RFRP-3 infusion elicited a significant increase in growth hormone

RFRP-3 infusion elicited a significant increase in growth hormonereleasing hormone mRNA and plasma growth hormone levels compared to control rats. Neither peptide had an effect on KiSS-1 mRNA expression. Conclusion:

These data suggest that endogenous rat RFRP-3 does not affect the timing of puberty in male rats but may be associated with peripubertal rise in growth hormone secretion. Copyright (C) 2008 S. Karger AG, Basel”
“A locally-isolated Pseudomonas aeruginosa USM AR2 possessing the ability to produce glycolipid-type biosurfactant (rhamnolipid) was used in this research to explore fermentation technology for rhamnolipid production. Rhamnolipid concentration in 2.5 L fed-batch fermentation was improved from 0.173 to 8.06 g/L by manipulating the feeding strategy and cultivation protocol. The culture was fed with petroleum diesel and complex medium. The highest find more rhamnolipid concentration

was achieved when the culture was initially fed with both petroleum diesel and complex medium, followed by feeding of petroleum diesel only at the end of the stationary phase. Severe foaming problem was resolved by modifying and integrating a foam recycler to the bioreactor. This successfully extended the cultivation period and increased the yield of final rhamnolipid. No antifoam agent was added as this modified bioreactor allowed cultivation to proceed even under foam generation. The viscosity measurement, surface tension activity test, and drop-collapse test were performed as an indirect measure of rhamnolipid presence. (C) KSBB”
“The case of a 30-year-old woman who had already experienced two incidents of angioneurotic VX 770 edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup HDAC activity assay revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting,

may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found.”
“The purpose of the study was to determine the effects of compression garments on recovery following damaging exercise. A systematic review and meta-analysis was conducted using studies that evaluated the efficacy of compression garments on measures of delayed onset muscle soreness (DOMS), muscular strength, muscular power and creatine kinase (CK). Studies were extracted from a literature search of online databases. Data were extracted from 12 studies, where variables were measured at baseline and at 24 or 48 or 72 h postexercise. Analysis of pooled data indicated that the use of compression garments had a moderate effect in reducing the severity of DOMS (Hedges’ g=0.403, 95% CI 0.236 to 0.569, p smaller than 0.001), muscle strength (Hedges’ g=0.462, 95% CI 0.221 to 0.703, p smaller than 0.001), muscle power (Hedges’ g=0.487, 95% CI 0.267 to 0.707, p smaller than 0.001) and CK (Hedges’ g=0.


“In this study, a number of 2′,4′-BNA- and 2′,4′-BNA(NC)-m


“In this study, a number of 2′,4′-BNA- and 2′,4′-BNA(NC)-modified

siRNAs were designed and synthesized. Their thermal stability, nuclease resistance and gene silencing properties against cultured mammalian cells were evaluated and compared selleckchem with those of natural siRNAs. The 2′,4′-BNA- and 2′,4′-BNA(NC)-modified siRNAs (named siBNA and siBNA(NC), respectively) showed very high T(m) values, were remarkably stable in serum sample and showed promising RNAi properties equal to those exhibited by natural siRNAs. Thermally stable siBNAs composed of slightly modified sense and antisense strands were capable of suppressing gene expression equal to that of natural siRNA. A number of modifications on the sense strand by 2′,4′-BNA or 2′,4′-BNA(NC), either consecutively or separated by natural RNA nucleotides, is tolerable in RNAi machinery. Modifications at the Argonauate 3-MA PI3K/Akt/mTOR inhibitor (Ago2) cleavage site of the sense strand (9-11th positions from the 5′-end of the sense strand) produced variable results depending on siRNA composition. Mostly, modification at the 10th position diminished siRNA activity. In moderately

modified siRNAs, modification at the 11th position displayed usual RNAi activity, while modification at the 9th position showed variable results depending on siRNA composition. (C) 2010 Elsevier Ltd. All rights reserved.”
“The clinical and public health importance of influenza and other respiratory viruses has accelerated the development of highly sensitive molecular diagnostics, but data are limited regarding preanalytical stages of diagnostic testing. We evaluated CyMol, an alcohol-based transport medium, for its ability to maintain specimen integrity for up to 21 days of storage at various temperatures; for its ability to inactivate virus; and for its compatibility with antigen-or nucleic acid-based diagnostics for respiratory viruses in clinical samples. In mock-infected samples, both universal transport medium (UTM-RT) and CyMol maintained see more equivalent viral

quantities for at least 14 days at room temperature or colder, whereas a dry swab collection maintained viral quantities only if refrigerated or frozen. CyMol inactivated influenza virus within 5 min of sample immersion. UTM-RT- and CyMol-collected nasal swab specimens from 73 symptomatic students attending a campus health clinic were positive for a respiratory virus in 56.2% of subjects by multiplex PCR testing, including influenza A and B viruses, rhinovirus/enteroviruses, coronaviruses, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, and adenovirus. Detection by PCR was equivalent in UTM-RT- and CyMol-collected specimens and in self-and staff-collected swabs.

These results suggest that deregulation of STAT activity plays a

These results suggest that deregulation of STAT activity plays a role in vorinostat resistance in CTCL, and strategies that block this pathway may improve vorinostat response. Furthermore, these findings may be of prognostic value in predicting the response of CTCL patients to vorinostat.”
“Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-b peptide play a central role in Alzheimer’s disease pathogenesis, being implicated in synaptic dysfunction.

Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term CH5183284 datasheet potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control

nontoxic oligomers had none of such effects. These Galunisertib in vitro results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer’s disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid beta peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease. (C) 2013 Elsevier Inc. All find more rights reserved.”
“P>Serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is negatively regulated by 5-HT1A autoreceptors on raphe neurons, and is implicated in mood disorders. Pet-1/FEV is an

ETS transcription factor expressed exclusively in serotonergic neurons and is essential for serotonergic differentiation, although its regulation of 5-HT receptors has not yet been studied. Here, we show by electrophoretic mobility shift assay that recombinant human Pet-1/FEV binds directly to multiple Pet-1 elements of the human 5-HT1A receptor promoter to enhance its transcriptional activity. In luciferase reporter assays, mutational analysis indicated that while several sites contribute, the Pet-1 site at -1406 bp had the greatest effect on 5-HT1A promoter activity. To address the effect of Pet-1 on 5-HT1A receptor regulation in vivo, we compared the expression of 5-HT1A receptor RNA and protein in Pet-1 null and wild-type littermate mice. In the raphe nuclei of Pet-1-/- mice tryptophan hydroxylase 2 (TPH2) RNA, and 5-HT and TPH immunostaining were greatly reduced, indicating a deficit in 5-HT production.

(C) 2015 Elsevier B V All rights reserved “
“The aim this s

(C) 2015 Elsevier B.V. All rights reserved.”
“The aim this study was to determine the in vitro susceptibility to fosfomycin of bacteria isolated from urine samples of pregnant women with urinary tract infection. Samples of urine

culture with bacterial growth of pregnant women were collected from clinical laboratories in Tubarao, state of Santa Catarina, Brazil, between September 2012 and May 2013. In the experimental stage, the colonies were tested for sensitivity to fosfomycin by using the Kirby-Bauer method. The following information relating to the samples was also collected: patients’ age, colony count, type(s) of identified bacterial(s) and result of the antimicrobial sensitivity test. Student’s t-test was used for mean comparison. A total of 134 samples were selected for the study. The age of the subjects ranged from 15 to 40 years (mean 26.7). Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) Napabucasin cost were the most commonly identified species. In 89% of cases, the microorganisms Mizoribine research buy were sensitive

to fosfomycin. E. coli and S. aureus were the main species of bacteria responsible for urinary tract infections in women in the study area. The most prevalent microorganisms in pregnant women with urinary tract infection were susceptible to fosfomycin. (C) 2015 Published by Elsevier Editora Ltda.”
“To study the effect of mitochondrial permeability transition pore (PTP) opening on NAD(P)H localization, intact cells were exposed to the Ca(2+) ionophore A23187. PTP opening, mitochondrial membrane potential, mitochondrial volume, and NAD(P)H localization were assessed by time-lapse laser confocal microscopy using the calcein-cobalt technique, tetramethylrhodamine methyl ester, MitoTracker, and NAD(P)H auto-fluorescence, respectively. Concomitant with PTP opening, NAD(P)H fluorescence increased outside mitochondria. These events occurred in all cells and were prevented by cyclosporin A. Mitochondrial membrane potential

was not systematically collapsed, whereas mitochondrial volume did not change, confirming that A23187 induced transient PTP opening in a subpopulation CX-6258 nmr of cells and suggesting that mitochondrial swelling did not immediately occur after PTP opening in intact cells. NAD(P)H autofluorescence remained elevated after PTP opening, particularly after membrane potential had been collapsed by an uncoupler. Extraction of nucleotide for NAD(P)H quantification confirmed that PTP opening led to an increase in NAD(P)H content. Because the oxygen consumption rate decreased, whereas the lactate/pyruvate ratio increased after PTP opening in intact cells, we conclude that PTP opening inhibits respiration and dramatically affects the cytosolic redox potential in intact cells.”
“The assembly of a bipolar spindle is crucial for symmetric partitioning of duplicated chromosomes during cell division.

They analyzed the current status of scientific knowledge on low-

They analyzed the current status of scientific knowledge on low- and no-calorie sweeteners (LNCS) and developed a consensus Decalogue on their use; this constitutes the Chinchon Declaration. Sweeteners, including sugar, represent a subject of undeniable interest and are currently a popular topic, although areas relating to their safety and benefits

remain unknown to segments of academia and the general public. The nature of LNCS makes them vulnerable to biased and even contradictory information. They are food additives that are broadly used as sugar substitutes to sweeten foods, medicines and food supplements when non-nutritional or non-caloric alternatives are needed. The Chinchon

Decalogue is the outcome of a meeting for reflection Selleckchem Sotrastaurin and consensus by a group of experts with backgrounds in different scientific disciplines (toxicology, clinical nutrition, community nutrition, physiology, food science, public health, pediatrics, endocrinology and nutrition, nursing, pharmaceutical care and food legislation). SHP099 datasheet The Decalogue includes different aspects of LNCS related to regulation, use, benefits and safety. In general, benefits of LNCS have been traditionally neglected in comparison with the tendency for emphasising unexisting or unproven possible risks. The need to strengthen research on LNCS in Spain was emphasized, as well as the need to educate both professionals and the public.”
“Background: To evaluate the effectiveness of Microlux/DL with and without IPI-145 solubility dmso toluidine blue in screening of potentially malignant and malignant oral lesions. Materials and Methods: In

this diagnostic clinical trial clinical examination was carried out by two teams: 1) two oral medicine consultants, and 2) two general dentists. Participants were randomly and blindly allocated for each examining team. A total of 599 tobacco users were assessed through conventional oral examination (COE); the examination was then repeated using Microlux/DL device and toluidine blue. Biopsy of suspicious lesions was performed. Also clinicians opinions regarding the two tools were obtained. Results: The sensitivity and, specificity and positive predictive value (PVP) of Microlux/DL for visualization of suspicious premalignant lesions considering COE as a gold standard (i.e screening device) were 94.3%, 99.6% and 96.2% respectively, while they were 100%, 32.4% and 17.9% when considering biopsy as a gold standard. Moreover, Microlux/DL enhanced detection of the lesion and uncovered new lesions compared to COE, whereas it did not alter the provisional clinical diagnosis, or alter the biopsy site. On the other hand, adding toluidine blue dye did not improve the effectiveness of the Microlux/DL system.

Four of these patients (Group 2, 4/13, 31%) appeared to be resist

Four of these patients (Group 2, 4/13, 31%) appeared to be resistant to chemotherapy, others (9/13, 69%) showed response to therapy,

though the response time was variable. Leukemic cells with compact nucleolus morphologically resembled prolymphocytes, but hematologically and immunophenotypically did not fulfill the diagnostic criteria for prolymphocyte population. None of our B-CLL patients had the signs of transformation to prolymphocytic or other type of B cell neoplasms during the follow up. Our results indicate the possibility of relationship between the presence of malignant lymphocytes with compact nucleoli and unfavorable outcome in patients with B-CLL. The simplicity and utility MK-4827 of the nucleolar test as a possible prognostic parameter may help to identify the subset of patients with early B-CLL disease that will run a more progressive course.”
“A

robust synthesis of (5Z,8Z,11Z,13E)(15S)-15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15(S)-HETE) sodium salt was established, utilising a biooxidalion process. Treatment of arachidonic acid with soybean lipoxidase in 0.1 M sodium tetraborate buffer under oxygen pressure resulted in formation of the hydroperoxide, 15(S)HPETE. Addition of sodium borohydride Vorinostat to the reaction mixture reduced the hydroperoxide to 15(S)-HETE, which was then purified by column chromatography. 15(S)-HETE sodium salt was prepared by treatment of an ethanol solution of HETE with aqueous sodium hydrogen carbonate. Multiple 10-g batches of 15(S)-HETE sodium salt with >98% enantiomeric excess and >98% chemical purity were prepared to support clinical trials.”
“Temporal evolution of polymerization-induced spinodal decomposition (PISD) under electric fields was investigated numerically in ethylene glycol/phenolic resin solutions with different initial composition. A model composed of the nonlinear Cahn-Hilliard-Cook equation for spinodal decomposition and a rate equation for curing reaction was utilized to describe the PISD phenomenon. As initial composition varied, deformed droplet-like this website and aligned bi-continuous structures

were observed in the presence of an electric field. Moreover, the anisotropic parameter (D), determined from the 2D-FFT power spectrum, was employed to quantitatively characterize the degree of morphology anisotropy. The value of D increased quickly in the early stage and then decreased in the intermediate stage of spinodal decomposition, which was attributed to the resistance of coarsening process to morphology deformation and the decline of electric stress caused by polymerization reaction. The results can also provide a guidance on how to control the morphology of monolithic porous polymer and carbon materials with anisotropic structures. (C) 2013 AIP Publishing LLC.”
“Lavoisiera bergii Cogn., Macairea radula (Bonpl.) DC, and Trembleya parviflora (D. Don) Cogn. are shrubby species of the family Melastomataceae.


“In patients

with type 2 diabetes mellitus (T2DM),


“In patients

with type 2 diabetes mellitus (T2DM), the physiologic glucagon-like peptide-1 (GLP-1) response, which is involved in glucose regulation through several mechanisms, is dysfunctional. GLP-1 receptor agonists can fill an unmet therapeutic need in the treatment of T2DM: improving glycemic control without increasing the risk of hypoglycemia (except with concomitant sulfonylureas) and reducing weight in a substantial proportion of patients. GLP-1 receptor agonists have impacted established disease treatment algorithms for T2DM. For example, in 2009 the American Diabetes Association and European Association for the Study of Diabetes revised their consensus treatment algorithm to incorporate GLP-1 receptor agonists. GLP-1 receptor Selleckchem LEE011 agonists were originally represented by exenatide BID (ExBID), a short-acting agent requiring twice-daily injections at meal-time. The longer-acting agent liraglutide, requiring once-daily injections, recently received regulatory approval. Several other long-acting agents are in clinical development, learn more one of which is the once-weekly formulation of exenatide (exenatide once weekly [ExQW]). This article reviews the clinical

development of ExQW in the DURATION program. Patients in theses clinical trials were receiving various background treatments, ranging from lifestyle therapy to combination oral therapy, although the majority

(68%) received metformin monotherapy. Specifically, safety, glycemic control, and weight were compared in patients treated with ExQW versus ExBID, sitagliptin, pioglitazone, or insulin glargine. Moreover, measures of beta-cell function, cardiovascular risk, inflammation, and hepatic health were investigated. During ExQW clinical development, consistent clinical efficacy (glycosylated hemoglobin, -1.5% to -1.9%; weight, -2kg to -4 kg) and safety data were observed in patients with T2DM treated with ExQW.”
“The influence of strain on the thermally induced dewetting mechanism Selleck KU-57788 of silicon films is reported. This study shows that the initial strain level in the silicon film significantly affects the final size and shape of the silicon agglomerates resulting from the film dewetting. With the increase of the biaxial strain up to 1.6%, the size of the silicon agglomerates is significantly reduced while their density increases. Moreover, the shape of the agglomerates becomes elongated when the strain favors one of the in-plane crystallographic directions to minimize the total energy of the system. A quantitative analysis of the dewetting mechanism is presented in terms of the agglomerates size and density versus the strain level. Finally, phenomenological laws are extracted, which predict the size and shape of the agglomerates. (C) 2013 AIP Publishing LLC.

Biopsy results had no significant impact on subsequent treatment

Biopsy results had no significant impact on subsequent treatment in 69% of patients who met clinical diagnostic criteria (P = .7); in the remaining 31%, biopsy results altered subsequent treatment with either corticosteroid initiation or discontinuation. CONCLUSIONS: The pathologic results of the TAB did not significantly affect treatment in most patients. (C) 2015 Elsevier

Inc. All rights reserved.”
“Background: Preparations from anthroposophical medicine (AM) are clinically used to treat inflammatory disorders. We wanted to investigate effects of a selection of AM medications for parenteral use in cell-based selleck chemicals llc systems in vitro. Methods: Colchicum officinale tuber D3, Mandragora D3, Rosmarinus officinale 5 % and Bryophyllum 5 % were selected for the experiments. Induction of apoptosis and necrosis (human lymphocytes and dendritic cells [DCs]) and proliferation of lymphocytes as well as maturation (expression

of CD14, CD83 and CD86) and cytokine secretion (IL-10, IL12p70) of DCs were analyzed. Furthermore, proliferation of allogeneic human T lymphocytes was investigated in vitro in coculture experiments using mature DCs in comparison to controls. Results: The respective preparations did not induce apoptosis or necrosis in lymphocytes or DCs. Compound C chemical structure Lymphocyte proliferation was dose-dependently reduced by Colchicum officinale tuber D3 while the viability was unchanged. Rosmarinus officinale 5 %, but not the other preparations, dose-dependently inhibited

the maturation of immature DCs, reduced secretion of IL-10 and IL-12p70 and slightly inhibited proliferation of allogeneic CD4+ T-lymphocytes in coculture experiments with DCs. Conclusion: The selected preparations from AM for parenteral use are nontoxic to lymphocytes and DCs. Rosmarinus PCI32765 officinale 5 % has immunosuppressive properties on key functions of the immune system which propose further investigation.”
“Background: Schizophrenia is characterized by impaired social cognition, including emotion processing. Behavioral studies have reported impaired performance on various emotion processing tasks, and imaging studies in patients have observed aberrant activity within the underlying neural circuitry. Also, subjects at increased genetic risk of developing schizophrenia, including unaffected siblings of patients, show behavioral impairments in emotion processing. It is unclear, however, whether and how the underlying neural system is disrupted in these subjects. In this study, we investigated whether siblings of patients with schizophrenia show abnormal brain activation during basic emotion processing.\n\nMethods: Brain activity was measured using functional magnetic resonance imaging in 24 unaffected siblings of patients with schizophrenia and 25 healthy control subjects while they viewed and rated neutral, positive, and negative pictures.

Many factors such as host cell development, cell bank establishme

Many factors such as host cell development, cell bank establishment, cell culture, protein production, purification, analysis, formulation, storage, and handling are critical for ensuring the purity, activity,

and safety of the finished product. Good Manufacturing Practice (GMP) for biodrugs has been developed in certain regions such as the EU, US, and Japan. Due to differences in manufacturing methods and systems, product-specific GMP guidelines are evolving. In general, there are variations in GMP guidelines between countries, which lead to difficulty SB273005 Cytoskeletal Signaling inhibitor for the manufacturers in conforming to different standards, thus entailing delays in the commercialization of biodrugs. There is a need to develop a unified regulatory guideline for biodrug manufacturing across various countries, which would be helpful in the marketing of products and trade. This review deals with the comparative framework and analysis of GMP regulation of biodrugs.”
“Background: Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass

grafting (CABG) surgery. The objective of this study was to determine the impact of POAF on both short- and long-term mortality following isolated CABG. Hypothesis: POAF is associated with a poorer short and long-term mortality following CABG. Methods: We retrospectively analyzed the preoperative and operative data of 6728 consecutive patients undergoing a first isolated CABG. Results: The incidence of POAF was 27.8%. Operative mortality was higher in patients PXD101 ic50 selleck chemical with POAF compared to those without

POAF (2.3% vs 0.9%, P < 0.001). On multivariate analysis, POAF remained an independent predictor of operative mortality (odds ratio [OR]: 1.78, P = 0.01). Patients with POAF also had reduced long-term survival (6-year survival: 85.3% vs 89.2%, P < 0.001). After adjusting for other predictors of mortality, POAF was significantly associated with increased long-term mortality (hazard ratio [HR]: 1.35, P = 0.04). Of note, after adjustment for potential confounders, statin treatment had a highly protective effect in POAF patients for both operative mortality (OR: 0.38, P = 0.003) and long-term mortality (HR: 0.62, P = 0.03), whereas it had no significant effect in patients without POAF. Conclusions: POAF is an independent predictor of both short- and long-term mortality following CABG. Moreover, statin therapy was independently associated with better survival in patients with POAF. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research. Dr. Mathieu is a research scholar from the Fonds de Recherches en Sante du Quebec, Montreal, Canada. Dr. Despres has served as a speaker for Abbott Laboratories, AstraZeneca, Solvay Pharma, GlaxoSmithKline, and Pfizer Canada Inc.

Results: We are developing a model discovery framework that uses

Results: We are developing a model discovery framework that uses a cell-based modeling platform combined with evolutionary search to automatically search for and identify plausible mechanisms for the biological behavior described in PlanformDB. To automate the evolutionary search we developed a way to compare the output of the modeling platform to the morphological descriptions stored in PlanformDB. We used a flexible

connected component algorithm to create a graph representation of the virtual worm from the robust, cell-based simulation data. These graphs can then be validated and compared with target data from PlanformDB using the well-known graph-edit distance calculation, which provides a quantitative metric of similarity between graphs. The graph edit distance calculation was integrated into a fitness function that was able to guide automated SNX-5422 mw selleck compound searches for unbiased models of planarian regeneration. We present a cell-based model of planarian that can regenerate anatomical regions following bisection of the organism, and show that the automated model discovery

framework is capable of searching for and finding models of planarian regeneration that match experimental data stored in PlanformDB. Conclusion: The work presented here, including our algorithm for converting cell-based models into graphs for comparison with data stored in an external data repository, has made feasible the automated development, training, and validation of computational models using morphology-based data. This work is part of an ongoing project to automate the search process, which will greatly expand our ability to identify, consider, and test biological mechanisms in the field of regenerative biology.”
“Autophagy is a catabolic process conserved among eukaryotes. Under nutrient starvation, a portion of the cytoplasm is non-selectively sequestered into autophagosomes. Consequently, ribosomes are

delivered to the vacuole/lysosome for destruction, but the precise mechanism of autophagic RNA degradation and its physiological implications for cellular metabolism remain unknown. We characterized autophagy-dependent RNA catabolism using a combination of metabolome and molecular https://www.selleckchem.com/products/Pazopanib-Hydrochloride.html biological analyses in yeast. RNA delivered to the vacuole was processed by Rny1, a T2-type ribonuclease, generating 3-NMPs that were immediately converted to nucleosides by the vacuolar non-specific phosphatase Pho8. In the cytoplasm, these nucleosides were broken down by the nucleosidases Pnp1 and Urh1. Most of the resultant bases were not re-assimilated, but excreted from the cell. Bulk non-selective autophagy causes drastic perturbation of metabolism, which must be minimized to maintain intracellular homeostasis.