Altering cold-regulated gene expression decouples the salicylic acid-growth trade-off in Arabidopsis.

In Arabidopsis (Arabidopsis thaliana), overproduction of salicylic acid (SA) increases disease resistance and abiotic stress tolerance but penalizes growth. This growth-defense trade-off has hindered the adoption of SA-based disease management strategies in agriculture. However, investigation of how SA inhibits plant growth has been challenging because many SA-hyperaccumulating Arabidopsis mutants have developmental defects due to the pleiotropic effects of the underlying genes. Here, we heterologously expressed a bacterial SA synthase gene in Arabidopsis and observed that elevated SA levels decreased plant growth and reduced the expression of cold-regulated (COR) genes in a dose-dependent manner. Growth suppression was exacerbated at below-ambient temperatures. Severing the SA-responsiveness of individual COR genes was sufficient to overcome the growth inhibition caused by elevated SA at ambient and below-ambient temperatures while preserving disease- and abiotic-stress-related benefits. Our results show the potential of decoupling SA-mediated growth and defense trade-offs for improving crop productivity.

Reversing anxiety by targeting a stress-responsive signaling pathway.

Current treatments of anxiety and depressive disorders are plagued by considerable side effects and limited efficacies, underscoring the need for additional molecular targets that can be leveraged to improve medications. Here, we have identified a molecular cascade triggered by chronic stress that exacerbates anxiety- and depressive-like behaviors. Specifically, chronic stress enhances Src kinase activity and tyrosine phosphorylation of calmodulin, which diminishes MyosinVa (MyoVa) interaction with Neuroligin2 (NL2), resulting in decreased inhibitory transmission and heightened anxiety-like behaviors. Importantly, pharmacological inhibition of Src reinstates inhibitory synaptic deficits and effectively reverses heightened anxiety-like behaviors in chronically stressed mice, a process requiring the MyoVa-NL2 interaction. These data demonstrate the reversibility of anxiety- and depressive-like phenotypes at both molecular and behavioral levels and uncover a therapeutic target for anxiety and depressive disorders.

On the rise of fear speech in online social media.

Recently, social media platforms are heavily moderated to prevent the spread of online hate speech, which is usually fertile in toxic words and is directed toward an individual or a community. Owing to such heavy moderation, newer and more subtle techniques are being deployed. One of the most striking among these is fear speech. Fear speech, as the name suggests, attempts to incite fear about a target community. Although subtle, it might be highly effective, often pushing communities toward a physical conflict. Therefore, understanding their prevalence in social media is of paramount importance. This article presents a large-scale study to understand the prevalence of 400K fear speech and over 700K hate speech posts collected from Gab.com. Remarkably, users posting a large number of fear speech accrue more followers and occupy more central positions in social networks than users posting a large number of hate speech. They can also reach out to benign users more effectively than hate speech users through replies, reposts, and mentions. This connects to the fact that, unlike hate speech, fear speech has almost zero toxic content, making it look plausible. Moreover, while fear speech topics mostly portray a community as a perpetrator using a (fake) chain of argumentation, hate speech topics hurl direct multitarget insults, thus pointing to why general users could be more gullible to fear speech. Our findings transcend even to other platforms (Twitter and Facebook) and thus necessitate using sophisticated moderation policies and mass awareness to combat fear speech.

Hypersonic Bose-Einstein condensates in accelerator rings.

Some of the most sensitive and precise measurements-for example, of inertia1, gravity2 and rotation3-are based on matter-wave interferometry with free-falling atomic clouds. To achieve very high sensitivities, the interrogation time has to be very long, and consequently the experimental apparatus needs to be very tall (in some cases reaching ten or even one hundred metres) or the experiments must be performed in microgravity in space4-7. Cancelling gravitational acceleration (for example, in atomtronic circuits8,9 and matter-wave guides10) is expected to result in compact devices with extended interrogation times and therefore increased sensitivity. Here we demonstrate smooth and controllable matter-wave guides by transporting Bose-Einstein condensates (BECs) over macroscopic distances. We use a neutral-atom accelerator ring to bring BECs to very high speeds (16 times their sound velocity) and transport them in a magnetic matter-wave guide for 15 centimetres while fully preserving their internal coherence. The resulting high angular momentum of more than 40,000h per atom (where h is the reduced Planck constant) gives access to the higher Landau levels of quantum Hall states, and the hypersonic velocities achieved, combined with our ability to control potentials with picokelvin precision, will facilitate the study of superfluidity and give rise to tunnelling and a large range of transport regimes of ultracold atoms11-13. Coherent matter-wave guides are expected to enable interaction times of several seconds in highly compact devices and lead to portable guided-atom interferometers for applications such as inertial navigation and gravity mapping.

Regulation of NLGN3 and the Synaptic Rho-GEF Signaling Pathway by CDK5.

Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that are involved in synapse assembly and function. The NLGN gene family consists of 5 genes (NLGN1-3, 4X, and 4Y). NLGN3 forms heterodimers with other NLGNs and is expressed at both excitatory and inhibitory synapses, although the distinct role at different synapses is not fully understood. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that targets various neuronal substrates to impact neuronal migration, neurite outgrowth, synaptic transmission, and plasticity. Both NLGNs and their presynaptic binding partners neurexins are highly associated with neurodevelopmental disorders. The NLGN3 gene is on the X chromosome and variants in NLGN3 have been linked to the pathophysiology in neurodevelopmental disorders. To better understand the endogenous modulation of NLGN3, we generated an HA-tagged knock-in mouse. We found that Cdk5 associates with NLGN3 in vivo and phosphorylates NLGN3 on serine 725 (S725) in the knock-in mouse of either sex. The phosphorylation affects the NLGN3 association with Kalirin-7, a postsynaptic guanine nucleotide exchange factors for Rho GTPase family proteins. We further observed that the phosphorylation modulates NLGN3 surface expression and NLGN3-mediated synaptic currents in cultured rat neurons. Thus, we characterized NLGN3 as a novel Cdk5 substrate and revealed the functional consequences of NLGN3 S725 phosphorylation in neurons. Our study provides a novel molecular mechanism underlying Cdk5-mediated regulation of postsynaptic cell adhesion molecules.SIGNIFICANCE STATEMENT NLGN3 is involved in synapse assembly and function at both excitatory and inhibitory synapses and has been associated with the pathophysiology of neurodevelopmental disorders. Cdk5 has brain-specific activity and is involved in neuronal transmission, synapse function, and plasticity. Here, we characterize NLGN3 as a Cdk5 substrate for the first time and show that Cdk5-mediated phosphorylation regulates NLGN3 function. We demonstrate that NLGN3 S725 is a Cdk5 phosphorylation site, and reveal that the site is important for NLGN3 association with Kalirin-7, NLGN3 surface expression, and NLGN3-mediated synaptic transmission.

Fusarium wilt pandemic: current understanding and molecular perspectives.

Plant diseases pose a severe threat to the food security of the global human population. One such disease is Fusarium wilt, which affects many plant species and causes up to 100% yield losses. Fusarium pathogen has high variability in its genetic constitution; therefore, it has evolved into different physiological races to infect different plant species spread across the different geographical regions of the world. The pathogen mainly affects plant roots, leading to colonizing and blocking vascular bundle cells, specifically xylem vessels. This blocking results in chlorosis, vascular discoloration, leaf wilting, shortening of plant, and, in severe cases, premature plant death. Due to the soil-borne nature of the wilt pathogen, neither agronomic nor plant protection measures effectively reduce the incidence of the disease. Therefore, the most cost-effective management strategy for Fusarium wilt is developing varieties resistant to a particular race of the fungus wilt prevalent in a given region. This strategy requires understanding the pathogen, its disease cycle, and epidemiology with climate-changing scenarios. Hence, in the review, we will discuss the pathogenic aspect and genetics of the Fusarium wilt, including molecular interventions for developing climate-smart wilt tolerant/resistant varieties of crops. Overall, this review will add to our knowledge for advancing the breeding of resistance against the wilt pandemic.

Synergistic reduction of nitrophenols by Au-CDs nanoconjugates with NaBH4.

Developing sustainable and innovative approaches for the efficient reduction of nitrophenols is crucial for environmental remediation, for managing health concerns posed by their widespread presence as hazardous pollutants in industrial effluents and contaminated water. We report the use of 12.9 ± 1 nm (TEM data) sized gold carbon dot nanoconjugates (Au@CDs) for catalytic conversion of o, m, p-nitrophenols to aminophenols by sodium borohydride. A simple approach was followed to synthesize ultra-small and highly stable Au@CDs, using citric acid and PEG as reducing and stabilizing agents. X-ray diffraction analysis verified the formation of nano-crystalline nanoconjugates. These nanoconjugates showed a remarkable catalytic activity in the range of 0.22-0.33 s-1(varying with nanoconjugate concentration) which was much higher compared to conventional chemical methods of reduction. All the catalytic reaction experiments were performed at room temperature (27 ± 2 °C). Furthermore, an increase in rate constant was observed with increasing concentration of nanoconjugates. The catalytic activity of Au@CDs nanoconjugates was observed to be in order of m-nitrophenol > o-nitrophenol > p-nitrophenol with apparent rate constant (kaap) values of 0.068, 0.043 and 0.031, respectively. Comparative analysis with GNPs, CDs and Au@CDs nanoconjugates stated that the nanoconjugates had superior catalytic activity. The research can have significant implications in the development of new strategies for environmental remediation and biomedical applications.

Molecular cloning and characterization of heat-responsive LcOPR1, a gene encoding oxophytodienoic acid reductase in lentil.

Improving crop plants using biotechnological implications is a promising and modern approach compared to traditional methods. High-temperature exposure to the reproductive stage induces flower abortion and declines grain filling performance, leading to smaller grain production and low yield in lentil and other legumes. Thus, cloning effective candidate genes and their implication in temperature stress tolerance in lentil (Lens culinaris Medik.) using biotechnological tools is highly demandable. The 12-oxophytodienoic acid reductases (OPRs) are flavin mononucleotide-dependent oxidoreductases with vital roles in plants. They are members of the old yellow enzyme (OYE) family. These enzymes are involved in the octadecanoid pathway, which contributes to jasmonic acid biosynthesis and is essential in plant stress responses. Lentil is one of the vital legume crops affected by the temperature fluctuations caused by global warming. Therefore, in this study, the LcOPR1 gene was successfully cloned and isolated from lentils using RT-PCR to evaluate its functional responses in lentil under heat stress. The bioinformatics analysis revealed that the full-length cDNA of LcOPR1 was 1303 bp, containing an 1134 bp open reading frames (ORFs), encoding 377 amino acids with a predicted molecular weight of 41.63 and a theoretical isoelectric point of 5.61. Bioinformatics analyses revealed that the deduced LcOPR1 possesses considerable homology with other plant 12-oxophytodienoic acid reductases (OPRs). Phylogenetic tree analysis showed that LcOPR1 has an evolutionary relationship with other OPRs in different plant species of subgroup I, containing enzymes that are not required for jasmonic acid biosynthesis. The expression analysis of LcOPR1 indicated that this gene is upregulated in response to the heat-stress condition and during recovery in lentil. This study finding might be helpful to plant breeders and biotechnologists in LcOPR1 engineering and/or plant breeding programs in revealing the biological functions of LcOPR1 in lentils and the possibility of enhancing heat stress tolerance by overexpressing LcOPR1 in lentil and other legume plants under high temperature.

Genome wide screening to discover novel toxin-antitoxin modules in Mycobacterium indicus pranii; perspective on gene acquisition during mycobacterial evolution.

Mycobacterium indicus pranii (MIP), a benign saprophyte with potent immunomodulatory attributes, holds a pivotal position in mycobacterial evolution, potentially serving as the precursor to the pathogenic Mycobacterium avium complex (MAC). Despite its established immunotherapeutic efficacy against leprosy and notable outcomes in gram-negative sepsis and COVID-19 cases, the genomic and biochemical features of MIP remain largely elusive. This study explores the uncharted territory of toxin-antitoxin (TA) systems within MIP, hypothesizing their role in mycobacterial pathogenicity regulation. Genome-wide screening, employing diverse databases, unveils putative TA modules in MIP, setting the stage for a comparative analysis with known modules in Mycobacterium tuberculosis, Mycobacterium smegmatis, Escherichia coli, and Vibrio cholerae. The study further delves into the TA network of MAC and Mycobacterium intracellulare, unraveling interactive properties and family characteristics of identified TA modules in MIP. This comprehensive exploration seeks to illuminate the contribution of TA modules in regulating virulence, habitat diversification, and the evolutionary pathogenicity of mycobacteria. The insights garnered from this investigation not only enhance our understanding of MIP's potential as a vaccine candidate but also hold promise in optimizing tuberculosis drug regimens for expedited recovery.

Exploring a facile preparation method for Co-Ni/MoS2-derived nanohybrid from wheat straw extract and its physicochemical properties.

This study presents a novel approach for the fabrication of a Co,Ni/MoS2-derived nanohybrid material using wheat straw extract. The facile synthesis method involves a sol-gel process, followed by calcination, showcasing the potential of agricultural waste as a sustainable reducing and chelating reagent. The as-prepared nanohybrid has been characterized using different techniques to analyse its physicochemical properties. X-ray diffraction analysis confirmed the successful synthesis of the nanohybrid material, identifying the presence of NiMoO4, CoSO4 and Mo17O47 as its components. Fourier-transform infrared spectroscopy differentiated the functional groups present in the wheat straw biomass and those in the nanohybrid material, highlighting the formation of metal-oxide and sulphide bonds. Scanning electron microscopy revealed a heterogeneous morphology with agglomerated structures and a grain size of around 70 nm in the nanohybrid. Energy-dispersive X-ray spectroscopy analysis shows the composition of elements with weight percentages of (Mo) 9.17%, (S) 6.21%, (Co) 12.48%, (Ni) 12.18% and (O) 50.46% contributing to its composition. Electrochemical analysis performed through cyclic voltammetry showcased the exceptional performance of the nanohybrid material as compared with MoS2, suggesting its possible applications for designing biosensors and related technologies. Thus, the research study presented herein underscores the efficient utilization of natural resources for the development of functional nanomaterials with promising applications in various fields. This study paves a way for manufacturing innovation along with advancement of novel synthesis method for sustainable nanomaterial for future technological developments.

Drought stress in maize: stress perception to molecular response and strategies for its improvement.

Given the future demand for food crops, increasing crop productivity in drought-prone rainfed areas has become essential. Drought-tolerant varieties are warranted to solve this problem in major crops, with drought tolerance as a high-priority trait for future research. Maize is one such crop affected by drought stress, which limits production, resulting in substantial economic losses. It became a more serious issue due to global climate change. The most drought sensitive among all stages of maize is the reproductive stages and the most important for overall maize production. The exact molecular basis of reproductive drought sensitivity remains unclear due to genes' complex regulation of drought stress. Understanding the molecular biology and signaling of the unexplored area of reproductive drought tolerance will provide an opportunity to develop climate-smart drought-tolerant next-generation maize cultivars. In recent decades, significant progress has been made in maize to understand the drought tolerance mechanism. However, improving maize drought tolerance through breeding is ineffective due to the complex nature and multigenic control of drought traits. With the help of advanced breeding techniques, molecular genetics, and a precision genome editing approach like CRISPR-Cas, candidate genes for drought-tolerant maize can be identified and targeted. This review summarizes the effects of drought stress on each growth stage of maize, potential genes, and transcription factors that determine drought tolerance. In addition, we discussed drought stress sensing, its molecular mechanisms, different approaches to developing drought-resistant maize varieties, and how molecular breeding and genome editing will help with the current unpredictable climate change.

The potentialities of omics resources for millet improvement.

Millets are nutrient-rich (nutri-rich) cereals with climate resilience attributes. However, its full productive potential is not realized due to the lack of a focused yield improvement approach, as evidenced by the available literature. Also, the lack of well-characterized genomic resources significantly limits millet improvement. But the recent availability of genomic data and advancement in omics tools has shown its enormous potential to enhance the efficiency and precision faced by conventional breeding in millet improvement. The development of high throughput genotyping platforms based on next-generation sequencing (NGS) has provided a low-cost method for genomic information, specifically for neglected nutri-rich cereals with the availability of a limited number of reference genome sequences. NGS has created new avenues for millet biotechnological interventions such as mutation-based study, GWAS, GS, and other omics technologies. The simultaneous discovery of high-throughput markers and multiplexed genotyping platform has aggressively aided marker-assisted breeding for millet improvement. Therefore, omics technology offers excellent opportunities to explore and combine useful variations for targeted traits that could impart high nutritional value to high-yielding cultivars under changing climatic conditions. In millet improvement, an in-depth account of NGS, integrating genomics data with different biotechnology tools, is reviewed in this context.

Gold-carbon dot (Au@Cd) nanoconjugates based electrochemical sensing of cholesterol and effect of nitrogen ion implantation on sensitivity.

Serum cholesterol dysregulation is associated with prognosis and diagnosis of many diseases and effective biosensor will improvise their management. A novel electrochemical biosensor was fabricated based on gelatin-Au@CD nanoconjugate films for cholesterol detection. Initially, the surface of indium titanium oxide (ITO) coated glass was modified by drop casting of gelatin-Au@CD nanoconjugates to prepare the electrodes. Electrochemical studies for detection of bioanalytes(such as urea (U), ascorbic acid (AA), oxalic acid (OA), gallic acid (GA), cholesterol (Chox), dextrose (D), l-cysteine (Cys) and citric acid (CA)) were performed using cyclic voltammetry. The presence of nanoconjugates provided an appropriate environment for enhanced electrochemical response for cholesterol. These electrodes exhibited a linear response towards the presence of cholesterol in the linear concentration range of 2-20 mM with a correlation coefficient of 0.95, and the superior sensitivity of 1.36 µA/mM/cm2. Additionally, enhanced sensitivity (2.99 µA/mM/cm2) of nitrogen ion irradiated films up to a fluence of 1016 ions/cm2 was noticed because of morphological changes in the electrode surface brought about by irradiation. Approximately 54% enhancement was found when the ion fluence was 1016 ions/cm2. The designed nanoconjugate electrode showed excellent response towards cholesterol sensing and eliminates the requirement of any enzymes making the overall process simpler, cost-effective and allows for room temperature storage.

Biocompatible gelatin/carbon dot nanocomposite based urea sensor and the effect of nitrogen ion implantation.

In this study, we have fabricated a novel platform for sensing of urea using gelatin/carbon dots nanocomposite system. The sensor electrode was created by depositing the nanocomposite gel onto thin glass plates coated with indium tin oxide (ITO) using the drop casting technique. The behavior of these electrodes was investigated against a number of bioanalytes in the concentration range of 2-20 mM by cyclic voltammetry. The system was observed to be highly selective for urea with a sensitivity of 1.65 µA/mM/cm in the experimental linear range of 2-20 mM. Furthermore, the gelatin/CD-ITO electrode were also subjected to 50 KeV N2+ ion beam irradiation with varying fluence in the range of 1012 to 1016 ions/cm2. Sensing profile of the irradiated samples for urea suggested enhancement in sensitivity to 2 µA/mM cm2, when the ion fluence was 5 × 1015 ions/cm2. This enhancement after irradiation suggests a clear dependence of detection on the fluence of the ion beam. The observed excellent sensitivity of radiation processed nanocomposite material can be used as an enzyme-free platform for urea detection. Additionally, the CDs showed fluorescence quenching on treatment with mere 50 µM urea suggesting the high sensitivity of the platform.

CRAC channel opening is determined by a series of Orai1 gating checkpoints in the transmembrane and cytosolic regions.

The initial activation step in the gating of ubiquitously expressed Orai1 calcium (Ca2+) ion channels represents the activation of the Ca2+-sensor protein STIM1 upon Ca2+ store depletion of the endoplasmic reticulum. Previous studies using constitutively active Orai1 mutants gave rise to, but did not directly test, the hypothesis that STIM1-mediated Orai1 pore opening is accompanied by a global conformational change of all Orai transmembrane domain (TM) helices within the channel complex. We prove that a local conformational change spreads omnidirectionally within the Orai1 complex. Our results demonstrate that these locally induced global, opening-permissive TM motions are indispensable for pore opening and require clearance of a series of Orai1 gating checkpoints. We discovered these gating checkpoints in the middle and cytosolic extended TM domain regions. Our findings are based on a library of double point mutants that contain each one loss-of-function with one gain-of-function point mutation in a series of possible combinations. We demonstrated that an array of loss-of-function mutations are dominant over most gain-of-function mutations within the same as well as of an adjacent Orai subunit. We further identified inter- and intramolecular salt-bridge interactions of Orai subunits as a core element of an opening-permissive Orai channel architecture. Collectively, clearance and synergistic action of all these gating checkpoints are required to allow STIM1 coupling and Orai1 pore opening. Our results unravel novel insights in the preconditions of the unique fingerprint of CRAC channel activation, provide a valuable source for future structural resolutions, and help to understand the molecular basis of disease-causing mutations.

Macrophages in Microbial Pathogenesis: Commonalities of Defense Evasion Mechanisms.

Macrophages are key arsenals of the immune system against invaders. After compartmental isolation of a pathogen in phagosomes, the host immune response attempts to neutralize the pathogen. However, pathogens possess the ability to subvert these assaults and can also convert macrophages into their replicative niche. The multiple host defense evasion mechanisms employed by these pathogens include phagosome maturation arrest, molecular mimicry through secretory antigens, interference with host signaling, active radical neutralization, inhibition of phagosome acidification, alteration of programmed cell death, and other mechanisms. Macrophage biology as a part of the host-pathogen interaction has expanded rapidly in the past decade. The present review aims to shed some light upon the macrophage defense evasion strategies employed by pathogens. We have also incorporated recent knowledge in the field of macrophage dynamics during infection and evolutionary perspectives of macrophage dynamics.

PSD-95 binding dynamically regulates NLGN1 trafficking and function.

PSD-95 is a scaffolding protein that regulates the synaptic localization of many receptors, channels, and signaling proteins. The NLGN gene family encodes single-pass transmembrane postsynaptic cell adhesion molecules that are important for synapse assembly and function. At excitatory synapses, NLGN1 mediates transsynaptic binding with neurexin, a presynaptic cell adhesion molecule, and also binds to PSD-95, although the relevance of the PSD-95 interaction is not clear. We now show that disruption of the NLGN1 and PSD-95 interaction decreases surface expression of NLGN1 in cultured neurons. Furthermore, PKA phosphorylates NLGN1 on S839, near the PDZ ligand, and dynamically regulates PSD-95 binding. A phosphomimetic mutation of NLGN1 S839 significantly reduced PSD-95 binding. Impaired NLGN1/PSD-95 binding diminished synaptic NLGN1 expression and NLGN1-mediated synaptic enhancement. Our results establish a phosphorylation-dependent molecular mechanism that regulates NLGN1 and PSD-95 binding and provides insights into excitatory synaptic development and function.

Early wound-responsive cues regulate the expression of WRKY family genes in chickpea differently under wounded and unwounded conditions.

Insect wounding activates a large number of signals that function coordinately to modulate gene expression and elicit defense responses. How each signal influences gene expression in absence of wounding is also important since it can shed light on changes occurring during the shift to wound response. Using simulated Helicoverpa armigera herbivory on chickpea, we had identified at least 14 WRKY genes that showed 5-50 fold increase in expression within 5-20 min of wounding. Our studies show that contrary to their collective effects upon wounding, individual chemical cues show distinct and often opposite effects in absence of wounding. In particular, jasmonic acid, a key early defense hormone, reduced transcripts of most WRKY genes by > 50% upon treatment of unwounded chickpea leaves as did salicylic acid. Neomycin (a JA biosynthesis inhibitor) delayed and also reduced early wound expression. H2O2 transiently activated several genes within 5-20 min by 5-8 fold while ethylene activated only a few WRKY genes by 2-5 fold. The summation of the individual effects of these chemical cues does not explain the strong increase in transcript levels upon wounding. Detailed studies of a 931 nt region of the CaWRKY41 promoter, show strong wound-responsive GUS expression in Arabidopsis even in presence of neomycin. Surprisingly its expression was lost in the coi1, ein2 and myc2myc3myc4 mutant backgrounds suggesting the requirement of intact ethylene and JA signaling pathways (dependent on MYCs) for wound-responsive expression. The studies highlight the complexity of gene regulation by different chemical cues in the presence and absence of wounding. Supplementary Information: The online version contains Supplementary material available at 10.1007/s12298-022-01170-y.

The post-synaptic scaffolding protein tamalin regulates ligand-mediated trafficking of metabotropic glutamate receptors.

Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal functions and have also been implicated in multiple neuropsychiatric disorders like fragile X syndrome, autism, and others. mGluR trafficking not only plays important roles in controlling the spatiotemporal localization of these receptors in the cell but also regulates the activity of these receptors. Despite this obvious significance, the cellular machineries that control the trafficking of group I metabotropic glutamate receptors in the central nervous system have not been studied in detail. The post-synaptic scaffolding protein tamalin has been shown to interact with group I mGluRs and also with many other proteins involved in protein trafficking in neurons. Using a molecular replacement approach in mouse hippocampal neurons, we show here that tamalin plays a critical role in the ligand-dependent internalization of mGluR1 and mGluR5, members of the group I mGluR family. Specifically, knockdown of endogenous tamalin inhibited the ligand-dependent internalization of these two receptors. Both N-terminal and C-terminal regions of tamalin played critical roles in mGluR1 endocytosis. Furthermore, we found that tamalin regulates mGluR1 internalization by interacting with S-SCAM, a protein that has been implicated in vesicular trafficking. Finally, we demonstrate that tamalin plays a critical role in mGluR-mediated internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, a process believed to be the cellular correlate for mGluR-dependent synaptic plasticity. Taken together, these findings reveal a mechanistic role of tamalin in the trafficking of group I mGluRs and suggest its physiological implications in the brain.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.