2 The periodontal host response contains both protective and destructive elements.3 The factors that drive the host anti-bacterial response towards a destructive or protective response seem not to be understood completely. Dendritic cells (DCs) are a class

of specialized antigen-presenting cells that play an important role in the recruitment and activation of cells of the innate immune system, and deliver co-stimulatory signals to activate naïve T cells, thus triggering the initiation of the adaptive immune response.4 The cytokines secreted from DCs greatly affect the quality of the innate and adaptive immune responses.5 Depending on their differentiation and maturation Idelalisib molecular weight state, DCs can tolerize T cells, or direct HSP inhibitor cancer their differentiation towards protective or pathogenic immunity.6 Thus, the interactions between DCs and cells of the innate and adaptive immune system are important in the pathogenesis of many infectious diseases.7 and 8 DCs are

derived from precursor cells present in bone marrow and peripheral blood, mainly monocytes. Then migrate to oral tissues and live there as resident DCs, acting as sentinels in host defense; or differentiate in the sites of infection when they find an invading pathogen. In the immature state, DCs capture antigens efficiently, but as they mature, they undergo phenotypic changes that facilitate their migration towards lymphoid organs and their unique ability to prime T cells.4 and 9 It is known that bacterial LPS can estimulate the production of chemokines and cytokines, specially GM-CSF, that modulates DC movement and maturation.4

However, the effects of periodontal bacteria on DC differentiation, maturation and function/activation remain poorly understood. Few studies have been performed and their results are contradictory. Experiments Gefitinib datasheet by Jotwani et al.10 and Aroonrerk et al.11 showed that in vitro-generated MDDCs pulsed with Porphyromonas gingivalis underwent maturation (shown as an increase in CD83+), regulation of co-stimulatory molecules (CD80, CD86), release of both pro-inflammatory (IL-1β, IL-12p70) and anti-inflammatory (IL-10) cytokines, and secreted immunomodulatory molecules, such as PGE2. In contrast, studies by Cohen et al. 12 and Kanaya et al. 9 suggested that P. gingivalis either inhibited maturation of DCs, which had increased CD1a expression (characteristic of immature DCs) or was only weakly immunostimulatory. In the present study, we hypothesized that monocyte-derived dendritic cells (MDDCs) from individuals with periodontitis may be more easily directed towards a pro-inflammatory response than DCs from periodontally healthy subjects. We also hypothesized that pathogenic bacteria may influence the pro-inflammatory response to modulate MDDCs maturation.

2). The RSG processes for each region – lasting from seven to 12 months – allowed for iterative rounds of MPA proposal development, evaluation, and refinement. In each region, initial steps included convening a BRTF, SAT, and RSG for the region, preparing a regional profile (a document characterizing the ecology and socioeconomics of the region), assembling regional data, developing additional

selleck products region-specific advice, undertaking joint fact-finding, and conducting directed education and outreach efforts. Initiative and CDFG staff did most of this work but joint fact finding and community outreach also involved stakeholders in the study region. This step included developing regional objectives, beginning to identify potential locations for proposed MPAs, evaluating and recommending potential changes to existing MPAs and assembling alternative draft MPA proposals in an iterative process. The RSG had primary responsibility for designing alternative MPA proposals. Their work was supported by Initiative staff and contractors with diverse skills, including facilitators, and utilized data and decision tools developed and maintained by Initiative staff in cooperation with CDFG staff (Merrifield et al.,

2013). External groups PKC inhibitor (not members of the RSG) also developed and submitted proposed MPAs, which entered the regional study process early in the work of the RSG (Fig. 2) and were available to inform the work of RSG members. Generally, there were two or three iterative rounds of MPA network proposal development, evaluation, and refinement in each region. At designated times in the Initiative process, alternative MPA proposals were evaluated for conformance with science guidelines by the SAT (Carr et al., 2010; Saarman et al., 2013) and for conformance with administrative feasibility guidelines developed by CDFG. In the third and fourth study regions, State

Parks and Initiative staff provided assessments of MPA proposals regarding compatibility with existing state recreation and public access opportunities. Initiative staff also provided basic statistical evaluations of proposals against goals of the MLPA. The BRTF also provided feedback on preliminary proposals Levetiracetam based on several factors including: SAT guidelines, CDFG feasibility guidelines, socio-economic impacts, and cross-sectoral support. RSG members revised proposals for MPAs through an iterative process in response to additional information, and feedback, especially from the SAT and CDFG assessments, while encouraged by BRTF exhortations to the RSG to heed those assessments. Facilitators of the stakeholder processes used a variety of techniques to support these changes, including ranking, voting and testing (Fox et al., 2013b). The BRTF provided feedback and guidance to the RSG and helped to identify and make tradeoffs anticipating what they would forward to the Commission.

1999, Niedźwiedź 2003, Groisman et al. 2005). The first investigations into the spatial distribution and synoptic conditions leading to the formation of extreme precipitation events in Lithuania were carried out by Pečiūrienė (1988) and Tylienė(1988), who analysed heavy rain and strong snowfall events. According to their results, the highest recurrence of extreme precipitation is Selleckchem ABT-199 associated with a cold front wave where a secondary depression forms. Bukantis & Valiuškevičienė(2005) found that daily heavy precipitation events had decreased in a large part of Lithuania in 1925–2003; only on the coast were positive tendencies observed. Further

changes in precipitation extremes VX-809 concentration are forecast for the 21st century. The majority of GCM and RCM simulation outputs show an increase in the recurrence of heavy precipitation events during the next one hundred years in Europe (Christensen & Christensen

2004), while negative changes in total precipitation are expected for the southern part of the continent. This means large changes in precipitation frequency rather than in intensity (Räisänen et al. 2004). Also, an increase in heavy precipitation events with a high return period is very likely in Europe (Beniston 2007). However, some investigations show that extreme precipitation events were still underestimated in RCM (Räisänen et al. 2003). Statistical downscaling of GCM (HadCM3 and

ECHAM5) outputs has shown that changes in the annual amount of precipitation in Lithuania will be insignificant. The decrease in summer and autumn precipitation will be compensated by a large increase during winter and spring (Rimkus et al. 2007). A significant increase in the unevenness of precipitation distribution in summer is very likely. More intensive and prolonged droughts will be often followed by very short-lived but extremely intensive rains. The aim of this study was to analyse daily and 3-day heavy precipitation events in Lithuania from 1961 to 2008. The spatial distribution, long-term dynamics and changes in recurrence with a high return period were investigated, and the atmospheric circulation during extreme precipitation events was examined. In addition, possible Phosphatidylinositol diacylglycerol-lyase changes in the recurrence of daily and 3-day heavy precipitation events in the 21st century were evaluated according to the CCLM (COSMO Climate Limited-area Model) model outputs. Daily data from 17 meteorological stations were used for the analysis of heavy precipitation events in Lithuania (Figure 1). The research covers the period from 1961 to 2008. Stations with almost complete daily precipitation data sets were selected. At some stations, the observations had single gaps (< 1%) which were filled using the ratio method.

So, data concerning the symptom index for acidic reflux and WAR should also be reported preoperatively in all studies evaluating the efficacy of endoscopic procedures in GERD patients to show whether they are hypersensitive to WAR. This would increase the role of surgical or endoscopic therapies

in the control of this kind of reflux, which can be diagnosed only by impedance pH testing. Accordingly, we recommend that Koch et al1 report the preoperative results of the symptom index for both acidic reflux and WAR in their future studies. “
“The pregnancy classification ascribed to meperidine in the ASGE document, “Guidelines for endoscopy in pregnant and lactating women” (Gastrointest Endosc 2012;76:18-24) was incorrectly denoted as B. According to current FDA labeling, meperidine is a pregnancy category C medication. “
“In the article, “Comparison of standard forward-viewing Antidiabetic Compound Library mode versus ultrawide-viewing

mode of a novel colonoscopy platform: a prospective, multicenter study in the detection of simulated polyps in an in vitro colon model (with video),” by Gralnek et al. (Gastrointest Endosc 2013;77:472-9), some of the data in Table 2 was presented incorrectly. The correct table appears below. “
“In the ASGE Guideline from the ASGE Technology Committee, “Endoscopic closure devices” (Gastrointest Endosc 2012;76:244-51), OTSC® is a trademark of Ovesco Endoscopy AC (Tubingen, Germany). The trademark was omitted in the original article. Table 2 makes note of an experimental clip device, FK228 price which is not the same as the OTSC® made by Ovesco. “
“The Evidence-Based Reviews in Surgery article “What is the Preferred Surgery for Perforated Left-Sided Diverticulitis?,” by Dixon and colleagues, which appeared in the March 2014 issue of the Journal of the American College of Surgeons, volume 218, pages 495–497, had an error in the introduction on page 495.

The Evidence-Based Reviews in Surgery program is not else “supported by an educational grant from Ethicon Inc and Ethicon Endo Surgery Inc.” The editors apologize for this error. “
“Hiatal hernias are common and increase with age. The sliding type of hiatal hernia contributes to the pathophysiology of gastroesophageal reflux disease (GERD); a paraesophageal hernia (PEH) is associated with potentially catastrophic complications including bleeding, incarceration, and perforation. Reduction of a hiatal hernia and crural closure are integral parts of an antireflux operation or PEH repair. In the past, most of these procedures were done open, either via a transabdominal or a transthoracic approach, and failure was most commonly in the form of a slipped or disrupted fundoplication. However, since the 1990s, a shift has occurred and the majority of procedures both for reflux and PEH repair are being done laparoscopically.

Histologically, early lesions of BOS demonstrate submucosal lymphocytic inflammation and disruption of the epithelium of small airways, followed by a buildup of granulation tissue in the airway lumen, resulting in partial obstruction. Subsequently, granulation tissue organizes in a cicatricial pattern with resultant fibrosis and eventually completely obliterates the airway lumen [23]. It is difficult to define the distinct stages of OB development, but each stage has different main pathological features. Our results demonstrate that orthotopic

tracheal allografts were partially obstructed, in which the mucosa underwent Tofacitinib denudation and squamous metaplasia as well as re-epithelization to various degrees, while the submucosa had few myofibroblasts but rising number of inflammatory cells. On the other hand, Torin 1 heterotopic allografts were completely occluded within 4 weeks after transplant, in which the trachea had barely epithelium but abundant inflammatory cells and myofibroblasts. Therefore, pathological changes found in orthotopic and heterotopic allografts are respectively similar to those in different stages of BOS development in patients who received lung transplant. Both orthotopic

and heterotopic tracheal grafts are nonvascularized grafts, and there is no supply of blood to the grafts other than from angiogenesis, which is passively derived from surrounding tissue during the course of wound healing after transplantation. Although our study confirmed that the angiogenesis ability among various transplant sites was different, all the orthotopic syngeneic grafts basically retained normal histological structures. We speculate that transplant site would not be a major factor affecting the development of OB. In lung transplanted patients, OB is preceded by a decrease in microvascular supply to the small airways. This ischemic event may lead to airway damage or increase the tendency buy CHIR-99021 of scar tissue formation as a repair mechanism. The small airways then appear to respond to this insult by angiogenesis [24] and [25]. Compared with orthotopic

allografts, heterotopic allografts formed lesions with less neovascularized vessels but more fibrous tissues like those in the more mature stage of scar formation. Hence, pathological changes in orthotopic and heterotopic allografts may represent the different stages of OB development: those of orthotopic allografts exhibit the early stage of OB development while heterotopic allografts exhibit the advanced stage, but the general trend of lesion development was identical. 20 years after the implementation of the first OB research model [7], the question is “what is the ideal model of OB.” First, this model is time and cost saving: it is not practical to spend over months waiting for the development of OB lesions, while some models are limited in their high cost and availability.

This result is supported by additional trends and significant decreases in trabecular number, thickness and connectivity, as well as increases in trabecular spacing and structural model index (SMI) (Figs. 2E,G–J) in cancellous bone within the distal femur of immature HFD-fed mice compared to mature mice. Further, the cortical bone was significantly thinner in HFD than LFD mice (Fig. 2F). The polar moment of inertia and the moment

of inertia about the medial-lateral axis of the femoral mid-shaft, however, were not significantly affected by the diet in either age group. The cancellous BMD of the Stem Cells inhibitor distal femur (Fig. 2C) exhibited a significant interaction between diet and age groups, indicating that the two age groups may have been affected differently, but the diet and age group main effects were not significant. As with the distal femur, HFD decreased vertebral cancellous bone volume relative to LFD controls as demonstrated by 3D renderings of micro-CT images (Figs. 3A,B). Within the L3 vertebral bodies, the trabecular BVF was again significantly lower in the HFD compared to the LFD groups (Fig. 3D), but the decrement was not as drastic as that observed in the femur. Unlike the distal femur, this effect was equivalent across the age groups as the interactive effect was insignificant.

Despite the significantly lower trabecular BVF in the HFD-fed mice, the Conn.D, Tb.N, Tb.Sp, and Tb.Th as well as the cortical shell thickness Omipalisib datasheet (Figs. 3F–J) were not

significantly affected by the HFD. The total cross-sectional (transverse) bone area measurements had similar trends to the BVF, with significant reductions in the HFD-fed mice and trends towards a greater deficit in HFD-fed immature mice (Fig. 3E). Consistent with the lower trabecular BVF and total cross-sectional bone area of the vertebrae, we observed a significantly lower maximum compressive force, yield force, stiffness and energy to maximal loading in the HFD-fed mice (Figs. 4D–G). In accordance with the structural changes, this reduction in compressive strength was similar between the two age groups. After adjusting the compressive force by the cross-sectional bone areas to estimate the apparent much stresses, the HFD did not significantly affect the maximum stress, yield stress, modulus, or toughness (Figs. 4H–K). This suggests that the bone tissue quality may not be significantly affected by the HFD after 12 weeks in either immature or mature mice. After transitioning the HFD-fed mice to a LFD for an additional 12 weeks, the body weight in both age groups returned to that of age-matched LFD:LFD mice (Figs. 5A–B, Table S1). The increased fasting glucose and serum leptin concentrations were also returned to normal levels in both age groups after the diet correction (Figs. 5C–D, Table S1). Interestingly, the fasting glucose levels of the mature LFD:LFD group were significantly higher than the mature HFD:LFD group (Table S1).

The experimental protocols were approved by the Ethical Committee for the Use of Laboratory Animals of the Universidade Estadual Paulista “Júlio de Mesquita Filho”, Campus de Dracena. Mitochondria were isolated by standard differential centrifugation (Pedersen et al., 1978). Rats were learn more sacrificed by decapitation, and the liver was immediately removed, sliced into 50 ml of medium containing 250 mM sucrose, 1 mM EGTA, and 10 mM HEPES-KOH, pH 7.2, and homogenized three times for 15 s at 1-min intervals with a Potter-Elvehjem homogenizer. Homogenate was centrifuged at 770g for 5 min, and the resulting supernatant further

centrifuged at 9800g for 10 min. The pellet was suspended in 10 ml of medium containing 250 mM sucrose, 0.3 mM EGTA, and 10 mM HEPES-KOH, pH 7.2 and centrifuged at 4500g for 15 min. The final mitochondrial pellet was suspended in 1 ml of medium containing 250 mM sucrose and 10 mM HEPES-KOH,

pH 7.2 and was used within 3 h. The mitochondrial protein concentration was determined by a biuret assay with BSA as the standard ( Cain and Skilleter, 1987). The disrupted mitochondria were obtained by heat shock treatment after three consecutive cycles of freezing in liquid nitrogen and thawing in a water bath heated to 37 °C. The membrane fragments were kept at 4 °C and were used in the assessment of mitochondrial enzymatic activity within 3 h. Mitochondrial respiration was monitored using a Clark-type oxygen electrode (Strathkelvin Instruments Limited, Glasgow, Scotland, UK), and respiratory parameters were determined according Staurosporine chemical structure to Chance and Williams (1955). One milligram of mitochondrial protein was added to 1 ml of respiration buffer containing 125 mM sucrose, 65 mM KCl, and Unoprostone 10 mM HEPES-KOH, pH 7.4, plus 0.5 mM EGTA and 10 mM K2HPO4, at 30 °C. Oxygen consumption was measured using 5 mM glutamate + 5 mM malate, 5 mM succinate (+2.5 μM rotenone) or 200 μM N,N,N,N-tetramethyl-p-phenylene diamine (TMPD) + 3 mM ascorbate as respiratory substrates in the absence (state-4

respiration) or the presence of 400 nmol ADP (state-3 respiration). The mitochondrial membrane potential (Δψ) was estimated spectrofluorimetrically using model RF-5301 PC Shimadzu fluorescence spectrophotometer (Tokyo, Japan) at the 495/586 nm excitation/emission wavelength pair. Safranine O (10 μM) was used as a probe (Zanotti and Azzone, 1980). Mitochondria (2 mg protein) energized with 5 mM glutamate + 5 mM malate were incubated in a medium containing 125 mM sucrose, 65 mM KCl, 10 mM HEPES-KOH, pH 7.4, and 0.5 mM EGTA (2 ml final volume). ATP levels were determined using the firefly luciferin–luciferase assay system (Lemasters and Hackenbrock, 1976). After incubation in the presence of ABA, the mitochondrial suspension (1 mg protein/ml) was centrifuged at 9000g for 5 min at 4 °C, and the pellet was treated with 1 ml of ice-cold 1 M HClO4.

1% tween-20. Conjugation

pads were then dried for 30 min at 37 °C and fixed, with an ~ 2 mm overlap with the nitrocellulose, on the backing card. Finally, Fusion5 membrane was employed as the sample pad with an ~ 2 mm overlap with the conjugation pad. The entire assembly was housed in a plastic cassette (Fig. 1). PD-1/PD-L1 inhibitor drugs Whole, 2% and 1% milk were obtained from a local grocery store. Apple juice and orange juice were obtained from a refrigerated vending machine. Spiked milk samples were assessed by two methods: (1) following a 10-fold dilution with double deionized water and (2) following centrifugation at 12,000 ×g at 4 °C for 20 min to remove fatty content. Following spike with toxin, orange and apple juice were both Etoposide purchase neutralized using 1 M NaOH. Orange juice samples were tested by two methods: (1) following a 2-fold dilution with phosphate buffer; and (2) following centrifugation to remove pulp. Apple juice samples were tested:

(1) directly after spiking and; (2) following a 2-fold dilution with phosphate buffer. Here, we investigated the application of mAb capture/detector pairs for BoNT/A and BoNT/B, developed previously in our laboratory, in a LFD. For the BoNT/A LFD, F1-2 and a control goat-anti mouse IgG were separately immobilized on a nitrocellulose membrane at 1 mg/mL using a BioJet Quanti Dispenser. The F1-51 mAb was conjugated to 40 nm gold particles and applied by immersion onto a conjugate release pad. A serial dilution of purified toxin, ranging from 100 Sinomenine to 0.2 ng/mL, was prepared in a phosphate buffer, and the assay was initiated by the application of diluted toxin (50 μL) to the sample pad (Fig. 2). A visible red line was resolved in ~ 10–15 min. As shown in Fig. 2A, detection of purified BoNT/A was easily visualized at concentrations of 100 to 5 ng/mL, and weakly visible at 1 and 0.2 ng/mL. No reactivity was observed when purified BoNT/B was applied at 100 ng/mL (data not shown) or with buffer alone. These results demonstrate the suitability of mAbs F1-2 and F1-51 for use in a sensitive and selective LFD to detect BoNT/A. A BoNT/B LFD was also developed using mAbs

developed in our laboratory. Anti-BoNT/B monoclonal antibody MCS-6-27 and control goat anti-mouse IgG were separately immobilized at 1 mg/mL on nitrocellulose, and mAb BoB-92-32 was employed as the detector antibody. A serial dilution, again ranging from 100 to 0.2 ng/mL of purified BoNT/B was evaluated. With a limit of detection of 5 ng/mL, the BoNT/B LFD was not as sensitive as the BoNT/A device (Fig. 2B). Increasing the concentration of the immobilized capture antibody did not improve the sensitivity of the assay (data not shown), however the BoNT/B LFD demonstrated high specificity, showing no reactivity with BoNT/A toxin (data not shown). As individual assays, the monoclonal antibody pairs for BoNT/A and /B demonstrated high specificity for their respective serotypes.

, 2002). Immunoblotting analysis: Here absolute amounts of γH2AX protein are measured and compared to the total H2AX and H2A content. However, different cell types have different γH2AX/H2AX and H2AX/H2A ratios yielding as a result different absolute amounts of γH2AX for the same number of DSBs (Rogakou et al., 1998). Overall, microscopic analysis of γH2AX is considered to be more sensitive than other methods such as

flow cytometry (Kim et al., 2011). Initial microscopy developments in this area were limited Obeticholic Acid to manual scoring of the samples which is restrictive in terms of sample generation (slide vs. microwell plate), operator time and subjectivity. New developments in the area of automated microscopy and image analysis software have increased the sensitivity of the results obtained by Everolimus solubility dmso HCS. Additionally, the use of microplates

and robotic systems has promoted the development of high throughput assays. Moreover, the use of software analysis allows objective quantitative scoring, avoiding operator subjectivity. The potential for multiplexing or evaluating various endpoints simultaneously is an attractive option as there would be a reduction in experimental time and resources. Therefore, from the current methods described above, HCS is considered a strong candidate for routine testing of γH2AX. In the last decade, the use of H2AX to assess DNA damage has grown exponentially as demonstrated by the number of publications (Fig. Levetiracetam 1A). This growth comes as a consequence of the diversification of scientific fields where H2AX is used (Fig. 1B). Initial studies were carried out in the field of radiation research, but once the relation between the phosphorylation of H2AX and DSBs was demonstrated

(Rogakou et al., 1998), the use of γH2AX soon expanded to other areas. The initial methodologies supported experimentation focused on DNA damage and repair mechanisms (Mukherjee et al., 2006, Marti et al., 2006, Celeste et al., 2003 and Bassing et al., 2003) to mention some. Other studies were orientated to assess the DNA damage potential of drugs, potency of chemotherapy agents and other medical materials (Tanaka et al., 2006, Ansteinsson et al., 2011 and Olive and Banath, 2009). Further optimisations in γH2AX detection allowed the use of this indicator of DSBs as a biomarker (Muslimovic et al., 2008 and Cornelissen et al., 2011). For example, Muslimovic et al. used non-fixed blood cells from irradiation patients to develop a biomarker that could potentially lead to modulation of radiological treatment (Muslimovic et al., 2008 and Johansson et al., 2011). The clinical use of γH2AX as a biomarker has been reviewed recently (Redon et al., 2010). In the field of genetic toxicology, Albino et al. proposed the use of γH2AX as a novel genotoxicity assay using flow cytometry (Albino et al., 2004) and was soon followed by Gallmeier et al. recommending immunocytochemistry (Gallmeier et al., 2005).

Broccoli diet marginally increased Nrf2 expression in brain of LPS-treated mice, although this increase did

not reach significance (P < .10). Lipopolysaccharide did not induce Nrf2 expression PI3K inhibitor at 24 hours after treatment ( Fig. 5). Neither diet, treatment, nor age effected Nrf2 expression in liver. NAD(P)H quinone oxidoreductase increased in liver of aged mice (P = .05). Analysis of brain tissue revealed an age × diet × treatment interaction (P < .05), where increased NQO1 expression was most evident in mice fed broccoli diet and given LPS. Lipopolysaccharide increased HMOX1 expression in brain and liver (P < .01), but dietary broccoli had no affect ( Fig. 6). Dietary interventions that reduce www.selleckchem.com/products/ch5424802.html aging-related inflammation garner significant research interest. Although broccoli and broccoli sprouts are drawing increased interest from medical and nutritional scientists, much of the research focus has been centered on the benefits of dietary broccoli for cancer treatment and prevention. In the present studies, we focused on the anti-inflammatory properties of compounds found in whole broccoli and sought to determine whether a broccoli-supplemented diet was beneficial for attenuating systemic

and central inflammation in aged mice. In these studies, 4 weeks of feeding a 10% freeze-dried broccoli diet mildly improved markers of glial reactivity in aged mice and tended to prevent age-induced increase in hepatic CYBB. In contrast to in vitro studies in which supraphysiological concentrations of SFN reduced Ribose-5-phosphate isomerase LPS-induced proinflammatory cytokines, dietary broccoli did not reduce proinflammatory cytokines in mice that were challenged with LPS. Cytochrome b-245 β expression is regulated by a number of transcription factors, including the redox sensitive nuclear factor κ light chain enhancer of activated B cells (NFκB). Our data and those of others suggest that CYBB expression increases with age, which may contribute to increased oxidative stress that occurs with age [33] and [37]. Although

CYBB expression levels are not a direct indication of reactive oxygen species (ROS), transcriptional regulation of CYBB has a marked impact on ROS production [38] and [39]. We demonstrate that dietary broccoli may prevent the age-induced elevation in CYBB, which may hold significance for reducing increased oxidative stress associated with aging. Using both in vitro and in vivo models, SFN conveys Nrf2-dependent neuroprotective effects to cultured astrocytes and microglia and to brain regions including hippocampus, striatum, and cortex [36], [40] and [41]. Consistent with previously published data, we saw transcriptional increases in GFAP in aged mice, suggesting increased astrocyte reactivity [42].