V. All rights reserved.”
“Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer’s disease (AD) neuropathology, including basal forebrain cholinergic neuron

(BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against PRIMA-1MET BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1 g/kg choline chloride) or choline supplemented (5.0 g/kg choline chloride) diet Between 13 and 17 months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs

in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship Selisistat research buy between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and

effective treatment approach for expectant mothers carrying a DS Prexasertib fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. (C) 2014 Elsevier Inc. All rights reserved.”
“In the work, a novel graphene-based solid phase microextraction-gas chromatography/mass spectrometry method was developed for the analysis of trace amount of volatile organic compounds in human exhaled breath vapor. The graphene fiber coating was prepared by a one-step hydrothermal reduction reaction. The fiber with porous and wrinkled structure exhibited excellent extraction efficiency toward eight studied volatile organic compounds (two n-alkanes, five n-aldehydes and one aromatic compound). Meanwhile, remarkable thermal and mechanical stability, long lifespan and low cost were also obtained for the fiber. Under the optimal conditions, the developed method provided low 123 limits of detection (1.0-4.5 ng L-1), satisfactory reproducibility (3.8-13.8%) and acceptable recoveries (93-122%). The method was applied successfully to the analysis of breath samples of lung cancer patients and healthy individuals. The unique advantage of this approach includes simple setup, non-invasive analysis, cost-efficient and sufficient sensitivity. The proposed method supply us a new possibility to monitor volatile organic compounds in human exhaled breath samples. (C) 2014 Elsevier B.V. All rights reserved.

\n\nResults: (1) Cognitive function is severely impaired in C5aR(-/-) mice, coincident with the down-regulated CREB/CEBP pathway in Selleck LGX818 brain. (2) Either the application of recombinant-human-C5a (hrC5a) or exogenous expression of C5a in the brain of a mouse model (C5a/GFAP) enhances this pathway. (3) Application of hrC5a in brain slices from Tg2576 mice significantly improves deficits in long-term potentiation (LTP), while this effect is blocked by a specific AMPA receptor antagonist. (4) Searching for a pharmacological approach to locally mediate C5a responses in the brain, we found that low-dose human intravenous immunoglobulin (IVIG) treatment improves synaptic plasticity and cognitive function

through C5a-mediated induction of the CREB/CEBP pathway, while the levels of A beta in the brain are not significantly affected.\n\nConclusion: This study for the first https://www.selleckchem.com/products/AZD8055.html time provides novel evidence suggesting that C5a may beneficially influence cognitive function in AD through an up-regulation of AMPA-CREB signaling pathway. IVIG may systematically improve cognitive function in AD brain by passing A beta

toxicity. Published by Elsevier Ltd.”
“Objective: To estimate the prevalence of depression in persons with epilepsy (PWE) and the strength of association between these 2 conditions.\n\nMethods: The MEDLINE (1948-2012), EMBASE (1980-2012), and PsycINFO (1806-2012) databases, reference lists of retrieved articles, and conference abstracts were searched. Content experts were also consulted. Two independent reviewers screened abstracts and extracted data. For inclusion, studies were population-based, original research, and reported on epilepsy and depression. Estimates of depression prevalence among PWE and of the association between epilepsy and depression (estimated with reported odds ratios [ORs]) are provided.\n\nResults: Of 7,106 abstracts screened, 23 articles reported on 14 unique data sources. Nine studies reported on 29,891 PWE who had an overall

prevalence of active (current or past-year) depression of 23.1% (95% confidence interval [CI] 20.6%-28.31%). Five of Galardin mw the 14 studies reported on 1,217,024 participants with an overall OR of active depression of 2.77 (95% CI 2.09-3.67) in PWE. For lifetime depression, 4 studies reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1-33.1), and 3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07-4.51) for PWE.\n\nConclusions: Epilepsy was significantly associated with depression and depression was observed to be highly prevalent in PWE. These findings highlight the importance of proper identification and management of depression in PWE. Neurology (R) 2013;80:590-599″
“Mammalian prions cause fatal neurodegenerative conditions including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals(1).

There is much room for future improvement.”
“In this study, apparent usability and affective quality were integrated in a design framework called the Usability Perception and Emotion Enhancement Model (UPEEM). The UPEEM was validated using structural 123 equation modeling (SEM). The methodology consists of four phases namely product selection, attribute identification, design alternative generation, and design alternative evaluation.

The first stage involved the selection of a product that highly involves the consumer. In the attribute identification stage, design elements of the product were identified. The possible values of these elements were also determined for use in the experimentation process. Design of experiments was used to identify how the attributes will be varied in the design

alternative stage and which of the attributes CX-6258 significantly contribute to affective quality, apparent usability, and desirability in the design evaluation stage. Results suggest that product attributes related to form are relevant in eliciting intense affect and perception of usability in mobile phones especially those directly related to functionality and aesthetics. This study considered only four product attributes among so many due to the constraints of the research design employed. Attributes related to aesthetic perception of a product enhance apparent usability such as those related to dimensional ratios. (C) 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.”
“We Selleck GW4869 present an updated assessment of soil contamination due to the nuclear accident at the Fukushima No. 1 nuclear power plant on 11 March 2011. A safe limit for the spatial dose rate (micro-Sv/h) of gamma rays from Cs-134,Cs-137 has been established in this work. Based on this value, the highly contaminated region within Fukushima Prefecture that must be decontaminated could be defined. Moreover, 4SC-202 a conceptual model for the

chemical speciation that occurred during the accident has been delineated. The compound model Cs2CO3 was found to be meaningful and practical (non-radioactive) to simulate contamination in our decontamination experiments. Finally, we explain the mechanism of action of our soil remediation technique, which effectively reduces the total volume of contaminated soil by isolating the highly Cs-adsorptive clay fraction. The adsorption of non-radioactive Cs atoms on clay particles with diameters <25 mu m were analyzed using micro-particle-induced X-ray emission (PIXE). (C) 2013 Elsevier B.V. All rights reserved.”
“OBJECTIVE: To describe a technique to approach the anterior inferior basal ganglia.

The depigmenting abilities of chloroquine and quinine salicylate were assessed in a human skin equivalent model (MelanoDerm). Both compounds were considerably more effective than arbutin, a widely used lightening agent. Our results indicate

that quinolines may be useful agents for “cosmeceutical” skin lightening and treatment of hyperpigmentation disorders.”
“Apoptosis is mediated by an intracellular biochemical system that mainly includes proteins (procaspases, caspases, inhibitors, Bcl-2 protein family as well as substances released from mitochondrial intermembrane space). The dynamics of caspase activation and target cleavage in apoptosis induced by granzyme B in a single K562 cell was studied using a mathematical model of the dynamics of granzyme B-induced apoptosis developed in this work. Also the first application of optimization Lazertinib approach to 3 determination of unknown kinetic

constants of biochemical apoptotic reactions was presented. The optimization approach involves solving of two problems: direct and inverse. Solving the direct optimization problem, we obtain the initial (baseline) concentrations of procaspases for known kinetic constants through conditional Stem Cell Compound Library order minimization of a cost function based on the principle of minimum protein consumption by the apoptosis system. The inverse optimization problem is aimed at determination of unknown kinetic constants of apoptotic biochemical reactions proceeding from the condition that the optimal concentrations of procaspases resulting from the solution of the direct optimization problem coincide with the observed ones, that is, those determined by biochemical methods. The Multidimensional Index Method was used

to perform numerical solution of the inverse optimization problem. (c) 2007 Elsevier Inc. All rights reserved.”
“Background and Purpose: The recent technologic advances in the newer generation of Selleck GW4869 flexible ureteroscopes have significantly enhanced the therapeutic and diagnostic efficacy of ureteroscopy. The purpose of our study was to assess ureteroscopy and lithotripsy of renal calculi without a safety wire, using the ureteroscope as the safety device.\n\nPatients and Methods: Medical records for patients undergoing ureteroscopy by a single surgeon were retrospectively reviewed from December 2006 to December 2009. Inclusion criteria for our study included all adult patients who underwent wireless flexible ureteroscopy for the management of renal calculi and had 1 month follow-up data.\n\nResults: Of the 568 patients who underwent ureteroscopy during this period, 268 patients met our study inclusion criteria. The mean age of the patients undergoing wireless ureteroscopy was 33 years, and the mean body mass index was 33.1 kg/m(2). Mean stone diameter of the renal calculi treated was 12.0+/-5.9 mm.

The aim

of this study was to use oscillatory changes in the electroencephalogram (EEG) related to informative cue processing, motor preparation, and top-down control to investigate neurophysiological differences between typically 4 developing (TD) adolescents, and those diagnosed with predominantly inattentive (IA) or combined (CB) (associated with symptoms of inattention as well as impulsivity/hyperactivity) subtypes of ADHD. Methods: The EEG was recorded from 57 rigorously screened adolescents (12 to17 years of age; 23 TD, Erismodegib 17 IA, and 17 CB), while they performed a cued flanker task. We examined the oscillatory changes in theta (3-5 Hz), alpha (8-12 Hz), and beta (22-25 Hz) EEG bands after cues that informed participants with which hand they would subsequently be required to respond. Results: Relative to TD adolescents, the IA group showed significantly less postcue alpha suppression, suggesting diminished processing of the cue in the visual cortex, whereas the CB

group showed significantly less beta suppression at the electrode contralateral to the cued response hand, suggesting poor motor planning. Finally, both ADHD subtypes showed weak functional connectivity between frontal theta and posterior alpha, suggesting common top-down control impairment. Conclusions: We found both distinct and common task-related neurophysiological impairments in ADHD subtypes. Our results suggest that task-induced changes in EEG oscillations provide an objective measure, GW4869 datasheet which in conjunction with other sources of information might help distinguish between ADHD subtypes and therefore aid in diagnoses YAP-TEAD Inhibitor 1 research buy and evaluation of treatment.”
“Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression

of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of beta-catenin and GSK3 beta. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased.

1 and 11.0 % among the three sites. The non-parametric bootstrapped potential source contribution function analysis was further applied to localize the regions of sources apportioned by the RCMB. For the majority of sources, source regions appeared as being located within short distances from the sampling sites (within the Peloponnesse Peninsula). More distant Greek areas of the NNE sector also appeared to be source regions for traffic emissions and secondary calcium sulfate dust.”
“Background. Single-incision laparoscopic surgery has been

increasingly adopted in pediatric surgery. Nevertheless, its feasibility Stattic and safety in neonates with congenital biliary malformations is unclear. This study reports successful single-incision laparoscopic hepaticojejunostomy (SILH) for neonates with extrahepatic biliary cystic lesions. Methods. Ten neonates with extrahepatic biliary

cystic lesions (choledochal cyst/correctable biliary atresia: 6/4) who underwent SILH between May 2011 and September 2011 were reviewed. Ultrasonography, upper gastrointestinal contrast studies, and laboratory tests were performed during the follow-up period. Results. Mean operative time, postoperative hospital stay, time to full feeding, and duration of drainage were comparable to our historic open-control groups of 15 neonates with choledochal cysts and 7 patients with Prexasertib molecular weight correctable biliary atresia. Median follow-up duration was 6.0 months. They regularly took medical

treatments during the follow-up periods. selective HDAC inhibitors The jaundice subsided or liver function was normalized within 3 months postoperatively. So far, no mortality or morbidity of cholangitis, bile leak, anastomotic stenosis, and intrahepatic reflux were encountered. Conclusions. In experienced hands, SILH for neonates with extrahepatic biliary cystic lesions is feasible and safe. It provides a new alternative for neonatal hepatobiliary surgery.”
“Murphy, S. E., Lee, E. A., Woodrow, L., Seguin, P., Kumar, J., Rajcan, I. and Ablett, G. R. 2009. Association of seed and agronomic traits with isoflavone levels in soybean. Can. J. Plant Sci. 89: 477-484. Soybean, Glycine max (L.) Merr., seeds contain isoflavones, compounds with potential human health benefits. This study investigated the association of seed and agronomic traits with isoflavone level in a genetically diverse group of soybean genotypes to provide more information for cultivar development. F(4:7) lines derived from several crosses were grown in four locations in 2005 and six locations in 2006 across Ontario and Quebec. Seed protein, oil and isoflavone contents were measured using near-infrared reflectance (NIR) on a plot basis. Seed yield was determined at 13% moisture and days to maturity (R8) were recorded.

We describe here experiences of determining markers of apoptosis in human platelets treated in vitro with pro-apoptotic chemical and physical stimuli. These include depolarization of mitochondrial inner membrane, cytochrome c release, expression of pro-apoptotic and anti-apoptotic proteins of Bcl-2 family, activation of apoptosis executioner caspase-3, exposure of phosphatidylserine, platelet shrinkage, fragmentation to microparticles, blebbing and filopod extrusion on the platelet surface. These assays serve to characterize platelet apoptosis in different cellular compartments (mitochondria, cytosol and plasma membrane) and at the whole-cell level. Methods commonly employed in studies of platelet apoptosis markers include check details flow

cytometry, Western blot analysis and electron microscopy. An integrated methodological approach, based on determination of different platelet apoptosis markers, represents a useful tool for examining platelet apoptosis in various physiological and pathological settings.”
“Background: The large caliber of head hair in hair transplantation imparts a coarse hairline, whereas natural hairlines are typically softer. In hirsute individuals, transplantation of leg hair to the hairline may result in a superior aesthetic appearance.\n\nObservation:

A total of 1025 leg hair follicles in 1 patient were grafted to an area 0.5 to 1.0 cm in front of and 0.5 to 1.0 cm internal to the vanguard hair of the original hairline and temporal recesses; the other patient received approximately 1000 leg hairs and 600 head hairs to advance SNS-032 cost and soften his hairline and to create a custom widow’s peak. Transplantation resulted in a fully grown and soft-looking hairline after 9 months in the first patient, with growth of 75% to 80% of the transplanted leg hair. The mean length of the transplanted leg hair was longer than the length of the original leg hair, with less curliness but similar hair width. Transplanted leg hair width was significantly finer compared with existing head hair width. After 4 years, results were sustained, minimizing concerns that subsequent

hair loss might result from leg hair cycle variations. In the second patient, selleck kinase inhibitor similar results were observed at 3 years.\n\nConclusion: The use of leg hair in transplantation provides additional options in patients with hairlines that need to be refined.”
“To examine the standard Mn and Cu concentrations in mixed saliva from children and the relationship between these levels and dental caries, resting mixed saliva samples obtained from 527 children of an elementary school in Kitakyushu City were collected at 10:00-11:30 a.m. during December 2004. The Mn and Cu concentrations were determined using simultaneous multi-element atomic absorption spectrometry. The standard Mn and Cu levels were 22.0 +/- 15.2 and 3.8 +/- 4.1 ng/mL, respectively, in the sound teeth group. Mn levels were significantly higher in boys (25.4 +/- 17.4 ng/mL) than girls (19.1 +/- 12.

Results: Three patients received first-line, four patients received second-line, and three patients received third-line treatment. All patients were able to receive a single-regimen of chemotherapy for more than a year. The survival of patients who received monthly chemotherapy was significantly better than survival of those who received

SOX or XELOX within 30 months after starting chemotherapy (p smaller than 0.05). Conclusion: For patients with very slow tumour growth rates, our monthly chemotherapy may be beneficial.”
“The renin-angiotensin system regulates the vascular fibrinolytic balance. In the human forearm vasculature, angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) increase the release

of t-PA through endogenous bradykinin. We tested the hypothesis that ACE inhibition and sex modulate the endogenous coronary release of tissue plasminogen activator (t-PA) in hypertensive selleck kinase inhibitor patients. Seventy-three patients underwent diagnostic coronary angiography and had normal coronary angiograms. Thirty-three patients (21 men and 12 women) were treated with imidapril (5 mg/day) for 4 weeks (ACE-I group), and 40 (23 men and 17 women) were not treated with ACE-I (non-ACE-I group). All of the women were postmenopausal. Coronary blood flow in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary t-PA release was determined as (coronary sinus-aorta gradient of t-PA)X(coronary blood flow)X[(100-hematocrit)/100]. Age, arterial pressure, heart rate, lipid levels, JQ-EZ-05 in vivo coronary flow, and the plasma level of t-PA at either aorta or coronary sinus were comparable among the 4 groups. In women, net t-PA release in the ACE-I group was significantly higher than that in the other groups (P<0.05; man non-ACE-I group: 1.4 +/- 2.6 ng/mL; woman non-ACE-I group: 1.4 +/- 3.1 ng/mL; man ACE-I group: -1.8 +/- 2.8 Quizartinib ng/mL; woman ACE-I group: 14.8 +/- 3.6 ng/mL). Correction for smoking status gave similar results. There was a significant negative correlation between serum ACE activity and coronary t-PA release in women (r=-0.38; P<0.05) but not in men. ACE inhibition

increases coronary release of t-PA in women but not in men. (Hypertension. 2010;56:364-368.)”
“A configuration that shows great promise in sensing applications is vertically aligned piezoelectric nanowire arrays that allow facile interfacing with electrical interconnects. Nano-electromechanical systems developed using piezoelectric nanowires have gained interest primarily for their potential in energy harvesting applications, because they are able to convert several different sources of mechanical energy into useful electrical power. To date, no results have demonstrated the capability to use aligned piezoelectric nanowire arrays as a highly accurate nano-electromechanical system based dynamic sensor with a wide operating bandwidth and unity coherence.

Multidisciplinary approach in decision who is a proper candidate for PEG tube placement is recommended.”
“Renal transplantation provides the best quality of life for the patients with chronic end-stage renal failure. However, the immunosuppression

necessary for graft survival may give rise to infectious complications, an increased risk of cardiovascular and neoplastic diseases, all of which can shorten the patient’s survival. The objective of this study was to evaluate the efficacy and safety of the proliferation signal inhibitor immunosuppressant drugs everolimus among patients who develop neoplasms after renal transplantation. HSP990 nmr This retrospective study included 25 patients (mean age -56.5 +/- 14.1 years) who were diagnosed with posttransplant neoplastic disease and immunosuppressed with calcineurin inhibitors (CNIs). Treatment was initiated with everolimus with or without CNIs. During the follow-up, the renal function (initial serum creatinine 1.4 mg/dL vs final serum creatinine 1.3 mg/dL) and proteinuria levels (initial 0.3 g/d vs final 0.4 g/d) remained stable. There was a low percentage of patients with relapse of their tumor. One patient had a relapse of bladder cancer with tumor progression at 3 years; another patient with melanoma developed lymph node invasion. There were

neither acute rejection episodes nor cardiovascular complications. The results suggested that tumor relapse was low. The results suggested that immunosuppression PF-00299804 in vivo with everolimus combined with low doses of CNIs or in single-drug therapy is safe immunosuppression for patients who develop posttransplant malignant diseases.”
“Purpose: Currently, no imaging modality is used routinely to assess tumor responses to radiotherapy OICR-9429 chemical structure within hours to days after the delivery of treatment. In this study, we show the

application of quantitative ultrasound methods to characterize tumor responses to cancer radiotherapy in vivo, as early as 24 hours after treatment administration.\n\nExperimental Design: Three mouse models of head and neck cancer were exposed to radiation doses of 0, 2, 4, and 8 Gray. Data were collected with an ultrasound scanner using frequencies of 10 to 30 MHz. Ultrasound estimates calculated from normalized power spectra and parametric images (spatial maps of local estimates of ultrasound parameters) were used as indicators of response.\n\nResults: Two of the mouse models (FaDu and C666-1) exhibited large hyperechoic regions at 24 hours after radiotherapy. The ultrasound integrated backscatter increased by 6.5 to 8.2 dB (P < 0.001) and the spectral slopes increased from 0.77 to 0.90 dB/MHz for the C666-1 tumors and from 0.54 to 0.78 dB/MHz for the FaDu tumors (P < 0.05), in these regions compared with preirradiated tumors. The hyperechoic regions in the ultrasound images corresponded in histology to areas of cell death.

Vincristine formulated in the targeted liposomes showed significantly higher levels of cytotoxicity towards Raji cells than the nontargeted liposomal drug. Therapeutic experiments in SCID mice implanted with Raj] cells showed significantly prolonged survival time with targeted liposomal vincristine compared to either free VCR or vincristine formulated in nontargeted liposomes. These studies suggest the potential of the mBAFF-modified liposomal

drugs in targeted therapy of B-cell malignancies. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Neural circuits are shaped by experience in early postnatal life. Distinct GABAergic connections within visual cortex determine the timing of the critical period for YM155 mw rewiring ocular dominance to establish visual acuity. We find that maturation of the parvalbumin (PV)-cell network that controls plasticity onset is regulated by a selective re-expression of the embryonic Otx2 homeoprotein. Visual experience promoted the accumulation of non-cell-autonomous Otx2 in PV-cells, and cortical infusion of exogenous Otx2 accelerated

both PV-cell development and critical period timing. Conversely, conditional removal of Otx2 from non-PV cells or from the visual pathway abolished plasticity. Thus, the experience-dependent transfer of a homeoprotein may establish the physiological milieu for postnatal plasticity of a neural circuit.”
“BACKGROUND: PI3K inhibitor Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein (TLS-CHOP)

(also known as FUS-DDIT3) chimeric oncoprotein is found in the majority of human myxoid liposarcoma (MLS), but its molecular function remains unclear.\n\nMETHODS: We knockdowned TLS-CHOP expression in MLS-derived cell lines by a specific small interfering RNA, and analysed the gene expression PRT062607 supplier profiles with microarray.\n\nRESULTS: TLS-CHOP knockdown inhibited growth of MLS cells, and induced an anticancer cytokine, melanoma differentiation-associated gene 7 (MDA-7)/interleukin-24 (IL-24) expression. However, double knockdown of TLS-CHOP and MDA-7/IL-24 did not inhibit MLS cell growth.\n\nCONCLUSION: Repression of MDA-7/IL-24 expression by TLS-CHOP is required for MLS tumour growth, and TLS-CHOP may become a promising therapeutic target for MLS treatment. British Journal of Cancer (2012) 106, 1976-1979. doi:10.1038/bjc.2012.199 www.bjcancer.com Published online 15 May 2012 (C) 2012 Cancer Research UK”
“In the present study, we review available information on the relevance of Eph and ephrins in numerous processes occurring in the thymus that regulate not only T cell differentiation but also thymic epithelial cell (TEC) development and organization. Eph/ephrins are a large family of receptors and ligands involved in organogenesis and homeostasis of adult tissues.