Leaf-cutting ant fungi produce cell wall degrading pectinase complexes reminiscent of phytopathogenic fungi

<p>Abstract</p> <p>Background</p> <p>Leaf-cutting (attine) ants use their own fecal material to manure fungus gardens, which consist of leaf material overgrown by hyphal threads of the basidiomycete fungus <it>Leucocoprinus gongylophorus </it>that lives in symbiosis with the ants. Previous studies have suggested that the fecal droplets contain proteins that are produced by the fungal symbiont to pass unharmed through the digestive system of the ants, so they can enhance new fungus garden growth.</p> <p>Results</p> <p>We tested this hypothesis by using proteomics methods to determine the gene sequences of fecal proteins in <it>Acromyrmex echinatior </it>leaf-cutting ants. Seven (21%) of the 33 identified proteins were pectinolytic enzymes that originated from the fungal symbiont and which were still active in the fecal droplets produced by the ants. We show that these enzymes are found in the fecal material only when the ants had access to fungus garden food, and we used quantitative polymerase chain reaction analysis to show that the expression of six of these enzyme genes was substantially upregulated in the fungal gongylidia. These unique structures serve as food for the ants and are produced only by the evolutionarily advanced garden symbionts of higher attine ants, but not by the fungi reared by the basal lineages of this ant clade.</p> <p>Conclusions</p> <p>Pectinolytic enzymes produced in the gongylidia of the fungal symbiont are ingested but not digested by <it>Acromyrmex </it>leaf-cutting ants so that they end up in the fecal fluid and become mixed with new garden substrate. Substantial quantities of pectinolytic enzymes are typically found in pathogenic fungi that attack live plant tissue, where they are known to breach the cell walls to allow the fungal mycelium access to the cell contents. As the leaf-cutting ant symbionts are derived from fungal clades that decompose dead plant material, our results suggest that their pectinolytic enzymes represent secondarily evolved adaptations that are convergent to those normally found in phytopathogens.</p

Transient Ureteral Obstruction Prevents against Kidney Ischemia/Reperfusion Injury via Hypoxia-Inducible Factor (HIF)-2α Activation

Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure

Differential expression of MUC genes in endometrial and cervical tissues and tumors

BACKGROUND: Mucin glycoprotein's are major components of mucus and are considered an important class of tumor associated antigens. The objective of this study was to investigate the expression of human MUC genes (MUC1, MUC2, MUC5B, MUC5AC and MUC8) in human endometrium and cervix, and to compare and quantitate the expression of MUC genes in normal and cancerous tissues. METHODS: Slot blot techniques were used to study the MUC gene expression and quantitation. RESULTS: Of the five-mucin genes studied, MUC1, MUC5B and MUC8 showed high expression levels in the normal and cancerous endometrial and cervical tissues, MUC2 and MUC5AC showed considerably lower expression. Statistically, higher levels of MUC1, MUC5B and MUC8 were observed in endometrial adenocarcinomas compared to normal tissues. In contrast, only MUC1 levels increased with no significant changes in expression of MUC5B and MUC8 in cervical tumors over normal cervical tissues. CONCLUSION: Endometrial tumors showed increased expression of MUC1, MUC5B and MUC8 over normal tissues. Only MUC1 appears to be increase, in cervical tumors. All the studied tissues showed high and consistent expression of MUC8 mRNA. Low to neglible levels of MUC2 and MUC5AC were observed in all studied endometrial and cervical tissues

Monoculture of Leafcutter Ant Gardens

Background -- Leafcutter ants depend on the cultivation of symbiotic Attamyces fungi for food, which are thought to be grown by the ants in single-strain, clonal monoculture throughout the hundreds to thousands of gardens within a leafcutter nest. Monoculture eliminates cultivar-cultivar competition that would select for competitive fungal traits that are detrimental to the ants, whereas polyculture of several fungi could increase nutritional diversity and disease resistance of genetically variable gardens. Methodology/Principal Findings -- Using three experimental approaches, we assessed cultivar diversity within nests of Atta leafcutter ants, which are most likely among all fungus-growing ants to cultivate distinct cultivar genotypes per nest because of the nests' enormous sizes (up to 5000 gardens) and extended lifespans (10–20 years). In Atta texana and in A. cephalotes, we resampled nests over a 5-year period to test for persistence of resident cultivar genotypes within each nest, and we tested for genetic differences between fungi from different nest sectors accessed through excavation. In A. texana, we also determined the number of Attamyces cells carried as a starter inoculum by a dispersing queens (minimally several thousand Attamyces cells), and we tested for genetic differences between Attamyces carried by sister queens dispersing from the same nest. Except for mutational variation arising during clonal Attamyces propagation, DNA fingerprinting revealed no evidence for fungal polyculture and no genotype turnover during the 5-year surveys. Conclusions/Significance -- Atta leafcutter ants can achieve stable, fungal monoculture over many years. Mutational variation emerging within an Attamyces monoculture could provide genetic diversity for symbiont choice (gardening biases of the ants favoring specific mutational variants), an analog of artificial selection.The research was supported by National Science Foundation awards DEB-0920138, DEB-0639879, and DEB-0110073 to UGM; DEB-0949689 to T.R. Schultz, N. Mehdiabadi, and UGM; and a Fellowship (02/05) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico to AR. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

<p>Abstract</p> <p>Background</p> <p>After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment.</p> <p>The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode.</p> <p>Methods</p> <p>SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan.</p> <p>Discussion</p> <p>SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01109693">NCT01109693</a></p

Interventions for hyperhidrosis in secondary care : a systematic review and value-of-information analysis

Background: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. Objective: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. Methods: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. Results and conclusions: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. Limitations: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. Future work: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses