Hasil untuk "Biotechnology"

Martin Steinegger, J. Söding

VOLUME 35 NUMBER 11 NOVEMBER 2017 NATURE BIOTECHNOLOGY performance was to combine the doublematch criterion with making k-mers as long as possible, which required finding similar and not just exact k-mers. This effectively bases our decision on up to 2 × 7 = 14 residues instead of just 2 × 3 in BLAST or 12 letters on a size-11 alphabet in DIAMOND. MMseqs2 is parallelized on three levels: time-critical parts are manually vectorized, queries can be distributed to multiple cores, and the target database can be split into chunks distributed to multiple servers. Because MMseqs2 needs no random memory access in its innermost loop, its runtime scales almost inversely with the number of cores used (Supplementary Fig. 2). MMseqs2 requires 13.4 GB plus 7 bytes per amino acid to store the database in memory, MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets

G. Boratyn, Christiam Camacho, Peter S. Cooper et al.

The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is http://blast.ncbi.nlm.nih.gov.

Lizeng Gao, Jie Zhuang, L. Nie et al.

A. Lu, E. Salabaş, F. Schüth

Wangxia Wang, B. Vinocur, A. Altman

A. Ragauskas, Charlotte K. Williams, B. Davison et al.

Biomass represents an abundant carbon-neutral renewable resource for the production of bioenergy and biomaterials, and its enhanced use would address several societal needs. Advances in genetics, biotechnology, process chemistry, and engineering are leading to a new manufacturing concept for converting renewable biomass to valuable fuels and products, generally referred to as the biorefinery. The integration of agroenergy crops and biorefinery manufacturing technologies offers the potential for the development of sustainable biopower and biomaterials that will lead to a new manufacturing paradigm.

Aoao Wu, Liu Xu, Yinzhu Zhang et al.

Tannic acid (TA), a polyphenolic compound derived from plants, exhibits anti-inflammatory, antibacterial, antiviral, and antioxidant biological activities. Salmonella, a prevalent foodborne pathogen, poses a significant threat to poultry, resulting in considerable economic losses for the animal husbandry industry. In this study, we investigated the protective effects of TA against lung and intestinal injuries induced by a transient Salmonella infection in broilers. After a ten-day infection period, although Salmonella was not detected in the intestinal content of broilers, the infected broilers exhibited reduced body weight and compromised intestinal barrier function. Salmonella infection facilitated the growth of detrimental bacteria in the lungs and ileums, triggering an inflammatory response. TA inhibited the pathogen's colonization in the lungs and reduced serum levels of lipopolysaccharide (LPS) as well as lung levels of myeloperoxidase (MPO). Moreover, TA down-regulated the expression of pro-inflammatory cytokines and hindered the polarization of M1 macrophages in the lungs.In summary, TA mitigates Salmonella-induced lung inflammation and immune imbalance by its anti-inflammatory, antioxidant and antibacterial properties in broilers.

Sunmee Choi, Suk Hyun Kwon, Gi Seok Kwon et al.

Potyviruses, a major group of plant viruses, utilize HC-Pro, a multifunctional protein, to suppress RNA silencing, a crucial plant defense mechanism. While HC-Pro’s role in RNA silencing suppression has been studied in several potyviruses, the specific mechanisms and interactions of HC-Pro from bean yellow mosaic virus (BYMV), a potyvirus with a broad host range, remain poorly understood. To address this knowledge gap, this study aimed to investigate the role of P1 and HC-Pro from BYMV in enhancing gene expression and suppressing RNA silencing in <i>Nicotiana benthamiana</i>. The findings revealed that BYMV HC-Pro significantly enhanced reporter transgene expression, likely through the suppression of RNA silencing pathways. This effect was further amplified by the presence of the P1 protein, another viral component. Analysis of HC-Pro mutants revealed that the conserved FRNK box within HC-Pro is crucial for its suppression activity and its ability to enhance gene expression. Furthermore, HC-Pro significantly downregulated the expression of key RNA silencing-related genes, including <i>DCL2</i>, <i>DCL4</i>, <i>RDR6</i>, <i>AGO1-1</i>, <i>AGO1-2</i>, and <i>AGO2</i>. These findings demonstrate that the BYMV P1::HC-Pro complex serves as a potent suppressor of RNA silencing and a promising tool for enhancing gene expression in plants. The results have significant implications for developing novel strategies in plant biotechnology, particularly for the production of high-value recombinant proteins.

Vladimir Vinarsky, Stefania Pagliari, Bacel Aldabash et al.

Abstract Cardiac diseases are fueled by extracellular matrix (ECM) remodelling. Together with the altered ECM chemical composition, the mechanical turmoil associated with ECM maladaptive remodelling in the pathological heart drives the shuttling of Yes Associated Protein 1 (YAP1) into cardiomyocyte (CM) nuclei that results either in cell cycle re-entry or cardiomyocyte hypertrophy. The mechanism of YAP1 reactivation and factors driving qualitatively different cellular outcomes is not well understood. Here we employed mechanical actuation as a proxy reproducing ECM remodelling in vitro to trigger YAP1 nuclear shuttling in contractile cardiomyocytes derived from human embryonic and induced pluripotent stem cells (hPSCs). By using hPSC lines in which YAP1 expression has been genetically depleted, super-resolution microscopy and electrophysiological measurements, we show that ECM-triggered nuclear presence of endogenous YAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of their electrophysiological properties and calcium dynamics. We eventually exploit engineered heart tissues (EHTs) to demonstrate that the net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth that results in reduced force development. These results suggest that the re-activation of endogenous YAP1 following ECM maladaptive remodelling promotes cardiomyocyte contractility by restructuring the sarcomere apparatus and the maturation of electrophysiological properties via transcriptionally dependent and independent mechanisms.

M. S. Rajeevan, B. Mini Devi

In an age of fast-paced technological change, patents have evolved into not only legal mechanisms of intellectual property, but also structured storage containers of knowledge full of metadata, categories, and formal innovation. This chapter proposes to reframe patents in the context of information science, by focusing on patents as knowledge artifacts, and by seeing patents as fundamentally tied to the global movement of scientific and technological knowledge. With a focus on three areas, the inventions of AIs, biotech patents, and international competition with patents, this work considers how new technologies are challenging traditional notions of inventorship, access, and moral accountability.The chapter provides a critical analysis of AI's implications for patent authorship and prior art searches, ownership issues arising from proprietary claims in biotechnology to ethical dilemmas, and the problem of using patents for strategic advantage in a global context of innovation competition. In this analysis, the chapter identified the importance of organizing information, creating metadata standards about originality, implementing retrieval systems to access previous works, and ethical contemplation about patenting unseen relationships in innovation ecosystems. Ultimately, the chapter called for a collaborative, transparent, and ethically-based approach in managing knowledge in the patenting environment highlighting the role for information professionals and policy to contribute to access equity in innovation.

Jing Sun, Jing Wang, Xin Jiang et al.

Abstract Background The intracellular bacterium Listeria monocytogenes is an attractive vector for cancer immunotherapy as it can effectively deliver tumor antigens to antigen-presenting cells, leading to a robust antitumor response. Results In this study, we developed a novel vaccine platform called Listeria-based Live Attenuated Double Substitution (LADS), which involves introducing two amino acid substitutions (N478AV479A) into the virulence factor listeriolysin O (LLO). LADS is a safe vaccine platform, with an attenuation of nearly 7000-fold, while retaining complete immunogenicity due to the absence of deletion of any virulence factors. We developed two LADS-based vaccines, LADS-E7 and LADS-AH1, which deliver the human papillomavirus (HPV) type 16 E7 oncoprotein and murine colon carcinoma immunodominant antigen AH1, respectively. Treatment with LADS-E7 or LADS-AH1 significantly inhibited and regressed established tumors, while also dramatically increasing the populations of tumor-infiltrated antigen-specific CD8+ T cells. RNA-sequencing analysis of tumor tissue samples revealed that LADS-E7 altered the expression of genes related to the immune response. Moreover, intratumoral injection of LADS-based vaccines induced strong antitumor responses, generating systemic antitumor responses to control distant tumor growth. Encouragingly, LADS-E7 or LADS-AH1 immunization effectively prevented tumor formation and growth. Conclusions Our findings demonstrate that LADS-based vaccines represent a more powerful platform for the development of immunotherapeutic and preventive vaccines against cancers and infectious diseases.

Ragavendran Chinnasamy, Kamaraj Chinnaperumal, Natarajan Devarajan et al.

Xuebing Han, Xiangdong Hu, Wei Jin et al.

Weaning is a critical transitional point in the life cycle of piglets. Early weaning can lead to post-weaning syndrome, destroy the intestinal barrier function and microbiota homeostasis, cause diarrhea and threaten the health of piglets. The nutritional components of milk and solid foods consumed by newborn animals can affect the diversity and structure of their intestinal microbiota, and regulate post-weaning diarrhea in piglets. Therefore, this paper reviews the effects and mechanisms of different nutrients, including protein, dietary fiber, dietary fatty acids and dietary electrolyte balance, on diarrhea and health of piglets by regulating intestinal function. Protein is an essential nutrient for the growth of piglets; however, excessive intake will cause many harmful effects, such as allergic reactions, intestinal barrier dysfunction and pathogenic growth, eventually aggravating piglet diarrhea. Dietary fiber is a nutrient that alleviates post-weaning diarrhea in piglets, which is related to its promotion of intestinal epithelial integrity, microbial homeostasis and the production of short-chain fatty acids. In addition, dietary fatty acids and dietary electrolyte balance can also facilitate the growth, function and health of piglets by regulating intestinal epithelial function, immune system and microbiota. Thus, a targeted control of dietary components to promote the establishment of a healthy bacterial community is a significant method for preventing nutritional diarrhea in weaned piglets.

Mirela Džehverović, Amela Pilav, Belma Jusić et al.

Numerous archaeological sites in Bosnia and Herzegovina represent a historical heritage and testify to the rich cultural, social, and political life of medieval Bosnia. Bobovac, the capital of the Bosnian Kingdom after King Tvrtko I's coronation in 1377, featured a royal complex with a palace, church, and fortification. Recent molecular-genetic research on skeletal remains from Bobovac aims to uncover medieval ancestors' customs and genetic origins. Fifteen well-preserved teeth samples from Bobovac were processed. STR amplification employed PowerPlex® Fusion and Investigator® 24plex QS Kits, with Y-STR profiles generated using the PowerPlex® Y23 System. Fourteen partial autosomal STR profiles were obtained, enabling sex determination and kinship analysis. STR amplification success varied due to ancient DNA degradation, with larger loci showing lower amplification rates. Kinship analysis confirmed appropriate marker selection, demonstrating high reliability for determining close relationships. Integrating aDNA analysis with archaeological research enhances our understanding of historical populations, connecting archaeology and forensic genetics to contribute to the broader narrative of human history.

Prasanth Tej Kumar Jagannadham, Thirugnanavel Anbalagan, Sonia Balyan et al.

Mandarin orange (Citrus reticulata Blanco) is the most common citrus fruit, covering nearly 42 % of the total citrus cultivation area in India. The main varieties of mandarin oranges cultivated in India include Nagpur Mandarin, Khasi Mandarin, Coorg Mandarin and Sikkim Mandarin. Globally, genomic data is being used to unravel the complexities and mysteries of citrus taxonomy. However, despite India being a primary centre of citrus origin, these valuable genomic resources remain underutilized. Here, we conducted whole genome resequencing of four mandarin genotypes viz., Nagpur Mandarin (22,861,254 bp raw reads), Sikkim Mandarin (24,160,847 bp raw reads), Coorg Mandarin (27,974,860 bp raw reads), and Khasi Mandarin (40,532,383 bp raw reads) using Illumina Novaseq 6000 sequencing platform with 28x sequencing coverage. These genomic sequences will provide valuable insights into the taxonomic complexities and evolutionary history of mandarin oranges. The identified SNPs can further be used to study the evolution of flowering patterns in citrus, especially under tropical and subtropical conditions. The NGS data obtained (FASTQ format) for all four mandarin genotypes have been deposited in the Indian Biological Data Centre (https://ibdc.dbtindia.gov.in/inda/submittedStudyHome) under INDA study Id INRP000149. The sample accession numbers are INS0004744 (Sikkim Mandarin), INS0004745 (Nagpur Mandarin), INS0004746 (Coorg Mandarin), INS0004747 (Khasi Mandarin).

Atiqur Rahman, Md. Hasan Sofiur Rahman, Md. Shakil Uddin et al.

The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop development. DNA methylation plays a part in the regulation of both the chromatin structure and gene expression, and the enzyme involved, DNA methyltransferase, executes the methylation process within the plant genome. By regulating crucial biological pathways, epigenetic changes actively contribute to the creation of the phenotype. Therefore, epigenome editing may assist in overcoming some of the drawbacks of genome editing, which can have minor off-target consequences and merely facilitate the loss of a gene’s function. These drawbacks include gene knockout, which can have such off-target effects. This review provides examples of several molecular characteristics of DNA methylation, as well as some plant physiological processes that are impacted by these epigenetic changes in the plants. We also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.

Yijia Xiao, Edward Sun, Yiqiao Jin et al.

RNAs are essential molecules that carry genetic information vital for life, with profound implications for drug development and biotechnology. Despite this importance, RNA research is often hindered by the vast literature available on the topic. To streamline this process, we introduce RNA-GPT, a multi-modal RNA chat model designed to simplify RNA discovery by leveraging extensive RNA literature. RNA-GPT integrates RNA sequence encoders with linear projection layers and state-of-the-art large language models (LLMs) for precise representation alignment, enabling it to process user-uploaded RNA sequences and deliver concise, accurate responses. Built on a scalable training pipeline, RNA-GPT utilizes RNA-QA, an automated system that gathers RNA annotations from RNACentral using a divide-and-conquer approach with GPT-4o and latent Dirichlet allocation (LDA) to efficiently handle large datasets and generate instruction-tuning samples. Our experiments indicate that RNA-GPT effectively addresses complex RNA queries, thereby facilitating RNA research. Additionally, we present RNA-QA, a dataset of 407,616 RNA samples for modality alignment and instruction tuning, further advancing the potential of RNA research tools.

Jacopo Nicoletti, Leonardo Puppulin, Julie Routurier et al.

Piezoelectricity, the generation of electric charge in response to mechanical stress, is a key property in both natural and synthetic materials. This study significantly boosts the piezoelectric response of chitosan, a biodegradable biopolymer, by integrating chitin/chitosan nanocrystals into natural chitosan-based thin film elastomers. The resulting materials achieve d$_{33}$ values of 15-19 pmV$^{-1}$, a marked improvement over the 5-9 pmV$^{-1}$ observed in pure chitosan films thanks to increased crystallinity from the nanocrystals. We utilize piezoresponse force microscopy (PFM) to accurately measure the d$_{33}$ coefficient, employing an engineered extraction method that eliminates the electrostatic contribution, which can overestimate the piezoelectric response. The resulting chitosan elastomers exhibit elastic deformation up to 40\% strain and a Young's modulus of approximately 100 MPa, similar to soft tissues. These properties, along with the fact that the employed materials can be entirely crafted from upcycled biowaste, make these elastomers ideal for prosthetics, wearable devices, energy harvesters, and sustainable transducers. Our findings underscore the potential of chitosan-based piezoelectric materials for advanced applications in biotechnology, soft robotics, and the green Internet of Things.

Ian Murphy, Keren Bobilev, Daichi Hayakawa et al.

Attaching enzymes to nanostructures has proven useful to the study of enzyme functionality under controlled conditions and has led to new technologies. Often, the utility and interest of enzyme-tethered nanostructures lie in how the enzymatic activity is affected by how the enzymes are arranged in space. Therefore, being able to conjugate enzymes to nanostructures while preserving the enzymatic activity is essential. In this paper, we present a method to conjugate single-stranded DNA to the enzyme urease while maintaining enzymatic activity. We show evidence of successful conjugation and quantify the variables that affect the conjugation yield. We also show that the enzymatic activity is unchanged after conjugation compared to the enzyme in its native state. Finally, we demonstrate the tethering of urease to nanostructures made using DNA origami with high site-specificity. Decorating nanostructures with enzymatically-active urease may prove to be useful in studying, or even utilizing, the functionality of urease in disciplines ranging from biotechnology to soft-matter physics. The techniques we present in this paper will enable researchers across these fields to modify enzymes without disrupting their functionality, thus allowing for more insightful studies into their behavior and utility.

Eric W. Hester, Sean P. Carney, Vishwesh Shah et al.

Liquid-liquid phase separation is key to understanding aqueous two-phase systems (ATPS) arising throughout cell biology, medical science, and the pharmaceutical industry. Controlling the detailed morphology of phase-separating compound droplets leads to new technologies for efficient single-cell analysis, targeted drug delivery, and effective cell scaffolds for wound healing. We present a computational model of liquid-liquid phase separation relevant to recent laboratory experiments with gelatin-polyethylene glycol mixtures. We include buoyancy and surface-tension-driven finite viscosity fluid dynamics with thermally induced phase separation. We show that the fluid dynamics greatly alters the evolution and equilibria of the phase separation problem. Notably, buoyancy plays a critical role in driving the ATPS to energy-minimizing crescent-shaped morphologies and shear flows can generate a tenfold speedup in particle formation. Neglecting fluid dynamics produces incorrect minimum-energy droplet shapes. The model allows for optimization of current manufacturing procedures for structured microparticles and improves understanding of ATPS evolution in confined and flowing settings important in biology and biotechnology.