Bacterial-fungal crosstalk is defined by a fungal lactone mycotoxin and its degradation by a bacterial lactonase.

Bacteria, fungi, and mammals contain lactonases that can degrade the Gram-negative bacterial quorum sensing (QS) molecules N-acyl homoserine lactones (AHLs). AHLs are critical for bacteria to coordinate gene expression and pathogenicity with population density. However, AHL-degrading lactonases present variable substrate ranges, including degradation of the Pencillium expansum lactone mycotoxin patulin. We selected Erwinia spp. as our model bacteria to further investigate this interaction. We find both native apple microbiome Erwinia spp. and the fruit tree pathogen Erwinia amylovora to be inhibited by patulin. At patulin concentrations that inhibited E. amylovora growth, expression of E. amylovora lactonase encoded by EaaiiA was increased. EaAiiA demonstrated the ability to degrade patulin in vitro, as well, as in vivo where it reduced apple disease and patulin production by P. expansum. Fungal-bacterial co-cultures revealed that the E. amylovora Δeaaiia strain failed to protect apples from P. expansum infections, which contained significant amounts of patulin. Our results suggest that bacterial lactonase production can modulate the pathogenicity of P. expansum in response to the secretion of toxic patulin. IMPORTANCE: Chemical signaling in the microbial world facilitates the regulation of gene expression as a function of cell population density. This is especially true for the Gram-negative bacterial signal N-acyl homoserine lactone (AHL). Lactonases that deactivate AHLs have attracted a lot of attention because of their antibacterial potential. However, the involvement of these enzymes in inhibiting fungal pathogens and the potential role of these enzymes in bacterial-fungal interactions are unknown. Here, we find that a bacterial enzyme involved in the degradation of AHLs is also induced by and degrades the fungal lactone mycotoxin, patulin. This work supports the potential use of bacterial enzymes and/or the producing bacteria in controlling the post-harvest fruit disease caused by the patulin-producing fungus Penicillium expansum.

Weighted false discovery rate controlling procedures for clinical trials.

Having identified that the lack of replicability of results in earlier phases of clinical medical research stems largely from unattended selective inference, we offer a new hierarchical weighted false discovery rate controlling testing procedure alongside the single-level weighted procedure. These address the special structure of clinical research, where the comparisons of treatments involve both primary and secondary endpoints, by assigning weights that reflect the relative importance of the endpoints in the error being controlled. In the hierarchical method, the primary endpoints and a properly weighted intersection hypothesis that represents all secondary endpoints are tested. Should the intersection hypothesis be among the rejected, individual secondary endpoints are tested. We identify configurations where each of the two procedures has the advantage. Both offer higher power than competing hierarchical (gatekeeper) familywise error-rate controlling procedures being used for drug approval. By their design, the advantage of the proposed methods is the increased power to discover effects on secondary endpoints, without giving up the rigor of addressing their multiplicity.

Directed evolution of an endoinulinase from Talaromyces purpureogenus toward efficient production of inulooligosaccharides.

Inulinases are fructofuranosyl hydrolases that target the ß-2,1 linkage of inulin and hydrolyze it into fructose, glucose and inulooligosaccharides (IOS), the latter are of growing interest as dietary fibers. Inulinases from various microorganisms have been purified, characterized and produced for industrial applications. However, there remains a need for inulinases with increased catalytic activity and better production yields to improve the hydrolysis process and fulfill the growing industrial demands for specific fibers. In this study, we used directed enzyme evolution to increase the yield and activity of an endoinulinase enzyme originated from the filamentous fungus Talaromyces purpureogenus (Penicillium purpureogenum ATCC4713). Our directed evolution approach yielded variants showing up to fivefold improvements in soluble enzyme production compared to the starting point which enabled high-yield production of highly purified recombinant enzyme. The distribution of the enzymatic reaction products demonstrated that after 24 h of incubation, the main product (57%) had a degree of polymerization of 3 (DP3). To the best of our knowledge, this is the first application of directed enzyme evolution to improve inulooligosaccharide production. The approach enabled the screening of large genetic libraries within short time frames and facilitated screening for improved enzymatic activities and properties, such as substrate specificity, product range, thermostability and pH optimum. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:868-877, 2018.

31 GHz Ge n-i-p waveguide photodetectors on Silicon-on-Insulator substrate.

We report on evanescently coupled Ge waveguide photodetectors that are grown on top of Si rib waveguides. A Ge waveguide detector with a width of 7.4mum and length of 50 mum demonstrated an optical bandwidth of 31.3 GHz at -2V for 1550nm. In addition, a responsivity of 0.89 A/W at 1550 nm and dark current of 169 nA were measured from this detector at -2V. A higher responsivity of 1.16 A/W was also measured from a longer Ge waveguide detector (4.4 x 100 mum2), with a corresponding bandwidth of 29.4 GHz at -2V. An open eye diagram at 40 Gb/s is also shown.

Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine.

Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.

Suicidal attempts admitted to a general hospital in the Western Galilee: an inter-ethnic comparison study.

BACKGROUND: Deliberate self-harm is a relatively frequent cause of consultation in the emergency room of general hospitals. Despite its importance, few epidemiological studies of self-injury in Israel have been carried out, and of these, they mostly covered selected population groups. OBJECTIVES: To provide epidemiological data on self-harm in patients examined in the emergency room of a general hospital in the Western Galilee, with special emphasis on differential sociodemographic and clinical characteristics of the Arab and Jewish subjects. METHODS: Demographic, clinical, and self-harm characteristics were extracted from hospital files for people aged 18 years and older admitted to the general hospital in Nahariya, Western Galilee, over a 24-month period (January 1996 to December 1997) following a suicidal attempt. Chi-square statistics, two-tailed t-tests, and logistic regression analyses were used to test the significance of inter-ethnic differences in risk factors. RESULTS: The overall incidence rate of suicidal attempts was 16.7 per 100,000 population of Northern District in 1996 (Arabs, 24.4 and Jews, 11.0); or 37.6 per 10,000 admissions (Arabs, 44.2 and Jews, 30.3). Among the Jewish male subjects, attempts rose markedly after the age of 40, while among their Arab counterparts the age distribution was even throughout all age groups. Among Jewish females, admissions for self-harm rose gradually with age, while among the Arab women there was a peak at the 20-29 year age group. Both ethnic groups differed significantly in their sociodemographic and clinical profiles, but they shared common characteristics with regard to the attempt. CONCLUSIONS: Our findings suggest differential ethnic patterns of risk factors for self-harm. Further in-depth investigation of deliberate self-harm is warranted to better explore these factors.

Molecular engineering of semiconductor surfaces and devices.

Grafting organic molecules onto solid surfaces can transfer molecular properties to the solid. We describe how modifications of semiconductor or metal surfaces by molecules with systematically varying properties can lead to corresponding trends in the (electronic) properties of the resulting hybrid (molecule + solid) materials and devices made with them. Examples include molecule-controlled diodes and sensors, where the electrons need not to go through the molecules (action at a distance), suggesting a new approach to molecule-based electronics.