Signal Sequence Research Articles

Comprehensive evaluation of the Infinium human MethylationEPIC v2 BeadChip

Infinium Methylation BeadChips are widely used to profile DNA cytosine modifications in large cohort studies for reasons of cost-effectiveness, accurate quantification, and user-friendly data analysis in characterizing these canonical epigenetic marks. In this work, we conducted a comprehensive evaluation of the updated Infinium MethylationEPIC v2 BeadChip (EPICv2). Our evaluation revealed that EPICv2 offers significant improvements over its predecessors, including expanded enhancer coverage, applicability to diverse ancestry groups, support for low-input DNA down to one nanogram, coverage of existing epigenetic clocks, cell type deconvolution panels, and human trait associations, while maintaining accuracy and reproducibility. Using EPICv2, we were able to identify epigenome and sequence signatures in cell line models of DNMT and SETD2 loss and/or hypomorphism. Furthermore, we provided probe-wise evaluation and annotation to facilitate the use of new features on this array for studying the interplay between somatic mutations and epigenetic landscape in cancer genomics. In conclusion, EPICv2 provides researchers with a valuable tool for studying epigenetic modifications and their role in development and disease.

Event-triggered finite-time fuzzy control approach for fractional-order nonlinear chaotic systems with input delay

In this paper, a novel fuzzy event-triggered control approach with guaranteed performance of practical finite-time tracking convergence is constructed for uncertain fractional-order nonlinear chaotic systems in the presence of time-varying input delay. Firstly, fuzzy logic systems are employed to deal with immeasurable systematic information. Secondly, fractional-order command filters are incorporated to circumvent the problem of “complexity explosion” in backstepping controller construction. Meanwhile, a sequence of fractional-order finite-time compensation signals are introduced to counteract the adverse influence of time-varying input delay rapidly. Furthermore, a novel practical finite-time chaos control approach based on event-triggered strategy is proposed, which not only facilitates the decrease of sampling frequency and controller burden dynamically, but also ensures the convergence of all tracking errors towards a small region around the origin in finite time. Finally, through the simulation research, the transient response performance and the chaos-suppression ability of fractional-order chaotic systems stabilized via the suggested approach are rigorously testified.

Molecular Mechanisms of DNA Sequence Selectivity in V(D)J Recombination.

Antigen receptor (AgR) diversity is central to the ability of adaptive immunity in jawed vertebrates to protect against pathogenic agents. The production of highly diverse AgR repertoires is initiated during B and T cell lymphopoiesis by V(D)J recombination, which assembles the receptor genes from component gene segments in a cut-and-paste recombination reaction. Recombination activating proteins, RAG1 and RAG2 (RAG1/2), catalyze V(D)J recombination by cleaving adjacent to recombination signal sequences (RSSs) that flank AgR gene segments. Previous studies defined the consensus RSS as containing conserved heptamer and nonamer sequences separated by a less conserved 12 or 23 base-pair spacer sequence. However, many RSSs deviate from the consensus sequence, and the molecular mechanism for semiselective V(D)J recombination specificity is unknown. The modulation of chromatin structure during V(D)J recombination is essential in the formation of diverse AgRs in adaptive immunity while also reducing the likelihood for off-target recombination events that can result in chromosomal aberrations and genomic instability. Here we review what is presently known regarding mechanisms that facilitate assembly of RAG1/2 with RSSs, the ensuing conformational changes required for DNA cleavage activity, and how the readout of the RSS sequence affects reaction efficiency.

Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia and accounts for 3–5% of cases. The molecular background of this translocation has been incompletely studied, especially in adult cases. We characterized the chromosomal breakpoints of 49 patients with TCF3::PBX1 and the corresponding reciprocal PBX1::TCF3 breakpoints in 15 cases at the molecular level, thus providing an extensive molecular overview of this translocation in a well-defined study patient population. Breakpoints were found to be remarkably clustered not only in TCF3 but also in PBX1. No association with DNA repeats or putative cryptic recombination signal sequence sites was observed. A simplified detection method for breakpoint identification was developed and the feasibility of patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD) was explored. A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established that could serve as a useful alternative to the classical method utilizing rearranged immune gene loci. This study provides the first extensive molecular data set on the chromosomal breakpoints of the t(1;19)/TCF3::PBX1 aberration in adult ALL. Based on the obtained data a generic MRD method was developed that has several theoretical advantages, including an on average higher sensitivity and a greater stability of the molecular marker in the course of disease.

Structural Similarities and Overlapping Activities among Dihydroflavonol 4-Reductase, Flavanone 4-Reductase, and Anthocyanidin Reductase Offer Metabolic Flexibility in the Flavonoid Pathway.

Flavonoids are potent antioxidants that play a role in defense against pathogens, UV-radiation, and the detoxification of reactive oxygen species. Dihydroflavonol 4-reductase (DFR) and flavanone 4-reductase (FNR) reduce dihydroflavonols and flavanones, respectively, using NAD(P)H to produce flavan-(3)-4-(di)ols in flavonoid biosynthesis. Anthocyanidin reductase (ANR) reduces anthocyanidins to flavan-3-ols. In addition to their sequences, the 3D structures of recombinant DFR, FNR and ANR from sorghum and switchgrass showed a high level of similarity. The catalytic mechanism, substrate-specificity and key residues of three reductases were deduced from crystal structures, site-directed mutagenesis, molecular docking, kinetics, and thermodynamic ana-lyses. Although DFR displayed its highest activity against dihydroflavonols, it also showed activity against flavanones and anthocyanidins. It was inhibited by the flavonol quercetin and high concentrations of dihydroflavonols/flavonones. SbFNR1 and SbFNR2 did not show any activity against dihydroflavonols. However, SbFNR1 displayed activity against flavanones and ANR activity against two anthocyanidins, cyanidin and pelargonidin. Therefore, SbFNR1 and SbFNR2 could be specific ANR isozymes without delphinidin activity. Sorghum has high concentrations of 3-deoxyanthocyanidins in vivo, supporting the observed high activity of SbDFR against flavonols. Mining of expression data indicated substantial induction of these three reductase genes in both switchgrass and sorghum in response to biotic stress. Key signature sequences for proper DFR/ANR classification are proposed and could form the basis for future metabolic engineering of flavonoid metabolism.

Molecular cloning and characterization of Pcal_0039, an ATP-/NAD+-independent DNA ligase from hyperthermophilic archaeon Pyrobaculum calidifontis

The genome sequence of hyperthermophilic archaeon Pyrobaculum calidifontis contains an open reading frame, Pcal_0039, which encodes a putative DNA ligase. Structural analysis disclosed the presence of signature sequences of ATP-dependent DNA ligases. We have heterologously expressed Pcal_0039 gene in Escherichia coli. The recombinant protein, majorly produced in soluble form, was purified and functionally characterized. Recombinant Pcal_0039 displayed nick-joining activity between 40 and 85 °C. Optimal activity was observed at 70 °C and pH 5.5. Nick-joining activity was retained even after heating for 1 h at 90 °C, indicating highly thermostable nature of Pcal_0039. The nick-joining activity, displayed by Pcal_0039, was metal ion dependent and Mg2+ was the most preferred. NaCl and KCl inhibited the nick-joining activity at or above 200 mmol/L. The activity catalyzed by recombinant Pcal_0039 was independent of addition of ATP or NAD+ or any other nucleotide cofactor. A mismatch adjacent to the nick, either at 3′- or 5′-end, abolished the nick-joining activity. These characteristics make Pcal_0039 a potential candidate for applications in DNA diagnostics. To the best of our knowledge, Pcal_0039 is the only DNA ligase, characterized from genus Pyrobaculum, which exhibits optimum nick-joining activity at pH below 6.0 and independent of any nucleotide cofactor.

Differentially expressed transcripts study during pregnancy and postpartum anestrus of yak (Bos grunniens)

Background: Yak is the main livestock species in the plateau area, and its reproductive performance is low, usually two years or three years. A very few of yaks recover within a certain period of time after delivery and smoothly enter the next estrous cycle, while most of them enter the postpartum anestrus and show no estrus performance. However, the key biological factors and influencing mechanisms that cause postpartum anestrus in yaks are not clear. Objective: To study the expression of differential transcripts in ovaries of yak during pregnancy and postpartum anestrus. Methods: Each three yaks in pregnancy and anestrus under natural grazing conditions in Haiyan County, Qinghai Province were selected and slaughtered, and their ovaries were collected and sent to Biomarker Technologies. Oxford Nanopore Technologies single-molecule real-time electrical signal sequencing technology was used to perform full-length transcriptome sequencing. Astalavista software was used to identify the types of alternative splicing events in yak estrus and pregnancy, and TAPIS pipeline was used to identify alternative polyadenylation. Results: The results showed that there were 1751 differentially expressed transcripts (DETs) between pregnancy and anestrus in yak, of which 808 were upregulated and 943 were downregulated. GO analysis showed that the biological processes of DETs were mainly reproductive, reproductive and rhythmic processes. KEGG analysis showed that the DET cell junction-related adhesion junction protein (β-catenin) and amino terminal kinase (JNK) were involved in FAs (local adhesion). Phosphatidylinositol-3-kinase (PI3K) is involved in the PI3K/AKT/mTOR signaling pathway. Circadian rhythm output cycle failure (Clock) and brain and muscle tissue aromatic hydrocarbon receptor nuclear transporter-like protein 1 (Bmal1) are involved in circadian rhythm signaling pathway. Conclusion: This study found that β-catenin, JNK, PI3K, Clock and Bmal1 were closely related to postpartum anestrus in yak.

PREDICTION OF STROKE USING EEG SIGNALS

A stroke is a disruption of blood supply to the brain that leads to disability. Rehabilitation can reduce brain damage and other complications and also recover disability due to stroke. One instrument that can be used in post-stroke patients monitoring is Electroencephalogram (EEG). EEG signals are recorded from several channel pairs. So apart from maintaining signal sequences, handling time connectivity between channels is also essential. Therefore, the signal sequence and time connectivity between channels need to be handled simultaneously on two dimensions. The vertical dimension was the multi-channel dimension, and the horizontal dimension was the signal sequences of each channel concerning time. The proposed system uses the 2D-Convolutional Neural Networks method to identify post-stroke based on EEG signals. First, a wavelet filter was used to obtain a frequency range of 1–13 Hz to represent post-stroke patients. The identification results are one of the three levels of stroke, i.e., No Stroke and Minor Stroke.

Heterologous Expression of Recombinant Proteins and Their Derivatives Used as Carriers for Conjugate Vaccines.

Carrier proteins that provide an effective and long-term immune response to weak antigens has become a real breakthrough in the disease prevention, making it available to a wider range of patients and making it possible to obtain reliable vaccines against a variety of pathogens. Currently, research is continuing both to identify new peptides, proteins, and their complexes potentially suitable for use as carriers, and to develop new methods for isolation, purification, and conjugation of already known and well-established proteins. The use of recombinant proteins has a number of advantages over isolation from natural sources, such as simpler cultivation of the host organism, the possibility of modifying genetic constructs, use of numerous promoter variants, signal sequences, and other regulatory elements. This review is devoted to the methods of obtaining both traditional and new recombinant proteins and their derivatives already being used or potentially suitable for use as carrier proteins in conjugate vaccines.

Hybrid thrust sequences – A new structural perspective

Thrust sequences show a range of geometric and kinematic characteristics in cross-sections and in map view. Two types of thrust sequences are commonly observed in thrust systems – forward-breaking and break-back thrust sequences. For nearly half a century, it has been hypothesized that forward-breaking and break-back thrust sequences represent end-members of a continuous spectrum of brittle and ductile structures. Many natural and experimental observations of transitional thrust sequences display both forward-breaking and break-back (hybrid) thrust sequences within the same thrust system. An explanation of hybrid thrust sequence development has neither been provided conceptually nor experimentally. We present geometric and kinematic results of natural observations and numerical experiments that show a transition from forward-breaking to break-back thrust sequences caused by the effects of stratigraphic variations, sedimentary environment, surface processes, critical-wedge effects, progressive deformation with an increase in compressive stress, presence of detachments and their frictional properties, and strain rate. We also discuss numerous geometric, kinematic, chronological and mechanical criteria to identify the characteristic signatures of hybrid thrust sequences. This study provides a template to distinguish different thrust sequences and to characterize the deformation conditions under which hybrid thrust sequences develop in contractional settings. Mechanical and field criteria, displacement patterns imaged on seismic reflection sections across onshore and offshore thrust systems, and the way that thrusts interact in terms of geometry, kinematics and strain, are used to illustrate thrust development.

Expression analysis of HSP70 gene in response to environmental stress in Spodoptera frugiperda (Lepidoptera: Noctuidae)

This study aimed to investigate the role of heat shock proteins in the response of Spodoptera frugiperda to environmental stress. Four Hsp70 genes of S. frugiperda were cloned using reverse transcription–polymerase chain reaction (RT-PCR) and their sequence characteristics were characterized using bioinformatics analysis. RT-qPCR was used to detect Hsp70 at different developmental stages, in different tissues, and under varying environmental stresses (45°C, 36°C, 4°C, ultraviolet-A, and emamectin benzoate) to quantify the relative expression of this gene. Four Hsp70 genes were obtained by cloning, namely SfHsp70-1, SfHsp70-2, SfHsp70-3, and SfHsp70-like, which encode 653, 686, 638, and 627 amino acids, respectively, and all contain the three Hsp70 family signature sequences. Neighbor-joining (NJ) method was used to construct phylogenetic tree, and four Hsp70 of the S. frugiperda species were clustered with Lepidoptera. The results of real-time PCR showed that the SfHsp70s gene was specifically expressed in different tissues at different developmental stages and its expression increased considerably under nearly all environmental stresses in adults. This study shows that the SfHsp70 gene contributes to a large extent to the resistance of S. frugiperda to environmental stress.

Multiplexed and amplified electrochemical aptasensor for sensitive assay of piperaquine and mefloquine

Simultaneous detection and quantification of antimalarial drugs is important for evaluating the spread of their resistance. On the base of the target-induced assembly of branched DNA nanostructure signal amplification and different electrochemical coding tags at distinct potentials, an aptasensing method for multiplexed and highly sensitive detection of piperaquine (PQ) and mefloquine (MQ) antimalarial drugs is established. The target drugs associate with and switch the conformation of the aptamers to release free ssDNA trigger sequences, which initiate the self-assembly of many methylene blue (MB)- and ferrocene (Fc)-labeled auxiliary signal sequences to form branched nano-assemblies on electrode. The electrode-captured MB and Fc tags thus yield highly magnified current reponses at well-resolved potentials for simultaneously monitoring PQ and MQ with respective detection limits as low as 0.061 ng mL−1 (i.e., 0.114 nM) and 0.17 ng mL−1 (i.e., 0.449 nM). Moreover, the simultaneous detection of PQ and MQ in diluted human serum samples has also been verified by the developed sensor, revealing its potential for multiplexed monitoring of different drugs in connection with the corresponding aptamers for various application purposes.

How biological codes break causal chains to enable autonomy for organisms

Autonomy, meaning freedom from exogenous control, requires independence of both constitution and cybernetic regulation. Here, the necessity of biological codes to achieve both is explained, assuming that Aristotelian efficient cause is ‘formal cause empowered by physical force’. Constitutive independence requires closure to efficient causation (in the Rosen sense); cybernetic independence requires transformation of cause–effect into signal-response relations at the organism boundary; the combination of both kinds of independence enables adaptation and evolution. Codes and cyphers translate information from one form of physical embodiment (domain) to another. Because information can only contribute as formal cause to efficient cause within the domain of its embodiment, translation can extend or restrict the range over which information is effective. Closure to efficient causation requires internalised information to be isolated from the cycle of efficient causes that it informs: e.g. Von Neumann self-replicator requires a (template) source of information that is causally isolated from the physical replication system. Life operationalises this isolation with the genetic code translating from the (isolated) domain of codons to that of protein interactions. Separately, cybernetic freedom is achieved at the cell boundary because transducers, which embody molecular coding, translate exogenous information into a domain where it no longer has the power of efficient cause. Information, not efficient cause, passes through the boundary to serve as stimulus for an internally generated response. Coding further extends freedom by enabling historically accumulated information to be selectively transformed into efficient cause under internal control, leaving it otherwise stored inactive. Code-based translation thus enables selective causal isolation, controlling the flow from cause to effect. Genetic code, cell-signalling codes and, in eukaryotes, the histone code, signal sequence based protein sorting and other code-dependent processes all regulate and separate causal chains. The existence of life can be seen as an expression of the power of molecular codes to selectively isolate and thereby organise causal relations among molecular interactions to form an organism.

Signal sequence receptor subunit 3: A novel indicator of immunosuppressive tumor microenvironment and clinical benefits from immunotherapy

BackgroundSignal sequence receptor subunit 3 (SSR3), a translocation-associated protein complex, plays a vital role in various diseases. However, its involvement in human cancers remains unclear. MethodsWe conducted a comprehensive analysis by integrating data from multiple sources, including the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression, Human Protein Atlas, cBioPortal, TIMER, and ImmuCellAI. Additionally, we incorporated data from a clinical trial, two immunotherapy cohorts, and in vitro experiments to investigate SSR3's impact on cancer prognosis and immune response. ResultsOur findings revealed a significant correlation between elevated SSR3 expression and unfavorable prognosis across various cancer types. Amplification is the most common genetic alteration in SSR3. Furthermore, functional enrichment analysis highlighted SSR3's regulatory role in promoting proliferation. In addition, SSR3 also serves as a pivotal mediator bridging the innate and adaptive immune systems and several related signaling pathways. Moreover, the correlation of SSR3 expression with tumor mutation burden in five cancer types, as well as with microsatellite instability in nine cancer types, suggests the potential of SSR3 as a predictive marker for immunotherapy response. To validate this hypothesis, we examined data from patients who underwent immunotherapy treatment. Our analysis revealed that individuals with low SSR3 expression demonstrated higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high SSR3 expression. ConclusionsOur study identifies SSR3 as a potential oncogene in humans, implicated in both tumorigenesis and cancer immunity. Elevated SSR3 expression is indicative of an immunosuppressive tumor microenvironment. Therefore, SSR3 holds promise as a potential prognostic biomarker and a target for immunotherapy in cancer treatment.

A Signal-Denoising Method for Electromagnetic Leakage from USB Keyboards

USB keyboards are commonly used as computer input devices and inevitably generate electromagnetic (EM) leakage signals during their operation, which carry input information. However, due to the weak energy of a keyboard’s EM signal and the small amount of effective information, the received leakage signal is often characterized by a low signal-to-noise ratio (SNR). This low SNR affects the subsequent detection and restoration of the information. In order to solve this problem, this paper proposes a denoising method for USB keyboard EM leakage signals and designs a self-attentive denoising adversarial network (SADAN) based on generative adversarial networks (GANs). The denoiser continuously enhances the denoising ability during the generative adversarial process, and the self-attention mechanism enables it to better learn the dependencies of the keyboard EM leak signal sequences, modelling the long-range relationships between the sequence sample points and reducing the impact of the number of network layers on the relationship acquisition. The method achieves noise suppression in the keyboard leakage signal, improving its SNR while preserving the effective information in the leakage signal and finally obtaining a denoised leakage signal that can be effectively restored to the information.

Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control

Nucleocytoplasmic transport (NCT) in neurons is critical for enabling proteins to enter the nucleus and regulate plasticity genes in response to environmental cues. Such experience-dependent (ED) neural plasticity is central for establishing memory formation and cognitive function and can influence the severity of neurodegenerative disorders like Alzheimer's disease (AD). ED neural plasticity is driven by histone acetylation (HA) mediated epigenetic mechanisms that regulate dynamic activity-dependent gene transcription profiles in response to neuronal stimulation. Yet, how histone acetyltransferases (HATs) respond to extracellular cues in the in vivo brain to drive HA-mediated activity-dependent gene control remains unclear. We previously demonstrated that extracellular stimulation of rat hippocampal neurons in vitro triggers Tip60 HAT nuclear import with concomitant synaptic gene induction. Here, we focus on investigating Tip60 HAT subcellular localization and NCT specifically in neuronal activity-dependent gene control by using the learning and memory mushroom body (MB) region of the Drosophila brain as a powerful in vivo cognitive model system. We used immunohistochemistry (IHC) to compare the subcellular localization of Tip60 HAT in the Drosophila brain under normal conditions and in response to stimulation of fly brain neurons in vivo either by genetically inducing potassium channels activation or by exposure to natural positive ED conditions. Furthermore, we found that both inducible and ED condition-mediated neural induction triggered Tip60 nuclear import with concomitant induction of previously identified Tip60 target genes and that Tip60 levels in both the nucleus and cytoplasm were significantly decreased in our well-characterized Drosophila AD model. Mutagenesis of a putative nuclear localization signal (NLS) sequence and nuclear export signal (NES) sequence that we identified in the Drosophila Tip60 protein revealed that both are functionally required for appropriate Tip60 subcellular localization. Our results support a model by which neuronal stimulation triggers Tip60 NCT via its NLS and NES sequences to promote induction of activity-dependent neuroplasticity gene transcription and that this process may be disrupted in AD.

Exploring Multi-Stage GAN with Self-Attention for Speech Enhancement

Multi-stage or multi-generator generative adversarial networks (GANs) have recently been demonstrated to be effective for speech enhancement. The existing multi-generator GANs for speech enhancement only use convolutional layers for synthesising clean speech signals. This reliance on convolution operation may result in masking the temporal dependencies within the signal sequence. This study explores self-attention to address the temporal dependency issue in multi-generator speech enhancement GANs to improve their enhancement performance. We empirically study the effect of integrating a self-attention mechanism into the convolutional layers of the multiple generators in multi-stage or multi-generator speech enhancement GANs, specifically, the ISEGAN and the DSEGAN networks. The experimental results show that introducing a self-attention mechanism into ISEGAN and DSEGAN leads to improvements in their speech enhancement quality and intelligibility across the objective evaluation metrics. Furthermore, we observe that adding self-attention to the ISEGAN’s generators does not only improves its enhancement performance but also bridges the performance gap between the ISEGAN and the DSEGAN with a smaller model footprint. Overall, our findings highlight the potential of self-attention in improving the enhancement performance of multi-generator speech enhancement GANs.

Genome-Wide Analysis of Family I84 Protease Inhibitor Genes in Three Bivalves Reveals Important Information About the Protein Family's Evolution.

Family I84 serine protease inhibitors are believed to be mollusk specific proteins involved in host defense. The molecular evolution of the family, however, remains to be understood. In this study, the genes of Family I84 protease inhibitors in 3 bivalves, Crassostrea gigas, Crassostrea virginica and Tegillarca granosa, were analyzed at the genomic level. A total of 66 Family I84 genes (22 in C. gigas, 28 in C. virginica and 16 in T. granosa) were identified from the 3 species. They distributed unevenly in the genomes involving 4 chromosomes in C. gigas and 5 chromosomes in C. virginica and T. granosa and some genes were tandemly duplicated. Most genes had 3 exons with 12 genes having 4 exons and 1 gene having 2 exons. All genes but 1 from C. gigas and 1 from T. granosa encoded peptides with a signal sequence at the N-terminus, and the properties of the predicted mature molecules were similar. Four conserved motifs were identified in the 66 amino acid sequences. Collinear analysis revealed higher collinearity between the 2 oyster species in general genes and in Family I84 genes. Phylogenetic analysis of the 66 genes with those previously reported from 3 other bivalves and 1 gastropod showed that Family I84 protease inhibitor genes from the same species tended to be grouped together in terminal branches of the constructed Maximum likelihood tree, but most internal nodes were poorly supported by the bootstrap values. In addition, differences in expression patterns between the genes of a same species were observed in the developmental stages and tissues of C. gigas and T. granosa. Moreover, the co-expression of genes within Family I84 and Family I84 genes with non-Family I84 were also detected in C. gigas and T. granosa. These results suggested that Family I84 protease inhibitor genes evolved by active duplications and structural and functional diversifications after the speciation of related mollusks, and the diversified protease inhibitor family was likely multifunctional.

Length-Dependent Translation Efficiency of ER-Destined Proteins.

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translation apparatus toward a specific organelle. Here, we focus on the mechanisms governing the translation of mRNAs, which encode proteins with an endoplasmic reticulum (ER) signal in human cells. The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches the ER membrane. The commonly accepted model suggests that mRNA that encodes a protein that contains an ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with the ER. In contrast to the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to low ribosome occupancy, the short mRNAs continue the cycle, always facing a translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.

Snakins: antimicrobial potential and prospects of genetic engineering for enhanced disease resistance in plants.

Snakins of the Snakin/Gibberellic Acid Stimulated in Arabidopsis (GASA) family are short sequenced peptides consisting of three different regions: a C-terminal GASA domain, an N-terminal signal sequence and a variable region. The GASA domain is comprised of 12 conserved cysteine residues responsible for the structural stability of the peptide. Snakins are playing a variety of roles in response to various biotic stresses such as bacterial, fungal, and nematodes infections and abiotic stress like water scarcity, saline condition, and reactive oxygen species. These properties make snakins very effective biotechnological tools for possible therapeutic and agricultural applications. This review was attempted to highlight and summarize the antifungal and antibacterial potential of snakins, also emphasizing their sequence characteristics, distributions, expression patterns and biological activities. In addition, further details of transgene expression in various plant species for enhanced fungal and bacterial resistance is also discussed, with special emphasis on their potential applications in crop protection and combating plant pathogens.