Search

Abstract Worldwide industrialization has grown at a rapid pace, contaminating water resources, particularly with phenolic pollutants that pose a risk to aquatic systems and human health. The goal of this study is to create an inexpensive magnetic composite that can effectively remove nitrophenol (o-NP) using adsorptive means. In this instance, a nonanyl chitosan (N-Cs) derivative was synthesized and then combined with activated petroleum coke (AP-coke) and magnetic Fe3O4 to boost its adsorbability towards o-NP and to facilitate its separation. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometer (XRD), Vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), and zeta potential were employed to characterize the magnetic composite. The experimental results indicated that the Fe3O4/AP-coke/N-Cs composite possesses a greater affinity toward o-NP with a maximal efficiency reached 88% compared to 22.8, 31.2, and 45.8% for Fe3O4, AP-coke and N-Cs, respectively. The equilibrium adsorption data coincided with the Langmuir, Freundlich, and Temkin isotherm models, with a maximum adsorption capacity of 291.55 mg/g at pH 6, whereas the pseudo second order kinetic model offered the best fit to the experimental data. Besides, the developed adsorbent preserved satisfactory adsorption characteristics after reuse for five successive cycles. The proposed adsorption mechanism involves the H-bonding, π-π interaction, hydrophobic interactions and electron donor-acceptor interactions. These findings hypothesize that the constructed magnetic composite could efficiently remove nitrophenols from polluted water with high performance and ease-separation.

Abstract Reinforcement of the Internet of Medical Things (IoMT) network security has become extremely significant as these networks enable both patients and healthcare providers to communicate with each other by exchanging medical signals, data, and vital reports in a safe way. To ensure the safe transmission of sensitive information, robust and secure access mechanisms are paramount. Vulnerabilities in these networks, particularly at the access points, could expose patients to significant risks. Among the possible security measures, biometric authentication is becoming a more feasible choice, with a focus on leveraging regularly-monitored biomedical signals like Electrocardiogram (ECG) signals due to their unique characteristics. A notable challenge within all biometric authentication systems is the risk of losing original biometric traits, if hackers successfully compromise the biometric template storage space. Current research endorses replacement of the original biometrics used in access control with cancellable templates. These are produced using encryption or non-invertible transformation, which improves security by enabling the biometric templates to be changed in case an unwanted access is detected. This study presents a comprehensive framework for ECG-based recognition with cancellable templates. This framework may be used for accessing IoMT networks. An innovative methodology is introduced through non-invertible modification of ECG signals using blind signal separation and lightweight encryption. The basic idea here depends on the assumption that if the ECG signal and an auxiliary audio signal for the same person are subjected to a separation algorithm, the algorithm will yield two uncorrelated components through the minimization of a correlation cost function. Hence, the obtained outputs from the separation algorithm will be distorted versions of the ECG as well as the audio signals. The distorted versions of the ECG signals can be treated with a lightweight encryption stage and used as cancellable templates. Security enhancement is achieved through the utilization of the lightweight encryption stage based on a user-specific pattern and XOR operation, thereby reducing the processing burden associated with conventional encryption methods. The proposed framework efficacy is demonstrated through its application on the ECG-ID and MIT-BIH datasets, yielding promising results. The experimental evaluation reveals an Equal Error Rate (EER) of 0.134 on the ECG-ID dataset and 0.4 on the MIT-BIH dataset, alongside an exceptionally large Area under the Receiver Operating Characteristic curve (AROC) of 99.96% for both datasets. These results underscore the framework potential in securing IoMT networks through cancellable biometrics, offering a hybrid security model that combines the strengths of non-invertible transformations and lightweight encryption.

Abstract Leptospirosis is caused by pathogenic bacteria of the genus Leptospira and is one of causative agents of reproductive problems leading to negative economic impact on bovine worldwide. The goal of this study was to investigate the seroprevalence of Leptospira spp. in cattle in some governorates of Egypt's Nile Delta and assess the risk factors for infection. A total of 410 serum samples were collected from cattle and examined using microscopic agglutination test. The overall seroprevalence was 10.2% and the most prevalent serovars were Icterohaemorrhagiae, Pomona and Canicola. In addition, the potential risk factors were associated Leptospira spp. infection were age, herd size, history of abortion, presence of dogs and rodent control. Thus, leptospirosis is common in dairy cattle in the Nile Delta and the presence of rodents in feed and dog-accessible pastures increases the risk of Leptospira spp. infection among animals.

Abstract We report on the synthesis and characterization of six novel 2,2′-bithiophene-based organic compounds (3a–c and 5a–c) that are designed to serve as co-sensitizers for dye-sensitized solar cells (DSSCs) based on TiO2. The compounds are linked to various donor and acceptor groups, and we confirm their chemical structures through spectral analyses. Our focus is on enhancing the performance of metal based N3, and the compounds were designed to operate at the nanoscale. We performed absorption and fluorescence emission measurements in dimethylformamide (DMF), where one of our compounds 5a exhibited the longest maximum absorption and maximum emission wavelengths, indicating the significant impact of the para methoxy group as a strong electron-donating group. Our dyes 5a + N3 (η = 7.42%) and 5c + N3 (η = 6.57%) outperformed N3 (η = 6.16%) alone, where the values of short current density (J SC ) and open circuit voltage (V OC ) for these two systems also improved. We also investigated the charge transfer resistance at the TiO2/dye/electrolyte interface using electrochemical impedance spectroscopy (EIS), which is important in the context of nanotechnology. According to the Nyquist plot, the 5a + N3 cocktail exhibited the lowest recombination rate, resulting in the highest V OC . Our theoretical calculations based on density functional theory (DFT) are also in agreement with the experimental process. These findings suggest that our compounds have great potential as efficient DSSC co-sensitizers. This study provides valuable insights into the design and synthesis of new organic compounds for use as co-sensitizers in DSSCs based on TiO2 and highlights the potential of these compounds for use in efficient solar energy conversion.

Abstract The preparation of adsorbents plays a vital role in the adsorption method. In particular, many adsorbents with high specific surface areas and unique shapes are essential for the adsorption strategy. A Zn–Mg–Al/layer double hydroxide (LDH) was designed in this study using a simple co-precipitation process. Adsorbent based on Zn–Mg–Al/LDH was used to remove crystal violet (CV) from the wastewater. The impacts of the initial dye concentration, pH, and temperature on CV adsorption performance were systematically examined. The adsorbents were analyzed both before and after adsorption using FTIR, XRD, and SEM. The roughness parameters and surface morphologies of the produced LDH were estimated using 3D SEM images. Under the best conditions (dose of adsorbent = 0.07 g and pH = 9), the maximum adsorption capacity has been achieved. Adsorption kinetics studies revealed that the reaction that led to the adsorption of CV dye onto Zn–Mg–Al/LDH was a pseudo-second-order model. Additionally, intraparticle diffusion suggests that Zn–Mg–Al/LDH has a fast diffusion constant for CV molecules (0.251 mg/(g min1/2)). Furthermore, as predicted by the Langmuir model, the maximal Zn–Mg–Al/LDH adsorption capacity of CV was 64.80 mg/g. The CV dimensionless separation factor (RL) onto Zn–Mg–Al/LDH was 0.769, indicating that adsorption was favorable. The effect of temperature was performed at 25, 35, and 45 °C in order to establish the thermodynamic parameters ∆Ho, ∆So, and ∆Go. The computed values indicated exothermic and spontaneous adsorption processes. The study presented here might be used to develop new adsorbents with enhanced adsorption capabilities for the purpose of protecting the water environment.

Abstract Aerobic rice cultivation progresses water productivity, and it can save almost 50% of irrigation water compared to lowland rice with the appropriate development of genotypes and management practices. Two field trials were conducted during 2020, and 2021 seasons to determine the validation of different rice varieties under aerobic cultivation based on their plant defense system, physio-morphological traits, stress indices, grain yield, and water productivity. The experiments were designed in a split-plot design with four replications. Two planting methods, transplanting and aerobic cultivation, were denoted as the main plots, and ten rice genotypes were distributed in the subplots. The results revealed that the planting method varied significantly in all measured parameters. The transplanting method with well watering had the highest value of all measured parameters except leaf rolling, membrane stability index, antioxidant, proline, and the number of unfilled grains. EHR1, Giza179 and GZ9399 as well as A22 genotypes a chief more antioxidant defense system that operated under aerobic conditions. Giza179, EHR1, GZ9399, and Giza178 showed high cell membrane stability and subsequently high validation under such conditions, and also showed efficiency in decreasing water consumption and improving water use efficiency. In conclusion, this study proves that Giza179, EHR1, GZ9399, Giza178, and A22 are valid genotypes for aerobic conditions.

Infection with Edwardsiella ictaluri, a causative agent of enteric septicemia of catfish, threatens profitable catfish production through inventory losses. We previously demonstrated that trans-cinnamaldehyde (TC) enhances the survival of catfish following E. ictaluri infection. The present study was conducted to investigate catfish immune responses to TC feeding and E. ictaluri infection. The expression of 13 proinflammatory, innate, and adaptive immune-related genes was evaluated over time in two sets of experiments using real-time polymerase chain reaction (PCR). In the first experiment, catfish were fed a basal diet with or without TC supplementation, while in the second they were fed a TC-supplemented or normal diet followed by infection with E. ictaluri. The catfish group infected with E. ictaluri and fed a TC-diet showed significant changes in the expression of innate and adaptive immune-related genes compared to control group. At 21 and 28 days post-infection, recovered fish showed significant increases in the expression of IgM in the anterior kidney and spleen. These results suggest that the supplemental dietary intake of TC can improve the immune status of catfish via engaging innate and adaptive immune responses and the production of memory cells in immunocompetent tissues. Together, this study provides an important foundation for the potential application of TC as an antimicrobial alternative in aquaculture.

Abstract Mucormycosis is a life-threatening opportunistic angioinvasive fungal infection. We aimed to describe the frequency, presentations, predictors, and in-hospital outcome of mucormycosis patients in the scope of CoronaVirusDisease-19 (COVID-19) during the third viral pandemic wave. This cross-sectional retrospective study included all patients who fulfilled the criteria of mucormycosis with concurrent confirmed covid19 infection admitted to Assuit University Hospital between March 2021 and July 2021. Overall, 433 patients with definite covid-19 infection, of which 33 (7.63%) participants were infected with mucormycosis. Mucormycosis was predominantly seen in males (21 vs. 12; p = 0.01). Diabetes mellitus (35% vs. 63.6%; p

Abstract Molecular pathology services for colorectal cancer (CRC) in Sudan represent a significant unmet clinical need. In a retrospective cohort study involving 50 patients diagnosed with CRC at three major medical settings in Sudan, we aimed to outline the introduction of a molecular genetic service for CRC in Sudan, and to explore the CRC molecular features and their relationship to patient survival and clinicopathological characteristics. Mismatch repair (MMR) and BRAF (V600E) mutation status were determined by immunohistochemistry. A mismatch repair deficient (dMMR) subtype was demonstrated in 16% of cases, and a presumptive Lynch Syndrome (LS) diagnosis was made in up to 14% of patients. dMMR CRC in Sudan is characterized by younger age at diagnosis and a higher incidence of right-sided tumours. We report a high mortality in Sudanese CRC patients, which correlates with advanced disease stage, and MMR status. Routine MMR immunohistochemistry (with sequential BRAF mutation analysis) is a feasible CRC prognostic and predictive molecular biomarker, as well as a screening tool for LS in low-middle-income countries (LMICs).

Abstract Two novel bithienyl fluorobenzamidine derivatives namely, 4-([2,2′:5′,2′′-terthiophen]-5-yl)-2-fluorobenzamidine hydrochloride salt (MA-1615), 5′-(4-amidino-3-fluorophenyl)-[2,2′-bithiophene]-5-carboxamidine dihydrochloride salt (MA-1740) were synthesized, characterized and their corrosion inhibition properties were evaluated by electrochemical methods for carbon steel (C-steel) in 1 M HCl. Experimental investigations revealed that the inhibition effectiveness of the investigated inhibitors (INHs) by the Tafel polarization method followed the order: MA-1740 (96.9%) > MA-1615 (95.6%), demonstrating higher efficiency than inhibitors of similar structure reported in the literature. The investigated bithiophene derivatives exhibit mixed-type corrosion inhibition characteristics by blocking the active sites on the surface of C-steel. EIS study revealed that the INHs behave as interface-type corrosion inhibitors. UV–Visible spectrometric measurements confirmed a complex formation between the Fe2+ cation released during the corrosion reactions and inhibitor molecules.

Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute to E. ictaluri virulence, the Type VI secretion system (T6SS) remains poorly understood. In this study, we constructed 13 E. ictaluri T6SS mutants using splicing by overlap extension PCR and characterized them, assessing their uptake and survival in channel catfish (Ictalurus punctatus) peritoneal macrophages, attachment and invasion in channel catfish ovary (CCO) cells, in vitro stress resistance, and virulence and efficacy in channel catfish. Among the mutants, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO exhibited reduced replication inside peritoneal macrophages. EiΔevpM, EiΔevpN, and EiΔevpO showed significantly decreased attachment to CCO cells, while EiΔevpN and EiΔevpO also displayed reduced invasion of CCO cells (p < 0.05). Overall, T6SS mutants demonstrated enhanced resistance to oxidative and nitrosative stress in the nutrient-rich medium compared to the minimal medium. However, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO were susceptible to oxidative stress in both nutrient-rich and minimal medium. In fish challenges, EiΔevpD, EiΔevpE, EiΔevpG, EiΔevpJ, and EiΔevpK exhibited attenuation and provided effective protection against E. ictaluri wild-type (EiWT) infection in catfish fingerlings. However, their attenuation and protective efficacy were lower in catfish fry. These findings shed light on the role of the T6SS in E. ictaluri pathogenesis, highlighting its significance in intracellular survival, host cell attachment and invasion, stress resistance, and virulence. The attenuated T6SS mutants hold promise as potential candidates for protective immunization strategies in catfish fingerlings.

SAMD9 and SAMD9L germline mutations have recently emerged as a new class of predispositions to pediatric myeloid neoplasms. Patients commonly have impaired hematopoiesis, hypocellular marrows, and a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML. We recently demonstrated that expressing SAMD9 or SAMD9L mutations in hematopoietic cells suppresses their proliferation and induces cell death. Here, we generated a mouse model that conditionally expresses mutant Samd9l to assess the in vivo impact on hematopoiesis. Using a range of in vivo and ex vivo assays, we showed that cells with heterozygous Samd9l mutations have impaired stemness relative to wild-type counterparts, which was exacerbated by inflammatory stimuli, and ultimately led to bone marrow hypocellularity. Genomic and phenotypic analyses recapitulated many of the hematopoietic cellular phenotypes observed in patients with SAMD9 or SAMD9L mutations, including lymphopenia, and pinpointed TGF-β as a potential targetable pathway. Further, we observed nonrandom genetic deletion of the mutant Samd9l locus on mouse chromosome 6, mimicking chromosome 7 deletions observed in patients. Collectively, our study has enhanced our understanding of mutant Samd9l hematopoietic phenotypes, emphasized the synergistic role of inflammation in exaggerating the associated hematopoietic defects, and provided insights into potential therapeutic options for patients.

Background: Chronic kidney disease (CKD)-associated pruritus is a common complicationin patients with end-stage renal disease. Objectives: To compare the capabilities of hemodialysis (HD) and ‏hemodiafiltration‏(HDF) in clearing toxins and their effects on pruritus inuremic patients. Patients and methods: The study included 40 adult subjects (18 years or older) who had maintenance dialysis for at least three months. Patients were divided into two groups: Group I: 20 patients underwent maintenance HDF (Intervention group), Group II: 20 patients underwent maintenance HD (Control group). Serum calcium levels, serum phosphorus levels, serum parathormone levels (PTH) and serum B2 microglobulin were assessed. The severity of pruritus measured by the visual analogue scale (VAS). Results: The prevalence of Uremic Pruritus in our study was 52.5% in all studied patients.We found a statistically significant difference (p-value < 0.05) between studied groups as regard Uremic Pruritis.The prevalence of UP was higher in HD group (70 %) in compare with HDF group (35 %). We found a Statistically significant difference (p-value < 0.05) between HDF group & HD group regard B2 mico-globulin &PTH. Levels of PTH and B2 microglobulin were significantly higher in HD group(175.2 ± 36.1pg/ml and 11.3 ± 2.1μg/ml, respectively) as compared with HDF group (207.9 ± 36.4pg/ml and 14.1 ± 4.04μg/ml, respectively). Conclusion: The prevalence and severity of Uremic Pruritus were significantlylower among HDF patients than HD patients. HDF can clear b2-MG and PTH and provide relief from pruritus efficiently more than HD.

Columnaris disease caused by Flavobacterium covae leads to substantial economic losses in commercially important fish species worldwide. The US channel catfish (Ictalurus punctatus) industry is particularly vulnerable to this disease. Therefore, there is an urgent need to develop a vaccine to reduce the economic losses caused by this disease. Secreted extracellular products (SEPs) are considered to be essential bacterial virulence factors that often provide immunogenicity and protection. The current study sought to identify the main SEPs of F. covae and to evaluate their potential to provide protection in channel catfish against columnaris disease. SDS-PAGE analysis of SEPs revealed five protein bands with molecular weights ranging from 13 to 99 kDa. Mass spectrometry analysis showed that these SEPs were hypothetical protein (AWN65_11950), zinc-dependent metalloprotease (AWN65_10205), DNA/RNA endonuclease G (AWN65_02330), outer membrane protein beta-barrel domain (AWN65_12620), and chondroitin-sulfate-ABC endolyase/exolyase (AWN65_08505). Catfish fingerlings were vaccinated with SEPs, SEPs emulsified with mineral oil adjuvant, or heat-inactivated SEPs, or they were sham-immunized through intraperitoneal (IP) injection. After 21 days, an F. covae challenge showed 58.77% and 46.17% survival in the catfish vaccinated with the SEPs and the SEPs emulsified with adjuvant compared to the sham-vaccinated control (100% mortality within 120 h post-infection). However, the heat-inactivated SEPs failed to provide significant protection (23.15% survival). In conclusion, although SEPs contain potentially important immunogenic proteins, further work is needed to optimize their use for long-lasting protection against columnaris disease in fish. These results are significant given the economic impact of columnaris disease on fish farming worldwide.

Virulent Aeromonas hydrophila (vAh) strains that cause motile Aeromonas septicemia (MAS) in farmed channel catfish (Ictalurus punctatus) have been an important problem for more than a decade. However, the routes of infection of vAh in catfish are not well understood. Therefore, it is critical to study the pathogenicity of vAh in catfish. To this goal, a new bioluminescence expression plasmid (pAKgfplux3) with the chloramphenicol acetyltransferase (cat) gene was constructed and mobilized into vAh strain ML09-119, yielding bioluminescent vAh (BvAh). After determining optimal chloramphenicol concentration, plasmid stability, bacteria number–bioluminescence relationship, and growth kinetics, the catfish were challenged with BvAh, and bioluminescent imaging (BLI) was conducted. Results showed that 5 to 10 µg/mL chloramphenicol was suitable for stable bioluminescence expression in vAh, with some growth reduction. In the absence of chloramphenicol, vAh could not maintain pAKgfplux3 stably, with the half-life being 16 h. Intraperitoneal injection, immersion, and modified immersion (adipose fin clipping) challenges of catfish with BvAh and BLI showed that MAS progressed faster in the injection group, followed by the modified immersion and immersion groups. BvAh was detected around the anterior mouth, barbels, fin bases, fin epithelia, injured skin areas, and gills after experimental challenges. BLI revealed that skin breaks and gills are potential attachment and entry portals for vAh. Once vAh breaches the skin or epithelial surfaces, it can cause a systemic infection rapidly, spreading to all internal organs. To our best knowledge, this is the first study that reports the development of a bioluminescent vAh and provides visual evidence for catfish–vAh interactions. Findings are expected to provide a better understanding of vAh pathogenicity in catfish.

Introduction: Most studies investigate sexual dysfunction in drug abusers; however, there are no data available about the pattern of drug abuse in patients with lifelong premature ejaculation (PE). Aim: To assess the pattern of drug abuse in patients with lifelong PE and to evaluate its potential effect on their hormonal profile. Methods: A cross-sectional study included patients with lifelong PE (n = 76) with no prescribed medications for 1 month and age-matched control without PE (n = 48). Participants were evaluated by history, examination, Arabic index of PE, and hormonal profile. A urine sample was screened by dipstick kits for the following drug abuse tramadol, opiate, tetrahydrocannabinol (cannabis), amphetamine, barbiturate, cocaine, and benzodiazepines. Positive results were confirmed with a immunoassay drug analyzer. Main outcome measures: The outcomes of this study are positive and negative drug abuse and hormonal profile changes. Results: Control patients and patients with PE showed median (interquartile range) of age 43 (33–46.8) and 38.5 (31–45) years, respectively. Drug abuse testing results showed significantly high positive drug abuse in patients with PE, 26 of 76 (34.2%), in comparison with control, 9 of 48 (19.1%) (P = .05). The most commonly abused drug was tetrahydrocannabinol in control, 3 of 9 (33.3%), and tramadol, 12 of 26 (46.2%), in patients with PE. Control patients and patients with PE with positive drug abuse had significantly higher smoking percent (P

Background Resident physicians in Sudan face a variety of physical and psychological stressors. Nevertheless, the prevalence of burnout syndrome among this critical population remains unknown. The purpose of this study was to estimate the prevalence rate of burnout and its associated factors in a sample of resident physicians in Sudan. Methods A cross-sectional design was used to assess the burnout syndrome among resident physicians at the teaching hospitals of Wad-Medani in Gezira state, east-central Sudan. Three hundred resident physicians at the dermatology, general surgery, pediatrics, obstetrics and gynecology, psychiatry, ear, nose and throat (ENT), oncology, urology, and internal medicine departments, were approached and invited to participate in the study. The Arabic version of the Maslach Burnout Inventory was distributed to respondents from July to October 2021. Results From the 300 resident physicians, 208 (69.3%) responded. The average age of the study population was 29.99 ± 3.01 years, with more than half were females (56.7%), single (59.6%), and with more than three years of residency experience (50.5%). In total, 86.1% met the criteria for burnout in at least one dimension and 13.9% in all three dimensions. On the dimension of emotional exhaustion (EE), 70.7% reported high levels of burnout. While, 44.2% reported high levels of depersonalization (DP), and 73.1% experienced a sense of decreased professional accomplishment (PA). There were significant differences in burnout, EE, and DP levels among different specialties, with the pediatrics-specialty trainees reported higher levels. Burnout syndrome was associated with the working hours per single duty; participants who reported working for more than 24 hours had experienced higher levels of burnout, EE, and DP. Conclusion Large-scale studies are required to assess the determinants of burnout syndrome among resident physicians in Sudan. In addition, Stakeholders should urgently implement effective remedies to protect the mental health of resident physicians.

Listeria monocytogenes is a ubiquitous opportunistic foodborne pathogen capable of survival in various adverse environmental conditions. Pathogenesis of L. monocytogenes is tightly controlled by a complex regulatory network of transcriptional regulators that are necessary for survival and adaptations to harsh environmental conditions both inside and outside host cells. Among these regulatory pathways are members of the DeoR-family transcriptional regulators that are known to play a regulatory role in sugar metabolism. In this study, we deciphered the role of FruR, a DeoR family protein, which is a fructose operon transcriptional repressor protein, in L. monocytogenes pathogenesis and growth. Following intravenous (IV) inoculation in mice, a mutant strain with deletion of fruR exhibited a significant reduction in bacterial burden in liver and spleen tissues compared to the parent strain. Further, the ΔfruR strain had a defect in cell-to-cell spread in L2 fibroblast monolayers. Constitutive activation of PrfA, a pleiotropic activator of L. monocytogenes virulence factors, did not restore virulence to the ΔfruR strain, suggesting that the attenuation was not a result of impaired PrfA activation. Transcriptome analysis revealed that FruR functions as a positive regulator for genes encoding enzymes involved in the pentose phosphate pathway (PPP) and as a repressor for genes encoding enzymes in the glycolysis pathway. These results suggested that FruR may function to facilitate NADPH regeneration, which is necessary for full protection from oxidative stress. Interestingly, deletion of fruR increased sensitivity of L. monocytogenes to H2O2, confirming a role for FruR in survival of L. monocytogenes during oxidative stress. Using anti-mouse neutrophil/monocyte monoclonal antibody RB6-8C5 (RB6) in an in vivo infection model, we found that FruR has a specific function in protecting L. monocytogenes from neutrophil/monocyte-mediated killing. Overall, this work clarifies the role of FruR in controlling L. monocytogenes carbon flow between glycolysis and PPP for NADPH homeostasis, which provides a new mechanism allowing metabolic adaptation of L. monocytogenes to oxidative stress.

Primary ciliary dyskinesia (PCD) is a human condition of dysfunctional motile cilia characterized by recurrent lung infection, infertility, organ laterality defects and partially penetrant hydrocephalus. We recovered a mouse mutant from a forward genetic screen that developed many of the hallmark phenotypes of PCD. Whole-exome sequencing identified this primary ciliary dyskinesia only (Pcdo) allele to be a nonsense mutation (c.5236A>T) in the Spag17 coding sequence creating a premature stop codon (K1746*). The Pcdo variant abolished several isoforms of SPAG17 in the Pcdo mutant testis but not in the brain. Our data indicate differential requirements for SPAG17 in different types of motile cilia. SPAG17 is essential for proper development of the sperm flagellum and is required for either development or stability of the C1 microtubule structure within the central pair apparatus of the respiratory motile cilia, but not the brain ependymal cilia. We identified changes in ependymal ciliary beating frequency, but these did not appear to alter lateral ventricle cerebrospinal fluid flow. Aqueductal stenosis resulted in significantly slower and abnormally directed cerebrospinal fluid flow, and we suggest that this is the root cause of the hydrocephalus. The Spag17Pcdo homozygous mutant mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Our data indicate that the c.5236A>T Pcdo variant is a hypomorphic allele of Spag17 that causes phenotypes related to motile, but not primary, cilia. Spag17Pcdo is a useful new model for elucidating the molecular mechanisms underlying central pair PCD pathogenesis in the mouse. This article has an associated First Person interview with the first author of the paper.

Aeromonas veronii is a gram-negative species abundant in aquatic environments that causes disease in humans as well as terrestrial and aquatic animals. In the current study, 41 publicly available A. veronii genomes were compared to investigate distribution of putative virulence genes, global dissemination of pathotypes, and potential mechanisms of virulence. The complete genome of A. veronii strain ML09-123 from an outbreak of motile aeromonas septicemia in farm-raised catfish in the southeastern United States was included. Dissemination of A. veronii strain types was discovered in dispersed geographical locations. Isolate ML09-123 is highly similar to Chinese isolate TH0426, suggesting the two strains have a common origin and may represent a pathotype impacting aquaculture in both countries. Virulence of strain ML09-123 in catfish in a dose-dependent manner was confirmed experimentally. Subsystem category disposition showed the majority of genomes exhibit similar distribution of genomic elements. The type I secretion system (T1SS), type II secretion system (T2SS), type 4 pilus (T4P), and flagellum core elements are conserved in all A. veronii genomes, whereas the type III secretion system (T3SS), type V secretion system (T5SS), type VI secretion system (T6SS), and tight adherence (TAD) system demonstrate variable dispersal. Distribution of mobile elements is dependent on host and geographic origin, suggesting this species has undergone considerable genetic exchange. The data presented here lends insight into the genomic variation of A. veronii and identifies a pathotype impacting aquaculture globally.

Ciliopathies are a group of developmental disorders that manifest with multi-organ anomalies. Mutations in TMEM67 (MKS3) cause a range of human ciliopathies, including Meckel-Gruber and Joubert syndromes. In this study we describe multi-organ developmental abnormalities in the Tmem67tm1Dgen/H1 knockout mouse that closely resemble those seen in Wnt5a and Ror2 knockout mice. These include pulmonary hypoplasia, ventricular septal defects, shortening of the body longitudinal axis, limb abnormalities, and cochlear hair cell stereociliary bundle orientation and basal body/kinocilium positioning defects. The basal body/kinocilium complex was often uncoupled from the hair bundle, suggesting aberrant basal body migration, although planar cell polarity and apical planar asymmetry in the organ of Corti were normal. TMEM67 (meckelin) is essential for phosphorylation of the non-canonical Wnt receptor ROR2 (receptor-tyrosine-kinase-like orphan receptor 2) upon stimulation with Wnt5a-conditioned medium. ROR2 also colocalises and interacts with TMEM67 at the ciliary transition zone. Additionally, the extracellular N-terminal domain of TMEM67 preferentially binds to Wnt5a in an in vitro binding assay. Cultured lungs of Tmem67 mutant mice failed to respond to stimulation of epithelial branching morphogenesis by Wnt5a. Wnt5a also inhibited both the Shh and canonical Wnt/β-catenin signalling pathways in wild-type embryonic lung. Pulmonary hypoplasia phenotypes, including loss of correct epithelial branching morphogenesis and cell polarity, were rescued by stimulating the non-canonical Wnt pathway downstream of the Wnt5a-TMEM67-ROR2 axis by activating RhoA. We propose that TMEM67 is a receptor that has a main role in non-canonical Wnt signalling, mediated by Wnt5a and ROR2, and normally represses Shh signalling. Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital conditions.

Listeria monocytogenes is an intracellular facultative pathogen that causes listeriosis, a foodborne zoonotic infection. There are differences in the pathogenic potential of L. monocytogenes subtypes and strains. Comparison of the genome sequences among L. monocytogenes pathogenic strains EGD-e and F2365 with nonpathogenic L. innocua CLIP1182 and L. monocytogenes strain HCC23 revealed a set of proteins that were present in pathogenic strains and had no orthologs among the nonpathogenic strains. Among the candidate virulence factors are five proteins: putrescine carbamoyltransferase; InlH/InlC2 family class 1 internalin; phosphotransferase system (PTS) fructose transporter subunit EIIC; putative transketolase; and transcription antiterminator BglG family. To determine if these proteins have a role in adherence and invasion of intestinal epithelial Caco-2 cells and/or contribute to virulence, five mutant strains were constructed. F2365ΔinlC2, F2365Δeiic, and F2365Δtkt exhibited a significant (p < 0.05) reduction in adhesion to Caco-2 cells compared to parent F2365 strain. The invasion of F2365ΔaguB, F2365ΔinlC2, and F2365ΔbglG decreased significantly (p < 0.05) compared with the parent strain. Bacterial loads in mouse liver and spleen infected by F2365 was significantly (p < 0.05) higher than it was for F2365ΔaguB, F2365ΔinlC2, F2365Δeiic, F2365Δtkt, and F2365ΔbglG strains. This study demonstrates that aguB, inlC2, eiic, tkt, and bglG play a role in L. monocytogenes pathogenicity.

Introduction: Erectile dysfunction (ED) can precede coronary artery disease. In addition, silent myocardial ischemia (SMI) is more common in diabetic patients and is a strong predictor of cardiac events and death. Aim: To evaluate the presence of SMI in patients with diabetes and ED using multidetector computed tomographic coronary angiography (MDCT-CA). Methods: This study evaluated patients with diabetes and ED without any history of cardiac symptoms or signs. Erectile function was evaluated with the Sexual Health Inventory for Men score, erection hardness score (EHS), and maximal penile circumferential change by an erectometer. MDCT-CA was used for the detection of coronary artery stenosis. Main Outcome Measures: Sexual Health Inventory for Men score, EHS, maximal penile circumferential change, and coronary artery stenosis by MDCT-CA. Results: Of 20 patients (mean age = 61.45 ± 10.7 years), MDCT-CA showed coronary artery stenosis in 13 (65%) in the form of one-vessel disease (n = 6, 30%), two-vessel disease (n = 2, 10%), and three-vessel disease (n = 5, 25%). Fifty percent of patients showed at least 50% vessel lumen obstruction of the left anterior descending coronary artery, which was the most commonly affected vessel (55%). Fifteen percent (3 of 20) of patients had greater than 90% stenosis, and two of them underwent an immediate coronary angioplasty with stenting to prevent myocardial infarction. Maximum coronary artery stenosis was positively correlated with age (P = 0.016, r = 0.529) and negatively correlated with EHS (P = .046, r = −0.449). Multivariate regression analysis using age and EHS showed that age was the only independent predictor of SMI (P = .04). Conclusion: MDCT-CA can be a useful tool to identify SMI in diabetic patients with ED, especially in those of advanced age and/or with severe ED.