Biotechnological applications of functional metagenomics in the food and pharmaceutical industries

peer-reviewedMicroorganisms are found throughout nature, thriving in a vast range of environmental conditions. The majority of them are unculturable or difficult to culture by traditional methods. Metagenomics enables the study of all microorganisms, regardless of whether they can be cultured or not, through the analysis of genomic data obtained directly from an environmental sample, providing knowledge of the species present, and allowing the extraction of information regarding the functionality of microbial communities in their natural habitat. Function-based screenings, following the cloning and expression of metagenomic DNA in a heterologous host, can be applied to the discovery of novel proteins of industrial interest encoded by the genes of previously inaccessible microorganisms. Functional metagenomics has considerable potential in the food and pharmaceutical industries, where it can, for instance, aid (i) the identification of enzymes with desirable technological properties, capable of catalyzing novel reactions or replacing existing chemically synthesized catalysts which may be difficult or expensive to produce, and able to work under a wide range of environmental conditions encountered in food and pharmaceutical processing cycles including extreme conditions of temperature, pH, osmolarity, etc; (ii) the discovery of novel bioactives including antimicrobials active against microorganisms of concern both in food and medical settings; (iii) the investigation of industrial and societal issues such as antibiotic resistance development. This review article summarizes the state-of-the-art functional metagenomic methods available and discusses the potential of functional metagenomic approaches to mine as yet unexplored environments to discover novel genes with biotechnological application in the food and pharmaceutical industries.Science Foundation Ireland(SFI)Grant Number 13/SIRG/215

Profile of a Successful Negotiation: The Crest Street Experience

How do you define "success" in a negotiated settlement? The following case study defines it as "Crest St"- a low income neighborhood moved out of the way of a highway in Durham, North Carolina. Although the parties didn't immediately concur with this appelation, their smiles belie their sense of pride in the outcome

Beneficial effects of training in self-distancing and perspective broadening for people with a history of recurrent depression.

Cognitive training designed to recalibrate maladaptive aspects of cognitive-affective processing associated with the presence of emotional disorder can deliver clinical benefits. This study examined the ability of an integrated training in self-distancing and perspective broadening (SD-PB) with respect to distressing experiences to deliver such benefits in individuals with a history of recurrent depression (≥3 prior episodes), currently in remission. Relative to an overcoming avoidance (OA) control condition, SD-PB: a) reduced distress to upsetting memories and to newly encountered events, both during training when explicitly instructed to apply SD-PB techniques, and after-training in the absence of explicit instructions; b) enhanced capacity to self-distance from and broaden perspectives on participants' experiences; c) reduced residual symptoms of depression. These data provide initial support for SD-PB as a low-intensity cognitive training providing a spectrum of cognitive and affective benefits for those with recurrent depression who are at elevated risk of future episodes

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins

Objective—We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Approach and Results—Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Conclusions—Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association

Effect of vaccination with a novel GnRH-based immunocontraceptive on immune responses and fertility in rats

1. As human-wildlife conflicts increase worldwide, novel methods are required for mitigating these conflicts. Fertility control, based on immunocontraceptives, has emerged as an alternative option to lethal methods for managing wildlife. 2. Immunocontraceptives are vaccines that generate an immune response to key components of an animal\u27s reproductive system. Some of these vaccines target the gonadotropin-releasing hormone (GnRH) and have been used successfully as contraceptives for many wildlife species. However, the need to capture animals for treatment limits the field applications of injectable vaccines. The availability of orally delivered immunocontraceptives would increase the breadth of applications of fertility control for wildlife management. 3. This study explored a new approach to developing an oral immunocontraceptive, exploiting the bioadhesive and immunologically active properties of killed Mycobacterium avium cell wall fragments (MAF). The MAF was conjugated to a GnRH recombinant protein called IMX294, used as a GnRH-specific immunogen. 4. An initial trial using the MAF-IMX294 conjugate provided the first evidence that an orally delivered immunocontraceptive vaccine could generate anti-GnRH antibody titres in laboratory rats. 5. Increasing the dose and frequency of vaccine administered to rats, in a second trial, enhanced the immune response, eliciting titres that reduced the proportion of females giving birth. This provided the first evidence of the contraceptive effect of an oral anti-GnRH vaccine. 6. Future work is required to further increase the immunogenic effect of the oral vaccine and to establish a dosing schedule that is effective for practical field applications

New Weapons to Fight Old Enemies: Novel Strategies for the (Bio)control of Bacterial Biofilms in the Food Industry

peer-reviewedBiofilms are microbial communities characterized by their adhesion to solid surfaces and the production of a matrix of exopolymeric substances, consisting of polysaccharides, proteins, DNA and lipids, which surround the microorganisms lending structural integrity and a unique biochemical profile to the biofilm. Biofilm formation enhances the ability of the producer/s to persist in a given environment. Pathogenic and spoilage bacterial species capable of forming biofilms are a significant problem for the healthcare and food industries, as their biofilm-forming ability protects them from common cleaning processes and allows them to remain in the environment post-sanitation. In the food industry, persistent bacteria colonize the inside of mixing tanks, vats and tubing, compromising food safety and quality. Strategies to overcome bacterial persistence through inhibition of biofilm formation or removal of mature biofilms are therefore necessary. Current biofilm control strategies employed in the food industry (cleaning and disinfection, material selection and surface preconditioning, plasma treatment, ultrasonication, etc.), although effective to a certain point, fall short of biofilm control. Efforts have been explored, mainly with a view to their application in pharmaceutical and healthcare settings, which focus on targeting molecular determinants regulating biofilm formation. Their application to the food industry would greatly aid efforts to eradicate undesirable bacteria from food processing environments and, ultimately, from food products. These approaches, in contrast to bactericidal approaches, exert less selective pressure which in turn would reduce the likelihood of resistance development. A particularly interesting strategy targets quorum sensing systems, which regulate gene expression in response to fluctuations in cell-population density governing essential cellular processes including biofilm formation. This review article discusses the problems associated with bacterial biofilms in the food industry and summarizes the recent strategies explored to inhibit biofilm formation, with special focus on those targeting quorum sensing.Science Foundation Irelan

Health-related quality of life among adolescents with eating disorders

Objective Health-related quality of life (HRQoL) is an emerging area of research in eating disorders (EDs) that has not been examined in adolescents in detail. The aim of the current study is to investigate HRQoL in an adolescent ED sample, examining the impact of ED symptoms on HRQoL. Methods Sixty-seven treatment-seeking adolescents (57 females) with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (EDNOS) completed self-report measures of HRQoL and ED symptoms. Results Participants reported poorer HRQoL in mental health domains than in physical health domains. Disordered attitudes, binge eating, and compensatory behaviors were associated with poorer mental health HRQoL, and body dissatisfaction was associated with poorer physical health HRQoL. Conclusion The current study assessed HRQoL among adolescents with EDs, finding several consistencies with the literature on adults with EDs. Future research should compare adolescents and adults with EDs on HRQoL

Cost-Effectiveness of Robot-Assisted Radical Cystectomy vs Open Radical Cystectomy for Patients With Bladder Cancer

IMPORTANCE: The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear. OBJECTIVES: To compare the cost-effectiveness of iRARC with that of ORC. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. INTERVENTIONS: Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). MAIN OUTCOMES AND MEASURES: Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. RESULTS: A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, -£576 to £2824 [US $1622 (95$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95$144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. CONCLUSIONS AND RELEVANCE: In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03049410

The Hubble Space Telescope Extragalactic Distance Scale Key Project. X. The Cepheid Distance to NGC 7331

The distance to NGC 7331 has been derived from Cepheid variables observed with HST/WFPC2, as part of the Extragalactic Distance Scale Key Project. Multi-epoch exposures in F555W (V) and F814W (I), with photometry derived independently from DoPHOT and DAOPHOT/ALLFRAME programs, were used to detect a total of 13 reliable Cepheids, with periods between 11 and 42 days. The relative distance moduli between NGC 7331 and the LMC, imply an extinction to NGC 7331 of A_V = 0.47+-0.15 mag, and an extinction-corrected distance modulus to NGC 7331 of 30.89+-0.14(random) mag, equivalent to a distance of 15.1 Mpc. There are additional systematic uncertainties in the distance modulus of +-0.12 mag due to the calibration of the Cepheid Period-Luminosity relation, and a systematic offset of +0.05+-0.04 mag if we applied the metallicity correction inferred from the M101 results of Kennicutt et al 1998.Comment: To be published in The Astrophysical Journal, 1998 July 1, v501 note: Figs 1 and 2 (JPEG files) and Fig 7 (multipage .eps file) need to be viewed/printed separatel