Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.     

Trypsin-like Inhibitor Domain (TIL)-Harboring Protein Is Essential for Aedes aegypti Reproduction

Cysteine-rich trypsin inhibitor-like domain (TIL)-harboring proteins are broadly distributed in nature but remain understudied in vector mosquitoes. Here we have explored the biology of a TIL domain-containing protein of the arbovirus vector Aedes aegypti, cysteine-rich venom protein 379 (CRVP379). CRVP379 was previously shown to be essential for dengue virus infection in Ae. aegypti mosquitoes. Gene expression analysis showed CRVP379 to be highly expressed in pupal stages, male testes, and female ovaries. CRVP379 expression is also increased in the ovaries at 48 h post-blood feeding. We used CRISPR-Cas9 genome editing to generate two mutant lines of CRVP379 with mutations inside or outside the TIL domain. Female mosquitoes from both mutant lines showed severe defects in their reproductive capability; mutant females also showed differences in their follicular cell morphology. However, the CRVP379 line with a mutation outside the TIL domain did not affect male reproductive performance, suggesting that some CRVP379 residues may have sexually dimorphic functions. In contrast to previous reports, we did not observe a noticeable difference in dengue virus infection between the wild-type and any of the mutant lines. The importance of CRVP379 in Ae. aegypti reproductive biology makes it an interesting candidate for the development of Ae. aegypti population control methods.     

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism’s response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.     

Supply Hub in Industrial Park (SHIP): The value of freight consolidation

Industrial parks, characterized as a cluster of enterprises situated in one location to share common resources, have played an indispensible role in boosting regional economic and industrial development. However, further development has been impeded by the shortage of land space, especially for the construction of warehouses. This paper proposes the concept of Supply Hub in Industrial Park (SHIP) as a promising approach addressing this challenge. SHIP is defined as a public provider of warehousing and logistics services for manufacturing enterprises located within an industrial park. The research reported in this paper focuses on evaluating the value of freight consolidation, one of the typical benefits of applying the SHIP approach. Two mathematical models of the supply chain in a typical industrial park are formulated: with and without SHIP. Genetic Algorithm (GA) is applied for solving the two models, and sensitivity experiments are conducted for comparative analysis between the two scenarios. The computational results show that through consolidating shipments, SHIP brings benefits to the whole industrial park. Total cost savings resulted from the application of SHIP would increase with the size of the supply chain, the vehicle capacity, and the rates of fixed transportation costs and holding costs of finished products at manufacturers.     

Book Review

Abstract

Data Base Directions, The Next Steps. John L. Berg, Editor. U. S. Department of Commerce, National Bureau of Standards. (Order from Superintendent of Documents, U. S. Government Printing Office, Washington, DC, 20402. Ask f o r SD Cat.No. C13.10:451.) 158 pages; $2.45.     

On the reliability of electrostatic NEMS/MEMS devices: Review of present knowledge on the dielectric charging and stiction failure mechanisms and novel characterization methodologies

This paper reviews the state of the art knowledge related to critical failure mechanisms in electrostatic micro- and nano-electromechanical systems (MEMS and NEMS) which are the dielectric charging and stiction. It describes also the recent employed nanoscale characterization techniques for these phenomena based on Kelvin probe force microscopy (KPFM) and force–distance curve measurements. The influence of relative humidity and dielectric deposition conditions on the charging/discharging processes is discussed. Moreover, different stiction mechanisms induced by electrostatic force and/or meniscus formation are analyzed. Finally, novel characterization methods are presented and used to correlate between the results from MEMS devices and metal–insulator–metal (MIM) capacitors. These methods are employed in view of application in electrostatic capacitive MEMS switches and could be easily extended to explore other NEMS/MEMS devices. The study provides an accurate understanding of the charging and stiction related failure mechanisms, presents guidelines for a proper packaging environment, and reveals precise explanations for the literature reported device level measurements of electrostatic MEMS devices.