Acinetobacter baumannii strain was inoculated at various solid surfaces. A bacteriophage, enriched in the same strain, was applied on the inoculated surfaces. Phenol (carbolic acid) was used as a positive control. We show that bacteriophages can be used as infection control agents. In our assay, they killed XDR Acinetobacter baumannii present on solid surfaces. Our bacteriophage was extremely effective at reducing the CFU of inoculated strain to almost undetectable levels.

microbiology↗

bioRxiv2019

Comparative genomics confirms a rare melioidosis human-to-human transmission event and reveals incorrect phylogenomic reconstruction due to polyclonality

Human-to-human transmission of the melioidosis bacterium, Burkholderia pseudomallei, is exceedingly rare, with only a handful of suspected cases documented to date. Here, we used whole-genome sequencing (WGS) to characterise one such unusual B. pseudomallei transmission event, which occurred between a breastfeeding mother with mastitis and her child. Two strains corresponding to multilocus sequence types (STs) 259 and 261 were identified in the mothers sputum from both the primary culture sweep and in purified colonies, confirming an unusual polyclonal infection in this patient. In contrast, primary culture sweeps of the mothers breast milk and the childs cerebrospinal fluid and blood samples contained only ST-259, indicating monoclonal transmission to the child. Analysis of purified ST-259 isolates showed no genetic variation between mother and baby isolates, providing the strongest possible evidence of B. pseudomallei transmission, probably via breastfeeding. Next, phylogenomic analysis of all isolates, including the mothers mixed ST-259/261 sputum sample was performed to investigate the effects of mixtures on phylogenetic inference. Inclusion of this mixture caused a dramatic reduction in the number of informative SNPs, resulting in branch collapse of ST-259 and ST-261 isolates, and several instances of incorrect topology in a global B. pseudomallei phylogeny, resulting in phylogenetic incongruence. Although phylogenomics can provide clues about the presence of mixtures within WGS datasets, our results demonstrate that this methodology can lead to phylogenetic misinterpretation if mixed genomes are not correctly identified and omitted. Using current bioinformatic tools, we demonstrate a robust method for bacterial mixture identification and strain parsing that avoids these pitfalls.\n\nImpact StatementBurkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of high mortality. B. pseudomallei infections occur almost exclusively through contact with contaminated soil and water. Using whole-genome sequencing (WGS), we investigated a rare case of suspected B. pseudomallei transmission from mother to child. The mothers sputum, breast milk and the babys blood and cerebrospinal fluid (CSF) specimens were collected, and DNA was extracted from both pure colonies and primary culture sweeps to capture potential strain mixtures. In-depth analysis of genetic variants identified two strains in the mothers sputum belonging to multilocus sequence types ST-259 and ST-261, whereas the child was infected with only ST-259. Comparative genomics revealed no genetic differences between mother and child ST-259 isolates, providing the strongest possible evidence of transmission to the child via breast milk. The sputum strain mixture was subsequently used to develop a bioinformatic method for identification and quantification of mixtures from WGS data. Using this method, we found ST-259 and ST-261 at an 87%:13% ratio, respectively. Finally, we demonstrate the negative impact that even a single strain mixture event can have on both within-ST and global phylogenomic inferences. Our findings highlight the need for bioinformatic quality control to avoid unintended consequences of phylogenomic incongruence and branch collapse.\n\nData SummaryO_LIWhole-genome sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) and GenBank under BioProject accession number PRJNA559002.\nC_LIO_LIThe GenBank accession number for MSHR0643 assembly is VXLH00000000.1.\nC_LIO_LIThe SRA accession numbers for all raw sequence data are listed in Table 1.\nC_LI\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@c3b580org.highwire.dtl.DTLVardef@c11407org.highwire.dtl.DTLVardef@9e443org.highwire.dtl.DTLVardef@169014borg.highwire.dtl.DTLVardef@d4026c_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSummary of ST-259 and ST-261 Burkholderia pseudomallei isolates.\n\nC_TABLECAPTION C_TBL RepositoriesAll sequencing data generated as part of this study can be found under the NCBI BioProject PRJNA559002 with accession numbers listed in Table 1.

microbiology↗

bioRxiv2019

Real-time optoacoustic tracking of single moving micro-objects in deep tissue-mimicking phantoms

Medical imaging plays an important role in diagnosis and treatment of multiple diseases. It is a field under continuous development which seeks for improved sensitivity and spatiotemporal resolution to allow the dynamic monitoring of diverse biological processes that occur at the micro- and nanoscale. Emerging technologies for targeted diagnosis and therapy such as nanotherapeutics, micro-implants, catheters and small medical tools also need to be precisely located and monitored while performing their function inside the human body. In this work, we show for the first time the real-time tracking of moving single micro-objects below centimeter thick tissue-mimicking phantoms, using multispectral optoacoustic tomography (MSOT). This technique combines the advantages of ultrasound imaging regarding depth and resolution with the molecular specificity of optical methods, thereby facilitating the discrimination between the spectral signatures of the micro-objects from those of intrinsic tissue molecules. The resulting MSOT signal is further improved in terms of contrast and specificity by coating the micro-objects surface with gold nanorods, possessing a unique absorption spectrum, which will allow their discrimination from surrounding biological tissues when translated to in vivo settings.

biophysics↗

bioRxiv2019

Molecular signatures of non-typeable Haemophilus influenzae lung adaptation in paediatric chronic lung disease

Non-typeable Haemophilus influenzae (NTHi), an opportunistic pathogen of the upper airways of healthy children, can infect the lower airways, driving chronic lung disease. However, the molecular basis underpinning NTHi transition from a commensal to a pathogen is not clearly understood. Here, we performed comparative genomic and transcriptomic analyses of 12 paired, isogenic NTHi strains, isolated from the nasopharynx (NP) and bronchoalveolar lavage (BAL) of 11 children with chronic lung disease, to identify convergent molecular signatures associated with lung adaptation. Comparative genomic analyses of the 12 NP-BAL pairs demonstrated that five were genetically identical, with the remaining seven differing by only 1 to 3 mutations. Within-patient transcriptomic analyses identified between 2 and 58 differentially expressed genes in 8 of the 12 NP-BAL pairs, including pairs with no observable genomic changes. Whilst no convergence was observed at the gene level, functional enrichment analysis revealed significant under-representation of differentially expressed genes belonging to Coenzyme metabolism, Function unknown, Translation, ribosomal structure and biogenesis Cluster of Orthologous Groups categories. In contrast, Carbohydrate transport and metabolism, Cell motility and secretion, Intracellular trafficking and secretion, and Energy production categories were over-represented. This observed trend amongst genetically-unrelated NTHi strains provides evidence of convergent transcriptional adaptation of NTHi to paediatric airways that deserves further exploration. Understanding the pathoadaptative mechanisms that NTHi employs to infect and persist in the lower paediatric airways is essential for devising targeted diagnostics and treatments aimed at minimising disease severity, and ultimately, preventing NTHi lung infections and subsequent chronic lung disease in children.

microbiology↗