Molecular mechanisms of Evening Complex activity in Arabidopsis.

The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX-ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity.

Optical backscattering and linear polarization properties of the colony forming cyanobacterium Microcystis.

Light scattering characteristics of the cyanobacterium Microcystis are investigated with numerical models for sphere aggregates. During summer bloom seasons, Microcystis is prevalent in many inland waters across the globe. Monitoring concentrations with remote sensing techniques requires knowledge of the inherent optical properties (IOPs), especially the backscattering properties of Microcystis cells and colonies in natural settings. In situ measurements in waters dominated by Microcystis blooms have previously detected extremely high backscattering ratios, i.e., bb/b>0.043 at 443 nm [1], the highest to our knowledge in the natural environment. These highbb/bvalues could hold promise as a diagnostic tool in identifying and monitoring Microcystis using optical approaches. However, it has been unclear how this type of optically 'soft' organic particle can generate such highbb/bvalues. In this study, the Multiple Sphere T-matrix (MSTM) model is used to calculate the IOPs of model colonies, including bb/b. Colony sizes in the model ranged from several cells to several hundred and both colony packing density and cell gas vacuole content were varied. Results are compared with model results for equivalent-volume spheres (EVS) and direct in situ measurements. Colony formation was required in the modeling to reproduce the high bb/bconsistent with in situ measurements. The combination of moderate to very dense colony (packing density >30%) and high gas vacuole content in individual cells (volume percentage >20%) was the most favorable condition leading to rapid increases in bb/bwith increasing number of cells Ncell of the colony. Significant linear correlations were observed betweenbb/b and Ncell1/3 for these colonies, wherebb/b increased beyond 0.04 once cell number reached about 1000 cells in the case with the most densely packed cells and highest gas vacuole content. Within commonly observed colony sizes (Ncell <106), colonies with high gas vacuole content exhibited bb/bvalues up to 0.055, consistent with direct measurements from Lake Erie. Polarized scattering was also of interest as a diagnostic tool, particularly with future Earth-orbiting polarimeters being deployed for the NASA Plankton, Aerosols, Cloud, ocean Ecosystem (PACE) mission. The Degree of Linear Polarization (DoLP), expressed by the ratio of two Mueller matrix elements-P12/P11, decreased with increasing colony cell number for Microcystis. Another ratio of two Mueller matrix elementsP22/P11, an index for nonsphericity, also decreased with increasing colony size. In addition to higher relative backscattering, greater colony packing density and larger gas vacuole sizes both led to lower DoLP peak magnitude and lowerP22/P11. An optical opposition feature due to constructive phase interference that was observed previously for cosmic dusts is also present for these modeled colonies, manifested by a narrow intensity peak and negative polarization dip near exact backscattering direction, gradually forming as colony size increases.

Evidence for ubiquitous preferential particle orientation in representative oceanic shear flows.

In situ measurements were undertaken to characterize particle fields in undisturbed oceanic environments. Simultaneous, co-located depth profiles of particle fields and flow characteristics were recorded using a submersible holographic imaging system and an acoustic Doppler velocimeter, under different flow conditions and varying particle concentration loads, typical of those found in coastal oceans and lakes. Nearly one million particles with major axis lengths ranging from ∼14 µm to 11.6 mm, representing diverse shapes, sizes, and aspect ratios were characterized as part of this study. The particle field consisted of marine snow, detrital matter, and phytoplankton, including colonial diatoms, which sometimes formed "thin layers" of high particle abundance. Clear evidence of preferential alignment of particles was seen at all sampling stations, where the orientation probability density function (PDF) peaked at near horizontal angles and coincided with regions of low velocity shear and weak turbulent dissipation rates. Furthermore, PDF values increased with increasing particle aspect ratios, in excellent agreement with models of spheroidal particle motion in simple shear flows. To the best of our knowledge, although preferential particle orientation in the ocean has been reported in two prior cases, our findings represent the first comprehensive field study examining this phenomenon. Evidence of nonrandom particle alignment in aquatic systems has significant consequences to aquatic optics theory and remote sensing, where perfectly random particle orientation and thus isotropic symmetry in optical parameters is assumed. Ecologically, chain-forming phytoplankton may have evolved to form large aspect ratio chains as a strategy to optimize light harvesting.

A comprehensive review on frontotemporal dementia: its impact on language, speech and behavior.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder defined by the selective deterioration of the frontal and temporal lobes of the brain. This comprehensive review explored the effect of FTD on language, speech, and behavior. Early symptoms include difficulty in word finding, reduced speech output, and comprehension deficits, often leading to aphasia. The study discussed the profound behavioral changes observed in FTD patients, including apathy, disinhibition, compulsive behaviors, and loss of empathy, the importance of an accurate and early diagnosis, and its challenges. We even reviewed the potential for targeted therapies and the essential role of multidisciplinary care in managing the language, speech, and behavioral aspects of FTD. By examining objective data and comprehensive research on the subject, this study offers valuable insights into FTD's profound effects on language, speech, and behavior, assisting in improved clinical management and potential therapeutic strategies for this devastating condition.

A demência frontotemporal (DFT) é uma doença neurodegenerativa progressiva definida pela deterioração seletiva dos lobos frontal e temporal do cérebro. Esta revisão abrangente explorou o efeito da DFT na linguagem, na fala e no comportamento. Os primeiros sintomas incluem dificuldade em encontrar palavras, redução da produção de fala e déficits de compreensão, muitas vezes levando à afasia. A revisão discutiu as profundas mudanças comportamentais observadas em pacientes com DFT, incluindo apatia, desinibição, comportamentos compulsivos e perda de empatia, a importância de um diagnóstico preciso e precoce e seus desafios. Também foi revisado o potencial para terapias direcionadas e o papel essencial do cuidado multidisciplinar no gerenciamento dos aspectos de linguagem, fala e comportamentais da DFT. Ao examinar os dados objetivos e a pesquisa abrangente sobre o assunto, esta revisão oferece insights valiosos sobre os efeitos profundos da DFT na linguagem, na fala e no comportamento, auxiliando no melhor manejo clínico e em possíveis estratégias terapêuticas para essa condição devastadora.

Meiotic chromosome organization and its role in recombination and cancer.

Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the conserved and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers.

An innovative technique for nasotracheal fiberoptic intubation using SNPA and its comparison with conventional technique: RCT.

Background: Awake nasotracheal fiberoptic intubation by conventional technique is time consuming and requires expertise. Complications encountered in the conventional technique sometime leads to procedure failure. Objective: The primary aim of this study was to compare the innovative technique using split nasopharyngeal airway (SNPA) with the conventional technique for nasotracheal fiberoptic intubation in terms of time taken for intubation. Method: This was a prospective, randomized, and single blind study conducted with 80 patients who were scheduled for maxillofacial surgery. Patients were randomized into two groups, group CFBI (conventional fiberoptic intubation) and group SNPA (split nasopharyngeal airway). In both the groups patients were prepared for awake fiberoptic naso-tracheal intubation. In Group CFBI (N = 41) awake naso-tracheal intubation was achieved by conventional technique of bronchoscope first approach. In Group SNPA (N = 39) spirally split nasopharyngeal airway was used first as a conduit for the passage of fiberoptic bronchoscope. The primary objective was to assess the time taken for intubation. The secondary objectives were to assess the rate of complications in the form of bleeding, cough, desaturation during the procedure, laryngospasm, and nasal bleeding. Result: The time taken for intubation was 6.15 ± 3.0 minutes in CFBI group and 3.10 ± 1.35 minutes in SNPA group and this this difference was statically significant with P value <0.001. Desaturation during the procedure was more in CFBI (99.46 ± 0.75) compared to SNPA (99 ± 0) group with significant difference P value <0.001. Conclusion: Split nasopharyngeal airway was used as conduit for the passage for the flexible fibreoptic bronchoscope and it considerably reduced the time required for fiberoptic nasotracheal intubation compared to the conventional technique of endotracheal tube first approach. Split nasopharyngeal airway provided better intubating conditions with lesser complications and superior patient comfort.

Effect of 3% Hypertonic Saline Resuscitation on Lactate Clearance and Its Comparison With 0.9% Normal Saline in Traumatic Injury Patients: A Prospective Randomized Control Trial.

BACKGROUND:  Fluid resuscitation with normal saline (NS) can aggravate lactate production. The objective of this study was to evaluate the efficacy of small-volume resuscitation using 3% hypertonic sodium chloride (HS) and its comparison with NS in trauma patients. The primary endpoint was an increase in lactate clearance after 1 hr of fluid resuscitation. The secondary endpoint was the incidence of hemodynamic stability, the volume of transfusion, correction of metabolic acidosis, and complications such as fluid overload and abnormal serum sodium levels. MATERIALS AND METHODS: It was a prospective, randomized, single-blind study. The study was conducted on 60 patients who arrived at the trauma center for emergency operative intervention. Inclusion criteria for patient selection were trauma victims of age more than 18 years and the requirement of emergency operative intervention for trauma except for traumatic brain injury. Patients were divided into two groups: Group HS (hypertonic saline) and Group NS (normal saline). Patients were resuscitated with either 3% HS (4ml/kg) or 0.9% NS (20ml/kg). RESULTS: The HS group had higher lactate clearance at 1 hour compared to the NS group, and this difference was statistically significant with a p-value of <0.001. When hemodynamic parameters were compared at 30 and 60 minutes after resuscitation, the HS group had a significantly lower heart rate (p<0.05 at 30 minutes and <0.001 at 60 minutes, respectively), a higher mean arterial pressure at 60 minutes (p<0.001), a higher pH at 60 minutes (p< 0.05), and a higher bicarbonate concentration at 60 minutes (p<0.05). The HS and NS groups had significant differences in serum sodium levels at 60 minutes (p<0.001). CONCLUSIONS: Resuscitation with 3% hypertonic saline improved lactate clearance. Lower volumes of fluid infusion for resuscitation achieved better hemodynamic stability and correction of metabolic acidosis in the hypertonic saline group. Our study shows that hypertonic saline can be a promising fluid for small-volume resuscitation in trauma patients with compensated mild to moderate shock.

In situ digital holographic microscopy for rapid detection and monitoring of the harmful dinoflagellate, Karenia brevis.

Karenia brevis blooms, also known as red tide, are a recurring problem in the coastal Gulf of Mexico. These blooms have the capacity to inflict substantial damage to human and animal health as well as local economies. Thus, monitoring and detection of K. brevis blooms at all life stages and cell concentrations is essential for ensuring public safety. Current K. brevis monitoring methods have several limitations, including size resolution limits and concentration ranges, limited capacity for spatial and temporal profiling, and/or small sample volume processing. Here, a novel monitoring method wherein an autonomous digital holographic imaging microscope (AUTOHOLO), that overcomes these limitations and can characterize K. brevis concentrations in situ, is presented. Using the AUTOHOLO, in situ field measurements were conducted in the coastal Gulf of Mexico during an active K. brevis bloom over the 2020-21 winter season. Surface and sub-surface water samples collected during these field studies were also analyzed in the lab using benchtop holographic imaging and flow cytometry for validation. A convolutional neural network was trained for automated classification of K. brevis at all concentration ranges. The network was validated with manual counts and flow cytometry, yielding a 90% accuracy across diverse datasets with varying K. brevis concentrations. The usefulness of pairing the AUTOHOLO with a towing system was also demonstrated for characterizing particle abundance over large spatial distances, which could potentially facilitate characterization of spatial distributions of K. brevis during bloom events. Future applications of the AUTOHOLO can include integration into existing HAB monitoring networks to enhance detection capabilities for K. brevis in aquatic environments around the world.

Comparative Study Between Ultrasound-guided Lumbar Paravertebral Block and Lumbar Epidural Block with Ropivacaine for Postoperative Pain Relief in Patient Undergoing Total Hip Replacement Surgery: A Prospective Randomised, Double-blind Study.

Background: Total hip replacement (THR) is mostly performed in patients above 65 years of age. Patients of this age group typically have comorbidities, therefore safe techniques for anaesthesia and analgesia with minimal side effects should be chosen and should allow early mobilisation. Lumbar paravertebral block is less explored in this domain. The primary objective of this study is to compare the efficacy of ultrasound-guided lumbar paravertebral and epidural block using ropivacaine (0.25%) with fentanyl as adjuvant for postoperative pain in patients undergoing unilateral THR. Settings and Design: Randomised, controlled, double-blind, prospective study carried out in the Department of Anaesthesiology at Banaras Hindu University. Methods and Material: After receiving institutional ethical committee clearance and written informed consent from patients, this study was carried out from February 2019 to February 2020. Sixty adult patients who required THR and fulfilled the inclusion criteria were randomised into two groups. The thirty patients in Group A received a continuous infusion of 5 ml/hr (0.25%) ropivacaine + 2 mcg/ml fentanyl via lumbar epidural catheter. The thirty patients in Group B received a continuous infusion of 5 ml/hr (0.25%) ropivacaine + 2 mcg/ml fentanyl via lumbar paravertebral catheter. Visual analogue scale (VAS) was used to evaluate pain scores. Rescue analgesia use and duration of hospital stay was calculated and compared in postoperative period. The statistical analysis of data was done by using software Statistical Package for Social Sciences SPSS for Windows (Version 23.0), and chi-square test was used for categorical variables. To compare the two groups of mean Student's t-test and for more than two groups one-way analysis of variance, the ANOVA test was used. Results: In Group A, 16.7% patients required rescue analgesic, and in Group B, 26.7% required rescue analgesia which is comparable and non-significant. The mean duration of hospital stay in Group A is 7.50 days. Compared to 6.47 days in Group B, this difference is statistically significant (p-0.000). Conclusions: Analgesia provided by paravertebral block is not superior to epidural block, but paravertebral block did reduce the duration of hospital stay and provided better haemodynamic stability.

A comprehensive review on frontotemporal dementia: its impact on language, speech and behavior / Uma revisão abrangente sobre demência frontotemporal: seu impacto na linguagem, fala e comportamento

ABSTRACT. Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder defined by the selective deterioration of the frontal and temporal lobes of the brain. This comprehensive review explored the effect of FTD on language, speech, and behavior. Early symptoms include difficulty in word finding, reduced speech output, and comprehension deficits, often leading to aphasia. The study discussed the profound behavioral changes observed in FTD patients, including apathy, disinhibition, compulsive behaviors, and loss of empathy, the importance of an accurate and early diagnosis, and its challenges. We even reviewed the potential for targeted therapies and the essential role of multidisciplinary care in managing the language, speech, and behavioral aspects of FTD. By examining objective data and comprehensive research on the subject, this study offers valuable insights into FTD's profound effects on language, speech, and behavior, assisting in improved clinical management and potential therapeutic strategies for this devastating condition.

RESUMO. A demência frontotemporal (DFT) é uma doença neurodegenerativa progressiva definida pela deterioração seletiva dos lobos frontal e temporal do cérebro. Esta revisão abrangente explorou o efeito da DFT na linguagem, na fala e no comportamento. Os primeiros sintomas incluem dificuldade em encontrar palavras, redução da produção de fala e déficits de compreensão, muitas vezes levando à afasia. A revisão discutiu as profundas mudanças comportamentais observadas em pacientes com DFT, incluindo apatia, desinibição, comportamentos compulsivos e perda de empatia, a importância de um diagnóstico preciso e precoce e seus desafios. Também foi revisado o potencial para terapias direcionadas e o papel essencial do cuidado multidisciplinar no gerenciamento dos aspectos de linguagem, fala e comportamentais da DFT. Ao examinar os dados objetivos e a pesquisa abrangente sobre o assunto, esta revisão oferece insights valiosos sobre os efeitos profundos da DFT na linguagem, na fala e no comportamento, auxiliando no melhor manejo clínico e em possíveis estratégias terapêuticas para essa condição devastadora.

Carbohydrates and polyphenolics of extracts from genetically altered plant acts as catalysts for in vitro synthesis of silver nanoparticle.

Eco-friendly biosynthetic approach for silver nanoparticles production using plant extracts is an exciting advancement in bio-nanotechnology and has been successfully attempted in nearly 41 plant species. However, an established model plant system for systematically unraveling the biochemical components required for silver nanoparticles production is lacking. Here we used Arabidopsis thaliana as the model plant for silver nanoparticles biosynthesis in vitro. Employing biochemical, spectroscopic methods, selected mutants and over-expressor plants of Arabidopsis involved in pleotropic functions and sugar homeostasis, we show that carbohydrates, polyphenolics and glyco-proteins are essential components which stimulated silver nanoparticles synthesis. Using molecular genetics as a tool, our data enforces the requirement of sugar conjugated proteins as essentials for AgNPs synthesis over protein alone. Additionally, a comparative analysis of AgNPs synthesis using the aqueous extracts of some of the plant species found in a brackish water ecosystem (Gracilaria, Potamogeton, Enteromorpha and Scendesmus) were explored. Plant extract of Potamogeton showed the highest potential of nanoparticles production comparable to that of Arabidopsis among the species tested. Silver nanoparticles production in the model plant Arabidopsis not only opens up a possibility of using molecular genetics tool to understand the biochemical pathways and components in detail for its synthesis.

A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation.

Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life1, yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus, forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound significantly more weakly to DNA. R-loop formation results in transcriptional pausing, which has been shown to coincide with splicing factor recruitment and AS2-4. This report presents a novel mechanistic insight for how at least a subset of circRNAs probably contribute to increased splicing efficiency of their cognate exon-skipped messenger RNA and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.

Lipid Based Nanosystems for Curcumin: Past, Present and Future.

Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.