Novel method to manage weeds in the rainfed groundnut (var. VRI 8 and TMV 14) using nano encapsulated herbicide formulations

The groundnut crop harbours heavy weed infestation due to its small stature and slow growing nature. The current weed management practices of hand weeding and use of commercial herbicides are unsuitable because of high labour cost and inadequate moisture availability to activate herbicides.  In order to release the herbicide in a smart way, this experiment aimed to study the efficacy of encapsulated herbicides . Field experiments were conducted during Kharif 2021 and late Rabi 2022 under rainfed conditions in randomised block design with three replications. The treatments consisted of sulfentrazone, oxyfluorfen, diclosulam and metolachlor in both commercial and encapsulated form using two doses, hand weeding at 20 and 40 DAS, weed free plot and weedy check. Minimum weed density (28.33 and 17.30 No./m2 at 90 DAS during Kharif and late Rabi respectively) and weed dry weight (65.33 and 61.25 g/m2 at 90 DAS during Kharif and late Rabi respectively) were observed in hand weeding at 20 and 40 DAS (T19) followed by diclosulam @ 25 g ha-1 with encapsulation (T7). Maximum weed density and weed dry weight was observed in metolachlor @ 1 kg/ha with encapsulation (T8). Higher productivity was observed in hand weeding at 20 and 40 DAS (T19) (1802 kg ha-1  and 1753 kg ha-1  pod yield during Kharif and late Rabi respectively) and higher profitability was obtained in diclosulam @ 25 g ha-1 with encapsulation (T7) (1.80 and 2.01 B:C ratio during (Kharif and late Rabi respectively). Nano-encapsulated herbicides can thus significantly improve weed control in rainfed groundnut

Opioid-related (ORL1) receptors are enriched in a subpopulation of sensory neurons and prolonged activation produces no functional loss of surface N-type calcium channels.

The opioid-related receptor, ORL1, is activated by the neuropeptide nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage-activated (HVA) calcium channel currents (I(Ca)) via a G-protein-coupled mechanism. Endocytosis of ORL1 receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage-gated calcium channel (VGCC) internalization via physical interaction between ORL1 and the N-type channel. However, there is no direct electrophysiological evidence for this mechanism in dorsal root ganglion (DRG) neurons or their central nerve terminals. The present study tested this using whole-cell patch-clamp recordings of HVA I(Ca) in rat DRG neurons and primary afferent excitatory synaptic currents (eEPSCs) in spinal cord slices. DRG neurons were classified on the basis of diameter, isolectin-B4 (IB4) binding and responses to capsaicin, N/OFQ and a μ-opioid agonist, DAMGO. IB4-negative neurons less than 20 μm diameter were selectively responsive to N/OFQ as well as DAMGO. In these neurons, ORL1 desensitization by a supramaximal concentration of N/OFQ was not followed by a decrease in HVA I(Ca) current density or proportion of whole-cell HVA I(Ca) contributed by N-type VGCC as determined using the N-type channel selective blocker, ω-conotoxin CVID. There was also no decrease in the proportion of N-type I(Ca) when neurons were incubated at 37°C with N/OFQ for 30 min prior to recording. In spinal cord slices, N/OFQ consistently inhibited eEPSCs onto dorsal horn neurons. As observed in DRG neurons, preincubation of slices in N/OFQ for 30 min produced no decrease in the proportion of eEPSCs inhibited by CVID. In conclusion, no internalization of the N-type VGCC occurs in either the soma or central nerve terminals of DRG neurons following prolonged exposure to high, desensitizing concentrations of N/OFQ.NHMRC Grant: 056992

Novel omega-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration

Background: Antagonists of N-type voltage-gated calcium channels (VGCC), Ca(v)2.2, can manage severe chronic pain with intrathecal use and may be effective systemically. A series of novel omega-conotoxins that selectively inhibit N-type VGCCs was isolated from Conus catus. In the present study, the potency and reversibility of omega-conotoxins CVID, CVIE and CVIF to inhibit N-type calcium currents were investigated in mouse isolated dorsal root ganglion (DRG) neurons. The systemic potency of each omega-conotoxin to reverse signs of mouse chronic inflammatory pain was also compared

High-voltage activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury

Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8-to 11-wkold males (n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium-to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The alpha 2 delta-1 subunit was upregulated by 1.7-fold and gamma-3, gamma-2, and beta-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium-to large-diameter neurons

MrIC, a novel alpha-conotoxin agonist in the presence of PNU at endogenous alpha-7 nicotinic acetylcholine receptors

alpha-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs have led to significant advances in our understanding of the structure and function of these key ion channels. Here we report the discovery of a novel 4/7 alpha-conotoxin, MrIC from the venom duct of Conus marmoreus, which acts as an agonist at the endogenous human alpha 7 nAChR in SH-SY5Y cells pretreated with PNU120596 (PNU). This unique agonist activity of MrIC at alpha 7 nAChRs may guide the development of novel alpha 7 nAChR modulators

Green Synthesis of Silver Nanoparticles Using Argyreia nervosa Leaf Extract and Their Antimicrobial Activity

The biogenic synthesis of silver nanoparticles (AgNPs) has attracted many researchers due to their physical, chemical, optical, and biological properties, embracing a range of activities such as antibacterial, antifungal, anti-inflammatory, and anticancer activities. The purpose of this work is to synthesize and characterize AgNPs using Argyreia nervosa (AN) plant leaf extract, as well as to test their antimicrobial applications. In this work, silver nitrate (AgNO3) at 0.1 mM concentration and stable AgNPs were synthesized and observed by monitoring the color change of the solution from light yellow to brown. The UV–Vis spectrum shows a peak at 445 nm, confirming the formation of AN-AgNPs and Fourier transform infrared (FTIR) results confirm the presence of chemical groups which act as reducing agents stabilizing the AN-AgNPs and antimicrobial capping agents enhancing antimicrobial properties of AN-AgNPs. The crystalline behavior of these AN-AgNPs is confirmed through X-ray powder diffraction (PXRD) peaks. The morphology of AN-AgNPs and their sizes were studied (sizes range from 10 to 40 nm) using scanning electron microscopy (SEM). The disk diffusion assay shows the antimicrobial activity over Escherichia coli pathogenic microorganisms of clinical interest. The obtained results confirm a more significant antimicrobial effect of the biogenic AN-AgNPs maintaining low cytotoxicity. This work presents a potential way to produce non-toxic biogenic AgNPs with enhanced antibacterial activity, which can meet the increasing global demand for biogenic AgNPs as an alternative to antibiotics

The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity

Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage sensors are important for the interaction of Pre1a with NaV channels but cannot account for its unique subtype selectivity. Through analysis of the binding regions we ascertained that the variability of the S1-S2 loops between NaV channels contributes substantially to the selectivity profile observed for Pre1a, particularly with regards to fast inactivation. A serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a’s potent and selective inhibitory effect on the fast inactivation process of NaV1.1 and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV channels may be necessary for functional modulation, and that targeting the diverse S1-S2 region within voltage-sensing domains provides an avenue to develop subtype selective tools

MrIC, a Novel α‑Conotoxin Agonist in the Presence of PNU at Endogenous α7 Nicotinic Acetylcholine Receptors

α-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs have led to significant advances in our understanding of the structure and function of these key ion channels. Here we report the discovery of a novel 4/7 α-conotoxin, MrIC from the venom duct of <i>Conus marmoreus</i>, which acts as an agonist at the endogenous human α7 nAChR in SH-SY5Y cells pretreated with PNU120596 (PNU). This unique agonist activity of MrIC at α7 nAChRs may guide the development of novel α7 nAChR modulators