Bacillus tequilensis influences metabolite production in tomato and restores soil microbial diversity during Fusarium oxysporum infection.

This study evaluates cellular damage, metabolite profiling, and defence-related gene expression in tomato plants and soil microflora during Fusarium wilt disease after treatment with B. tequilensis PBE-1. Histochemical analysis showed that PBE-1 was the primary line of defence through lignin deposition and reduced cell damage. GC-MS revealed that PBE-1 treatment ameliorated stress caused by F. oxysporum infection. PBE-1 also improved transpiration, photosynthesis, and stomatal conductance in tomato. qRT-PCR suggested that the defence-related genes FLS2, SERK, NOS, WRKYT, NHO, SAUR, and MYC2, which spread infection, were highly upregulated during F. oxysporum infection, but either downregulated or expressed normally in PBE-1 + P treated plants. This indicates that the plant not only perceives the bio-control agent as a non-pathogen entity but its presence in normal metabolism and gene expression within the host plant is maintained. The study further corroborated findings that application of PBE-1 does not cause ecological disturbances in the rhizosphere. Activity of soil microflora across four treatments, measured by Average Well Colour Development (AWCD), showed continuous increases from weeks 1 to 4 post-pathogen infection, with distinct substrate usage patterns like tannic and fumaric acids impacting microbial energy source utilization and diversity. Principal Component Analysis (PCA) and diversity indices like McIntosh, Shannon, and Simpson further illustrated significant microbial community shifts over the study period. In conclusion, our findings demonstrate that B. tequilensis PBE-1 is an ideal bio-agent for field application during Fusarium wilt disease management in tomato.

The cost of childhood atopic dermatitis in a multi-ethnic Asian population: a cost-of-illness study.

BACKGROUND: Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. OBJECTIVES: The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. METHODS: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. RESULTS: The average annual cost per child with atopic dermatitis was estimated at U.S. dollars (USD) 7943 (mild USD 6651, moderate USD 7935 and severe USD 14 335) in 2017 prices. The major cost was for informal caregiving (46% of the total cost) followed by out-of-pocket expenses (37%). Healthcare utilization contributed to 17% of the total cost of which 43% was for medications. CONCLUSIONS: Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The costs related to atopic dermatitis are also strongly related to disease severity. This information is important for policy makers and other health planners when considering how to better support affected families. What's already known about the topic? Childhood atopic dermatitis is a costly disease for society. However, comprehensive cost estimations are lacking. Previous cost studies are old, based on small sample sizes or are healthcare-setting specific. What does this study add? This study comprises a health economic evaluation assessing different levels of care and includes various categories of costs. The result showed that informal caregiving was the most prominent cost for children with atopic dermatitis.

Simultaneous robotic assisted laparoscopic prostatectomy (RALP) and inguinal herniorrhaphy (IHR): proof-of-concept analysis from a high-volume center.

PURPOSE: Inguinal hernia (IH) is detected in approximately 33% of RALP's either pre or intraoperatively wherein all are repaired during RALP to circumvent future herniorrhaphy (Fukuta et al., Urology 68(2):267-271, 2006; Nielsen, Urology 66(5):1034-1037, 2005). Some debate this policy by quoting the potential risk of mesh lying close to the vesicourethral anastomosis leading to infections and adhesions. The current study was initiated to elucidate the feasibility and outcomes of simultaneous inguinal herniorrhaphy (IHR) during RALP. METHODS: Historic analysis of prospectively maintained data of 1224 RALP patients, as per inclusion criteria, between 2012 and 2017 was done, among whom 143 patients had a concurrent IHR using 3DmaxTM polypropylene monofilament mesh. Patients were then compared for demographics, peri-operative features, and outcomes. RESULTS: The mean age and AUA score were significantly different (p < 0.002, p < 0.01 respectively) between patients undergoing only RALP and RALP with IHR. BMI was not significantly different. One hundred forty-three patients (11.6%) underwent IHR at 155 hernial sites, 12 sites being bilateral. One hundred and one sites (65.2%) were diagnosed intraoperatively. The mean console time was 67.4 ± 11.5 min for RALP which increased by 6.9 ± 10.7 min in unilateral and by 10.7 ± 8.6 min in bilateral IHR. There were no mesh-associated or Clavien Dindo class II-V complications. Mean follow-up was 36 ± 1.4 months with no recurrences. CONCLUSION: This study reiterates the feasibility and advisability of repairing most inguinal hernias encountered during RALP as it is without any significant alteration of peri-operative morbidity, is associated with excellent post-operative outcomes, and obviates the need for a future surgical procedure.

Reverse indentation size effects in gamma irradiated blood compatible blend films of chitosan-poly (vinyl alcohol) for possible medical applications.

In the present work binary blends of polyvinyl alcohol (PVA) and chitosan (CS) were prepared by solution cast method and characterized by analytical methods like FTIR, XRD and SEM for seeking structural and morphological information. The blends were exposed to gamma radiation and evaluated for their improved mechanical strength. It was found that the tensile strength and microhardness increased after irradiation of CS-PVA films. Plastic effect due to absorption of water molecules and scissoring effect due to gamma irradiation were found to decrease the softness or increase the microhardness of the blends. Improved mechanical properties were attributed to intermolecular and intramolecular hydrogen bonds and adhesive nature of the blends also. The blends were also investigated for water intake behavior and in vitro blood compatibility property on the basis of certain in vitro tests like protein adsorption, haemolysis and blood clot formation on the un-irradiated and irradiated blend samples. The increased % swelling with time could be assigned to the fact that increasing water content facilitates the phase separation process within the blend which results in advancement in interstitial nano-void spaces which are occupied by water molecules. The blood compatibility results showed that when the amount of CS was varied from 0.5% to 2%, the amount of blood clot and percent haemolysis decreased while the protein adsorption increased with increasing CS content of the blend films.

Diffusion of Na(I), Cs(I), Sr(II) and Eu(III) in smectite rich natural clay.

Diffusion of Na(I), Cs(I), Sr(II) and Eu(III) in smectite rich natural clay, proposed as a backfill material in the Indian geological repository, was studied using the out-diffusion method. Radiotracers (22)Na, (137)Cs, (85)Sr and (154)Eu were used; the first three are carrier-free enabling experimental work at sub-micromolar metal ion concentration, and Eu(III) tracer (154)Eu was used at sub millimolar concentration. An out-diffusion methodology, wherein a thin planar source of radioactivity placed between two clay columns diffuses out, was used to obtain the apparent diffusion coefficient (Da) values. This methodology enabled determination of diffusion coefficient even for strongly sorbing (154)Eu. Da values for (22)Na, (137)Cs, (85)Sr and (154)Eu were 2.35 (±0.14) × 10(-11), 2.65 (±0.09) × 10(-12), 3.32 (±0.15) × 10(-11) and 1.23 (±0.15) × 10(-13) m(2) s(-1), respectively. Da values were found to be in fair agreement with literature data reported for similar mineralogical sediments. Sorption of radionuclides on the clay was also determined in the present study and differences in Da values were rationalized on the basis of sorption data. Distribution ratios (Kd) for Cs(I) and Eu(III) were higher than that for Sr(II), which in turn was higher than that for Na(I).

Targeting glutamine metabolism in multiple myeloma enhances BIM binding to BCL-2 eliciting synthetic lethality to venetoclax.

Multiple myeloma (MM) is a plasma cell malignancy that is largely incurable due to development of resistance to therapy-elicited cell death. Nutrients are intricately connected to maintenance of cellular viability in part by inhibition of apoptosis. We were interested to determine if examination of metabolic regulation of BCL-2 proteins may provide insight on alternative routes to engage apoptosis. MM cells are reliant on glucose and glutamine and withdrawal of either nutrient is associated with varying levels of apoptosis. We and others have demonstrated that glucose maintains levels of key resistance-promoting BCL-2 family member, myeloid cell leukemic factor 1 (MCL-1). Cells continuing to survive in the absence of glucose or glutamine were found to maintain expression of MCL-1 but importantly induce pro-apoptotic BIM expression. One potential mechanism for continued survival despite induction of BIM could be due to binding and sequestration of BIM to alternate pro-survival BCL-2 members. Our investigation revealed that cells surviving glutamine withdrawal in particular, enhance expression and binding of BIM to BCL-2, consequently sensitizing these cells to the BH3 mimetic venetoclax. Glutamine deprivation-driven sensitization to venetoclax can be reversed by metabolic supplementation with TCA cycle intermediate α-ketoglutarate. Inhibition of glucose metabolism with the GLUT4 inhibitor ritonavir elicits variable cytotoxicity in MM that is marginally enhanced with venetoclax treatment, however, targeting glutamine metabolism with 6-diazo-5-oxo-l-norleucine uniformly sensitized MM cell lines and relapse/refractory patient samples to venetoclax. Our studies reveal a potent therapeutic strategy of metabolically driven synthetic lethality involving targeting glutamine metabolism for sensitization to venetoclax in MM.

Positive effect of reduced aeration rate on secretion of alpha-amylase and neutral proteases during pressurised fermentation of thermophilic Bacillus caldolyticus.

The thermophilic microorganism Bacillus caldolyticus was incubated in laboratory scale stirred bioreactors under pressurised conditions at different aeration rates. Increased amounts of CO2/bicarbonate were solubilised under the chosen conditions. A reduction in aeration rate from 1 vvm to 0.1 vvm resulted in accumulation of CO2 and bicarbonate up to 126 mg l(-1) and 733 mg l(-1), respectively and also increased secretion of α-amylase and neutral proteases (increases of 123% and 52%, respectively). In this paper, the effect of reduced aeration rate on CO2/bicarbonate concentration and enzyme activities is presented. The selected fermentation conditions are closely related to those prevalent in large scale bioreactors and may offer the possibility of achieving high enzyme yields at reduced aeration costs on an industrial scale.

Effect of partial pressure of CO2 on the production of thermostable alpha-amylase and neutral protease by Bacillus caldolyticus.

Controlling the concentration of dissolved oxygen is a standard feature in aerobic fermentation processes but the measurement of dissolved CO2 concentrations is often neglected in spite of its influence on the cellular metabolism. In this work room air and room air supplemented with 5% and 10% carbon dioxide were used for aeration during the cultivation of the thermophilic microorganism Bacillus caldolyticus (DSM 405) on starch to produce alpha-amylase (E.C. 3.2.1.1) and neutral protease (E.C. 3.4.24.27/28). The increased CO2 concentrations resulted in a 22% raise in activity of secreted alpha-amylase and a 43% raise in protease activity when compared with aeration with un-supplemented room air. There was no effect on the final biomass concentration. Furthermore, the lag-phase of fermentation was reduced by 30%, further increasing the productivity of alpha-amylase production. Determinations of dissolved CO2 in the culture broth were conducted both in situ with a probe as well as using exhaust gas analysis and both the methods of quantification showed good qualitative congruence.

Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination.

AIMS: Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v.) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. METHODS: C57Bl/6 mice were fed cuprizone (0.2%) for 2 weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional 2 weeks of dietary cuprizone treatment, CNS tissues were analysed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). RESULTS: Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, glial fibrillary acidic protein. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. CONCLUSIONS: These findings indicated that systemically administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells.

Relevance of microbial coculture fermentations in biotechnology.

The purpose of this article is to review coculture fermentations in industrial biotechnology. Examples for the advantageous utilization of cocultures instead of single cultivations include the production of bulk chemicals, enzymes, food additives, antimicrobial substances and microbial fuel cells. Coculture fermentations may result in increased yield, improved control of product qualities and the possibility of utilizing cheaper substrates. Cocultivation of different micro-organisms may also help to identify and develop new biotechnological substances. The relevance of coculture fermentations and the potential of improving existing processes as well as the production of new chemical compounds in industrial biotechnology are pointed out here by means of more than 35 examples.

Molecular stages of rapid and uniform neuralization of human embryonic stem cells.

Insights into early human development are fundamental for our understanding of human biology. Efficient differentiation of human embryonic stem cells (hESCs) into neural precursor cells is critical for future cell-based therapies. Here, using defined conditions, we characterized a new method for rapid and uniform differentiation of hESCs into committed neural precursor cells (designated C-NPCs). Dynamic gene expression analysis identified several distinct stages of ESC neuralization and revealed functional modules of coregulated genes and pathways. The first wave of gene expression changes, likely corresponding to the transition through primitive ectoderm, started at day 3, preceding the formation of columnar neuroepithelial rosettes. The second wave started at day 5, coinciding with the formation of rosettes. The majority of C-NPCs were positive for both anterior and posterior markers of developing neuroepithelium. In culture, C-NPCs became electrophysiologically functional neurons; on transplantation into neonatal mouse brains, C-NPCs integrated into the cortex and olfactory bulb, acquiring appropriate neuronal morphologies and markers. Compared to rosette-NPCs,(1) C-NPCs exhibited limited in vitro expansion capacity and did not express potent oncogenes such as PLAG1 or RSPO3. Concordantly, we never detected tumors or excessive neural proliferation after transplantation of C-NPCs into mouse brains. In conclusion, our study provides a framework for future analysis of molecular signaling during ESC neuralization.

Aerobic biodegradation of 2,4-DNT and 2,6-DNT: performance characteristics and biofilm composition changes in continuous packed-bed bioreactors.

This manuscript deals with continuous experiments for biodegradation of individual dinitrotoluenes by a defined mixed culture in packed-bed reactors (PBRs) containing either poraver or fire-clay as packing material. Removal efficiencies and volumetric biodegradation rates were measured as a function of the loading rate of 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) under steady-state conditions. The poraver reactor showed higher removal efficiencies for both the DNTs. The removal efficiency for 2,4-DNT remained greater than 90% in the poraver reactor whereas it dropped steadily from 85 to 65% in the fire-clay reactor as the organic loading rates were increased from 19 to 60 mg L(-1)day(-1). Similar trends were seen for the volumetric degradation rate as well. In both the reactors, 2,4-DNT degraded more effectively than 2,6-DNT. The microbial consortium was characterized both in the inoculum as well as in the operating PBR. Cell numbers per gram dry packing material were similar in the two reactors. However, there was a distinct difference in the nature of microorganisms that were found in the two packings. The fire-clay contained a larger number of cells that were not primary degraders of DNTs.

Quantum nature of photon signal emitted by Xanthoria parietina and its implications to biology.

The properties of living systems are usually described in the semi-classical framework that makes phenomenological division of properties into four classes--matter, psyche, soft consciousness and hard consciousness. Quantum framework provides a scientific basis of this classification of properties. The scientific basis requires the existence of macroscopic quantum entity entangled with quantum photon field of a living system. Every living system emits a photon signal with features indicating its quantum nature. Quantum nature of the signal emitted by a sample of X. parietina is confirmed by analysing photo count distributions obtained in 20000 measurements of photon number in contiguous bins of sizes of 50, 100, 200, 300 and 500 ms. The measurements use a broadband detector sensitive in 300-800 nm range (Photo count distributions of background noise and observed signal are measured similarly. These measurements background noise corrected squeezed state parameters of the signal. The parameters are signal strength expressed in counts per bin, r = 0.06, theta = 2.76 and phi = 0.64. The parameters correctly reproduce photo count distribution of any bin size in 50 ms-6 s range. The reproduction of photo count distributions is a credible evidence of spontaneous emission of photon signal in a quantum squeezed state for macroscopic time by the sample. The evidence is extrapolated to other living systems emitting similar photon signals. It is suggested that every living system is associated with a photon field in squeezed state. The suggestion has far reaching implications to biology and provides two ways of observing and manipulating a living system--either through matter or field or a combination of the two. Some implications and possible scenarios are elaborated.

Delayed luminescence of high homeopathic potencies on sugar globuli.

Delayed luminescence signals of Arg.met. CMf (100Mf), Canth. CMf, Bov. CMf absorbed onto sugar globuli was observed by exciting them at their known resonance frequency of 2.060 MHz. Arn. CMf also showed delayed luminescence when excited at 2.060 MHz and at 1.828 MHz. Alc. LMK (50MK) could not be excited by 2.060 MHz and showed properties of control globuli. Canth. LMK could not be excited at 2.006 MHz. The delayed luminescence signals were characterized by the coefficient B(2) typical of the delayed luminescence of non-living complex systems, and by the coefficient B(0) typical of living systems. Both coefficients can be considered as indicative of holistic quantum structures in homeopathic potencies.

Aerobic biodegradation of dinitrotoluenes in batch systems by pure and mixed cultures.

Biodegradation characteristics of 2,4- and 2,6-dinitrotoluenes (DNTs) individually by pure strains and defined mixed cultures obtained from a mixed culture isolated from a slate packed bed bioreactor is described. Batch degradation experiments were carried out with free cells in submerged cultivations. The degradation rate and efficiency of five best individual bacterial strains, bacterial consortia comprising three and five of these strains, and the complete mixed culture were evaluated and compared. All the strains showed ability to degrade both the DNTs. All but one strain degraded both DNTs at the same rate. The degradation rate as well as the degradation efficiency by the mixed cultures was higher than that by the individual strains. The complete mixed culture showed 15-20 x higher degradation rate than the individual bacterial strains.

Effect of colorpuncture on spontaneous photon emission in a subject suffering from multiple sclerosis.

Spontaneous photon signals from four sites of a human subject suffering from multiple sclerosis were detected in 3600 bins of 50 milliseconds by a photo multiplier sensitive in 160-630 nm, before and after a session of colorpuncture treatment. Measurements were made in 22 sessions over a period of 9 months. Each signal was analyzed to determine if it was a quantum signal in a squeezed state. The analysis first generates 10 signals of bin sizes (50 to 500 milliseconds at 50 millisecond intervals) by merging the counts at contiguous bins of the observed signal and then estimates three squeezed state parameters (r, theta and phi) in these ten signals and nine other combinations of signals. All estimations yield r=2.72.10(-10), theta = 101.91 degrees and phi = 69.53 degrees for TolX=10(-8) in every signal of a healthy subject. These are normal values of the parameters. Other values of parameters in a signal of any estimation indicate some ailment. The deviation from the squeezed state description of a signal is quantified by a new property, "coherency index", which appears to be a good indicator of health. A session of colorpuncture treatment changed coherency indices of signals from different sides and provided relief to the subject suffering from multiple sclerosis. The changes in coherency indices and relief were temporary. Changes in coherency indices lasting for longer periods occurred after many sessions of treatment.

Preparation, characterization and microhardness study of semi interpenetrating polymer networks of polyvinyl alcohol and crosslinked polyacrylamide.

Semi-IPNs based on polyvinyl alcohol (PVA) and crosslinked polyacrylamide (PAM) were prepared and characterized. Various compositions of semi-interpenetrating polymer networks (semi-IPNs) were prepared by varying concentrations of PVA, acrylamide (AM) and crosslinker N,N'-methylene bis acrylamide (MBA) in the feed mixtures and polymerized using a suitable redox system comprising of potassium persulphate and metabisulphite. The prepared semi-IPNs were characterized by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) methods. The prepared semi-IPNs were also investigated for microhardness measurements.