How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

After more than fifteen years from the first high-throughput experiments for human protein–protein interaction (PPI) detection, we are still wondering how close the completion of the genome-scale human PPI network reconstruction is, what needs to be further explored and whether the biological insights gained from the holistic investigation of the current network are valid and useful. The unique structure of PICKLE, a meta-database of the human experimentally determined direct PPI network developed by our group, presently covering ~80% of the UniProtKB/Swiss-Prot reviewed human complete proteome, enables the evaluation of the interactome expansion by comparing the successive PICKLE releases since 2013. We observe a gradual overall increase of 39%, 182%, and 67% in protein nodes, PPIs, and supporting references, respectively. Our results indicate that, in recent years, (a) the PPI addition rate has decreased, (b) the new PPIs are largely determined by high-throughput experiments and mainly concern existing protein nodes and (c), as we had predicted earlier, most of the newly added protein nodes have a low degree. These observations, combined with a largely overlapping k-core between PICKLE releases and a network density increase, imply that an almost complete picture of a structurally defined network has been reached. The comparative unsupervised application of two clustering algorithms indicated that exploring the full interactome topology can reveal the protein neighborhoods involved in closely related biological processes as transcriptional regulation, cell signaling and multiprotein complexes such as the connexon complex associated with cancers. A well-reconstructed human protein interactome is a powerful tool in network biology and medicine research forming the basis for multi-omic and dynamic analyses.

In-Depth Understanding of Granule Compression Behavior under Variable Raw Material and Processing Conditions

Tablet manufacturing involves the processing of raw materials through several unit operations. Thus, the mitigation of input-induced variability should also consider the downstream processability of intermediary products. The objective of the present work was to study the effect of variable raw materials and processing conditions on the compression properties of granules containing two active pharmaceutical ingredients (APIs) and microcrystalline cellulose. Differences in compressibility and tabletability of granules were highlighted in function of the initial particle size of the first API, granule polydispersity and fragmentation. Moreover, interactions were underlined with the atomizing pressure. Changing the supplier of the second API was efficiently controlled by adapting the binder addition rate and atomizing pressure during granulation, considering the starting crystal size. By fitting mathematical models on the available compression data, the influence of diluent source on granule compactibility and tabletability was identified. These differences resumed to the ease of compaction, tableting capacity and pressure sensitivity index due to variable water binding capacity of microcrystalline cellulose. Building the design space enabled the identification of suitable API types and the appropriate processing conditions (spray rate, atomizing pressure, compression force) required to ensure the desired tableting performance.

Accumulation of Antibiotic Resistance Genes in Pakchoi (Brassica Chinensis L.) Grown in Chicken Manure-fertilized Soil Amended With Fresh and Aged Biochars

Biochar has been used to alleviate the contamination of antibiotic resistance genes (ARGs) in soil and to inhibit ARGs transfer from soil to plants. However, the effect of aged biochar on ARGs abundance in soil and ARGs enrichment in plants are scarcely investigated. In this study, a pot experiment was conducted to compare the effects of fresh and aged biochars on the accumulation of five typical ARGs including tetX, tetW, sul2, ermB and intI1 in a chicken manure-fertilized soil and in pakchoi (Brassica chinensis L.). Results showed that both biochars significantly decreased the abundance of tetW, sul2, and ermB and increased the abundance of tetX and intI1 in soil. However, the accumulation of all tested ARGs in pakchoi were significantly decreased by both biochars. At the lower addition rate (1%), the fresh biochar was superior to the aged biochar in decreasing the accumulation of some genes (tetW, tetX, and sul2) in pakchoi, whereas an opposite tendency was observed for other genes (ermB and intI1). As the addition rate increased to 2%, the difference between the two biochars diminished and a similar capacity of decreasing ARGs transfer was observed. The reduction in ARGs accumulation in pakchoi was highly related to the type of ARGs, the biochar addition level and the aging of biochar. Our results provide insights into the naturally aged biochar on the fate of ARGs in a soil-plant system.

Combined Effect of Marble Waste as Powder and Aggregate Form on the Proprieties of the Mortar

Recycling and recovery of waste are now considered as a solution for the future to protect the environment. The marble processing workshops on the other hand, generate a large amount of waste in the form of powder and small parts. Due to these facts, the aim of this study is to valorize marble waste in the form of powder and crushed aggregates (sand) as additions in cementitious matrix building materials. The characterization of the materials used to formulate mortars based on natural dune sand with marble powder and mortars based on mixed sand (dunes sand and crushed sand) and marble powder was measure. In this sense, several series have been studied, varying the addition rate of the marble powder in order to reduce the porosity of the cement matrix, using crushed marble sand to increase the granular cohesion and using of a reducing water admixture (MEDAPLAST SP40) for more performance mortars. Very appreciable results were observed for a dosage of 15% of marble powder and for the combination of 15% of marble powder with 20% of crushed marble sand. This research recommends recycling 35% of marble waste in the cement matrix that contribute effectively to the preservation of the environment.

Nanoprecipitation of Biocompatible Poly(malic acid) Derivative, Its Ability to Encapsulate a Molecular Photothermal Agent and Photothermal Properties of the Resulting Nanoparticles

Biocompatible nanoparticles (NPs) of hydrophobic poly(benzyl malate) (PMLABe) were prepared by nanoprecipitation. The influence of nanoprecipitation parameters (initial PMLABe, addition rate, organic solvent/water ratio and stirring speed) were studied to optimize the resulting formulations in terms of hydrodynamic diameter (Dh) and dispersity (PDI). PMLABe NPs with a Dh of 160 nm and a PDI of 0.11 were isolated using the optimized nanoprecipitation conditions. A hydrophobic near infra-red (NIR) photothermally active nickel-bis(dithiolene) complex (Ni8C12) was then encapsulated into PMLABe NPs using the optimized nanoprecipitation conditions. The size and encapsulation efficiency of the NPs were measured, revealing that up to 50 weight percent (wt%) of Ni8C12 complex can efficiently be encapsulated with a slight increase in Dh of the corresponding Ni8C12-loaded NPs. Moreover, we have shown that NP encapsulating Ni8C12 were stable under storage conditions (4 °C) for at least 10 days. Finally, the photothermal properties of Ni8C12-loaded NPs were evaluated and a high photothermal efficiency (62.7 ± 6.0%) waswas measured with NPs incorporating 10 wt% of the Ni8C12 complex.

Phanerozoic record of mantle-dominated arc magmatic surges in the Zealandia Cordillera

We integrated new and existing bedrock and detrital zircon dates from the Zealandia Cordillera to explore the tempo of Phanerozoic arc magmatism along the paleo-Pacific margin of southeast Gondwana. We found that episodic magmatism was dominated by two high-magma-addition-rate (MAR) events spaced ~250 m.y. apart in the Devonian (370–368 Ma) and the Early Cretaceous (129–105 Ma). The intervening interval between high-MAR events was characterized by prolonged, low-MAR activity in a geographically stable location for more than 100 m.y. We found that the two high-MAR events in Zealandia have distinct chemistries (S-type for the Devonian and I-type for the Cretaceous) and are unlikely to have been related by a repeating, cyclical process. Like other well-studied arc systems worldwide, the Zealandia Cordillera high-MAR events were associated with upper-plate deformation; however, the magmatic events were triggered by enhanced asthenospheric mantle melting in two distinct arc-tectonic settings—a retreating slab and an advancing slab, respectively. Our results demonstrate that dynamic changes in the subducting slab were primary controls in triggering mantle flare-up events in the Phanerozoic Zealandia Cordillera.

Supplemental Material: Phanerozoic record of mantle-dominated arc magmatic surges in the Zealandia Cordillera

Detailed analytical methods and U-Pb zircon geochronology results, zircon cathodoluminescence images, Tera-Wasserburg plots, and tables containing igneous and detrital zircon data and volume addition rate calculations.<br>