Main Text In this issue

Main Text
In this issue of Stem Cell Reports, two critically important studies describe negative results of a neural stem cell (NSC) product (HuCNS-SC) intended for clinical use in a model of cervical spinal cord injury (SCI) (Anderson et al., 2017) and in a model of Alzheimer’s disease (Marsh et al., 2017). Anderson et al. reported that they relayed their negative results to the company 6 months ahead of the first patient dosing, and yet the decision was made to continue with a cervical SCI clinical trial. Data obtained from the first six patients in this clinical Pathway Study showed an initial small improvement that did not persist at later study time points (up to 1 year), and a decision was made to terminate the trial in May 2016; for business reasons, the company providing HuCNS-SC, StemCells Inc., folded. The two reports raise several important questions. Why did research grade NSCs show benefit in pre-clinical models of cervical SCI whereas a comparable clinical lot did not (Anderson et al., 2017)? Was the preclinical failure predictive of failure for the clinical Pathway Study? And how should stakeholders—regulatory officials, physicians, and participants—be best informed about failed efficacy data in order to decide whether to continue with or participate in a clinical study? The need for discussion about how cell products are characterized and tested for comparability and how these data are used is heightened by the drive to accelerate the approval process for regenerative therapy products, already accomplished in several countries and expected to result from the US 21st Century Cures Act.
After demonstrating efficacy of research-grade HuCNS-SC MRS 2578 Supplier in murine thoracic spinal cord injury models, the Cummings lab was excited to explore the application of this product to the more severe cervical injury. Anderson et al. (2017) performed a controlled, masked study to assess the efficacy of HuCNS-SC for cervical SCI using a clinical cell line (CCL) supplied by StemCells Inc. A “comparable” research grade cell line (RCL) was also provided by StemCells Inc. All the cell preparations were shipped overnight with appropriate monitoring and transplanted on day of receipt. The RCL product showed efficacy for SCI in immunodeficient Rag2γ mice injected with 75,000 cells at 9 days or 60 days post injury. Locomotor function was significantly improved at 12 weeks when RCL NSCs were transplanted at 9 days post injury, with less effect for 60 day post-injury transplants. The CCL groups, however, showed no locomotor improvement at either time point and, in fact, a possible worsening of outcomes associated with more extensive CCL engraftment. Based on the lack of efficacy in the CCL studies, these results might explain the lack of efficacy in the Pathway Study.
In a companion study aimed at demonstrating the therapeutic potential of StemCells Inc.’s HuCNS-SC in an Alzheimer’s disease animal model, clinical-grade cells were transplanted into the brain of Rag-5xfAD mice. Despite robust engraftment, treated animals did not improve cognition, increase BDNF, or increase synaptic density at 5 months after transplantation. This was in contrast to prior studies using a research grade HuCNS-SC preparation provided by StemCells Inc. that showed promising results in an Alzheimer’s disease model at 1 month post transplantation (Ager et al., 2015). In addition, the longer duration study found periventricular cell clusters in a subset of animals—clusters resembling rare neurocytoma tumors according to one of the pathologists. This study amplifies concern about differences between the test cell preparations and points to the importance of performing longer-term functional and safety studies in pre-clinical models of central nervous system repair.
With the increasing use of pluripotent-derived cell types for CNS repair, it has become possible to generate sufficient FCP to allow both pre-clinical testing and clinical study on the same lot. This resolves uncertainty regarding FCP potency and provides a fully tested “off-the-shelf” product, albeit one limited by having to directly transplant cryopreserved product and to start with a single stem cell source capable of generating lots of adequate size. Furthermore, the approach does not resolve the longer-term problem, as eventually even a large lot of FCP will run out. Moreover, in the case of individualized iPSC-based treatment or the use of HLA-matched iPSC banks, it may not be feasible to test every FCP in definitive pre-clinical animal studies. Given the possibility for variation demonstrated by the papers in this issue, should each new cell line be given a unique identifier that is disclosed to investigators and participants in the clinical trial so that they understand which cells are provided and the levels of functional characterization performed on those cells? When the cell product is labeled the same (in this case all are labeled HuCNS-SC), how can patients and physicians know the extent of testing that has been performed on a particular line and understand the risks contributed by product variability in order to make an informed decision on whether to participate in a trial? This point is discussed along with further background to their studies on StemCells Inc.’s products and implications for clinical advancement of cell therapies (Anderson and Cummings, 2016).

br Method br Result br Discussion

Method

Result

Discussion
Sleepiness is a physiological phenomenon, regulated by two processes: processes S (homeostatic) and C (circadian) [28]. The process S (homeostatic) depends on sleep and wakefulness; the need for sleep increases as wakefulness continues and the process C (circadian) recommends a control of an endogenous circadian pacemaker, which affects thresholds for the onset and offset of a sleep period [28]. The interaction of these two processes determines the sleep/wake cycle and can be used to describe fluctuations in alertness and vigilance. According to this two-process model of sleep regulation, sleep pressure accumulates during wakefulness and dissipates in the course of the following sleep episode [29]. The first hypothesis suggests that sleepiness especially impairs cognitive performances that depend on the prefrontal cortex [30]. These include higher functions, such as language, executive functions, divergent thinking, and creativity.
The more sensitive, approach used to identify cognitive processing abnormalities is to measure event-related potentials (ERPs). In ERP, P300 is an endogenous component that is altered with impairment to attention [31]. The latencies and amplitudes of these characteristic electrical T-5224 responses provide information on cognitive T-5224 processing. The delayed latency and reduced amplitude have been reported using auditory signal [25]. The impairment of behavioral task has been reported due to result of sleep restriction [32]. These alterations in P300 component reflect delays in the time taken to discriminate sensory stimuli that is allotted to the participants [33]. The electrophysiological measures of ERPs showed dynamic changes in attention as a result of sleep restriction as seen in the reduced amplitude in P300 component of the ERP and a decrease in the amplitude of the P300 waveform has been suggested to be associated with a decrease in attention [34].
We observed at subsequent on 4th day and 7th day of restricted sleep period; the latency of P300 wave was prolonged and decreased amplitude in restricted sleep watchmen. Our finding is consistent with previous studies of sleep restriction, where they have found that four or more days of partial sleep restriction involving less than 7 (<7) hours sleep per night resulted in cumulative adverse effects on neurobehavioral functions and increase lapses of attention on the psychomotor task [35,36] and whenever there is difficulty in discriminating between stimuli, P300 latency increased with drowsiness preceding sleep onset [37]. We also observed prolongation of reaction time (the failure to respond to a stimulus within a timely fashion) in restricted sleep watchmen; on 4th day and 7th day of restricted sleep period. This supports some of the previous studies on association between sleep loss and reaction time, where the reaction time has been decreased under total or partial sleep loss [38–41]. It is assumed that reaction tasks would be especially susceptible to sleep restriction because of may be sleepiness [42,43], short duration and limited capacity of iconic memory [44], obstruction in assignation of spatial attention [45,46] or decreased oculomotor function[43]. The actual mechanism behind Sleep restriction leads to decreased reaction times and reduced the levels of alertness [47–49] is still controversial. One hypothesis suggest that sleep restriction influences “bottom-up” attention and arousal processes on a global level, mediated by wake-state instability [50]. These disruptions lead to performance decline on attention and vigilance tasks [40]. Another hypothesis suggest that sleep restriction has domain-specific effects that target specific “top-down” brain areas, notably the prefrontal cortex (PFC) functions, such as flexible thinking, verbal fluency, inhibition, and memory [16,23,51–53]. A more integrative approach encompassing these different theoretical accounts suggests that sleep restriction primarily negatively impacts PFC functions, which influence both top-down and bottom-up processes [54].

The Chi squared and Fisher s exact

The Chi-squared and Fisher\’s exact hypotheses tests were used for comparing proportions. Poisson regression with robust variance was employed to analyze the factors associated with excess weight (overweight and obesity), allowing identification of both risk and protective factors in qualitative variables having a high prevalence (>10%) with lower bias in prevalence ratios [21].

Results
The pilots that AV-951 participated in the study were all male and had a mean age of 39.2 years (SD=9.8 years), range 21–67 years. Mean time working in the profession was 15.3 years (SD=10.1) and in the present company was 5.9 years (SD=4.8 years). The mean monthly flying hours reported was 65.4h (SD=9.6h) and mean time off was 9.2 days (SD=1.4 days). The mean work day duration was 8.8h (SD=1.4h) for the morning shift, 8.0h (SD=1.7h) for the evening shift and 7.6h (SD=6.5h) for the night shift.
On the bivariate model, having diagnosed diseases, sleeping <6h on days off, working as a pilot for >10 years, working the night-shift for ≥16 years, having sleepiness often or always and difficulty relaxing, were associated with overweight (Table 1).
On the adjusted multiple model, working night shifts for 6–10 years and having difficulty relaxing continued to be associated with overweight, where perceived morningness was a protective factor based on the inter-relationship of the above-cited independent variables (Table 1).
The majority of obese pilots were aged ≥39 years (p<0.01), had a partner (a) (p<0.01), secondary education or below (p=0.04), worked in the profession for ≥21 years (p<0.01) and on night-shifts for ≥6 years (p=0.01), practiced ≤150min of weekly physical activity (p<0.01), had diagnosed diseases (p<0.01), ≤6h of sleep during days off (p=0.01) and difficulty relaxing after work (p<0.01). There was also a tendency for a greater proportion of pilots with sleepiness to be obese than eutrophic (p=0.06). On bivariate analysis, sleepiness, <150min of weekly physical exercise, diagnosed diseases, sleeping <6h on days off, working ≥21 years as a pilot, working for 6–10 years and ≥16 years on night-shifts, and difficulty relaxing after work, were associated with obesity (Table 2). On the adjusted multiple model, <150min of weekly physical activity, diagnosed diseases, inadequate sleep during days off, working 6–10 years on night-shifts, and difficulty relaxing after work were associated with obesity (Table 2).
Discussion
Based on the sample studied, a high prevalence of excess weight (overweight and obesity) was found in Brazilian commercial airline pilots. This prevalence was similar to the rate found in a population of Brazilian men aged 18 years or older with a prevalence of overweight of 56.5% and obesity of 17.6%, which is considered very high [22].
A study by Marqueze et al. [5] comparing the prevalence of overweight and obesity of Brazilian truck drivers who worked irregular shifts and had a high prevalence of overweight (51.6%) and obesity (22.6%) revealed that the pilots had slightly higher rates of overweight and slightly lower rates of obesity than truckers. The study of Whitfield-Jacobson et al. [23], also involving truck drivers, in Sao Paulo, southeastern of Brazil, found 85.9% prevalence of excess weight and, of this group, 56.5% were classified as obese. The descriptive, cross-sectional by Freitas et al. [24] assessing nutritional status of civil construction workers also identified a high prevalence of overweight (41.9%) although this was lower than the rate found among the pilots. The same study, however, reported a higher prevalence of obesity (22.6%) than that of the pilots.
By contrast, the study conducted by Fernandes and Vaz [25] involving 366 Brazilian young workers of construction company (aged 21–25 years), found a lower prevalence of both overweight and obesity (33.1% and 6.5%, respectively) compared to the pilots studied. The same was observed in the study of Souza et al. [26], involving 15 Brazilian rubber-tappers and 30 cane cutters (mean age 29.86 years ±8.57 years), which also found a lower prevalence of excess weight, with 40% overweight and 6.7% obese among cane cutters; and 13.3% overweight and no obesity among the rubber-tappers. These lower prevalences of excess weight in the cited studies compared to pilots may be due to greater energy expenditure associated with the type of work performed, i.e. largely physical. Another relevant factor is the lower age of the participants and that both studies involved small samples of workers.

br Eric Calcagno Diputado Nacional

Eric Calcagno
Diputado Nacional Provincia de Buenos Aires. Tiene un Diploma internacional de Administración Pública por la École nationale d’administration, Paris, Francia. Diploma de estudios avanzados (dea) de Sociología. Université de Paris V, Réné Descartes Paris, Francia. Especialización en Teoría de la Decisión. Diploma del Magistère en Ciencias Sociales, Universidad de Paris V, Réné Descartes, Paris, Francia. Maestría de Sociología General, Université de Paris V, Réné Descartes, Paris, Francia. Especialización en Teoría de las Organizaciones. Licenciado de Sociología por la Universidad de Paris V, Réné Descartes, Paris, Francia. Diploma de Estudios Universitarios Generales de Sociología (d.e.u.g.), Universidad de Paris V, Réné Descartes, Paris, Francia. Bachillerato bilingüe especializado en literatura y matemáticas. Liceo Franco- Argentino “Jean Mermoz”, Buenos Aires, Argentina. Ha escrito varios libros y ha publicado artículos en Página 12, Le Monde Diplomatique, El Dipló, Realidad Económica, Miradas al Sur, Revista 23, entre otros.

Héctor Guillen Romo
Realizó la licenciatura de economía en la Universidad Nacional Autónoma de México, la maestría de economía en El ABT-888 Colegio de México y el Doctorado de Estado en ciencias económicas en la Universidad de Paris I Posteriormente, realizó un postdoctoradoen economía en la Universidad de Picardie (Amiens, Francia). Fue profesor titular de tiempo completo en el Departamento de Economía de la Universidad Autónoma Metropolitana de México entre 1975 y 1990. Impartió cátedra en El Colegio de México y en el itam. Ha sido profesor visitante en la Universidad Federal de Paraiba (Brasil), en la Universidad Nacional Autónoma de Honduras y en las Universidades de Reims y Lille en Francia. Desde 1990 hasta la fecha es profesor titular de tiempo completo en el Departamento de Economía de la Universidad de Paris viii. Sus áreas de especialidad son Moneda, Finanzas Internacionales y Desarrollo Económico. Entre sus publicaciones se encuentran: La Contrarrevolución neoliberal en México, era. México.1997; El sexenio de crecimiento cero. México, 1982/1988. era México. 1990; Orígenes de la crisis en México. 1940/1982. era, México, 1984; así como varias colaboraciones en revistas especializadas,

Antonio Gazol Sánchez
Economista por la unam. Profesor de la Facultad de Economía, unam; Titular de la Cátedra Extraordinaria “Maestro Octaviano Campos Salas” sobre Comercio Exterior e Industrialización en la Facultad de Economía, unam (2001-2005); profesor de la Facultad de Ciencias Políticas y Sociales, unam (1967-1980); profesor de la Escuela de Economía de la Universidad Anáhuac (1967-1972), profesor del Centro de Estudios de Comercio Internacional del imce (1971-1972). Presidente del Colegio Nacional de Economistas (1981-1983); Premio de Economía Banamex, 2o lugar (1967); ha publicado varios libros entre los que destacan: Complementación Industrial e Integración Económica, Ed. Sela, 1966; El Tercer Mundo ante el Mercado Común Europeo, fce, 1973; Bloques Económicos, Facultad de Economía, unam. Asimismo es autor de varios artículos en revistas especializadas; también ha presentado ponencias, conferencias, capítulos de libros y ensayos diversos. Ha sido servidor público (1959-1998) y ha ejercido como consultor privado; Coordinador del Centro de Educación Continua, Facultad de Economía, unam (1998-2001) y Subdirector de Planeación, unam, 2008 a nondisjunction la fecha.

Alejandro Ulises Dabat Latrubesse
De nacionalidad argentina, es investigador titular “C” de T.C., miembro del Sistema Nacional de Investigadores nivel III adscrito al Instituto de Investigaciones Económicas de la unam. Economista especializado en política y economía mundial desde una perspectiva interdisciplinaria. Autor de una veintena de libros, numerosos artículos y muchas otras publicaciones entre las que destacan El mundo y las naciones y Capitalismo mundial y capitalismos nacionales.

CB-5083 This study adds to the growing body of research

This study adds to the growing body of research showing a link between environmental exposures and LTL (), and suggests that POPs may be able to activate telomerase or other telomere-elongating mechanisms. Activation of telomerase is a critical, early event in carcinogenesis for the majority of cancer types. Once telomere CB-5083 has been hijacked by cancer cells, they will be able to overcome cellular senescence and apoptosis, and will have better survival. Changes in LTL are believed to be a reflection of these in situ processes (). Questions remain about the exact mechanism by which POPs induce longer telomeres, and the temporal sequence of the relationship, both of which will need to be answered before this observed relationship can be exploited clinically. Other important confounders such as various nutrient intakes and body fat will need to be ruled out as well, and POP-induced LTL changes will need to be evaluated for their effects on human disease.
Cross-sectional and prospective studies of telomeres have identified inconsistent relationships between LTL and cancer, with authors identifying both longer and shorter telomeres as predisposing to cancer risk, frequently across different cancers (). This is another question that will need to be answered to assess the relationships between POPs, LTL, and cancer. While NHANES includes self-reported data on prior cancer diagnoses, which was explored in this study, the number of available cancer cases is relatively small, and lacks detailed clinical information (e.g., histology) that would be relevant to this area of research and available through inclusion of formal medical records. Nonetheless finding significant, dose-dependent changes in LTL associated with so many different types of POPs demonstrates that this is a promising area of research. Future prospective, longitudinal studies incorporating detailed data on medical history, lifestyle, and environmental exposures will help completely elucidate the causal mechanisms involved in the complex and dynamic relationship between carcinogens and LTL.

The accumulating epidemiological evidence of elevated cancer risk and mortality in individuals exposed to polychlorinated biphenyls (PCBs) led to their recent classification as human carcinogen by the International Agency for Research on Cancer (IARC) (). However, the mechanisms by which PCBs are linked to cancer are still unclear.
In this issue, Scinicariello and Buser () conducted a study of the association between leukocyte telomere length (LTL) and PCB blood levels in a nationally representative sample of the civilian US adult population using data from the National Health and Nutrition Examination Survey (NHANES). The authors showed that higher PCB blood levels were associated with longer LTL, and hypothesized that there could be a link to PCB-related carcinogenesis. A separate study reported similar relationships between LTL and PCB blood levels in a subset of NHANES participants (). However, a small study of healthy Koreans () showed that this relationship was only present at low PCB levels. In contrast, short LTL has been associated with a number of environmental or occupational exposures including particulate matter, black carbon, benzene, toluene, polycyclic aromatic hydrocarbons, N-nitrosamines, pesticides, and lead (reviewed in ), all of which may contribute to PCB blood levels. Telomere shortening in response to chemical exposures may be explained, at least in part, by the induction of an oxidative stress DNA damage response ().
Telomeres, the long (TTAGGG) nucleotide repeats and an associated protein complex at chromosome ends, are essential for maintaining chromosomal stability. They shorten with each cell division and therefore are markers for cellular replicative capacity, cellular senescence, and aging. Telomere shortening and chromosomal instability has been described at early stages of carcinogenesis, suggesting a role of telomere dysfunction in cancer initiation ().

cyclosporin Population specific templates are necessary for

Population-specific templates are necessary for modern structural and functional neuroimaging research. This work, along with studies conducted by Lee et al. (2005) and Tang et al. (2010) imply that cyclosporin templates created with North American populations do not provide optimal references for processing MR brain images of Chinese or Asian populations. Similarly, our study and several other neuroimaging studies examining North American developmental populations (Altaye et al., 2008; Muzik et al., 2000; Wilke et al., 2002), suggest that using average adult MRI templates for research with infants and children may result in excessive deformation, inaccurate measurements, and the misinterpretation of results (Richards and Xie, 2015). Therefore, population-specific (e.g., age, nationality) should be recommended to promote the quality and accuracy of measurements and interpretations. This current study should lay the foundation for creating more comprehensive population-specific templates, such as younger Asian child templates and gender-specific Asian child templates, in the future.
In conclusion, Chinese age-specific average MRI templates are recommended for neuroimaging research with Chinese or Asian children and adolescents. We have created the first brain and head average MRI templates constructed specifically for Asian pediatric populations. Given the similarity between the Korean (Lee et al., 2005) and Chinese (Tang et al., 2010) adult MRI templates, it is likely that these templates will be useful for research with other Asian pediatric populations as well. Our Chinese age-specific pediatric templates may be used to replace or complement the default templates included in popular neuroimaging processing programs (e.g., FSL, SPM).

Template availability
The Chinese average head and brain MRI templates are publicly available for research including clinical and experimental studies of brain development. Data access is limited to scientific professionals for research purposes. The template volumes are available in compressed NIFTI format (http://nifti.nimh.nih.gov). The data are on a file server that may be accessed with the Secure Shell (SSH) file transfer protocols (SCP or SFTP). Instructions for access are given online on our website: (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/ChineseChildren).

Conflicts of interest

Introduction
Perceptual expertise for visual words enables individuals to rapidly and effortlessly decode visual words (McCandliss et al., 2003). At the neural level, a cortical area located in the left occipito-temporal cortex (termed as Visual Word Form Area, VWFA) has been identified for specifically processing written words (e.g. Cohen et al., 2000; McCandliss et al., 2003; Cohen and Dehaene, 2004; Liu et al., 2013). This area has been proposed to be associated with a negative ERP component, termed as N170, elicited by visual words between 150ms and 250ms after the onset of stimuli (Allison et al., 1994; Maurer et al., 2005a; Rossion et al., 2003; Brem et al., 2006). Compared to meaningless symbols, the word-related N170 shows larger amplitude in the left occipital-temporal region in skilled readers (Maurer et al., 2005a, 2006, 2008; cyclosporin Bentin et al., 1999). Further, this effect can be observed in different writing systems (Baker et al., 2007; Maurer et al., 2008; Wong et al., 2005; Lin et al., 2011; Zhao et al., 2012).
N170 markers for word expertise develop rapidly after children receive formal training in schools (Maurer et al., 2006; Brem et al., 2009; Cao et al., 2011; Zhao et al., 2014) and are attenuated in children who suffer from, or are at risk of dyslexia (Maurer et al., 2006; Brem et al., 2013). Word-related N170 expertise emerges even before children receive formal training. A higher N170 for words, relative to symbols, in the right hemisphere was found in kindergarten children (6 years old) with high letter knowledge (Maurer et al., 2005b). This N170 selectivity for words, together with left-lateralization, was also found in Chinese kindergarten children with high reading ability (S. Li et al., 2013).

Previously we demonstrated that injured kidney tissues can

Previously, we demonstrated that injured kidney tissues can induce bone marrow stromal GDC-0994 to differentiate into renal tubular epithelial-like cells in vitro and in vivo (Qian et al., 2008). However, another work reported that the beneficial effects of BMSCs are primarily mediated by complex paracrine actions, but not by their differentiation into target cells (Tögel et al., 2005). Recently, there is increasing evidence to indicate that immunomodulation does play a critical role in the therapeutic effect of multipotential stromal cells, since tissue injury is generally inflammation-related (Semedo et al., 2009; Aronin and Tuan, 2010; Jang et al., 2009). In particular, many studies have focused on the modulatory effect of stromal cells on macrophages (Kim and Hematti, 2009; Chen et al., 2008; Maggini et al., 2010). One study demonstrated that BMSCs can beneficially modulate the response of the host immune system to sepsis and interact with both circulating and tissue macrophages (Németh et al., 2009). Another report indicated that human gingiva-derived stromal cells can induce M2 polarization of macrophages, which may contribute to a marked acceleration of cutaneous wound healing (Zhang et al., 2010). In the present study, macrophage recruitment occurred rapidly in the interstitial area of injured kidneys and peaked at 5days after reperfusion, which was reduced significantly following hUCSC treatment. Furthermore, we sought to find out the role of chemokine MCP-1 in macrophage recruitment effected by hUCSCs. Our results showed that the number of MCP-1-positive tubular epithelial cells was also markedly reduced by hUCSC administration. Thus, these findings provide the first evidence that hUCSCs are capable of reducing macrophage infiltration in the injured kidneys, at least in part by downregulating the expression of MCP-1 in tubular epithelial cells.
In vivo, we performed macrophage depletion by lipo-Cl2MBP and chose to deplete macrophages at different stages of reperfusion, to find out whether they have distinct functions which would result in conflicting conclusions (Duffield et al., 2005). Our results show that macrophage abolishment during the early injury phase promotes the ameliorating effect of hUCSCs on renal IRI. This finding is in agreement with current evidence demonstrating the contribution of macrophages to the initiation of renal damage (Jo et al., 2006; Day et al., 2005). Conversely, macrophage depletion during the late repair phase led to a loss of the therapeutic effect of hUCSCs on kidney damage. One group reported that macrophages are involved in the repair phase and are beneficial for kidney repair after IRI (Vinuesa et al., 2008). Here, we provide the first evidence that macrophage infiltration during recovery may be essential for the protective role of hUCSCs in renal IRI.
In a coculture experiment, we found that hUCSCs suppressed the transcription of IL-1β and IL-6 mRNA in macrophages, whereas aginase-1 and IL-10 were upregulated. These findings suggest that hUCSCs can switch the cytokine expression of macrophages into an anti-inflammatory phenotype, characteristic of M2 macrophages, in vitro. In vivo, hUCSC-treated kidneys also showed a significant suppression of the expression of IL-1β and IL-6, and an upregulation of IL-10. Thus, our observations indicate that hUCSCs are capable of modulating the cytokine expression of macrophages, which may contribute to the resolution of inflammation at injury sites in renal IRI. On the other hand, flow cytometric analysis showed increased CD206 expression on the surface of macrophages cocultured with hUCSCs, and that the proportion of CD206+ macrophages was upregulated during recovery following hUCSC treatment in the kidney tissues. Taken together, our findings suggest that hUCSCs elicit the M2 polarization of macrophages, which may result in an accelerated recovery of renal IRI.

This proteomic analysis of Snail effects on adipocyte

This proteomic analysis of Snail effects on adipocyte differentiation in mesenchymal ARQ 621 identified inhibition of different transcription factors, cytokines or growth factors. Collectively, our results suggest an early effect of Snail on adipogenesis, upstream of C/EBPα and PPARγ proteins, which would be mediated through Nr2f6 and IL-17. We demonstrated the capacity of Snail to induce IL-17 expression in fibroblasts or mesenchymal cells [2].

Materials and methods

Acknowledgments
Alberto Peláez-García was a recipient of a FPI fellowship. Rodrigo Barderas was supported by the Ramón y Cajal Programme of the Spanish Ministry of Economy and Competitiveness (MINECO). This research was supported by grants to established research groups (AECC), BIO2012-31023 from the Spanish Ministry of Economy and Competitiveness, S2011/BMD-2344/ (Colomics2) from Comunidad de Madrid and Grant PRB2 (IPT13/0001 – ISCIII-SGEFI/FEDER) from ProteoRed-ISCIII.

Data
The aerobic chemoorganotrophic Gram-positive high G+C hydrocarbon-degrading mesophilic Dietzia sp. A 14101 was incubated on a range of media and substrates. The data presented here provides information on (1) the changes observed in the production of the long-chain compounds and (2) pigments produced by Dietzia sp. A 14101. Changes in the type and relative amount of the tentatively identified long-chain compounds are subtle. The production of pigments is coupled to growth on the water-immiscible hydrocarbon substrates. Some selected pictures illustrating identification of the cell-surface charge test of the bacterial membrane of Dietzia sp. A 14101 are included. The test is time-effective, requires only common laboratory equipment and fresh intact bacterial cells.

Experimental design, materials and methods

Specifications Table
Value of the data
Data, experimental design, materials and methods

Funding
This project was supported by funds from the Ministry of Innovation, Science and Research of North Rhine-Westphalia in the frame of CLIB-Graduate Cluster Industrial Biotechnology, contract no: 314-108 001 08.

Specifications Table
Value of the data

Data, experimental design, materials and methods
This data is important as a wide variation of Aβ soluble oligomer forms have been shown to result from different preparation conditions [1]. Thus, the value of the data is to facilitate future scientific efforts that require replication of this particular oligomer species. The data here pertain to a specific form of “native” oligomers (nOAβ) whose production follows the following criteria: (1) the nOAβ preparation initially starts with highly pure MAβ in>99% molar excess phosphate-saline buffer and (2) nOAβ must be generated from this initial MAβ preparation by time alone (no change in solution conditions or seeding). These criteria were selected to ensure that the only difference between preparations corresponding to the initial Aβ monomers (MAβ) and subsequently formed nOAβ oligomers is the degree of peptide assembly. Solvent conditions remain constant and oligomer formation is driven by inherent kinetic mechanisms from the monomer state without influence of amyloid “seeds”.

Data
A highly pure initial MAβ preparation is a criteria for the production of nOAβ. Fig. 1 confirms this initial state with SDS-PAGE Western blots performed on PICUP experiments with t=0, 1, and 30s of light exposure. The gel in Fig. 1 confirms the expected results of a single band at the expected monomer mass (4.3kD) in the negative control samples with no light exposure (0s lane) and a broad ladder of oligomer bands in the positive control (30s lane). The integrated signal of oligomers in the 30s lane was approximately equal to the 0sec PICUP lane indicating that no larger insoluble aggregates had formed at exposure times less than 30sec. Also, the oligomer distribution from infrared fluorescence is consistent with that of the 30s exposure of Aβ1–40 in the original PICUP study [2]. The PICUP experiment here used 1s of light exposure and retained monomer band as the highest intensity band but also produced 2–5 fainter higher-order bands that decreased in intensity at greater size. Compared with previous PICUP results, this finding is consistent with a monomeric Aβ sample because low amounts of 2–5mer bands are expected to result from diffusional collisions of monomeric polypeptides [2].

La enadid de resalta que la primera

La enadid de 2014 resalta que la primera causa de la migración de retorno (de otro país) o entre entidades federativas es para reunirse con la familia (40 migrantes por cien), y en segundo lugar por razones laborales o para estudiar. En la migración interna, cabe destacar que 6 de cada 100 migrantes interestatal declara que la principal razón ha sido la inseguridad pública y la violencia (enadid, 2014). Los datos del Centro de Monitoreo de Desplazamiento Interno o The Internal Displacement Monitoring Centre (idmc) consideran que en 2015, existían 287 430 desplazados buy cisapride causa de violencia criminal. Otros determinantes son los recurrentes eventos climáticos extremos (Yunez Naude y Mora Rivera, 2010), los cuales también suman más de 250 mil personas desalojadas desde 2013 (). Finalmente, se observan poblaciones indígenas desplazadas –entre otros en Chiapas, Oaxaca, Guerrero, Jalisco y Hidalgo, Comisión Mexicana de Defensa y Promoción de los Derechos Humanos (cmdph) 2004–, debido a conflictos por tierras, recursos naturales o intolerancia religiosa (idmc).
En la mayoría de las entidades (con la excepción de las zonas metropolitanas), la elección de migrar hacia otra entidad es todavía mayor a la de migrar a otro municipio de la misma entidad, en particular en Chiapas, Guerrero, Oaxaca, Michoacán y Veracruz, los estados con mayores niveles de pobreza. Cabe mencionar unos casos atípicos, como Baja California Sur y Quintana Roo donde llegaron entre 2005 y 2010, seis y siete veces más personas de otra entidad que desde otro municipio de la misma entidad. Asimismo, Aguascalientes, Baja California, Colima, Nayarit, Querétaro, Morelos, Hidalgo y Estado de México son las entidades con mayor atracción para la población de otro estado (Mapa 2). En contraposición, Guanajuato, Michoacán y Zacatecas muestran una menor intensidad en los diferentes flujos migratorios, esos estados presentan también municipios más dirigidos hacia la migración internacional que la interna Consejo Nacional de Población (Conapo) . Canales y Montiel (2007) señalan que municipios de Jalisco, del Bajío y Chihuahua tienen en su mayoría migrantes internacionales, mientras en Michoacán, Oaxaca y Durango, municipios presentan ambos perfiles de migración (interestatal e internacional).
El análisis del perfil de los migrantes internos por sexo y edad, muestra que se concentran en las edades activas, con mayor proporción entre 20 y 35 años (). Únicamente entre 15 y 29 años, la proporción de migrantes internos mujeres es mayor a Depressed state la de los hombres. Los hombres son históricamente más numerosos en la migración internacional (Espinoza Damián, 2012), entre 2009 y 2014, tres de cada cuatro migrantes internacionales eran hombres (enadid, 2014). Los datos de los Censos de población revelan que los hombres están además más presentes en la migración entre entidades federativas en tanto que las mujeres son predominantes en la migración entre municipios de la misma entidad (Figura 1). Sin embargo, muestran que la proporción de mujeres que emigran hacia la Ciudad de México, el Estado de México y Tlaxcala es mayor a la de hombres.
Se propone un análisis global del fenómeno y el presente artículo se divide en cuatro partes: i) migraciones entre entidades federativas; ii) migraciones entre municipios del territorio; iii) migraciones por tamaño de municipio, y iv) evolución de la distribución poblacional en diferentes tamaños de localidades. Este trabajo presenta series temporales, describe la heterogeneidad entre territorios de partidas y de destino, al igual que las características sociodemográficas de los migrantes. En conclusión se destaca las principales tendencias, y sus implicaciones en términos de condición de vida de la población e impacto sobre el medio ambiente, además de recomendaciones de políticas públicas. Los insumos para el análisis son esencialmente los resultados de los Censos y Conteos de población y viviendas, los microdatos de las muestras de esos Censos para los años 2000, 2010 y 2015, y las bases del Sistema de Integración Territorial (iter) del Instituto Nacional de Estadística y Geografía (inegi).

The periods over which we are

The periods over which we are comparing these variables are three: one last period of state-led growth strategy 1970-1981, a period of the “‘Structural Adjustment Program” 1982-1993, and a period of full operation of nafta, 1994-2015.
The initial period 1970-81 was chosen because it was the one that covered the two political administrations of Mexico, right before the introduction of the neoliberal economic reforms. The government policies followed in these two administrations were blamed for the foreign exchange crisis that allowed the imf and the World Bank to impose on Mexico a Structural Adjustment Program (sap), which in fact started in 1982 causing a deep economic crisis that year. The period 1982-1993 was then considered the period in which many of the neoliberal economic reforms were applied in Mexico under the coverage of the sap. Finally, the period 1994-2015 is the one in which nafta has prevailed regarding trade and financial flows. This is the period we are focusing on mainly.

Conclusions
We have showed in the various graphs and tables, with data from official sources, that the Export-led growth strategy followed by the Mexican government, from 1983 to the present has failed in two of the selected indicators: gdp and Employment growth. nafta was one of the same reforms carried out by the Mexican government, widening up those neoliberal reforms by opening up the capital account of the Balance of Payments and accepting that there were no KN-93 hydrochloride cost flows rules under nafta. In short, free movement of one factor of production, capital, no movement of the other, labor.
The additional source of growth which was foreign direct investment (fdi) since 1994, did not stimulate growth either. fdi as maintained a high level of foreign exchange inflow to Mexico, as Exports have done. Still, there has been not substantial, nor sustained, gdp growth in the nafta period.
With respect to gdp, we have seen that the Exports’ boom in the first years of nafta (see Figure 5) did not match a corresponding growth of gdp; and the following years while exports kept growing at a lower rate in real terms, gdp followed a stagnant tendency as well as employment.
The reason for this failure is not a simple one: there was a big transformation of the Mexican economy, not only there were not industrial, trade and monetary policies for growth, but the very institutions and organizations that made possible those policies for the State-led growth strategy, were either sold to the private sector, closed, or changed in their purpose, like the banking for development system. A famous Mexican Secretary of Commerce in 1992 is said to have declared that “‘the best policy is the non-existent one”, paraphrasing –maybe unconsciously– the us Civil War General Sheridan in the nineteenth century, saying: “‘The only good Indian is a dead Indian”.

Introducción
Los países de América Latina han protagonizado dos oleadas de regionalismo en el siglo xx, en la década de 1970 y en la de 1990, como lo señala Pomfret (2001). Durante esas décadas los países firmaron varios acuerdos de integración regional, cada uno con diferentes características, dimensiones y grado de concreción. La integración comercial entre los países integrantes del continente americano ha sido un largo proceso. El comercio entre éstos ha sido importante desde hace varias décadas, no sólo por los compromisos que implica la firma de un acuerdo, sino también por razones de carácter geográficas e históricas que comparten sus pueblos.
Desde el establecimiento de la Comisión Económica para América Latina y el Caribe (cepal), ha existido en América Latina un discurso económico a favor de la integración regional como instrumento para ampliar los mercados y generar condiciones para el desarrollo económico. Este discurso ha influido en la creación de varios acuerdos tales como la Asociación Latinoamericana de Libre Comercio (alalc) que luego pasaría a ser Asociación Latinoamericana de Integración (aladi), el Mercado Común Centroamericano (mcca), el Mercado Común del Sur (Mercosur), el Pacto Andino (que luego se llamará Comunidad Andina (can)) y la Comunidad de Estados Latinoamericanos y Caribeños (celac).