Publications by authors named "Farhan Ali"

68 Publications

Plasticity and domestication of root anatomy in maize-teosinte derived population.

J Exp Bot 2021 Sep 6. Epub 2021 Sep 6.

College of Resources and Environmental Sciences, National Academy of Agriculture Green Development, Key Laboratory of Plant-Soil Interactions of MOE, China Agricultural University, Beijing, 100193, China.

Maize (Zea mays L.) underwent profound changes during domestication in root anatomy for environmental adaptation. However, the genetic mechanism of maize root anatomy domestication and plasticity remains unclear. In this study, a high-resolution mapping was performed for nine root anatomical traits using a maize-teosinte population (mexicana × Mo17) across three environments. Large genetic variations were detected for different root anatomical traits. The cortex area, stele area, aerenchyma area, xylem vessels number and cortical cell number had large variations across three environments, indicating high plasticity. Sixteen quantitative trait loci (QTL) were identified, including seven QTL with QTL × Environment interaction (EIQTL) for high plastic traits and nine QTL without QTL × Environment interaction (SQTL). Most of the root loci were consistent with shoot QTL depicting domestication signals. Combining transcriptome and genome-wide association study (GWAS) revealed that ZmPILS4 serve as a candidate gene underlying a major QTL of xylem traits. The near-isogenic lines (NILs) with lower expression of ZmPILS4 had 18-24% more IAA concentration in the root tip and 8-15% more xylem vessels. Significant domestication signal in promoter region suggested that ZmPILS4 was involved in maize domestication and adaptation. These results divulged the potential genetic basis of root anatomy plasticity and domestication.
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http://dx.doi.org/10.1093/jxb/erab406DOI Listing
September 2021

Case report of a female child with right nasal chondromyxoid fibroma.

J Pak Med Assoc 2021 Jul;71(7):1897-1899

Department of Histopathology, Dow University of Health Sciences, Karachi, Pakistan.

Chondromyxoid fibroma is a rare tumour, representing <1% of all primary bone neoplasm. We report the case of a four-year-old female child with a one-year history of nasal obstruction and facial swelling. A large enhanced lesion with amorphous densities spreading into the right cribriform plate and floor of sphenoid sinus, laterally into the right lamina papyracea, inferolaterally into the medial wall of maxillary sinus, posteriorly into the nasopharynx and superior aspect of oropharynx was observed on CT scan. The mass was excised by Caldwell Luc's endoscopic medial maxillectomy via sublabial approach. CMF was confirmed histopathologically.
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http://dx.doi.org/10.47391/JPMA.720DOI Listing
July 2021

Environmental friendly sustainable application of plant-based mordants for cotton dyeing using Arjun bark-based natural colorant.

Environ Sci Pollut Res Int 2021 May 27. Epub 2021 May 27.

Applied Chemistry Research Centre, PCSIR Laboratories Complex, Ferozepur Road, Lahore, Pakistan.

Ecofriendly exploration of Arjun bark (Terminalia arjuna) is a herbal natural colorant for cotton dyeing. This is because the demand for natural dyes has been increased worldwide due to their therapeutic usage and other food, textiles, agriculture, engineering, and medical applications. Therefore, this study has been carried out due to the isolation of colorant from Arjun bark in an acidified methanolic medium after exposure to ultrasonic rays up to 60 min. Additionally, using bio-mordants, it has been found that the application of 10% of Zeera (Cuminum cyminum) extract as meta-bio-mordant, 3% of Ilaichi (Elettaria cardamomum) extract as meta-bio-mordant, and10 % of Harmal (Peganum harmala) and Neem (Azadirachta indica) extract as meta-bio-mordants has given excellent color strength. These bio-mordants have not only made the coloration process more eco-friendly, viable, and greener, but also improved color strength with various tonal effects from red to reddish brown shades. Thus, it has been found that ultrasonic treatment as an environment-friendly tool has not only enhanced the color strength of natural colorant isolated from Arjun bark onto the cotton fabric under mild conditions.
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http://dx.doi.org/10.1007/s11356-021-14536-8DOI Listing
May 2021

Docking analysis for identification of lead compound and 3d pharmacophore generation against gsk-3β involved in bipolar disorder.

Pak J Pharm Sci 2020 Nov;33(6):2547-2552

Department of Biosciences, Comsats Institute of Information Technology, Sahiwal, Pakistan.

Bipolar disorder is a psychiatric illness that strikes between mania and depression, caused by both genetic and environmental factors. It is the sixth leading cause of disability worldwide and 3% of the global population suffers from this disorder. Focusing on the drugs used for psychotherapy and their associated side effects, there is a need to design and develop new anti-bipolar drugs with lesser side effects and improved efficacy. Molecular docking and pharmacophore modeling were performed to identify lead and the construction of pharmacophore triangle. One compound demonstrated best docking results that fit appropriately in the pocket of protein. In this study, an efficient compound for GSK-3B involved in bipolar disorder was identified through docking analysis. Distances were calculated among pharmacophore features like Aromatic Ring, Hydrophobic, HBD and HBA. Pharmacophore triangle was designed for three different classes that are Aromatic, HBD and HBA. This pharmacophore modeling can be useful for designing of novel drugs because this 3D pharmacophore showed best merging properties.
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November 2020

Computational Method for Classification of Avian Influenza A Virus Using DNA Sequence Information and Physicochemical Properties.

Front Genet 2021 28;12:599321. Epub 2021 Jan 28.

State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Accurate and fast characterization of the subtype sequences of Avian influenza A virus (AIAV) hemagglutinin (HA) and neuraminidase (NA) depends on expanding diagnostic services and is embedded in molecular epidemiological studies. A new approach for classifying the AIAV sequences of the HA and NA genes into subtypes using DNA sequence data and physicochemical properties is proposed. This method simply requires unaligned, full-length, or partial sequences of HA or NA DNA as input. It allows for quick and highly accurate assignments of HA sequences to subtypes H1-H16 and NA sequences to subtypes N1-N9. For feature extraction, k-gram, discrete wavelet transformation, and multivariate mutual information were used, and different classifiers were trained for prediction. Four different classifiers, Naïve Bayes, Support Vector Machine (SVM), K nearest neighbor (KNN), and Decision Tree, were compared using our feature selection method. This comparison is based on the 30% dataset separated from the original dataset for testing purposes. Among the four classifiers, Decision Tree was the best, and Precision, Recall, F1 score, and Accuracy were 0.9514, 0.9535, 0.9524, and 0.9571, respectively. Decision Tree had considerable improvements over the other three classifiers using our method. Results show that the proposed feature selection method, when trained with a Decision Tree classifier, gives the best results for accurate prediction of the AIAV subtype.
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http://dx.doi.org/10.3389/fgene.2021.599321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877484PMC
January 2021

A hybrid broadband metalens operating at ultraviolet frequencies.

Sci Rep 2021 Jan 27;11(1):2303. Epub 2021 Jan 27.

Department of Physics, Koc University, 34450, Istanbul, Turkey.

The investigation on metalenses have been rapidly developing, aiming to bring compact optical devices with superior properties to the market. Realizing miniature optics at the UV frequency range in particular has been challenging as the available transparent materials have limited range of dielectric constants. In this work we introduce a low absorption loss and low refractive index dielectric material magnesium oxide, MgO, as an ideal candidate for metalenses operating at UV frequencies. We theoretically investigate metalens designs capable of efficient focusing over a broad UV frequency range (200-400 nm). The presented metalenses are composed of sub-wavelength MgO nanoblocks, and characterized according to the geometric Pancharatnam-Berry phase method using FDTD method. The presented broadband metalenses can focus the incident UV light on tight focal spots (182 nm) with high numerical aperture ([Formula: see text]). The polarization conversion efficiency of the metalens unit cell and focusing efficiency of the total metalens are calculated to be as high as 94%, the best value reported in UV range so far. In addition, the metalens unit cell can be hybridized to enable lensing at multiple polarization states. The presented highly efficient MgO metalenses can play a vital role in the development of UV nanophotonic systems and could pave the way towards the world of miniaturization.
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http://dx.doi.org/10.1038/s41598-021-81956-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840775PMC
January 2021

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy.

Pharmacotherapy 2021 02 7;41(2):205-211. Epub 2021 Feb 7.

Department of Pharmacy Practice and Science, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.

Background And Objectives: Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations.

Methods: This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis.

Results: Four patients were enrolled to investigate the need for dosing adjustments. The average sieving coefficient for ceftaroline was 0.81 ± 0.1, indicating high filter efficiency. The average volume of distribution was 41.8 L (0.48 L/kg) and is within the previously reported range in patients with normal renal function. Non-renal clearance accounted for more than 50% of the total clearance observed in patients. The observed pharmacokinetic profiles suggest that the pharmacodynamic target for 2-log CFU reduction from baseline (%fT >1 mg/L of 50%) was met for each patient. Due to the impact of CRRT and non-renal clearance, dosing recommendations were derived for different ranges of effluent flow rates and adjusted body weights. For a patient with an adjusted body weight of 70 kg and receiving CRRT at an effluent flow rate of 3 L/h, a ceftaroline fosamil dosing regimen of 400 mg every 12 h is proposed.

Conclusion: Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.
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http://dx.doi.org/10.1002/phar.2502DOI Listing
February 2021

Paediatric Bickerstaff brainstem encephalitis: A rare case report.

J Pak Med Assoc 2020 Nov;70(11):2054-2056

Department of Paediatric Unit III Dr. Ruth KM Pfau Civil Hospital, Karachi, Pakistan.

Bickerstaff Brainstem Encephalitis, a rare variant of Guillain- Barre Syndrome has an estimated prevalence of eight per 100 million individuals. It presents with the classic triad of ataxia, ophthalmoplegia and altered consciousness. We report the case of a 10-year-old child who presented with low grade fever, hypersomnia and inability to walk. Central nervous system examination revealed ophthalmoplegia and multiple cranial nerve palsies. However, CSF examination showed lack of albuminocytological dissociation with no previous history of respiratory or gastrointestinal tract infection. Unavailability of Anti-GQ1b antibodies led to a diagnosis based on suggestive clinical features, abnormal MRI signals and prompt response to corticosteroid administration. Intravenous Methyl Prednisolone in a dose of 30mg/kg/day was administered for 10 days followed by oral Prednisolone 2 mg/kg/day. After complete recovery the patient was discharged, Prednisolone was tapered gradually and eventually discontinued after four months.
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http://dx.doi.org/10.5455/JPMA.51328DOI Listing
November 2020

A Narrow-Band Multi-Resonant Metamaterial in Near-IR.

Materials (Basel) 2020 Nov 14;13(22). Epub 2020 Nov 14.

Department of Physics, Koc University, Istanbul 34450, Turkey.

We theoretically investigate a multi-resonant plasmonic metamaterial perfect absorber operating between 600 and 950 nm wavelengths. The presented device generates 100% absorption at two resonance wavelengths and delivers an ultra-narrow band (sub-20 nm) and high quality factor (Q=44) resonance. The studied perfect absorber is a metal-insulator-metal configuration where a thin MgF2 spacer is sandwiched between an optically thick gold layer and uniformly patterned gold circular nanodisc antennas. The localized and propagating nature of the plasmonic resonances are characterized and confirmed theoretically. The origin of the perfect absorption is investigated using the impedance matching and critical coupling phenomenon. We calculate the effective impedance of the perfect absorber and confirm the matching with the free space impedance. We also investigate the scattering properties of the top antenna layer and confirm the minimized reflection at resonance wavelengths by calculating the absorption and scattering cross sections. The excitation of plasmonic resonances boost the near-field intensity by three orders of magnitude which enhances the interaction between the metamaterial surface and the incident energy. The refractive index sensitivity of the perfect absorber could go as high as S=500 nm/RIU. The presented optical characteristics make the proposed narrow-band multi-resonant perfect absorber a favorable platform for biosensing and contrast agent based bioimaging.
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http://dx.doi.org/10.3390/ma13225140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696973PMC
November 2020

Holding the Secret: A Rare Case of Nausea and Vomiting Due to Ligamentous Compression of the Celiac Axis.

Cureus 2020 Aug 13;12(8):e9726. Epub 2020 Aug 13.

Internal Medicine, Arnot Ogden Medical Center, Elmira, USA.

Dunbar syndrome also known as median arcuate ligament syndrome (MALS) or celiac artery compression syndrome (CACS) is a rare syndrome resulting from the external compression of the celiac trunk from the median arcuate ligament. A 78-year-old female with multiple chronic conditions presented with intermittent, post-prandial epigastric pain associated with early satiety, decreased appetite for òne year. Multiple tests including gastric emptying scan and hepatobiliary scan with cholecystokinin (CCK) were normal. Contrast-enhanced computed tomography (CECT) abdomen/pelvis showed thickening of a median arcuate ligament. Further imaging with end-inspiratory phase computed tomography (CT) angiography of the abdomen and 3D reconstruction of images, revealed approximately 1 cm length segment of proximal celiac arterial narrowing, measuring 70% maximally (at its origin) and characteristic hooked appearance of the proximal celiac artery with post-stenotic dilation diagnostic of MALS. Our case report emphasizes the importance of MALS in the differential diagnosis of chronic, intermittent abdominal pain.
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http://dx.doi.org/10.7759/cureus.9726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489444PMC
August 2020

An Overview of Methods for Cardiac Rhythm Detection in Zebrafish.

Biomedicines 2020 Sep 4;8(9). Epub 2020 Sep 4.

Master Program in Nanotechnology, Chung Yuan Christian University, Chung-Li 320314, Taiwan.

The heart is the most important muscular organ of the cardiovascular system, which pumps blood and circulates, supplying oxygen and nutrients to peripheral tissues. Zebrafish have been widely explored in cardiotoxicity research. For example, the zebrafish embryo has been used as a human heart model due to its body transparency, surviving several days without circulation, and facilitating mutant identification to recapitulate human diseases. On the other hand, adult zebrafish can exhibit the amazing regenerative heart muscle capacity, while adult mammalian hearts lack this potential. This review paper offers a brief description of the major methodologies used to detect zebrafish cardiac rhythm at both embryonic and adult stages. The dynamic pixel change method was mostly performed for the embryonic stage. Other techniques, such as kymography, laser confocal microscopy, artificial intelligence, and electrocardiography (ECG) have also been applied to study heartbeat in zebrafish embryos. Nevertheless, ECG is widely used for heartbeat detection in adult zebrafish since ECG waveforms' similarity between zebrafish and humans is prominent. High-frequency ultrasound imaging (echocardiography) and modern electronic sensor tag also have been proposed. Despite the fact that each method has its benefits and limitations, it is proved that zebrafish have become a promising animal model for human cardiovascular disease, drug pharmaceutical, and toxicological research. Using those tools, we conclude that zebrafish behaviors as an excellent small animal model to perform real-time monitoring for the developmental heart process with transparent body appearance, to conduct the in vivo cardiovascular performance and gene function assays, as well as to perform high-throughput/high content drug screening.
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http://dx.doi.org/10.3390/biomedicines8090329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554775PMC
September 2020

Chilaiditi Syndrome: A Rare Case of Chest Pain due to Colonic Interposition.

Cureus 2020 Jul 20;12(7):e9288. Epub 2020 Jul 20.

Internal Medicine, Arnot Ogden Medical Center, Elmira, USA.

We present an unusual case of Chilaiditi syndrome that manifests under the guise of multiple systemic signs and symptoms. An 81-year-old female patient with a history of coronary artery disease and hypothyroidism presented to emergency department (ED) with chest heaviness associated with nausea, shortness of breath, diffuse abdominal pain and constipation. Her symptoms were similar to the previous episode of ST-segment elevation myocardial infarction. The clinical team ruled out acute coronary syndrome based on electrocardiogram (EKG) and troponin levels. On further testing, CT of the abdomen revealed the interposition of colon on the dome of diaphragm consistent with Chilaiditi sign. The patient was diagnosed with Chilaiditi syndrome based on the characteristic radiological finding and the symptomatic presentation. Conservative management with bowel rest and laxative bowel regimen resolved her symptoms without further complications. A high index of suspicion is required for the early diagnosis and can prevent further complications and mitigate the need for laparoscopic intervention.
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http://dx.doi.org/10.7759/cureus.9288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437093PMC
July 2020

Self-mutilation of Fingers Following Median Nerve Injury: Case Reports and Literature Review.

Cureus 2020 Apr 28;12(4):e7872. Epub 2020 Apr 28.

Pediatric Orthopaedics and Trauma, Al Jalila Children's Speciality Hospital, Dubai, ARE.

Self-mutilation of fingers following nerve injuries is extremely rare, but it can lead to serious complications, including amputation if not treated timely. We report here what we believe to be the first English language reports of self-mutilation of fingers following median nerve injury caused by a supracondylar humeral fracture.
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http://dx.doi.org/10.7759/cureus.7872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255529PMC
April 2020

Nanoscopic Visualization of Restricted Nonvolume Cholinergic and Monoaminergic Transmission with Genetically Encoded Sensors.

Nano Lett 2020 06 12;20(6):4073-4083. Epub 2020 May 12.

State Key Laboratory of Membrane Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.

How neuromodulatory transmitters diffuse into the extracellular space remains an unsolved fundamental biological question, despite wide acceptance of the volume transmission model. Here, we report development of a method combining genetically encoded fluorescent sensors with high-resolution imaging and analysis algorithms which permits the first direct visualization of neuromodulatory transmitter diffusion at various neuronal and non-neuronal cells. Our analysis reveals that acetylcholine and monoamines diffuse at individual release sites with a spread length constant of ∼0.75 μm. These transmitters employ varied numbers of release sites, and when spatially close-packed release sites coactivate they can spillover into larger subcellular areas. Our data indicate spatially restricted (i.e., nonvolume) neuromodulatory transmission to be a prominent intercellular communication mode, reshaping current thinking of control and precision of neuromodulation crucial for understanding behaviors and diseases.
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http://dx.doi.org/10.1021/acs.nanolett.9b04877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519949PMC
June 2020

Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity.

Biol Psychiatry 2020 10 19;88(7):541-553. Epub 2020 Feb 19.

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut; Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Background: When exposed to chronic social stress, animals display behavioral changes that are relevant to depressive-like phenotypes. However, the cascading relationship between incremental stress exposure and neural dysfunctions over time remains incompletely understood.

Methods: We characterized the longitudinal effect of social defeat on goal-directed actions and prefrontal cortical activity in mice using a novel head-fixed sucrose preference task and two-photon calcium imaging.

Results: Behaviorally, stress-induced loss of reward sensitivity intensifies over days. Motivational anhedonia, the failure to translate positive reinforcements into future actions, requires multiple sessions of stress exposure to become fully established. For neural activity, individual layer 2/3 pyramidal neurons in the cingulate and medial secondary motor subregions of the medial prefrontal cortex have heterogeneous responses to stress. Changes in ensemble activity differ significantly between susceptible and resilient mice after the first defeat session and continue to diverge following successive stress episodes before reaching persistent abnormal levels.

Conclusions: Collectively, these results demonstrate that the cumulative impact of an ethologically relevant stress can be observed at the level of cellular activity of individual prefrontal neurons. The distinct neural responses associated with resilience versus susceptibility suggests the hypothesis that the negative impact of social stress is neutralized in resilient animals, in part through an adaptive reorganization of prefrontal cortical activity.
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http://dx.doi.org/10.1016/j.biopsych.2020.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434704PMC
October 2020

Dynamics of genetic variation in transcription factors and its implications for the evolution of regulatory networks in Bacteria.

Nucleic Acids Res 2020 05;48(8):4100-4114

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, Karnataka 560065, India.

The evolution of regulatory networks in Bacteria has largely been explained at macroevolutionary scales through lateral gene transfer and gene duplication. Transcription factors (TF) have been found to be less conserved across species than their target genes (TG). This would be expected if TFs accumulate mutations faster than TGs. This hypothesis is supported by several lab evolution studies which found TFs, especially global regulators, to be frequently mutated. Despite these studies, the contribution of point mutations in TFs to the evolution of regulatory network is poorly understood. We tested if TFs show greater genetic variation than their TGs using whole-genome sequencing data from a large collection of Escherichia coli isolates. TFs were less diverse than their TGs across natural isolates, with TFs of large regulons being more conserved. In contrast, TFs showed higher mutation frequency in adaptive laboratory evolution experiments. However, over long-term laboratory evolution spanning 60 000 generations, mutation frequency in TFs gradually declined after a rapid initial burst. Extrapolating the dynamics of genetic variation from long-term laboratory evolution to natural populations, we propose that point mutations, conferring large-scale gene expression changes, may drive the early stages of adaptation but gene regulation is subjected to stronger purifying selection post adaptation.
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http://dx.doi.org/10.1093/nar/gkaa162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192604PMC
May 2020

Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsense Shank3 mutation.

Mol Psychiatry 2021 Jun 11;26(6):1945-1966. Epub 2020 Mar 11.

Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06511, USA.

The SHANK3 gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, and schizophrenia. Most studies of SHANK3 in the neocortex and hippocampus have focused on disturbances in pyramidal neurons. However, GABAergic interneurons likewise receive excitatory inputs and presumably would also be a target of constitutive SHANK3 perturbations. In this study, we characterize the prefrontal cortical microcircuit in awake mice using subcellular-resolution two-photon microscopy. We focused on a nonsense R1117X mutation, which leads to truncated SHANK3 and has been linked previously to cortical dysfunction. We find that R1117X mutants have abnormally elevated calcium transients in apical dendritic spines. The synaptic calcium dysregulation is due to a loss of dendritic inhibition via decreased NMDAR currents and reduced firing of dendrite-targeting somatostatin-expressing (SST) GABAergic interneurons. Notably, upregulation of the NMDAR subunit GluN2B in SST interneurons corrects the excessive synaptic calcium signals and ameliorates learning deficits in R1117X mutants. These findings reveal dendrite-targeting interneurons, and more broadly the inhibitory control of dendritic spines, as a key microcircuit mechanism compromised by the SHANK3 dysfunction.
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http://dx.doi.org/10.1038/s41380-020-0708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483244PMC
June 2021

A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study.

Mol Divers 2021 May 31;25(2):661-671. Epub 2020 Jan 31.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA.

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9-11, oxadiazole, pyrazole and sulfinyl analogs 13-15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity.
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http://dx.doi.org/10.1007/s11030-020-10038-wDOI Listing
May 2021

Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines.

Nat Commun 2020 01 7;11(1):72. Epub 2020 Jan 7.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.

A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST) interneurons selectively inhibit dendrites and regulate synaptic inputs, yet their response to systemic NMDAR antagonism is unknown. Here, we report that ketamine acutely suppresses the activity of SST interneurons in the medial prefrontal cortex of the awake mouse. The deficient dendritic inhibition leads to greater synaptically evoked calcium transients in the apical dendritic spines of pyramidal neurons. By manipulating NMDAR signaling via GluN2B knockdown, we show that ketamine's actions on the dendritic inhibitory mechanism has ramifications for frontal cortex-dependent behaviors and cortico-cortical connectivity. Collectively, these results demonstrate dendritic disinhibition and elevated calcium levels in dendritic spines as important local-circuit alterations driven by the administration of subanesthetic ketamine.
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http://dx.doi.org/10.1038/s41467-019-13809-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946708PMC
January 2020

Parvalbumin-Positive Neuron Loss and Amyloid-β Deposits in the Frontal Cortex of Alzheimer's Disease-Related Mice.

J Alzheimers Dis 2019 ;72(4):1323-1339

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.

Alzheimer's disease (AD) has several hallmark features including amyloid-β (Aβ) plaque deposits and neuronal loss. Here, we characterized Aβ plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6-9-month-old 5xFAD mice harboring mutations associated with familial AD. We used immunofluorescence staining to compare three regions in the frontal cortex-prelimbic (PrL), cingulate (Cg, including Cg1 and Cg2), and secondary motor (M2) cortices-along with primary somatosensory (S1) cortex. We quantified the density of Aβ plaques, which showed significant laminar and regional vulnerability. There were more plaques of larger sizes in deep layers compared to superficial layers. Total plaque burden was higher in frontal regions compared to S1. We also found layer- and region-specific differences across genotype in the density of PV interneurons. PV neuron density was lower in 5xFAD mice than wild-type, particularly in deep layers of frontal regions, with Cg (-50%) and M2 (-39%) exhibiting the largest reduction. Using in vivo two-photon imaging, we longitudinally visualized the loss of frontal cortical PV neurons across four weeks in the AD mouse model. Overall, these results provide information about Aβ deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable.
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http://dx.doi.org/10.3233/JAD-181190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123545PMC
December 2020

Interpreting calcium signals from neuronal cell bodies, axons, and dendrites: a review.

Neurophotonics 2020 Jan 30;7(1):011402. Epub 2019 Jul 30.

Yale University, Department of Psychiatry, School of Medicine, New Haven, Connecticut, United States.

Calcium imaging is emerging as a popular technique in neuroscience. A major reason is that intracellular calcium transients are reflections of electrical events in neurons. For example, calcium influx in the soma and axonal boutons accompanies spiking activity, whereas elevations in dendrites and dendritic spines are associated with synaptic inputs and local regenerative events. However, calcium transients have complex spatiotemporal dynamics, and since most optical methods visualize only one of the somatic, axonal, and dendritic compartments, a straightforward inference of the underlying electrical event is typically challenging. We highlight experiments that have directly calibrated calcium signals recorded using fluorescent indicators against electrophysiological events. We address commonly asked questions such as: Can calcium imaging be used to characterize neurons with high firing rates? Can the fluorescent signal report a decrease in spiking activity? What is the evidence that calcium transients in subcellular compartments correspond to distinct presynaptic axonal and postsynaptic dendritic events? By reviewing the empirical evidence and limitations, we suggest that, despite some caveats, calcium imaging is a versatile method to characterize a variety of neuronal events .
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http://dx.doi.org/10.1117/1.NPh.7.1.011402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664352PMC
January 2020

Bilateral proximal tibia stress fracture following bilateral distal femoral hemiepiphysiodesis - A rare complication.

J Clin Orthop Trauma 2019 Jul-Aug;10(4):804-806. Epub 2018 Jun 26.

Royal Manchester Children's Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom.

Correction of lower limb deformities by hemiepiphyseodesis with 8-plates is gaining popularity among deformity surgeons. Complications including metal failure, recurrence of deformity have been reported but stress fracture has not been reported. We have encountered bilateral proximal metaphyseal tibia stress fractures following correction of valgus deformity of both knees by hemiepiphyseodesis of distal femur following inadvertent overcorrection to a varus deformity following loss of follow up. The varus deformity has been reversed by guided growth of distal femoral physis resulting in fracture union and normal gait pattern. We herewith emphasize the importance of timely follow up with removal of 8 plates for hemiepiphysiodesis in deformity correction to prevent unexpected complication. We are reporting a rare complication of proximal tibial stress fractures following distal femur hemiepiphysiodesis done for valgus deformity with 8-plates.
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http://dx.doi.org/10.1016/j.jcot.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611963PMC
June 2018

Study on structural insight of the analysis of negative effects of opioids analgesics in naltrexone with TLR4 Mutations.

Pak J Pharm Sci 2019 Jan;32(1(Supplementary)):345-351

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

Chronic pain has been defined as the persistence that remained for more than three months. The extent of previous time duration with the normal time of natural healing phase becomes poor and results in reduced life quality and morbidity. Opioids are well recognized therapy for pain management and the clinical prescriptions based on opioids have been defined with increasing implicating behavior among patients suffering with chronic pain. The association between the pain and immunity has long been established since the involvement of interleukin-1β (IL-1β) in sickness that is considered with the induced hyperalgesia. In the context of pharmacodynamics Toll like receptors (TLRs) are involved in the negative effects of opioids as analgesics. The soluble factors released by immune cells as well as from the disruptive cells bind to TLRs. This binding leads the pre and post-synaptic ends on endothelial and microglial cells that exhibit the activation of complex inhibitory and excitatory process at the synapses site. In TLRs, TLR4 is mostly reported that is strongly associated in specifically in areas of T cells and macrophages. The current study is designed to investigate the structural insights of the opioids and TLR4 interactions by using computational approach in the aspect of recognizing the chemical combinatorial factors that are involved in the pain management. This study targets that how opioids interact with TLR4 and the process of chemical interaction that leads to negative effects of opioids at neuroimmune interface as well as to investigate the extent of particular naltrexone that mediates with the negative effects of opioids.
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January 2019

Flexibility in motor timing constrains the topology and dynamics of pattern generator circuits.

Nat Commun 2018 03 6;9(1):977. Epub 2018 Mar 6.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, 02138, USA.

Temporally precise movement patterns underlie many motor skills and innate actions, yet the flexibility with which the timing of such stereotyped behaviors can be modified is poorly understood. To probe this, we induce adaptive changes to the temporal structure of birdsong. We find that the duration of specific song segments can be modified without affecting the timing in other parts of the song. We derive formal prescriptions for how neural networks can implement such flexible motor timing. We find that randomly connected recurrent networks, a common approximation for how neocortex is wired, do not generally conform to these, though certain implementations can approximate them. We show that feedforward networks, by virtue of their one-to-one mapping between network activity and time, are better suited. Our study provides general prescriptions for pattern generator networks that implement flexible motor timing, an important aspect of many motor skills, including birdsong and human speech.
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http://dx.doi.org/10.1038/s41467-018-03261-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840308PMC
March 2018

Prevalence of subclinical hypothyroidism in adults visiting primary health-care setting in Riyadh.

J Community Hosp Intern Med Perspect 2018 6;8(1):11-15. Epub 2018 Feb 6.

Department of Family Medicine & Primary Health Care, King Abdul Aziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia.

: Subclinical hypothyroidism is an asymptomatic condition with normal thyroxin and raised thyroid stimulating hormone (TSH) level. The objective of the study was to determine the prevalence of subclinical hypothyroidism in primary health care (PHC) settings in Riyadh and explore the relationship of TSH level with age, gender, family history, body mass index, and co-morbid conditions. : A cross-sectional study of adult visitors to nine satellites PHC clinics in military housing in Riyadh was carried out. TSH concentration and free T4 levels were measured. Data were collected by nurses and physicians during routine clinical practice in primary care. Descriptive analysis was performed on all variables in study, and relationships were explored using chi-square, -test, analysis of variance, and linear regression. : A total of 340 out of 394 participants in the study gave blood samples. Subclinical hyperthyroidism was identified in 2.1% ( = .001) and subclinical hypothyroidism in 10.3% ( = .001) of the PHC visitors. TSH levels were found to be significantly higher ( = .047) in elderly population of ≥60 years and those with family history of thyroid disease. Non-significant upward trends were noted in TSH levels with hyperlipidemia and increasing blood pressure. No overt hyperthyroidism or hypothyroidism was found in our study sample. : Subclinical hypothyroidism has a prevalence of 10% of adults visiting PHC's. TSH levels are higher in the elderly, which warrants screening of those aged 60 years and above.
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http://dx.doi.org/10.1080/20009666.2017.1422672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804806PMC
February 2018

Dissection of Recombination Attributes for Multiple Maize Populations Using a Common SNP Assay.

Front Plant Sci 2017 30;8:2063. Epub 2017 Nov 30.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, China.

Recombination is a vital characteristic for quantitative trait loci mapping and breeding to enhance the yield potential of maize. However, recombination characteristics in globally used segregating populations have never been evaluated at similar genetic marker densities. This study aimed to divulge the characteristics of recombination events, recombinant chromosomal segments, and recombination frequency for four dissimilar populations. These populations were doubled haploid (DH), recombination inbred line (RIL), intermated B73xMo17 (IBM), and multi-parent advanced generation inter-cross (MAGIC), using the Illumina MaizeSNP50 BeadChip to provide markers. Our results revealed that the average number of recombination events was 16, 41, 72, and 86 per line in DH, RIL, IBM, and MAGIC populations, respectively. Accordingly, the average length of recombinant chromosomal segments was 84.8, 47.3, 29.2, and 20.4 Mb in DH, RIL, IBM, and MAGIC populations, respectively. Furtherly, the recombination frequency varied in different genomic regions and population types [DH (0-12.7 cM/Mb), RIL (0-15.5 cM/Mb), IBM (0-24.1 cM/Mb), MAGIC (0-42.3 cM/Mb)]. Utilizing different sub-sets of lines, the recombination bin number and size were analyzed in each population. Additionally, different sub-sets of markers and lines were employed to estimate the recombination bin number and size via formulas for relationship in these populations. The relationship between recombination events and recombination bin length was also examined. Our results contribute to determining the most suitable number of genetic markers, lines in each population, and population type for successful mapping and breeding.
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http://dx.doi.org/10.3389/fpls.2017.02063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714861PMC
November 2017

The Tomato DOF Daily Fluctuations 1, TDDF1 acts as flowering accelerator and protector against various stresses.

Sci Rep 2017 08 31;7(1):10299. Epub 2017 Aug 31.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan), College of Life Science and Technology, Huazhong Agricultural University, Wuhan Hubei, 430070, China.

Adaptation to environmental changes is an important fitness trait for crop development. Photoperiod is an essential factor in seasonal control of flowering time. Sensing of day-length requires an interaction between the Photoperiod and the endogenous rhythms that is controlled by plant circadian clock. Thus, circadian clock is a critical regulator and internal molecular time-keeping mechanism, controlling key agricultural traits in crop plants such as the ability to adjust their growth and physiology to anticipate diurnal environmental changes. Here, we describe the gene Tomato Dof Daily Fluctuations 1 (TDDF1), which is involved in circadian regulation and stress resistance. Large daily oscillations in TDDF1 expression were retained after transferring to continuous dark (DD) or light (LL) conditions. Interestingly, overexpressing TDDF1 induce early flowering in tomato through up-regulation of the flowering-time control genes, moreover, by protein-protein interaction with the floral inducer SFT gene. Notably, overexpressing TDDF1 in tomato was associated with chlorophyll overaccumulation by up-regulating the related biosynthetic genes. TDDF1 expression results in improved drought, salt, various hormones stress tolerance alongwith resistance to late blight caused by Phytophthora infestans. This study can be a distinctive strategy to improve other economically important crops.
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http://dx.doi.org/10.1038/s41598-017-10399-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578996PMC
August 2017

Posttraumatic stress disorder after myocardial infarction and coronary artery bypass grafting.

Int J Crit Illn Inj Sci 2017 Apr-Jun;7(2):84-90

Department of Cardiology, St. Luke's University Health Network, Bethlehem, PA, USA.

Post traumatic stress disorder is a psychiatric disease that is usually precipitated by life threatening stressors. Myocardial infarction, especially in the young can count as one such event. The development of post traumatic stress after a coronary event not only adversely effects psychiatric health, but leads to increased cardiovascular morbidity and mortality. There is increasing evidence that like major depression, post traumatic stress disorder is also a strong coronary risk factor. Early diagnosis and treatment of this disease in patients with acute manifestations of coronary artery disease can improve patient outcomes.
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http://dx.doi.org/10.4103/IJCIIS.IJCIIS_27_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479081PMC
June 2017

Genomewide Mutational Diversity in Population Evolving in Prolonged Stationary Phase.

mSphere 2017 May-Jun;2(3). Epub 2017 May 24.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, Karnataka, India.

Prolonged stationary phase is an approximation of natural environments presenting a range of stresses. Survival in prolonged stationary phase requires alternative metabolic pathways for survival. This study describes the repertoire of mutations accumulating in starving populations in lysogeny broth. A wide range of mutations accumulates over the course of 1 month in stationary phase. Single nucleotide polymorphisms (SNPs) constitute 64% of all mutations. A majority of these mutations are nonsynonymous and are located at conserved loci. There is an increase in genetic diversity in the evolving populations over time. Computer simulations of evolution in stationary phase suggest that the maximum frequency of mutations observed in our experimental populations cannot be explained by neutral drift. Moreover, there is frequent genetic parallelism across populations, suggesting that these mutations are under positive selection. Finally, functional analysis of mutations suggests that regulatory mutations are frequent targets of selection. Prolonged stationary phase in bacteria, contrary to its name, is highly dynamic, with extreme nutrient limitation as a predominant stress. Stationary-phase cultures adapt by rapidly selecting a mutation(s) that confers a growth advantage in stationary phase (GASP). The phenotypic diversity of starving populations has been studied in detail; however, only a few mutations that accumulate in prolonged stationary phase have been described. This study documented the spectrum of mutations appearing in during 28 days of prolonged starvation. The genetic diversity of the population increases over time in stationary phase to an extent that cannot be explained by random, neutral drift. This suggests that prolonged stationary phase offers a great model system to study adaptive evolution by natural selection.
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http://dx.doi.org/10.1128/mSphere.00059-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444009PMC
May 2017
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