“
“Mutualistic microorganisms are well known to play a key role in providing nutrients for successful growth and reproduction in many insects. Several recent studies indicate that they can be equally important for the protection of the host and its nutritional resources against pathogen attack. In particular, different actinobacteria have been found to defend ants, beetles and

wasps against detrimental microorganisms by producing antibiotics. The extraordinary abilities of actinobacteria to exploit a wide variety of carbon and nitrogen sources and their extensive repertoire of secondary metabolites probably predispose this group to engage in protective symbioses. Defensive mutualisms with actinobacteria might constitute a general and widespread theme in the ecology and evolution of arthropods, and the study of the secondary metabolites involved promises to uncover novel drug candidates for human medicine.”
“There

Bleomycin price is strong evidence that vascular risk factors play a role in the development of Alzheimer’s Selleckchem IACS-10759 disease (AD) or vascular dementia (vaD). Ethanol (EtOH) and cholesterol are such vascular risk factors, and we recently showed that hypercholesterolemia causes pathologies similar to AD [Ullrich et al. (2010) Mol Cell Neurosci 45, 408-417] The aim of this study was to investigate the effects of long-term (12 months) EtOH treatment (20% v/v in drinking water) alone or long-term 5% cholesterol diet alone or a combination (mix) in adult Sprague Dawley rats. Long-term EtOH treatment Flucloronide (plasma EtOH levels 58 +/- 23 mg/dl) caused significant impairment of spatial memory, reduced the number of choline acetyltransferase- and p75 neurotrophin receptor-positive nucleus basalis of Meynert neurons, decreased cortical acetylcholine, elevated

cortical monocyte chemoattractant protein-1 and tissue-type plasminogen activator, enhanced microglia, and markedly induced anti-rat immunoglobulin G-positive blood brain barrier leakage. The effect of long-term hypercholesterolemia was similar. Combined long-term treatment of rats with 20% EtOH and 5% cholesterol (mix) did not potentiate treatment with EtOH alone, but instead counteracted some of the EtOH-associated effects. In conclusion, our data show that vascular risk factors EtOH and cholesterol play a role in cognitive impairment and possibly vaD. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome.

Tesofensine (0.5-3.0 mg/kg, s.c.) induced a dose-dependent and marked decline in food intake with an ED50 of 1.3 mg/kg. The hypophagic

response of tesofensine (1.5 mg/kg, s.c.) was almost completely reversed by co-administration of prazosin (1.0 mg/kg, alpha(1) adrenoceptor antagonist) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D-1 receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, alpha(2) adrenoceptor antagonist), haloperidol (0.03 mg/kg, D-2 receptor antagonist), NGB2904 (0.1 mg/kg, D-3 receptor antagonist), or ritanserin (0.03 mg/kg, 5-HT2A/C receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug’s ability to indirectly stimulate alpha(1) Epacadostat cost adrenoceptor and DA D-1 CRT0066101 chemical structure receptor function. Neuropsychopharmacology ( 2010) 35, 1464-1476; doi: 10.1038/npp.2010.16; published online 3 March 2010″
“Recent studies have implicated alterations in the expression of polyamine-related genes in the brains of suicide completers including widespread downregulation

of spermidine/spermine N1-acetyltransferase, the key enzyme in polyamine catabolism, suggesting compensatory mechanisms attempting to increase brain levels of polyamines. Given the complexity of the polyamine system, quantification of the levels of the polyamines is an essential step in understanding the downstream effects of dysregulated gene expression. We developed a method using high-resolution capillary gas chromatography ( GC) in combination with mass spectrometry ( MS) for quantitation of polyamines from post-mortem brain tissue, which allowed us to accurately measure spermidine and putrescine concentrations in post-mortem brain tissues. Using this method, we analyzed putrescine and spermidine levels in a total of 126 samples from Brodmann areas 4, 8/9, and 11, from 42 subjects, comprising 16 suicide completers with major depression, 13 non-depressed suicide completers,

and 13 control subjects. Both putrescine and spermidine levels fell within the expected nanomolar ranges and were significantly elevated in the brain of suicide completers with a history of major depression as compared with controls. These Alectinib mouse results were not accounted by possible confounders. This is the first GC-MS study to analyze the expression of putrescine and spermidine from post-mortem brain tissue and confirms the hypothesis raised by previous studies indicating alterations in putrescine and spermidine levels in suicide/major depression. Neuropsychopharmacology ( 2010) 35, 1477-1484; doi: 10.1038/npp.2010.17; published online 3 March 2010″
“Changes in the brain’s cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer’s disease, schizophrenia, and depression.

Conclusions

During the early phase of this influenza pandemic, there was a sudden increase in the rate of severe pneumonia and a shift in the age distribution

of patients with such illness, which was reminiscent of past pandemics and suggested relative protection for persons who were exposed to H1N1 strains during childhood before the 1957 pandemic. If resources or vaccine supplies are limited, these findings suggest a rationale for focusing prevention efforts on younger populations.”
“Early events in white spot syndrome virus (WSSV) morphogenesis, particularly the formation of viral membranes, are poorly understood. The major envelope proteins of WSSV are VP28, VP26, VP24, and VP19. Our previous results indicated that VP28 interacts with VP26 and Gemcitabine in vitro VP24. In the present study, we used coimmunoprecipitation assays and pull-down assays to confirm that the four major proteins in the WSSV envelope can form a multiprotein complex. Yeast two-hybrid assays were also used to test for interactions among the four Selleck AZD6094 proteins. In summary, three pairwise protein interactions (VP19-VP28,VP19-VP24, and VP24-VP26) and one self-association (VP24-VP24) were identified for the first time.”
“Background

In late March 2009, an outbreak of a respiratory illness later proved to

be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary hospital for respiratory illnesses in Mexico City who had laboratory-confirmed S-OIV infection, also Immune system known as swine flu.

Methods

We used retrospective medical chart reviews to collect data on the hospitalized patients. S-OIV infection was confirmed in specimens with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay.

Results

From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City. More than

half of the 18 case patients were between 13 and 47 years of age, and only 8 had preexisting medical conditions. For 16 of the 18 patients, this was the first hospitalization for their illness; the other 2 patients were referred from other hospitals. All patients had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and bilateral patchy pneumonia. Other common findings were an increased creatine kinase level ( in 62% of patients) and lymphopenia ( in 61%). Twelve patients required mechanical ventilation, and seven died. Within 7 days after contact with the initial case patients, a mild or moderate influenza-like illness developed in 22 health care workers; they were treated with oseltamivir, and none were hospitalized.

“
“Background/Aims: The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na+ channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The

present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na+ exretion, blood pressure and extracellular fluid volume regulation. Methods: Experiments were performed in gene-targeted mice lacking functional JAK3 (jak3(-/-)) and in wild type mice (jak3(+/+)). Colonic ENaC activity was estimated from find more amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na+ concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay. Results: The amiloride (50 mu M)-induced deflection of the transepithelial potential difference was significantly lower and fecal Na+ excretion significantly higher in jak3(-/-) mice than in jak3(+/+) mice. Moreover, systolic IACS-10759 mouse arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher

in jak3(-/-) mice than in jak3(+/+) mice. Both, absolute and fractional renal Na+ excretion were significantly lower in jak3(-/-) mice than in jak3(+/+) mice. Conclusions: JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na+ loss, decrease of blood pressure, increased aldosterone release and subsequent

stimulation of renal tubular Na+ reabsorption. Copyright (C) 2013 S. Karger AG, Basel”
“The well-established method for high-throughput construction of an expression system of the yeast Saccharomyces cerevisiae uses homologous recombination between an expression plasmid and a target gene (with homologous regions of the plasmid on both ends added by PCR). This method has been widely used for membrane proteins using plasmids containing GFP, and has been successfully used to investigate the cellular localization and solubilization conditions of the proteins. Although the methanol-utilizing yeast Pichia pastoris is Flucloronide known as an excellent expression host, a method for high-throughput construction of an expression system like that in S. cerevisiae has not been reported. In this study, we have attempted to construct expression systems via homologous recombination in P. pastoris. The insertion of genes into a plasmid could be easily checked by colony-PCR. Expression systems for seven membrane proteins of medaka fish (Oryzias latipes) and yeast (S. cerevisiae) were constructed, and the expression of proteins was analyzed by fluorescence spectra, fluorescence microscopy, and SDS-PAGE (in-gel fluorescence detection). (c) 2010 Elsevier Inc. All rights reserved.

Two major quantitative trait loci (QTL) for morphine consumption and preference exist between these strains on chromosomes (Chrs.) 6 and 10 when

the two-bottle choice involves morphine in saccharin vs quinine in saccharin. Here, we report the refinement of the Chr. 10 QTL in subcongenic strains of D2. B6-Mop2 congenic mice described previously. With these subcongenic mouse strains, we have divided the introgressed region of Chr. 10 containing the QTL gene(s) into two segments, one between the acromere and Stxbp5 (in D2.B6-Mop2-P1 mice) and the other between marker D10Mit211 and marker D10Mit51 (in D2.B6-Mop2-D1 mice). We find that, similar to B6 mice, the D2.B6-Mop2-P1 congenic mice exhibit a strong preference for morphine over quinine, whereas D2.B6-Mop2-D1 check details Givinostat chemical structure congenic mice avoid morphine (similar to D2 mice). We have also created a line of double congenic mice, B6.D2-Mop2. Qui, which contains both Chr. 10 and Chr. 6 QTL. We find that they are intermediate in their morphine preference scores when compared with B6 and D2 animals. Overall, these data suggest that the gene(s) involved in morphine preference in the morphine-quinine two-bottle choice paradigm are contained within the proximal region of Chr. 10 (which

harbors Oprm1) between the acromere and Stxbp5, as well as on distal Chr. 6 between marker D6Mit10 and the telomere.”
“The storage conditions of the donor kidney may influence the deleterious consequences of ischemia/reperfusion (IR), which remains a major source of complications in clinical practice. Delayed graft function (DGF), seen in 20% to 50% of transplanted cadaver kidneys, is a major risk factor affecting early and long-term graft survival, patient management, and costs of transplantation. Cold preservation plays a key role in this process and is based on hypothermia and high potassium solutions. In this review, the authors focused on the major molecular mechanisms of cold storage (CS) injury at the cellular level, which have been recently

evidenced with modern Amoxicillin biochemical and cell biologic methods. These newly uncovered aspects of cold preservation injury are often not fully addressed by preservation solutions in current clinical practice. The role of new molecules such as polyethylene glycol (PEG) is presented and their properties are analyzed in the organ preservation context. PEG improves organ function recovery and reduces inflammation and fibrosis development in several models. Because organs shortage is also a real public health problem, organs from non-heart beating donors or marginal donors are now used to expand pool of organs. As a consequence, the development of better organ preservation methods remains a major target and deserves scientific consideration.”
“WNT signaling is a fundamental molecular pathway in both embryogenesis and disease. Nephron development is dependent on WNT signaling.

We consistently demonstrate differences in epitope presentation kinetics, with very early presentation, within 3 h postinfection, for the protective KF11Gag, KK10Gag epitopes, and KY9Pol but only late presentation for VL9Vpr. We show that this early presentation relies on the antigen being presented from incoming viral particles and is correlated with rapid CD8(+) T cell activation and clearance of virus-infected cells. Additionally, our data indicate a dose-response dependency learn more between the levels of CD8(+) T cell activation and the amount of virus inoculum.

These data reflect a proof of principle emphasizing the importance of identifying early-presented viral epitopes for rapid elimination of HIV-1-infected cells.”
“The endosporic male gametophyte of the water fern, Marsilea vestita, provides a unique opportunity to study the mechanisms that control cell fate determination during a burst of rapid development. In this review, we show how the spatial and temporal control of development

in this simple gametophyte involves several distinct modes of RNA processing that allow the translation of specific mRNAs at distinct stages during gametogenesis. During the early part of development, nine successive cell division cycles occur in precise planes within a closed volume to see more produce seven sterile cells and 32 spermatids. There is no cell movement in the gametophyte; so, cell position and size within the spore wall define cell fate. After the division cycles have been completed, the spermatids become sites for the de novo formation of basal bodies, for the assembly of a complex cytoskeleton, for nuclear and cell elongation,

and for ciliogenesis. In contrast, the adjacent sterile cells exhibit none of these changes. Metalloexopeptidase The spermatids differentiate into multiciliated, corkscrew-shaped gametes that resemble no other cells in the entire plant. Development is controlled post-transcriptionally. The transcripts stored in the microspore are released (unmasked) in the gametophyte at different times during development. At the start of these studies, we identified several key mRNAs that undergo translation at specific stages of gametophyte development. We developed RNA silencing protocols that enabled us to block the translation of these proteins and thereby establish their necessity and sufficiency for the completion of specific stages of gametogenesis. In addition, RNAi enabled us to identify additional proteins that are essential for other phases of development. Since the distributions of mRNAs and the proteins they encode are not identical in the gametophyte, transcript processing is apparently important in allowing translation to occur under strict temporal and spatial control. Transcript polyadenylation occurs in the spermatogenous cells in ways that match the translation of specific mRNAs.

Materials and Methods: The study population included 177 men eligible for active surveillance who fulfilled clinicobiological criteria and biopsy criteria as group 1-less than 3 positive cores and

less than 3 mm total tumor length, group 2-less than 3 positive cores with cancer involvement of less than 50% in any core and group 3-less than 33% of positive cores. Prostate specific antigen density cutoffs were also studied in these groups. Pathological findings on radical prostatectomy specimens and biochemical recurrence-free survival were studied. Median followup after radical prostatectomy was 34 months.

Results: A majority of Gleason score 6 disease was observed in group 1 (51.7%) whereas a majority of Gleason score 7 or greater disease was reported in groups 2 (53.6%) Selleck R788 and 3 (55.4%). Extracapsular extension was noted in 17.5% of radical prostatectomy specimens in group 3 vs 11.2% in group 1 (p = 0.175). The risk of AZD5153 mw overall unfavorable disease (defined as pT3-4 stage and/or Gleason score 8 or greater) was significantly higher in men with cancer involvement of 3 mm or greater on initial biopsy (27.3% vs

13.5%, respectively, p = 0.023). The 3-year biochemical recurrence-free survival rate was 94.0% and was not affected by the 3 active surveillance definitions.

Conclusions: Even with the use of a 21-core biopsy protocol the rate of unfavorable disease in radical prostatectomy specimens remains increased in men eligible for active surveillance. Patients must be informed of this risk of misclassification. which ranges from 20% to 28% in men who fulfill the less stringent biopsy criteria.”
“Elucidation of the cellular and molecular mechanisms of the circadian clock, along with the realization that these mechanisms are operative in both central and peripheral tissues, has revolutionized circadian biology. Tyrosine-protein kinase BLK Further, these

observations have resulted in an explosion of interest in the health implications of circadian organization and disorganization at both molecular and physiological levels. Thus, recent research has implicated mutations and polymorphisms of circadian clock genes in diabetes and obesity, cardiovascular disease, and cancer. At the neuro-behavioral level, circadian clock genes have also been implicated in sleep disorders, drug and alcohol addiction, and other psychiatric conditions. While such findings are frequently described as revealing “”non-circadian”" effects of clock genes, it remains possible that most of these non-circadian effects are in fact secondary to the loss of cellular and systemic rhythmicity. This review summarizes the evidence linking circadian clock genes to biobehavioral dysregulation, and considers criteria for defining a pleiotropic clock gene effect as non-circadian. (C) 2010 Elsevier Ltd. All rights reserved.

The propensity score analysis identified statistically significant decreased odds of developing reversible adverse outcomes in patients undergoing deep hypothermic circulatory arrest (odds ratio, 0.32; confidence interval, 0.12-0.85). Specifically, significantly lower rates of acute renal failure (22% vs 46.4%, P = .03) and find more liver failure

(17.8% vs 34.3%, P = .04) were observed in the deep hypothermic circulatory arrest group compared with the non-deep hypothermic circulatory arrest group. In addition, there were decreased odds of reversible adverse outcomes (odds ratio, 0.22; confidence interval, 0.06-0.79) developing in patients with a stage II elephant trunk procedure.

Conclusions: During descending thoracic aortic and thoracoabdominal aortic aneurysm repairs, the use of deep hypothermic circulatory arrest results in improved postoperative adverse outcome rates Aurora Kinase inhibitor compared with non-deep hypothermic circulatory

arrest techniques. The development of reversible adverse outcomes is strongly associated with the development of permanent adverse outcomes. (J Thorac Cardiovasc Surg 2012;143:186-93)”
“Searching a spectral library for the identification of protein MS/MS data has proven to be a fast and accurate method, while yielding a high identification rate. We investigated the potential to increase peptide discovery rate, with little increase in computational time, by constructing a workflow based on a sequence search with Phenyx followed by a library search with SpectraST. Searching a consensus library compiled from the search results of the prior Phenyx search increased the number of confidently matched spectra by up to 156%. Additionally matched spectra by SpectraST included noisy spectra, spectra representing missed cleaved peptides as well as spectra from post-translationally modified peptides.”
“Extensive research

has ADAM7 been accumulated demonstrating that sleep is essential for processes of memory consolidation in adults. In children and infants, a great capacity to learn and to memorize coincides with longer and more intense sleep. Here, we review the available data on the influence of sleep on memory consolidation in healthy children and infants, as well as in children with attention-deficit/hyperactivity disorder (ADHD) as a model of prefrontal impairment, and consider possible mechanisms underlying age-dependent differences. Findings indicate a major role of slow wave sleep (SWS) for processes of memory consolidation during early development. Importantly, longer and deeper SWS during childhood appears to produce a distinctly superior strengthening of hippocampus-dependent declarative memories, but concurrently prevents an immediate benefit from sleep for procedural memories, as typically observed in adults. Studies of ADHD children point toward an essential contribution of prefrontal cortex to the preferential consolidation of declarative memory during SWS.

This timing corresponds well to morphologic changes that occur in the retina during different stages of angiogenesis.

CONCLUSION: Quizartinib The neonatal rodent retina, which has a cellular architecture similar to that of the brain, has active and quantifiable angiogenic activity during the neonatal period and can be used as a simple and convenient model to study cerebral angiogenesis.”
“BACKGROUND: Although there are several large-species animal models for saccular aneurysms, there is a need for a simple, reproducible

saccular aneurysm model in mice.

OBJECTIVE: To develop a murine saccular aneurysm model, which replicates key characteristics that occur in the formation of human cerebral aneurysms.

METHODS: Elastase

is applied extravascularly to the right common carotid artery. We induced saccular aneurysm formation by our method in C57BL/6 mice (n = 30). Aneurysms and control arteries (left common carotid arteries) were harvested at 1 week, 2 weeks, and 3 weeks postinjury (n = 10 for each time point), measured, and stained for elastin content. To demonstrate BMP-derived cell recruitment to the aneurysms, bone marrow from UBC-gfp transgenic mice was transplanted this website into irradiated C57BL/6 recipients to create C57BL/6. gfp chimeras. Additionally, bone marrow from DsRed transgenic mice was transplanted into irradiated C57BL/6 recipients to create C57BL/6. DsRed chimeras, and bone marrow from B5/EGFP transgenic mice was transplanted into irradiated FVB recipients to create FVB. gfp chimeras. The elastase injury or sham operations were performed in the C57BL/6. gfp, C57BL/6. DsRed, and FVB. gfp chimeras. Aneurysms and sham vessels were harvested at 3 weeks and examined for BMP-derived cell recruitment. Additionally, aneurysms were stained for matrix metalloproteinase-9, which is overexpressed in human cerebral

aneurysm tissue.

RESULTS: Aneurysms consistently demonstrated significant loss of elastin in the vessel wall and had significantly larger diameters Flavopiridol (Alvocidib) than control vessels (591 +/- 238 mu m vs 328 +/- 61 mu m; P = .003 for aneurysms 3 weeks postinjury). Aneurysms from C57BL/6. gfp, FVB. gfp, and C57BL/6. DsRed chimeras consistently revealed significant BMP-derived cell recruitment in the aneurysm wall that was not seen in sham-operated vessels nor in control left common carotid arteries. Aneurysms demonstrated overexpression of matrix metalloproteinase-9.

CONCLUSION: We describe a novel murine elastase saccular aneurysm model that replicates the histopathology and BMP-derived cell-mediated processes that will be a valuable instrument for studying the cell-mediated processes in cerebral aneurysm formation.”
“Objectives: This study evaluated the feasibility and outcomes of percutaneous transhepatic balloon angioplasty (PTBA) of the hepatic vein in the management of Budd-Chiari syndrome (BCS) secondary to hepatic venous outflow obstruction.

Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting

cell (APC) and elicits effector responses dominated by recipient T cells. In allograft rejection, the engagement of recipient and donor cells results in recruitment of T-helper (Th) cells of the Th1 and Th17 lineage to the graft. Citarinostat In cases in which the alloresponse is dominated by regulatory T cells (Tregs), rejection can be prevented and the allograft tolerated with minimum or no immunosuppression. Here, we review the pathways of allorecognition that underlie CAD and the T-cell effector phenotypes elicited as part of the alloresponse. Future therapies including depletion of donor-reactive lymphocytes, costimulation blockade, negative vaccination using dendritic cell subtypes, and Treg therapy are inferred from an understanding of these

mechanisms of allograft rejection. Kidney International (2010) 78 (Suppl 119), S2-S12; doi:10.1038/ki.2010.416″
“Individuals with Down syndrome have well known cognitive and sensorimotor impairments, however, the underlying neural processes are poorly understood. The objective of this study was to investigate the underlying spatial localization and functional connectivity during voluntary movements of the right index finger. Adults with Down syndrome and healthy control adults participated in this study. Cortical responses were recorded with a 151-channel magnetoencephalographic system. In the Down syndrome group, we observed two distinct patterns of brain AR-13324 manufacturer activation, an ipsilateral pattern and a contralateral

pattern in the low-frequency band. The two distinct patterns of neural activation and the altered underlying network dynamics have not been reported previously, and may reflect differences in sensorimotor organization. NeuroReport 22:358-364 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Using IKBKE kidneys from expanded-criteria donors to alleviate organ shortage has raised concern on reduced transplant outcomes. In this paper, we review how critical donor-related factors such as donor age, brain death, and consequences of ischemia-reperfusion injury (IRI) determine graft quality and impact chronic allograft nephropathy. We propose that combinatorial effects of organ-intrinsic features associated with increasing age and unspecific injuries related to brain death and IRI will impact innate and adaptive immune responses. Future research will need to explore avenues to optimize donor management, organ preservation, adapted immunosuppressive strategies, as well as modifications of the allocation of suboptimal allografts.”
“Stem cells have the ability to self renew and are therefore a good source for cell therapy following ischemia.