Nanoformulations for dismantling fungal biofilms: The latest arsenals of antifungal therapy.

Globally, fungal infections have evolved as a strenuous challenge for clinicians, particularly in patients with compromised immunity in intensive care units. Fungal co-infection in Covid-19 patients has made the situation more formidable for healthcare practitioners. Surface adhered fungal population known as biofilm often develop at the diseased site to elicit antifungal tolerance and recalcitrant traits. Thus, an innovative strategy is required to impede/eradicate developed biofilm and avoid the formation of new colonies. The development of nanocomposite-based antibiofilm solutions is the most appropriate way to withstand and dismantle biofilm structures. Nanocomposites can be utilized as a drug delivery medium and for fabrication of anti-biofilm surfaces capable to resist fungal colonization. In this context, the present review comprehensively described different forms of nanocomposites and mode of their action against fungal biofilms. Amongst various nanocomposites, efficacy of metal/organic nanoparticles and nanofibers are particularly emphasized to highlight their role in the pursuit of antibiofilm strategies. Further, the inevitable concern of nanotoxicology has also been introduced and discussed with the exigent need of addressing it while developing nano-based therapies. Further, a list of FDA-approved nano-based antifungal formulations for therapeutic usage available to date has been described. Collectively, the review highlights the potential, scope, and future of nanocomposite-based antibiofilm therapeutics to address the fungal biofilm management issue.

Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.

Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.

Nanosensor based approaches for quantitative detection of heparin.

Heparin, being a widely employed anticoagulant in numerus clinical complications, requires strict quantification and qualitative screening to ensure the safety of patients from potential threat of thrombocytopenia. However, the intricacy of heparin's chemical structures and low abundance hinders the precise monitoring of its level and quality in clinical settings. Conventional laboratory assays have limitations in sensitivity and specificity, necessitating the development of innovative approaches. In this context, nanosensors emerged as a promising solution due to enhanced sensitivity, selectivity, and ability to detect heparin even at low concentrations. This review delves into a range of sensing approaches including colorimetric, fluorometric, surface-enhanced Raman spectroscopy, and electrochemical techniques using different types of nanomaterials, thus providing insights of its principles, capabilities, and limitations. Moreover, integration of smart-phone with nanosensors for point of care diagnostics has also been explored. Additionally, recent advances in nanopore technologies, artificial intelligence (AI) and machine learning (ML) have been discussed offering specificity against contaminants present in heparin to ensure its quality. By consolidating current knowledge and highlighting the potential of nanosensors, this review aims to contribute to the advancement of efficient, reliable, and economical heparin detection methods providing improved patient care.

Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach.

BACKGROUND: Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. RESULTS: We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. CONCLUSION: The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world's population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

Biochemical and metabolomic insights into antifungal mechanism of berberine against Candida glabrata.

An unprecedented expansion of antifungal therapy failure incidences in healthcare settings of Candida glabrata is the matter of global concern that needs to be addressed efficiently and effectively. In this pursuit, the present study has investigated the antifungal mechanism of benzylisoquinoline alkaloid berberine using biochemical, metabolic, and gene expression analysis, with the aim to delineate its therapeutic activity against C. glabrata and differentially fluconazole-responsive clinical isolates. Interestingly, the clinical isolates were found to be highly susceptible to berberine. Berberine was found to control the surface properties like hydrophobicity and charge of the cells. The cell membrane composition was altered by berberine, where the ergosterol and fatty acids were affected. The efflux pump activity was inhibited, and osmotic stress was generated in C. glabrata cells upon berberine exposure. The berberine has also generated oxidative stress and activated antioxidant system in C. glabrata cells. Furthermore, these observations were supported by the transcriptional expression study of C. glabrata cell genes (CDR1, RLM1, SLT2, SUR4, KRE1) and metabolomics analysis. Based on fold change analysis, the study identified 20 differential metabolites upon berberine treatment, which belong to central carbon, amino acids, and nucleotide pathways. The checkerboard analysis revealed the potentiation of some classically used antifungal drugs by berberine, thus suggesting it as a combinatorial nutraceutical adjuvant for the eradication of fungal infections. KEY POINTS: • Berberine exhibited better potency against azole-resistant clinical isolates • Berberine modulated metabolites of different pathways • Berberine generated oxidative stress and blocked efflux pump activity.

Neuroprotection in glaucoma.

Neuroprotective therapies in glaucoma may play a role in preventing ischemia and oxidative damage that results in apoptosis of retinal ganglion cells and optic nerve damage. Although intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma, disease progression commonly occurs despite IOP control, suggesting that factors other than IOP play a role in its pathogenesis and can potentially act as targets for neuroprotection. Factors including mediators of apoptosis, ischemic changes, poor ocular blood flow and neurotoxins have been hypothesized to play a role in glaucoma progression. Neuroprotective targets include glutamate-induced neurotoxicity, nitric oxidase synthetase, neurotropins, calcium channel receptors, free radicals, vascular insufficiency, the rho-kinase pathway, and more. Drugs related to these factors are being evaluated for their role in neuroprotection, although this area of investigation faces several challenges including limited evidence for these agents' efficacy in clinical studies. Additionally, while IOP-lowering therapies are considered neuroprotective as they generally slow the progress of glaucoma progression, they are limited by the extent of their effect beyond IOP control. The aim of this article is to review the current treatment options available for neuroprotection and to explore the drugs in the pipeline.

REM Sleep Deprivation Alters Learning-Induced Cell Proliferation and Generation of Newborn Young Neurons in the Dentate Gyrus of the Dorsal Hippocampus.

The hippocampus-dependent "trace-appetitive conditioning task" increases cell proliferation and the generation of newborn young neurons. Evidence suggests that adult hippocampal neurogenesis and rapid eye movement (REM) sleep play an essential role in memory consolidation. On the other hand, REM sleep deprivation (REM-SD) induces detrimental effects on training-induced cell proliferation in the hippocampus's dentate gyrus (DG). Nonetheless, the role of REM sleep in the trace-appetitive memory and fate determination of the newly proliferated cells is not known. Here, we have studied the following: (I) the effects of 24 h of REM-SD (soon after training) on trace- and delay-appetitive memory and cell proliferation in the adult DG and (II) the effects of chronic (96 h) REM-SD (3 days after the training, the period in which newly generated cells progressed toward the neuronal lineage) on trace-appetitive memory and the generation of newborn young neurons. We used a modified multiple platform method for the selective REM-SD without altering non-REM (NREM) sleep. We found that 24 h of REM-SD, soon after trace-conditioning, impaired the trace-appetitive memory and the training-induced cell proliferation. Nevertheless, 96 h of REM-SD (3 days after the training) did not impair trace memory. Interestingly, 96 h of REM-SD altered the generation of newborn young neurons. These results suggest that REM sleep plays an essential role in training-induced cell proliferation and the fate determination of the newly generated cells toward the neuronal lineage.

Heavy metal detoxification mechanisms by microalgae: Insights from transcriptomics analysis.

Heavy metal pollution in ecosystem is a global threat. The associated toxicity and carcinogenic nature of heavy metals/metalloids such as mercury, cadmium, lead, and arsenic are imposing a severe risk to both ecological diversity and human lives. Harnessing the adaptive feature of microalgae for remediating toxic heavy metal has reached a milestone in past few decades. Transcriptomics analyses have provided mechanistic insights to map the dynamics of cellular events under heavy metal stress, thus deciphering the strategic responses of microalgae. Here, the present review comprehensively addresses the elicited molecular responses of microalgae to detoxify the heavy metal stress. The review highlights the intricate role of biochemical components and signaling networks mediating stress responsive transitions of microalgae at physiological level. Furthermore, the differential gene expression signifying the transporters involved in uptake, distribution/sequestration, and efflux of heavy metal has also been reviewed. In a nutshell, this study provided a comprehensive understanding of the molecular mechanisms adopted by microalgae at transcriptome level to nullify the oxidative stress while detoxifying the heavy metals.

Elucidating the bioremediation mechanism of Scenedesmus sp. IITRIND2 under cadmium stress.

Cadmium (Cd) is a non-biodegradable pollutant that has become a global threat due to its bioaccumulation and biomagnification in higher trophic levels of the food chain. Green technologies such as phycoremediation is an emerging approach and possess edge over conventional methods to remediate Cd from the environment. The present investigation elucidates the adaptive mechanism of a freshwater microalga, Scenedesmus sp. IITRIND2 under Cd stress. The microalga showed excellent tolerance to Cd stress with IC50 value of ~32 ppm. The microalga showed phenomenal removal efficiency (~80%) when exposed to 25 ppm of Cd. Such a high uptake of Cd by the cells was accompanied with increased total lipid content (~33% of dry cell weight). Additionally, the elevated level of ROS, lipid peroxidation, glycine-betaine, and antioxidant enzymes evidenced the activation of efficient antioxidant machinery for alleviating the Cd stress. Further, analysis of the fatty acid methyl ester (FAME) presented a steady increase in saturated and polyunsaturated fatty acids with biodiesel properties complying the American and European fuel standards. The study proposes an integrated approach for bioremediation of toxic Cd using hyper-tolerant microalgal strains along with biodiesel production from the generated algal biomass.

The COVID-19: Current understanding.

In December 2019, China reported several cases of a new coronavirus disease (COVID-19). The COVID-19 outbreak, which was initially limited to Wuhan, China, has rapidly spread worldwide. Infection of the disease occurs through exposure to the virus through inhalation of respiratory droplets or if a person touches a mucosal surface after touching an object with the virus on it. The common symptoms of COVID-19 are fever, dry cough, dyspnea (difficult or labored breathing), fatigue, chest pain, and myalgia (muscle pain), etc. Real-time polymerase chain reaction is used to detect the virus in sputum, throat, nasal swabs, and secretion of lower respiratory samples. Early diagnosis, isolation, and supportive care are necessary for the treatment of the patients. The present review aims to provide recent information on COVID-19 related to its epidemiology, clinical symptoms, and management. This article also summarizes the current understanding of severe acute respiratory syndrome coronavirus-2 and its history of origin.

Training on an Appetitive Trace-Conditioning Task Increases Adult Hippocampal Neurogenesis and the Expression of Arc, Erk and CREB Proteins in the Dorsal Hippocampus.

Adult hippocampal neurogenesis (AHN) plays an essential role in hippocampal-dependent memory consolidation. Increased neurogenesis enhances learning, whereas its ablation causes memory impairment. In contrast, few reports suggest that neurogenesis reduces after learning. Although the interest in exploring the role of adult neurogenesis in learning has been growing, the evidence is still limited. The role of the trace- and delay-appetitive-conditioning on AHN and its underlying mechanism are not known. The consolidation of trace-conditioned memory requires the hippocampus, but delay-conditioning does not. Moreover, the dorsal hippocampus (DH) and ventral hippocampus (VH) may have a differential role in these two conditioning paradigms. Here, we have investigated the changes in: (A) hippocampal cell proliferation and their progression towards neuronal lineage; and (B) expression of Arc, Erk1, Erk2, and CREB proteins in the DH and VH after trace- and delay-conditioning in the rat. The number of newly generated cells significantly increased in the trace-conditioned but did not change in the delay-conditioned animals compared to the control group. Similarly, the expression of Arc protein significantly increased in the DH but not in the VH after trace-conditioning. Nonetheless, it remains unaltered in the delay-conditioned group. The expression of pErk1, pErk2, and pCREB also increased in the DH after trace-conditioning. Whereas, the expression of only pErk1 pErk2 and pCREB proteins increased in the VH after delay-conditioning. Our results suggest that appetitive trace-conditioning enhances AHN. The increased DH neuronal activation and pErk1, pErk2, and pCREB in the DH may be playing an essential role in learning-induced cell-proliferation after appetitive trace-conditioning.

Evaluation of Taenia solium cyst fluid-based enzyme linked immunoelectro transfer blot for Neurocysticercosis diagnosis in urban and highly endemic rural population of North India.

BACKGROUND: Neurocysticercosis (NCC) is infection by cestode Taenia solium/pork tapeworm. Sero-diagnosis of NCC is still a challenge. Radiological imaging (CT/MRI) are cost intensive, requires technical expertise and resource intensive. Hence, its availability is restricted in endemic zone. Existing Enzyme electro immune transfer blot (EITB) antigens are difficult to make and is not standardized for endemic population. Therefore, there is a definite need for easy and reliable EITB tool. METHODS: T. solium metacestode were harvested from naturally infected swine post slaughter. The cyst fluid/vesicular fluid was aspirated and processed with ultracentrifugation and immune blot was performed with this antigen. RESULTS: A total of 406 cases [rural 256 (NCC 78, seizures other than NCC 108 and healthy controls 70); urban 150 (NCC 41, seizures other than NCC 59 and healthy controls 50)] were enrolled. Positive EITB (detection of band <50 kDa) was significantly associated with NCC patients of urban population only (p < 0.001) but not in rural populations (p = 0.292). However, identification of 15 kDa band had significant association with NCC both in urban and rural populations with overall sensitivity of 91.5% and specificity of 91.6%. Presence of 35 kDa band was associated with multiple NCC (p < 0.001). The study shows that 15 kDa reactive band on EITB is highly sensitive and specific for diagnosis of NCC in endemic population. CONCLUSIONS: Presence of 35 kDa band on EITB was associated with infection by multiple cysticerci. The observations demand purification of cyst fluid antigens to develop simple and easy to execute test in field studies.

Unveiling Taenia solium kinome profile and its potential for new therapeutic targets.

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.[Figure: see text].

Development of multi-epitope chimeric vaccine against Taenia solium by exploring its proteome: an in silico approach.

Objective: Taenia solium is a neglected tropical disease; larvae of this parasite infect central nervous system i.e. Neurocysticercosis, and adults mature and survive into intestine i.e. Taeniasis. Globally more than 50 million people are at the risk of infection. This is one of the main etiological agents for onset of new early epilepsy in developing countries. However, there is no vaccine available to protect human from its infection. Hence, there is an urgent need for a good vaccine.Methods: We applied immune-informatics approach to design a multi-epitope chimeric vaccine consisting of both B and T-cell epitopes.Results: From the whole transcriptome of Taenia, we identified five suitable peptides present on cell membrane, epitope identification on these peptides were done by using various immunoinformatic software. Physiochemical properties were determined and the tertiary structure of vaccine was predicted, validated and refined, and to increase antigenicity we added linker to them. Best-modeled protein-complex was used for docking study with TLR1-2, TLR4, TLR3 and TLR7 and stability of molecular complex was determined by molecular dynamics simulation.Conclusions: Overall, we attempted to design an efficient subunit chimeric vaccine, which could stimulate humoral and cellular immune responses and could protect against both neurocysticercosis and taeniasis.

Design and analysis of visible photonics resonators coated with CuO thin film.

The optical and structural properties of CuO film deposited on n-Si via spin-coating method have been ascertained for diverse annealing times. The characterizations were made using x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV-vis spectroscopy, ellipsometry spectroscopy and photoluminescence. A detailed analysis revealed the favorable behavior of CuO film for visible photonics resonators such as Fabry-Perot (FP) and ring resonators. The best suitable property was obtained for a film annealed for 15 min. Accordingly, the CuO-film-coated resonators were simulated and analyzed theoretically using the MODE Solutions tool by Lumerical and MATLAB. In the FP resonator, the transmission intensity, contrast factor and finesse were computed for different annealing times and angles of light incidence. Further, for the CuO ring resonator, an eigenmode solver was incorporated (in the wavelength range 300-900 nm) to compute the effective refractive index, propagation constant, group velocity, losses, dispersion and transmission intensity. Additionally, utilizing the basic expressions, the free spectral range, full-width at half-maximum and quality factor were derived.

Assessing the robust growth and lipid-accumulating characteristics of Scenedesmus sp. for biodiesel production.

In the present investigation, different salts of nitrogen and carbon sources were tested for their potential to boost biomass and lipid content in Scenedesmus sp. IITRIND2. Among the nitrogen sources, ammonium bicarbonate/nitrate cultures showed maximum dry cell weight (DCW) of ~ 1.8 g/L and lipid yield (~ 40%) while the addition of C6 sugars (glucose and mannose) and sodium acetate enhanced the DCW (~ 3 g/L) and lipid accumulation (~ 40%) compared with disaccharides, C4 and C5 sugars. On evaluating the synergistic effects of the nitrogen and carbon sources, maximum DCW (3.66 g/L) was obtained in ammonium bicarbonate + sodium acetate cultures with a lipid yield of 37.15%. The fatty acid profile of the derived biodiesel was similar to that of plant oils. The results clearly established the robust capability of the novel microalga to efficiently adapt, sustain, and grow in different carbon and nitrogen sources along with high lipid productivity, making it a potential source for biodiesel production.

Neglected Agent Eminent Disease: Linking Human Helminthic Infection, Inflammation, and Malignancy.

Helminthic parasitic infection is grossly prevalent across the globe and is considered a significant factor in human cancer occurrence induced by biological agents. Although only three helminths (Schistosoma haematobium, Clonorchis sinensis, and Opisthorchis viverrini) so far have been directly associated with carcinogenesis; there are evidence suggesting the involvement of other species too. Broadly, human helminthiasis can cause chronic inflammation, genetic instability, and host immune modulation by affecting inter- and intracellular communications, disruption of proliferation-anti-proliferation pathways, and stimulation of malignant stem cell progeny. These changes ultimately lead to tumor development through the secretion of soluble factors that interact with host cells. However, the detailed mechanisms by which helminths introduce and promote malignant transformation of host cells are still not clear. Here, we reviewed the current understanding of immune-pathogenesis of helminth parasites, which have been associated with carcinogenesis, and how these infections initiate carcinogenesis in the host.

Quadruple Negative Breast Cancers (QNBC) Demonstrate Subtype Consistency among Primary and Recurrent or Metastatic Breast Cancer.

PURPOSE: Despite the availability of current standards of care treatments for triple negative breast cancer (TNBC), many patients still die from this disease. Quadruple negative tumors, which are TNBC tumors that lack androgen receptor (AR), represent a more aggressive subtype of TNBC; however, the molecular features are not well understood. METHODS: Immunohistochemistry of estrogen receptor (ER), progesterone receptor (PR), HER2, and AR was determined in 244 primary and 630 recurrent/metastatic site biopsies. Expression was correlated with a panel of 25 cancer-related genes and proteins by IHC and in situ hybridization (ISH). RESULTS: We observed that 80.2% (65 of 81) of primary TNBC tumors and 75.7% (159 of 210) of recurrent/metastatic TNBC tumors are QNBC. Bivariate fit analysis demonstrated that QNBC (n = 224) significantly (P < .03) correlated with younger aged patients at initial biopsy compared to AR positive TNBC patients (n = 51). In paired primary tissue samples and primary to recurrent/metastatic samples, at least 70% Luminal, HER2 enriched, and QNBC subtype did not change molecular profile. But, TNBC seems to be the "unstable" subtype. Within the total cohort, discordance in molecular profiles was identified in both synchronous (20%) and asynchronous (21%) intra-individual analyses. Irrespective of sample type, (Synchronous or Asynchronous), QNBC demonstrated higher concordant than TNBC. IHC and ISH results of the cancer related genes, demonstrated that gene/protein expression differ by molecular profile: TNBC (HR-/HER2-, AR+) and QNBC (HR-/HER2-, AR-). IHC in metastatic tumors, showed that the percentage of tumors positive of EGFR were higher, while PTEN and TLE3 were lower in QNBC compared to TNBC. CONCLUSION: Standard treatment of Breast Cancer (BC) relies on reliable assessment by IHC analysis of ER, PR, and HER2. Our analyses suggest that the heterogeneity of TNBC is at least partially associated with the presence or absence of AR expression, suggesting that QNBC should be considered as a clinically relevant BC subtype. IHC analysis of AR appears to be a practical assay to determine the most aggressive TNBC subtypes and identifies tumors that could benefit from available targeted therapies.

Training on an Appetitive (Delay)-Conditioning Task Enhances Oscillatory Waves During Sleep in the Cortical and Amygdalar Network.

Oscillating waves during sleep play an essential role in memory consolidation. The cortical slow wave activity (SWA) and sigma waves during NREM sleep and theta waves during REM sleep increase after a variety of memory tasks including declarative, procedural and associative learning tasks. These oscillatory waves during sleep help to promote neural dialog between circuitries, which possibly plays a causal role in memory consolidation. However, the role of sleep-associated oscillating waves in a complex appetitive-conditioning paradigm is not clear. The parietal cortex and amygdala are involved in the cognitive evaluation of the environmental stimuli, and appetitive conditioning. Here, we have studied the changes in sleep architecture and oscillatory waves during NREM and REM sleep in the parietal cortices and amygdalar-local field potential (A-LFP) after appetitive-conditioning in the rat. We observed that REM sleep increased significantly after appetitive conditioning, which significantly positively correlated with performance on the appetitive-conditioning task. Further, the cortical SWA (0.1-4.5 Hz), and sigma (12-14.25 Hz) waves during NREM sleep, theta (6-9 Hz) waves during REM sleep, the amygdalar SWA (0.1-3.75 Hz) during NREM sleep and theta (6-8.25 Hz) waves during REM sleep significantly increased after appetitive conditioning. Interestingly, the augmented oscillatory waves significantly positively correlated with the performances on the appetitive-conditioning task. Our results suggest that the augmented REM sleep after conditioning may be required for the consolidation of appetitive-conditioned memory. Further, a significant correlation between augmented power in oscillatory waves during sleep and performance suggesting that these waves may be playing a crucial role in the consolidation of appetitive-conditioned memory.

AR negative triple negative or "quadruple negative" breast cancers in African American women have an enriched basal and immune signature.

There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered "Quadruple negative" Breast Cancers ("QNBC"). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed. Cox hazard ratios were used to determine correlations to PAM50 breast cancer subtypes, and TNBC subtypes. Overall, AR-negative patients are diagnosed at a younger age compared to AR-positive patients, with the average age of AA AR-negative patients being, 49. AA breast tumors express AR at lower rates compared to Whites, independent of ER and PR expression (p<0.0001). AR-negative patients have a (66.60; 95% CI, 32-146) odds ratio of being basal-like compared to other PAM50 subtypes, and this is associated with an increased time to progression and decreased overall survival. AA "QNBC" patients predominately demonstrated BL1, BL2 and IM subtypes, with differential expression of E2F1, NFKBIL2, CCL2, TGFB3, CEBPB, PDK1, IL12RB2, IL2RA, and SOS1 genes compared to white patients. Immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 were significantly upregulated in both overall "QNBC" and AA "QNBC" patients as well. Thus, AR could be used as a prognostic marker for breast cancer, particularly in AA "QNBC" patients.