Illuminating the Biochemical Interaction of Antimicrobial Few-Layer Black Phosphorus with Microbial Cells Using Synchrotron macro-ATR-FTIR

In the fight against drug-resistant pathogenic bacterial and fungal cells, low-dimensional materials are emerging as a promising alternative treatment method. Specifically, few-layer black phosphorus (BP) has demonstrated its effectiveness against...

Pharmacological activity and biochemical interaction of zingerone: a flavour additive in spice food

Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone) is one of the non-volatile and nontoxic compounds of ginger. It is also called vanillylacetone with a crystalline solid form which is sparingly soluble in water and more soluble in ether. The contribution of this compound in ginger is about 9.25%. The chemical structure is made of a phenolic ring with methoxy group attached to benzene ring. Gingerol can be heated to form zingerone by retroaldol reaction. It has been reported that zingerone has multiple pharmacological activities. It is effective against diarrhoea causing enterotoxigenic bacteria that leads to infant death. It is also used against intestinal gastric, oxidative stress, weak immunity, obesity. During its activity against cancer, it governs the expression of different cell cycle protein and TGF-?1 expression. Antioxidant response is controlled by inducing the activity of ROS neutralising enzymes like superoxide dismutase, catalase and glutathione reductase. It can also reduce various inflammations by restricting the activity of interleukins. This review summarizes the multiple pharmacology activities of zingerone against various important diseases like cancers, tumors, inflammations, oxidative conditions, microbial infections, biofilm formations, thrombosis and other diseases. In addition, the molecular regulation of these pharmacological responses by zingerone is also critically discussed.

Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state

Integral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can interact with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex (IRC), in evolutionarily distant yeasts. Although an N-terminal domain is required for Heh2 targeting to the INM, we demonstrate that stable interactions with the NPC are mediated by a C-terminal winged helix (WH) domain, thus decoupling INM targeting and NPC binding. Inhibiting Heh2’s interactions with the NPC by deletion of the Heh2 WH domain leads to NPC clustering. Interestingly, Heh2’s association with NPCs can also be disrupted by knocking out several outer ring nucleoporins. Thus, Heh2’s association with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division.

Three-dimensional ultrastructure of the brain pericyte-endothelial interface

Pericytes and endothelial cells share membranous interdigitations called “peg-and-socket” interactions that facilitate their adhesion and biochemical crosstalk during vascular homeostasis. However, the morphology and distribution of these ultrastructures have remained elusive. Using a combination of 3D electron microscopy techniques, we examined peg-and-socket interactions in mouse brain capillaries. We found that pegs extending from pericytes to endothelial cells were morphologically diverse, exhibiting claw-like morphologies at the edge of the cell and bouton-shaped swellings away from the edge. Reciprocal endothelial pegs projecting into pericytes were less abundant and appeared as larger columnar protuberances. A large-scale 3D EM data set revealed enrichment of both pericyte and endothelial pegs around pericyte somata. The ratio of pericyte versus endothelial pegs was conserved among the pericytes examined, but total peg abundance was heterogeneous across cells. These data show considerable investment between pericytes and endothelial cells, and provide morphological evidence for pericyte somata as sites of enriched physical and biochemical interaction.

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

The masticatory system is a complex and highly organized group of structures, including craniofacial bones (maxillae and mandible), muscles, teeth, joints, and neurovascular elements. While the musculoskeletal structures of the head and neck are known to have a different embryonic origin, morphology, biomechanical demands, and biochemical characteristics than the trunk and limbs, their particular molecular basis and cell biology have been much less explored. In the last decade, the concept of muscle-bone crosstalk has emerged, comprising both the loads generated during muscle contraction and a biochemical component through soluble molecules. Bone cells embedded in the mineralized tissue respond to the biomechanical input by releasing molecular factors that impact the homeostasis of the attaching skeletal muscle. In the same way, muscle-derived factors act as soluble signals that modulate the remodeling process of the underlying bones. This concept of muscle-bone crosstalk at a molecular level is particularly interesting in the mandible, due to its tight anatomical relationship with one of the biggest and strongest masticatory muscles, the masseter. However, despite the close physical and physiological interaction of both tissues for proper functioning, this topic has been poorly addressed. Here we present one of the most detailed reviews of the literature to date regarding the biomechanical and biochemical interaction between muscles and bones of the masticatory system, both during development and in physiological or pathological remodeling processes. Evidence related to how masticatory function shapes the craniofacial bones is discussed, and a proposal presented that the masticatory muscles and craniofacial bones serve as secretory tissues. We furthermore discuss our current findings of myokines-release from masseter muscle in physiological conditions, during functional adaptation or pathology, and their putative role as bone-modulators in the craniofacial system. Finally, we address the physiological implications of the crosstalk between muscles and bones in the masticatory system, analyzing pathologies or clinical procedures in which the alteration of one of them affects the homeostasis of the other. Unveiling the mechanisms of muscle-bone crosstalk in the masticatory system opens broad possibilities for understanding and treating temporomandibular disorders, which severely impair the quality of life, with a high cost for diagnosis and management.

ABSCISIC ACID INSENSITIVE5 Interacts With RIBOSOMAL S6 KINASE2 to Mediate ABA Responses During Seedling Growth in Arabidopsis

ABSCISIC ACID INSENSITIVE5 (ABI5) is an important regulator of abscisic acid (ABA) signaling pathway involved in regulating seed germination and postgerminative growth in Arabidopsis, which integrates various phytohormone pathways to balance plant growth and stress responses. However, the transcriptional regulatory mechanisms underlying ABI5 and its interacting proteins remain largely unknown. Here, we found that inhibition of AtTOR could increase ABA content by up-regulating the expression levels of ABA biosynthesis-related genes, and thus activated the expression of ABA-responsive genes. Pharmacological assay showed that abi5-1 mutant was insensitive to TOR inhibitor AZD8055, whereas AtABI5 overexpression lines were hypersensitive to AZD8055 in Arabidopsis. Biochemical interaction assays demonstrated that ABI5 physically interacted with the RIBOSOMAL S6 KINASE2 (S6K2) protein in plant cell. S6K2 positively regulated ABA responses during seedling growth and upregulated ABA-responsive genes expression. Furthermore, genetic and physiological analysis indicated that AtS6K2 overexpression lines enhanced resistance to drought treatment while AtS6K2 interference lines were sensitive to drought. These results indicated that AtABI5 interacted with AtS6K2 to positively modulate ABA responses during seedling growth and shed light on a underlying mechanism of the crosstalk between TOR and ABA signaling pathways in modulating seedling growth in Arabidopsis.

BIOMEDICAL ENGINEERING OF SCLEROSTIN ACTION IN THE BONE REMODELING

Mathematical modeling of biological processes has bridged the fields of experimental as well as theoretical research and has carried forward remarkable innovation. Sclerostin is a fundamental communication element for bone remodeling and its activity regulates the reabsorption and deposition of new bone tissue. During this research, we have presented several studies, which illustrate the function of sclerostin in communication with the Wnt signaling pathways. This article features the sclerostin-based pathological patterns related to diseases such as bone cancer. To have a good remodeling process, the osteocytes must recruit the pre-osteoblast cells from the mesenchymal stem cells with the help of the signal mechanism given by the Wnt pathway. The Wnt signal pathway is a complex transduction of a pool of well-conserved genes whose expression regulates various activities like gene translation, cell adhesion, cell differentiation, mitogenic stimulation and polarity cell. The complexity of the interaction of the Wnt pathway is due to the ligands of Wnt itself, to the proteins R-spondin and norrin. The receptors on the surface of the cell, then, activate a process of transduction of the intracellular signal that initiates gene transduction. The hypothesis of a sort of “steady state” has therefore proved indispensable to establish a sort of common base on which the two phases. This paper seeks to give a qualitative view of the action of sclerostin through a simple mathematical model. We use a logic related to stimulation and inhibition signals of new tissue production and illustrate the role of sclerostin in the mechanical and biochemical interaction during the bone remodeling process.

3D And 2D RNA Structure Prediction Of The BRCA2 Gene And Its Silencing RNA In The Breast Cancer

<p><em>Breast cancer is one of the most threatening diseases for women. It is found that BRCA2 gene plays a significant role in breast cancer, provided that mutations occurred. The objective of this </em><em>study</em><em> is to determine whether the bioinformatics approach could provide</em><em> the</em><em> gene networking, molecular simulation, and computational metabolomics information to </em><em>shed</em><em> the relation between BRCA2 gene mutation with </em><em>b</em><em>reast cancer progression. The methods are utilizing molecular simulation tools to comprehend the biochemical interaction of BRCA2 gene with other </em><em>oncogenic </em><em>genes. Lastly, the molecular docking tool is devised to provide </em><em>the </em><em>molecular interactions information. </em><em>I</em><em>t could be implied that the Computer-Aided Drug Design (CADD)-based in silico transcriptomics tools could provide </em><em>the </em><em>fine-grained information on the exact role of BRCA2 gene in the progression of breast cancer. The clinical impact of this </em><em>study</em><em> could only be measured after the wet laboratory experiment is conducted to validate the computational approach</em><em> results</em></p>

Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis

Apoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechanism by which Tim-4 transduces signals to phagocytes during Tim-4-mediated efferocytosis is incompletely understood. Here, we report that Tim-4 collaborates with Mertk during efferocytosis through a biochemical interaction with Mertk. Proximal localization between the two proteins in phagocytes was observed by immunofluorescence and proximal ligation assays. Physical association between Tim-4 and Mertk, which was mediated by an interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk, was also detected with immunoprecipitation. Furthermore, the effect of Mertk on Tim-4-mediated efferocytosis was abolished by GST-MertkFnIII, a soluble form of the fibronectin type-III domain of Mertk that disrupts the interaction between Tim-4 and Mertk. Taken together, the results from our study suggest that a physical interaction between Tim-4 and Mertk is necessary for Mertk to enhance efferocytosis mediated by Tim-4.