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The current work aims to propose an adequate thermodynamic model, in addition to proposing and evaluating two composite models for the thermal decomposition of insulating mineral oil (IMO), considering that the models based on classical diagnostic methods do not have the ability to satisfactorily reproduce empirical data. The simulation results obtained using the proposed model showed better agreement with the presented data than the results obtained using classical models. The proposed model was also used in the development of a phenomenological based diagnostic method. The characteristics of this new phenomenological proposal and the classical diagnostic methods of dissolved gas analysis are compared and discussed; the proposed method showed better performance when compared to Rogers, Doernenburg, or IEC and equivalent performance to Duval triangle method commonly used in this field of knowledge. The general procedure for applying the new diagnostic method is also described. In order to account for the event's dynamics, the suggested model in particular made it feasible to replicate intermediate scenes of equilibrium C(s). Compared to the findings from the classical models found in the literature, the two-dimensional simulation results generated with this model demonstrated a better agreement with the actual data.

This study aims at identifying the role of social communication tools in education from the Saudi female students' perspectives that are studying at the college of education in King Saud University-Riyadh. This study used a survey, which was distributed to 500 female students. The results showed that 90% of respondents used social media where 95% said social media improved interaction with other and raised the sense of social responsibility, 56% used all tools of social media. 45% used social media more than 6 hours daily. 61% believed that social networks promoted democratic values and spread political culture.62% of respondents used social media to do homework or academic projects and researches. 99% of respondents believed that social media allowed following new information about their academic specialty and obtained specialized scientific consulting. 79% of respondents believed that one goal of creating accounts in social networks were learning specific science knowledge or a foreign language. 9% of respondents benefited from social media in social educational consulting. 44% of respondents preferred to debate in scientific and educational topics. 84% of respondents agreed that social networks provided the opportunity to form relationships with those interested in a particular scientific subject and exchanged experiences and information with them.

Neurodegenerative diseases drastically affect human beings without distinction; it does not matter if they are male or female. Sometimes, it is not clear why a person in their life developed a well-known disease in the world such as Parkinson’s disease (PD). Nowadays, various novel machine learning-based algorithms for evaluating Parkinson’s disease have been designed. The most recent strategy, which was developed using deep learning and can forecast the severity of Parkinson’s disease, is the one described here. To identify this disease, a thorough medical history, previous treatment history, physical examinations, and some blood tests and brain films must be completed. Diagnoses are more critical since they are less expensive and less time-consuming. Voice data from 253 people used in the current study corroborates the doctor’s diagnosis of Parkinson’s disease. To acquire the best results from the data, preprocessing is done. To perform the balancing procedure, a systematic sampling strategy was used to select the data that would be analyzed. Several data groups were constructed using a feature selection technique based on the label’s effect strength. Classification algorithms and performance evaluation criteria employ DT, SVM, and kNN. The classification algorithm and data group with the highest performance value were chosen, and the model was created due to this selection. The SVM approach was employed when constructing the model, and 45% of the original data set data were used. The data was sorted from most relevant to least important. 86% performance accuracy was achieved, in addition to excellent results in all other areas of the project. As a result, it has been established that medical decision support will be provided to the doctor with the assistance of the data set obtained from the speech recordings of the individual who may have Parkinson’s disease and the model that has been developed.

A smart, environmentally friendly superabsorbent polymer was prepared using solvents. It was polymerization on the microwave rays at a medium capacity and for 25 minutes, where the yellow gel was obtained. The polymer was cut and washed with absolute ethanol and methanol and was dried at a temperature of 60°C. Then, the polymer was extracted and milled with ceramic fat until obtaining a very soft powder, and the tests were taken as a formula for a scanning electron microscope and infrared spectrum. The results showed that the absorption value of polymer is at the equivalent acid function, where the absorption capacity was 467.32 grams. At room temperature, the water retention rate was 71%, and at 50°C, it was 52%, and the gel content was 90%. The results showed an improvement in the properties of the gypsum soil in terms of virtual density, porous, and acidic function, reaching 7.3%. The proportion of significant elements (P, N, Ca, K, Na) and moisture content in the soil was 64%, the cumulative tip amount and the consistency of soil granules through wet and dry palm, penetration resistance, electrical conductivity 4 ms, and organic material content were as follows, and the results were very high.

Alumina nanoparticles were prepared by sol-gel method, where the obtained nanosize was 35 nm, and the nanomaterial was coated with PVP polymer, where the nanomaterial was dispersed by ultrasonic waves for half an hour, and then, the polymer was added, and under high magnetic stirring for 24 hours, it was dried at a temperature of 60°C for 24 hours. Cadmium salt solutions were prepared with different concentrations of 10, 30, and 60 ppm, and the nanomaterial was immersed in the prepared solutions at different times of 10, 30, and 60 minutes, and the measurement was done by an atomic absorption device. By means of the electronic scanner, a difference appeared in the nanosize, and this indicates that the packaging has completely occurred.

The aim of this work was to present the creation of appropriate tools to evaluate the coping strategies in Oral-Health-related Quality of Life (OHrQOL) implemented by persons with schizophrenia (PWS), the Schizophrenia Coping Oral Health Profile (SCOOHP), and the results of a feasibility study.

Multidrug-resistant bacterial infections present a serious challenge to global health. In addition to the spread of antibiotic resistance, some bacteria can form persister cells which are tolerant to most antibiotics and can lead to treatment failure or relapse. In the present work, we report the discovery of a new class of small molecules with potent antimicrobial activity against Gram-positive bacteria and moderate activity against Gram-negative drug-resistant bacterial pathogens. The lead compound SIMR 2404 had a minimal inhibitory concentration (MIC) of 2 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate Staphylococcus aureus (VISA). The MIC values against Gram-negative bacteria such as Escherichia coli and Actinobacteria baumannii were between 8-32 μg/mL. Time-kill experiments show that compound SIMR 2404 can rapidly kill tested bacteria. Compound SIMR 2404 was also found to rapidly kill MRSA persisters which display high levels of tolerance to conventional antibiotics. In antibiotic evolution experiments, MRSA quickly developed resistance to ciprofloxacin but failed to develop resistance to compound SIMR 2404 even after 24 serial passages. Compound SIMR 2404 was not toxic to normal human fibroblast at a concentration of 4 μg/mL which is twice the MIC concentration against MRSA. However, at a concentration of 8 μg/mL or higher, it showed cytotoxic activity indicating that it is not ideal as a candidate against Gram-negative bacteria. The acceptable toxicity profile and rapid antibacterial activity against MRSA highlight the potential of these molecules for further studies as anti-MRSA agents. [ABSTRACT FROM AUTHOR]

Background: Upper limb lymphedema is a common and troublesome complication that follows breast cancer surgery. Aim and Objectives: To find the incidence and identify risk factors for the development of upper limb lymphedema among patients treated for breast cancer. Material and Methods: This was a prospective observational study of 135 patients who underwent different breast cancer surgeries for invasive breast cancer. A description of the patients' demographics and details related to the tumour and axillary clearance were recorded. Using the circumference measurements, lymphoedema was defined as a difference in volume of = 200 ml between the two arms after six months of surgery. Results: Age, type of surgery (mastectomy versus breast preserving surgery), and adjuvant radiotherapy were not risk factors for lymphedema (p = 0.9977, 0.7794 and 0.852 respectively).A significant correlation was found between BMI above 25 kg/m², advanced stage, higher number of excised lymph nodes and more than 5 involved lymph nodes, and the development of lymphedema (p = 0.0001, 0.002, 0.01 and 0.009 respectively). Positive lymph nodes was a powerful predictor of lymphedema (p = 0.0003). Conclusion: Lymphedema can affect every third patient who is operated on for breast cancer. Advanced stage, increased BMI above 25 kg/m2, increased number of excised lymph node together with increased number of involved lymph nodes, are significant risk factors for breast cancer related lymphedema. [ABSTRACT FROM AUTHOR]

The current work aims to propose an adequate thermodynamic model, in addition to proposing and evaluating two composite models for the thermal decomposition of insulating mineral oil (IMO), considering that the models based on classical diagnostic methods do not have the ability to satisfactorily reproduce empirical data. The simulation results obtained using the proposed model showed better agreement with the presented data than the results obtained using classical models. The proposed model was also used in the development of a phenomenological based diagnostic method. The characteristics of this new phenomenological proposal and the classical diagnostic methods of dissolved gas analysis are compared and discussed; the proposed method showed better performance when compared to Rogers, Doernenburg, or IEC and equivalent performance to Duval triangle method commonly used in this field of knowledge. The general procedure for applying the new diagnostic method is also described. In order to account for the event's dynamics, the suggested model in particular made it feasible to replicate intermediate scenes of equilibrium C(s). Compared to the findings from the classical models found in the literature, the two-dimensional simulation results generated with this model demonstrated a better agreement with the actual data. [ABSTRACT FROM AUTHOR]

Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the General Oral Health Assessment Index Questionnaire (GOHAI) items for differential item functioning (DIF) according to demographic characteristics (gender, age) and mental health status (schizophrenic disorders versus general population) using Rasch analysis.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initially emerged in December 2019 and has subsequently expanded globally, leading to the ongoing pandemic. The extensive spread of various SARS-CoV-2 variants possesses a serious public health threat. An extensive literature search along with deep analysis was performed to describe and evaluate the characteristics of SARS-CoV-2 variants of concern in relation to the effectiveness of the current vaccines and therapeutics. The obtained results showed that several significant mutations have evolved during the COVID-19 pandemic. The developed variants and their various structural mutations can compromise the effectiveness of several vaccines, escape the neutralizing antibodies, and limit the efficiency of available therapeutics. Furthermore, deep analysis of the available data enables the prediction of the future impact of virus mutations on the ongoing pandemic along with the selection of appropriate vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Technologies are increasingly independent and play important roles in society. Artificial intelligence (AI) is a branch of science that can improve various environments and processes. The health sector stands out among these contexts, especially ophthalmology and dentistry. Studies evaluating the impact of using these technologies in these contexts are still developing. There are still few studies that assess how AI can impact the decision-making process of health professionals and how it can improve the quality of care provided to these professionals. In this sense, this study aims to evaluate the perception of the impact of AI on the decision-making process of health professionals and the quality of patient care from the perspective of ophthalmologists and dentists. The methodological strategy used was the application of an online questionnaire with eighteen professionals in these areas. Based on the respondents' opinions, we sought to assess how these decision-making processes are affected by the use of technologies and how they impact the quality of patient care. As a result, it was observed that AI has become essential and a facilitator of the diagnostic processes. However, it presents some challenges related to cost, accessibility, AI x  professional responsibility, and incentive of agreements. [ABSTRACT FROM AUTHOR]

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LcrV, a multifunctional protein, acts as a positive regulator of effector protein secretion for the type III secretion system (T3SS) in Yersinia pestis by interaction with the negative regulator LcrG. In this study, LcrV was analyzed to identify regions required for LcrG interaction. Random-linker insertion mutagenesis, deletion analysis, and site-directed mutagenesis of hydrophobic amino acids between residues 290 and 311 allowed the isolation of an LcrV mutant (LcrV L291R F308R) defective for LcrG interaction. The new residues identified in LcrG interaction lie in helix 12 of LcrV; residues in helix 7 of LcrV are known to be involved in LcrG interaction. Helix 7 and helix 12 of LcrV interact to form an intramolecular coiled coil; these new results suggest that the intramolecular coiled coil in LcrV is required for LcrG interaction and activation of the T3SS.

This correction notice states that the raw data for Figures 1 and 2 in the article titled "Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: a multi-omics approach" are missing from the Supporting Information. The authors have provided the data with the accession number GSE263609, which can be accessed at the provided link. The Data Availability statement in the article has been corrected to reflect this. [Extracted from the article]

Colon cancer is a disease characterized by the unusual and uncontrolled development of cells that are found in the large intestine. If the tumour extends to the lower part of the colon (rectum), the cancer may be colorectal. Medical imaging is the denomination of methods used to create visual representations of the human body for clinical analysis, such as diagnosing, monitoring, and treating medical conditions. In this research, a computational proposal is presented to aid the diagnosis of colon cancer, which consists of using hyperspectral images obtained from slides with biopsy samples of colon tissue in paraffin, characterizing pixels so that, afterwards, imaging techniques can be applied. Using computer graphics augmenting conventional histological deep learning architecture, it can classify pixels in hyperspectral images as cancerous, inflammatory, or healthy. It is possible to find connections between histochemical characteristics and the absorbance of tissue under various conditions using infrared photons at various frequencies in hyperspectral imaging (HSI). Deep learning techniques were used to construct and implement a predictor to detect anomalies, as well as to develop a computer interface to assist pathologists in the diagnosis of colon cancer. An infrared absorbance spectrum of each of the pixels used in the developed classifier resulted in an accuracy level of 94% for these three classes. [ABSTRACT FROM AUTHOR]

Introduction: Sacrococcygeal pilonidal sinus (PNS) is a common chronic benign disease of young age group, associated with morbidity, often with a prolong loss of normal activity. Still there is ongoing debate regarding the best treatment option as all the methods have complications, although; the current evidence supports the use of off-midline techniques because of lower recurrence rates and avoidance of all disadvantages of open treatment. This study was done to determine the postoperative outcome of rhomboid excision and Limberg flap reconstruction as a main procedure in the treatment of PNS disease in our institute. Patients and Method: A prospective study conducted at the Department of General Surgery-Baquba Teaching Hospital-Diyala-Iraq, from January 2017 to June 2019, in which 98 patients (78 male and 20 female) with chronic primary sacrococcygeal PNS were enrolled. The age of the patients ranged between 16 - 38 years. Patients with acute abscess were first treated by incision and drainage before definite surgery. Patients were operated by rhomboid excision and Limberg flap reconstruction. Results: In this study, 98 patients were enrolled, 78 male (79.59 %) and 20 female (20.4%) with male to female ratio of 3.9:1. The age of the patients ranged between 16 to 38 years with the mean age of 25 years. During the follow up period; 6 patients (6.12%) developed seroma, 4 patients (4.08%) had infection and 4 patients (4.08%) had recurrent sinus after few months and one patient (1.02%) had wound disruption. Conclusion: Rhomboid excision and Limberg flap reconstruction of PNS diseaseis safe and reliable technique with low complication and recurrence rates if performed according to appropriate surgical principles. [ABSTRACT FROM AUTHOR]

The serious challenge posed by multidrug-resistant bacterial infections with concomitant treatment failure and high mortality rates presents an urgent threat to the global health. We herein report the discovery of a new class of potent antimicrobial compounds that are highly effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The compounds were efficiently synthesized in one-pot employing a cascade of Groebke–Blackburn–Bienaymé and aza-Michael addition reactions. Phenotypic screening of the pilot library against various bacterial species including methicillin-sensitive and MRSA strains, has identified potent chemotypes with minimal inhibitory concentrations (MIC) of 3.125–6.25 μg/ml. The most potent compounds were fast-acting at eradicating exponentially growing MRSA, with killing achieved after 30 min of exposure to the compounds. They were also able to kill MRSA persister cells which are tolerant to most available medications. Microscopic analysis using fluorescence microscope and atomic force microscope indicate that these compounds lead to disruption of bacterial cell envelopes. Most notably, bacterial resistance toward these compounds was not observed after 20 serial passages in stark contrast to the significant resistance developed rapidly upon exposure to a clinically relevant antibiotic. Furthermore, the compounds did not induce significant hemolysis to human red blood cells. In vivo safety studies revealed a high safety profile of these motifs. These small molecules hold a promise for further studies and development as new antibacterial agents against MRSA infections. Antibacterial activity of small molecules which eradicate methicillin-resistant Staphylococcus aureus (MRSA) persisters. [ABSTRACT FROM AUTHOR]

Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence. [ABSTRACT FROM AUTHOR]

Overexpression of ferritin heavy chain (FTH1) often associates with good prognosis in breast cancer (BCa), particularly in the triple‐negative subtype (triple‐negative breast cancer). However, the mechanism by which FTH1 exerts its possible tumor suppressor effects in BCa is not known. Here, we examined the bearing of FTH1 silencing or overexpression on several aspects of BCa cell growth in vitro. FTH1 silencing promoted cell growth and mammosphere formation, increased c‐MYC expression, and reduced cell sensitivity to chemotherapy. In contrast, FTH1 overexpression inhibited cell growth, decreased c‐MYC expression, and sensitized cancer cells to chemotherapy; silencing of c‐MYC recapitulated the effects of FTH1 overexpression. These findings show for the first time that FTH1 suppresses tumor growth by inhibiting the expression of key oncogenes, such as c‐MYC. [ABSTRACT FROM AUTHOR]

We present a divergent strategy that permits access to diversely functionalized benzoxazepinium scaffolds fused to various heterocycles. The described strategy features a one-pot combination of the Groebke–Blackburn–Bienaymé reaction and an aza-Michael addition. Methyl (E)-4-(2-formylphenoxy)but-2-enoate and its derivatives are utilized as central elements in this cascade. These building blocks are reacted with a variety of functionalized amino-azines and tert -butyl isocyanide under ytterbium triflate [Yb(OTf)3 ] catalysis. The ensuing cascade represents a rapid, modular and atom-economic process that leads to the construction of a diverse collection of constrained benzoxazepinium systems from a wide substrate scope. [ABSTRACT FROM AUTHOR]

The discovery of antibiotics has transformed medical practices and saved countless lives. Antibiotic stewardship programs aimed at proper treatment, preventing overuse, AMR surveillance and minimizing AMR development were created by WHO and Centers for Disease Control and Prevention (CDC). (c) Antibiotic target alteration can be caused by mutations in the antibiotic binding site including penicillin-binding protein (PBP), DNA, RNA polymerase or ribosome. [Extracted from the article]

Summary: WaaL is an inner membrane glycosyltransferase that catalyzes the transfer of O‐antigen polysaccharide from its lipid‐linked intermediate to a terminal sugar of the lipid A‐core oligosaccharide, a conserved step in lipopolysaccharide biosynthesis. Ligation occurs at the periplasmic side of the bacterial cell membrane, suggesting the catalytic region of WaaL faces the periplasm. Establishing the membrane topology of the WaaL protein family will enable understanding its mechanism and exploit it as a potential antimicrobial target. Applying oxidative labeling of native methionine/cysteine residues, we previously validated a topological model for Escherichia coli WaaL, which differs substantially from the reported topology of the Pseudomonas aeruginosa WaaL, derived from the analysis of truncated protein reporter fusions. Here, we examined the topology of intact E. coli and P. aeruginosa WaaL proteins by labeling engineered cysteine residues with the membrane‐impermeable sulfhydryl reagent polyethylene glycol maleimide (PEG‐Mal). The accessibility of PEG‐Mal to targeted engineered cysteine residues in both E. coli and P. aeruginosa WaaL proteins demonstrates that both ligases share similar membrane topology. Further, we also demonstrate that P. aeruginosa WaaL shares similar functional properties with E. coli WaaL and that E. coli WaaL may adopt a functional dimer conformation. WaaL is an inner membrane glycosyltransferase that catalyzes the transfer of O‐antigen polysaccharide from its lipid‐linked intermediate to a terminal sugar of the lipid A‐core oligosaccharide, a conserved step in lipopolysaccharide biosynthesis. This work shows that in contrast to previous reports, Escherichia coli and Pseudomonas aeruginosa WaaL proteins share similar membrane topology and functional properties, and that E. coli WaaL may adopt a functional dimer conformation in vivo. [ABSTRACT FROM AUTHOR]

Background: The "General Oral Health Assessment Index" (GOHAI) was widely used in clinical or epidemiological studies worldwide, as it was available for use in different languages. Therefore, the aim of this study was to evaluate the psychometric characteristics of the GOHAI in a representative sample of patients with schizophrenia. Methods: A total of 90 schizophrenic patients (in-patients and out-patients) were recruited from the participants of the "buccodor study" (NCT02167724) between March and September 2015. They were selected using a random stratified sampling method according to their age, sex, or residential area (urban/rural area). GOHAI validity (construct, predictive, concurrent and known group validity) and internal consistency (reliability) were tested. Test-retest reliability was evaluated in 32 subjects. Results: The mean age was 47.34 (SD = 12.17). Internal consistency indicated excellent agreement, with a Cronbach's α value of 0.82 and average inter-item correlation of 0.65. Intraclass correlation coefficients for test-retest reliability with 95% confidence intervals were not significantly different (p > 0.05). Construct validity was supported by three factor that accounted for 60.94% of the variance observed. Predictive validity was corroborated as statistically significant differences were observed between a high GOHAI score, which was associated with self-perceived satisfaction with oral health, lower age and high frequency of toothbrushing. Concurrent validity was corroborated as statistically significant relationships were observed between the GOHAI scores and most objective measures of dental status. For known group validity, they was no significant difference of the mean GOHAI score between out or in-patients (p >0.05). Conclusion: Acceptable psychometric characteristics of the GOHAI could help caregivers to develop ways to improve the Oral Health related Quality Of Life of schizophrenic patients. Trial registration: Clinical Trials Gov NCT02167724. Date registered 17 June, 2014. [ABSTRACT FROM AUTHOR]

Lipid A anchors the lipopolysaccharide (LPS) to the outer membrane and is usually composed of a hexa-acylated diglucosamine backbone. Burkholderia cenocepacia, an opportunistic pathogen, produces a mixture of tetra- and penta-acylated lipid A. 'Late' acyltransferases add secondary acyl chains to lipid A after the incorporation of four primary acyl chains to the diglucosamine backbone. Here, we report that B. cenocepacia has only one late acyltransferase, LpxL (BCAL0508), which adds a myristoyl chain to the 2′ position of lipid A resulting in penta-acylated lipid A. We also identified PagL (BCAL0788), which acts as an outer membrane lipase by removing the primary β-hydroxymyristate (3-OH-C14:0) chain at the 3 position, leading to tetra-acylated lipid A. Unlike PagL, LpxL depletion caused reduced cell growth and defects in cell morphology, both of which were suppressed by overexpressing the LPS flippase MsbA (BCAL2408), suggesting that lipid A molecules lacking the fifth acyl chain contributed by LpxL are not good substrates for the flippase. We also show that intracellular B. cenocepacia within macrophages produced more penta-acylated lipid A, suggesting lipid A penta-acylation in B. cenocepacia is required not only for bacterial growth and morphology but also for adaptation to intracellular lifestyle. [ABSTRACT FROM AUTHOR]

Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood. B urkholderia species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in B urkholderia cenocepacia by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by hpnH and hpnG were essential for production of all C35 extended hopanoids, including bacteriohopanetetrol ( BHT), BHT glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production, while Δ hpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT glucosamine production while HpnJ is responsible for its conversion to the cyclitol ether. The Δ hpnH and Δ hpnG mutants could not grow under any stress condition tested, whereas Δ hpnI, Δ hpnJ and Δ hpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B . cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria. [ABSTRACT FROM AUTHOR]