Publications by authors named "H A Jacob"

988 Publications

Thermal, structural, antimicrobial, and physicochemical characterisation of thyme essential oil encapsulated in β- and γ-cyclodextrin.

J Microencapsul 2022 Jun 24;39(4):364-379. Epub 2022 Jun 24.

Energy and Building Research Center, Kuwait Institute for Scientific Research, Safat, Kuwait.

The present work aimed to encapsulate the thyme essential oil (TEO) in β-cyclodextrin (BCD) and γ-cyclodextrin (GCD) complexes in two selected cyclodextrin (CD) to TEO ratios (85/15 and 80/20 w/w) and compare the physicochemical, antioxidant, and antimicrobial properties of the encapsulated powders. The inclusion complexes between CD and TEO were prepared by blending aqueous CD and TEO in ethanol followed by freeze-drying. The powder properties were assessed by measuring particle size and microstructure using SEM, FTIR, and XRD. The median values of the particle sizes (GCD: 92.0 ± 4.69 and BCD: 46.2 ± 2.56-mm) significantly influenced the encapsulation efficiency, resulting in a higher encapsulation efficiency of the GCD (92.02 ± 10.79%) than that of the BCD (56.30 ± 12.19%). The encapsulated GCD/TEO (80/20) showed higher antioxidant activity and an antimicrobial inhibitory effect against and sv. . Overall, the GCD acts as a superior wall material to the BCD in the TEO encapsulation.
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http://dx.doi.org/10.1080/02652048.2022.2090626DOI Listing
June 2022

Correlates of individual voice and face preferential responses during resting state.

Sci Rep 2022 05 3;12(1):7117. Epub 2022 May 3.

Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health (TüCMH), University of Tübingen, Calwerstrasse 14, 72076, Tübingen, Germany.

Human nonverbal social signals are transmitted to a large extent by vocal and facial cues. The prominent importance of these cues is reflected in specialized cerebral regions which preferentially respond to these stimuli, e.g. the temporal voice area (TVA) for human voices and the fusiform face area (FFA) for human faces. But it remained up to date unknown whether there are respective specializations during resting state, i.e. in the absence of any cues, and if so, whether these representations share neural substrates across sensory modalities. In the present study, resting state functional connectivity (RSFC) as well as voice- and face-preferential activations were analysed from functional magnetic resonance imaging (fMRI) data sets of 60 healthy individuals. Data analysis comprised seed-based analyses using the TVA and FFA as regions of interest (ROIs) as well as multi voxel pattern analyses (MVPA). Using the face- and voice-preferential responses of the FFA and TVA as regressors, we identified several correlating clusters during resting state spread across frontal, temporal, parietal and occipital regions. Using these regions as seeds, characteristic and distinct network patterns were apparent with a predominantly convergent pattern for the bilateral TVAs whereas a largely divergent pattern was observed for the bilateral FFAs. One region in the anterior medial frontal cortex displayed a maximum of supramodal convergence of informative connectivity patterns reflecting voice- and face-preferential responses of both TVAs and the right FFA, pointing to shared neural resources in supramodal voice and face processing. The association of individual voice- and face-preferential neural activity with resting state connectivity patterns may support the perspective of a network function of the brain beyond an activation of specialized regions.
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http://dx.doi.org/10.1038/s41598-022-11367-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065073PMC
May 2022

The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.

BMC Med Genomics 2022 04 1;15(1):74. Epub 2022 Apr 1.

Genomics Research Center, AbbVie Inc, North Chicago, Illinois, 60064, USA.

Background: The remarkable growth of genome-wide association studies (GWAS) has created a critical need to experimentally validate the disease-associated variants, 90% of which involve non-coding variants.

Methods: To determine how the field is addressing this urgent need, we performed a comprehensive literature review identifying 36,676 articles. These were reduced to 1454 articles through a set of filters using natural language processing and ontology-based text-mining. This was followed by manual curation and cross-referencing against the GWAS catalog, yielding a final set of 286 articles.

Results: We identified 309 experimentally validated non-coding GWAS variants, regulating 252 genes across 130 human disease traits. These variants covered a variety of regulatory mechanisms. Interestingly, 70% (215/309) acted through cis-regulatory elements, with the remaining through promoters (22%, 70/309) or non-coding RNAs (8%, 24/309). Several validation approaches were utilized in these studies, including gene expression (n = 272), transcription factor binding (n = 175), reporter assays (n = 171), in vivo models (n = 104), genome editing (n = 96) and chromatin interaction (n = 33).

Conclusions: This review of the literature is the first to systematically evaluate the status and the landscape of experimentation being used to validate non-coding GWAS-identified variants. Our results clearly underscore the multifaceted approach needed for experimental validation, have practical implications on variant prioritization and considerations of target gene nomination. While the field has a long way to go to validate the thousands of GWAS associations, we show that progress is being made and provide exemplars of validation studies covering a wide variety of mechanisms, target genes, and disease areas.
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http://dx.doi.org/10.1186/s12920-022-01216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973751PMC
April 2022

KSR induces RAS-independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors.

Mol Oncol 2022 Mar 21. Epub 2022 Mar 21.

Experimental Oncology, Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.

The kinase suppressor of rat sarcoma (RAS) proteins (KSR1 and KSR2) have long been considered as scaffolding proteins required for optimal mitogen-activated protein kinase (MAPK) pathway signalling. However, recent evidence suggests that they play a more complex role within this pathway. Here, we demonstrate that ectopic expression of KSR1 or KSR2 is sufficient to activate the MAPK pathway and to induce cell proliferation in the absence of RAS proteins. In contrast, the ectopic expression of KSR proteins is not sufficient to induce cell proliferation in the absence of either rapidly accelerated fibrosarcoma (RAF) or MAPK-ERK kinase proteins, indicating that they act upstream of RAF. Indeed, KSR1 requires dimerization with at least one member of the RAF family to stimulate proliferation, an event that results in the translocation of the heterodimerized RAF protein to the cell membrane. Mutations in the conserved aspartic acid-phenylalanine-glycine motif of KSR1 that affect ATP binding impair the induction of cell proliferation. We also show that increased expression levels of KSR1 decrease the responsiveness to the KRAS inhibitor sotorasib in human cancer cell lines, thus suggesting that increased levels of expression of KSR may make tumour cells less dependent on KRAS oncogenic signalling.
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http://dx.doi.org/10.1002/1878-0261.13213DOI Listing
March 2022

Clinical feasibility evaluation of digital dental articulation for three-piece maxillary orthognathic surgery: a proof-of-concept study.

Int J Oral Maxillofac Surg 2022 Aug 17;51(8):1043-1049. Epub 2022 Feb 17.

Department of Oral and Maxillofacial Surgery, Houston Methodist, Houston, TX, USA; Department of Surgery (Oral and Maxillofacial Surgery), Weill Medical College, Cornell University, New York, NY, USA. Electronic address:

Digital dental articulation for three-piece maxillary orthognathic surgery is challenging. The purpose of this proof-of-concept study was to evaluate the clinical feasibility of a newly developed mathematical algorithm to digitally establish the final occlusion for three-piece maxillary surgery. Five patients with jaw deformities who had undergone a three-piece double-jaw surgery that was planned virtually were randomly selected for this study. The final occlusion had been hand-articulated using stone casts, scanned into the computer and used in the surgery. These hand-articulated occlusions served as the control group. To form the experimental group, the three-piece maxillary dental arch was articulated again automatically from the patient's original occlusion using the mathematical algorithm. The hand- and algorithm-articulated occlusions were then evaluated qualitatively by two experienced orthodontists. A quantitative evaluation was also performed. The results of the qualitative evaluation showed that all of the three-piece occlusions, hand- and algorithm-articulated, were clinically acceptable based on the American Board of Orthodontics grading system. When compared, two of the algorithm-articulated occlusions were clearly better (40%), one was the same (20%), and two were slightly worse (40%) than the hand-articulated occlusions. All of the quantitative measurements were comparable between the two articulation methods. In conclusion, the results of this study demonstrate that it is clinically feasible to digitally articulate the three-piece maxillary arch to the intact mandibular dental arch.
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http://dx.doi.org/10.1016/j.ijom.2022.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253058PMC
August 2022
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