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The current study is intended to enhance unique bioactive and eco-friendly composite films following a simple solvent-casting approach by incorporating cerium oxide nanoparticles (CeO 2 NPs) with a chitosan (CS)/polyvinyl alcohol (PVA) matrix. Antimicrobial activity, preservation impact, mechanisms for the edible berry tomatoes and physicochemical properties of the produced films were tested. FTIR, SEM-EDX, XRD, UV-vis spectroscopy and contact angle were used to characterize the films. Incorporated (3.0 wt%) CeO 2 NPs practically developed composite film's thermal stability, structural, mechanical, bioactive, antioxidant, barrier and wettability properties. The tomatoes' look, weight loss and stiffness were better preserved after 25 days of storage at room temperature (25 ± 5 °C) when 3.0 wt% CeO 2 NPs films were used instead of the original CS/PVA film. CS and CeO 2 NPs have unique physiochemical and antibacterial properties. Food packaging extensively investigates the modified films as antimicrobials and preservatives to increase the shelf life of packaged foods, owing to their ability to inhibit gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa), and filamentous fungi (Bipolaris sorokiniana, Fusarium op., and Alternaria sp.). Our findings indicated that the CeO 2 /CS/PVA composite films could be used as effective wrapping materials for food preservation., Competing Interests: Declaration of competing interest No conflict of interest has been reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The increasing level of atmospheric CO 2 requires the urgent development of effective capture technologies. This comprehensive review thoroughly examines various methods for the synthesis of carbon materials, modification techniques for converting biomass feedstock into carbon materials and pivotal factors impacting their properties. The novel aspect of this review is its in-depth comparison of how these modifications specifically affect the pore structure and surface area together with the exploration of the mechanism underlying the enhancement of CO 2 adsorption performance. Additionally, this review addresses research gaps and provides recommendations for future studies concerning the advantages and drawbacks of CO 2 adsorbents and their prospects for commercialization and economic feasibility. This article revealed that among the various strategies, template carbonization offers a viable option for providing control of the material pore diameter and structure without additional modification treatments. Optimizing the pore structure of activated carbons, particularly those activated with agents such as KOH and ZnCl 2 , together with synthesizing hybrid activated carbons using multiple activating agents, is crucial for enhancing their CO 2 capture performance. Cost-benefit analysis suggests that biomass-derived activated carbons can significantly meet the escalating demand for CO 2 capture materials, offering economic advantages and supporting sustainable waste management., Competing Interests: The authors declare that they have no known financial or personal conflicts of interest that could have influenced the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Synthetic organic dyes are becoming the major class of water pollutants leading to malignant detriments to the ecology. Consequently, this research focuses on remediating this circumstance utilizing a novel catalytic material, namely, cerium-doped spinel ferrite Ni 0.6 Cu 0.4 Ce x Fe 2- x O 4 ( x = 0.0, 0.5, 1.0, 1.5), developed using the chemical coprecipitation technique and characterized using FTIR, XRD, FE-SEM, EDX and VSM analysis. The particles have shown band gap values ranging from 4.29 to 2.01 eV. The as-synthesized nano-sized particles were employed as a photocatalyst to degrade the complex structure of congo red (CR) dye. About 91% of the dye was degraded with 60 mg of the catalyst under visible light irradiation with the highest cerium-doping ( x = 1.5) at a pH below 6.8, which was the zero-surface charge pH for the particle. Batch studies were performed to optimize all the conditions, including the dose, concentration, pH, and different light energy sources. Recyclability of the catalyst was also investigated, which was supported by the higher stability of the recovered particles through XRD analysis. Reaction kinetics for this system were evaluated along with three isotherm models. Moreover, the scavenging test indicated that the major active species leading to this degradation was hole (h + ), and a schematic degradation mechanism is presented. Following that, this model can successfully be used for wastewater treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

The present perspective emphasizes the green synthesis of CeO 2 -NPs using Oroxylum indicum fruit extract. The synthesized NPs were characterized utilizing analytical techniques, including FT-IR, UV-vis, XRD, SEM-EDX, and VSM. Of them, XRD analysis ratifies the cubic fluorite crystal structure along with a particle size of 23.58 nm. EDX results support the presence of cerium and oxygen in a proper ratio. The surface morphology of NPs, however, was scrutinized using SEM. The lower IC 50 value (20.8 μg mL -1 ) of NPs compared to the reference substance, ascorbic acid (33.2 μg mL -1 ), demonstrates CeO 2 -NPs to be a compatible antioxidant. Moreover, the drug-releasing capability of CeO 2 -NPs was a buffer pH-dependent parameter. The acidic pH solution was 20.5%, while the basic pH solution was 16.9%. The drug-releasing capability was analyzed using the Higuchi model and Korsmeyer-Peppas kinetics. The values of the determination coefficient ( R 2 ) were found to be 0.9944 and 0.9834, respectively. The photocatalytic activity of CeO 2 -NPs was evaluated, considering methylene blue as a model dye. The degradation percentage was attained up to 56.77% after it had been exposed for 150 min. Apart from this, the synthesized NPs were screened against two fungus species, Bipolaris sorokiniana and Fusarium . The percentage of growth was measured at 56% and 49%, respectively., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Transfer RNAs (tRNA) are non-coding RNAs. Encouraged by biological applications discovered for peptides derived from other non-coding genomic regions, we explore the possibility of deriving epitope-based vaccines from tRNA encoded peptides (tREP) in this study. Epitope-based vaccines have been identified as an effective strategy to mitigate safety and specificity concerns observed in vaccine development. In this study, we explore the potential of tREP as a source for epitope-based vaccines for virus pathogens. We present a computational workflow that uses verified data sources and community-validated predictive tools to produce a ranked list of plausible epitope-based vaccines starting from tRNA sequences. The top epitope, bound to the predicted HLA molecule, for the virus pathogen is computationally validated through 200 ns molecular dynamics (MD) simulations followed by binding free energy calculations. The simulation results indicate that two tRNA encoded epitope-based vaccines, RRHIDIVV and IMVRFSAE for Mamastrovirus 3 and Norovirus GII, respectively, are likely candidates. Peptides originating from tRNAs provide unexplored opportunities for vaccine design. Encouraged by our previous experimental study, which established the inhibitory properties of tREPs against infectious parasites, we have proposed a computationally validated set of peptides derived from tREPs as vaccines for viral pathogens.

The present study aimed at (a) determining the concentration of macro-minerals and toxic metals in fish species collected from biofloc and traditional fish farms; (b) assessing the contribution of macro-minerals to our daily diet; and (c) evaluating the health risks of children and adults based on the US Environmental Protection Agency (USEPA) deterministic model. Significantly higher concentrations of macro-minerals and significantly lower levels of toxic metals (at < 0.05 level) were found in most of the biofloc fish species compared to the market fish samples. The values of the target hazard quotient (THQ) were less than 1.0 for all individual trace metals in all species, which indicated that there were no noncarcinogenic health risks. Furthermore, the value of the hazard index (HI) in three samples of Tilapia from the market exceeded the recommended value of 1.0, while all samples from the biofloc fish tank were within the maximum tolerable limit, which suggested that the daily consumption of Tilapia fishes from the market may result in considerable harmful effects. Target cancer risk (TCR) for Pb in all of the studied samples was within the range of 10 -6 and 10 -4 , hence the adults and children would not experience any kinds of carcinogenic effects. The result obtained from this comparative study revealed that the consumption of fish species from both local market and biofloc fish farms was almost safe, but the value of TCR in Pb was higher in traditional fish samples than that of biofloc tanks, hence fish samples from biofloc farms were more suitable for consumption., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, polymer-supported magnetic iron oxide nanoparticles (MIO-NPs) have gained a lot of attention in biomedical and healthcare applications due to their unique magnetic properties, low toxicity, cost-effectiveness, biocompatibility, and biodegradability. In this study, waste tissue papers (WTP) and sugarcane bagasse (SCB) were utilized to prepare magnetic iron oxide (MIO)-incorporated WTP/MIO and SCB/MIO nanocomposite particles (NCPs) based on in situ co-precipitation methods, and they were characterized using advanced spectroscopic techniques. In addition, their anti-oxidant and drug-delivery properties were investigated. Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) analyses revealed that the shapes of the MIO-NPs, SCB/MIO-NCPs, and WTP/MIO-NCPs were agglomerated and irregularly spherical with a crystallite size of 12.38 nm, 10.85 nm, and 11.47 nm, respectively. Vibrational sample magnetometry (VSM) analysis showed that both the NPs and the NCPs were paramagnetic. The free radical scavenging assay ascertained that the WTP/MIO-NCPs, SCB/MIO-NCPs, and MIO-NPs exhibited almost negligible antioxidant activity in comparison to ascorbic acid. The swelling capacities of the SCB/MIO-NCPs and WTP/MIO-NCPs were 155.0% and 159.5%, respectively, which were much higher than the swelling efficiencies of cellulose-SCB (58.3%) and cellulose-WTP (61.6%). The order of metronidazole drug loading after 3 days was: cellulose-SCB < cellulose-WTP < MIO-NPs < SCB/MIO-NCPs < WTP/MIO-NCPs, whereas the sequence of the drug-releasing rate after 240 min was: WTP/MIO-NCPs < SCB/MIO-NCPs < MIO-NPs < cellulose-WTP < cellulose-SCB. Overall, the results of this study showed that the incorporation of MIO-NPs in the cellulose matrix increased the swelling capacity, drug-loading capacity, and drug-releasing time. Therefore, cellulose/MIO-NCPs obtained from waste materials such as SCB and WTP can be used as a potential vehicle for medical applications, especially in a metronidazole drug delivery system.

In this study, the concentrations of iodine in household salt samples (n = 690) were determined by following the iodometric titration method, and the health risks of Bangladeshi people were assessed based on the semi-probabilistic approach and the US Environmental Protection Agency (USEPA) deterministic model. After adjusting 20% of cooking losses, the iodine concentration (mean, range) in salt samples of Phultala, Dighalia, Terokhada, Rupsha, Batiaghata, Dumuria, Paikgacha, Koyra, Dacope, and KCC was (29.68 ± 8.67, 14.39-48.26), (31.05 ± 6.68, 15.24-43.18), (26.94 ± 5.57, 16.09-45.72), (24.33 ± 5.61, 12.70-37.26), (26.69 ± 6.73, 10.16-44.87), (27.20 ± 8.44, 9.31-53.34), (27.71 ± 8.09, 8.46-47.42), (28.39 ± 7.80, 11.01-46.57), (28.20 ± 7.97, 3.38-49.10), and (29.21 ± 6.62, 18.62-40.64) mg/kg, respectively. The iodine contents in 97.25% of samples were within the standard fortification level of Bangladesh (15-50 mg/kg), while 2.61% of samples were below this limit. The semi-probabilistic risk assessment studies showed that 80.14% of samples at a low ingestion rate could provide optimal nutrition (150-299 μg/day) to the whole population. Contrarily, at medium, moderate-high, and high consumption rates 34.93%, 65.22%, and 85.94% of samples, respectively, belonged to above the requirements to excessive exposure categories (300-1100 μg/day), which might cause iodine-induced diseases. The target hazard quotient (THQ) values for the adults in most of the samples were within the threshold risk limit (THQ < 1.0), whereas THQ values in 6.82% to 85.97% of samples for the children at low to high ingestion rates, respectively exceeded this limit, which revealed that the adults were almost safe, but the children might face non-carcinogenic health effects. Therefore, regular monitoring of iodine concentration in iodized salts should be done to prevent iodine deficiency or iodine-induced disorders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, magnetite nanoparticles (Fe 3 O 4 NPs) were synthesized using Baccaurea ramiflora leaf extracts and characterized by visual observation, UV-Vis, FTIR, XRD, FESEM, and EDS. The UV-Vis spectrum showed continuous absorption at 300-500 nm, confirming the formation of Fe 3 O 4 NPs. FTIR revealed that compounds containing the O-H group act as reducing agents during Fe 3 O 4 NPs formation. Agglomerated spherical NPs were observed in the FESEM image. The prominent peak at ~6.4 keV in the EDS spectrum ascertained the existence of Fe, while the sharp peak at ~0.53 keV confirmed the presence of elemental oxygen. XRD patterns affirmed the crystalline nature. The size of as-synthesized NPs was observed to be 8.83 nm. The catalytic activity of Fe 3 O 4 NPs for the reduction of methylene blue (MB) dye was monitored by UV-Vis. The maximum absorption peak of MB dye at 664 nm was almost diminished within 20 min, which revealed Fe 3 O 4 NPs could be an excellent catalyst for wastewater treatment.

Malaria infection caused by Plasmodium falciparum is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent need for new anti-malarials. Herein, we report the highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives, inspired from naturally occurring dependensin against chloroquine (CQ) sensitive and resistant P. falciparum strains. Chemically synthesized, four dependensin analogs 85(A-D) exhibited growth inhibition at nanomolar concentrations ranging from 63.96 to 725.8 nM by blocking the parasite development at the ring and early trophozoite stages. The growth inhibitory activity of dependensin analogs was correlated with their anti-plasmodial lactate dehydrogenase activity by computational analysis. Molecular docking, 50 ns simulation and a 2D-Quantitative Structure-Activity Relationship (2D-QSAR) modelling revealed the interaction with their putative target P. falciparum lactate dehydrogenase (PfLDH). Here, developing the predictive 2D descriptors such as thermodynamic, spatial, electronic, and topological with multiple linear regression analysis (MLRA), the structural requirements for potent and selective PfLDH inhibitory activity has been identified. The strong binding of compound 85D to the catalytic Nicotinamide adenine dinucleotide (NADH) binding pocket of the PfLDH further supported the PfLDH targeting potential of dependensin analogs. Overall, this study revealed a highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives with their putative anti-PfLDH activity.Communicated by Ramaswamy H. Sarma.

We asked if transfer RNA (tRNA) ever got an opportunity of translating its own sequence during evolution, what would have been the function of such tRNA-encoded peptides (tREPs)? If not, could one artificially synthesize tREPs to study the corresponding functional outcomes? Here, we report a novel, first-in-the-class, chemically synthesized tREP-18 molecule originating from the Escherichia coli tRNA sequence showing potent antileishmanial property. As a first step, E. coli tRNAs were computationally translated into peptide sequence equivalents and a database of full-length hypothetical tREPs was created. The tREP sequences were sent into sequence, structure, and energy filters to narrow down potential peptides for experimental validation. Based on the functional predictions, tREPs were screened against antiparasitic targets, leading to the identification of tREP-18 as a potential antiparasitic peptide. The in vitro assay of chemically synthesized tREP-18 on the Ag83 strain of Leishmania donovani showed its potent antileishmanial property (IC50 value of 22.13 nM). The atomic force microscopy and scanning electron microscopy images indicated significant alteration in the cytoskeletal architecture of tREP-18-treated parasites. Also, tREP-18 seems to destabilize the mitochondrial membrane potential of parasites, disrupting their cellular integrity and leading to parasitic death. The cellular assays of the tREP-18 peptide on the BS12 strain, a clinical isolate of post-kala azar dermal leishmaniasis, demonstrated its significant efficacy at an IC50 value of 15 nM. The tREP-18 peptide showed a toxic effect on the amastigote stage of the parasite, showing macrophage pathogen clearance at a concentration of 22.5 nM. This study provides the proof of the concept of making a new class of functional peptides from tRNA sequences. It also opens a huge untapped tRNA-peptide space toward novel discoveries and applications. In the future, it would be interesting to perform tREP edits and redesign tREPs toward specific applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Proteins are integral part of all living beings, which are building blocks of many amino acids. To be functionally active, amino acids chain folds up in a complex way to give each protein a unique 3D shape, where a minor error may cause misfolded structure. Genetic disorder diseases i.e. Alzheimer, Parkinson, etc. arise due to misfolding in protein sequences. Thus, identifying patterns of amino acids is important for inferring protein associated genetic diseases. Recent studies in predicting amino acids patterns focused on only simple protein misfolded disease i.e. Chromaffin Tumor, by association rule mining. However, more complex diseases are yet to be attempted. Moreover, association rules obtained by these studies were not verified by usefulness measuring tools., Results: In this work, we analyzed protein sequences associated with complex protein misfolded diseases (i.e. Sickle Cell Anemia, Breast Cancer, Cystic Fibrosis, Nephrogenic Diabetes Insipidus, and Retinitis Pigmentosa 4) by association rule mining technique and objective interestingness measuring tools. Experimental results show the effectiveness of our method., Conclusion: Adopting quantitative experimental methods, this work can form more reliable, useful and strong association rules i. e. dominating patterns of amino acid of complex protein misfolded diseases. Thus, in addition to usual applications, the identified patterns can be more useful in discovering medicines for protein misfolded diseases and thereby may open up new opportunities in medical science to handle genetic disorder diseases., (© 2021. The Author(s).)

Biofoundry is a place where biomanufacturing meets automation. The highly modular structure of a biofoundry helps accelerate the design-build-test-learn workflow to deliver products fast and in a streamlined fashion. In this perspective, we describe our efforts to build Biofoundry India, where we see the facility add a substantial value in supporting research, innovation and entrepreneurship. We describe three key areas of our focus, harnessing the potential of non-expressing parts of the sequenced genomes, using deep learning in pathway reconstruction and synthesising enzymes and metabolites. Toward the end, we describe specific challenges in building such facility in India and the path to mitigate some of those working with the other biofoundries worldwide., (© The Author(s) 2021. Published by Oxford University Press.)

Ice cream is a popular frozen dairy product and a possible source of dietary minerals. However, ice cream may also contain toxic metals, which may cause several health implications. The current study aimed to determine the content of toxic elements in ice cream samples using inductively coupled plasma-optical emission spectrometry (ICP-OES) and to assess the health risks of consumers based on target cancer risk (TCR), target hazard quotient (THQ), and hazardous index (HI). The determined concentration (median, range) of all studied elements had shown a descending order of Al (9.36, 5.37-14.26) > Zn (5.94, 1.95-10.22) > Cu (1.73, 1.02-3.77) > Ni (0.95, 0.67-1.80) > Fe (0.79, 0.10-1.64) > Cr (0.43, 0.28-0.73) > Mn (0.42, 0.11-1.03) > Pb (0.34, 0.09-0.79) > Cd (0.08, 0.04-0.14) mg/kg (fresh weight). The values of THQ and HI (except 16% for children) were lower than the maximum threshold risk limit (TRL = 1.0), indicating no potential non-carcinogenic health effects might occur. Similarly, the TCR of Cr and Pb for both adults and children was within the permissible limit of 10 -4 -10 -6 , which suggested that the consumer would not experience potential lifetime carcinogenic health risks. However, the overall analyses revealed that the consumption of ice cream is almost safe for people, but the combined impact of all metals (HI) in some samples is a matter of health concern. Henceforth, regular monitoring of toxic metals in ice creams should be done to assure food safety and hygiene.

Recognizing the sport of cricket on the basis of different batting shots can be a significant part of context-based advertisement to users watching cricket, generating sensor-based commentary systems and coaching assistants. Due to the similarity between different batting shots, manual feature extraction from video frames is tedious. This paper proposes a hybrid deep-neural-network architecture for classifying 10 different cricket batting shots from offline videos. We composed a novel dataset, CricShot10, comprising uneven lengths of batting shots and unpredictable illumination conditions. Impelled by the enormous success of deep-learning models, we utilized a convolutional neural network (CNN) for automatic feature extraction, and a gated recurrent unit (GRU) to deal with long temporal dependency. Initially, conventional CNN and dilated CNN-based architectures were developed. Following that, different transfer-learning models were investigated-namely, VGG16, InceptionV3, Xception, and DenseNet169-which freeze all the layers. Experiment results demonstrated that the VGG16-GRU model outperformed the other models by attaining 86% accuracy. We further explored VGG16 and two models were developed, one by freezing all but the final 4 VGG16 layers, and another by freezing all but the final 8 VGG16 layers. On our CricShot10 dataset, these two models were 93% accurate. These results verify the effectiveness of our proposed architecture compared with other methods in terms of accuracy.

Human fall identification can play a significant role in generating sensor based alarm systems, assisting physical therapists not only to reduce after fall effects but also to save human lives. Usually, elderly people suffer from various kinds of diseases and fall action is a very frequently occurring circumstance at this time for them. In this regard, this paper represents an architecture to classify fall events from others indoor natural activities of human beings. Video frame generator is applied to extract frame from video clips. Initially, a two dimensional convolutional neural network (2DCNN) model is proposed to extract features from video frames. Afterward, gated recurrent unit (GRU) network finds the temporal dependency of human movement. Binary cross-entropy loss function is calculated to update the attributes of the network like weights, learning rate to minimize the losses. Finally, sigmoid classifier is used for binary classification to detect human fall events. Experimental result shows that the proposed model obtains an accuracy of 99%, which outperforms other state-of-the-art models.

Foggy images suffer from low contrast and poor visibility problem along with little color information of the scene. It is imperative to remove fog from images as a pre-processing step in computer vision. The Dark Channel Prior (DCP) technique is a very promising defogging technique due to excellent restoring results for images containing no homogeneous region. However, having a large homogeneous region such as sky region, the restored images suffer from color distortion and block effects. Thus, to overcome the limitation of DCP method, we introduce a framework which is based on sky and non-sky region segmentation and restoring sky and non-sky parts separately. Here, isolation of the sky and non-sky part is done by using a binary mask formulated by floodfill algorithm. The foggy sky part is restored by using Contrast Limited Adaptive Histogram Equalization (CLAHE) and non-sky part by modified DCP. The restored parts are blended together for the resultant image. The proposed method is evaluated using both synthetic and real world foggy images against state of the art techniques. The experimental result shows that our proposed method provides better entropy value than other stated techniques along with have better natural visual effects while consuming much lower processing time.

Background and Aim: The emergence of antimicrobial resistance (AMR) in commensal organism, such as Escherichia coli of food animals, is an alarming issue for global health. It increases the possibility of transmitting AMR determinant(s) to human bacterial pathogens by transferable genetic materials, particularly by plasmids. Hence, it is important to know which resistant genes are being carried by commensal organisms in food chain in a country and their level of temporal loads. As a result, pre-emptive measures can be advocated with an aim to reduce their risks in their primary source of circulation which consequently would benefit the public health., Materials and Methods: Commensal E. coli strains from broiler chickens on randomly selected 30 farms and the farm environments were examined for the frequencies of isolation of resistant strains to oxytetracycline and ciprofloxacin. Five birds were randomly selected from each farm to collect cloacal swab samples (total of 150 samples). Furthermore, a total of 150 environmental samples comprising one each from feed, water, soil, litter, and litter damping site of each farm were screened for the isolation of commensal E. coli strains. Strains thus obtained were initially tested for their resistance to oxytetracycline and ciprofloxacin by Kirby-Bauer disk diffusion method. Oxytetracycline-resistant strains were further screened for the presence of resistance determining genes, namely, tetA , tetB , and tetC by uniplex polymerase chain reactions. Risks associated with the isolation frequency of oxytetracycline- and ciprofloxacin-resistant E. coli were also assessed by univariable logistic regression analysis., Results: The results revealed that all E. coli isolates, regardless of the source of origin, were resistant to oxytetracycline, while 78.4% (95% confidence interval [CI] 69.1-85.5%) showed resistance to ciprofloxacin. All the randomly selected (20) oxytetracycline-resistant strains harbored the tetA gene, whereas tetB and tetC were reported in three and two isolates, respectively. After univariable analysis, only one variable, that is, strain 1 of broiler chickens compared to two other strains was found to be positively associated with the isolation of ciprofloxacin-resistant E. coli (odds ratio 12.75 [95% CI 1.0-157.1], p=0.047)., Conclusion: Resistance emerged against oxytetracycline and ciprofloxacin in commensal E. coli strains circulating in live poultry and farm environments in Bangladesh seems to be very high. Thus, human infection with drug-resistant E. coli strains through food chain will critically compromise the therapeutic measures currently available., (Copyright: © Das, et al.)

Aims: To investigate plasmid-borne colistin resistance mechanism (plasmid-mediated colistin resistance [ mcr-1 ]) in Escherichia coli of human, veterinary, and environmental origin in Bangladesh. Materials and methods: A total of 810 samples were collected from different sources. Isolation and identification of E. coli was performed using classical bacteriology and then tested for antimicrobial susceptibility. Colistin-resistant isolates were further analyzed for mcr-1 gene using PCR. Minimum inhibitory concentration (MIC) was determined using microbroth dilution technique. After sequencing of mcr-1 gene, phylogenetics was conducted to see the relationship with other mcr-1 gene sequences. Results: A total of 358 E. coli were isolated from 810 samples of humans, animals, environment, and food in Bangladesh. Of them 49 (15.9%) isolates were phenotypically resistant to colistin and 254 (70.9%) were resistant to multiple antimicrobials. mcr-1 gene was detected in three E. coli isolates of poultry source. For the three mcr-1 positive isolates the MIC of colistin sulfate was 4, 8, and 128 μg/mL. Gene sequencing of two of the three mcr-1 positive isolates and phylogenetic analysis showed close similarities of one isolate to other mcr-1 sequences available at GenBank while the other appeared to have evolved locally. Conclusion: First-ever report on circulation of mcr-1 E. coli of livestock origin in Bangladesh.

MicroRNAs (miRNAs) are small non-coding RNA molecules of around 22 nucleotides in length. They are crucially involved in the post transcriptional regulation and thus play a significant role in the modulation of different diseases. Several studies have suggested that miRNA expression is dysregulated in various cancers through different mechanisms and the dysregulated miRNA in return affects different cancer hallmarks including cell proliferation, cell death suppression, metastasis and angiogenesis. Compilation of the available miRNA data can be a stimulator for proper understanding of the correlation between the miRNA expression and cancer progression. In this review, we have focussed on the role of miR-760 in the progression of different cancer. MicroRNA-760 (miR-760) has been found to be down regulated in various cancers, thus it can be utilized as a possible prognostic marker for cancer detection. Here, we have tried to fill a gap regarding the role of miR-760 in relation to cervical cancer also. Moreover, unravelling the role of miR-760 in different cancers will enlighten the researchers with proper understanding of biology of miR-760 in regulation of different cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Despite several reports describing the dual role of miR-145 as an oncogene and a tumor suppressor in cancer, not much has been resolved and understood., Method: In this study, the potential targets of miR-145 were identified bio-informatically using different target prediction tools. The identified target genes were validated in vitro by dual luciferase assay. Wound healing and soft agar colony assay assessed cell proliferation and migration. miR-145 expression level was measured quantitatively by RT-PCR at different stages of breast tumor. Western blot was used to verify the role of miR-145 in EMT transition using key marker proteins., Result: Wound healing and soft agar colony assays, using miR-145 over-expressing stably transfected MCF7 cells, unraveled its role as a pro-proliferation candidate in cancerous cells. The association between miR-145 over-expression and differential methylation patterns in representative target genes ( DR5 , BCL2 , TP53 , RNF8 , TIP60 , CHK2 , and DCR2 ) supported the inference drawn. These in vitro observations were validated in a representative set of nodal positive tumors of stage 3 and 4 depicting higher miR-145 expression as compared to early stages. Further, the role of miR-145 in epithelial-mesenchymal (EMT) transition found support through the observation of two key markers, Vimentin and ALDL , where a positive correlation with Vimentin protein and a negative correlation with ALDL mRNA expression were observed., Conclusion: Our results demonstrate miR-145 as a pro-cancerous candidate, evident from the phenotypes of aggressive cellular proliferation, epithelial to mesenchymal transition, hypermethylation of CpG sites in DDR and apoptotic genes and upregulation of miR-145 in later stages of tumor tissues., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Irrawaddy squirrel (Callosciurus pygerythrus) may play an important role in the transmission of zoonotic bacteria, but little is known about the carriage of zoonotic bacteria in this common frugivorous rodent in Bangladesh. We aimed to investigate the presence of common zoonotic bacterial pathogens in Irrawaddy squirrel in the southeast part of Bangladesh. A total of 27 rectal and 27 oro-nasal swabs were collected from 27 healthy wild Irrawaddy squirrels. Four common zoonotic bacteria were isolated following routine laboratory procedures, and were identified based on colony morphology, and biochemical and staining properties. The pathogenic potential of the identified bacteria was confirmed by detection of virulence genes by PCR. All isolates were subjected to antimicrobial susceptibility test against seven antibiotics from six generic groups which are commonly used in human and veterinary medicine in Bangladesh. The prevalence of Escherichia coli, Salmonella spp., Yersinia spp. and Staphylococcus spp. was 44.4% (95% CI, 32.0-57.6), 13% (95% CI, 6.1-24.7), 44.4% (95% CI, 32.0-57.6), and 72.2% (95% CI, 59.0-82.5), respectively. We identified potential zoonotic virulence genes in all of these four bacterial species. Antimicrobial susceptibility testing revealed the presence of several multidrug resistant bacterial strains in squirrels. To the best of our knowledge, this is the first report in Bangladesh of the detection of antibiotic resistant zoonotic bacteria in Irrawaddy squirrels. The findings underpin the role of Irrawaddy squirrel as a source of pathogenic antibiotic resistant bacteria, consequently, fruit rejected because of squirrel consumption and squirrel-bites deserve more concern than previously., (© 2018 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Background and Aim: Newcastle disease is one of the most common diseases affecting poultry in Bangladesh. The disease can cause up to 100% mortality but is preventable if birds are timely and properly vaccinated with a vaccine of standard virus titer. Different live vaccines are commercially available in the country - most, if not all, are produced using lentogenic strains of the virus with variable virulence. One of the disadvantages of these vaccines is that they are not stable at high environmental temperature, and therefore, a proper cold chain must be maintained during transportation and storage. Information on how long these vaccine viruses can withstand environmental temperature, which is near the vicinity of 37°C in the summer season in Bangladesh, is scanty. The aim of this research was to measure the effect of temperature on virus titer of live ND virus vaccines and to develop a real-time reverse transcription polymerase chain reaction (rRT-PCR) standard curve to indirectly determine hemagglutination (HA) titer of virus by this highly sensitive method., Materials and Methods: In this study, thermostability of five commercial live vaccines containing LaSota, F, Clone 30, and B1 type LaSota strains was observed for up to 35 days keeping them at 37°C. From the most thermostability yielding sample, two rRT-PCR standard curves were developed: (1) By plotting the cycle threshold (C T ) values as obtained from 10-fold serial dilutions up to 10 -3 against their corresponding log (to the base 10) dilutions and (2) by plotting the C T values obtained from serial HA dilutions up to 2 -4 against their corresponding HA titer dilutions. The PCR efficiencies based on which the graphs were fitted were also evaluated., Results: The vaccine from the LaSota strain withstood 37°C for 35 days with a gradual declination of HA titer over time, and this vaccine also had the highest initial HA titer, which was 2 11 . The vaccine made from F strain was inactivated quickly, and it had the lowest HA titer at the beginning of the study. The first standard curve developed can be used to assess the level of virus titer in a diluted sample compared with the titer in the original undiluted vaccine preparation by plotting the C T value obtained from the dilution by rRT-PCR. The second standard curve can be used to calculate the HA titer of a vaccine dilution by plotting the C T value as obtained from the dilution by rRT-PCR., Conclusion: The regression equations for the first and second graphs were y=-3.535x+14.365 and y=-1.081x+13.703, respectively, suggesting that, for every 3.53 cycles, the PCR product would have increased 10 times and 2 times for every 1.08 cycles, respectively, indicating nearly (but not exactly) 100% PCR efficiency.

Background: There are genes whose function remains obscure as they may not have similarities to known regions in the genome. Such known 'unknown' genes constituting the Open Reading Frames (ORF) that remain in the epigenome are termed as orphan genes and the proteins encoded by them but having no experimental evidence of translation are termed as 'Hypothetical Proteins' (HPs)., Objectives: We have enhanced our former database of Hypothetical Proteins (HP) in human (HypoDB) with added annotation, application programming interfaces and descriptive features. The database hosts 1000+ manually curated records of the known 'unknown' regions in the human genome. The new updated version of HypoDB with functionalities (Blast, Match) is freely accessible at http://www.bioclues.org/hypo2., Methods: The total collection of HPs were checked using experimentally validated sets (from Swiss-Prot) or non-experimentally validated set (TrEMBL) or the complete set (UniProtKB). The database was designed with java at the core backend, integrated with databases, viz. EMBL, PIR, HPRD and those including descriptors for structural databases, interaction and association databases., Results: The HypoDB constituted Application Programming Interfaces (API) for implicitly searching resources linking them to other databases like NCBI Link-out in addition to multiple search capabilities along with advanced searches using integrated bio-tools, viz. Match and BLAST were incorporated., Conclusion: The HypoDB is perhaps the only open-source HP database with a range of tools for common bioinformatics retrievals and serves as a standby reference to researchers who are interested in finding candidate sequences for their potential experimental work., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

MicroRNAs (miRNAs), are small non-coding RNAs of approximately 22 nucleotides in length, playing an important role in regulating gene expression post-transcriptionally. Understanding the effect of miRNA regulation in a pathway-specific manner unravels the approaches adopted to apprehend biological mechanisms, the information, which is scanty for researchers, not primed already for miR related research. Here, we describe a quick perspective in 5 steps with probable approaches and assays at every level to unravel the specific role of a microRNA, miR-145a-5p, as an example. This perspective as a guide would help in identifying novel targets for a microRNA, as shown for miR-145a-5p, which down-regulated the mRNA expression of ADD3 and BRCA2, using bioinformatic tools and experimental assays., (Copyright © 2017 Elsevier B.V. All rights reserved.)

CRISPR-Cas9 is an RNA-mediated adaptive immune system that protects bacteria and archaea from viruses or plasmids. Herein we discuss the recent development of CRISPR-Cas9 into a key technology for genome editing, targeting, and regulation in a wide range of organisms and cell types. It requires a custom designed single guide-RNA (sgRNA), a Cas9 endonuclease, and PAM sequences in the target region. The sgRNA-Cas9 complex binds to its target and creates a double-strand break (DSB) that can be repaired by non-homologous end joining (NHEJ) or by the homology-directed repair (HDR) pathway, modifying or permanently replacing the genomic target sequence. Additionally, we highlight recent advances in the repurposing of CRISPR-Cas9 for repression, activation, and loci imaging. In this review, we underline the current progress and the future potential of the CRISPR-Cas9 system towards biomedical, therapeutic, industrial, and biotechnological applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are small non-coding RNAs ~22 nucleotides long that do not encode for proteins but have been reported to influence gene expression in normal and abnormal health conditions. Though a large body of scientific literature on miRNAs exists, their network level profile linking molecules with their corresponding phenotypes, is less explored. Here, we studied a network of 191 human miRNAs reported to play a role in 30 human cardiac diseases. Our aim was to study miRNA network properties like hubness and preferred associations, using data mining, network graph theory and statistical analysis. A total of 16 miRNAs were found to have a disease node connectivity of >5 edges (i.e., they were linked to more than 5 diseases) and were considered hubs in the miRNAcardiac disease network. Alternatively, when diseases were considered as hubs, >10 of miRNAs showed up on each 'disease hub node'. Of all the miRNAs associated with diseases, 19 miRNAs (19/24= 79.1% of upregulated events) were found to be upregulated in atherosclerosis. The data suggest micro RNAs as early stage biological markers in cardiac conditions with potential towards microRNA based therapeutics.

Expression of synthetic proteins from intergenic regions of E. coli and their functional association was recently demonstrated (Dhar et al. in J Biol Eng 3:2, 2009. doi:10.1186/1754-1611-3-2). This gave birth to the question: if one can make 'user-defined' genes from non-coding genome-how big is the artificially translatable genome? (Dinger et al. in PLoS Comput Biol 4, 2008; Frith et al. in RNA Biol 3(1):40-48, 2006a; Frith et al. in PLoS Genet 2(4):e52, 2006b). To answer this question, we performed a bioinformatics study of all reported E. coli intergenic sequences, in search of novel peptides and proteins, unexpressed by nature. Overall, 2500 E. coli intergenic sequences were computationally translated into 'protein sequence equivalents' and matched against all known proteins. Sequences that did not show any resemblance were used for building a comprehensive profile in terms of their structure, function, localization, interactions, stability so on. A total of 362 protein sequences showed evidence of stable tertiary conformations encoded by the intergenic sequences of E. coli genome. Experimental studies are underway to confirm some of the key predictions. This study points to a vast untapped repository of functional molecules lying undiscovered in the non-expressed genome of various organisms.

MicroRNAs are a ~22 nucleotide small non-coding RNAs found in animals, plants and viruses. They regulate key cellular processes by enhancing, degrading or silencing protein coding targets. Currently most of the data on miRNA is available from Drosophila . Given their important post-transcriptional role in several organisms, there is a need to understand the miRNA mediated processes in normal and abnormal conditions. Here we report four novel microRNAs ast - mir - 2502, ast - mir - 2559, ast - mir - 3868 and ast - mir - 9891 in Anopheles stephensi identified from a set of 3,052 transcriptome sequences, showing average minimum free energy of -31.8 kcal/mol of duplex formation with mRNA indicating their functional relevance. Phylogenetic study shows conservation of sequence signatures within the Class Insecta. Furthermore, 26 potential targets of these four miRNAs have been predicted that play an important role in the mosquito life-cycle. This work leads to novel leads and experimental possibilities for improved understanding of gene regulatory processes in mosquito.

Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer's disease (AD). Secondary and tertiary protein structure predictions followed by protein-protein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD.

Motivation: Recently, we made synthetic proteins from non-coding DNA of Escherichia coli. Encouraged by this, we asked: can we artificially express pseudogenes into novel and functional proteins? What kind of structures would be generated? Would these proteins be stable? How would the organism respond to the artificial reactivation of pseudogenes?, Results: To answer these questions, we studied 16 full-length protein equivalents of pseudogenes. The sequence-based predictions indicated interesting molecular and cellular functional roles for pseudogene-derived proteins. Most of the proteins were predicted to be involved in the amino acid biosynthesis, energy metabolism, purines and pyrimidine biosynthesis, central intermediary metabolism, transport and binding. Interestingly, many of the pseudogene-derived proteins were predicted to be enzymes. Furthermore, proteins showed strong evidence of stable tertiary structures. The prediction scores for structure, function and stability were found to be favorable in most of the cases., Impact: To our best knowledge, this is the first such report that predicts the possibility of making functional and stable proteins from pseudogenes. In future, it would be interesting to experimentally synthesize and validate these predictions., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Ecologically significant species in controlling pests, Oecophylla smaragdina uses its venom to paralyze their prey and to communicate with their colony mates. But no significant analysis of the ant's venom gland secretions has been carried out hitherto. This study describes the identification of venom constituents of Oecophylla smaragdina using coupled gas chromatography and mass spectroscopy (GC-MS) analysis. The results indicate the anticipated presence of a neurotoxin i.e., 2, 5 dipropyl decahydroquinoline and phenol, 2, 4-bis (1, 1 dimethylethyl). This is the first report on presence of decahydroquinolines in the venom of formicinae ant species of genera Oecophylla., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Metabolic engineering is an important area of research that involves editing genetic networks to overproduce a certain substance by the cells. Using a combination of genetic, metabolic, and modeling methods, useful substances have been synthesized in the past at industrial scale and in a cost-effective manner. Currently, metabolic engineering is being used to produce sufficient, economical, and eco-friendly biofuels. In the recent past, a number of efforts have been made towards engineering biosynthetic pathways for large scale and efficient production of biofuels from biomass. Given the adoption of metabolic engineering approaches by the biofuel industry, this paper reviews various approaches towards the production and enhancement of renewable biofuels such as ethanol, butanol, isopropanol, hydrogen, and biodiesel. We have also identified specific areas where more work needs to be done in the future.

The aim of this work was to detect allosteric hotspots signatures characterizing protein regions acting as the 'key drivers' of global allosteric conformational change. We computationally estimated the relative strength of intra-molecular interaction in allosteric proteins between two putative allostery-susceptible sites using a co-evolution model based upon the optimization of the cross-correlation in terms of free-energy-transfer hydrophobicity scale (Tanford scale) distribution along the chain. Cross-Recurrence Quantification Analysis (Cross-RQA) applied on the sequences of allostery susceptible sites showed evidence of strong interaction amongst allosteric susceptible sites. This could be due to transient weak molecular bonds between allostery susceptible patches enabling regions far-apart to come together. Further, using a large protein dataset, by comparing allosteric protein set with a randomly generated sequence population as well as a generic protein set, we reconfirmed our earlier findings that hydrophobicity patterning (as formalized by Recurrence Quantification Analysis (RQA) descriptors) may serve as determinant of allostery and its relevance in the transmission of allosteric conformational change. We applied RQA to free-energy-transfer hydrophobicity-transformed amino acid sequences of the allostery dataset to extract allostery specific global sequence features. These free-energy-transfer hydrophobicity-based RQA markers proved to be representative of allosteric signatures and not related to the differences between randomly generated and real proteins. These free-energy-transfer hydrophobicity-based RQA markers when evaluated by pattern recognition tools could distinguish allosteric proteins with 92% accuracy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Identification of hub proteins from sequence is a challenge in molecular biology. Therefore, it is of interest to predict protein hubs in networks. We describe the prediction of protein "hub" using physiochemical, thermodynamic and conformational properties of amino acid residues in sequence. We have used twenty sequence based features to identify hub behaviour. Linear discriminant analysis and normalised Bayesian approach were utilized for identifying hub proteins solely using these sequence features in E. coli/H. sapiens datasets with accuracies of 99.5/98.6, 87.8/89.6 and 90.1/92.6, respectively.

Allostery is the phenomenon of changes in the structure and activity of proteins that appear as a consequence of ligand binding at sites other than the active site. Studying mechanistic basis of allostery leading to protein design with predetermined functional endpoints is an important unmet need of synthetic biology. Here, we screened the amino acid sequence landscape in search of sequence-signatures of allostery using Recurrence Quantitative Analysis (RQA) method. A characteristic vector, comprised of 10 features extracted from RQA was defined for amino acid sequences. Using Principal Component Analysis, four factors were found to be important determinants of allosteric behavior. Our sequence-based predictor method shows 82.6% accuracy, 85.7% sensitivity and 77.9% specificity with the current dataset. Further, we show that Laminarity-Mean-hydrophobicity representing repeated hydrophobic patches is the most crucial indicator of allostery. To our best knowledge this is the first report that describes sequence determinants of allostery based on hydrophobicity. As an outcome of these findings, we plan to explore possibility of inducing allostery in proteins.

Biological systems are inherently noisy. Predicting the outcome of a perturbation is extremely challenging. Traditional reductionist approach of describing properties of parts, vis-a-vis higher level behaviour has led to enormous understanding of fundamental molecular level biology. This approach typically consists of converting genes into junk (knock-down) and garbage (knock-out) and observe how a system responds. To enable broader understanding of biological dynamics, an integrated computational and experimental strategy was formally proposed in mid 1990s leading to the re-emergence of Systems Biology. However, soon it became clear that natural systems were far more complex than expected. A new strategy to address biological complexity was proposed at MIT (Massachusetts Institute of Technology) in June 2004, when the first meeting of synthetic biology was held. Though the term 'synthetic biology' was proposed during 1970s (Szybalski in Control of gene expression, Plenum Press, New York, 1974), the usage of the original concept found an experimental proof in 2000 with the demonstration of a three-gene circuit called repressilator (Elowitz and Leibler in Nature, 403:335-338, 2000). This encouraged people to think of forward engineering biology from a set of well described parts.

We present chest radiographs, echocardiographic image, and selective coronary angiogram of an 18-year old patient with Hutchinson-Gilford progeria syndrome.

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior. Currently, there are only hints of such organizing principles but no absolute evidences. Here, we present an approach as old as Mendel that could help uncover fundamental organizing principles in biology. Our approach essentially consists of identifying constants at various levels and weaving them into a hierarchical chassis. As we identify and organize constants, from pair-wise interactions to networks, our understanding of the fundamental principles in biology will improve, leading to a theory in biology.

Background: The current knowledge of genes and proteins comes from 'naturally designed' coding and non-coding regions. It would be interesting to move beyond natural boundaries and make user-defined parts. To explore this possibility we made six non-natural proteins in E. coli. We also studied their potential tertiary structure and phenotypic outcomes., Results: The chosen intergenic sequences were amplified and expressed using pBAD 202/D-TOPO vector. All six proteins showed significantly low similarity to the known proteins in the NCBI protein database. The protein expression was confirmed through Western blot. The endogenous expression of one of the proteins resulted in the cell growth inhibition. The growth inhibition was completely rescued by culturing cells in the inducer-free medium. Computational structure prediction suggests globular tertiary structure for two of the six non-natural proteins synthesized., Conclusion: To our best knowledge, this is the first study that demonstrates artificial synthesis of non-natural proteins from existing genomic template, their potential tertiary structure and phenotypic outcome. The work presented in this paper opens up a new avenue of investigating fundamental biology. Our approach can also be used to synthesize large numbers of non-natural RNA and protein parts for useful applications.

Unlabelled: The computational prediction of protein-protein interactions (PPI) is an essential complement to direct experimental evidence. Traditional approaches rely on less available or computationally predicted surface properties, show database-specific performances and are computationally expensive for large-scale datasets. Several sensitivity and specificity issues remain. Here, we report a novel method based on 'Amino-acid Residue Associations' (ARA) among interacting proteins which utilizes the accurate and easily available primary sequence. Large scale PPI datasets for six model species (from E. coli to human) were studied. The ARA method shows up to 73%sensitivity and 78% specificity. Furthermore, the method performs remarkably well in terms of stability and generalizability. The performance of ARA method benchmarked against existing prediction techniques shows performance improvement upto 25%. Ability of ARA method to predict PPI across species and across databases is also demonstrated. Overall, the ARA method provides a significant improvement over existing ones in correctly identifying large scale protein-protein interactions,irrespective of the data resource, network size or organism., Availability: The MATLAB code for ARA approach will be made available upon request.

Hubs are ubiquitous network elements with high connectivity. One of the common observations about hub proteins is their preferential attachment leading to scale-free network topology. Here we examine the question: does rich protein always get richer, or can it get poor too? To answer this question, we compared similar and well-annotated hub proteins in six organisms, from prokaryotes to eukaryotes. Our findings indicate that hub proteins retain, gain or lose connectivity based on the context. Furthermore, the loss or gain of connectivity appears to correlate with the functional role of the protein in a given system.

Systems biology is an approach to explain the behaviour of a system in relation to its individual components. Synthetic biology uses key hierarchical and modular concepts of systems biology to engineer novel biological systems. In my opinion the next step in biology is to use molecule-to-phenotype data using these approaches and integrate them in the form a periodic table. A periodic table in biology would provide chassis to classify, systematize and compare diversity of component properties vis-a-vis system behaviour. Using periodic table it could be possible to compute higher- level interactions from component properties. This paper examines the concept of building a bio-periodic table using protein fold as the fundamental unit.

One of the earliest events in the signal transduction cascade that initiates a DNA damage checkpoint is the phosphorylation on serine 139 of histone H2AX (gammaH2AX) at DNA double-strand breaks (DSBs). However, the role of gammaH2AX in DNA repair is poorly understood. To address this question, we generated chicken DT40 cells carrying a serine to alanine mutation at position 139 of H2AX (H2AX(-/S139A)) and examined their DNA repair capacity. H2AX(-/S139A) cells exhibited defective homologous recombinational repair (HR) as manifested by delayed Rad51 focus formation following ionizing radiation (IR) and hypersensitivity to the topoisomerase I inhibitor, camptothecin (CPT), which causes DSBs at replication blockage. Deletion of the Rad51 paralog gene, XRCC3, also delays Rad51 focus formation. To test the interaction of Xrcc3 and gammaH2AX, we disrupted XRCC3 in H2AX(-/S139A) cells. XRCC3(-/-)/H2AX(-/S139A) mutants were not viable, although this synthetic lethality was reversed by inserting a transgene that conditionally expresses wild-type H2AX. Upon repression of the wild-type H2AX transgene, XRCC3(-/-)/H2AX(-/S139A) cells failed to form Rad51 foci and exhibited markedly increased levels of chromosomal aberrations after CPT treatment. These results indicate that H2AX and XRCC3 act in separate arms of a branched pathway to facilitate Rad51 assembly.

In tissue development, juxtacrine signaling often propagates across cells, carrying and delivering temporal and spatial information for cells to make correct patterning. Observed complex and accurate tissue patterning indicates that signaling propagation via ligand-receptor interactions is precisely controlled. It is important and interesting to reveal the possible control mechanisms. The directionality of signaling in cells, which is a common issue for all intercellular signaling pathways, is a critical aspect. To understand the propagation of Notch signaling in presomitic mesoderm cells in the mouse, a novel method is used to build a multicellular model to simulate Notch signaling. Simulation reveals that the transient block of Notch by Notch induced Lfng and the delayed removal of the block by another Notch induced protein Hes7 may explain the observed unidirectional propagation of Notch signaling in these cells. Both mutation in and overexpression of lfng cause the same signaling profile in the tissue, due to the inappropriate timing of Notch signaling block by Lfng. The reverse Notch/Delta signaling quickly develops into reciprocating signaling among cells, causing irregular expression of cyclic genes. Irregular Notch signaling in cells would change their response to the positional information provided by the Fgf8 gradient, resulting in disordered and irregular somite segmentation. As Notch signaling is highly conserved, we hypothesize that the mechanism of controlling unidirectional propagation of signaling in cells by transient receptor block may exist in other tissues and in other vertebrates. Our simulation results also suggest that segmentation clock and unidirectional propagation may be inherently coupled in Notch signaling.