The Association of Cytokines IL-2, IL-6, TNF-α, IFN-γ, and IL-10 With the Disease Severity of COVID-19: A Study From Bangladesh.

Introduction Clinically, the early prediction of the severity of COVID-19 is often challenging, as a dramatic change in severity can occur without warning. The severity of COVID-19 disease is associated with an increased level of inflammatory mediators, including cytokines. This study aimed to evaluate the association of the levels of cytokines interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10 with the severity of COVID-19 in Bangladesh. Materials and methods This cross-sectional study included a total of 60 confirmed cases of COVID-19, comprising 30 severe cases (Group A) and 30 non-severe cases (Group B), and 10 healthy individuals (Group C) attending Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2021 to February 2022. The cytokine assay was performed using the human Th1/Th2/Th17 cytokine kit BD cytometric bead array (CBA) on the BD Accuri C6 Plus flow cytometer. Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York). Results The mean ages of the patients in Groups A, B, and C were 60.73±5.97, 57.13±7.68, and 48.10±9.13 years, respectively, with a male predominance in all groups. The mean IL-2, IL-6, IL-10, and TNF-α levels had a positive correlation with the increased age group and male gender, although it was not statistically significant. The mean IL-6 and IFN-γ levels were significantly higher among severe cases (216.95±147.78 and 0.98±0.95 pg/mL, respectively) compared to non-severe cases (94.29±128.79 and 0.41±0.61 pg/mL, respectively) and healthy individuals (1.08±1.97 and 0.15±0.28 pg/mL, respectively). Furthermore, the anti-inflammatory cytokine IL-10 was also significantly higher among severe cases (17.92±21.87 pg/mL) compared to non-severe cases (5.38±6.73 pg/mL) and healthy individuals (1.62±1.65 pg/mL). Conclusion IL-6, IFN-γ, and IL-10 have a significant association with the severity of COVID-19 disease. Clinicians treating patients with COVID-19 can consider the level of these cytokines as biomarkers of severity.

Lamina Cribrosa Insertions Into the Sclera Are Sparser, Narrower, and More Slanted in the Anterior Lamina.

Purpose: The lamina cribrosa (LC) depends on the sclera for support. The support must be provided through the LC insertions. Although a continuous insertion over the whole LC periphery is often assumed, LC insertions are actually discrete locations where LC collagenous beams meet the sclera. We hypothesized that LC insertions vary in number, size, and shape by quadrant and depth. Methods: Coronal cryosections through the full LCs from six healthy monkey eyes were imaged using instant polarized light microscopy. The images were registered into a stack, on which we manually marked LC insertion outlines, nothing their position in-depth and quadrant (inferior, superior, nasal, or temporal). From the marks, we determined the insertion number, width, angle to the canal wall (90 degrees = perpendicular), and insertion ratio (fraction of LC periphery represented by insertions). Using linear mixed effect models, we determined if the insertion characteristics were associated with depth or quadrant. Results: Insertions in the anterior LC were sparser, narrower, and more slanted than those in deeper LC (P values < 0.001). There were more insertions spanning a larger ratio of the canal wall in the middle LC than in the anterior and posterior (P values < 0.001). In the nasal quadrant, the insertion angles were significantly smaller (P < 0.001). Conclusions: LC insertions vary substantially and significantly over the canal. The sparser, narrower, and more slanted insertions of the anterior-most LC may not provide the robust support afforded by insertions of the middle and posterior LC. These variations may contribute to the progressive deepening of the LC and regional susceptibility to glaucoma.

Fibrous finite element modeling of the optic nerve head region.

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. STATEMENT OF SIGNIFICANCE: The microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

Difference in presentation, outcomes, and hospital epidemiologic trend of COVID-19 among first, second, and third waves: a review of hospital records and prospective cohort study.

This study aimed to examine the differences in epidemiologic and disease aspects among patients with coronavirus disease-19 (COVID-19). Methods: The authors reviewed the hospital records between April 2020 and September 2021 and followed up on the patients for post-COVID complications. Findings: Older adult patients were predominantly affected during the third wave, and middle-aged patients were predominantly affected during the first and second waves. Men were predominantly admitted, considering the three waves, although more women were admitted in the second wave. Cough was more common in the second and third waves than in the first wave 522 (59.7%). Respiratory distress was the most common in the third wave, 251(67.1%), and least common in the first wave, 403 (46.1%). Anosmia was more common in the third wave 116 (31.2%). In the third wave, patients presenting in a critical state 23 (6.2%) and with severe disease 152 (40.8%) were more common. The hospital admission median (IQR) was longer in the first wave, 12 (8-20), than in other waves. More patients were admitted in the first wave (52%) than in the other waves, and patients received more oxygen in the third wave (75%) than in the other waves. Death occurred more commonly in the first wave (51%) than in the other waves. The positivity rate was higher in the third wave (22.8%) than in the other waves. In the third wave, the positivity rate was higher in women (24.3%) than in men. Post-COVID cough increased in the second wave, and fatigue was higher in the third wave than in the other waves. Tiredness and memory loss were greater during the second wave than in other waves. Conclusion: The authors found differences in the presentation, outcomes, and hospital epidemiologic trend of COVID-19 among the three waves.

A direct fiber approach to model sclera collagen architecture and biomechanics.

Sclera collagen fiber microstructure and mechanical behavior are central to eye physiology and pathology. They are also complex, and are therefore often studied using modeling. Most models of sclera, however, have been built within a conventional continuum framework. In this framework, collagen fibers are incorporated as statistical distributions of fiber characteristics such as the orientation of a family of fibers. The conventional continuum approach, while proven successful for describing the macroscale behavior of the sclera, does not account for the sclera fibers are long, interwoven and interact with one another. Hence, by not considering these potentially crucial characteristics, the conventional approach has only a limited ability to capture and describe sclera structure and mechanics at smaller, fiber-level, scales. Recent advances in the tools for characterizing sclera microarchitecture and mechanics bring to the forefront the need to develop more advanced modeling techniques that can incorporate and take advantage of the newly available highly detailed information. Our goal was to create a new computational modeling approach that can represent the sclera fibrous microstructure more accurately than with the conventional continuum approach, while still capturing its macroscale behavior. In this manuscript we introduce the new modeling approach, that we call direct fiber modeling, in which the collagen architecture is built explicitly by long, continuous, interwoven fibers. The fibers are embedded in a continuum matrix representing the non-fibrous tissue components. We demonstrate the approach by doing direct fiber modeling of a rectangular patch of posterior sclera. The model integrated fiber orientations obtained by polarized light microscopy from coronal and sagittal cryosections of pig and sheep. The fibers were modeled using a Mooney-Rivlin model, and the matrix using a Neo-Hookean model. The fiber parameters were determined by inversely matching experimental equi-biaxial tensile data from the literature. After reconstruction, the direct fiber model orientations agreed well with the microscopy data both in the coronal plane (adjusted R2 = 0.8234) and in the sagittal plane (adjusted R2 = 0.8495) of the sclera. With the estimated fiber properties (C10 = 5746.9 MPa; C01 = -5002.6 MPa, matrix shear modulus 200 kPa), the model's stress-strain curves simultaneously fit the experimental data in radial and circumferential directions (adjusted R2's 0.9971 and 0.9508, respectively). The estimated fiber elastic modulus at 2.16% strain was 5.45 GPa, in reasonable agreement with the literature. During stretch, the model exhibited stresses and strains at sub-fiber level, with interactions among individual fibers which are not accounted for by the conventional continuum methods. Our results demonstrate that direct fiber models can simultaneously describe the macroscale mechanics and microarchitecture of the sclera, and therefore that the approach can provide unique insight into tissue behavior questions inaccessible with continuum approaches.

Exercise hormone irisin is a critical regulator of cognitive function.

Identifying secreted mediators that drive the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in ageing or Alzheimer's disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function. Genetic deletion of Fndc5/irisin (global Fndc5 knock-out (KO) mice; F5KO) impairs cognitive function in exercise, ageing and AD. Diminished pattern separation in F5KO mice can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of the cognitive benefits of exercise and is a potential therapeutic agent for treating cognitive disorders including AD.

ErbB3 is a critical regulator of cytoskeletal dynamics in brain microvascular endothelial cells: Implications for vascular remodeling and blood brain barrier modulation.

Neuregulin (NRG)1 - ErbB receptor signaling has been shown to play an important role in the biological function of peripheral microvascular endothelial cells. However, little is known about how NRG1/ErbB signaling impacts brain endothelial function and blood-brain barrier (BBB) properties. NRG1/ErbB pathways are affected by brain injury; when brain trauma was induced in mice in a controlled cortical impact model, endothelial ErbB3 gene expression was reduced to a greater extent than that of other NRG1 receptors. This finding suggests that ErbB3-mediated processes may be significantly compromised after injury, and that an understanding of ErbB3 function would be important in the of study of endothelial biology in the healthy and injured brain. Towards this goal, cultured brain microvascular endothelial cells were transfected with siRNA to ErbB3, resulting in alterations in F-actin organization and microtubule assembly, cell morphology, migration and angiogenic processes. Importantly, a significant increase in barrier permeability was observed when ErbB3 was downregulated, suggesting ErbB3 involvement in BBB regulation. Overall, these results indicate that neuregulin-1/ErbB3 signaling is intricately connected with the cytoskeletal processes of the brain endothelium and contributes to morphological and angiogenic changes as well as to BBB integrity.

Pathology of an outbreak of highly pathogenic avian influenza A(H5N1) virus of clade 2.3.2.1a in turkeys in Bangladesh.

A mixed-aged flock of 130 turkeys in Bangladesh reported the sudden death of 1 bird in September 2017. Highly pathogenic avian influenza A(H5N1) virus was detected in 3 turkeys, and phylogenetic analysis placed the viruses in the reassortant clade 2.3.2.1a. The birds had clinical signs of depression, diarrhea, weakness, closed eyes, and finally death. The mortality rate of the flock was 13% over the 6 d prior to the flock being euthanized. At autopsy, we observed congestion in lungs and brain, hemorrhages in the trachea, pancreas, breast muscle, coronary fat, intestine, bursa of Fabricius, and kidneys. Histopathology revealed hemorrhagic pneumonia, hemorrhages in the liver and kidneys, and hemorrhages and necrosis in the spleen and pancreas. Significant changes in the brain included gliosis, focal encephalomalacia and encephalitis, and neuronophagia.

Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice.

BACKGROUND: Despite considerable research on exercise-induced neuroplasticity in the brain, a major ongoing challenge in translating findings from animal studies to humans is that clinical and preclinical settings employ very different techniques. OBJECTIVE: Here we aim to bridge this divide by using diffusion tensor imaging MRI (DTI), an advanced imaging technique commonly applied in human studies, in a longitudinal exercise study with mice. METHODS: Wild-type mice were exercised using voluntary free-wheel running, and MRI scans were at baseline and after four weeks and nine weeks of running. RESULTS: Both hippocampal volume and fractional anisotropy, a surrogate for microstructural directionality, significantly increased with exercise. In addition, exercise levels correlated with effect size. Histological analysis showed more PDGFRα+ oligodendrocyte precursor cells in the corpus callosum of running mice. CONCLUSIONS: These results provide compelling in vivo support for the concept that similar adaptive changes occur in the brains of mice and humans in response to exercise.

Identification and characterization of high-yielding, short-duration rice genotypes for tropical Asia.

Previous efforts to increase the yield of tropical rice (Oryza sativa L.) have focused on medium-duration varieties. However, there is increasing demand for high-yielding short-duration varieties that can adapt to intensified cropping systems and climate change. Our goal was to identify physiological traits associated with high yield in elite short-duration genotypes suitable for tropical Asia. We conducted field experiments in five consecutive growing seasons at the International Rice Research Institute, the Philippines. We selected genotypes in the first two seasons, then performed a detailed characterization of the most promising genotypes in the following three seasons. Of the 50 advanced-generation genotypes, three had consistently high yield and early maturity, with yields 11 to 38% higher than that of 'IRRI104' ('IR50404-57-2-2-3'), a short-duration variety that is widely grown in Southeast Asia. These genotypes were 20 to 32 cm taller than IRRI104. We found that for grain growth, low source capacity, defined as stem nonstructural carbohydrates at heading plus biomass accumulation after heading, was the major factor for the low yield of IRRI104. Although sink capacity (spikelets m-2 × grain weight) in the promising genotypes was comparable to that of IRRI104, they had a 25 to 53% higher source-sink ratio (source capacity/sink capacity) than IRRI104, which was attributed to larger leaf area and greater biomass accumulation during the grain-filling stage. This result suggests that slight changes in plant development to promote height combined with increased leaf area around heading would improve the yield of short-duration rice varieties in tropical Asia.

The effect of adding graphene oxide nanoplatelets to Portland cement: Potential for dental applications.

BACKGROUND: The potential of graphene-based materials to improve the physiomechanical properties of Portland cement-based materials without compromising biocompatibility is of interest to dental researchers and remains to be discovered. AIM: This study investigated the effects of adding graphene oxide nanoplatelets (GONPs) on the surface microhardness and biocompatibility of Portland cement. MATERIALS AND METHODS: Three prototype Portland cement powder formulations were prepared by adding 0, 1, and 3 wt % GONPs in powder form to Portland cement. Prototype cement specimens were in the form of disks, with a diameter of 10 mm and a thickness of 2 mm. In experiment 1, surface microhardness was measured using the through indenter viewing hardness tester, 20 surface hardness values were obtained from all specimens. In experiment 2, Balb/C 3T3 fibroblasts were cultured with the material disks and the viability of cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. STATISTICAL ANALYSIS: The data were analyzed using the analysis of variance followed by Dunnett test (α = 0.05) or Tukey test (α = 0.05). RESULTS: In response to material disks, the addition of 1 wt % GONPs had a proliferative effect on cells at day 3 and day 7 with a significant difference from the control. The addition of 3 wt % GONPs showed a remarkable increase in surface microhardness; however, it exhibited initial cytotoxicity. CONCLUSIONS: The addition of 1 wt % GONPs to Portland cement improved surface microhardness without compromising biocompatibility; therefore, it has a greater potential for dental applications. The results of this work give other researchers leads in future assessments of this prototype material.

Micromechanical poroelastic and viscoelastic properties of ex-vivo soft tissues.

Soft biological tissues demonstrate strong time-dependent mechanical behavior, arising from their intrinsic viscoelasticity and fluid flow-induced poroelasticity. It is increasingly recognized that time-dependent mechanical properties of soft tissues influence their physiological functions and are linked to several pathological processes. Nevertheless, soft tissue time-dependent characteristics, especially their micromechanical variation with tissue composition and location, remain poorly understood. Nanoindentation is a well-established technique to measure local elastic properties but has not been fully explored to determine micro-scale time-dependent properties of soft tissues. Here, a nanoindentation-based experimental strategy is implemented to characterize the micro-scale poroelastic and viscoelastic behavior of mouse heart, kidney, and liver tissues. It is demonstrated that heart tissue exhibits substantial mechanical heterogeneity where the elastic modulus varies spatially from 1 to 30 kPa. In contrast, both kidney and liver tissues show relatively homogeneous response with elastic modulus 0.5-3 kPa. All three tissues demonstrate marked load relaxation under constant indentation, where the relaxation behavior is observed to be largely dominated by tissue viscoelasticity. Intrinsic permeability varies among different tissues, where heart tissue is found to be less permeable compared to kidney and liver tissues. Overall, the results presented herein provide key insights into the time-dependent micromechanical behavior of different tissues and can therefore contribute to studies of tissue pathology and tissue engineering applications.

Biochemical and histopathological effects of mobile phone radiation on the liver of Swiss albino mice

The electromagnetic radiation from the mobile phone is a subject of recent study because of the enormous increase in mobile phone use through-out the world. The objective of this experiment was therefore to investigate the biochemical and histopathological effects of mobile phone radiation on male Swiss albino mice’s liver. Male mice were categorized into three groups in this research: control group (A), exposed group for 40 minutes (B) and exposed group for 60 minutes (C). Experimental groups were exposed to radiation per day for 60 days from 4G connected mobile phones. The control group received no radiation. At the end of the radiation exposure, biochemical (alanine transaminase (ALT) and aspartate transaminase (AST)) and histological tests were performed. The results indicated that there was significant (P < 0.05) increase in mean values of ALT and AST in both radiation-exposed groups of mice if com-pared to the control group. Histopathologically marked infiltration of mononuclear cellular aggregates were present surrounding the bile duct and hepatic artery in the liver of 60-minute-exposure group, whereas in 40-minute-exposure group con-gestion was observed in the portal vein and the central vein of the liver. The findings revealed and evidenced that mobile phone radiation has harmful effects on enzyme activity and liver tis

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Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage.

OBJECTIVE: To determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia. METHODS: Serial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied. RESULTS: sVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1ß, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial-cadherin fragments. CONCLUSIONS: These results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

Proteome Analyses Reveal Macrophomina phaseolina's Survival Tools When Challenged by Burkholderia contaminans NZ.

A phytopathogenic fungus, Macrophomina phaseolina, which infects a wide range of plants, is an important consideration in agronomy. A jute endophytic bacterium, Burkholderia contaminans NZ, was found to have a promising effect in controlling the fungus in in vitro culture conditions. Using the iTRAQ LC-MS/MS method for quantitative proteomics study, an analysis of the whole proteome of Macrophomina phaseolina with or without B. contaminans NZ challenge identified 2204 different proteins, of which 137 were found to have significant deviation in expression. Kyoto encyclopedia of genes and genomes pathway analysis identified most of the upregulated proteins to be functionally related to energy production (26.11%), as well as defense and stress response (23.45%), while there was significant downregulation in oxidative stress protection pathways (42.61%), growth and cell wall integrity (30.95%), and virulence (23.81%). Findings of this study suggest the development of a battle when the phytopathogen encounters the bacterium. B. contaminans NZ manages to arrest the growth of the fungus and decrease its pathogenicity, but the fungus apparently survives under "hibernating" conditions by upregulating its energy metabolism. This first ever proteomic study of M. phaseolina will go a long way in understanding and developing strategies for its effective control.

Peste des petits ruminants virus infection of Black Bengal goats showed altered haematological and serum biochemical profiles.

In Bangladesh, veterinarians often claim to reduce the mortality of natural peste des petits ruminants (PPR) outbreaks with the help of supportive fluid and electrolyte therapy. Information on haematological and biochemical parameters of PPR-infected goats, which is often altered because of associated tissue damages, is necessary to formulate the appropriate supportive therapy. This study determined the haematological and serum biochemical parameters of Black Bengal goats naturally infected with PPR virus. Blood and serum samples from 13 PPR-affected Black Bengal goats from 13 field outbreaks and 5 healthy goats were collected and analysed by routine haematological and biochemical examination. Haematological analysis of PRR-affected goats showed severe anaemia characterised by significant decrease in the values of haemoglobin, total erythrocyte counts (TECs) and packed cell volume (PCV). On the contrary, PPR-affected goats showed marked leucocytosis with absolute increase in lymphocytes and neutrophils counts compared to the healthy goats. Biochemical analysis revealed significant decrease in total protein and albumin level and increased creatine kinase, aspartate transaminase and alanine transaminase that mirrored the gross and histopathological changes in the PPR-affected goats. Significant increase in the values of sodium and chloride ions was found in the sera of PPR-infected goats. Peste des petits ruminants virus altered the haematological and serum biochemical parameters of the infected goats. Antidiarrheal agents with aqua solution together with other drugs to support liver and kidney function could help improve therapy of PPR-infected goats.

The lantibiotic nukacin ISK-1 exists in an equilibrium between active and inactive lipid-II binding states.

The lantibiotic nukacin ISK-1 exerts antimicrobial activity through binding to lipid II. Here, we perform NMR analyses of the structure of nukacin ISK-1 and the interaction with lipid II. Unexpectedly, nukacin ISK-1 exists in two structural states in aqueous solution, with an interconversion rate on a time scale of seconds. The two structures differ in the relative orientations of the two lanthionine rings, ring A and ring C. Chemical shift perturbation induced by the titration of lipid II reveals that only one state was capable of binding to lipid II. On the molecular surface of the active state, a multiple hydrogen-bonding site formed by amino acid residues in the ring A region is adjacent to a hydrophobic surface formed by residues in the ring C region, and we propose that these sites interact with the pyrophosphate moiety and the isoprene chain of the lipid II molecule, respectively.

Phylogeography of Diaphorina citri (Hemiptera: Liviidae) and its primary endosymbiont, 'Candidatus Carsonella ruddii': an evolutionary approach to host-endosymbiont interaction.

BACKGROUND: In insects, little is known about the co-evolution between their primary endosymbionts and hosts at the intraspecific level. This study examined co-diversification between the notorious agricultural pest Diaphorina citri and its primary endosymbionts (P-endosymbiont), 'Candidatus Carsonella ruddii' at the population level. RESULTS: Maximum likelihood, haplotype network, principal components and Bayesian clustering identified three lineages for D. citri and its P-endosymbiont: a Western clade containing individuals from Pakistan, Bhutan (Phuentsholing), Vietnam (Son La), USA, Myanmar and China (Ruili, Yunnan); a Central clade, with accessions originating from Southwest China, Bhutan (Tsirang) and Bangladesh; and an Eastern clade containing individuals from Southeast Asia, and East and South China. A more diverse genetic structure was apparent in the host mitochondrial DNA than their P-endosymbionts; however, the two sets of data were strongly congruent. CONCLUSION: This study provides evidence for the co-diversification of D. citri and its P-endosymbiont during the migration from South Asia to East and Southeast Asia. We also suggest that the P-endosymbiont may facilitate investigations into the genealogy and migration history of the host. The biogeography of D. citri and its P-endosymbiont indicated that D. citri colonized and underwent a secondary dispersal from South Asia to East and Southeast Asia. © 2018 Society of Chemical Industry.

LiaRS reporter assay: A simple tool to identify lipid II binding moieties in lantibiotic nukacin ISK-1.

Binding to lipid II is an important step in the mode of action of most lantibiotics targeting the bacterial cell wall. We applied the Bacillus subtilis two-component system, LiaRS, that is known to respond to antibiotics interfering with lipid II cycle, in order to evaluate lipid II binding activity of known bacteriocins and also to identify lipid II binding moieties in lantibiotic nukacin ISK-1. Using this method, we confirmed that the methyllanthionine ring in nukacin ISK-1 is crucial for lipid II binding as previously indicated. In this study, we further identified that the three N-terminal lysine residues (K1, K2, and K3) and the glycine (G5) residue in nukacin ISK-1 are also important in lipid II binding.