Bio-Membrane Internalization Mechanisms of Arginine-Rich Cell-Penetrating Peptides in Various Species

Recently, membrane-active peptides or proteins that include antimicrobial peptides (AMPs), cytolytic proteins, and cell-penetrating peptides (CPPs) have attracted attention due to their potential applications in the biomedical field. Among them, CPPs have been regarded as a potent drug/molecules delivery system. Various cargoes, such as DNAs, RNAs, bioactive proteins/peptides, nanoparticles and drugs, can be carried by CPPs and delivered into cells in either covalent or noncovalent manners. Here, we focused on four arginine-rich CPPs and reviewed the mechanisms that these CPPs used for intracellular uptake across cellular plasma membranes. The varying transduction efficiencies of them alone or with cargoes were discussed, and the membrane permeability was also expounded for CPP/cargoes delivery in various species. Direct membrane translocation (penetration) and endocytosis are two principal mechanisms for arginine-rich CPPs mediated cargo delivery. Furthermore, the amino acid sequence is the primary key factor that determines the cellular internalization mechanism. Importantly, the non-cytotoxic nature and the wide applicability make CPPs a trending tool for cellular delivery.

The use of logistics principles in the organization of local work

In the context of growing competition between rail transport and other transport types, there is a need to improve the transportation process. In modern conditions, railway transport is the main link in the logistics chain of moving goods from the shipper to the receiver. The efficiency of the railway transport complex can be improved by using logistics principles in the organization of local work on the network sections. In this study, we suggest ways to solve the problem of improving the quality of service for freight owners and the efficiency of organizing local work, which is relevant for railways. To make decisions aimed at improving the efficiency of the organization of local work, a procedure for determining the costs of organizing and promoting local trains was developed, taking into account the costs on maintaining the railway infrastructure. Not only the operational activity of the railways, but also the quality of transport customers service, compliance with the regulatory deadlines for cargo delivery, depends on the choice of the optimal option for organizing local car traffic into trains and their promotion along the section. The option is selected by comparing the costs for each of the possible options for organizing local car traffic into trains and moving them along the section.

Unconventional COPII-mediated secretory protein trafficking continues in the absence of the Sar1 GTPase

Coat protein complex II (COPII) plays an integral role in the packaging of secretory cargoes within membrane-enclosed transport carriers that leave the endoplasmic reticulum (ER) from discrete membrane subdomains. Lipid bilayer remodeling necessary for this process is driven initially by membrane penetration of the coat subunit Sar1 and further stabilized by assembly of a multi-layer complex of several COPII proteins. However, the relative contributions of these distinct factors to transport carrier formation and protein trafficking remain unclear. Here, we demonstrate that anterograde cargo transport from the ER continues in the absence of Sar1, although the unconventional carriers that form fail to efficiently deliver their contents to subsequent compartments in the secretory pathway. Instead, cargoes accumulate immediately adjacent to the perinuclear Golgi under these conditions, together with components of the COPII coat. Our findings highlight new mechanisms by which COPII promotes transport carrier biogenesis and strongly suggests that the Sar1 GTPase plays a critical role in transport carrier uncoating ahead of membrane fusion and secretory cargo delivery at acceptor compartments.

PIKfyve inhibition reveals a novel role for Inpp4b in the regulation of PtdIns(3)P and lysosome dynamics

Lysosome membranes contain diverse phosphoinositide (PtdIns) lipids that co-ordinate lysosome function and dynamics. The PtdIns repertoire on lysosomes is tightly regulated by the action of diverse PtdIns kinases and phosphatases. Specific roles for PtdIns in lysosomal function and dynamics are currently unclear and require further investigation. PIKfyve, a lipid kinase which synthesizes PtdIns(3,5)P2 from PtdIns(3)P, controls lysosome fusion-fission cycles, autophagosome turnover and endocytic cargo delivery. We have recently characterized a role for INPP4B, a PtdIns phosphatase which hydrolyses PtdIns(3,4)P2 to form PtdIns(3)P, in the regulation of lysosomal biogenesis and function. To gain a better understanding of PtdIns homeostasis on lysosomes, we investigated the consequence of disrupting PIKfyve in Inpp4b-deficient mouse embryonic fibroblasts. Surprisingly, simultaneous inhibition of Inpp4b and PIKfyve functions impair lysosome fission and exacerbate lysosome enlargement and inhibit autophagic flux. Further examination into the underlying processes that may explain exaggerated lysosome enlargement revealed elevated levels of lysosome-associated PtdIns(3)P as contributing factors that control lysosome morphology in cells where Inpp4b and PIKfyve are disrupted. Overall, our study suggests that lysosomal functions are regulated by Inpp4b, through a paradoxical role in suppressing the induction of PtdIns(3)P production.

Influence of mountain traffic conditions on the functional state of a bus driver

Ensuring the transport process requires proper interaction of all parts of the system "driver - car - road - environment" and its subsystems. In this case, the driver is often a "weak" component of the system, and his actions can reduce the level of road users` safety. It should be noted that the reliability of the driver can be considered as the probability of his trouble-free and error-free operation, as well as the proper level of his regulatory mechanisms functioning. In this case, to analyze the activities and readiness of the driver for his professional activities, indicators of functional status are often used. Thus, the study of the "human factor" in the transport process is an important task to ensure the reliability of the whole transport system. Today the most of all transportation is carried out by road. The timeliness and safety of cargo delivery and passenger safety depend on the driver's actions. At the same time, the driver is influenced by a considerable number of external environmental factors during his work. One of the most important factors is the mountainous traffic conditions, which often have many changes in plan and the profile of roads. Another feature of such traffic conditions is the height above sea level, affecting the human body, particularly its functional state. Considering the above, the paper measures the heart rate variability of bus drivers moving on a route that was partly in the mountain's conditions. During the research, video recording and registration of the vehicle's geolocation were also carried out. This made it possible to establish indicators of the driver`s functional state in specific periods. After processing the obtained values, the influence of mountainous traffic conditions on the bus drivers` indicator of regulatory systems’ activity was established.

Analisis Faktor Internal dan Eksternal Perusahaan terhadap Penurunan Pengiriman Barang Kargo di PT. Lintas Maju Nusantara

PT Lintas Maju Nusantara is one of the cargo delivery companies in Bekasi City. In the latest period, there has been a significant decline in cargo shipments. This research was conducted with the aim of knowing the internal and external factors that caused the decline in shipments, and ways to overcome the decline. This research focused on internal factors which include facilities, services, marketing, and employees of PT Lintas Maju Nusantara, and external factors which include competitors, customers, and government regulations. The research method used was quasi-qualitative with data collection techniques in the form of interviews, observation, and documentation. The results of this study indicate that the facilities owned by the company still require attention. On the other hand competitors and government regulations have also become a strong factor in the decline in cargo shipments that occurred at PT Lintas Maju Nusantara.

Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes

Cell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane is a hallmark and supports optimal lipid–peptide interactions. Incorporation of hydrophobic moieties, such as carboranes (CBs), has the potential to increase the lipophilicity of peptides, and thus, to facilitate the formation of secondary structures. Herein, we present synthesis and biophysical as well as biological characterization of carborane-CPP conjugates having incorporated one or more CB clusters. Our results highlight the possibility to modulate the secondary structure of CPPs by the addition of CB’s leading to constructs with altered membrane activity and promising use in terms of nucleic acid delivery.