Members Of Class Research Articles

Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC50 = 2.49 μM) and has demonstrated selectivity towards FLT3 ITD-mutated MV4-11 AML cells, with an IC50 of 4.3 μM. By utilizing the scaffold of the previous hit, sixteen new compounds were synthesized and screened against NCI-60 human cancer cell lines. This leads to the discovery of a potent antiproliferative compound, namely 5l, with an average GI50 value against leukemia and colon cancer subpanels equalling 3.39 and 5.97 µM, respectively. Screening against a specific set of 10 kinases that are associated with carcinogenesis indicates that compound 5l has a potent FLT3 inhibition (IC50 = 36.21 ± 1.07 nM). Remarkably, compound 5l was three times more effective as a CDK2 inhibitor (IC50 = 8.17 ± 0.32 nM) compared to sunitinib (IC50 = 27.90 ± 1.80 nM). Compound 5l was further analyzed by means of docking and molecular dynamics simulation for CDK2 and FLT3 active sites which provided a rational for the observed strong inhibition of kinases. These results suggest a novel structural scaffold candidate that simultaneously inhibits CDK2 and FLT3 and gives encouragement for further development as a potential therapeutic for leukemia and colon cancer.

A reminder-peptidoglycan cell walls indeed occur in the archaeal domain, specifically in the members of Methanobacteria and Methanopyri classes.

A reminder-peptidoglycan cell walls indeed occur in the archaeal domain, specifically in the members of Methanobacteria and Methanopyri classes.

Are the class 18 myosins Myo18A and Myo18B specialist sarcomeric proteins?

Initially, the two members of class 18 myosins, Myo18A and Myo18B, appeared to exhibit highly divergent functions, complicating the assignment of class-specific functions. However, the identification of a striated muscle-specific isoform of Myo18A, Myo18Aγ, suggests that class 18 myosins may have evolved to complement the functions of conventional class 2 myosins in sarcomeres. Indeed, both genes, Myo18a and Myo18b, are predominantly expressed in the heart and somites, precursors of skeletal muscle, of developing mouse embryos. Genetic deletion of either gene in mice is embryonic lethal and is associated with the disorganization of cardiac sarcomeres. Moreover, Myo18Aγ and Myo18B localize to sarcomeric A-bands, albeit the motor (head) domains of these unconventional myosins have been both deduced and biochemically demonstrated to exhibit negligible ATPase activity, a hallmark of motor proteins. Instead, Myo18Aγ and Myo18B presumably coassemble with thick filaments and provide structural integrity and/or internal resistance through interactions with F-actin and/or other proteins. In addition, Myo18Aγ and Myo18B may play distinct roles in the assembly of myofibrils, which may arise from actin stress fibers containing the α-isoform of Myo18A, Myo18Aα. The β-isoform of Myo18A, Myo18Aβ, is similar to Myo18Aα, except that it lacks the N-terminal extension, and may serve as a negative regulator through heterodimerization with either Myo18Aα or Myo18Aγ. In this review, we contend that Myo18Aγ and Myo18B are essential for myofibril structure and function in striated muscle cells, while α- and β-isoforms of Myo18A play diverse roles in nonmuscle cells.

From Institution to Community: Implementing the Pathway Home Approach for High-Risk Members With Behavioral Health Needs Transitioning From an Adult Home.

Coordinated Behavioral Care began using its Pathway Home program to serve a subset of New York State Adult Home Settlement class members. Through its multidisciplinary team approach, Pathway Home is utilizing its multiphase model in assisting individuals with Serious Mental Illness leaving an Adult Home to successfully transition and remain in the community. The Pathway Home program is a community-based service and serves class members wherever is needed to assist in their recovery and transition from an Adult Home. This includes meeting class members in Adult Homes and various settings in the community. The New York State Adult Home Settlement presents a variety of systemic, care management, and individual member challenges. Adding the Pathway Home approach to an already existing, yet insufficient care management model strengthens the initiative's goal to transition and retain members safely into the community. Through the approach's adaptability and flexibility in providing community-based care, Pathway Home's successful cross-system collaboration is worthy of replication for other high need populations. A programmatic review for Pathway Home Adult Home+ teams gleaned the following key points for the field to consider in future care management practices. Class member self-efficacy and cross-system collaboration are essential in facilitating a class member's move into the community. Member choice and educating class members on their rights to move and options as well as community exposure prior to transition are important in assessing how a member fares outside of the Adult Home. Members determining their own care can reduce the risk of adverse outcomes and reinstitutionalization. Current low-touch care management programs are insufficient for members with complex needs living in institutions. These care management programs need to be augmented with a whole person approach, delivered by a multidisciplinary team.

Intracellular Allosteric Antagonist of the Olfactory Receptor OR51E2.

Olfactory receptors are members of class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs). Their expression and function have been increasingly studied in nonolfactory tissues, and many have been identified as potential therapeutic targets. In this manuscript, we focus on the discovery of novel ligands for the olfactory receptor family 51 subfamily E2 (OR51E2). We performed an artificial intelligence-based virtual drug screen of a ∼2.2 million small molecule library. Cell-based functional assay identified compound 80 (C80) as an antagonist and inverse agonist, and detailed pharmacological analysis revealed C80 acts as a negative allosteric modulator by significantly decreasing the agonist efficacy, while having a minimal effect on receptor affinity for agonist. C80 binds to an allosteric binding site formed by a network of nine residues localized in the intracellular parts of transmembrane domains 3, 5, 6, 7, and H8, which also partially overlaps with a G protein binding site. Mutational experiments of residues involved in C80 binding uncovered the significance of the C2406.37 position in blocking the activation-related conformational change and keeping the receptor in the inactive form. Our study provides a mechanistic understanding of the negative allosteric action of C80 on agonist-ctivated OR51E2. We believe the identification of the antagonist of OR51E2 will enable a multitude of studies aiming to determine the functional role of this receptor in specific biologic processes. SIGNIFICANCE STATEMENT: OR51E2 has been implicated in various biological processes, and its antagonists that can effectively modulate its activity have therapeutic potential. Here we report the discovery of a negative allosteric modulator of OR51E2 and provide a mechanistic understanding of its action. We demonstrate that this modulator has an inhibitory effect on the efficacy of the agonist for the receptor and reveal a network of nine residues that constitute its binding pocket, which also partially overlaps with the G protein binding site.

A novel inhibitor of the mitochondrial respiratory complex I with uncoupling properties exerts potent antitumor activity

Cancer cells are highly dependent on bioenergetic processes to support their growth and survival. Disruption of metabolic pathways, particularly by targeting the mitochondrial electron transport chain complexes (ETC-I to V) has become an attractive therapeutic strategy. As a result, the search for clinically effective new respiratory chain inhibitors with minimized adverse effects is a major goal. Here, we characterize a new OXPHOS inhibitor compound called MS-L6, which behaves as an inhibitor of ETC-I, combining inhibition of NADH oxidation and uncoupling effect. MS-L6 is effective on both intact and sub-mitochondrial particles, indicating that its efficacy does not depend on its accumulation within the mitochondria. MS-L6 reduces ATP synthesis and induces a metabolic shift with increased glucose consumption and lactate production in cancer cell lines. MS-L6 either dose-dependently inhibits cell proliferation or induces cell death in a variety of cancer cell lines, including B-cell and T-cell lymphomas as well as pediatric sarcoma. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI-1) partially restores the viability of B-lymphoma cells treated with MS-L6, demonstrating that the inhibition of NADH oxidation is functionally linked to its cytotoxic effect. Furthermore, MS-L6 administration induces robust inhibition of lymphoma tumor growth in two murine xenograft models without toxicity. Thus, our data present MS-L6 as an inhibitor of OXPHOS, with a dual mechanism of action on the respiratory chain and with potent antitumor properties in preclinical models, positioning it as the pioneering member of a promising drug class to be evaluated for cancer therapy.MS-L6 exerts dual mitochondrial effects: ETC-I inhibition and uncoupling of OXPHOS. In cancer cells, MS-L6 inhibited ETC-I at least 5 times more than in isolated rat hepatocytes. These mitochondrial effects lead to energy collapse in cancer cells, resulting in proliferation arrest and cell death. In contrast, hepatocytes which completely and rapidly inactivated this molecule, restored their energy status and survived exposure to MS-L6 without apparent toxicity.

IF1 Knockout Protects Against Doxorubicin-Induced Cardiac Dysfunction by Improving Cardiomyocyte Energetics

Doxorubicin (DOX), a member of the Anthracycline antibiotics class, has been used as a potent chemotherapy agent against solid tumors. However, its use is limited by its cardiotoxicity. It is well-documented that mitochondrial dysfunction is one of the main mechanisms of DOX-induced cardiotoxicity. ATP synthase inhibitory subunit 1 (ATPIF1, or IF1) is an endogenous inhibitor of mitochondrial ATP synthase. Recent studies indicate that IF1 may suppress mitochondrial respiration via inhibiting ATP synthase. Others and our previous studies demonstrated that IF1 inactivation exerts hepatic and cardiac protective effects. We hypothesize that the absence of IF1 protects the heart from DOX-induced cardiotoxicity by improving mitochondrial energy metabolism. We first investigate the impact of IF1 KO on mitochondrial respiration using the high-resolution respirometer (OROBOROS) on freshly isolated cardiac mitochondria from IF1 KO and WT mice. IF1 KO mitochondria did show substantially increased state 2, state 3, and state 4 respiration rates compared with those of WT. We then investigated if WT and IF1 KO mice respond differently to DOX treatment. WT and IF1 KO mice at the ages of 12-16 weeks either received DOX 3mg/kg/every other day or vehicle intraperitoneally for two weeks. In vivo, cardiac function was evaluated using the VEVO F2 Echocardiographic system (Visual Sonic) 4 and 6 weeks after initiation of DOX and vehicle administration. Compared with the vehicle-treated WT mice, left ventricular ejection fraction (LVEF) was substantially decreased in DOX-treated WT mice compared with vehicle-treated WT mice. In contrast, LVEF in DOX-IF1 KO mice was substantially less reduced compared with vehicle-treated IF1 KO mice. We next investigated if improving cellular energetics is the critical mechanism underlying the protective effects of IF1 KO. Mouse neonatal cardiomyocyte (NMCM) isolated from WT and IF1 KO mice were cultured and treated with 0.5 and 1mM Dox for 24 hours. Cellular energetics were measured with the Mito stress assay using the Seahorse Bioanalyzer (96Xpro, Agilent). Basal, maximal, and ATP production-linked oxygen consumption rates were markedly decreased in DOX-treated-NMCM but not in DOX-treated IF1 KO NMCM compared with Vehicle-treated NMCM. In summary, the above in vivo and in vitro investigations support that IF1 inactivation is protective against DOX cardiac toxicity, at least partly, via improving cellular energetics; therefore, inactivating IF1 may be a potential therapeutic target to prevent and mitigate DOX-induced cardiomyopathy in patients. This research was supported by project number 5R01HL160969 from the National Heart Lung and Blood Institute at the NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evolution of surface conductivity in SmB6 under nonmagnetic (Yb2+) and magnetic (Eu2+) doping

Among of rare-earth (RE) hexaborides only two compounds SmB6 and YbB6 are discussed in literature to be members of a new class of 3D topological insulators. However, their ground states originate due to different physical mechanisms, including Kondo 4f-5d hybridization and 5d-2p band inversion, respectively. Here we report a comparative study of magnetotransport (resistivity and transverse magnetoresistance) measured on high quality single crystals of YbxSm1-xB6 and EuxSm1-xB6 solid solutions (x ≤ 0.05) at temperatures 1.7 − 300 K in magnetic fields up to 82 kOe. The choice of dopant was determined by the fact that the presence of magnetic/nonmagnetic (Eu2+/Yb2+) impurity in parent SmB6 matrix should lift/not lift the topological protection of surface states. Based on the two-gap paradigm the x-evolution of electron spectra in YbxSm1-xB6 and EuxSm1-xB6 was studied. Our data show that both the 4f lattice coherence (Eg) and the intrinsic gap (Ea) related to many-body states survive under RE doping at least for x ≈ 0.02 − 0.024. We also suggest that the point x(Eu) = 0.05 can be treated as an upper limit of the small gap closing in EuxSm1-xB6 materials. In YbxSm1-xB6 family a negative linear transverse magnetoresistance (TMR) was detected for the first time in the regime of surface conductivity (T < T∗ ≈ 5 K). The TMR anomaly at T∗ caused possibly by the topological protection of surface states in SmB6 is found to survive in Eu-doped compounds but disappears almost completely for Yb-doped compositions in the same fixed magnetic fields. This paradoxical observation is not consistent with general predictions of the topological Kondo insulator (TKI) model.

Missing metals in DQ stars: a compelling clue to their origin

ABSTRACT White dwarf stars frequently experience external pollution by heavy elements, and yet the intrinsically carbon-enriched DQ spectral class members fail to exhibit this phenomenon, representing a decades-old conundrum. This study reports a high-resolution spectroscopic search for Ca ii in classical DQ white dwarfs, finding that these stars are stunted both in pollution frequency and heavy element mass fractions, relative to the wider population. Compared to other white dwarf spectral classes, the average external accretion rate is found to be at least three orders of magnitude lower in the DQ stars. Several hypotheses are considered which need to simultaneously account for (i) an apparent lack of accreted metals, (ii) a dearth of circumstellar planetary material, (iii) an observed deficit of unevolved companions in post-common envelope binaries, (iv) relatively low helium mass fractions, and remnant masses that appear smaller than for other spectral classes, (v) a high incidence of strong magnetism, and (vi) modestly older disc kinematics. Only one hypothesis is consistent with all these constraints, suggesting DQ white dwarfs are the progeny of binary evolution that altered both their stellar structures and their circumstellar environments. A binary origin is already suspected for the warmer and more massive DQ stars, and is proposed here as an inclusive mechanism to expose core carbon material, in a potential evolutionary unification for the entire DQ spectral class. In this picture, DQ stars are not descended from DA or DB white dwarfs that commonly host dynamically active planetary systems.

Comparison of Empagliflozin with other SGLT-2i and the Pharmacological Effects of Empagliflozin

Diabetes mellitus is a pathological illness that is distinguished by compromised metabolic function due to defects in the synthesis and response of insulin, leading to substantial health complications. T2D is now recognized as a pressing global health concern, affecting a large population worldwide. Several studies have demonstrated that Empagliflozin can be categorized as a member of the drug class known as SGLT-2 inhibitors (SGLT-2i). This particular medication has been found to be effective in the treatment of T2D. This article elucidates the pharmacological effects of the substance in question, namely its capacity to reduce blood glucose levels, provide cardioprotection (mitigation of oxidative stress in the myocardium, mitigation of cardiac inflammation, decrease cell death in the cardiac tissue, betterment of Disrupted Electrolyte Homeostasis), influence cardiovascular outcomes, address obesity, impact renal function, and perhaps exhibit anticancer properties. The present study also aims to examine the comparative effects of empagliflozin in relation to other inhibitors across various domains, including cardiovascular events, worsening renal function, metabolic outcomes, and all-cause mortality.

Towards unsettling the racial nation-state: affective interventions in an Australian literature classroom

ABSTRACT As the adoption of the Immigration Restriction Act 1901 (otherwise known as the White Australia policy) reveals, whiteness has always been fundamental to the Australian nation-state. White sovereignty is constitutive of the Australian nation, making it a racial state. But the devastating impact of whiteness on those deemed ‘not-white’ remains largely unacknowledged. Drawing on framing of affective economies and an empirical study tracing how secondary school students in a Literature class negotiate their identities amidst structures of colonialism, I explore the affective dynamics of these negotiations with attention to how emotions align some bodies with particular communities and situate some outside of nation. Within a pedagogic intervention aiming to disrupt canonical assumptions, I collected written responses, recorded group discussions from all class members, and interviewed a selection of these students. Data analysis demonstrates that many in the class were oriented to whiteness as ‘Australianness’ at the expense of other possible cultural identities offered by their biographies, often resulting in emotions of shame or disorientation. It invites us to think beyond national borders to avert the deleterious effects ‘nation-ness’ can have on those it excludes and to work towards implementing pedagogic interventions that might unsettle the racial nation-state.

Unveiling Therapeutic Potential: Targeting Fusobacterium nucleatum's Lipopolysaccharide Biosynthesis for Endodontic Infections-An In Silico Screening Study.

Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

An autonomous plasmid as an inovirus phage satellite.

Bacterial viruses (phages) are potent agents of lateral gene transfer and thus are important drivers of evolution. A group of mobile genetic elements, referred to as phage satellites, exploits phages to disseminate their own genetic material. Here, we isolated a novel member of the family Inoviridae, Shewanella phage Dolos, along with an autonomously replicating plasmid, pDolos. Dolos causes a chronic infection in its host Shewanella oneidensis by phage production with only minor effects on the host cell proliferation. When present, plasmid pDolos hijacks Dolos functions to be predominantly packaged into phage virions and released into the environment and, thus, acts as a phage satellite. pDolos can disseminate further genetic material encoding, e.g., resistances or fluorophores to host cells sensitive to Dolos infection. Given the rather simple requirements of a plasmid for takeover of an inovirus and the wide distribution of phages of this group, we speculate that similar phage-satellite systems are common among bacteria.IMPORTANCEPhage satellites are mobile genetic elements, which hijack phages to be transferred to other host cells. The vast majority of these phage satellites integrate within the host's chromosome, and they all carry remaining phage genes. Here, we identified a novel phage satellite, pDolos, which uses an inovirus for dissemination. pDolos (i) remains as an autonomously replicating plasmid within its host, (ii) does not carry recognizable phage genes, and (iii) is smaller than any other phage satellites identified so far. Thus, pDolos is the first member of a new class of phage satellites, which resemble natural versions of phagemids.

Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7.

Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, like ActC. Collectively, our results establish ActE as a specific signaling ligand which activates the type I receptor, ALK7.

Penyuluhan Tentang Edukasi Asi Eksklusif Guna Persiapan Pemberian Asi Eksklusif di PMB Nosita Damayanti Simo

Exclusive breastfeeding has been stated in various regulations and legislation in Indonesia. One of them is based on the decision of the Minister of Health of the Republic of Indonesia Number 450/MENKES/SK/IV/2004 concerning exclusive breastfeeding..According to Roesli, this is because breast milk is the right intake because its composition always adapts to the baby's body and the development of the systems within the body. Education is expected to be a means of obtaining information, knowledge and a means of discussing problems faced by breastfeeding mothers.How to increase mothers' knowledge and understanding regarding the importance of preparing for exclusive breastfeeding through exclusive breastfeeding education for pregnant women so as to increase coverage of exclusive breastfeeding in Simo Village, Boyolali Regency. Methods for implementing outreach activities aboutExclusive breastfeeding education to prepare for exclusive breastfeeding at PMB Nosita Damayanti SimoThis is a method of health education in the form of counseling. The target is third trimester pregnant women who are members of the pregnant women class. The result was that there were 15 counseling participants who experienced an increase in knowledge after being given education about exclusive breastfeeding from 21 participants. Advice for pregnant women in the third trimester is to give breast milk as soon as the baby is born until 6 months. Keywords: Education, exclusive breastfeeding

Current Epidemiological Status and Antibiotic Resistance Profile of Serratia marcescens.

The spread of antibiotic resistance represents a serious worldwide public health issue, underscoring the importance of epidemiology research in determining antimicrobial strategies. The purpose of this research was to investigate antibiotic resistance in Serratia marcescens isolates from clinical samples over seven years at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in Salerno, Italy. S. marcescens is an important opportunistic pathogen associated with a wide spectrum of clinical diseases, including pneumonia, keratitis, meningitis, and urinary tract and wound infections. Outbreaks of nosocomial infections by S. marcescens strains have been documented in high-risk settings, mainly affecting immunocompromised patients and newborns. The primary objective of this study is to assess the rates of antibiotic resistance over the years to deal with a future emergency which includes the failure of various therapies due to antibiotic resistance. During the investigation, a total of 396 species of S. marcescens were isolated from various clinical samples, mainly from broncho-aspirates and sputum (31.6%) and blood cultures (21.5%). Antibiotics that showed the greatest susceptibility included ceftazidime/avibactam, amikacin, trimethoprim/sulfamethoxazole, and selected members of the cephalosporin class. However, a disconcerting trend of increasing rates of carbapenem resistance was outlined over the observation period. The absence of effective countermeasures, combined with growing antibiotic resistance that negates the effectiveness of multiple antibiotics, highlights the potential for S. marcescens infections to trigger serious clinical complications and increased mortality rates. The surveillance of Serratia marcescens infections constitutes a pivotal element in refining empiric therapy to mitigate the dissemination of antimicrobial resistance.

Acidithiobacillia class members originating at sites within the Pacific Ring of Fire and other tectonically active locations and description of the novel genus 'Igneacidithiobacillus'.

Recent studies have expanded the genomic contours of the Acidithiobacillia, highlighting important lacunae in our comprehension of the phylogenetic space occupied by certain lineages of the class. One such lineage is 'Igneacidithiobacillus', a novel genus-level taxon, represented by 'Igneacidithiobacillus copahuensis' VAN18-1T as its type species, along with two other uncultivated metagenome-assembled genomes (MAGs) originating from geothermally active sites across the Pacific Ring of Fire. In this study, we investigate the genetic and genomic diversity, and the distribution patterns of several uncharacterized Acidithiobacillia class strains and sequence clones, which are ascribed to the same 16S rRNA gene sequence clade. By digging deeper into this data and contributing to novel MAGs emerging from environmental studies in tectonically active locations, the description of this novel genus has been consolidated. Using state-of-the-art genomic taxonomy methods, we added to already recognized taxa, an additional four novel Candidate (Ca.) species, including 'Ca. Igneacidithiobacillus chanchocoensis' (mCHCt20-1TS), 'Igneacidithiobacillus siniensis' (S30A2T), 'Ca. Igneacidithiobacillus taupoensis' (TVZ-G3 TS), and 'Ca. Igneacidithiobacillus waiarikiensis' (TVZ-G4 TS). Analysis of published data on the isolation, enrichment, cultivation, and preliminary microbiological characterization of several of these unassigned or misassigned strains, along with the type species of the genus, plus the recoverable environmental data from metagenomic studies, allowed us to identify habitat preferences of these taxa. Commonalities and lineage-specific adaptations of the seven species of the genus were derived from pangenome analysis and comparative genomic metabolic reconstruction. The findings emerging from this study lay the groundwork for further research on the ecology, evolution, and biotechnological potential of the novel genus 'Igneacidithiobacillus'.

SN 2020udy: A New Piece of the Homogeneous Bright Group in the Diverse Iax Subclass

We present optical observations and analysis of the bright type Iax supernova SN 2020udy hosted by NGC 0812. The evolution of the light curve of SN 2020udy is similar to that of other bright type Iax SNe. Analytical modeling of the quasi-bolometric light curves of SN 2020udy suggests that 0.08 ± 0.01 M ⊙ of 56Ni would have been synthesized during the explosion. The spectral features of SN 2020udy are similar to those of the bright members of type Iax class, showing a weak Si ii line. The late-time spectral sequence is mostly dominated by iron group elements with broad emission lines. Abundance tomography modeling of the spectral time series of SN 2020udy using TARDIS indicates stratification in the outer ejecta; however, to confirm this, spectral modeling at a very early phase is required. After maximum light, uniform mixing of chemical elements is sufficient to explain the spectral evolution. Unlike in the case of normal type Ia SNe, the photospheric approximation remains robust until +100 days, requiring an additional continuum source. Overall, the observational features of SN 2020udy are consistent with the deflagration of a carbon–oxygen white dwarf.

Issues around vulnerability among people attended by a Portuguese community-based association: a qualitative secondary analysis

IntroductionDespite vulnerability being a poorly understood concept is a key concept in health and social care disparities. Typically, vulnerable groups include individuals with physical and/or mental disabilities, children, the elderly, members of the lower social classes, and refugees. In Portugal, the pandemic was responsible for worsening inequalities in access to health and social care for the most vulnerable. To the best of our knowledge, there is a dearth of qualitative research on vulnerability from the viewpoint of those who are vulnerable or work with the most vulnerable.ObjectivesAs expressions of vulnerability are strongly influenced by cultural factors, this study aims to examine issues of vulnerability among people who attend and work in a Portuguese community-based association.Methods Secondary analysis of qualitative data from twelve vulnerable people and fifteen professionals who attended these people. The manifestations of the vulnerability reported by participants included being homeless, being a migrant, having an infectious disease, being drug dependent, living with socioeconomic difficulties (unemployment), and experiencing a process of loss and grief. They also reported having a mental or physical health problem, or both. Depression and anxiety were the most often reported mental health disorders. Regarding the academic background of professionals, most of them (n = 12) are from social sciences (e.g., social workers, social mediators, and psychologists).ResultsThree main themes emerged from the study: (1) meanings of human vulnerability; (2) barriers to vulnerability mitigation; and (3) approaches to addressing vulnerability. Our findings revealed that vulnerability is a very dynamic process of openness to conditions that impact individual outcomes. However, there is a conceptual gap: being vulnerable is perceived as something negative, but vulnerability also has the potential to change priorities in life for the better. Some participants emphasized the importance of self-care to avoid becoming vulnerable themselves, particularly in terms of mental health.ConclusionsUnderstanding the social determinants of vulnerability is necessary to achieve satisfactory care for human groups. Practitioners need to be aware of these larger societal dynamics, understand them, and make sure their services are responsive to cultural differences. In order to develop interventions that promote social and health outcomes, practitioners should be encouraged to share knowledge on best practices.Disclosure of InterestNone Declared

Hepatoxicity Induced from Exposure of Male Rats to Low Doses of Tributyltin Chloride

Tributyltin (TBT) is a contaminant found all over the world. It is a member of the organotin class, which includes several widely disseminated, very hazardous compounds that have been linked to endocrine disruption. Consumption of TBT-contaminated seafood and drinking water are the most common routes of exposure among the susceptible population to man at low doses. The main goal of this study is to recognize the hepatotoxicity of low doses of TBT chloride (10-2000 µg/Kg body weight) in male rats for 45 days. TBT significantly induce hepatic impairment of antioxidant systems, oxidative stress, lipid peroxidation, and histological abnormalities in the liver architecture. In conclusion: the TBT at low doses could induce hepatotoxicity at low levels due to its lipophilic properties and the ability for accumulation in tissues.