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Chemical characterization of red imported fire ants with colony development
The red imported fire ant, Solenopsis invicta Buren, poses a significant threat to public health due to its venomous stings. While the chemistry of fire ants has been well investigated, most studies have focused on ants from mature colonies. The dynamic changes in chemical compositions during colony development have been less explored. In this study, we established S. invicta colonies using newly collected queens from the field and then tracked the chemistry of workers as the colonies developed. Our findings reveal that the chemistry of fire ant workers undergoes significant changes with the development of the colonies. However, the change in chemical diversity was not necessarily in the same direction for all individual glands.
Mitochondrial disease patients and rotavirus infection complications
Rotavirus (RV) is an agent of gastroenteritis and, to a lesser extent, neurological manifestations including seizures and epilepsy. Before the development of effective vaccines, rotavirus was among the leading global drivers of life-threatening diarrhea in neonates and children less than five years of age.
Building and implementing best practices for referral and management of severe asthma in Canadian healthcare
Severe asthma (SA) is asthma that remains uncontrolled despite patient adherence to mainteneance therapies and management of contributing factors, or asthma which worsens when high-dose treatments are reduced. It is estimated that 5-10% of asthma patients in Canada have SA. The condition is a significant burden on patients’ quality of life, and is associated with increased number and severity of exacerbations, hospitalizations, and mortality
Possible therapeutic targets for SARS-CoV-2 infection and COVID-19
SARS-CoV-2 infection causes COVID-19, which has emerged as a health emergency worldwide. SARS-CoV-2 infects cells by binding to ACE2 receptors and enters into the cytoplasm following its escape from endolysosomes. Once in the cytoplasm, the virus replicates and eventually causes various pathological conditions including acute respiratory distress syndrome (ARDS) that is caused by pro-inflammatory cytokine storms.
Monitoring clinical trials in infectious diseases
In early 2020, the contagious and deadly virus, SARS-CoV-2, was identified. The virus spread rapidly worldwide and was declared a pandemic by the World Health Organization (WHO) in March of 2020 [1]. While many who became infected remained asymptomatic, an alarming number of infected individuals developed severe symptoms, often requiring hospitalization and intensive care, or resulting in death.
Policy and law changes to address healthcare inequities for minority populations during COVID-19
While other countries have begun to see a flattening of the Severe Acute Respiratory Syndrome – Coronavirus-2 (SARS-CoV-2) curve, the United States continues to see a rise in cases, with approximately 7.4 million confirmed cases to date. Even more worrisome, various news articles have begun to shed light on the healthcare inequities that have become increasingly more transparent during this crisis.
How to inhibit breast cancer and breast cancer metastasis with Akt inhibitors: Lessons learned from studies in mice
The PI3K/Akt signaling pathway is frequently hyperactivated in different types of breast cancer. In the past two decades, major efforts have been made to develop inhibitors of this pathway to treat cancer patients.
Non-alcoholic fatty liver disease: Role of nuclear receptor superfamily members and approaches to treatment
Non-alcoholic fatty liver disease (NAFLD) is an increasing health problem when left untreated. NAFLD is defined as accumulation of fat in 5% of the hepatocytes. NAFLD can convert into non-alcoholic steatohepatitis (NASH) which is defined as inflammatory NAFLD. Both NAFLD and NASH are observed in individuals suffering from metabolic syndrome and type 2 diabetes (T2D).
Non-alcoholic fatty liver disease: Role of PNPLA3 and its association with environmental chemicals
Non-alcoholic fatty liver disease (NAFLD) represents an escalating global health concern. Its prevalence varies significantly across different regions, in Asia it ranges from 30-32%, with notably higher prevalence in the Middle East. Europe reports a prevalence of 27-33%, while North America shows a range of 35-48%.
Recombinant protein synthesis and isolation of human interferon alpha-2 in cyanobacteria
Interferons (IFNs) are a class of small immunological proteins that are secreted by infected cells during viral or bacterial infections to combat and prevent infection propagation [1]. They play important roles in triggering signal cascade processes inside the cell that activate other immune cells and limit viral multiplication.
PDE4 inhibition and enhancement of human memory and cognition
Two distinct, but intertwining, threads of inquiry have demonstrated that the PDE4, or cAMP-selective, phosphodiesterases, have an essential role in human cognition, learning and memory. Study of genetically-modified preclinical models, and of humans with mutations in the PDE4D gene, has provided some of the most rigorous proof of the importance of PDE4 signaling in the CNS. More recently, clinical trials of PDE4-selective inhibitors have shown promising clinical activity in disorders of cognition and memory.
PAK1 and PAK4 as therapeutic targets for Ewing sarcoma: a commentary
Ewing sarcoma (ES) is an aggressive pediatric bone tumor that is prone to metastasis. Due to low five-year survival rates and limited therapeutic options for metastatic disease, there is a dire clinical need for improved ES treatments. Targeting p21-activated kinases (PAKs) may be key. PAK1 and PAK4 are associated with aggressive ES and poor patient outcomes, although their molecular mechanisms remain largely uncharacterized in this disease.
RAD51 Inhibitor Reverses Etoposide-Induced Genomic Toxicity and Instability in Esophageal Adenocarcinoma Cells
In normal cells, homologous recombination (HR) is strictly regulated and precise and plays an important role in preserving genomic integrity by accurately repairing DNA damage. RAD51 is the recombinase which mediates homologous base pairing and strand exchange during DNA repair by HR. We have previously reported that HR is spontaneously elevated (or dysregulated) in esophageal adenocarcinoma (EAC) and contributes to ongoing genomic changes and instability. The purpose of this study was to evaluate the impact of RAD51 inhibitor on genomic toxicity caused by etoposide, a chemotherapeutic agent.
The interplay of regulatory T cells, endoplasmic reticulum stress, and unfolded protein response activation in post-transplant alloimmune hepatitis and autoimmune hepatitis
The incidence and prevalence of autoimmune hepatitis (AIH) globally is 1.28 per 100,000 population-years (95% CI, 1.01-1.63) and 15.65 per 100,000 population (95% CI, 13.42-18.24), respectively [1]. The incidence and prevalence in children is 0.4 and 3.0 cases per 100,000 children [2], and in adults 17 per 100,000 [3,4].
The beneficial role of vitamin B12 in injury induced by ischemia/reperfusion: beyond scavenging superoxide?
Vitamin B12 is one of the most complex non-protein compounds as described by Dorothy Hodgkin, a Nobel Prize-winning chemist, who discovered the molecular crystal structure of B12. Cobalamins (vitamin B12 derivatives) contain the rare transition metal, cobalt (Co), positioned in the center of a corrin ring and weakly bound to carbon. While cobalamins are synthesized only in certain bacteria and archaea, not in mice or humans, they are co-enzymes essential for all life except for plants. For example, in higher vertebrates, methyl-cobalamin and 5’-deoxyadenosyl-cobalamin are essential for the function of methionine synthase and methylmalonyl CoA mutase, respectively.
Breaking malignant nuclei as a non-mitotic mechanism of taxol/paclitaxel
Discovered in a large-scale screening of natural plant chemicals, Taxol/paclitaxel and the taxane family of compounds are surprisingly successful anti-cancer drugs, used in treatment of the majority of solid tumors, and especially suitable for metastatic and recurrent cancer. Paclitaxel is often used in combination with platinum agents and is administrated in a dose dense regimen to treat recurrent cancer.
Immuno-oncologic care during COVID-19: Challenges and opportunities for improving clinical care and investigation
Cancer care has been greatly impacted during the COVID-19 pandemic. The number of cases and deaths caused by the COVID-19 pandemic continues to escalate throughout the United States and the world. Worldwide, over 150 million people have been diagnosed with the coronavirus and more than 3 million have died.
Chromatin dynamics: Nucleosome occupancy and sensitivity as determinants of gene expression and cell fate
The nucleosome, consisting of ~150bp of DNA wrapped around a core histone octamer, is a regulator of nuclear events that contributes to gene expression and cell fate. Nucleosome organization at promoters and their associated remodeling events are important regulators of access to the genome. Occupancy alone, however, is not the only nucleosomal characteristic that plays a role in genome regulation. Nucleosomes at the transcription start sites (TSSs) of genes show differential sensitivity to micrococcal nuclease (MNase) and this differential sensitivity is linked to transcription and regulatory factor binding events.
Challenges in the humanized mouse model for cancer: A commentary
The complexity of the tumor microenvironment has been a challenge for understanding the mechanisms of therapy resistance. The development of improved animal models that closely mimic human disease is key for understanding and treating diseases. Recently, a new humanized mouse model has been developed that enables the study of human immune cells in tumor host-cell interactions
Changing the landscape of non-small cell lung cancer disparities
In the United States, lung and bronchus cancers are the second most common types of cancer and are responsible for the largest number of deaths from cancer, with African Americans suffering disproportionately from lung and bronchus cancers. This disparity likely results from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health.
COVID-19 in patients with and without cancer: Examining differences in patient characteristics and outcomes
This study examines differences between patients with and without cancer in patient demographic and clinical characteristics and COVID-19 mortality and discusses the implications of these differences in relation to existing cancer disparities and COVID-19 vulnerabilities. Data was collected as a part of a retrospective study on a cohort of COVID-19 positive patients across Mount Sinai Health System from March 28, 2020 to April 26, 2020. Descriptive, comparative, and regression analyses were applied to examine differences between patients with and without cancer in demographic and clinical characteristics and COVID-19 mortality and whether cancer status predicts COVID-19 mortality controlling for these covariates using SAS 9.4. Results showed that, of 4641 patients who tested positive for COVID-19, 5.1% (N=236) had cancer.
Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy
Prenatal care for patients with cardiac disease is complex, often involving close surveillance, intensive monitoring, and peripartum interventions that can result in mother infant separation after birth. Though these experiences can be distressing for patients, little is known about postpartum depression rates in this high-risk population. Characterizing postpartum depression and identifying risk factors might inform risk reduction strategies.
Beneficial effects of nicotinamide on hypertensive mice with impaired endothelial nitric oxide function
Nicotinamide (Nam, amide form of niacin acid or nicotinate), a precursor for nicotinamide adenine dinucleotide (NAD+), is important for normal physiological function of organisms. Nam also suppresses mobilization of Ca2+ from sarcoplasmic reticulum into cytoplasm through inhibiting ADP-ribose cyclase. Previously, we have demonstrated that a pharmacological dose of Nam normalizes maternal blood pressure in mouse models of preeclampsia, a pregnancy related hypertensive disorder.
Implications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine
Lung cancer is the leading cause of cancer death among both men and women in the United States. Because lung cancer is genetically heterogeneous, tailored therapy alone or in combination with chemotherapy would increase patient overall survival as compared with the one-size-fits-all chemotherapy. TP53-mutant lung cancer accounts for more than half of all lung cancer cases and is oftentimes more aggressive and resistant to chemotherapy. Directly targeting mutant p53 has not yet been successful, so identification of novel therapy targets and biomarkers in the TP53-mutant lung cancer is urgently needed to increase the overall survival in this subgroup.
Environmental determinants for protein structuring and amyloid transformation
Amyloid transformation under laboratory conditions is achieved by shaking an aqueous solution of any protein. The shaking time varies significantly, demonstrating the variable degree of ease of structural transformation in a given protein. The structural specificity that distinguishes amyloid forms from biologically active proteins is the flatness (two-dimensionality) of the form of each chain in the amyloid fibril.
Can a study that’s not statistically significant be meaningful?
In ongoing efforts to bring innovation to healthcare, technology and patient self-management are at an important intersection. Our study, "A Mobile App for Chronic Disease Self-Management for Individuals with Low Health Literacy: A Multisite Randomized Controlled Clinical Trial” [1], serves as a potentially useful contribution to this intersection by addressing the challenges faced by older adults with chronic conditions and low health literacy in managing chronic health conditions.
Mechanisms of troponin release into serum in cardiac injury associated with COVID-19 patients
In the early phases of the pandemic caused by the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) the emphasis of diagnosis and treatment was on acute respiratory distress syndrome (ARDS).
Do arrestin oligomers have specific functions?
Arrestins were discovered as key players in the conserved two-step homologous desensitization of G protein-coupled receptors (GPCRs): they specifically bind active phosphorylated GPCRs, precluding their coupling to cognate G proteins, thereby stopping (“arresting”) G protein-mediated receptor signaling [1].
Can language use in social media help in the treatment of severe mental illness?
Nationally, patients experience multiple barriers to receiving mental health care. In many parts of the US, access to mental health providers is limited. For many patients, getting an appointment with a psychiatrist is difficult and often takes weeks. When patients are able to schedule appointments with a psychiatrist, the visits are usually short and aimed mostly at prescribing medications. For patients with serious conditions like schizophrenia or major depression, the consequences of unattended emergence or worsening of symptoms during those time intervals can be severe.
Transcription factor motif activity as a biomarker of muscle aging
In prior work, we analyzed gene expression profiles of mouse, rat and human gastrocnemius muscles to identify conserved regulators of muscle aging processes. By further comparing data obtained from different muscles we found stronger conservation of aging-related factors at the level of molecular pathways than at the level of individual genes.
Association between physical function and perceived stress among U.S. Chinese older adults
Objectives: Physical function impairment can cause great stress to older adults. The purpose of the study is to investigate the association between self-reported and directly-observed physical function on perceived stress among U.S. Chinese older adults.
High-resolution 3D fluorescent imaging of intact tissues
Histological analysis of fluorescently labeled tissues has been a critical tool to understand molecular organization in situ. However, assessing molecular structures within large cells and in the context of human organ anatomy has been challenging because it requires penetration of staining reagents and light deep into opaque tissues, while also conforming to the spatial constraints of high-resolution objective lenses.
Allosteric interactions among voltage-sensor modules of sodium channels probed by scorpion toxin modifiers
Gating of voltage-dependent sodium channels involves coordinated movements of the voltage sensors in the voltage-sensing modules (VSMs) of the four domains (DI-DIV) in response to membrane depolarization. Zhu et al. have recently examined the effects of charge reversal substitutions at the VSM of domain III on the action of scorpion alpha- and beta-toxins that intercept the voltage sensors in domains IV and II, respectively. The increased activity of both toxin types on the mutant channels has suggested that the VSM module at domain III interacts allosterically with the VSM modules in domains IV and II during channel gating thus affecting indirectly the action of both scorpion toxin classes.
Endoplasmic reticulum stress and mitochondrial dysfunctions in metal-induced neurological pathology
Although essential metal ions are required in the body, neurotoxicity occurs when exposed to a concentration of metal that the body cannot accommodate. In the case of non-essential metals which are important in industry, these elements have the property of causing neurotoxicity even at small concentrations. When such neurotoxicity progresses chronically, it can contribute to various neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Therefore, research on the relationships between neurotoxicity and metal metabolism are being actively conducted, and some recent research has suggested that the mechanisms of metal-induced neurotoxicity critically involve endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Hence, this mini-review is to summarize some examples of such evidence and raise new questions in attempting to address metal-induced neurotoxicity with ER stress and mitochondria dysfunctions, two important topics for the effects of metals in neurodegenerative diseases.
Immunotherapy as a treatment to confront the ongoing opioid epidemic- A review
Substance use disorders continue to be major medical and social problems worldwide. The use of opiate has grown substantially over the past three decades reaching the dimensions of a global epidemic. Current drug treatments have many limitations: long treatment times, dependency on treatment medications, relapses after treatment, high costs of treatment, and non-adherence by affected persons. Most of the available drug treatments for opiate addiction belong to the opioid family. Some worry that the availability of the drugs may simply cause substituting one opioid medication for another.
ALS Skeletal Muscle: Victim or Culprit
Aside its function in locomotion, posture maintenance and respiration, the hSKM is reported to be a critical metabolic regulator [1]. The hSKM is acknowledged as the primary site of glucose metabolism and storage [1]. Additionally, it serves as a reserve for amino acids [1,2]. In recently times, the hSKM has also been described as an endocrine organ.
Duration and magnitude of bidirectional fluctuation in blood pressure: the link between cerebrovascular dysfunction and cognitive impairment following spinal cord injury
Individuals with spinal cord injury (SCI) have a significantly increased risk for cognitive impairment that is associated with cerebrovascular remodeling and endothelial dysfunction. The sub-acute stage following high thoracic SCI is characterized by increased fibrosis and stiffness of cerebral arteries. However, a more prolonged duration after SCI exacerbates cerebrovascular injury by damaging endothelium. Endothelial dysfunction is associated with reduced expression of transient receptor potential cation channel 4 that mediates the production of nitric oxide and epoxyeicosatrienoic acids following shear stress and the response to carbachol and other endothelium-dependent vasodilators.
Unique genotypic features of HIV-1 C gp41 membrane proximal external region variants during pregnancy relate to mother-to-child transmission via breastfeeding
Mother-to-child transmission (MTCT) through breastfeeding remains a major source of pediatric HIV-1 infection worldwide. To characterize plasma HIV-1 subtype C populations from infected mothers during pregnancy that related to subsequent breast milk transmission, an exploratory study was designed to apply next generation sequencing and a custom bioinformatics pipeline for HIV-1 gp41 extending from heptad repeat region 2 (HR2) through the membrane proximal external region (MPER) and the membrane spanning domain (MSD).
Involvement of TGFβ signaling pathway in oxidative stress and diabetic retinopathy
Diabetic Retinopathy (DR) is a leading cause of blindness in the U.S. However, not much is known of underlying molecular mechanism and how oxidative stress contributes to its development. In the present study, we investigated the involvement of TGFβ signaling pathway on the effect of oxidative stress on VEGF secretion and viability of retinal cells. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concerns that have arisen are the underlying effects of antioxidants in elevating VEGF secretion in diabetes.
From observation to diagnosis: Implications of calcified sclero-choroidal choristomas in mosaic RASopathies
The identification of calcified sclero-choroidal choristomas (CaSCCs) in patients with mosaic RASopathies introduces a new dimension to understanding ocular manifestations in these genetic disorders.
Recent advances on visual cycle protein research and progress on clinical translation
Since the publication of our previous paper, Visual cycle proteins: Structure, function, and roles in human retinal disease (Tsin, et.al, JBC 293:13016, 2018) there has been significant progress on multiple topics discussed in this paper. In the present communication, we further explore research advances on two visual cycle proteins: DES1 and IRBP.
Post-allogeneic stem cell transplant FLT3-targeted maintenance therapy: updates and considerations for clinical practice
Acute myeloid leukemia (AML) is characterized by multiple molecular and cytogenetic abnormalities, with increasing data to support clinical and prognostic implications to guide clinical decision making. One of the most well described mutations involves fms-like tyrosine kinase 3 (FLT3) that results in a constitutively active tyrosine kinase and is generally associated with poor prognosis involving shorter overall survival and higher rates of relapse.
The significance of triple-capsid-mutant AAV8 for treatment of Sanfilippo Syndrome Type B
Sanfilippo Syndrome Type-B remains an untreatable childhood neurodegenerative disease with great burden for both patient and caregiver. Very few clinical trials have been undertaken to treat the disease, and none of these have yet yielded clinically obtainable products for patients. Caused by a simple enzyme function deficiency, Sanfilippo Syndrome Type-B has been considered a great prospect for gene-therapy interventions.
Utilization of electronic health records for the assessment of adiponectin receptor autoantibodies during the progression of cardio-metabolic comorbidities
Diabetes is a complex, multi-symptomatic disease whose complications drives increases in healthcare costs as the diabetes prevalence grows rapidly world-wide. Real-world electronic health records (EHRs) coupled with patient biospecimens, biological understanding, and technologies can characterize emerging diagnostic autoimmune markers resulting from proteomic discoveries.
Mind-body approaches for reducing the need for post-operative opioids: Evidence and opportunities
While opioids remain our most potent analgesics in the management of pain, the many potential harms of prescription opioids have become increasingly clear. Despite the analgesic benefits for people with acute and chronic pain [1], opioid therapy (especially long-term opioid treatment) can result in significant problems such as opioid misuse, the development of opioid use disorder, and overdose. Some authors report that up to 20-30% of patients in primary and tertiary care settings who are maintained on long-term opioid therapy misuse opioids (i.e., use them in a manner other than how the opioids are prescribed) [2,3]. Misuse of opioids can cause or exacerbate additional health problems in people with chronic pain [1,4], and in fact, roughly 10% of patients prescribed long-term opioid therapy may develop an opioid use disorder (OUD), although prevalence varies between studies depending on differences in methodology and operational definitions [3].
Adiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetes
The protein hormone adiponectin regulates glucose and fatty acid metabolism by binding to two PAQR-family receptors (AdipoR1 and AdipoR2). Both receptors feature a C-terminal segment which is released by proteolysis to form a freely circulating C-terminal fragment (CTF) found in the plasma of normal individuals but not in some undefined diabetes patients. The AdipoR1-CTF344-376 is a competitive inhibitor of tumor necrosis factor α cleavage enzyme (TACE) but it contains a shorter peptide domain (AdipoR1 CTF351-362) that is a strong non-competitive inhibitor of insulin-degrading enzyme (IDE).
Association between the prevalence of obstructive lung disease and the use of aspirin in a diabetic population
Aspirin (acetylsalicylic acid), a non-steroidal anti-inflammatory drug, inhibits cyclooxygenases (COX-1 and COX-2), which catalyze the conversion of arachidonic acid to prostaglandins [1-3]. In control environments, low-dose aspirin (75 mg or 81 mg) inhibits COX-1 and disrupts the production of thromboxane, reducing platelet aggregation
Molecular signatures of aggressive pediatric liver cancer
Liver masses account for 5 to 6% of pediatric cancer, which includes hepatoblastoma (HBL) along with rare cases of hepatocellular carcinoma (HCC). The most dangerous form of pediatric liver cancer is aggressive HBL, which can be characterized by chemo-resistance and multiple nodules or metastases at diagnosis, all correlating with worse clinical prognosis. Despite intensive studies and a significant improvement in overall outcomes, very little is known about the key molecular pathways which determine the aggressiveness of pediatric liver cancer.
Role of the rapid delayed rectifier K current in human induced pluripotent stem cells derived cardiomyocytes
The action potential (AP) in cardiac tissue is important for initiating and coordinating contractions in the heart. In addition, the long refractory period minimizes the potential for developing extrasystoles and arrhythmias. The AP is generated by coordinate changes in different ionic currents. In human (or canine) adult ventricular cells, the depolarization phase of the AP is mainly through the influx of Na+ and Ca2+ through specific voltage gated channels.
Clay eating in pregnancy in French Guiana: How does one understand the practices and act for prevention?
Geophagy is described in most countries of the world as a practice observed in pregnant women. In industrialized countries, it results from migrant populations who carry with them their cultural habits and practices. This is the case in France and more particularly in Guiana, an overseas territory. Originally used to treat the ills of pregnancy, it is today considered to be dangerous for the woman and her unborn child.
MSICS is a Simple Solution for a Big Problem
Manual small-incision cataract surgery (MSICS) is a sutureless cataract surgery that has multiple advantages over traditional phacoemulsification and extracapsular cataract extraction (ECCE) procedures. SICS became the procedure of choice for international ophthalmology, where the microscopes and operating room can be more challenging, in addition to the more advanced pathology often seen.
Neodymium:YAG laser posterior capsulotomy in the lateral decubitus position
Here we report a novel method of performing a Neodyminium:YAG (Nd:YAG) laser posterior capsulotomy in an adult patient, unable to tolerate the procedure awake with topical anaesthesia in the outpatient clinic setting. The procedure was performed by altering the chin rest and arms of the Nd:YAG laser machine so that the procedure could be undertaken in an anaesthetized patient in the operating theatre, in the lateral decubitus position, with the laser machine upright in its normal position.