Biological rhythms research: a personal account

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Elucidating the Cellular Physiology Associated with the Herbicide (Glyphosate) Resistance and Tolerance in Agricultural Weeds Using Metabolomics Approach

Current management practices overemphasizes on herbicides to manage weeds in crop production systems. However, indiscriminate use of herbicides to manage weeds has resulted in the development of resistance in several weed biotypes. Over-application on glyphosate to manage weeds in cropping system that uses RoundUp® Ready™ trait has resulted in the dominance of glyphosate resistant weeds across cropping systems. Glyphosate resistance is an important, economically unviable and rapidly escalating problem across agricultural production systems. To combat herbicide resistance, current recommendations advocate for changes in chemical and cultural practices of weed control, including rotation of herbicide regimen with herbicides with alternate modes of action, and formulation of cultural practices that would penalize the expression of resistance. Some of the bottlenecks in practicing these approaches are the current lack of knowledge about the weed cellular physiology that ensues resistance expression, the potential metabolic cost associated with this resistance expression, and the occurrence of compensatory pathways that could defray the cost of resistance expression. Adopting an alternate herbicide regimen without an understanding of the cellular physiology of resistance expression would result in the development of herbicide cross resistance in weeds, which would further aggravate the problem. To bridge this knowledge-gap, in this studies, metabolomics approach and complementary biochemical analyses were used to track the changes in cellular metabolism in weed species and biotypes that are resistant and naturally tolerant to glyphosate. In Ipomoea lacunosa, non-targeted metabolic profiling captured the differences in metabolic pool levels in two biotypes (WAS and QUI) with contrasting glyphosate tolerance (GR50 = 151 g ae ha-1 and 59 g ae ha-1). Metabolic profiling followed by pathway topological analysis captured innate metabolic differences (22 significantly different metabolites) between WAS and QUI biotypes. Despite the glyphosate dose being half the GR50 rate, shikimic acid accumulation was observed in both the biotypes. However, regardless of EPSPS inhibition, no changes in aromatic amino abundance was observed in the QUI biotype and WAS biotype, indicating their tolerance to the glyphosate. The results from this study implies that though I. lacunosa is tolerant to glyphosate, glyphosate exposure induces cellular metabolic perturbations. The varying tolerance to glyphosate could thus be due to physiological and metabolic adaptations between the different biotypes. Following through, metabolite and biochemical profiling of a susceptible (S) and resistant (R) biotype of Amaranthus palmeri identified physiological perturbations induced by glyphosate in both the biotypes at 8 and 80 hours after treatment (HAT). Compared to the S-biotype, the R-biotype had a 17 fold resistance to the normal field recommended rate of glyphosate. At 8HAT, shikimic acid accumulation in both S- and R-biotypes in response to glyphosate application indicated that the R-biotype was equally susceptible to glyphosate toxicity. The metabolite pool of glyphosate-treated R-biotype was similar to that of the water-treated (control) S and R-biotype, indicating physiological recovery at 80 HAT. A key finding from this study is that despite being resistant to glyphosate, Palmer amaranth biotypes initially sustained metabolic perturbation from glyphosate. However, what differentiates them from the susceptible biotypes is their ability to recover from the glyphosate induced metabolic disruptions. In response to glyphosate, glyphosate-treated R-biotype had lower reactive oxygen species (ROS) damage, higher ROS scavenging activity, and higher levels of secondary compounds of the shikimate pathway, leading to the finding that elevated anti-oxidant mechanisms in A. palmeri complements the resistance conferred due to increased EPSPS copy number. Furthermore, metabolite dynamics in response to glyphosate application studied using stable isotope resolved metabolomics revealed that despite glyphosate toxicity induced decrease in soluble proteins, a proportional increase in both 14N and 15N amino acids was observed in the susceptible plants. This indicates that following glyphosate treatment, a potential increase in de novo amino acid synthesis, coupled with a lower protein synthesis, and higher protein catabolism is observed in the S-biotype. In contrast, the R-biotype, though affected by glyphosate initially, had higher de novo amino acid synthesis without significant disruptions. Moreover, it is to be noted that although the initial assimilation of inorganic nitrogen to organic forms is less affected in the S-biotype than the R-biotype by glyphosate, amino acid biosynthesis downstream of glutamine is disproportionately disrupted. It is thus concluded that the herbicide-induced amino acid abundance in the S-biotype is contributed to by both protein catabolism, and de novo synthesis of amino acids such as glutamine and asparagine. Due to variability in the genetic makeup of populations, each biotype would exhibit different physiological manifestations when exposed to the same rate of glyphosate. Biochemical and metabolic profiling of five different Palmer amaranth biotypes indicated that both the S- and R-biotypes had comparable innate phytochemical profile and similar abundance in flavonoids and phenolic. However, compared to the S-biotypes, the R-biotypes had innately higher anti-oxidant capacity, and the antioxidant capacity was observed to correlate with the GR50 such that antioxidant capacity increased with increasing GR50. Upon treatment with glyphosate, there were significant alterations in the metabolic pool levels across all biotypes. After glyphosate treatment, the content of total phenolic and flavonoids decrease in S-biotypes, whereas the abundance of these metabolites either remained the same, or increased in the R-biotypes. These results indicate that antioxidant capacity is a complementary function aiding in conferring glyphosate resistance and the phytochemistry and the antioxidant capacity is partly induced after glyphosate application, rather than being constitutively expressed. Overall, these study demonstrates that, across biotypes and species, irrespective of their degree of resistance/tolerance, glyphosate not only perturbs shikimate pathway, but also a multitude of other metabolic pathways that are independent of shikimate pathway (secondary toxic effects) as early as eight hours after treatment. While in the susceptible biotypes these metabolic perturbations result in rapid cellular damage, these metabolic perturbations fail to translate to cellular damage in the resistant biotypes. The results indicate that the resistance of A. palmeri biotypes that were used in these studies partially stems from their ability to rapidly induce the production of phenylpropanoids soon after the glyphosate application. This induction of phytochemicals could quench the reactive molecules that are initially produced during the secondary metabolic perturbations, and would thus complement the glyphosate resistance in Amaranthus biotypes conferred by EPSPS gene amplification

Glyphosate Application Causes Physiological Perturbations in Amino Acid Profiles of Palmer amaranth- A Study of Susceptible and Resistant Biotypes of Amaranthus palmeri

Glyphosate is the most widely used herbicide in the world. It is used to control perennial grasses and weeds having broad leaves. Glyphosate works by inhibiting the plant specific enzyme 5-enolpyruvylshikimate-3-phospate synthase that catalyzes the conversion of shikimic acid to chorismate, which serves as the precursor to production of aromatic amino acids, namely tyrosine, phenylalanine and tryptophan

Pulses of darkness shift the phase of a circadian rhythm in an insectivorous bat

The circadian rhythm of a tropical insectivorous bat, Taphozous melanopogon, free-runs in dim light and responds to dark breaks of a few hours' duration with 'advances' and 'delays' as a function of the phase experiencing the "black out". Similarly phase shifts also follow perturbations by light breaks. The time course and the wave form of the phase response curves obtained from experiments using pulsed light and pulsed darkness are mirror images of each other

Benign struma ovarii-a rare monodermal ovarian teratoma-a case report

Struma ovarii is a rare ovarian tumour, first described in 1889 by Boettlin. It is defined by the presence of thyroid tissue comprising of >50% of overall mass. It comprises 1% of all ovarian tumours and 2-5% of all ovarian teratomas. Preoperative diagnosis of struma ovarii is difficult because symptoms, clinical presentation and ultrasound are often similar to that of ovarian carcinoma. Hence most of the patients are diagnosed post operatively. Most cases of strum aovarii are benign and can be treated by excision of the ovary or by unilateral salpingo-oophorectomy. In a small number of cases, there are complications, the most important being the development of malignancy or ascites associated with pleural effusion producing a pseudo-Meigs' syndrome. This is a case of struma ovary presented with features of pseudo-Meig’s syndrome. A 68 year old post-menopausal woman presented with acute abdomen and respiratory distress with an ultrasound diagnosis of ovarian torsion, ascites and pleural effusion and found to have atrial thrombus on evaluation. She had undergone staging laparotomy, TAH+ BSO, omental biopsy and peritoneal fluid cytology. Histopathology revealed predominantly benign and mature colloid filled thyroid follicles of varying sizes lined by cuboidal epithelium surrounded by lymphocytic infiltrate and congested blood vessels, which was suggestive of struma ovary.

Micromechanical Modeling for Material Design of Durable Infrastructural Materials: The Influence of Aggregate and Matrix Modification on Elastic Behavior of Mortars

This paper reports the fundamental difference in microstress distributions in traditional hardened cement paste with quartz inclusions and a cement paste with lightweight aggregate (LWA) inclusions using microstructurebased numerical simulation involving finite element method with periodic boundary conditions. Variation of relative stress distributions under varying component material properties and varying microstructural features in both the systems is elucidated for a comprehensive understanding. The presented microstructure-based numerical technique accurately captures the stress concentrations inside microheterogeneous systems, which is otherwise not detectible using analytical homogenization schemes. Numerical simulations reveal that strengthening and stiffening of matrix and interfacial transition zone (ITZ) with silica fume incorporation as cement replacement in LWA incorporated cementitious systems has a detrimental effect in terms of overall strength of the material, contrary to traditional quartz-based cement mortar system. Proper selection of stiffness and strength of LWA inclusions is critical towards performance of such materials. This paper links the microstructure with mechanical behavior of two different microheterogeneous materials and provides valuable input towards material design of such non-traditional cementitious systems with different inclusions

Up-frequency conversion in a two-resonant-wave high-gain free-electron-laser amplifier

A free-electron laser is able to resonate at two different frequencies, both in free space and in a waveguide. The two waves have positive and negative slippage. We describe the nonlinear interaction between the two waves by a set of partial differential equations which in free space do not require the slowly varying envelope approximation (SVEA). In a waveguide a less restrictive SVEA is applied to each wave. By injecting a small signal at the low frequency, a strong signal and bunching are produced at the high frequency. This effect suggests a new method of generating short wavelength radiation

Role of Knowledge Management in Strengthening Corporate Governance in the Organisation

Knowledge is an asset for every individual and organisation, Knowledge includes set of know how, process technology, marketing strategy, accounting system, managerial skills etc. there is a great deal  in the corporate and business world that information and knowledge can be vital tools in the organisation. Fairness, transparency, responsibility and accountability is the basic principles of corporate governance. During last 25 years business world had grown rapidly. Simultaneously many corporate failures and scams also being happening all over the world including India. So there is a need of strict corporate governance code implementation in every organisation. So effective knowledge development in this regard is very much essential for the success of corporate governance. Knowledge regarding basic principles of corporate governance, sustainability in business, Corporate Social responsibility is essential to all responsible corporate members like any other marketing and technical knowledge. This research paper is based on secondary data and primary data.  In this paper researcher having   main objective to identify the role of knowledge management in effective corporate governance in the organisation. Keywords: Corporate Governance, Sustainable development, Knowledge Management, Corporate Committee. DOI: 10.7176/IKM/9-11-01 Publication date: December 31st 201

The Cleanroom-Free, Cheap, and Rapid Fabrication of Nanoelectrodes with Low zM Limits of Detection

Nanoscale electrodes have been a topic of intense research for many decades. Their enhanced sensitivities, born out of an improved signal-to-noise ratio as electrode dimensions decrease, make them ideal for the development of low-concentration analyte sensors. However, to date, nanoelectrode fabrication has typically required expensive equipment and exhaustive, time-consuming fabrication methods that have rendered them unsuitable for widespread use and commercialization. Herein, a method of nanoband electrode fabrication using low cost materials and equipment commonly found in research laboratories around the world is reported. The materials' cost to produce each nanoband is less than €0.01 and fabrication of a batch takes less than 1 h. The devices can be made of flexible plastics and their designs can be quickly and easily iterated. Facile methods of combining these nanobands into powerful devices, such as complete three-electrode systems, are also displayed. As a proof of concept, the electrodes are functionalized for the detection of a DNA sequence specific to SARS-CoV-2 and found to display single molecule sensitivity

THE HUMAN-RESTRICTED DUPLICATED FORM OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS

The \u3b17 nicotine acetylcholine receptor (\u3b17nAChR, CHRNA7) is a homo-pentameric ligand-gated ion channel widely expressed in the Central Nervous System (CNS). Recent evidence has demonstrated its expression also in non-neuronal tissues, including monocytes and macrophages, where it mediates the Cholinergic Anti-Inflammatory Pathway, a neuronal reflex providing the central control of systemic inflammation. Recently, the human-restricted duplicated gene of the \u3b17nAChR, called CHRFAM7A (\u3b17dup) has been discovered. It is the product of the partial duplication and fusion of exon 5-10 of CHRNA7 gene with the novel exons D, C, B and A belonging to the FAM7A gene, of unknown function. The CHRFAM7A gene is expressed in human immune cells and in the CNS and is translated into two proteins, of 45 kDa and 36 kDa, which are the result of alternative splicing. The \u3b17dup protein assembles with the \u3b17 conventional subunits and exerts a dominant negative regulation on the \u3b17nAChR function. The importance of the \u3b17dup protein in the human inflammatory process has been confirmed by the demonstration of its responsiveness to pro-inflammatory stimuli: indeed, the Lipopolysaccharide (LPS) treatment of THP-1 monocytic cells and of human primary monocytes and macrophages down-regulates CHRFAM7A transcript and protein through a transcriptional mechanism reliant on the NF-\u3baB transcription factor. Moreover, unpublished data demonstrated that LPS has the opposite effect on the \u3b17 transcript in monocytes and macrophages, leading to CHRNA7 up-regulation. In this study, we have investigated the transcriptional mechanisms leading to CHRFAM7A expression in the THP-1 monocytic cells and in neuroblastoma SH-SY5Y cells and we demonstrate that the CHRFAM7A gene is endowed with several complex transcriptional mechanisms leading to fine expression modulation, including the presence of alternative and tissue-specific Transcription Start Site (TSS), alternative splicing mechanism, tissue-specific transcriptional elements and intronic silencer elements. Moreover, we demonstrated that the CHRFAM7A down-regulation exerted by LPS involve the chromatin remodeling of CHRFAM7A promoter in THP-1 cells. Increasing evidence has linked CHRNA7 expressional and functional dysregulation to several neurodegenerative disorders, including Alzheimer\u2019s disease. The treatment with the acetylcholinesterase inhibitor Donepezil is effective in temporary ameliorating the cognitive symptoms of AD, by increasing the synaptic levels of ACh and counteracting the cholinergic loss, which is characteristic of AD. However, emerging findings sustained that Donepezil can exert its therapeutic effect also by modulating the immune response and potentiating the Cholinergic Anti-Inflammatory Pathway. So far, the role of CHRFAM7A gene in AD pathogenesis or pharmacological response has not been elucidated. In the present study, we have investigated the expression profile of CHRNA7 and CHRFAM7A genes in human nervous and immune tissues obtained from AD patients, highlighting expressional alterations of both the \u3b17 conventional and duplicated form. Moreover, we have investigated the effect of the AChEI Donepezil on CHRFAM7A and CHRNA7 transcription in THP-1 cells, human primary macrophages and SH-SY5Y cells, collecting new insights about the possible role of the \u3b17dup gene as a pharmacological target in AD therapy