Light at the end of the tunnel: integrating signaling pathways in the coordination of lateral root development.

Root system architecture (RSA) encompasses a range of physical root attributes, including the lateral roots (LRs), root hairs and adventitious roots, in addition to the primary or main root. This overall structure is a crucial trait for efficient water and mineral capture alongside providing anchorage to the plant in the soil and is vital for plant productivity and fitness. RSA dynamics are dependent upon various environmental cues such as light, soil pH, water, mineral nutrition and the belowground microbiome. Among these factors, light signaling through HY5 significantly influences the flexibility of RSA by controlling different signaling pathways that converge at photoreceptors-mediated signaling, also present in the 'hidden half'. Furthermore, several phytohormones also drive the formation and emergence of LRs and are critical to harmonize intra and extracellular stimuli in this regard. This review endeavors to elucidate the impact of these interactions on RSA, with particular emphasis on LR development and to enhance our understanding of the fundamental mechanisms governing the light-regulation of LR growth and physiology.

Molecular mechanism of poly(vinyl alcohol) mediated prevention of aggregation and stabilization of insulin in nanoparticles.

It is a challenge to formulate polymer based nanoparticles of therapeutic proteins as excipients and process conditions affect stability and structural integrity of the protein. Hence, understanding the protein stability and complex aggregation phenomena is an important area of research in therapeutic protein delivery. Herein we investigated the comparative role of three kinds of surfactant systems (Tween 20:Tween 80), small molecular weight poly(vinyl alcohol) (SMW-PVA), and high molecular weight PVA (HMW-PVA) in prevention of aggregation and stabilization of hexameric insulin in poly(lactide-co-glycolide) (PLGA) based nanoparticle formulation. The nanoparticles were prepared using solid-in-oil-in-water (S/O/W) emulsification method with one of the said surfactant system in inner aqueous phase. The thermal unfolding analysis of released insulin using circular dichroism (CD) indicated thermal stability of the hexameric form. Insulin aggregation monitored by differential scanning calorimetry (DSC) suggested the importance of nuclei formation for aggregation and its prevention by HMW-PVA. Additional guanidinium hydrochloride based equilibrium unfolding and in silico (molecular docking) studies suggested maximum stability of released insulin from formulation containing HMW-PVA (F3). Furthermore, in vivo studies of insulin loaded nanoparticle formulation (F3) in diabetic rats showed its bioactivity. In conclusion, our studies highlight the importance of C-terminal residues of insulin in structural integrity and suggest that the released insulin from formulation containing HMW-PVA in inner aqueous phase was conformationally and thermodynamically stable and bioactive in vivo.

Sugar signals pedal the cell cycle!

Cell cycle involves the sequential and reiterative progression of important events leading to cell division. Progression through a specific phase of the cell cycle is under the control of various factors. Since the cell cycle in multicellular eukaryotes responds to multiple extracellular mitogenic cues, its study in higher forms of life becomes all the more important. One such factor regulating cell cycle progression in plants is sugar signalling. Because the growth of organs depends on both cell growth and proliferation, sugars sensing and signalling are key control points linking sugar perception to regulation of downstream factors which facilitate these key developmental transitions. However, the basis of cell cycle control via sugars is intricate and demands exploration. This review deals with the information on sugar and TOR-SnRK1 signalling and how they manoeuvre various events of the cell cycle to ensure proper growth and development.

Complex genetic interaction between glucose sensor HXK1 and E3 SUMO ligase SIZ1 in regulating plant morphogenesis.

Sugar signaling forms the basis of metabolic activities crucial for an organism to perform essential life activities. In plants, sugars like glucose, mediate a wide range of physiological responses ranging from seed germination to cell senescence. This has led to the elucidation of cell signaling pathways involving glucose and its counterparts and the mechanism of how these sugars take control over major hormonal pathways such as auxin, ethylene, abscisic acid and cytokinin in Arabidopsis. Plants use HXK1(Hexokinase) as a glucose sensor to modulate changes in photosynthetic gene expression in response to high glucose levels. Other proteins such as SIZ1, a major SUMO E3 ligase have recently been implicated in controlling sugar responses via transcriptional and translational regulation of a wide array of sugar metabolic genes. Here, we show that these two genes work antagonistically and are epistatic in controlling responsiveness toward high glucose conditions.

Peroneal Artery Pseudoaneurysm after Surgery for Non-union of Tibia: A Case Report with Review of Literature.

Introduction: Arterial pseudoaneurysm is a hematoma that is formed after damage to the arterial wall. We report a rare case of peroneal artery pseudoaneurysm after open reduction and internal fixation with interlocking nailing and partial fibulectomy for non-union for the right tibia in a 31-year-old male. The patient presented with a bleeding sinus over the leg swelling, and it was managed with an exploration of the pseudoaneurysm and ligation of the peroneal artery. Case Report: A 30-year-old male patient presented with a non-union tibia on the right side and had undergone plating of the tibia at another institute for a fracture of both bone legs approximately 18 months ago. The revision surgery was performed in which a previously inserted implant was removed and an interlocking nail was inserted, along with a partial fibulectomy. The post-operative period was uneventful. At 8 weeks after the second surgery, the patient came with a complaint of swelling at the outer aspect of the right leg. Computed tomography and angiography confirmed a peroneal artery pseudoaneurysm of 3.2 × 2.8 × 3.8 cm. Pseudoaneurysm was explored, and the artery was overrun with a Figure-8 stitches using a monofilamentous, and non-absorbable suture. Conclusion: This case report highlights the occurrence of pseudoaneurysm after an orthoapedic procedure such as a partial fibulectomy. A high level of clinical suspicion, proper imaging, and early endovascular or surgical intervention is recommended to prevent complications.

Molecular mechanism of improved structural integrity of protein in polymer based microsphere delivery system.

Polymer-based delivery systems provide a promising alternative to multidose intake of many drugs/vaccines. Protein aggregation and inactivation, however, are major problems associated with the encapsulation of proteins in microspheres. With this in mind, we investigated the structural integrity of a model protein bovine serum albumin (BSA) released from poly(lactide-co-glycolide) (PLGA) based microspheres. BSA was encapsulated using solid-in-oil-in-water (S/O/W) double emulsification method with different mixtures of surfactants (carboxymethyl cellulose (CMC):Tween 20/CMC:Tween 80/Tween 20:Tween 80) and with or without polyethylene glycol (PEG). The morphology of BSA-loaded microspheres was analyzed using dynamic light scattering (DLS) and scanning electron microscopy (SEM). BSA released from lyophilized microspheres was evaluated for the structural, conformational and thermal stability by using various spectroscopic and calorimetric techniques. Conformational analysis showed greater increase in secondary structural content of BSA in sample containing PEG and surfactant mixture of CMC and Tween 20 as compared to that containing other two mixtures of surfactants. The differential scanning calorimetric (DSC) analysis of released BSA from all PEG containing samples showed an increase in thermal stability of the protein. Furthermore, fluorescence spectra showed compactness of BSA. In conclusion our studies suggest macromolecular crowding, molecular confinement and increase in Gibbs free energy with strong electrostatic forces of repulsion between microspheres, the last phenomenon due to chosen surfactants, to be responsible for making the protein more compact and structurally integrated and result in a potential encapsulation process for improved protein integrity in final formulation.

Molecular mechanism of polyethylene glycol mediated stabilization of protein.

The effect of different molar ratios of polyethylene glycol (PEG) on the conformational stability of protein, bovine serum albumin (BSA), was studied. The binding of PEG with BSA was observed by fluorescence spectroscopy by measuring the fluorescence intensity after displacement of PEG with chromophore ANS and had further been confirmed by measuring the intrinsic fluorescence of tryptophan residues of BSA. Co-lyophilization of BSA with PEG at optimum BSA:PEG molar ratio led to the formation of the stable protein particles. Circular dichroism (CD) spectroscopy study suggested that a conformational change had occurred in the protein after PEG interaction and demonstrated the highest stability of protein at the optimum BSA:PEG molar ratio of 1:0.75. Additional differential scanning calorimetry (DSC) study suggested strong binding of PEG to protein leading to thermal stability at optimum molar ratio. Molecular mechanism operating behind the polyethylene glycol (PEG) mediated stabilization of the protein suggested that strong physical adsorption of PEG on the hydrophobic core of the protein (BSA) along with surface adsorption led to the stability of protein.

Genetics on early onset inflammatory bowel disease: An update.

Inflammatory bowel disease (IBD) is more common in adults than in children. Onset of IBD before 17 years of age is referred as pediatric onset IBD and is further categorized as very early onset IBD (VEO-IBD) for children who are diagnosed before 6 years of age, infantile IBD who had the disease before 2 years of age and neonatal onset IBD for children less than 28 days of life. Children presenting with early onset disease may have a monogenic basis. Knowledge and awareness of the clinical manifestations facilitates early evaluation and diagnosis. Next generation sequencing is helpful in making the genetic diagnosis. Treatment of childhood IBD is difficult; targeted therapies and hematopoietic stem cell transplantation form the mainstay. In this review we aim to summarize the genetic defects associated with IBD phenotype. We describe genetic location and functions of various genetic defect associated with VEO-IBD with their key clinical manifestations. We also provide clinical clues to suspect these conditions and approaches to the diagnosis of these disorders and suitable treatment options.