Sleep and Human Aging.

PubMed

Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

2017-04-05

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? Copyright © 2017. Published by Elsevier Inc.

Canonical Wnt Signaling as a Specific Mark of Normal and Tumorigenic Mammary Stem Cells

DTIC Science & Technology

2011-02-01

aggressive mammary tumors. 15. SUBJECT TERMS Breast cancer stem cells, Wnt signaling, canonical Wnt signaling, B-catenin, normal stem cells, adult stem...Wnt pathway is associated with abnormal mouse mammary development, tumorigenesis, and human breast cancer. In addition, increasing evidence suggests...activation occurs in human breast cancer and is required for proliferation of various other stem cell compartments, addressing how Wnt signaling promotes

A pseudoisochromatic test of color vision for human infants.

PubMed

Mercer, Michele E; Drodge, Suzanne C; Courage, Mary L; Adams, Russell J

2014-07-01

Despite the development of experimental methods capable of measuring early human color vision, we still lack a procedure comparable to those used to diagnose the well-identified congenital and acquired color vision anomalies in older children, adults, and clinical patients. In this study, we modified a pseudoisochromatic test to make it more suitable for young infants. Using a forced choice preferential looking procedure, 216 3-to-23-mo-old babies were tested with pseudoisochromatic targets that fell on either a red/green or a blue/yellow dichromatic confusion axis. For comparison, 220 color-normal adults and 22 color-deficient adults were also tested. Results showed that all babies and adults passed the blue/yellow target but many of the younger infants failed the red/green target, likely due to the interaction of the lingering immaturities within the visual system and the small CIE vector distance within the red/green plate. However, older (17-23 mo) infants, color- normal adults and color-defective adults all performed according to expectation. Interestingly, performance on the red/green plate was better among female infants, well exceeding the expected rate of genetic dimorphism between genders. Overall, with some further modification, the test serves as a promising tool for the detection of early color vision anomalies in early human life. Copyright © 2014 Elsevier B.V. All rights reserved.

Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

PubMed Central

Yue, Rui; Shen, Bo; Morrison, Sean J

2016-01-01

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin. DOI: http://dx.doi.org/10.7554/eLife.18782.001 PMID:27976999

Data Collection and Simulation of Ecological Habitat and Recreational Habitat in the Shenandoah River, Virginia

USGS Publications Warehouse

Krstolic, Jennifer L.

2015-01-01

Time-series analyses were used to investigate changes in habitat availability with increased water withdrawals of 10, 20, and almost 50 percent (48.6 percent) up to the 2040 amounts projected by local water supply plans. Adult and sub-adult smallmouth bass frequently had habitat availability outside the normal range for habitat conditions during drought years, yet 10- or 20-percent increases in withdrawals did not contribute to a large reduction in habitat. When withdrawals were increased by 50 percent, there was an additional decrease in habitat. During 2002 drought scenarios, reduced habitat availability for sub-adult redbreast sunfish or river chub was only slightly evident with 50-percent increased withdrawal scenarios. Recreational habitat represented by canoeing decreased lower than normal during the 2002 drought. For a recent normal year, like 2012, increased water-withdrawal scenarios did not affect habitat availability for fish such as adult and sub-adult smallmouth bass, sub-adult redbreast sunfish, or river chub. Canoeing habitat availability was within the normal range most of 2012, and increased water-withdrawal scenarios showed almost no affect. For both ecological fish habitat and recreational canoeing habitat, the antecedent conditions (habitat within normal range of habitat or below normal) appear to govern whether additional water withdrawals will affect habitat availability. As human populations and water demands increase, many of the ecological or recreational stresses may be lessened by managing the timing of water withdrawals from the system.

Normalizing and scaling of data to derive human response corridors from impact tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

2014-06-03

It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. Published by Elsevier Ltd.

Metabolic Signature of Antipsychotics used in the Treatment of Autism

DTIC Science & Technology

2014-10-01

adipokine release in mature human adipocytes. Methods Rat Model: Adult female Sprague-Dawley rats under normal diet were given cookie dough ...metabolic disturbances. Adult female rats were given cookie dough mixed with vehicle, olanzapine or ziprasidone at 4 mg/kg twice/day for 7 days. Fig 1

Course of Relational and Non-Relational Recognition Memory across the Adult Lifespan

ERIC Educational Resources Information Center

Soei, Eleonore; Daum, Irene

2008-01-01

Human recognition memory shows a decline during normal ageing, which is thought to be related to age-associated dysfunctions of mediotemporal lobe structures. Whether the hippocampus is critical for human general relational memory or for spatial relational memory only is still disputed. The human perirhinal cortex is thought to be critically…

Human pancreatic polypeptide in children and young adults.

PubMed

Hanukoglu, A; Chalew, S; Kowarski, A A

1990-01-01

Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults.

A preliminary study of differentially expressed genes in expanded skin and normal skin: implications for adult skin regeneration.

PubMed

Yang, Mei; Liang, Yimin; Sheng, Lingling; Shen, Guoxiong; Liu, Kai; Gu, Bin; Meng, Fanjun; Li, Qingfeng

2011-03-01

In adults, severely damaged skin heals by scar formation and cannot regenerate to the original skin structure. However, tissue expansion is an exception, as normal skin regenerates under the mechanical stretch resulting from tissue expansion. This technique has been used clinically for defect repair and organ reconstruction for decades. However, the phenomenon of adult skin regeneration during tissue expansion has caused little attention, and the mechanism of skin regeneration during tissue expansion has not been fully understood. In this study, microarray analysis was performed on expanded human skin and normal human skin. Significant difference was observed in 77 genes, which suggest a network of several integrated cascades, including cytokines, extracellular, cytoskeletal, transmembrane molecular systems, ion or ion channels, protein kinases and transcriptional systems, is involved in the skin regeneration during expansion. Among these, the significant expression of some regeneration related genes, such as HOXA5, HOXB2 and AP1, was the first report in tissue expansion. Data in this study suggest a list of candidate genes, which may help to elucidate the fundamental mechanism of skin regeneration during tissue expansion and which may have implications for postnatal skin regeneration and therapeutic interventions in wound healing.

The Use of Electrophysiological and Cognitive Variables in the Assessment of Degradation During Periods of Sustained Wakefulness

DTIC Science & Technology

1992-12-01

spectral components. Spectral components were selected on the basis of their relation to states of alertness. In normal human adults , diffuse low...deterioration of handwriting , and ultimately, loss of consciousness. Belyavin and Wright (1987) reported that while EEG changes could not predict vigilance in...a function of alertness level. In human adults , two independent laboratories have shown that MLR components Pa (30 to 35 ms) and Nb (40 to 50 ms

Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm.

PubMed

Zhan, Jun; Yang, Mei; Zhang, Jing; Guo, YongQing; Liu, Wei; Zhang, HongQuan

2015-05-01

Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.

Engineering stromal-epithelial interactions in vitro for ...

EPA Pesticide Factsheets

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema.

PubMed

Golpon, H A; Geraci, M W; Moore, M D; Miller, H L; Miller, G J; Tuder, R M; Voelkel, N F

2001-03-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.

HOX Genes in Human Lung

PubMed Central

Golpon, Heiko A.; Geraci, Mark W.; Moore, Mark D.; Miller, Heidi L.; Miller, Gary J.; Tuder, Rubin M.; Voelkel, Norbert F.

2001-01-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3′ end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases. PMID:11238043

Localization of survival motor neuron protein in human apoptotic-like and regenerating muscle fibers, and neuromuscular junctions.

PubMed

Broccolini, A; Engel, W K; Askanas, V

1999-06-03

Mutations in the gene encoding survival motor neuron (SMN) protein are found in > 98% of patients with autosomal-recessive spinal muscular atrophy. We investigated the possible role of SMN in normal and abnormal human muscle by immunostaining biopsies of 20 patients with various neuromuscular diseases using monoclonal antibodies against SMN. SMN was strongly expressed cytoplasmically in chronic peripheral neuropathies, in about 80% of chronically denervated, very atrophic muscle fibers containing clumps of TUNEL-positive pyknotic nuclei: about 60% of those fibers also had cytoplasmic Bcl-2 and Bax immunoreactivity. In regenerating muscle fibers of various myopathies SMN co-localized with desmin, Bcl-2 and Bax; it was also present at the postsynaptic domain of normal human neuromuscular junctions. Thus, SMN may play a role in normal and pathological processes of adult human muscle fibers.

In-vivo Reflectance Measurements from Human Skin

NASA Astrophysics Data System (ADS)

Delgado, J. A.; Cornejo, A.; Cunill, M.; Báez, J. J.; Matos, R.; Anasagasti, L.; Santiago, C.

2006-09-01

We evaluate the potential of using a standard commercial spectrophotometer, specifically designed to meet the growing requirement for color control in the digital-imaging application field, to perform in-vivo diffuse reflectance measurements from adult human skin. We report and discuss diffuse reflectance spectra for three practical situations: a) reflectance versus skin type, b) reflectance from normal skin with different grade of solar exposition, c) reflectance from normal skin versus reflectance from seborrheic keratosis. Results show, that using the above spectrophotometer we can easily differentiate two sites of different solar exposition. Besides, significant differences are found in the normal skin diffuse reflectance for patients with different skin types.

Rsu1 regulates ethanol consumption in Drosophila and humans.

PubMed

Ojelade, Shamsideen A; Jia, Tianye; Rodan, Aylin R; Chenyang, Tao; Kadrmas, Julie L; Cattrell, Anna; Ruggeri, Barbara; Charoen, Pimphen; Lemaitre, Hervé; Banaschewski, Tobias; Büchel, Christian; Bokde, Arun L W; Carvalho, Fabiana; Conrod, Patricia J; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lubbe, Steven; Martinot, Jean-Luc; Paus, Tomás; Smolka, Michael N; Spanagel, Rainer; O'Reilly, Paul F; Laitinen, Jaana; Veijola, Juha M; Feng, Jianfeng; Desrivières, Sylvane; Jarvelin, Marjo-Riitta; Schumann, Gunter; Rothenfluh, Adrian

2015-07-28

Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla.

The adult human pubic symphysis: a systematic review

PubMed Central

Becker, Ines; Woodley, Stephanie J; Stringer, Mark D

2010-01-01

The pubic symphysis is a unique joint consisting of a fibrocartilaginous disc sandwiched between the articular surfaces of the pubic bones. It resists tensile, shearing and compressive forces and is capable of a small amount of movement under physiological conditions in most adults (up to 2 mm shift and 1° rotation). During pregnancy, circulating hormones such as relaxin induce resorption of the symphyseal margins and structural changes in the fibrocartilaginous disc, increasing symphyseal width and mobility. This systematic review of the English, German and French literature focuses on the normal anatomy of the adult human pubic symphysis. Although scientific studies of the joint have yielded useful descriptive data, comparison of results is hampered by imprecise methodology and/or poorly controlled studies. Several aspects of the anatomy of the pubic symphysis remain unknown or unclear: the precise attachments of surrounding ligaments and muscles; the arrangement of connective tissue fibres within the interpubic disc and the origin, structure and function of its associated interpubic cleft; the biomechanical consequences of sexual dimorphism; potential ethnic variations in morphology; and its precise innervation and blood supply. These deficiencies hinder our understanding of the normal form and function of the joint, which is particularly relevant when attempting to understand the mechanisms underlying pregnancy-related pubic symphyseal pain, a neglected and relatively common cause of pubic pain. A better understanding of the normal anatomy of the human pubic symphysis should improve our understanding of such problems and contribute to better treatments for patients suffering from symphyseal pain and dysfunction. PMID:20840351

Human prolactin - 24-hour pattern with increased release during sleep.

NASA Technical Reports Server (NTRS)

Sassin, J. F.; Weitzman, E. D.; Kapen, S.; Frantz, A. G.

1972-01-01

Human prolactin was measured in plasma by radioimmunoassay at 20-minute intervals for a 24-hour period in each of six normal adults, whose sleep-wake cycles were monitored polygraphically. A marked diurnal variation in plasma concentrations was demonstrated, with highest values during sleep. Periods of episodic release occurred throughout the 24 hours.

Haptic Tracking Permits Bimanual Independence

ERIC Educational Resources Information Center

Rosenbaum, David A.; Dawson, Amanda A.; Challis, John H.

2006-01-01

This study shows that in a novel task--bimanual haptic tracking--neurologically normal human adults can move their 2 hands independently for extended periods of time with little or no training. Participants lightly touched buttons whose positions were moved either quasi-randomly in the horizontal plane by 1 or 2 human drivers (Experiment 1), in…

The effects of Sophora angustifolia and other natural plant extracts on melanogenesis and melanin transfer in human skin cells.

PubMed

Singh, Suman K; Baker, Richard; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond J

2013-01-01

Skin pigmentation is a multistep process of melanin synthesis by melanocytes, its transfer to recipient keratinocytes and its degradation. As dyspigmentation is a prominent marker of skin ageing, novel effective agents that modulate pigmentation safely are being sought for both clinical and cosmetic use. Here, a number of plant extracts were examined for their effect on melanogenesis (by melanin assay and Western blotting) and melanin transfer (by confocal immunomicroscopy of gp100-positive melanin granules in cocultures and by SEM analysis of filopodia), in human melanocytes and in cocultures with phototype-matched normal adult epidermal keratinocytes. Mulberry, Kiwi and Sophora extracts were assessed against isobutylmethylxanthine, hydroquinone, vitamin C and niacinamide. Compared with unstimulated control, all extracts significantly reduced melanogenesis in human melanoma cells and normal adult epidermal melanocytes. These extracts also reduced melanin transfer and reduced filopodia expression on melanocytes, similar to hydroquinone and niacinamide, indicating their effectiveness as multimode pigmentation actives. © 2013 John Wiley & Sons A/S.

Resistance to serum bactericidal activity distinguishes Brazilian purpuric fever (BPF) case strains of Haemophilus influenzae biogroup aegyptius (H. aegyptius) from non-BPF strains. Brazilian Purpuric Fever Study Group.

PubMed

Porto, M H; Noel, G J; Edelson, P J

1989-04-01

We studied the ability of normal human serum to lyse H. influenzae biogroup aegyptius (H. aegyptius) isolates recovered from patients with Brazilian purpuric fever (BPF clone) or non-BPF clone strains. BPF clone isolates, although similar to non-BPF clone isolates with regard to the ability to fix C3 to their surfaces, could be distinguished from non-BPF clone strains by their resistance to lysis in vitro following incubation with normal adult human serum.

Head circumference: the forgotten tool for hydrocephalus management. A reference interval study in the Spanish population.

PubMed

Poca, Maria A; Martínez-Ricarte, Francisco R; Portabella, Mireia; Torné, Ramon; Fuertes, Maria L; González-Tartiere, Pilar; Sahuquillo, Juan

2013-11-01

In children, deviations from the normal range of head circumference (HC) have traditionally been related with CSF dynamics abnormalities. In adults, this neglected parameter is helpful in the diagnosis and understanding of the pathophysiology of some CSF abnormalities. It has been demonstrated that HC is related to height. Because humans have increased in stature dramatically during the last 50 years, pediatric charts for head growth physiology and normal HC values in adults should be reevaluated. The main aim of the present study was to assess HC in a series of 270 normal healthy Spanish adults and to determine any differences between sexes and age groups. A secondary aim was to discuss the relevance of this parameter in the management of hydrocephalus in adult people. HC measurements were taken using a measuring tape placed over the greatest frontal and occipital protuberances. The reference interval and the upper and lower thresholds for HC were calculated by 3 different methods: normal distribution, the non-parametrical percentile method, and the "robust method". The results were consistent and showed that Spanish adult men with a HC greater than 60 cm, and Spanish adult women with a HC greater than 58 cm should be considered macrocephalic. Microcephaly should be considered when HC is 53.6 cm in men and 51.3 cm in women. Adult age groups of either sex do not present any statistically significant differences in HC. HC obtained in Spanish adult people are greater than those reported in the classical Nellhaus graphs in both men and women aged 18. These findings should be considered in the management of hydrocephalus in adults today. Copyright © 2013 Elsevier B.V. All rights reserved.

Age-associated decrease in GDNF and its cognate receptor GFRα-1 protein expression in human skin.

PubMed

Adly, Mohamed A; Assaf, Hanan A; Hussein, Mahmoud Rezk Abdelwahed

2016-06-01

Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Development of a Scientific Basis for Analysis of Aircraft Seating Systems

DTIC Science & Technology

1975-01-01

JOINT MOVEMENTS IN NORMAL MALE HUMAN ADULTS, Human Biology , Vol. 9, pp. 197-211, 1937. 10. Brinkley, J. W., DEVELOPMENT OF AEROSPACE ESCAPE SYSTEMS...Resisting Torque 21 8 Human Joint Resisting Torques: (a) Displacement- Limiting Moment; (b) Muscular Resistance 22 9 Fxternal Forces of Cushions, Floor...head strike on rigid cockpit structure. Also, the relatively low tolerance of the human b.ody to accelerations in a direction parallel to the spine

Telomere erosion varies during in vitro aging of normal human fibroblasts from young and adult donors.

PubMed

Figueroa, R; Lindenmaier, H; Hergenhahn, M; Nielsen, K V; Boukamp, P

2000-06-01

The life span of normal fibroblasts in vitro (Hayflick limit) depends on donor age, and telomere shortening has been proposed as a potential mechanism. By quantitative fluorescence in situ hybridization and Southern blot analysis, we show progressive telomere loss to about 5 kb mean telomere restriction fragment length in fibroblasts from two adult donors within 40 population doublings, whereas in fibroblasts from two infant donors, telomere erosion is reduced, leaving a mean telomere restriction fragment length of approximately 7 kb at senescence (after approximately 60 population doublings). Aging of fibroblasts from both infant and adult donors was not accompanied by chromosomal abnormalities but was correlated with increased telomere repeat-binding factor 2 expression at both the protein and transcriptional level.

Modeling the clinical and economic implications of obesity using microsimulation.

PubMed

Su, W; Huang, J; Chen, F; Iacobucci, W; Mocarski, M; Dall, T M; Perreault, L

2015-01-01

The obesity epidemic has raised considerable public health concerns, but there are few validated longitudinal simulation models examining the human and economic cost of obesity. This paper describes a microsimulation model as a comprehensive tool to understand the relationship between body weight, health, and economic outcomes. Patient health and economic outcomes were simulated annually over 10 years using a Markov-based microsimulation model. The obese population examined is nationally representative of obese adults in the US from the 2005-2012 National Health and Nutrition Examination Surveys, while a matched normal weight population was constructed to have similar demographics as the obese population during the same period. Prediction equations for onset of obesity-related comorbidities, medical expenditures, economic outcomes, mortality, and quality-of-life came from published trials and studies supplemented with original research. Model validation followed International Society for Pharmacoeconomics and Outcomes Research practice guidelines. Among surviving adults, relative to a matched normal weight population, obese adults averaged $3900 higher medical expenditures in the initial year, growing to $4600 higher expenditures in year 10. Obese adults had higher initial prevalence and higher simulated onset of comorbidities as they aged. Over 10 years, excess medical expenditures attributed to obesity averaged $4280 annually-ranging from $2820 for obese category I to $5100 for obese category II, and $8710 for obese category III. Each excess kilogram of weight contributed to $140 higher annual costs, on average, ranging from $136 (obese I) to $152 (obese III). Poor health associated with obesity increased work absenteeism and mortality, and lowered employment probability, personal income, and quality-of-life. This validated model helps illustrate why obese adults have higher medical and indirect costs relative to normal weight adults, and shows that medical costs for obese adults rise more rapidly with aging relative to normal weight adults.

Adult Human Gingival Epithelial Cells as a Source for Whole-tooth Bioengineering

PubMed Central

Angelova Volponi, A.; Kawasaki, M.; Sharpe, P.T.

2013-01-01

Teeth develop from interactions between embryonic oral epithelium and neural-crest-derived mesenchyme. These cells can be separated into single-cell populations and recombined to form normal teeth, providing a basis for bioengineering new teeth if suitable, non-embryonic cell sources can be identified. We show here that cells can be isolated from adult human gingival tissue that can be expanded in vitro and, when combined with mouse embryonic tooth mesenchyme cells, form teeth. Teeth with developing roots can be produced from this cell combination following transplantation into renal capsules. These bioengineered teeth contain dentin and enamel with ameloblast-like cells and rests of Malassez of human origin. PMID:23458883

[Human brown adipose tissue].

PubMed

Virtanen, Kirsi A; Nuutila, Pirjo

2015-01-01

Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

Resistance to serum bactericidal activity distinguishes Brazilian purpuric fever (BPF) case strains of Haemophilus influenzae biogroup aegyptius (H. aegyptius) from non-BPF strains. Brazilian Purpuric Fever Study Group.

PubMed Central

Porto, M H; Noel, G J; Edelson, P J

1989-01-01

We studied the ability of normal human serum to lyse H. influenzae biogroup aegyptius (H. aegyptius) isolates recovered from patients with Brazilian purpuric fever (BPF clone) or non-BPF clone strains. BPF clone isolates, although similar to non-BPF clone isolates with regard to the ability to fix C3 to their surfaces, could be distinguished from non-BPF clone strains by their resistance to lysis in vitro following incubation with normal adult human serum. PMID:2786003

Radioimmunoassay of human Hageman factor (factor XII). [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, H.; Ratnoff, O.D.; Pensky, J.

A specific, sensitive, and reproducible radioimmunoassay for human Hageman factor (HF, factor XII) has been developed with purified human HF and monospecific rabbit antibody. Precise measurements of HF antigen were possible for concentrations as low as 0.1 percent of that in normal pooled plasma. A good correlation (correlation coefficient = 0.82) existed between the titers of HF measured by clot-promoting assays and radioimmunoassays among 42 normal adults. Confirming earlier studies, HF antigen was absent in Hageman trait plasma, but other congenital deficient plasmas, including those of individuals with Fletcher trait and Fitzgerald trait, contained normal amounts of HF antigen. HFmore » antigen was reduced in the plasmas of patients with disseminated intravascular coagulation or advanced liver cirrhosis, but it was normal in those of patients with chronic renal failure or patients under treatment with warfarin. HF antigen was detected by this assay in plasmas of primates, but not detectable in plasmas of 11 nonprimate mammalian and one avian species.« less

Production of MPS VII mouse (Gustm(hE540A·mE536A)Sly) doubly tolerant to human and mouse β-glucuronidase

PubMed Central

Tomatsu, Shunji; Orii, Koji O.; Vogler, Carole; Grubb, Jeffrey H.; Snella, Elizabeth M.; Gutierrez, Monica; Dieter, Tatiana; Holden, Christopher C.; Sukegawa, Kazuko; Orii, Tadao; Kondo, Naomi; Sly, William S.

2006-01-01

Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal recessive lysosomal storage disease caused by β-glucuronidase (GUS) deficiency. A naturally occurring mouse model of that disease has been very useful for studying experimental approaches to therapy. However, immune responses can complicate evaluation of the long-term benefits of enzyme replacement or gene therapy delivered to adult MPS VII mice. To make this model useful for studying the long-term effectiveness and side effects of experimental therapies delivered to adult mice, we developed a new MPS VII mouse model, which is tolerant to both human and murine GUS. To achieve this, we used homologous recombination to introduce simultaneously a human cDNA transgene expressing inactive human GUS into intron 9 of the murine Gus gene and a targeted active site mutation (E536A) into the adjacent exon 10. When the heterozygote products of germline transmission were bred to homozygosity, the homozygous mice expressed no GUS enzyme activity but expressed inactive human GUS protein highly and were tolerant to immune challenge with human enzyme. Expression of the mutant murine Gus gene was reduced to about 10% of normal levels, but the inactive murine GUS enzyme also conferred tolerance to murine GUS. This MPS VII mouse model should be useful to evaluate therapeutic responses in adult mice receiving repetitive doses of enzyme or mice receiving gene therapy as adults. Heterozygotes expressed only 9.5–26% of wild-type levels of murine GUS instead of the expected 50%, indicating a dominant-negative effect of the mutant enzyme monomers on the activity of GUS tetramers in different tissues. Corrective gene therapy in this model should provide high enough levels of expression of normal GUS monomers to overcome the dominant negative effect of mutant monomers on newly synthesized GUS tetramers in most tissues. PMID:12700165

Effect of the N-terminal residues on the quaternary dynamics of human adult hemoglobin

NASA Astrophysics Data System (ADS)

Chang, Shanyan; Mizuno, Misao; Ishikawa, Haruto; Mizutani, Yasuhisa

2016-05-01

The protein dynamics of human hemoglobin following ligand photolysis was studied by time-resolved resonance Raman spectroscopy. The time-resolved spectra of two kinds of recombinant hemoglobin expressed in Escherichia coli, normal recombinant hemoglobin and the α(V1M)/β(V1M) double mutant, were compared with those of human adult hemoglobin (HbA) purified from blood. A frequency shift of the iron-histidine stretching [ν(Fe-His)] band was observed in the time-resolved spectra of all three hemoglobin samples, indicative of tertiary and quaternary changes in the protein following photolysis. The spectral changes of the α(V1M)/β(V1M) double mutant were distinct from those of HbA in the tens of microseconds region, whereas the spectral changes of normal recombinant hemoglobin were similar to those of HbA isolated from blood. These results demonstrated that a structural change in the N-termini is involved in the second step of the quaternary structure change of hemoglobin. We discuss the implications of these results for understanding the allosteric pathway of HbA.

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis.

PubMed

Filipiak, Eliza; Suliborska, Dagmara; Laszczynska, Maria; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Marchlewska, Katarzyna; Kula, Krzysztof; Slowikowska-Hilczer, Jolanta

2013-10-08

It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER) α and β. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate the localization of ERα in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical biopsies were fixed in Bouin's fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring 10 to -1), the number of Leydig cells (scoring 1 to 5), the areal fraction of intertubular space (IS), measurements of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic sections. Immunohistochemical staining was applied with monoclonal antibodies against ERα. The mean spermatogenesis score was 10 points; IS - 30.6 ± 8.1%; seminiferous tubule diameter - 193.9 ± 19.4 μm; thickness of tubular wall - 7.44 ± 1.1 μm; number of Leydig cells - 1.6 ± 1.1 points. Immunohistochemical staining showed the localization of ERα to be in the Sertoli and Leydig cell cytoplasm, while ERα was absent in germ cells. The results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence of ERα in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may affect testicular function.

Electrocardiogram reference intervals for clinically normal wild-born chimpanzees (Pan troglodytes).

PubMed

Atencia, Rebeca; Revuelta, Luis; Somauroo, John D; Shave, Robert E

2015-08-01

To generate reference intervals for ECG variables in clinically normal chimpanzees (Pan troglodytes). 100 clinically normal (51 young [< 10 years old] and 49 adult [≥ 10 years old]) wild-born chimpanzees. Electrocardiograms collected between 2009 and 2013 at the Tchimpounga Chimpanzee Rehabilitation Centre were assessed to determine heart rate, PR interval, QRS duration, QT interval, QRS axis, P axis, and T axis. Electrocardiographic characteristics for left ventricular hypertrophy (LVH) and morphology of the ST segment, T wave, and QRS complex were identified. Reference intervals for young and old animals were calculated as mean ± 1.96•SD for normally distributed data and as 5th to 95th percentiles for data not normally distributed. Differences between age groups were assessed by use of unpaired Student t tests. RESULTS Reference intervals were generated for young and adult wild-born chimpanzees. Most animals had sinus rhythm with small or normal P wave morphology; 24 of 51 (47%) young chimpanzees and 30 of 49 (61%) adult chimpanzees had evidence of LVH as determined on the basis of criteria for humans. Cardiac disease has been implicated as the major cause of death in captive chimpanzees. Species-specific ECG reference intervals for chimpanzees may aid in the diagnosis and treatment of animals with, or at risk of developing, heart disease. Chimpanzees with ECG characteristics outside of these intervals should be considered for follow-up assessment and regular cardiac monitoring.

Comparative study of the primary cilia in thyrocytes of adult mammals

PubMed Central

Utrilla, J C; Gordillo-Martínez, F; Gómez-Pascual, A; Fernández-Santos, J M; Garnacho, C; Vázquez-Román, V; Morillo-Bernal, J; García-Marín, R; Jiménez-García, A; Martín-Lacave, I

2015-01-01

Since their discovery in different human tissues by Zimmermann in 1898, primary cilia have been found in the vast majority of cell types in vertebrates. Primary cilia are considered to be cellular antennae that occupy an ideal cellular location for the interpretation of information both from the environment and from other cells. To date, in mammalian thyroid gland, primary cilia have been found in the thyrocytes of humans and dogs (fetuses and adults) and in rat embryos. The present study investigated whether the existence of this organelle in follicular cells is a general event in the postnatal thyroid gland of different mammals, using both immunolabeling by immunofluorescence and electron microscopy. Furthermore, we aimed to analyse the presence of primary cilia in various thyroid cell lines. According to our results, primary cilia are present in the adult thyroid gland of most mammal species we studied (human, pig, guinea pig and rabbit), usually as a single copy per follicular cell. Strikingly, they were not found in rat or mouse thyroid tissues. Similarly, cilia were also observed in all human thyroid cell lines tested, both normal and neoplastic follicular cells, but not in cultured thyrocytes of rat origin. We hypothesize that primary cilia could be involved in the regulation of normal thyroid function through specific signaling pathways. Nevertheless, further studies are needed to shed light on the permanence of these organelles in the thyroid gland of most species during postnatal life. PMID:26228270

Circular RNA expression profiles and features in human tissues: a study using RNA-seq data.

PubMed

Xu, Tianyi; Wu, Jing; Han, Ping; Zhao, Zhongming; Song, Xiaofeng

2017-10-03

Circular RNA (circRNA) is one type of noncoding RNA that forms a covalently closed continuous loop. Similar to long noncoding RNA (lncRNA), circRNA can act as microRNA (miRNA) 'sponges' to regulate gene expression, and its abnormal expression is related to diseases such as atherosclerosis, nervous system disorders and cancer. So far, there have been no systematic studies on circRNA abundance and expression profiles in human adult and fetal tissues. We explored circRNA expression profiles using RNA-seq data for six adult and fetal normal tissues (colon, heart, kidney, liver, lung, and stomach) and four gland normal tissues (adrenal gland, mammary gland, pancreas, and thyroid gland). A total of 8120, 25,933 and 14,433 circRNAs were detected by at least two supporting junction reads in adult, fetal and gland tissues, respectively. Among them, 3092, 14,241 and 6879 circRNAs were novel when compared to the published results. In each adult tissue type, we found at least 1000 circRNAs, among which 36.97-50.04% were tissue-specific. We reported 33 circRNAs that were ubiquitously expressed in all the adult tissues we examined. To further explore the potential "housekeeping" function of these circRNAs, we constructed a circRNA-miRNA-mRNA regulatory network containing 17 circRNAs, 22 miRNAs and 90 mRNAs. Furthermore, we found that both the abundance and the relative expression level of circRNAs were higher in fetal tissue than adult tissue. The number of circRNAs in gland tissues, especially in mammary gland (9665 circRNA candidates), was higher than that of other adult tissues (1160-3777). We systematically investigated circRNA expression in a variety of human adult and fetal tissues. Our observation of different expression level of circRNAs in adult and fetal tissues suggested that circRNAs might play their role in a tissue-specific and development-specific fashion. Analysis of circRNA-miRNA-mRNA network provided potential targets of circRNAs. High expression level of circRNAs in mammary gland might be attributed to the rich innervation.

Comparison of primary human fibroblasts and keratinocytes with immortalized cell lines regarding their sensitivity to sodium dodecyl sulfate in a neutral red uptake cytotoxicity assay.

PubMed

Olschläger, Veronika; Schrader, Andreas; Hockertz, Stefan

2009-01-01

Cell lines present a valuable tool for in vitro assessment of skin damage caused by application of cosmeticals or pharmaceuticals. They form a reproducible test system under controllable test conditions and, in many cases, can be used as alternatives to animal testing in order to assess the compatibility of drugs or cosmetics and human skin. Yet, it can not necessarily be assumed that the behavior of cultured cells, when treated with different substances, is exactly consistent with the behavior of cells being part of a live organism. Becoming immortal, cells exhibit changes in genotype and/or phenotype, possibly resulting in modified reactions to external influences. Therefore, to obtain results close to in vivo studies, it seems apparent to use primary cells for testing that have not yet undergone any modifications. To compare the properties of primary fibroblasts (Normal Human Dermal Fibroblasts, NHDF) and primary keratinocytes (Normal Human Epidermal Keratinocytes, NHEK) with those of immortal cell lines (3T3 (ACC 173) Swiss albino mouse fibroblasts and HaCaT (human, adult, low calcium, high temperature, human adult skin keratinocytes) cells), their sensitivities in cytotoxicity assays have been assessed. While both fibroblast cell cultures showed similar sensitivities towards sodium dodecyl sulfate (SDS), primary keratinocytes died at SDS concentrations about three times lower than the immortal HaCaT cells.

Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

PubMed Central

González-Losa, Maria del Refugio; Manzano-Cabrera, Luis; Rueda-Gordillo, Florencio; Hernández-Solís, Sandra E.; Puerto-Solís, Luis

2008-01-01

High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies. PMID:24031173

Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

PubMed

Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

2011-11-01

The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas. Copyright © 2010 Elsevier GmbH. All rights reserved.

A survey of human brain transcriptome diversity at the single cell level.

PubMed

Darmanis, Spyros; Sloan, Steven A; Zhang, Ye; Enge, Martin; Caneda, Christine; Shuer, Lawrence M; Hayden Gephart, Melanie G; Barres, Ben A; Quake, Stephen R

2015-06-09

The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

Tinnitus with a normal audiogram: Relation to noise exposure but no evidence for cochlear synaptopathy.

PubMed

Guest, Hannah; Munro, Kevin J; Prendergast, Garreth; Howe, Simon; Plack, Christopher J

2017-02-01

In rodents, exposure to high-level noise can destroy synapses between inner hair cells and auditory nerve fibers, without causing hair cell loss or permanent threshold elevation. Such "cochlear synaptopathy" is associated with amplitude reductions in wave I of the auditory brainstem response (ABR) at moderate-to-high sound levels. Similar ABR results have been reported in humans with tinnitus and normal audiometric thresholds, leading to the suggestion that tinnitus in these cases might be a consequence of synaptopathy. However, the ABR is an indirect measure of synaptopathy and it is unclear whether the results in humans reflect the same mechanisms demonstrated in rodents. Measures of noise exposure were not obtained in the human studies, and high frequency audiometric loss may have impacted ABR amplitudes. To clarify the role of cochlear synaptopathy in tinnitus with a normal audiogram, we recorded ABRs, envelope following responses (EFRs), and noise exposure histories in young adults with tinnitus and matched controls. Tinnitus was associated with significantly greater lifetime noise exposure, despite close matching for age, sex, and audiometric thresholds up to 14 kHz. However, tinnitus was not associated with reduced ABR wave I amplitude, nor with significant effects on EFR measures of synaptopathy. These electrophysiological measures were also uncorrelated with lifetime noise exposure, providing no evidence of noise-induced synaptopathy in this cohort, despite a wide range of exposures. In young adults with normal audiograms, tinnitus may be related not to cochlear synaptopathy but to other effects of noise exposure. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Gastrocnemius mitochondrial respiration: are there any differences between men and women?

PubMed

Thompson, Jonathan R; Swanson, Stanley A; Casale, George P; Johanning, Jason M; Papoutsi, Evlampia; Koutakis, Panagiotis; Miserlis, Dimitrios; Zhu, Zhen; Pipinos, Iraklis I

2013-11-01

Work on human and mouse skeletal muscle by our group and others has demonstrated that aging and age-related degenerative diseases are associated with mitochondrial dysfunction, which may be more prevalent in males. There have been, however, no studies that specifically examine the influence of male or female sex on human skeletal muscle mitochondrial respiration. The purpose of this study was to compare mitochondrial respiration in the gastrocnemius of adult men and women. Gastrocnemius muscle was obtained from male (n = 19) and female (n = 11) human subjects with healthy lower-extremity musculoskeletal and arterial systems and normal ambulatory function. All patients were undergoing operations for the treatment of varicose veins in their legs. Mitochondrial respiration was determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Complex I-, II-, III-, and IV-dependent respiration was measured individually and normalized to muscle weight, total protein content, and citrate synthase (CS, index of mitochondrial content). Male and female patients had no evidence of musculoskeletal or arterial disease and did not differ with regard to age, race, body mass index, or other clinical characteristics. Complex I-, II-, III-, and IV-dependent respiration normalized to muscle weight, total protein content, and CS did not statistically differ for males compared with females. Our study evaluates, for the first time, gastrocnemius mitochondrial respiration of adult men and women who have healthy musculoskeletal and arterial systems and normal ambulatory function. Our data demonstrate there are no differences in the respiration of gastrocnemius mitochondria between men and women. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

Harvesting of males delays female breeding in a socially monogamous mammal; the beaver.

PubMed

Parker, Howard; Rosell, Frank; Mysterud, Atle

2007-02-22

Human exploitation may skew adult sex ratios in vertebrate populations to the extent that males become limiting for normal reproduction. In polygynous ungulates, females delay breeding in heavily harvested populations, but effects are often fairly small. We would expect a stronger effect of male harvesting in species with a monogamous mating system, but no such study has been performed. We analysed the effect of harvesting males on the timing of reproduction in the obligate monogamous beaver (Castor fiber). We found a negative impact of harvesting of adult males on the timing of parturition in female beavers. The proportion of normal breeders sank from over 80%, when no males had been shot in the territories of pregnant females, to under 20%, when three males had been shot. Harvesting of males in monogamous mammals can apparently affect their normal reproductive cycle.

Spatial vision in older adults: perceptual changes and neural bases.

PubMed

McKendrick, Allison M; Chan, Yu Man; Nguyen, Bao N

2018-05-17

The number of older adults is rapidly increasing internationally, leading to a significant increase in research on how healthy ageing impacts vision. Most clinical assessments of spatial vision involve simple detection (letter acuity, grating contrast sensitivity, perimetry). However, most natural visual environments are more spatially complicated, requiring contrast discrimination, and the delineation of object boundaries and contours, which are typically present on non-uniform backgrounds. In this review we discuss recent research that reports on the effects of normal ageing on these more complex visual functions, specifically in the context of recent neurophysiological studies. Recent research has concentrated on understanding the effects of healthy ageing on neural responses within the visual pathway in animal models. Such neurophysiological research has led to numerous, subsequently tested, hypotheses regarding the likely impact of healthy human ageing on specific aspects of spatial vision. Healthy normal ageing impacts significantly on spatial visual information processing from the retina through to visual cortex. Some human data validates that obtained from studies of animal physiology, however some findings indicate that rethinking of presumed neural substrates is required. Notably, not all spatial visual processes are altered by age. Healthy normal ageing impacts significantly on some spatial visual processes (in particular centre-surround tasks), but leaves contrast discrimination, contrast adaptation, and orientation discrimination relatively intact. The study of older adult vision contributes to knowledge of the brain mechanisms altered by the ageing process, can provide practical information regarding visual environments that older adults may find challenging, and may lead to new methods of assessing visual performance in clinical environments. © 2018 The Authors Ophthalmic & Physiological Optics © 2018 The College of Optometrists.

Procedures for ambient-pressure and tympanometric tests of aural acoustic reflectance and admittance in human infants and adults

PubMed Central

Keefe, Douglas H.; Hunter, Lisa L.; Feeney, M. Patrick; Fitzpatrick, Denis F.

2015-01-01

Procedures are described to measure acoustic reflectance and admittance in human adult and infant ears at frequencies from 0.2 to 8 kHz. Transfer functions were measured at ambient pressure in the ear canal, and as down- or up-swept tympanograms. Acoustically estimated ear-canal area was used to calculate ear reflectance, which was parameterized by absorbance and group delay over all frequencies (and pressures), with substantial data reduction for tympanograms. Admittance measured at the probe tip in adults was transformed into an equivalent admittance at the eardrum using a transmission-line model for an ear canal with specified area and ear-canal length. Ear-canal length was estimated from group delay around the frequency above 2 kHz of minimum absorbance. Illustrative measurements in ears with normal function are described for an adult, and two infants at 1 month of age with normal hearing and a conductive hearing loss. The sensitivity of this equivalent eardrum admittance was calculated for varying estimates of area and length. Infant-ear patterns of absorbance peaks aligned in frequency with dips in group delay were explained by a model of resonant canal-wall mobility. Procedures will be applied in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function. PMID:26723319

GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.

PubMed

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.

Changes in radiation dose with variations in human anatomy: larger and smaller normal-stature adults.

PubMed

Marine, Patrick M; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

2010-05-01

A systematic evaluation has been performed to study how specific absorbed fractions (SAFs) vary with changes in adult body size, for persons of different size but normal body stature. A review of the literature was performed to evaluate how individual organ sizes vary with changes in total body weight of normal-stature individuals. On the basis of this literature review, changes were made to our easily deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed; SAFs for photons were generated for 10th, 25th, 75th, and 90th percentile adults; and comparisons were made to the reference (50th) percentile SAF values. Differences in SAFs for organs irradiating themselves were between 0.5% and 1.0%/kg difference in body weight, from 15% to 30% overall, for organs within the trunk. Differences in SAFs for organs outside the trunk were not greater than the uncertainties in the data and will not be important enough to change calculated doses. For organs irradiating other organs within the trunk, differences were significant, between 0.3% and 1.1%/kg, or about 8%-33% overall. The differences are interesting and can be used to estimate how different patients' dosimetry might vary from values reported in standard dose tables.

Cell Cycle Regulators during Human Atrial Development

PubMed Central

Kim, Won Ho; Joo, Chan Uhng; Ku, Ja Hong; Ryu, Chul Hee; Koh, Keum Nim; Koh, Gou Young; Ko, Jae Ki

1998-01-01

Objectives The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. Methods Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery, Cyclin and CDK proteins were determined by Western blot analysis, CDK activities were determined by phosphorylation amount using specific substrate. Results Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP 1 protein increased markedly in the adult period, while p21C IP 1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. Conclusion These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP 1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans. PMID:9735660

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair.

PubMed

Garcin, Clare L; Huttner, Kenneth M; Kirby, Neil; Schneider, Pascal; Hardman, Matthew J

2016-05-01

The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit

PubMed Central

2014-01-01

Background Children with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial. Objective The objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies. Results Eighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty. Conclusion Our experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment. PMID:25075207

Dietary Precursors of Serotonin and Newborn State Behavior.

ERIC Educational Resources Information Center

Yogman, Michael W.; Zeisel, Steven

Although previous research with adult humans and nonhumans has suggested a relationship between sleep behavior and brain serotonin levels, no studies have been made of the relationship of normal children's or infants' sleep patterns to serotonin levels, tryptophan metabolism, or diet. This study investigates the relationship between dietary…

Mechanical ventilation alone, and in the presence of sepsis, impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Modeling and simulation of normal and hemiparetic gait

NASA Astrophysics Data System (ADS)

Luengas, Lely A.; Camargo, Esperanza; Sanchez, Giovanni

2015-09-01

Gait is the collective term for the two types of bipedal locomotion, walking and running. This paper is focused on walking. The analysis of human gait is of interest to many different disciplines, including biomechanics, human-movement science, rehabilitation and medicine in general. Here we present a new model that is capable of reproducing the properties of walking, normal and pathological. The aim of this paper is to establish the biomechanical principles that underlie human walking by using Lagrange method. The constraint forces of Rayleigh dissipation function, through which to consider the effect on the tissues in the gait, are included. Depending on the value of the factor present in the Rayleigh dissipation function, both normal and pathological gait can be simulated. First of all, we apply it in the normal gait and then in the permanent hemiparetic gait. Anthropometric data of adult person are used by simulation, and it is possible to use anthropometric data for children but is necessary to consider existing table of anthropometric data. Validation of these models includes simulations of passive dynamic gait that walk on level ground. The dynamic walking approach provides a new perspective of gait analysis, focusing on the kinematics and kinetics of gait. There have been studies and simulations to show normal human gait, but few of them have focused on abnormal, especially hemiparetic gait. Quantitative comparisons of the model predictions with gait measurements show that the model can reproduce the significant characteristics of normal gait.

An ultra-sensitive biophysical risk assessment of light effect on skin cells.

PubMed

Bennet, Devasier; Viswanath, Buddolla; Kim, Sanghyo; An, Jeong Ho

2017-07-18

The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.

Rethinking schizophrenia in the context of normal neurodevelopment

PubMed Central

Catts, Vibeke S.; Fung, Samantha J.; Long, Leonora E.; Joshi, Dipesh; Vercammen, Ans; Allen, Katherine M.; Fillman, Stu G.; Rothmond, Debora A.; Sinclair, Duncan; Tiwari, Yash; Tsai, Shan-Yuan; Weickert, Thomas W.; Shannon Weickert, Cynthia

2013-01-01

The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis. PMID:23720610

Human face processing is tuned to sexual age preferences

PubMed Central

Ponseti, J.; Granert, O.; van Eimeren, T.; Jansen, O.; Wolff, S.; Beier, K.; Deuschl, G.; Bosinski, H.; Siebner, H.

2014-01-01

Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. PMID:24850896

Vestibular Evoked Myogenic Potentials in Normal Mice and Phex Mice With Spontaneous Endolymphatic Hydrops

PubMed Central

Sheykholeslami, Kianoush; Megerian, Cliff A.; Zheng, Qing Y.

2010-01-01

Objective and Background Vestibular evoked myogenic potentials (VEMPs) have been recorded from the neck musculature and the cervical spinal cord in humans and a limited number of laboratory animals in response to loud sound. However, the mouse VEMP has yet to be described. Evaluation of the sacculocollic pathway via VEMPs in mice can set the stage for future evaluations of mutant mice that now play an important role in research regarding human auditory and vestibular dysfunction. Materials and Methods Sound-evoked potentials were recorded from the neck extensor muscles and the cervical spinal cord in normal adult mice and in circling PhexHyp-Duk/y mice with known vestibular abnormalities, including endolymphatic hydrops (ELH). Results Biphasic potentials were recorded from all normal animals. The mean threshold of the VEMP response in normal adult mice was 60 dB normal hearing level with a mean peak latency of 6.25 ± 0.46 and 7.95 ± 0.42 milliseconds for p1 and n1 peaks, respectively. At the maximum sound intensity used (100 dB normal hearing level), 4 of 5 Phex mice did not exhibit VEMP responses, and 1 showed an elevated threshold, but normal response, with regard to peak latency and amplitude. The histologic findings in all of these Phex mice were consistent with distended membranous labyrinth, displaced Reissner membrane, ganglion cell loss, and ELH. Conclusion This is the first report of VEMP recordings in mice and the first report of abnormal VEMPs in a mouse model with ELH. The characteristics of these potentials such as higher response threshold in comparison to auditory brainstem response, myogenic nature of the response, and latency correlation with the cervical recording (accessory nerve nucleus) were similar to those of VEMPs in humans, guinea pigs, cats, and rats, suggesting that the mouse may be used as an animal model in the study of VEMPs. The simplicity and reliability of these recordings make the VEMP a uniquely informative test for assessing vestibular function, and these results suggest that they may be informative in mice with various mutations. However, further investigation is necessary. PMID:19300299

Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells

PubMed Central

Chanson, Lea; Brownfield, Douglas; Garbe, James C.; Kuhn, Irene; Stampfer, Martha R.; Bissell, Mina J.; LaBarge, Mark A.

2011-01-01

Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells. PMID:21300877

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

DOE PAGES

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

2017-03-22

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

PubMed

Gusterson, Barry; Eaves, Connie J

2018-06-05

Human breast cancers referred to as "basal-like" are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Left-right asymmetry of the Maxwell spot centroids in adults without and with dyslexia.

PubMed

Le Floch, Albert; Ropars, Guy

2017-10-25

In human vision, the brain has to select one view of the world from our two eyes. However, the existence of a clear anatomical asymmetry providing an initial imbalance for normal neural development is still not understood. Using a so-called foveascope, we found that for a cohort of 30 normal adults, the two blue cone-free areas at the centre of the foveas are asymmetrical. The noise-stimulated afterimage dominant eye introduced here corresponds to the circular blue cone-free area, while the non-dominant eye corresponds to the diffuse and irregular elliptical outline. By contrast, we found that this asymmetry is absent or frustrated in a similar cohort of 30 adults with normal ocular status, but with dyslexia, i.e. with visual and phonological deficits. In this case, our results show that the two Maxwell centroid outlines are both circular but lead to an undetermined afterimage dominance with a coexistence of primary and mirror images. The interplay between the lack of asymmetry and the development in the neural maturation of the brain pathways suggests new implications in both fundamental and biomedical sciences. © 2017 The Author(s).

Fetal myosin immunoreactivity in human dystrophic muscle.

PubMed

Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

1986-01-01

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Contraction-induced injury to single permeabilized muscle fibers from normal and congenitally-clefted goat palates.

PubMed

Rader, Erik P; Cederna, Paul S; Weinzweig, Jeffrey; Panter, Kip E; Yu, Deborah; Buchman, Steven R; Larkin, Lisa M; Faulkner, John A

2007-03-01

Levator veli palatini muscles from normal palates of adult humans and goats are predominantly slow oxidative (type 1) fibers. However, 85% of levator veli palatini fibers from cleft palates of adult goats are physiologically fast (type 2). This fiber composition difference between cleft and normal palates may have implications in palatal function. For limb muscles, type 2 muscle fibers are more susceptible to lengthening contraction-induced injury than are type 1 fibers. We tested the hypothesis that, compared with single permeabilized levator veli palatini muscle fibers from normal palates of adult goats, those from cleft palates are more susceptible to lengthening contraction-induced injury. Congenital cleft palates were the result of chemically-induced decreased movement of the fetal head and tongue causing obstruction of palatal closure. Each muscle fiber was maximally activated and lengthened. Fiber type was determined by contractile properties and gel electrophoresis. Susceptibility to injury was assessed by measuring the decrease in maximum force following the lengthening contraction, expressed as a percentage of the initial force. Compared with fibers from normal palates that were all type 1 and had force deficits of 23 +/- 1%, fibers from cleft palates were all type 2 and sustained twofold greater deficits, 40 +/- 1% (p = .001). Levator veli palatini muscles from cleft palates of goats contain predominantly type 2 fibers that are highly susceptible to lengthening contraction-induced injury. This finding may have implications regarding palatal function and the incidence of velopharyngeal incompetence.

Effects of nitrogen dioxide on pulmonary function in human subjects: an environmental chamber study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerr, H.D.; Kulle, T.J.; McIlhany, M.L.

Twenty human subjects with asthma and chronic bronchitis and 10 healthy adults were exposed to 0.5 ppM of nitrogen dioxide for 2 hr in an environment chamber. Seven of the 13 subjects with asthma experienced symptoms with exposure, while only one each of the subjects with bronchitis and the normal group experienced symptoms. Functional residual pulmonary capacity increased for those with asthma and bronchitis. 18 references, 5 tables.

Stem-Cell-Based Tumorigenesis in Adult Drosophila.

PubMed

Hou, S X; Singh, S R

2017-01-01

Recent studies suggest that a small subset of cells within a tumor, the so-called cancer stem cells (CSCs), are responsible for tumor propagation, relapse, and the eventual death of most cancer patients. CSCs may derive from a few tumor-initiating cells, which are either transformed normal stem cells or reprogrammed differentiated cells after acquiring initial cancer-causing mutations. CSCs and normal stem cells share some properties, but CSCs differ from normal stem cells in their tumorigenic ability. Notably, CSCs are usually resistant to chemo- and radiation therapies. Despite the apparent roles of CSCs in human cancers, the biology underlying their behaviors remains poorly understood. Over the past few years, studies in Drosophila have significantly contributed to this new frontier of cancer research. Here, we first review how stem-cell tumors are initiated and propagated in Drosophila, through niche appropriation in the posterior midgut and through stem-cell competition for niche occupancy in the testis. We then discuss the differences between normal and tumorigenic stem cells, revealed by studying Ras V12 -transformed stem-cell tumors in the Drosophila kidney. Finally, we review the biology behind therapy resistance, which has been elucidated through studies of stem-cell resistance and sensitivity to death inducers using female germline stem cells and intestinal stem cells of the posterior midgut. We expect that screens using adult Drosophila neoplastic stem-cell tumor models will be valuable for identifying novel and effective compounds for treating human cancers. © 2017 Elsevier Inc. All rights reserved.

Getting to Know You: The Prospect of Challenging Ableism through Adult Learning

ERIC Educational Resources Information Center

McLean, Margaret A.

2011-01-01

Ableism is discrimination on the grounds that being able bodied is the normal and superior human condition. In contrast, being "disabled" is linked to ill health, incapacity, and dependence. These understandings become institutionalized in the beliefs, language, and practices of nondisabled people and create barriers to equitable social…

Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells.

PubMed

Cereser, Biancastella; Jansen, Marnix; Austin, Emily; Elia, George; McFarlane, Taneisha; van Deurzen, Carolien Hm; Sieuwerts, Anieta M; Daidone, Maria G; Tadrous, Paul J; Wright, Nicholas A; Jones, Louise; McDonald, Stuart Ac

2018-01-01

It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser-capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi-lineage differentiation within CCO-deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO-deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

PubMed

Casey, Alison E; Sinha, Ankit; Singhania, Rajat; Livingstone, Julie; Waterhouse, Paul; Tharmapalan, Pirashaanthy; Cruickshank, Jennifer; Shehata, Mona; Drysdale, Erik; Fang, Hui; Kim, Hyeyeon; Isserlin, Ruth; Bailey, Swneke; Medina, Tiago; Deblois, Genevieve; Shiah, Yu-Jia; Barsyte-Lovejoy, Dalia; Hofer, Stefan; Bader, Gary; Lupien, Mathieu; Arrowsmith, Cheryl; Knapp, Stefan; De Carvalho, Daniel; Berman, Hal; Boutros, Paul C; Kislinger, Thomas; Khokha, Rama

2018-06-19

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. © 2018 Casey et al.

Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome.

PubMed

Lottrup, G; Nielsen, J E; Maroun, L L; Møller, L M A; Yassin, M; Leffers, H; Skakkebæk, N E; Rajpert-De Meyts, E

2014-08-01

What is the differentiation stage of human testicular interstitial cells, in particular Leydig cells (LC), within micronodules found in patients with infertility, testicular cancer and Klinefelter syndrome? The Leydig- and peritubular-cell populations in testes with dysgenesis contain an increased proportion of undifferentiated cells when compared with control samples, as demonstrated by increased delta-like homolog 1 (DLK1) and decreased insulin-like peptide 3 (INSL3) expression. Normal LC function is essential for male development and reproduction. Signs of LC failure, including LC micronodules, are often observed in patients with reproductive disorders. In this retrospective study, a panel of markers and factors linked to the differentiation of LCs was investigated in 33 fetal and prepubertal human specimens and in 58 adult testis samples from patients with testicular germ cell tumours, including precursor carcinoma in situ (CIS), infertility or Klinefelter syndrome. The expression patterns of DLK1, INSL3, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) and smooth muscle actin (SMA) were investigated by immunohistochemistry and quantitative RT-PCR. The percentage of positive LCs was estimated and correlated to total LC numbers and serum levels of reproductive hormones. DLK1, INSL3 and COUP-TFII expression changed during normal development and was linked to different stages of LC differentiation: DLK1 was expressed in all fetal LCs, but only in spindle-shaped progenitor cells and in a small subset of polygonal LCs in the normal adult testis; INSL3 was expressed in a subset of fetal LCs, but in the majority of adult LCs; and COUP-TFII was expressed in peritubular and mesenchymal stroma cells at all ages, in fetal LCs early in gestation and in a subset of adult LCs. CYP11A1 was expressed in the majority of LCs regardless of age and pathology and was the best general LC marker examined here. SMA was weakly expressed in peritubular cells in the fetal and infantile testis, but strongly expressed in the adult testis. In pathological testes, the numbers of DLK1-positive interstitial cells were increased. The proportion of DLK1-positive LCs correlated with total LC numbers (R = 0.53; P < 0.001) and was higher in testis with enlargement of the peritubular layers (P < 0.01), which was also highly associated with DLK1 expression in the peritubular compartment (P < 0.001). INSL3 expression was absent in some, but not all LC micronodules, and in the majority of LCs, it was mutually exclusive of DLK1. The number of samples was relatively small and no true normal adult controls were available. True stereology was not used for LC counting, instead LCs were counted in three fields of 0.5 µm(2) surface for each sample. The population of LCs, especially those clustered in large nodules, are heterogeneous and comprise cells at different stages of differentiation. The study demonstrated that the differentiation and function of LCs, and possibly also peritubular cells, are impaired in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of interest. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Expressed sequence tag analysis of adult human lens for the NEIBank Project: over 2000 non-redundant transcripts, novel genes and splice variants.

PubMed

Wistow, Graeme; Bernstein, Steven L; Wyatt, M Keith; Behal, Amita; Touchman, Jeffrey W; Bouffard, Gerald; Smith, Don; Peterson, Katherine

2002-06-15

To explore the expression profile of the human lens and to provide a resource for microarray studies, expressed sequence tag (EST) analysis has been performed on cDNA libraries from adult lenses. A cDNA library was constructed from two adult (40 year old) human lenses. Over two thousand clones were sequenced from the unamplified, un-normalized library. The library was then normalized and a further 2200 sequences were obtained. All the data were analyzed using GRIST (GRouping and Identification of Sequence Tags), a procedure for gene identification and clustering. The lens library (by) contains a low percentage of non-mRNA contaminants and a high fraction (over 75%) of apparently full length cDNA clones. Approximately 2000 reads from the unamplified library yields 810 clusters, potentially representing individual genes expressed in the lens. After normalization, the content of crystallins and other abundant cDNAs is markedly reduced and a similar number of reads from this library (fs) yields 1455 unique groups of which only two thirds correspond to named genes in GenBank. Among the most abundant cDNAs is one for a novel gene related to glutamine synthetase, which was designated "lengsin" (LGS). Analyses of ESTs also reveal examples of alternative transcripts, including a major alternative splice form for the lens specific membrane protein MP19. Variant forms for other transcripts, including those encoding the apoptosis inhibitor Livin and the armadillo repeat protein ARVCF, are also described. The lens cDNA libraries are a resource for gene discovery, full length cDNAs for functional studies and microarrays. The discovery of an abundant, novel transcript, lengsin, and a major novel splice form of MP19 reflect the utility of unamplified libraries constructed from dissected tissue. Many novel transcripts and splice forms are represented, some of which may be candidates for genetic diseases.

Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

PubMed

Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

2015-09-01

Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

SEM Imaging for Observation of Morphological Changes in Anaemic Human Blood Cell

NASA Astrophysics Data System (ADS)

Datta, Triparna; Roychoudhury, Uttam

Scanning Electron Microscopy (SEM) is utilized to elucidate the morphological changes in anaemic human red blood cells. Haemoglobin concentration in human blood is in the range of 11.5-13.5 g/dl in healthy adults. Haemoglobin concentration in anaemic red blood is below the lower limit of normal range. Sometimes, the nature of the abnormal shape of the blood cell determines the cause of anaemia. Normally, there occurs a variation in the diameter of the red blood cell (RBC) for different types of anaemia. Increased variation of size in blood cell is termed anisocytosis (a type of anaemia) (Mohan H, Text book of pathology, New Delhi). In case of anisocytosis, diameter of cells larger than normal cell is observed. The classification of anaemia by the size of blood cell is logical, i.e. common morphological abnormality of human blood cell (Davidson's principle and practice of medicine, Publisher Churchill Livingstone, London). Cells are studied under ZEISS SEM with different magnification and applied potential of kV range. Thus the diameters of RBCs in SEM have been compared with RBCs photographed with light microscope. Anaemic cells are observed overlapped with each other with increasing diameter.

Estimation of Somatomedin-C Levels in Normals and Patients with Pituitary Disease by Radioimmunoassay

PubMed Central

Furlanetto, Richard W.; Underwood, Louis E.; Van Wyk, Judson J.; D'Ercole, A. Joseph

1977-01-01

The development of a radioimmunoassay for somatomedin-C has for the first time made it possible to discriminate between serum concentrations of a single peptide or closely related group of peptides and the net somatomedin activity measured by less specific bioassay and radioreceptor techniques. Antibodies to human somatomedin-C were raised in rabbits using a somatomedin-C ovalbumin complex as the antigen. A variety of peptide hormones at concentrations up to 1 μM are not recognized by the antibody. Insulin at concentrations >0.1 μM cross reacts in a non-parallel fashion; purified somatomedin-A is only 3% as active as somatomedin-C; and radiolabeled cloned rat liver multiplication stimulating activity does not bind to the antibody. Immunoreactive somatomedin-C can also be quantitated in the sera of a variety of subhuman species. Unusual assay kinetics, which are manifest when reactants are incubated under classic “equilibrium” assay conditions, appear to result from the failure of 125I-somatomedin-C to readily equilibrate with the somatomedin-C serum binding protein complex. It is, therefore, necessary to use nonequilibrium assay conditions to quantitate somatomedin-C in serum. With this assay it is possible to detect somatomedin-C in normal subjects using as little as 0.25 μl of unextracted serum. Serum somatomedin-C concentrations in normal subjects were lowest in cord blood and rose rapidly during the first 4 yr of life to near adult levels. In 23 normal adult volunteers, the mean serum somatomedin-C concentration was 1.50±0.10 U/ml (SEM) when compared to a pooled adult serum standard. 19 children with hypopituitary dwarfism had concentrations below 0.20 U/ml. 17 of these were below 0.1 U/ml, the lower limit of sensitivity of the assay. The mean concentration in 14 adults with active acromegaly was 6.28±0.37 U/ml (SEM), five times greater than the normal volunteers. Significant increases in serum somatomedin-C concentrations were observed in 8 of 10 hypopituitary children within 72 h after the parenteral administration of human growth hormone. Three patients with Cushing's disease had elevated serum somatomedin-C concentrations (2.61±0.14 U/ml [SEM]). Three patients with hyperprolactinemia had normal concentrations (1.74±0.11 U/ml [SEM]). The important new discovery brought to light by quantitation of immunoassayable somatomedin in patient sera is that all previously used assays detect, in addition to somatomedin-C, serum substances that are not under as stringent growth hormone control. PMID:893668

Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolozin, B.; Scicutella, A.; Davies, P.

1988-08-01

ALZ-50 is a monoclonal antibody that recognizes a protein of apparent molecular mass 68 kilodaltons (A68). The protein is present in the brains of patients with Alzheimer disease but is not detectable in normal adult brain tissue. The authors report that ALZ-50-reactive neurons are found in normal fetal and neonatal human brain and in brain tissue from neonatal individuals with Down syndrome. Reactive neurons decrease sharply in number after age 2 and reappear in older individuals with Down syndrome and in patients with Alzheimer disease.

Genetics of renal hypoplasia: insights into the mechanisms controlling nephron endowment.

PubMed

Cain, Jason E; Di Giovanni, Valeria; Smeeton, Joanna; Rosenblum, Norman D

2010-08-01

Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice.

In vivo studies of brain development by magnetic resonance techniques.

PubMed

Inder, T E; Huppi, P S

2000-01-01

Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000. Copyright 2000 Wiley-Liss, Inc.

Early manifestation of arm-leg coordination during stepping on a surface in human neonates.

PubMed

La Scaleia, Valentina; Ivanenko, Y; Fabiano, A; Sylos-Labini, F; Cappellini, G; Picone, S; Paolillo, P; Di Paolo, A; Lacquaniti, F

2018-04-01

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Attitudes of Korean adults towards human dignity: A Q methodology approach

PubMed Central

Kae Hwa, JO; Gyeong-Ju, AN; DOORENBOS, Ardith Z.

2013-01-01

Aim The aim of this study was to identify the perceived attitudes of Korean adults towards human dignity in order to determine the relationship of human dignity to its social and cultural background. Methods The Q methodology research technique was used to explore perceived attitude typology on the basis of the respondents’ ranking order for different statements. A convenience sampling method was used to select 40 Korean adults who were interested in human dignity to create statements. From the questionnaires, in-depth interviews, and a literature review, a total of 158 statements was obtained. The final 34 Q samples were selected from a review by two nursing professors and a Q methodology expert. Moreover, 38 respondents participated as P samples by sorting 34 Q statements on a nine-point normal distribution scale. The data were analyzed by using the QUANL software package. Results The following four types of attitudes about human dignity were identified in Korea: a happiness-oriented–self-pursuit type, relationship-oriented–self-recognition type, reflection-oriented–self-unification type, and discrimination-oriented–self-maintenance type. Conclusions The results indicate that approaches to developing human dignity education need to take this typology into account and the characteristics of the participants who fall into each category. These results provide general guidelines to understand Korean values for professional practice in various healthcare settings. PMID:22583944

Attitudes of Korean adults towards human dignity: a Q methodology approach.

PubMed

Jo, Kae Hwa; An, Gyeong-Ju; Doorenbos, Ardith Z

2012-06-01

The aim of this study was to identify the perceived attitudes of Korean adults towards human dignity in order to determine the relationship of human dignity to its social and cultural background. The Q methodology research technique was used to explore perceived attitude typology on the basis of the respondents' ranking order for different statements. A convenience sampling method was used to select 40 Korean adults who were interested in human dignity to create statements. From the questionnaires, in-depth interviews, and a literature review, a total of 158 statements was obtained. The final 34 Q samples were selected from a review by two nursing professors and a Q methodology expert. Moreover, 38 respondents participated as P samples by sorting 34 Q statements on a nine-point normal distribution scale. The data were analyzed by using the QUANL software package. The following four types of attitudes about human dignity were identified in Korea: a happiness-oriented-self-pursuit type, relationship-oriented-self-recognition type, reflection-oriented-self-unification type, and discrimination-oriented-self-maintenance type. The results indicate that approaches to developing human dignity education need to take this typology into account and the characteristics of the participants who fall into each category. These results provide general guidelines to understand Korean values for professional practice in various healthcare settings. © 2011 The Authors. Japan Journal of Nursing Science © 2011 Japan Academy of Nursing Science.

The Effect of IQ Level on the Degree of Cognitive Deterioration Experienced during Acute Hypoglycemia in Normal Humans.

ERIC Educational Resources Information Center

Gold, Ann E.; And Others

1995-01-01

Whether IQ level exerts a differential effect on the impairment of cognitive performance induced during acute hypoglycemia was studied for 24 nondiabetic adults. At various levels of hypoglycemia, no overall effect of IQ on deterioration was noted. Higher IQ did not apparently protect against adverse effects. (SLD)

GPR30, the Non-Classical Membrane G Protein Related Estrogen Receptor, Is Overexpressed in Human Seminoma and Promotes Seminoma Cell Proliferation

PubMed Central

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Background Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. Results We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. Conclusion These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas. PMID:22496838

The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians.

PubMed

Baron-Cohen, S; Wheelwright, S; Skinner, R; Martin, J; Clubley, E

2001-02-01

Currently there are no brief, self-administered instruments for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum. In this paper, we report on a new instrument to assess this: the Autism-Spectrum Quotient (AQ). Individuals score in the range 0-50. Four groups of subjects were assessed: Group 1: 58 adults with Asperger syndrome (AS) or high-functioning autism (HFA); Group 2: 174 randomly selected controls. Group 3: 840 students in Cambridge University; and Group 4: 16 winners of the UK Mathematics Olympiad. The adults with AS/HFA had a mean AQ score of 35.8 (SD = 6.5), significantly higher than Group 2 controls (M = 16.4, SD = 6.3). 80% of the adults with AS/HFA scored 32+, versus 2% of controls. Among the controls, men scored slightly but significantly higher than women. No women scored extremely highly (AQ score 34+) whereas 4% of men did so. Twice as many men (40%) as women (21%) scored at intermediate levels (AQ score 20+). Among the AS/HFA group, male and female scores did not differ significantly. The students in Cambridge University did not differ from the randomly selected control group, but scientists (including mathematicians) scored significantly higher than both humanities and social sciences students, confirming an earlier study that autistic conditions are associated with scientific skills. Within the sciences, mathematicians scored highest. This was replicated in Group 4, the Mathematics Olympiad winners scoring significantly higher than the male Cambridge humanities students. 6% of the student sample scored 32+ on the AQ. On interview, 11 out of 11 of these met three or more DSM-IV criteria for AS/HFA, and all were studying sciences/mathematics, and 7 of the 11 met threshold on these criteria. Test-retest and interrater reliability of the AQ was good. The AQ is thus a valuable instrument for rapidly quantifying where any given individual is situated on the continuum from autism to normality. Its potential for screening for autism spectrum conditions in adults of normal intelligence remains to be fully explored.

Human face processing is tuned to sexual age preferences.

PubMed

Ponseti, J; Granert, O; van Eimeren, T; Jansen, O; Wolff, S; Beier, K; Deuschl, G; Bosinski, H; Siebner, H

2014-05-01

Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

PubMed

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

PubMed

Macdonald, Ian R; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2016-02-01

Acetylcholinesterase and butyrylcholinesterase accumulate with brain β-amyloid (Aβ) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aβ plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aβ plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aβ accumulation, during life. Current Aβ imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aβ imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aβ and cholinesterase activity to visualize Aβ plaque load for comparison with radioligand uptake. Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aβ plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aβ plaques from both AD and cognitively normal individuals. Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aβ plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aβ plaques. Imaging cholinesterase activity associated with Aβ plaques in the living brain may contribute to the definitive diagnosis of AD during life. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Normalizing the environment recapitulates adult human immune traits in laboratory mice.

PubMed

Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

2016-04-28

Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

Production and Assessment of Decellularized Pig and Human Lung Scaffolds

PubMed Central

Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-01-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production. PMID:23638920

Production and assessment of decellularized pig and human lung scaffolds.

PubMed

Nichols, Joan E; Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-09-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

Challenges of primate embryonic stem cell research.

PubMed

Bavister, Barry D; Wolf, Don P; Brenner, Carol A

2005-01-01

Embryonic stem (ES) cells hold great promise for treating degenerative diseases, including diabetes, Parkinson's, Alzheimer's, neural degeneration, and cardiomyopathies. This research is controversial to some because producing ES cells requires destroying embryos, which generally means human embryos. However, some of the surplus human embryos available from in vitro fertilization (IVF) clinics may have a high rate of genetic errors and therefore would be unsuitable for ES cell research. Although gross chromosome errors can readily be detected in ES cells, other anomalies such as mitochondrial DNA defects may have gone unrecognized. An insurmountable problem is that there are no human ES cells derived from in vivo-produced embryos to provide normal comparative data. In contrast, some monkey ES cell lines have been produced using in vivo-generated, normal embryos obtained from fertile animals; these can represent a "gold standard" for primate ES cells. In this review, we argue a need for strong research programs using rhesus monkey ES cells, conducted in parallel with studies on human ES and adult stem cells, to derive the maximum information about the biology of normal stem cells and to produce technical protocols for their directed differentiation into safe and functional replacement cells, tissues, and organs. In contrast, ES cell research using only human cell lines is likely to be incomplete, which could hinder research progress, and delay or diminish the effective application of ES cell technology to the treatment of human diseases.

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

PubMed Central

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

Increased reprogramming of human fetal hepatocytes compared with adult hepatocytes in feeder-free conditions.

PubMed

Hansel, Marc C; Gramignoli, Roberto; Blake, William; Davila, Julio; Skvorak, Kristen; Dorko, Kenneth; Tahan, Veysel; Lee, Brian R; Tafaleng, Edgar; Guzman-Lepe, Jorge; Soto-Gutierrez, Alejandro; Fox, Ira J; Strom, Stephen C

2014-01-01

Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions. Of these, 37 hiPSC lines were generated from fetal hepatocytes, 2 hiPSC lines from normal hepatocytes, and 1 hiPSC line from hepatocytes of a patient with Crigler-Najjar syndrome, type 1. All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunocytochemistry, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with six factors, while fetal hepatocytes could be reprogrammed with three (OCT4, SOX2, NANOG) or four factors (OCT4, SOX2, NANOG, LIN28 or OCT4, SOX2, KLF4, C-MYC). The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. These studies confirm that hiPSCs can be generated from adult and fetal hepatocytes including those with genetic diseases. Fetal hepatocytes reprogram much more efficiently than adult hepatocytes, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation.

Aural Acoustic Stapedius-Muscle Reflex Threshold Procedures to Test Human Infants and Adults.

PubMed

Keefe, Douglas H; Feeney, M Patrick; Hunter, Lisa L; Fitzpatrick, Denis F

2017-02-01

Power-based procedures are described to measure acoustic stapedius-muscle reflex threshold and supra-threshold responses in human adult and infant ears at frequencies from 0.2 to 8 kHz. The stimulus set included five clicks in which four pulsed activators were placed between each pair of clicks, with each stimulus set separated from the next by 0.79 s to allow for reflex decay. Each click response was used to detect the presence of reflex effects across frequency that were elicited by a pulsed broadband-noise or tonal activator in the ipsilateral or contralateral test ear. Acoustic reflex shifts were quantified in terms of the difference in absorbed sound power between the initial baseline click and the later four clicks in each set. Acoustic reflex shifts were measured over a 40-dB range of pulsed activators, and the acoustic reflex threshold was objectively calculated using a maximum 10 likelihood procedure. To illustrate the principles underlying these new reflex tests, reflex shifts in absorbed sound power and absorbance are presented for data acquired in an adult ear with normal hearing and in two infant ears in the initial and follow-up newborn hearing screening exams, one with normal hearing and the other with a conductive hearing loss. The use of absorbed sound power was helpful in classifying an acoustic reflex shift as present or absent. The resulting reflex tests are in use in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function in infant and adult ears.

Contribution of human growth hormone-releasing hormone receptor (GHRHR) gene sequence variation to isolated severe growth hormone deficiency (ISGHD) and normal adult height.

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Carrascosa, Antonio; Andaluz, Pilar; Albisu, M Ángeles; Clemente, María; Gussinyé, Miquel; Yeste, Diego; Audí, Laura

2012-10-01

Molecular causes of isolated severe growth hormone deficiency (ISGHD) in several genes have been established. The aim of this study was to analyse the contribution of growth hormone-releasing hormone receptor (GHRHR) gene sequence variation to GH deficiency in a series of prepubertal ISGHD patients and to normal adult height. A systematic GHRHR gene sequence analysis was performed in 69 ISGHD patients and 60 normal adult height controls (NAHC). Four GHRHR single-nucleotide polymorphisms (SNPs) were genotyped in 248 additional NAHC. An analysis was performed on individual SNPs and combined genotype associations with diagnosis in ISGHD patients and with height-SDS in NAHC. Twenty-one SNPs were found. P3, P13, P15 and P20 had not been previously described. Patients and controls shared 12 SNPs (P1, P2, P4-P11, P16 and P21). Significantly different frequencies of the heterozygous genotype and alternate allele were detected in P9 (exon 4, rs4988498) and P12 (intron 6, rs35609199); P9 heterozygous genotype frequencies were similar in patients and the shortest control group (heights between -2 and -1 SDS) and significantly different in controls (heights between -1 and +2 SDS). GHRHR P9 together with 4 GH1 SNP genotypes contributed to 6·2% of height-SDS variation in the entire 308 NAHC. This study established the GHRHR gene sequence variation map in ISGHD patients and NAHC. No evidence of GHRHR mutation contribution to ISGHD was found in this population, although P9 and P12 SNP frequencies were significantly different between ISGHD and NAHC. Thus, the gene sequence may contribute to normal adult height, as demonstrated in NAHC. © 2012 Blackwell Publishing Ltd.

Plasma Electrolyte Distributions in Humans-Normal or Skewed?

PubMed

Feldman, Mark; Dickson, Beverly

2017-11-01

It is widely believed that plasma electrolyte levels are normally distributed. Statistical tests and calculations using plasma electrolyte data are often reported based on this assumption of normality. Examples include t tests, analysis of variance, correlations and confidence intervals. The purpose of our study was to determine whether plasma sodium (Na + ), potassium (K + ), chloride (Cl - ) and bicarbonate [Formula: see text] distributions are indeed normally distributed. We analyzed plasma electrolyte data from 237 consecutive adults (137 women and 100 men) who had normal results on a standard basic metabolic panel which included plasma electrolyte measurements. The skewness of each distribution (as a measure of its asymmetry) was compared to the zero skewness of a normal (Gaussian) distribution. The plasma Na + distribution was skewed slightly to the right, but the skew was not significantly different from zero skew. The plasma Cl - distribution was skewed slightly to the left, but again the skew was not significantly different from zero skew. On the contrary, both the plasma K + and [Formula: see text] distributions were significantly skewed to the right (P < 0.01 zero skew). There was also a suggestion from examining frequency distribution curves that K + and [Formula: see text] distributions were bimodal. In adults with a normal basic metabolic panel, plasma potassium and bicarbonate levels are not normally distributed and may be bimodal. Thus, statistical methods to evaluate these 2 plasma electrolytes should be nonparametric tests and not parametric ones that require a normal distribution. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

PubMed

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease

PubMed Central

Sun, Binggui; Halabisky, Brian; Zhou, Yungui; Palop, Jorge J.; Yu, Guiqiu; Mucke, Lennart; Gan, Li

2009-01-01

SUMMARY Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer’s disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid β (Aβ), the key AD pathogen, affects the development and function of adult-born neurons remains unknown. Adult-born granule cells (GCs) in human amyloid precursor protein (hAPP) transgenic mice, an AD model, showed greater dendritic length, spine density, and functional responses than controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABAA receptors to suppress GABAergic signaling or late inhibition of calcineurin to enhance glutamatergic signaling normalized the development of adult-born GCs in hAPP mice with high Aβ levels. Aβ-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD. PMID:19951690

Behaviour of Solitary Adult Scandinavian Brown Bears (Ursus arctos) when Approached by Humans on Foot

PubMed Central

Moen, Gro Kvelprud; Støen, Ole-Gunnar; Sahlén, Veronica; Swenson, Jon E.

2012-01-01

Successful management has brought the Scandinavian brown bear (Ursus arctos L.) back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006–2009, we approached 30 adult (21 females, 9 males) GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80%) left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%). Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m) than passive bears (69±47 m), and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans. PMID:22363710

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Merkel cells are long-lived cells whose production is stimulated by skin injury✰

PubMed Central

Wright, Margaret C.; Logan, Gregory J.; Bolock, Alexa M.; Kubicki, Adam C.; Hemphill, Julie A.; Sanders, Timothy A.; Maricich, Stephen M.

2017-01-01

Mechanosensitive Merkel cells are thought to have finite lifespans, but controversy surrounds the frequency of their replacement and which precursor cells maintain the population. We found by embryonic EdU administration that Merkel cells undergo terminal cell division in late embryogenesis and survive long into adulthood. We also found that new Merkel cells are produced infrequently during normal skin homeostasis and that their numbers do not change during natural or induced hair cycles. In contrast, live imaging and EdU experiments showed that mild mechanical injury produced by skin shaving dramatically increases Merkel cell production. We confirmed with genetic cell ablation and fate-mapping experiments that new touch dome Merkel cells in adult mice arise from touch dome keratinocytes. Together, these independent lines of evidence show that Merkel cells in adult mice are long-lived, are replaced rarely during normal adult skin homeostasis, and that their production can be induced by repeated shaving. These results have profound implications for understanding sensory neurobiology and human diseases such as Merkel cell carcinoma. PMID:27998808

Merkel cells are long-lived cells whose production is stimulated by skin injury.

PubMed

Wright, Margaret C; Logan, Gregory J; Bolock, Alexa M; Kubicki, Adam C; Hemphill, Julie A; Sanders, Timothy A; Maricich, Stephen M

2017-02-01

Mechanosensitive Merkel cells are thought to have finite lifespans, but controversy surrounds the frequency of their replacement and which precursor cells maintain the population. We found by embryonic EdU administration that Merkel cells undergo terminal cell division in late embryogenesis and survive long into adulthood. We also found that new Merkel cells are produced infrequently during normal skin homeostasis and that their numbers do not change during natural or induced hair cycles. In contrast, live imaging and EdU experiments showed that mild mechanical injury produced by skin shaving dramatically increases Merkel cell production. We confirmed with genetic cell ablation and fate-mapping experiments that new touch dome Merkel cells in adult mice arise from touch dome keratinocytes. Together, these independent lines of evidence show that Merkel cells in adult mice are long-lived, are replaced rarely during normal adult skin homeostasis, and that their production can be induced by repeated shaving. These results have profound implications for understanding sensory neurobiology and human diseases such as Merkel cell carcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Elemental composition of some essential cations in human ocular tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panessa-Warren, B.J.; Kraner, H.W.; Warren, J.B.

1983-01-01

To obtain data on the baseline elemental content in normal adult sensory retina, RPE and iris, normal non-diabetic eyes were analyzed and these results were used for comparison to similarly prepared samples from diabetic donor eyes. To determine if the concentrations of the cations, Ca, Ba and Zn were altered by the age, alimentation and exposure to light of the donor, tissue from children (from 25 weeks gestation to 8-1/2 years old) was also analyzed by x-ray fluorescence spectroscopy, proton induced x-ray emission spectroscopy, and light and electron (scanning and transmission) microscopy.

Neural substrates related to auditory working memory comparisons in dyslexia: An fMRI study

PubMed Central

CONWAY, TIM; HEILMAN, KENNETH M.; GOPINATH, KAUNDINYA; PECK, KYUNG; BAUER, RUSSELL; BRIGGS, RICHARD W.; TORGESEN, JOSEPH K.; CROSSON, BRUCE

2010-01-01

Adult readers with developmental phonological dyslexia exhibit significant difficulty comparing pseudowords and pure tones in auditory working memory (AWM). This suggests deficient AWM skills for adults diagnosed with dyslexia. Despite behavioral differences, it is unknown whether neural substrates of AWM differ between adults diagnosed with dyslexia and normal readers. Prior neuroimaging of adults diagnosed with dyslexia and normal readers, and post-mortem findings of neural structural anomalies in adults diagnosed with dyslexia support the hypothesis of atypical neural activity in temporoparietal and inferior frontal regions during AWM tasks in adults diagnosed with dyslexia. We used fMRI during two binaural AWM tasks (pseudowords or pure tones comparisons) in adults diagnosed with dyslexia (n = 11) and normal readers (n = 11). For both AWM tasks, adults diagnosed with dyslexia exhibited greater activity in left posterior superior temporal (BA 22) and inferior parietal regions (BA 40) than normal readers. Comparing neural activity between groups and between stimuli contrasts (pseudowords vs. tones), adults diagnosed with dyslexia showed greater primary auditory cortex activity (BA 42; tones > pseudowords) than normal readers. Thus, greater activity in primary auditory, posterior superior temporal, and inferior parietal cortices during linguistic and non-linguistic AWM tasks for adults diagnosed with dyslexia compared to normal readers indicate differences in neural substrates of AWM comparison tasks. PMID:18577292

Prevalence of Central Obesity among Adults with Normal BMI and Its Association with Metabolic Diseases in Northeast China.

PubMed

Zhang, Peng; Wang, Rui; Gao, Chunshi; Jiang, Lingling; Lv, Xin; Song, Yuanyuan; Li, Bo

2016-01-01

The present study aimed to investigate the prevalence of central obesity among adults with normal BMI and its association with metabolic diseases in Jilin Province, China. A population-based cross-sectional study was conducted in 2012 in Jilin Province of China. Information was collected by face to face interview. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Log-binomial regression analyses were used to find the independent factors associated with central obesity and to explore the adjusted association between central obesity and metabolic diseases among adults with normal BMI. Among the adult residents with normal BMI in Jilin Province, 55.6% of participants with central obesity self-assessed as normal weight and 27.0% thought their body weight were above normal. 12.7% of central obesity people took methods to lose weight, while 85.3% didn't. Female, older people and non-manual worker had higher risk to be central obesity among adults with normal BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI, the PRs were 1.337 (1.224-1.461), 1.323 (1.193-1.456) and 1.261 (1.152-1.381) separately when adjusted for gender, age and BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI in Jilin Province, China. The low rates of awareness and control of central obesity among adults with normal BMI should be improved by government and health department.

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.

PubMed

Seed, Mike; van Amerom, Joshua F P; Yoo, Shi-Joon; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars; Jaeggi, Edgar; Jansz, Michael S; Macgowan, Christopher K

2012-11-26

We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12. This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

A simple and efficient method for generating Nurr1-positive neuronal stem cells from human wisdom teeth (tNSC) and the potential of tNSC for stroke therapy.

PubMed

Yang, Kuo-Liang; Chen, Mei-Fang; Liao, Chia-Hsin; Pang, Cheng-Yoong; Lin, Py-Yu

2009-01-01

We have isolated human neuronal stem cells from exfoliated third molars (wisdom teeth) using a simple and efficient method. The cultured neuronal stem cells (designated tNSC) expressed embryonic and adult stem cell markers, markers for chemotatic factor and its corresponding ligand, as well as neuron proteins. The tNSC expressed genes of Nurr1, NF-M and nestin. They were used to treat middle cerebral artery occlusion (MCAO) surgery-inflicted Sprague-Dawley (SD) rats to assess their therapeutic potential for stroke therapy. For each tNSC cell line, a normal human impacted wisdom tooth was collected from a donor with consent. The tooth was cleaned thoroughly with normal saline. The molar was vigorously shaken or vortexed for 30 min in a 50-mL conical tube with 15-20mL normal saline. The mixture of dental pulp was collected by centrifugation and cultured in a 25-cm(2) tissue culture flask with 4-5mL Medium 199 supplemented with 5-10% fetal calf serum. The tNSC harvested from tissue culture, at a concentration of 1-2x10(5), were suspended in 3 microL saline solution and injected into the right dorsolateral striatum of experimental animals inflicted with MCAO. Behavioral measurements of the tNSC-treated SD rats showed a significant recovery from neurologic dysfunction after MCAO treatment. In contrast, a sham group of SD rats failed to recover from the surgery. Immunohistochemistry analysis of brain sections of the tNSC-treated SD rats showed survival of the transplanted cells. These results suggest that adult neuronal stem cells may be procured from third molars, and tNSC thus cultivated have potential for treatment of stroke-inflicted rats.

ATM activation in normal human tissues and testicular cancer.

PubMed

Bartkova, Jirina; Bakkenist, Christopher J; Rajpert-De Meyts, Ewa; Skakkebaek, Niels E; Sehested, Maxwell; Lukas, Jiri; Kastan, Michael B; Bartek, Jiri

2005-06-01

The ATM kinase is a tumor suppressor and key regulator of biological responses to DNA damage. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for example during physiological processes that generate DSBs, is unknown. Here we produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM (pS-ATM), and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors. Our data show that regardless of proliferation and differentiation, most human tissues contain only the S1981-nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V(D)J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was detected in a higher proportion of cancer cells, and also in normal fetal gonocytes, and a wider range of adult spermatocyte differentiation stages. Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation

PubMed Central

Nakahara, Hiroyuki; Hasegawa, Akihiko; Otabe, Koji; Ayabe, Fumiaki; Matsukawa, Tetsuya; Onizuka, Naoko; Ito, Yoshiaki; Ozaki, Toshifumi; Lotz, Martin K.; Asahara, Hiroshi

2013-01-01

Objective To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissues and ligament cells from normal and osteoarthritis-affected knees. Methods Knee joints were obtained at autopsy within 24-48 hours postmortem from 13 normal donors (age 36.9±11.0 years), 16 OA donors (age 79.7±11.4 years) and 8 old donors without OA (age 76.9±12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative PCR. ACL-derived cells were used to study regulation of MKX expression by IL-1β. MKX was knocked down by siRNA to analyze function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry showed that MKX positive cells were significantly reduced in ACL tissues from OA donors in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX gene expression and reduced ligament ECM genes, COL1A1 and TNXB. On the other hand, SOX9, chondrocyte master transcription factor, was up regulated by IL-1β treatment. Importantly, knock down of MKX expression by siRNA upregulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB were decreased. Conclusion Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints and this may be in part mediated by IL-1β. MKX appears necessary to maintain the tissue specific cellular differentiation status and ECM production in adult human tendons and ligaments. PMID:23686683

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction.

PubMed

Gatford, Kathryn L; Kaur, Gunveen; Falcão-Tebas, Filippe; Wadley, Glenn D; Wlodek, Mary E; Laker, Rhianna C; Ebeling, Peter R; McConell, Glenn K

2014-05-01

Individuals born after intrauterine growth restriction (IUGR) are at an increased risk of developing diabetes in their adult life. IUGR impairs β-cell function and reduces β-cell mass, thereby diminishing insulin secretion. IUGR also induces insulin resistance, with impaired insulin signaling in muscle in adult humans who were small for gestational age (SGA) and in rodent models of IUGR. There is epidemiological evidence in humans that exercise in adults can reduce the risk of metabolic disease following IUGR. However, it is not clear whether adult IUGR individuals benefit to the same extent from exercise as do normal-birth-weight individuals, as our rat studies suggest less of a benefit in those born IUGR. Importantly, however, there is some evidence from studies in rats that exercise in early life might be able to reverse or reprogram the long-term metabolic effects of IUGR. Studies are needed to address gaps in current knowledge, including determining the mechanisms involved in the reprogramming effects of early exercise in rats, whether exercise early in life or in adulthood has similar beneficial metabolic effects in larger animal models in which insulin resistance develops after IUGR. Human studies are also needed to determine whether exercise training improves insulin secretion and insulin sensitivity to the same extent in IUGR adults as in control populations. Such investigations will have implications for customizing the recommended level and timing of exercise to improve metabolic health after IUGR.

Kinematic measurements of the vocal-fold displacement waveform in typical children and adult populations: quantification of high-speed endoscopic videos.

PubMed

Patel, Rita; Donohue, Kevin D; Unnikrishnan, Harikrishnan; Kryscio, Richard J

2015-04-01

This article presents a quantitative method for assessing instantaneous and average lateral vocal-fold motion from high-speed digital imaging, with a focus on developmental changes in vocal-fold kinematics during childhood. Vocal-fold vibrations were analyzed for 28 children (aged 5-11 years) and 28 adults (aged 21-45 years) without voice disorders. The following kinematic features were analyzed from the vocal-fold displacement waveforms: relative velocity-based features (normalized average and peak opening and closing velocities), relative acceleration-based features (normalized peak opening and closing accelerations), speed quotient, and normalized peak displacement. Children exhibited significantly larger normalized peak displacements, normalized average and peak opening velocities, normalized average and peak closing velocities, peak opening and closing accelerations, and speed quotient compared to adult women. Values of normalized average closing velocity and speed quotient were higher in children compared to adult men. When compared to adult men, developing children typically have higher estimates of kinematic features related to normalized displacement and its derivatives. In most cases, the kinematic features of children are closer to those of adult men than adult women. Even though boys experience greater changes in glottal length and pitch as they mature, results indicate that girls experience greater changes in kinematic features compared to boys.

Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity.

PubMed

Ren, Chunli; Finkel, Steven E; Tower, John

2009-03-01

Immune function declines with age in Drosophila and humans, and autophagy is implicated in immune function. In addition, autophagy genes are required for life span extension caused by reduced insulin/IGF1-like signaling and dietary restriction in Caenorhabditiselegans. To test if the autophagy pathway might be limiting for immunity and/or life span in adult Drosophila, the Geneswitch system was used to cause conditional inactivation of the autophagy genes Atg5, Atg7 and Atg12 by RNAi. Conditional inhibition of Atg genes in adult flies reduced lysotracker staining of adult tissues, and reduced resistance to injected Escherichia coli, as evidenced by increased bacterial titers and reduced fly survival. However, survival of uninjected flies was unaffected by Atg gene inactivation. The data indicate that Atg gene activity is required for normal immune function in adult flies, and suggest that neither autophagy nor immune function are limiting for adult life span under typical laboratory conditions.

Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche.

PubMed

Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

2014-05-13

Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Human testis and testis cancer specimens from orchidectomies were cultured in 'hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

Radioimmunoassay of Human Serum Thyrotrophin

PubMed Central

Hall, Reginald; Amos, Jacqueline; Ormston, Brian J.

1971-01-01

The double antibody radioimmunoassay of serum thyroid-stimulating hormone (TSH) allows measurement of circulating levels of the hormone in most normal subjects. The serum TSH level in normal subjects is 1·6 ± 0·8μU/ml. Patients with non-toxic goitre and acromegaly have normal TSH levels. Values are always raised in hypothyroid patients (with primary thyroid disease) and are significantly lowered in those with hyperthyroidism. Of the many stimuli used in an attempt to raise TSH levels in normal adult subjects only three—synthetic thyrotrophin-releasing hormone, ethinyloestradiol, and carbimazole plus iodides—have been effective. The major clinical application of the TSH immunoassay lies in the diagnosis of minor degrees of hypothyroidism. An impaired response of serum TSH to synthetic thyrotrophin-releasing hormone should also help in the diagnosis of hypopituitarism affecting TSH production. PMID:5548300

SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pyakuryal, A; Moroz, B; Lee, C

2016-06-15

Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatricmore » and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.« less

Antibody responses to bacteriophage phi X-174 in human subjects exposed to the antarctic winter-over model of spaceflight

NASA Technical Reports Server (NTRS)

Shearer, W. T.; Lugg, D. J.; Rosenblatt, H. M.; Nickolls, P. M.; Sharp, R. M.; Reuben, J. M.; Ochs, H. D.

2001-01-01

BACKGROUND: It has been proposed that exposure to long-term spaceflight conditions (stress, isolation, sleep disruption, containment, microbial contamination, and solar radiation) or to ground-based models of spaceflight will alter human immune responses, but specific antibody responses have not been fully evaluated. OBJECTIVE: We sought to determine whether exposure to the 8-month Antarctic winter-over model of spaceflight would alter human antibody responses. METHODS: During the 1999 Australian National Antarctic Research Expeditions, 11 adult study subjects at Casey, Antarctica, and 7 control subjects at Macquarie Island, sub-Antarctica, received primary and secondary immunizations with the T cell-dependent neoantigen bacteriophage phi X-174. Periodic plasma samples were analyzed for specific antibody function. RESULTS: All of the subjects from Casey, Antarctica, cleared bacteriophage phi X-174 normally by 1 week after primary immunization, and all had normal primary and secondary antibody responses, including immunologic memory amplification and switch from IgM to IgG antibody production. One subject showed a high normal pattern, and one subject had a low normal pattern. The control subjects from Macquarie Island also had normal immune responses to bacteriophage phi X-174. CONCLUSIONS: These data do not support the hypothesis that de novo specific antibody responses of subjects become defective during the conditions of the Antarctic winter-over. Because the Antarctic winter-over model of spaceflight lacks the important factors of microgravity and solar radiation, caution must be used in interpreting these data to anticipate normal antibody responses in long-term spaceflight.

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

NASA Technical Reports Server (NTRS)

Rubin, A. L.

1977-01-01

Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells

PubMed Central

Somervaille, Tim C. P.; Matheny, Christina J.; Spencer, Gary J.; Iwasaki, Masayuki; Rinn, John L.; Witten, Daniela M.; Chang, Howard Y.; Shurtleff, Sheila A.; Downing, James R.; Cleary, Michael L.

2009-01-01

Summary The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. PMID:19200802

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype.

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Mullis, Primus E; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype

PubMed Central

Audí, Laura; Mullis, Primus E.; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E.

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life. PMID:26580071

Normally Occurring Human Anti-GM1 Immunoglobulin M Antibodies and the Immune Response to Bacteria

PubMed Central

Alaniz, María E.; Lardone, Ricardo D.; Yudowski, Silvia L.; Farace, María I.; Nores, Gustavo A.

2004-01-01

Anti-GM1 antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children <1 month of age but could be detected after 1 month of age. Although most of the children older than 6 months of age were positive, there were still a few negative children. The appearance of anti-GM1 IgM antibodies showed a perfect concordance with two well-characterized antibacterial antibodies, anti-Forssman and anti-blood group A, which indicates a similar origin. We also studied IgM reactivity with lipopolysaccharides (LPSs) from gram-negative bacteria isolated from stool samples from healthy babies and from Escherichia coli HB101 in serum from individuals of different ages. We found a positive reaction with both LPSs in all the children more than 1 month of age analyzed, even in those that were negative for anti-GM1 antibodies. Anti-GM1 IgM antibodies were purified from adult serum by affinity chromatography and tested for the ability to bind LPSs from different bacteria. This highly specific preparation showed reactivity only with LPS from a strain of Campylobacter jejuni isolated from a patient with diarrhea. We conclude that normally occurring IgM antibodies are generated after birth, probably during the immune defense against specific bacterial strains. PMID:15039337

Loud Music Exposure and Cochlear Synaptopathy in Young Adults: Isolated Auditory Brainstem Response Effects but No Perceptual Consequences.

PubMed

Grose, John H; Buss, Emily; Hall, Joseph W

2017-01-01

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

Metabolic Studies in Military Nutrition.

DTIC Science & Technology

1977-05-01

The Surgeon General’s Office over a period of years has undertaken an extensive research program into the chemistry, nutrition , and wholesomeness of...Research and Nutrition Laboratory has undertaken the studies of the wholesomeness of food preserved by ionizing radiation. Work on radiated food has been...physiological, metabolic, and nutritional research in normal young adult men has been going on making use of volunteer human test subjects.

Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks.

PubMed

Pellacani, Davide; Bilenky, Misha; Kannan, Nagarajan; Heravi-Moussavi, Alireza; Knapp, David J H F; Gakkhar, Sitanshu; Moksa, Michelle; Carles, Annaick; Moore, Richard; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M; Aparicio, Samuel; Hirst, Martin; Eaves, Connie J

2016-11-15

The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

PubMed Central

Blake, Sophia M; Stricker, Stefan H; Halavach, Hanna; Poetsch, Anna R; Cresswell, George; Kelly, Gavin; Kanu, Nnennaya; Marino, Silvia; Luscombe, Nicholas M; Pollard, Steven M; Behrens, Axel

2016-01-01

Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors. DOI: http://dx.doi.org/10.7554/eLife.08711.001 PMID:26984279

Kinematic Measurements of the Vocal-Fold Displacement Waveform in Typical Children and Adult Populations: Quantification of High-Speed Endoscopic Videos

PubMed Central

Donohue, Kevin D.; Unnikrishnan, Harikrishnan; Kryscio, Richard J.

2015-01-01

Purpose This article presents a quantitative method for assessing instantaneous and average lateral vocal-fold motion from high-speed digital imaging, with a focus on developmental changes in vocal-fold kinematics during childhood. Method Vocal-fold vibrations were analyzed for 28 children (aged 5–11 years) and 28 adults (aged 21–45 years) without voice disorders. The following kinematic features were analyzed from the vocal-fold displacement waveforms: relative velocity-based features (normalized average and peak opening and closing velocities), relative acceleration-based features (normalized peak opening and closing accelerations), speed quotient, and normalized peak displacement. Results Children exhibited significantly larger normalized peak displacements, normalized average and peak opening velocities, normalized average and peak closing velocities, peak opening and closing accelerations, and speed quotient compared to adult women. Values of normalized average closing velocity and speed quotient were higher in children compared to adult men. Conclusions When compared to adult men, developing children typically have higher estimates of kinematic features related to normalized displacement and its derivatives. In most cases, the kinematic features of children are closer to those of adult men than adult women. Even though boys experience greater changes in glottal length and pitch as they mature, results indicate that girls experience greater changes in kinematic features compared to boys. PMID:25652615

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

PubMed

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-06-11

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Normal Aging and Linguistic Decrement.

ERIC Educational Resources Information Center

Emery, Olga B.

A study investigated language patterning, as an indication of synthetic mental activity, in comparison groups of normal pre-middle-aged adults (30-42 years), normal elderly adults (75-93), and elderly adults (71-91) with Alzheimer's dementia. Semiotic theory was used as the conceptual context. Linguistic measures included the Token Test, the…

Generation of a KLF15 homozygous knockout human embryonic stem cell line using paired CRISPR/Cas9n, and human cardiomyocytes derivation.

PubMed

Noack, Claudia; Haupt, Luis Peter; Zimmermann, Wolfram-Hubertus; Streckfuss-Bömeke, Katrin; Zelarayán, Laura Cecilia

2017-08-01

Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy.

PubMed

Bartkova, J; Rajpert-de Meyts, E; Skakkebaek, N E; Bartek, J

1999-04-01

D-type cyclins are proto-oncogenic components of the 'RB pathway', a G1/S regulatory mechanism centred around the retinoblastoma tumour suppressor (pRB) implicated in key cellular decisions that control cell proliferation, cell-cycle arrest, quiescence, and differentiation. This study focused on immunohistochemical and immunochemical analysis of human adult testis and 32 testicular tumours to examine the differential expression and abundance of cyclins D1, D2, and D3 in relation to cell type, proliferation, differentiation, and malignancy. In normal testis, the cell type-restricted expression patterns were dominated by high levels of cyclin D3 in quiescent Leydig cells and the lack of any D-type cyclin in the germ cells, the latter possibly representing the only example of normal mammalian cells proliferating in the absence of these cyclins. Most carcinoma-in-situ lesions appeared to gain expression of cyclin D2 but not D1 or D3, while the invasive testicular tumours showed variable positivity for cyclins D2 and D3, but rarely D1. An unexpected correlation with differentiation rather than proliferation was found particularly for cyclin D3 in teratomas, a conceptually significant observation confirmed by massive up-regulation of cyclin D3 in the human teratocarcinoma cell line NTera2/D1 induced to differentiate along the neuronal lineage. These results suggest a possible involvement of cyclin D2 in the early stages of testicular oncogenesis and the striking examples of proliferation-independent expression point to potential dual or multiple roles of the D-type cyclins, particularly of cyclin D3. These findings extend current concepts of the biology of the cyclin D subfamily, as well as of the biology and oncopathology of the human adult testis. Apart from practical implications for the assessment of proliferation and oncogenic aberrations in human tissues and tumours, this study may inspire further research into the emerging role of the cyclin D proteins in the establishment and/or maintenance of the differentiated phenotypes. Copyright 1999 John Wiley & Sons, Ltd.

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

PubMed

Anderson, S W; Bechara, A; Damasio, H; Tranel, D; Damasio, A R

1999-11-01

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Brain Arteriovenous Malformation Pathogenesis: A Response-to-Injury Paradigm

PubMed Central

Kim, Helen; Su, Hua; Weinsheimer, Shantel; Pawlikowska, Ludmila; Young, William L.

2011-01-01

Brain arteriovenous malformations (AVMs) are a rare but important cause of intracranial hemorrhage (ICH) in young adults. In this paper, we review both human and animal studies of brain AVM, focusing on the: (1) natural history of AVM hemorrhage; (2) genetic and expression studies of AVM susceptibility and hemorrhage; and (3) strategies for development of a brain AVM model in adult mice. These data target various mechanisms which must act in concert to regulate normal angiogenic response to injury. Based on the various lines of evidence reviewed in this paper, we propose a “response-to-injury” model of brain AVM pathogenesis. PMID:21725736

Adult mesenchymal stem cells and cell-based tissue engineering

PubMed Central

Tuan, Rocky S; Boland, Genevieve; Tuli, Richard

2003-01-01

The identification of multipotential mesenchymal stem cells (MSCs) derived from adult human tissues, including bone marrow stroma and a number of connective tissues, has provided exciting prospects for cell-based tissue engineering and regeneration. This review focuses on the biology of MSCs, including their differentiation potentials in vitro and in vivo, and the application of MSCs in tissue engineering. Our current understanding of MSCs lags behind that of other stem cell types, such as hematopoietic stem cells. Future research should aim to define the cellular and molecular fingerprints of MSCs and elucidate their endogenous role(s) in normal and abnormal tissue functions. PMID:12716446

Placenta-an alternative source of stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matikainen, Tiina; Laine, Jarmo

2005-09-01

The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst ismore » destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications.« less

High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

PubMed Central

Adam, Marion; Urbanski, Henryk F.; Garyfallou, Vasilios T.; Welsch, Ulrich; Köhn, Frank M.; Schwarzer, J. Ullrich; Strauss, Leena; Poutanen, Matti; Mayerhofer, Artur

2011-01-01

Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signaling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild-type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through prepubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of Tumor necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signaling of the testis in health and disease. PMID:22413766

Distortion product otoacoustic emission (2f1-f2) amplitude growth in human adults and neonates.

PubMed

Abdala, C

2000-01-01

Distortion product otoacoustic emissions (DPOAEs) are thought to be by-products of an active amplification process in the cochlea and thus serve as a metric for evaluating the integrity of this process. Because the cochlear amplifier functions in a level-dependent fashion, DPOAEs recorded as a function of stimulus level (i.e., a DPOAE growth function) may provide important information about the range and operational characteristics of the cochlear amplifier. The DPOAE growth functions recorded in human adults and neonates may provide information about the maturation of these active cochlear processes. Two experiments were conducted. Experiment I included normal-hearing adults and term-born neonates. The 2f1-f2 DPOAE growth functions were recorded for both age groups at three f2 frequencies. Experiment II was an extension of the first experiment but added a subject group of premature neonates. The results of these studies indicate that DPOAE growth functions most often show amplitude saturation and nonmonotonic growth for all age groups. However, premature neonates show monotonic growth and the absence of amplitude saturation more often than adults. Those premature neonates who do show saturation also show an elevated threshold for amplitude saturation relative to adults. In contrast, term neonates are adultlike for most measures except that they show a larger percentage of nonsaturating growth functions than adults. These results may indicate immaturity in cochlear amplifier function prior to term birth in humans. Outer hair cell function and/or efferent regulation of outer hair cell function are hypothesized sources of this immaturity, although some contribution from the immature middle ear cannot be ruled out.

MERP1: a mammalian ependymin-related protein gene differentially expressed in hematopoietic cells.

PubMed

Gregorio-King, Claudia C; McLeod, Janet L; Collier, Fiona McL; Collier, Gregory R; Bolton, Karyn A; Van Der Meer, Gavin J; Apostolopoulos, Jim; Kirkland, Mark A

2002-03-20

We have utilized differential display polymerase chain reaction to investigate the gene expression of hematopoietic progenitor cells from adult bone marrow and umbilical cord blood. A differentially expressed gene was identified in CD34+ hematopoietic progenitor cells, with low expression in CD34- cells. We have obtained the full coding sequence of this gene which we designated human mammalian ependymin-related protein 1 (MERP1). Expression of MERP1 was found in a variety of normal human tissues, and is 4- and 10-fold higher in adult bone marrow and umbilical cord blood CD34+ cells, respectively, compared to CD34- cells. Additionally, MERP1 expression in a hematopoietic stem cell enriched population was down-regulated with proliferation and differentiation. Conceptual translation of the MERP1 open reading frame reveals significant homology to two families of glycoprotein calcium-dependant cell adhesion molecules: ependymins and protocadherins.

Antisense oligonucleotide–mediated MDM4 exon 6 skipping impairs tumor growth

PubMed Central

Dewaele, Michael; Tabaglio, Tommaso; Willekens, Karen; Bezzi, Marco; Teo, Shun Xie; Low, Diana H.P.; Koh, Cheryl M.; Rambow, Florian; Fiers, Mark; Rogiers, Aljosja; Radaelli, Enrico; Al-Haddawi, Muthafar; Tan, Soo Yong; Hermans, Els; Amant, Frederic; Yan, Hualong; Lakshmanan, Manikandan; Koumar, Ratnacaram Chandrahas; Lim, Soon Thye; Derheimer, Frederick A.; Campbell, Robert M.; Bonday, Zahid; Tergaonkar, Vinay; Shackleton, Mark; Blattner, Christine; Marine, Jean-Christophe; Guccione, Ernesto

2015-01-01

MDM4 is a promising target for cancer therapy, as it is undetectable in most normal adult tissues but often upregulated in cancer cells to dampen p53 tumor-suppressor function. The mechanisms that underlie MDM4 upregulation in cancer cells are largely unknown. Here, we have shown that this key oncogenic event mainly depends on a specific alternative splicing switch. We determined that while a nonsense-mediated, decay-targeted isoform of MDM4 (MDM4-S) is produced in normal adult tissues as a result of exon 6 skipping, enhanced exon 6 inclusion leads to expression of full-length MDM4 in a large number of human cancers. Although this alternative splicing event is likely regulated by multiple splicing factors, we identified the SRSF3 oncoprotein as a key enhancer of exon 6 inclusion. In multiple human melanoma cell lines and in melanoma patient–derived xenograft (PDX) mouse models, antisense oligonucleotide–mediated (ASO-mediated) skipping of exon 6 decreased MDM4 abundance, inhibited melanoma growth, and enhanced sensitivity to MAPK-targeting therapeutics. Additionally, ASO-based MDM4 targeting reduced diffuse large B cell lymphoma PDX growth. As full-length MDM4 is enhanced in multiple human tumors, our data indicate that this strategy is applicable to a wide range of tumor types. We conclude that enhanced MDM4 exon 6 inclusion is a common oncogenic event and has potential as a clinically compatible therapeutic target. PMID:26595814

Human Performance: Psychological and Physiological Sex Differences (A Selected Bibliography)

DTIC Science & Technology

1980-02-01

1969. 8. Drummond, M. L. Effects of auditory distraction and hunger arousal on task performance of obese and normal weight mentally retarded adults...children on selected tests of the Halstead-Reitan Neuropsychological Test Battery (Doctoral dissertation, Rutgers University - The State University...741, 9. King, G. D., Hannay, p. J., Masek, B. J., & Burns, J. W. Effects of anxiety and sex on neuropsychological tests. Journal of Consulting and

Adult human neural stem cell therapeutics: Current developmental status and prospect.

PubMed

Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

2015-01-26

Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics.

Continued Expression of Neonatal Myosin Heavy Chain in Adult Dystrophic Skeletal Muscle

NASA Astrophysics Data System (ADS)

Bandman, Everett

1985-02-01

The expression of myosin heavy chain isoforms was examined in normal and dystrophic chicken muscle with a monoclonal antibody specific for neonatal myosin. Adult dystrophic muscle continued to contain neonatal myosin long after it disappeared from adult normal muscle. A new technique involving western blotting and peptide mapping demonstrated that the immunoreactive myosin in adult dystrophic muscle was identical to that found in neonatal normal muscle. Immunocytochemistry revealed that all fibers in the dystrophic muscle failed to repress neonatal myosin heavy chain. These studies suggest that muscular dystrophy inhibits the myosin gene switching that normally occurs during muscle maturation.

Effects of nitrogen dioxide on pulmonary function in human subjects: an environmental chamber study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerr, H.D.; Kulle, T.J.; McIlhany, M.L.

Twenty human subjects with asthma and chronic bronchitis and 10 normal, healthy adults were exposed to 0.5 ppM of nitrogen dioxide for 2 h in an environmental chamber. Seven of the 13 subjects with asthma experienced symptoms with exposure, while only one each of the subjects with chronic bronchitis and the healthy, normal group experienced symptoms. Significant pulmonary function changes from control values with exposure to NO/sub 2/ were observed in decreased quasistatic compliance for the 10 normal subjects and the 20 subjects with asthma and chronic bronchitis. In addition, functional residual capacity increased significantly for the 20 subjects withmore » asthma and chronic bronchitis. The subjects with asthma and the subjects with chronic bronchitis as separate groups, however, did not show any significant changes with exposure. With this study we are reasonably confident that exposure of subjects with asthma and chronic bronchitis to 0.5 ppM NO/sub 2/ for 2 h does not produce a significant decrement in their pulmonary function.« less

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult.

PubMed

Herrlinger, Stephanie A; Shao, Qiang; Ma, Li; Brindley, Melinda; Chen, Jian-Fu

2018-04-26

The Zika virus (ZIKV) is a flavivirus currently endemic in North, Central, and South America. It is now established that the ZIKV can cause microcephaly and additional brain abnormalities. However, the mechanism underlying the pathogenesis of ZIKV in the developing brain remains unclear. Intracerebral surgical methods are frequently used in neuroscience research to address questions about both normal and abnormal brain development and brain function. This protocol utilizes classical surgical techniques and describes methods that allow one to model ZIKV-associated human neurological disease in the mouse nervous system. While direct brain inoculation does not model the normal mode of virus transmission, the method allows investigators to ask targeted questions concerning the consequence after ZIKV infection of the developing brain. This protocol describes embryonic, neonatal, and adult stages of intraventricular inoculation of ZIKV. Once mastered, this method can become a straightforward and reproducible technique that only takes a few hours to perform.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

Insulin-producing Cells from Adult Human Bone Marrow Mesenchymal Stromal Cells Could Control Chemically Induced Diabetes in Dogs: A Preliminary Study.

PubMed

Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Khater, Sherry M; Ashamallah, Sylvia A; Azzam, Maha M; Ghoneim, Mohamed A

2018-01-01

Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded in 2 TheraCyte capsules which were transplanted under the rectus sheath. One dog died 4 d postoperatively from pneumonia. Six dogs were followed up with for 6 to 18 mo. Euglycemia was achieved in 4 dogs. Their glucose tolerance curves exhibited a normal pattern demonstrating that the encapsulated cells were glucose sensitive and insulin responsive. In the remaining 2 dogs, the fasting blood sugar levels were reduced but did not reach normal values. The sera of all transplanted dogs contained human insulin and C-peptide with a negligible amount of canine insulin. Removal of the transplanted capsules was followed by prompt return of diabetes. Intracytoplasmic insulin granules were seen by immunofluorescence in cells from the harvested capsules. Furthermore, all pancreatic endocrine genes were expressed. This study demonstrated that the TheraCyte capsule or a similar device can provide adequate immunoisolation, an important issue when stem cells are considered for the treatment of type 1 diabetes mellitus.

Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche

PubMed Central

Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

2014-01-01

Background: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Methods: Human testis and testis cancer specimens from orchidectomies were cultured in ‘hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Results: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Conclusions: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche. PMID:24781282

Mechanical properties of the human hand digits: Age-related differences

PubMed Central

Park, Jaebum; Pazin, Nemanja; Friedman, Jason; Zatsiorsky, Vladimir M.; Latash, Mark L.

2014-01-01

Background Mechanical properties of human digits may have significant implications for the hand function. We quantified several mechanical characteristics of individual digits in young and older adults. Methods Digit tip friction was measured at several normal force values using a method of induced relative motion between the digit tip and the object surface. A modified quick-release paradigm was used to estimate digit apparent stiffness, damping, and inertial parameters. The subjects grasped a vertical handle instrumented with force/moment sensors using a prismatic grasp with four digits; the handle was fixed to the table. Unexpectedly, one of the sensors yielded leading to a quick displacement of the corresponding digit. A second-order, linear model was used to fit the force/displacement data. Findings Friction of the digit pads was significantly lower in older adults. The apparent stiffness coefficient values were higher while the damping coefficients were lower in older adults leading to lower damping ratio. The damping ratio was above unity for most data in young adults and below unity for older adults. Quick release of a digit led to force changes in other digits of the hand, likely due to inertial hand properties. These phenomena of “mechanical enslaving” were smaller in older adults although no significant difference was found in the inertial parameter in the two groups. Interpretations The decreased friction and damping ratio present challenges for the control of everyday prehensile tasks. They may lead to excessive digit forces and low stability of the grasped object. PMID:24355703

Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

PubMed Central

Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

2014-01-01

Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

[Geomagnetic field variations in the human prenatal period and cancer in adults].

PubMed

Iamshanov, V A

2007-01-01

Our earlier evidence pointed to a relationship between geomagnetic field (GMF) variations in pre- and early postnatal periods and appearance in the future of oncopathology in these patients. It appears to contribute to risk for such malignancies in adults as breast, lung, liver, bladder, kidney, prostate, hypophysis cancer, ovarian carcinoma, skin melanoma, Hodgkin's disease, lymphoma, and probably stomach cancer. No link was detected between esophageal, thyroid, colorectal cancer or cervical carcinoma, on the one hand, and GMF variations in prenatal period, on the other. It is suggested that low intensity of GMF is associated with increased death of macrophages and other granulocytes as well as nitric oxide formation both in fetal and maternal organism. The latter factor induces genes responsible for detoxication. In adults, under normal or disturbed GMF conditions, detoxication processes take care of excessive blood-nitric oxide. Both in fetus and mother, due to high GMF intensity, granulocyte decay is inhibited thus causing nitric oxide levels to fall. As a consequence, detoxication fails. That accounts for excessive blood-nitric oxide formation at adult stage when GMF intensity is low or normal. Nitric oxide causes certain nitrosamines to form, which are tissue-specific carcinogens. Therefore, the lower level of GMF oscillations was in pre- and early postnatal periods than in more late terms tumors appeared (for example, the negative correlation for breast cancer took place).

Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.

PubMed

Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido

2007-02-07

Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

Dietary exposure to aflatoxin in human male infertility in Benin City, Nigeria.

PubMed

Ibeh, I N; Uraih, N; Ogonar, J I

1994-01-01

To discover the relationship between aflatoxin levels, if any, in serum of infertile men in comparison with random controls from the community. In a parallel experiment, adult male rats were given an aflatoxin-contaminated diet. 100 adult males, yielding 50 semen samples, from men attending Infertility Clinics at a university teaching hospital and 50 normal men in the same community. The staple foods of the men were assayed for aflatoxin content. The rats were given the aflatoxin-rich diet, and their spermatozoa were examined and their ability to reproduce assessed. A random sampling of semen from 100 adult males comprising 50 samples drawn from infertile men and 50 drawn from normal individuals within the same community revealed the presence of aflatoxins in 20 semen samples from the infertile group (40.0%) and four samples from the fertile group (8.0%). The mean aflatoxin concentrations were 1.660 +/- 0.04 micrograms/mL (infertile men) and 1.041 +/- 0.01 micrograms/mL (fertile men). Infertile men with aflatoxin in their semen showed a higher percentage of spermatozoal abnormality (50.0%) than the fertile men (10.0-15.0%). Dietary exposure of adult male Albino rats to aflatoxin (8.5 micrograms AF1/g of Guinea growers feed for 14 days) produced deleterious effects on the spermatozoa of the affected rats, producing features that resemble those seen in semen of infertile men exposed to aflatoxin.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

PubMed Central

2017-01-01

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment. SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy. PMID:28213439

Sense of agency in the human brain.

PubMed

Haggard, Patrick

2017-04-01

In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cognitive and behavioural experiments, and a growing understanding of the brain circuits that generate this distinctive but elusive experience. The sense of agency is a mental and neural state of cardinal importance in human civilization, because it is frequently altered in psychopathology and because it underpins the concept of responsibility in human societies.

[Human bioaging acceleration as Chernobyl radiation consequence].

PubMed

Neĭfakh, E A; Liuman, G K

2013-01-01

To monitor human bioaging as a health integral index by blood plasma markers as a molar ratio for biochemically coupled monomers of intracellular lipofuscin, an intracellular polymeric aging pigment with free-radical crossed shifts, has been developed. Lipofuscin includes cell debris with catabolites of lipoperoxic cascade and lipid antioxidants. The latter were detected in the plasma samples of normal adults and children, as well as in Chernobyl clean-up workers (24-62 years old by 1990) with external total gamma-doses of 0.9-145 cSv for 4.2 years. Dynamics for bioaging markers as the molar ratio of blood levels of lipoperoxic catabolites to their antioxidants reflected normal physiologic peculiarities for the studied age periods: oxygen stress for newborns, adaptation during childhood, stability for the middle age and an increased lipoperoxidation (mainly for aging men) due to the age weakening of the antioxidant control. The ratio for the fractions of ma- lone dialdehyde (MDA), a lipoperoxic final catabolite, showed the increase of its binding by plasma proteins in proportions to calendar ages for the norm, as it is the case for lipofuscin; The graph of the age normal molar ratio of protein-bound MDA to the free one was pre-set for calibrations into the developed computer Program to calculate Relative Aging Velocities (Wrel) by bioage increments during the period of human exposure to radiation from the CAPS damage. Wrel were increasing logarithmically to the obtained doses if the total radiation exceeded 4 cSv and exceeded their normal velocities at 50 cSv 10 times or more. Slowing down of Wrel in relation to the calendar age increment was found if the sum doses were lower than 4 cSv. Levels of the studied plasma metabolites as their bioage Moles/Moles markers relative to their norms are dynamically stationary in contrast to the lipofuscin intracellular irreversible accumulation. Earlier it was shown that the decreased vitamin E and A levels with the increased lipoperoxic metabolite blood levels that indicate health consequences for the irradiated CAPS personell with related cytogenetic deviations, as well as for the adult population and children from radio-polluted regions, were restored to norms or corrected by adequate peroral therapy with bioantioxidants.

Immunoperoxidase localization of a high-molecular-weight mucin recognized by monoclonal antibody 1D3.

PubMed

Gangopadhyay, A; Bhattacharya, M; Chatterjee, S K; Barlow, J J; Tsukada, Y

1985-04-01

The distribution of an antigen recognized by murine monoclonal antibody 1D3 (Bhattacharya, M., Chatterjee, S.K., Barlow, J. J., and Fuji, H. Cancer Res., 42: 1650-1654, 1982) was investigated in various types of human malignant and normal adult tissues by indirect immunoperoxidase assay in fixed paraffin-embedded sections. One hundred percent of ovarian mucinous cystadenocarcinomas expressed high levels of the antigen with intense staining of 80 to 100% of the tumoral area, thus confirming our previous finding with radioimmunoassay and absorption analyses. About 51% of colonic carcinomas, 33% of gastric carcinomas, and 22% of pancreatic carcinomas were also positive for this high-molecular-weight mucoprotein antigen. All other ovarian and nonovarian carcinomas tested including carcinoma of lung, breast, endometrium, cervix, and prostate were not stained by 1D3. In addition, sarcomas, melanomas, and lymphomas also did not express any detectable level of the antigen. When surveyed against various normal adult tissues, 1D3 had reactivity limited to the colon. Normal colon, however, exhibited reduced staining intensities compared to tumors or to the apparently normal colon adjacent to tumors. The antigen thus appears to be a colorectal tissue-specific antigen showing increased levels in ovarian mucinous cystadenocarcinomas and in some gastrointestinal tumors. 1D3 antigen is a potential tumor marker for mucinous ovarian and colonic tumors.

The mirror neuron system: grasping others' actions from birth?

PubMed

Lepage, Jean-François; Théoret, Hugo

2007-09-01

In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called 'mirror neurons', cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence detailing the existence of a mirror neuron system (MNS) in the adult brain, little is known about its normal development. Yet, a better understanding of the MNS in infants would be of considerable theoretical and clinical interest, as dysfunctions within the MNS have been demonstrated in neurodevelopmental disorders such as autism spectrum disorder. Arguments in favor of an innate, or very early, mechanism underlying action understanding mainly come from studies of neonatal imitation, the existence of which has been questioned by some. Here, we review evidence suggesting the presence of an MNS in the human child, as well as work that suggests, although indirectly, the existence of a mechanism matching the perception and the execution of actions in the human newborn.

The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract.

PubMed Central

Playford, R J; Hanby, A M; Gschmeissner, S; Peiffer, L P; Wright, N A; McGarrity, T

1996-01-01

BACKGROUND: While it is clear that luminal epidermal growth factor (EGF) stimulates repair of the damaged bowel, its significance in maintaining normal gut growth remains uncertain. If EGF is important in maintaining normal gut growth, the EGF receptor (EGF-R) should be present on the apical (luminal) surface in addition to the basolateral surface. AIMS/SUBJECTS/METHODS: This study examined the distribution of the EGF-R in the epithelium throughout the human gastro-intestinal tract using immunohistochemistry, electron microscopy, and western blotting of brush border preparations. RESULTS: Immunostaining of the oesophagus showed circumferential EGF-R positivity in the cells of the basal portions of the stratified squamous epithelium but surface cells were EGF-R negative. In the normal stomach, small intestine, and colon, immunostaining localised the receptor to the basolateral surface with the apical membranes being consistently negative. EGF-R positivity within the small intestine appeared to be almost entirely restricted to the proliferative (crypt) region. Western blotting demonstrated a 170 kDa protein in whole tissue homogenates but not in the brush border vesicle preparations. CONCLUSIONS: As the EGF-R is located only on the basolateral surfaces in the normal adult gastrointestinal tract, the major role of luminal EGF is probably to stimulate repair rather than to maintain normal gut growth. Images Figure 1 Figure 2 Figure 3 PMID:8977341

Role of the normal gut microbiota.

PubMed

Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

2015-08-07

Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

A Four-Dimensional Probabilistic Atlas of the Human Brain

PubMed Central

Mazziotta, John; Toga, Arthur; Evans, Alan; Fox, Peter; Lancaster, Jack; Zilles, Karl; Woods, Roger; Paus, Tomas; Simpson, Gregory; Pike, Bruce; Holmes, Colin; Collins, Louis; Thompson, Paul; MacDonald, David; Iacoboni, Marco; Schormann, Thorsten; Amunts, Katrin; Palomero-Gallagher, Nicola; Geyer, Stefan; Parsons, Larry; Narr, Katherine; Kabani, Noor; Le Goualher, Georges; Feidler, Jordan; Smith, Kenneth; Boomsma, Dorret; Pol, Hilleke Hulshoff; Cannon, Tyrone; Kawashima, Ryuta; Mazoyer, Bernard

2001-01-01

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders. PMID:11522763

[EMG activities of the head, neck and upper trunk muscles with mandibular movements in healthy adults and mandibular asymmetry patients].

PubMed

Jiang, Ting; Zhang, Zhenkang; Yang, Zhaohui; Yi, Biao; Feng, Hailan; Wang, Xing

2002-03-25

To study the activities of head, neck and upper trunk muscles during mandibular movements in healthy adults and mandibular asymmetry patients. Electromyographic integrogram was used to record and analyze the electromyographic activities of the anterior temporal (Ta), posterior temporal (Tp), sternocleidomastoid (SCM), and trapezius (TRAP) muscles in rest position and during mandibular movement among 10 normal adults and 10 mandibular asymmetry patients. All the four muscles showed constant electromyographic activities when the mandible was in the rest position. The activities of Ta, Tp, and SCM muscles increased with protrusion of mandible, mouth opening, tapping, maximum clenching, and chewing. The activities of Ta and Tp muscles of the patients were 1.7 times greater than that of the normal adults during mandibular movement without occlusion, and were weaker by 50% during mandibular movement with occlusion. The difference between electromyographic activities during mandibular movement and in rest position was less among patients than among normal adults. The TRAP muscle of the patients showed constant electromyographic activities with the activity volume nearly 1.8 times that of the normal adults. The difference between the muscle and its namesake at the opposite side was greater among the patients (21%) than among the normal adults (8%). All the four muscles participate in the maintenance of rest position of mandible and the realization of mandibular movements. The coordination of muscular activities among mandibular asymmetry patients is poorer than that among normal adults.

A human quadrupedal gait following poliomyelitis: From the Dercum-Muybridge collaboration (1885).

PubMed

Lanska, Douglas J

2016-03-01

Beginning in the late 1870s, before the invention of movie cameras or projectors, pioneering English American photographer Eadweard Muybridge photographed iconic image sequences of people and animals in motion using arrays of sequentially triggered single-image cameras. In 1885, Philadelphia neurologist Francis Dercum initiated a collaborative relationship with Muybridge at the University of Pennsylvania to photograph sequential images of patients with various neurologic disorders of movement, including an acquired pathologic quadrupedal gait in a young boy that developed as a consequence of poliomyelitis. This pathologic human quadrupedal gait was compared with other quadrupedal gaits filmed by Muybridge, including a toddler girl and an adult woman crawling on hands and knees, an adult woman bear crawling on hands and feet, and a baboon walking. All of the human quadrupedal gaits were lateral sequence gaits, whereas the baboon's walking gait was a diagonal sequence gait. Modern studies have confirmed the nonpathologic quadrupedal gait sequences of humans and nonhuman primates. Despite Dercum's assertion to the contrary, the limb placement pattern of the boy with a pathologic quadrupedal gait after poliomyelitis was not the typical gait of a primate quadruped, but rather was the typical gait sequence for normal human developmental and volitional quadrupedal gaits. © 2016 American Academy of Neurology.

Methodological standards and interpretation of video-electroencephalography in adult control rodents. A TASK1-WG1 report of the AES/ILAE Translational Task Force of the ILAE.

PubMed

Kadam, Shilpa D; D'Ambrosio, Raimondo; Duveau, Venceslas; Roucard, Corinne; Garcia-Cairasco, Norberto; Ikeda, Akio; de Curtis, Marco; Galanopoulou, Aristea S; Kelly, Kevin M

2017-11-01

In vivo electrophysiological recordings are widely used in neuroscience research, and video-electroencephalography (vEEG) has become a mainstay of preclinical neuroscience research, including studies of epilepsy and cognition. Studies utilizing vEEG typically involve comparison of measurements obtained from different experimental groups, or from the same experimental group at different times, in which one set of measurements serves as "control" and the others as "test" of the variables of interest. Thus, controls provide mainly a reference measurement for the experimental test. Control rodents represent an undiagnosed population, and cannot be assumed to be "normal" in the sense of being "healthy." Certain physiological EEG patterns seen in humans are also seen in control rodents. However, interpretation of rodent vEEG studies relies on documented differences in frequency, morphology, type, location, behavioral state dependence, reactivity, and functional or structural correlates of specific EEG patterns and features between control and test groups. This paper will focus on the vEEG of standard laboratory rodent strains with the aim of developing a small set of practical guidelines that can assist researchers in the design, reporting, and interpretation of future vEEG studies. To this end, we will: (1) discuss advantages and pitfalls of common vEEG techniques in rodents and propose a set of recommended practices and (2) present EEG patterns and associated behaviors recorded from adult rats of a variety of strains. We will describe the defining features of selected vEEG patterns (brain-generated or artifactual) and note similarities to vEEG patterns seen in adult humans. We will note similarities to normal variants or pathological human EEG patterns and defer their interpretation to a future report focusing on rodent seizure patterns. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Sensory-motor relationships in speech production in post-lingually deaf cochlear-implanted adults and normal-hearing seniors: Evidence from phonetic convergence and speech imitation.

PubMed

Scarbel, Lucie; Beautemps, Denis; Schwartz, Jean-Luc; Sato, Marc

2017-07-01

Speech communication can be viewed as an interactive process involving a functional coupling between sensory and motor systems. One striking example comes from phonetic convergence, when speakers automatically tend to mimic their interlocutor's speech during communicative interaction. The goal of this study was to investigate sensory-motor linkage in speech production in postlingually deaf cochlear implanted participants and normal hearing elderly adults through phonetic convergence and imitation. To this aim, two vowel production tasks, with or without instruction to imitate an acoustic vowel, were proposed to three groups of young adults with normal hearing, elderly adults with normal hearing and post-lingually deaf cochlear-implanted patients. Measure of the deviation of each participant's f 0 from their own mean f 0 was measured to evaluate the ability to converge to each acoustic target. showed that cochlear-implanted participants have the ability to converge to an acoustic target, both intentionally and unintentionally, albeit with a lower degree than young and elderly participants with normal hearing. By providing evidence for phonetic convergence and speech imitation, these results suggest that, as in young adults, perceptuo-motor relationships are efficient in elderly adults with normal hearing and that cochlear-implanted adults recovered significant perceptuo-motor abilities following cochlear implantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Impact of Adolescent Obesity on Adult Height.

PubMed

Brener, Avivit; Bello, Rachel; Lebenthal, Yael; Yackobovitch-Gavan, Michal; Phillip, Moshe; Shalitin, Shlomit

2017-01-01

Childhood obesity is a major health concern. Excess adiposity during childhood affects growth and puberty. Our aim was to assess whether genetic adult height is compromised in adolescents with obesity. In a retrospective study of 190 obese patients followed at our Pediatric Endocrinology Institute, adult height and delta height (the difference between adult height and mid-parental height) were compared to those of 150 healthy age-matched normal-weight controls. Review of medical files yielded the relevant clinical and anthropometric data of patients, controls, and parents. Of the 190 obese adolescents, 150 were morbidly obese. The median adult height of morbidly obese males was 174.3 cm, of obese males 174 cm, and of normal-weight males 176 cm (p = 0.025). Delta height of morbidly obese males was -0.5 cm, of obese males -0.8 cm, and of normal-weight males, 3 cm (p < 0.0001). The median adult height of morbidly obese females was 161.3 cm, of obese females 162.8 cm, and of normal-weight females 162 cm (p = 0.37). Delta height of morbidly obese females was -1.85 cm, of obese females -0.95 cm, and of normal-weight females 0.7 cm (p = 0.019). Impairment of potential genetic height was not associated with obesity-related comorbidities. Adolescents with obesity showed impairment of potential genetic adult height as compared to that of normal-weight subjects. © 2017 S. Karger AG, Basel.

Obesity does not increase External Mechanical Work per kilogram body mass during Walking

PubMed Central

Browning, Raymond C.; McGowan, Craig P.; Kram, Rodger

2009-01-01

Walking is the most common type of physical activity prescribed for the treatment of obesity. The net metabolic rate during level walking (Watts/kg) is ~10% greater in obese vs. normal weight adults. External mechanical work (Wext) is one of the primary determinants of the metabolic cost of walking, but the effects of obesity on Wext have not been clearly established. The purpose of this study was to compare Wext between obese and normal weight adults across a range of walking speeds. We hypothesized that Wext (J/step) would be greater in obese adults but Wext normalized to body mass would be similar in obese and normal weight adults. We collected right leg three-dimensional ground reaction forces (GRF) while twenty adults (10 obese, BMI=35.6 kg/m2 and 10 normal weight, BMI=22.1 kg/m2) walked on a level, dual-belt force measuring treadmill at six speeds (0.50–1.75 m/s). We used the individual limb method (ILM) to calculate external work done on the center of mass. Absolute Wext (J/step) was greater in obese vs. normal weight adults at each walking speed, but relative Wext (J/step/kg) was similar between the groups. Step frequencies were not different. These results suggest that Wext is not responsible for the greater metabolic cost of walking (W/kg) in moderately obese adults. PMID:19646701

Downregulation of missing in metastasis gene (MIM) is associated with the progression of bladder transitional carcinomas.

PubMed

Wang, Ying; Liu, Jiali; Smith, Elizabeth; Zhou, Kang; Liao, Jie; Yang, Guang-Yu; Tan, Ming; Zhan, Xi

2007-03-01

Missing in metastasis (MIM) gene encodes a putative metastasis suppressor. However, the role of MIM in tumorigenesis and metastasis has not yet been established. Western blot analysis using a MIM specific antibody demonstrated that MIM protein is present at varying levels in a variety of normal cells as well as tumor cell lines. Immunohistochemical staining of adult mouse tissues revealed abundant MIM immunoreactivity in uroepithelial cells in the bladder, neuron Purkinje cells in the cerebellum, and megakaryocytes in the bone marrow and spleen in addition. MIM immunoreactivity also was found in human normal bladder transitional epithelial cells. However, the reactivity was not seen in 69 percent of human primary transitional cell carcinoma specimens. Over 51 percent of the tumors at low grade display MIM staining similarly to the normal cells, whereas only 16.7 percent of the tumors at high-grade with poor differentiation show faint or mild staining. Furthermore, full-length MIM protein is highly expressed in SV-HUC-L an immortalized normal transitional epithelial cell line, moderately expressed in T24 and poorly expressed in J82 and TCCSUP transitional cell carcinoma cells. This finding indicates that downegulation of MIM expression may correlate with the transition of tumor cells from distinct epithelium-like morphology to less differentiated carcinomas.

Measurement of telomerase activity in dog tumors.

PubMed

Yazawa, M; Okuda, M; Setoguchi, A; Nishimura, R; Sasaki, N; Hasegawa, A; Watari, T; Tsujimoto, H

1999-10-01

Telomeres are specific structures present at the end of liner chromosomes. DNA polymerase can not synthesize the end of liner DNA and, as a result, the telomeres become progressively shortened by successive cell divisions. To overcome the end replication problem, telomerase adds new telomeric sequences to the end of chromosomal DNA. The enzyme activity is undetectable in most normal human adult somatic cells, in which shortening of the telomere is thought to limit the somatic-cell life span. In contrast to normal somatic cells, many human tumors possess telomerase activity. The present study looked at whether telomerase activity might serve as a marker for canine tumors. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Normal dog somatic tissues showed little or no telomerase activity, while normal testis exhibited a high level of telomerase activity. We measured telomerase activity in tumor samples from 45 dogs; 21 mammary gland tumors, 16 tumors developed in the skin and oral cavity, 7 vascular tumors and 1 Sertoli cell tumor. Greater than 95% of the tumor samples contained telomerase activity (3-924 U/2 micrograms protein). The results obtained in this study indicated that telomerase should be a useful diagnostic marker for a variety of dog tumors, and it may serve as a target for antitumor chemotherapy.

Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts.

PubMed

Miki, Yasuhiro; Hata, Shuko; Nagasaki, Shuji; Suzuki, Takashi; Ito, Kiyoshi; Kumamoto, Hiroyuki; Sasano, Hironobu

2016-06-15

Bisphenol A, one of the industrial chemicals used in plastics and in the coating of dishes and medical equipment, behaves as an endocrine disruptor in the human body. Bisphenol A can bind directly to several types of nuclear receptors, including steroid and xenobiotic receptor (SXR). SXR plays an important role in bone metabolism through the activation of osteoblasts in vitro, but SXR protein localization has not been reported in bone tissues. Additionally, it is not known whether bisphenol A acts on osteoblasts through SXR activation. Therefore, in this study, we first examined the immunolocalization of the SXR protein in human adult and fetal bone tissues. We then examined the effects of bisphenol A on human osteoblasts in vitro. SXR immunoreactivity was detected in osteoblasts, but not in osteoclasts, of both adult and fetal bone tissues. In fetal bone tissues, the mesenchymal cells or fetal connective tissue were also positive for SXR immunoreactivity. Expression of SXR target genes (tsukushi, matrilin-2, and CYP3A4) and SXR response element-luciferase activity were increased by bisphenol A treatment in normal osteoblasts transfected with SXR (hFOB/SXR) and in osteoblast-like cells (MG-63). Bisphenol A also stimulated cell proliferation and collagen accumulation in hFOB/SXR cells. These results suggest that, as in other tissues, SXR plays important roles in bone metabolism and fetal bone development and that bisphenol A may disturb bone homeostasis in both adult and fetus through SXR. Copyright © 2016 Elsevier Inc. All rights reserved.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

PubMed

Tsyb, A F; Yuzhakov, V V; Roshal', L M; Sukhikh, G T; Konoplyannikov, A G; Sushkevich, G N; Yakovleva, N D; Ingel', I E; Bandurko, L N; Sevan'kaeva, L E; Mikhina, L N; Fomina, N K; Marei, M V; Semenova, Zh B; Konoplyannikova, O A; Kal'sina, S Sh; Lepekhina, L A; Semenkova, I V; Agaeva, E V; Shevchuk, A S; Pavlova, L N; Tokarev, O Yu; Karaseva, O V; Chernyshova, T A

2009-01-01

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

Effects of noise exposure on young adults with normal audiograms I: Electrophysiology.

PubMed

Prendergast, Garreth; Guest, Hannah; Munro, Kevin J; Kluk, Karolina; Léger, Agnès; Hall, Deborah A; Heinz, Michael G; Plack, Christopher J

2017-02-01

Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3-6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

An optimal state estimation model of sensory integration in human postural balance

NASA Astrophysics Data System (ADS)

Kuo, Arthur D.

2005-09-01

We propose a model for human postural balance, combining state feedback control with optimal state estimation. State estimation uses an internal model of body and sensor dynamics to process sensor information and determine body orientation. Three sensory modalities are modeled: joint proprioception, vestibular organs in the inner ear, and vision. These are mated with a two degree-of-freedom model of body dynamics in the sagittal plane. Linear quadratic optimal control is used to design state feedback and estimation gains. Nine free parameters define the control objective and the signal-to-noise ratios of the sensors. The model predicts statistical properties of human sway in terms of covariance of ankle and hip motion. These predictions are compared with normal human responses to alterations in sensory conditions. With a single parameter set, the model successfully reproduces the general nature of postural motion as a function of sensory environment. Parameter variations reveal that the model is highly robust under normal sensory conditions, but not when two or more sensors are inaccurate. This behavior is similar to that of normal human subjects. We propose that age-related sensory changes may be modeled with decreased signal-to-noise ratios, and compare the model's behavior with degraded sensors against experimental measurements from older adults. We also examine removal of the model's vestibular sense, which leads to instability similar to that observed in bilateral vestibular loss subjects. The model may be useful for predicting which sensors are most critical for balance, and how much they can deteriorate before posture becomes unstable.

Pre-existing Epithelial Diversity in Normal Human Livers: A Tissue-tethered Cytometric Analysis in Portal/Periportal Epithelial Cells

PubMed Central

Isse, Kumiko; Lesniak, Andrew; Grama, Kedar; Maier, John; Specht, Susan; Castillo-Rama, Marcela; Lunz, John; Roysam, Badrinath; Michalopoulos, George; Demetris, Anthony J.

2012-01-01

Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BEC). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the Canals of Hering and/or metaplasia of pre-existing mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high resolution whole slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes pre-existed in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g. scatter plots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically-associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. Results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bi-potential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa. Conclusion Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable pre-existent hybrid epithelial diversity in normal human liver. This computationally-enabled tissue analysis approach offers much broader potential beyond the results presented here. PMID:23150208

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

PubMed

Miller, Jennifer L; James, G Andrew; Goldstone, Anthony P; Couch, Jessica A; He, Guojun; Driscoll, Daniel J; Liu, Yijun

2007-06-01

Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kovalevsky, Andrey, E-mail: ayk@lanl.gov; Chatake, Toshiyuki; Shibayama, Naoya

2010-11-01

Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F{sub o} − F{sub c} and 2F{sub o}more » − F{sub c} neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α{sub 1}β{sub 1} heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK{sub a} between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure.« less

Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

ERIC Educational Resources Information Center

Tan, Siang-Yang

1986-01-01

Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

Normal Q-angle in an adult Nigerian population.

PubMed

Omololu, Bade B; Ogunlade, Olusegun S; Gopaldasani, Vinod K

2009-08-01

The Q-angle has been studied among the adult Caucasian population with the establishment of reference values. Scientists are beginning to accept the concept of different human races. Physical variability exists between various African ethnic groups and Caucasians as exemplified by differences in anatomic features such as a flat nose compared with a pointed nose, wide rather than narrow faces, and straight rather than curly hair. Therefore, we cannot assume the same Q-angle values will be applicable to Africans and Caucasians. We established a baseline reference value for normal Q-angles among asymptomatic Nigerian adults. The Q-angles of the left and right knees were measured using a goniometer in 477 Nigerian adults (354 males; 123 females) in the supine and standing positions. The mean Q-angles for men were 10.7 degrees +/- 2.2 degrees in the supine position and 12.3 degrees +/- 2.2 degrees in the standing position in the right knee. The left knee Q-angles in men were 10.5 degrees +/- 2.6 degrees in the supine position and 11.7 degrees +/- 2.8 degrees in the standing position. In women, the mean Q-angles for the right knee were 21 degrees +/- 4.8 degrees in the supine position and 22.8 degrees +/- 4.7 degrees in the standing position. The mean Q-angles for the left knee in women were 20.9 degrees +/- 4.6 degrees in the supine position and 22.7 degrees +/- 4.6 degrees in the standing position. We observed a difference in Q-angles in the supine and standing positions for all participants. The Q-angle in adult Nigerian men is comparable to that of adult Caucasian men, but the Q-angle of Nigerian women is greater than that of their Caucasian counterparts.

Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

PubMed

Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

2016-02-01

Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

Age and Gender Effects on Wideband Absorbance in Adults with Normal Outer and Middle Ear Function

ERIC Educational Resources Information Center

Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

2015-01-01

Purpose: This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Method: Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance…

Expression of classical components of the renin-angiotensin system in the human eye.

PubMed

White, Andrew J R; Cheruvu, Sarat C; Sarris, Maria; Liyanage, Surabhi S; Lumbers, Eugenie; Chui, Jeanie; Wakefield, Denis; McCluskey, Peter J

2015-03-01

The purpose of this study was to determine the relative expression of clinically-relevant components of the renin-angiotensin system (RAS) in the adult human eye. We obtained 14 post-mortem enucleated human eyes from patients whom had no history of inflammatory ocular disease nor pre-mortem ocular infection. We determined the gene expression for prorenin, renin, prorenin receptor, angiotensin-converting enzyme, angiotensinogen and angiotensin II Type 1 receptor, on tissue sections and in cultured human primary retinal pigment epithelial and iris pigment epithelial (RPE/IPE) cell lines, using both qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR). Protein expression was studied using indirect immunofluorescence (IF). Almost all components of the classical RAS were found at high levels, at both the transcript and protein level, in the eyes' uvea and retina; and at lower levels in the cornea, conjunctiva and sclera. There was a much lower level of expression in the reference cultured RPE/IPE cells lines. This study describes the distribution of RAS in the normal adult human eye and demonstrates the existence of an independent ocular RAS, with uveal and retinal tissues showing the highest expression of RAS components. These preliminary findings provide scope for examination of additional components of this system in the human eye, as well as possible differential expression under pathological conditions. © The Author(s) 2014.

Life-long stability of neurons: a century of research on neurogenesis, neuronal death and neuron quantification in adult CNS.

PubMed

Turlejski, Kris; Djavadian, Ruzanna

2002-01-01

In this chapter we provide an extensive review of 100 years of research on the stability of neurons in the mammalian brain, with special emphasis on humans. Although Cajal formulated the Neuronal Doctrine, he was wrong in his beliefs that adult neurogenesis did not occur and adult neurons are dying throughout life. These two beliefs became accepted "common knowledge" and have shaped much of neuroscience research and provided much of the basis for clinical treatment of age-related brain diseases. In this review, we consider adult neurogenesis from a historical and evolutionary perspective. It is concluded, that while adult neurogenesis is a factor in the dynamics of the dentate gyrus and olfactory bulb, it is probably not a major factor during the life-span in most brain areas. Likewise, the acceptance of neuronal death as an explanation for normal age-related senility is challenged with evidence collected over the last fifty years. Much of the problem in changing this common belief of dying neurons was the inadequacies of neuronal counting methods. In this review we discuss in detail implications of recent improvements in neuronal quantification. We conclude: First, age-related neuronal atrophy is the major factor in functional deterioration of existing neurons and could be slowed down, or even reversed by various pharmacological interventions. Second, in most cases neuronal degeneration during aging is a pathology that in principle may be avoided. Third, loss of myelin and of the white matter is more frequent and important than the limited neuronal death in normal aging.

Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

DTIC Science & Technology

2011-09-01

the ETS family of transcription factors showing diverse expression patterns in human tissues (Turner and Watson, 2008). ERG, similar to other...and adult mouse tissues . Most striking of these observations was highly selective and abundant expression of erg protein in endothelial cells of...mouse tissues . We for the first time clarified that endogenous ERG was not expressed in normal mouse prostate epithelium (Mohamed et al., 2010

Effect of human alpha 2HS glycoprotein on mouse macrophage function.

PubMed Central

Lewis, J G; André, C M

1980-01-01

alpha 2HS glycoprotein was isolated from normal adult serum. The ability of alpha 2HS glycoprotein to promote the endocytosis of radiolabelled DNA and radiolabelled latex particles by mouse macrophages was investigated. The results using both radiolabelled latex particles and radiolabelled DNA show that alpha 2HS glycoprotein enhances the ability of mouse macrophages to take up these radiolabelled substrates as compared to control cells. Images Figure 1 Figure 2 PMID:7439929

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells

PubMed Central

West, Michael D.; Labat, Ivan; Sternberg, Hal; Larocca, Dana; Nasonkin, Igor; Chapman, Karen B.; Singh, Ratnesh; Makarev, Eugene; Aliper, Alex; Kazennov, Andrey; Alekseenko, Andrey; Shuvalov, Nikolai; Cheskidova, Evgenia; Alekseev, Aleksandr; Artemov, Artem; Putin, Evgeny; Mamoshina, Polina; Pryanichnikov, Nikita; Larocca, Jacob; Copeland, Karen; Izumchenko, Evgeny; Korzinkin, Mikhail; Zhavoronkov, Alex

2018-01-01

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1, encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro-derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition. PMID:29487692

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells.

PubMed

West, Michael D; Labat, Ivan; Sternberg, Hal; Larocca, Dana; Nasonkin, Igor; Chapman, Karen B; Singh, Ratnesh; Makarev, Eugene; Aliper, Alex; Kazennov, Andrey; Alekseenko, Andrey; Shuvalov, Nikolai; Cheskidova, Evgenia; Alekseev, Aleksandr; Artemov, Artem; Putin, Evgeny; Mamoshina, Polina; Pryanichnikov, Nikita; Larocca, Jacob; Copeland, Karen; Izumchenko, Evgeny; Korzinkin, Mikhail; Zhavoronkov, Alex

2018-01-30

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1 , encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro -derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition.

Redox environment in stem and differentiated cells: A quantitative approach.

PubMed

Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

2017-08-01

Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

PubMed

Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

2016-11-01

Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Adult-like processing of time-compressed speech by newborns: A NIRS study.

PubMed

Issard, Cécile; Gervain, Judit

2017-06-01

Humans can adapt to a wide range of variations in the speech signal, maintaining an invariant representation of the linguistic information it contains. Among them, adaptation to rapid or time-compressed speech has been well studied in adults, but the developmental origin of this capacity remains unknown. Does this ability depend on experience with speech (if yes, as heard in utero or as heard postnatally), with sounds in general or is it experience-independent? Using near-infrared spectroscopy, we show that the newborn brain can discriminate between three different compression rates: normal, i.e. 100% of the original duration, moderately compressed, i.e. 60% of original duration and highly compressed, i.e. 30% of original duration. Even more interestingly, responses to normal and moderately compressed speech are similar, showing a canonical hemodynamic response in the left temporoparietal, right frontal and right temporal cortex, while responses to highly compressed speech are inverted, showing a decrease in oxyhemoglobin concentration. These results mirror those found in adults, who readily adapt to moderately compressed, but not to highly compressed speech, showing that adaptation to time-compressed speech requires little or no experience with speech, and happens at an auditory, and not at a more abstract linguistic level. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Detection of herpes viruses in the cerebrospinal fluid of adults with suspected viral meningitis in Malawi.

PubMed

Benjamin, L A; Kelly, M; Cohen, D; Neuhann, F; Galbraith, S; Mallewa, M; Hopkins, M; Hart, I J; Guiver, M; Lalloo, D G; Heyderman, R S; Solomon, T

2013-02-01

We looked for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively), varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) DNA in Malawian adults with clinically suspected meningitis. We collected cerebrospinal fluid (CSF) from consecutive adults admitted with clinically suspected meningitis to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, for a period of 3 months. Those with proven bacterial or fungal meningitis were excluded. Real-time polymerase chain reaction (PCR) was performed on the CSF for HSV-1 and HSV-2, VZV, EBV and CMV DNA. A total of 183 patients presented with clinically suspected meningitis. Of these, 59 (32 %) had proven meningitis (bacterial, tuberculous or cryptococcal), 39 (21 %) had normal CSF and 14 (8 %) had aseptic meningitis. For the latter group, a herpes virus was detected in 9 (64 %): 7 (50 %) had EBV and 2 (14 %) had CMV, all were human immunodeficiency virus (HIV)-positive. HSV-2 and VZV were not detected. Amongst those with a normal CSF, 8 (21 %) had a detectable herpes virus, of which 7 (88 %) were HIV-positive. The spectrum of causes of herpes viral meningitis in this African population is different to that in Western industrialised settings, with EBV being frequently detected in the CSF. The significance of this needs further investigation.

Fitness and adiposity as predictors of functional limitation in adults.

PubMed

Maslow, Andréa L; Price, Anna E; Sui, Xuemei; Lee, Duck-chul; Vuori, Ikka; Blair, Steven N

2011-01-01

This study examined the associations of body mass index (BMI), waist circumference (WC), and cardiorespiratory fitness (CRF) with incident functional limitation (IFL) in adults. Patients (n = 2400), 30+ years [mean age, 45.2 (SD, 8.3); 12% women], completed a baseline health examination during 1979 to 1995. CRF was quantified by age-and sex-specific thirds for maximal treadmill exercise test duration. Adiposity was assessed by BMI and WC (grouped for analysis according to clinical guidelines). Incident IFL was identified from mail-back surveys during 1995, 1999, and 2004. After adjusting for potential confounders and either BMI or WC, CRF was inversely related to IFL (P trend < .001). The association between BMI and IFL was significant after adjusting for all confounders (P trend = .002), but not after additional adjustment for CRF (P trend = .23). After controlling for all confounders and CRF, high WC was associated with greater odds of IFL in those aged 30 to 49; normal WC was associated with greater odds of IFL in those aged 50+. CRF was a significant predictor of IFL in middle aged and older adults, independent of overall or abdominal adiposity. Clinicians should consider the importance of preserving functional capacity by recommending regular physical activity for normal-weight and overweight individuals. ©2011 Human Kinetics, Inc.

Hesperetin induces melanin production in adult human epidermal melanocytes.

PubMed

Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

2015-06-01

One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

PubMed Central

Campbell, Sean; Taylor, Ruth R.; Forge, Andrew; Hume, Clifford R.

2007-01-01

Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear. PMID:18157569

Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

PubMed

Sato, A; Ochi, H; Harada, Y; Yogo, T; Kanno, N; Hara, Y

2017-01-01

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells.

PubMed

Simara, Pavel; Tesarova, Lenka; Rehakova, Daniela; Farkas, Simon; Salingova, Barbara; Kutalkova, Katerina; Vavreckova, Eva; Matula, Pavel; Matula, Petr; Veverkova, Lenka; Koutna, Irena

2018-01-01

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (γH2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of γH2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes*

PubMed Central

Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

2016-01-01

Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

Lose-Shift Responding in Humans Is Promoted by Increased Cognitive Load

PubMed Central

Ivan, Victorita E.; Banks, Parker J.; Goodfellow, Kris; Gruber, Aaron J.

2018-01-01

The propensity of animals to shift choices immediately after unexpectedly poor reinforcement outcomes is a pervasive strategy across species and tasks. We report here on the memory supporting such lose-shift responding in humans, assessed using a binary choice task in which random responding is the optimal strategy. Participants exhibited little lose-shift responding when fully attending to the task, but this increased by 30%–40% in participants that performed with additional cognitive load that is known to tax executive systems. Lose-shift responding in the cognitively loaded adults persisted throughout the testing session, despite being a sub-optimal strategy, but was less likely as the time increased between reinforcement and the subsequent choice. Furthermore, children (5–9 years old) without load performed similarly to the cognitively loaded adults. This effect disappeared in older children aged 11–13 years old. These data provide evidence supporting our hypothesis that lose-shift responding is a default and reflexive strategy in the mammalian brain, likely mediated by a decaying memory trace, and is normally suppressed by executive systems. Reducing the efficacy of executive control by cognitive load (adults) or underdevelopment (children) increases its prevalence. It may therefore be an important component to consider when interpreting choice data, and may serve as an objective behavioral assay of executive function in humans that is easy to measure. PMID:29568264

Oxidative injury of the pulmonary circulation in the perinatal period: Short- and long-term consequences for the human cardiopulmonary system

PubMed Central

de Wijs-Meijler, Daphne P.; Duncker, Dirk J.; Tibboel, Dick; Schermuly, Ralph T.; Weissmann, Norbert; Merkus, Daphne; Reiss, Irwin K.M.

2017-01-01

Development of the pulmonary circulation is a complex process with a spatial pattern that is tightly controlled. This process is vulnerable for disruption by various events in the prenatal and early postnatal periods. Disruption of normal pulmonary vascular development leads to abnormal structure and function of the lung vasculature, causing neonatal pulmonary vascular diseases. Premature babies are especially at risk of the development of these diseases, including persistent pulmonary hypertension and bronchopulmonary dysplasia. Reactive oxygen species play a key role in the pathogenesis of neonatal pulmonary vascular diseases and can be caused by hyperoxia, mechanical ventilation, hypoxia, and inflammation. Besides the well-established short-term consequences, exposure of the developing lung to injurious stimuli in the perinatal period, including oxidative stress, may also contribute to the development of pulmonary vascular diseases later in life, through so-called “fetal or perinatal programming.” Because of these long-term consequences, it is important to develop a follow-up program tailored to adolescent survivors of neonatal pulmonary vascular diseases, aimed at early detection of adult pulmonary vascular diseases, and thereby opening the possibility of early intervention and interfering with disease progression. This review focuses on pathophysiologic events in the perinatal period that have been shown to disrupt human normal pulmonary vascular development, leading to neonatal pulmonary vascular diseases that can extend even into adulthood. This knowledge may be particularly important for ex-premature adults who are at risk of the long-term consequences of pulmonary vascular diseases, thereby contributing disproportionately to the burden of adult cardiovascular disease in the future. PMID:28680565

Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon.

PubMed

Lell, Bertrand; Mordmüller, Benjamin; Dejon Agobe, Jean-Claude; Honkpehedji, Josiane; Zinsou, Jeannot; Mengue, Juliana Boex; Loembe, Marguerite Massinga; Adegnika, Ayola Akim; Held, Jana; Lalremruata, Albert; Nguyen, The Trong; Esen, Meral; Kc, Natasha; Ruben, Adam J; Chakravarty, Sumana; Lee Sim, B Kim; Billingsley, Peter F; James, Eric R; Richie, Thomas L; Hoffman, Stephen L; Kremsner, Peter G

2018-02-01

Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria-exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers ( P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms ( P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria.

Prevalence of Neutralizing Antibodies against Adeno-Associated Virus (AAV) Types 2, 5, and 6 in Cystic Fibrosis and Normal Populations: Implications for Gene Therapy using AAV Vectors

PubMed Central

Halbert, Christine L.; Miller, A. Dusty; McNamara, Sharon; Emerson, Julia; Gibson, Ronald L.; Ramsey, Bonnie; Aitken, Moira L.

2014-01-01

Adeno-associated virus (AAV) vectors are promising candidates for gene therapy directed to the lungs, in particular for treatment of cystic fibrosis (CF). In animal models of lung gene transfer, neutralizing antibodies in serum made in response to vector exposure have been associated with a partial to complete block to repeat transduction by vectors with the same capsid type, thus transduction by AAV vectors might be inefficient in humans previously exposed to the same AAV type. AAV type 2 (AAV2) has been used in clinical trials of lung gene transfer, but AAV5 and AAV6 have been shown to mediate more efficient transduction in rodent lungs and in cultured human airway epithelia compared to that of AAV2. Here we have measured neutralizing antibodies against AAV type 2, 5, and 6 vectors in serum from children and adults with CF, and from normal adults. About 30% of adults were seropositive for AAV2, 20–30% were seropositive for AAV6, and 10–20% were seropositive for AAV5. CF children were seropositive for AAV types 2, 5, or 6 at rates of 4–15%. All individuals seropositive for AAV6 were also seropositive for AAV2, and the AAV6 titer was low compared to the AAV2 titer. AAV5-positive sera were lower both in titers and rates than those seen for AAV6. The results indicate that AAV type 2, 5 or 6 exposure is low in CF and control populations and even lower in CF children. PMID:16610931

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

PubMed

Bonin, L R; Madden, K; Shera, K; Ihle, J; Matthews, C; Aziz, S; Perez-Reyes, N; McDougall, J K; Conroy, S C

1999-03-01

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.

Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chanson, L.; Brownfield, D.; Garbe, J. C.

Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal humanmore » mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.« less

Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, H.; Goldsmith, G.H. Jr.

A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 ..mu..g PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range <0.003-0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35 +- 0.17more » U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency (Fitzgerald trait).« less

Strategies of Healthy Adults Walking on a Laterally Oscillating Treadmill

NASA Technical Reports Server (NTRS)

Brady, Rachel A.; Peters, Brian T.; Bloomberg, Jacob J.

2008-01-01

We mounted a treadmill on top of a six degree-of-freedom motion base platform to investigate locomotor responses produced by healthy adults introduced to a dynamic walking surface. The experiment examined self-selected strategies employed by participants when exposed to continuous, sinusoidal lateral motion of the support surface while walking. Torso translation and step width were used to classify responses used to stabilize gait in a novel, dynamic environment. Two response categories emerged. Participants tended to either fix themselves in space (FIS), allowing the treadbelt to move laterally beneath them, or they fixed themselves to the base (FTB), moving laterally as the motion base oscillated. The degree of fixation in both extremes varied across participants. This finding suggests that normal adults have innate and varied preferences for reacquiring gait stability, some depending more heavily on vision (FIS group) and others on proprioception (FTB group). Keywords: Human locomotion, Unstable surface, Treadmill, Adaptation, Stability

Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels. PMID:21321359

M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

PubMed Central

2013-01-01

Background Microglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation. Methods Using biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function. Results We found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide. Conclusions We show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit. PMID:23866312

Partial recovery of hemiparesis following hemispherectomy in infant monkeys.

PubMed

Burke, Mark W; Zangenehpour, Shahin; Ptito, Maurice

2010-01-22

Hemiparesis, unilateral weakness or partial paralysis, is a common outcome following hemispherectomy in humans. We use the non-human primate as an invaluable translational model for our understanding of developmental plasticity in response to hemispherectomy. Three infant vervet monkeys (Chlorocebus sabeus) underwent hemispherectomy at a median age of 9 weeks and two additional monkeys at 48 months. Gross motor assessment was conducted in a large open field that contained a horizontal bar spanning the width of the cage. Subjects were assessed yearly following surgery in infantile lesions for a period of 3 years. Adult-lesioned subjects were assessed 40 months following surgery. Shortly after surgery both infant and adult-lesioned subjects were unable to move the contralateral side of their body, but all subjects were able to walk within 6 months following surgery. At each time point the lower limb gait was normal in infant-lesioned subjects with no apparent limp or dragging, however the upper limb demonstrated significant impairment. Horizontal bar crossing was significantly impaired during the first 24 months following surgery. Adult-lesioned subjects also displayed upper limb movement impairments similar to infant-lesioned subjects. In addition the adult-lesioned subjects displayed a noticeable lower limb limp, which was not observed in the infant-lesioned group. Both groups at each time point showed a propensity for ipsiversive turning. The upper limb gait impairment and horizontal bar crossing of lesioned subjects are reminiscent of hemiparesis seen in hemisperectomized humans with the young-lesioned subjects showing a greater propensity for recovery. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Fourier analysis of human soft tissue facial shape: sex differences in normal adults.

PubMed Central

Ferrario, V F; Sforza, C; Schmitz, J H; Miani, A; Taroni, G

1995-01-01

Sexual dimorphism in human facial form involves both size and shape variations of the soft tissue structures. These variations are conventionally appreciated using linear and angular measurements, as well as ratios, taken from photographs or radiographs. Unfortunately this metric approach provides adequate quantitative information about size only, eluding the problems of shape definition. Mathematical methods such as the Fourier series allow a correct quantitative analysis of shape and of its changes. A method for the reconstruction of outlines starting from selected landmarks and for their Fourier analysis has been developed, and applied to analyse sex differences in shape of the soft tissue facial contour in a group of healthy young adults. When standardised for size, no sex differences were found between both cosine and sine coefficients of the Fourier series expansion. This shape similarity was largely overwhelmed by the very evident size differences and it could be measured only using the proper mathematical methods. PMID:8586558

Pneumocystis Pneumonia in Human Immunodeficiency Virus–infected Adults and Adolescents: Current Concepts and Future Directions

PubMed Central

Tasaka, Sadatomo

2015-01-01

Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus–infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim–sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern. PMID:26327786

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mintun, M.A.; Dennis, D.R.; Welch, M.J.

1987-11-01

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(/sup 68/Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of (/sup 68/Ga)citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escapemore » rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.« less

The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

PubMed

Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

2016-08-01

The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (p<0.01) followed by young adults and older adults. Female subjects (across all ages) had significantly lower plasma HMB concentrations. A significant positive correlation between HMB concentrations and appendicular lean mass normalized for body weight (%), appendicular lean mass (r=0.37; p<0.001) was observed in the young adults and older adults group. Handgrip strength was positively associated with plasma HMB concentrations in young adults (r=0.58; p<0.01) and the older adults group (r=0.28; p<0.01). The findings of the present study suggest that there is an age- related decline in endogenous HMB concentrations in humans and the HMB concentrations were positively correlated with appendicular lean mass and hand grip strength in young adults and older adults group. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

PubMed

Miszta-Lane, Helena; Mirbolooki, Mohammadreza; James Shapiro, A M; Lakey, Jonathan R T

2006-01-01

Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Differences in Relative Levels of 88 microRNAs in Various Regions of the Normal Adult Human Brain.

PubMed

Filatova, Elena V; Alieva, Anelya; Shadrina, Maria I; Slominsky, Petr A

2017-08-16

Since the discovery of microRNAs (miRNAs) in the 1990s, our knowledge about their biology has grown considerably. The increasing number of studies addressing the role of miRNAs in development and in various diseases emphasizes the need for a comprehensive catalogue of accurate sequence, expression and conservation information regarding the large number of miRNAs proposed recently in all organs and tissues. The objective of this study was to provide data on the levels of miRNA expression in 15 tissues of the normal human brain. We conducted an analysis of the relative levels of 88 of the most abundantly expressed and best characterized miRNA derived postmortem from well-characterized samples of various regions of the brains from five normal individuals. The cluster analysis revealed some differences in the relative levels of these miRNAs among the brain regions studied. Such diversity can be explained by different functioning of these brain regions. We hope that the data from the current study are a resource that will be useful to our colleagues in this exciting field, as more hypotheses will be generated and tested with regard to small noncoding RNA in the human brain in healthy and disease states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human growth hormone (GH1) gene polymorphism map in a normal-statured adult population

PubMed Central

Esteban, Cristina; Audí, Laura; Carrascosa, Antonio; Fernández-Cancio, Mónica; Pérez-Arroyo, Annalisa; Ulied, Angels; Andaluz, Pilar; Arjona, Rosa; Albisu, Marian; Clemente, María; Gussinyé, Miquel; Yeste, Diego

2007-01-01

Objective GH1 gene presents a complex map of single nucleotide polymorphisms (SNPs) in the entire promoter, coding and noncoding regions. The aim of the study was to establish the complete map of GH1 gene SNPs in our control normal population and to analyse its association with adult height. Design, subjects and measurements A systematic GH1 gene analysis was designed in a control population of 307 adults of both sexes with height normally distributed within normal range for the same population: −2 standard deviation scores (SDS) to +2 SDS. An analysis was performed on individual and combined genotype associations with adult height. Results Twenty-five SNPs presented a frequency over 1%: 11 in the promoter (P1 to P11), three in the 5′UTR region (P12 to P14), one in exon 1 (P15), three in intron 1 (P16 to P18), two in intron 2 (P19 and P20), two in exon 4 (P21 and P22) and three in intron 4 (P23 to P25). Twenty-nine additional changes with frequencies under 1% were found in 29 subjects. P8, P19, P20 and P25 had not been previously described. P6, P12, P17 and P25 accounted for 6·2% of the variation in adult height (P = 0·0007) in this population with genotypes A/G at P6, G/G at P6 and A/G at P12 decreasing height SDS (−0·063 ± 0·031, −0·693 ± 0·350 and −0·489 ± 0·265, Mean ± SE) and genotypes A/T at P17 and T/G at P25 increasing height SDS (+1·094 ± 0·456 and +1·184 ± 0·432). Conclusions This study established the GH1 gene sequence variation map in a normal adult height control population confirming the high density of SNPs in a relatively small gene. Our study shows that the more frequent SNPs did not significantly contribute to height determination, while only one promoter and two intronic SNPs contributed significantly to it. Studies in larger populations will have to confirm the associations and in vitro functional studies will elucidate the mechanisms involved. Systematic GH1 gene analysis in patients with growth delay and suspected GH deficiency/insufficiency will clarify whether different SNP frequencies and/or the presence of different sequence changes may be associated with phenotypes in them. PMID:17223997

Congenital deficiency of alpha feto-protein.

PubMed

Sharony, Reuven; Zadik, Idit; Parvari, Ruti

2004-10-01

Alpha-fetoprotein (AFP) is the main fetus serum glycoprotein with a very low concentration in the adult. AFP deficiency is a rare phenomenon. We studied two families with congenital AFP deficiency and searched for mutations in the AFP gene. We identified one mutation of 2 base deletion in exon 8, in both families, that leads to the congenital deficiency of AFP. The mutation nt930-931delCT (T294fs25X) creates a frameshift after codon 294 that leads to a stop codon after 24 amino acids, thus truncating the normal length of AFP of 609 amino acids. All the affected children were found to be homozygous for the mutation as was one of the fathers. The affected individuals were asymptomatic and presented normal development. This first identification of a mutation in the AFP gene demonstrates for the first time that deficiency of AFP is compatible with human normal fetal development and further reproduction in males.

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

PubMed Central

Tuohy, Vincent K.; Jaini, Ritika; Johnson, Justin M.; Loya, Matthew G.; Wilk, Dennis; Downs-Kelly, Erinn; Mazumder, Suparna

2016-01-01

We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC)—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC. PMID:27322324

Neurogenesis in the embryonic and adult brain: same regulators, different roles

PubMed Central

Urbán, Noelia; Guillemot, François

2014-01-01

Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region. PMID:25505873

Lowering the milk lactose content in vivo: potential interests, strategies and physiological consequences.

PubMed

Vilotte, Jean-Luc

2002-01-01

Lactose is the major sugar present in milk and an important osmotic regulator of lactation. It is digested by intestinal lactase, an enzyme expressed in new-borns. Its activity declines following weaning. As a result, adult mammals are normally lactose-intolerant and more than 75% of the human adult population suffers from lactase deficiency. A reduction in milk lactose content could be beneficial for nutritional but also agricultural and industrial purposes (less volume to transport, better milk coagulation, less effluent production). Several attempts to create transgenic mice producing milk with modified carbohydrate compositions have recently been described. Depending on whether these modifications resulted from an alteration of lactose synthesis or from lactose hydrolysis, striking physiological differences are observed.

Talker Differences in Clear and Conversational Speech: Perceived Sentence Clarity for Young Adults with Normal Hearing and Older Adults with Hearing Loss

ERIC Educational Resources Information Center

Ferguson, Sarah Hargus; Morgan, Shae D.

2018-01-01

Purpose: The purpose of this study is to examine talker differences for subjectively rated speech clarity in clear versus conversational speech, to determine whether ratings differ for young adults with normal hearing (YNH listeners) and older adults with hearing impairment (OHI listeners), and to explore effects of certain talker characteristics…

Seeing the Talker's Face Improves Free Recall of Speech for Young Adults with Normal Hearing but Not Older Adults with Hearing Loss

ERIC Educational Resources Information Center

Rudner, Mary; Mishra, Sushmit; Stenfelt, Stefan; Lunner, Thomas; Rönnberg, Jerker

2016-01-01

Purpose: Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. Method: Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13…

Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

PubMed Central

2012-01-01

Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877

Localization of congenital tegmen tympani defects.

PubMed

Tóth, Miklós; Helling, Kai; Baksa, Gábor; Mann, Wolf

2007-12-01

This study sets out to demonstrate the normal developmental steps of the tegmen tympani and thus explains the typical localization of congenital tegmental defects. For this study, 79 macerated and formalin-fixed human temporal bones from 14th fetal week to adults were observed and prepared. Macroscopic and microscopic examination of the prenatal and postnatal changes of the tegmen tympani during its development. Temporal bones from 14th fetal week to adults underwent descriptive anatomic studies to understand the normal development of the tegmen tympani and to find a possible cause of its congenital defects. The medial part of the tegmen tympani develops from the otic capsule during chondral ossification, thus forming the tegmental process of the petrous part. The lateral part shows membranous ossification. The tegmental process cases a temporary bony dehiscence lateral to the geniculate ganglion between the 23rd and 25th fetal week. Congenital defects develop near the geniculate ganglion and seem to be due to an incomplete development of tegmental process of otic capsule. Because of that, congenital lesion of the tegmen tympani can be defined as an inner ear defect.

Polymorphic Expression of a Human Superficial Bladder Tumor Antigen Defined by Mouse Monoclonal Antibodies

NASA Astrophysics Data System (ADS)

Fradet, Yves; Islam, Nazrul; Boucher, Lucie; Parent-Vaugeois, Carmen; Tardif, Marc

1987-10-01

Three mouse monoclonal antibodies (mAbs), which define a highly restricted antigen, were obtained by simultaneous immunizations with superficial papillary bladder tumor cells and mouse polyclonal serum against normal urothelium. The antigen was detected by the avidin/biotin/peroxidase method in 30/44 superficial bladder tumors (68%) but in only 4/27 infiltrating urothelial cancers (with much less intensity). No normal adult or fetal tissues tested expressed the antigen, including normal urothelium from 40 individuals, 13 of whom had a bladder tumor positive for the antigen. Only 1 of 45 nonbladder tumors showed some reactivity with one of the three mAbs. Serological tests on a large panel of human cancer cell lines and normal cultured cells were negative. The antigen is highly stable and well preserved on paraffin-embedded tissues. Electrophoretic transfer blot experiments with fresh tumor extracts showed that all three mAbs react with a determinant on a component of 300,000 Mr (pI 9.5) and 62,000 Mr (pI 6.5). The antigen shows polymorphic expression at the cellular level on tissue sections and also at a molecular level on immunoblots where the two bands are differentially detected on extracts of a series of tumors but are not visualized on normal urothelium extracts. The characteristics of this antigenic system suggest that it may provide some insights about the biology of bladder cancer. Specific detection of the antigen on 70% of superficial bladder tumors with normal cytology may be useful for their diagnosis and follow-up.

Evidence for Cardiomyocyte Renewal in Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergmann, O; Bhardwaj, R D; Bernard, S

2008-10-14

It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 20 to 0.3% at the age of 75. Less than 50% of cardiomyocytes are exchanged during a normal lifespan. The capacity to generate cardiomyocytes inmore » the adult human heart suggests that it may be rational to work towards the development of therapeutic strategies aiming to stimulate this process in cardiac pathologies.« less

Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant Women.

PubMed

Mutic, Abby D; Baker, Brenda J; McCauley, Linda A

2017-12-01

Human exposure to endocrine disrupting chemicals (EDCs) has become common as a result of widespread application of these chemicals to the food supply, environmental contamination, and occupational exposures (Caserta et al., 2011). However, relatively little is known about the effects of EDCs such as ethylene thiourea (ETU) in developing fetuses and the lasting implications of this disruption on human development from birth through adulthood. Of highest concern are chronic, low-dose exposures among industrial and agricultural workers. Current knowledge regarding the significance of endocrine thyroid signaling on normal human development raises serious concerns about the possible deleterious effects of EDCs in the developing fetus, children, and mature adults. Occupational health nurses are critical in identifying women and families at increased risk of ETU exposure and mitigating early exposures in pregnancy.

Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial.

PubMed

Mogul, Harriette R; Lee, Phillip D K; Whitman, Barbara Y; Zipf, William B; Frey, Michael; Myers, Susan; Cahan, Mindy; Pinyerd, Belinda; Southren, A Louis

2008-04-01

GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies. Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults. We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods. The study was conducted at outpatient treatment facilities at four U.S. academic medical centers. Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations. Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated. Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry. Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (P < or = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients). This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.

Facial aesthetics: babies prefer attractiveness to symmetry.

PubMed

Samuels, Curtis A; Butterworth, George; Roberts, Tony; Graupner, Lida; Hole, Graham

2013-01-01

The visual preferences of human infants for faces that varied in their attractiveness and in their symmetry about the midline were explored. The aim was to establish whether infants' visual preference for attractive faces may be mediated by the vertical symmetry of the face. Chimeric faces, made from photographs of attractive and unattractive female faces, were produced by computer graphics. Babies looked longer at normal and at chimeric attractive faces than at normal and at chimeric unattractive faces. There were no developmental differences between the younger and older infants: all preferred to look at the attractive faces. Infants as young as 4 months showed similarity with adults in the 'aesthetic perception' of attractiveness and this preference was not based on the vertical symmetry of the face.

Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM

PubMed Central

Ma, Dan; Shield, Julian P.H.; Dean, Wendy; Leclerc, Isabelle; Knauf, Claude; Burcelin, Rémy; Rutter, Guy A.; Kelsey, Gavin

2004-01-01

Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet β cell number and impaired β cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, β cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and β cell function in disease pathogenesis. PMID:15286800

Color vision tests comparison: Farnsworth D-15 versus Lanthony D-15

NASA Astrophysics Data System (ADS)

Szmigiel, Marta; Geniusz, Malwina; Geniusz, Maciej K.

2017-09-01

Disorder of color vision in humans is the inability to perceive differences between some or all of the colors that are normally perceived by others. Color blindness is usually a birth defect, a genetically determined. For this reason it is much more common in men than women. This paper presents the results of the test FarnsworthD-15 and Lanthony D-15 on a group of volunteers, both adults and children. The study was conducted to compare the results of both tests.

[Treatment of primary hypothyroidism in adult patients].

PubMed

Salmela, Pasi; Metso, Saara; Moilanen, Leena; Niskanen, Leo; Nuutila, Pirjo; Schalin-Jäntti, Camilla

2016-01-01

The diagnosis of hypothyroidism is based on the findings of an increased serum TSH (above the reference range) and decreased serum free T4 (below the reference range) concentration. Treatment of subclinical hypothyroidism is indicated if serum THS is above 10 mU/l. For less severe forms of subclinical hypothyroidism, the treatment should be individually tailored. The treatment of choice is synthetic human levothyroxine. The goals for treatment are amelioration of symptoms and normalization of TSH and free T4 concentrations.

Serum thymulin in human zinc deficiency.

PubMed Central

Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

1988-01-01

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

Structural Equation Analysis of the Wechsler Adult Intelligence Scale-Revised in a Normal Elderly Sample.

ERIC Educational Resources Information Center

Burton, D. Bradley; And Others

1994-01-01

A maximum-likelihood confirmatory factor analysis was performed by applying LISREL VII to the Wechsler Adult Intelligence Scale-Revised results of a normal elderly sample of 225 adults. Results indicate that a three-factor model fits best across all sample combinations. A mild gender effect is discussed. (SLD)

Judging Normality and Attractiveness in Faces: Direct Evidence of a More Refined Representation for Own-Race, Young Adult Faces.

PubMed

Zhou, Xiaomei; Short, Lindsey A; Chan, Harmonie S J; Mondloch, Catherine J

2016-09-01

Young and older adults are more sensitive to deviations from normality in young than older adult faces, suggesting that the dimensions of face space are optimized for young adult faces. Here, we extend these findings to own-race faces and provide converging evidence using an attractiveness rating task. In Experiment 1, Caucasian and Chinese adults were shown own- and other-race face pairs; one member was undistorted and the other had compressed or expanded features. Participants indicated which member of each pair was more normal (a task that requires referencing a norm) and which was more expanded (a task that simply requires discrimination). Participants showed an own-race advantage in the normality task but not the discrimination task. In Experiment 2, participants rated the facial attractiveness of own- and other-race faces (Experiment 2a) or young and older adult faces (Experiment 2b). Between-rater variability in ratings of individual faces was higher for other-race and older adult faces; reduced consensus in attractiveness judgments reflects a less refined face space. Collectively, these results provide direct evidence that the dimensions of face space are optimized for own-race and young adult faces, which may underlie face race- and age-based deficits in recognition. © The Author(s) 2016.

The effects of familiarity and complexity on appraisal of complex songs by cochlear implant recipients and normal hearing adults.

PubMed

Gfeller, Kate; Christ, Aaron; Knutson, John; Witt, Shelley; Mehr, Maureen

2003-01-01

The purposes of this study were (a) to develop a test of complex song appraisal that would be suitable for use with adults who use a cochlear implant (assistive hearing device) and (b) to compare the appraisal ratings (liking) of complex songs by adults who use cochlear implants (n = 66) with a comparison group of adults with normal hearing (n = 36). The article describes the development of a computerized test for appraisal, with emphasis on its theoretical basis and the process for item selection of naturalistic stimuli. The appraisal test was administered to the 2 groups to determine the effects of prior song familiarity and subjective complexity on complex song appraisal. Comparison of the 2 groups indicates that the implant users rate 2 of 3 musical genres (country western, pop) as significantly more complex than do normal hearing adults, and give significantly less positive ratings to classical music than do normal hearing adults. Appraisal responses of implant recipients were examined in relation to hearing history, age, performance on speech perception and cognitive tests, and musical background.

An anatomically comprehensive atlas of the adult human brain transcriptome

PubMed Central

Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

2014-01-01

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition

PubMed Central

McCoy, Erica L.; Iwanaga, Ritsuko; Jedlicka, Paul; Abbey, Nee-Shamo; Chodosh, Lewis A.; Heichman, Karen A.; Welm, Alana L.; Ford, Heide L.

2009-01-01

Six1 is a developmentally regulated homeoprotein with limited expression in most normal adult tissues and frequent misexpression in a variety of malignancies. Here we demonstrate, using a bitransgenic mouse model, that misexpression of human Six1 in adult mouse mammary gland epithelium induces tumors of multiple histological subtypes in a dose-dependent manner. The neoplastic lesions induced by Six1 had an in situ origin, showed diverse differentiation, and exhibited progression to aggressive malignant neoplasms, as is often observed in human carcinoma of the breast. Strikingly, the vast majority of Six1-induced tumors underwent an epithelial-mesenchymal transition (EMT) and expressed multiple targets of activated Wnt signaling, including cyclin D1. Interestingly, Six1 and cyclin D1 coexpression was found to frequently occur in human breast cancers and was strongly predictive of poor prognosis. We further show that Six1 promoted a stem/progenitor cell phenotype in the mouse mammary gland and in Six1-driven mammary tumors. Our data thus provide genetic evidence for a potent oncogenic role for Six1 in mammary epithelial neoplasia, including promotion of EMT and stem cell–like features. PMID:19726883

Comparison of human radiation exchange models in outdoor areas

NASA Astrophysics Data System (ADS)

Park, Sookuk; Tuller, Stanton E.

2011-10-01

Results from the radiation components of seven different human thermal exchange models/methods are compared. These include the Burt, COMFA, MENEX, OUT_SET* and RayMan models, the six-directional method and the new Park and Tuller model employing projected area factors ( f p) and effective radiation area factors ( f eff) determined from a sample of normal- and over-weight Canadian Caucasian adults. Input data include solar and longwave radiation measured during a clear summer day in southern Ontario. Variations between models came from differences in f p and f eff and different estimates of longwave radiation from the open sky. The ranges between models for absorbed solar, net longwave and net all-wave radiation were 164, 31 and 187 W m-2, respectively. These differentials between models can be significant in total human thermal exchange. Therefore, proper f p and f eff values should be used to make accurate estimation of radiation on the human body surface.

Isolation and characterization of 2 new human rotator cuff and long head of biceps tendon cells possessing stem cell-like self-renewal and multipotential differentiation capacity.

PubMed

Randelli, Pietro; Conforti, Erika; Piccoli, Marco; Ragone, Vincenza; Creo, Pasquale; Cirillo, Federica; Masuzzo, Pamela; Tringali, Cristina; Cabitza, Paolo; Tettamanti, Guido; Gagliano, Nicoletta; Anastasia, Luigi

2013-07-01

Stem cell therapy is expected to offer new alternatives to the traditional therapies of rotator cuff tendon tears. In particular, resident, tissue-specific, adult stem cells seem to have a higher regenerative potential for the tissue where they reside. Rotator cuff tendon and long head of the biceps tendon possess a resident stem cell population that, when properly stimulated, may be induced to proliferate, thus being potentially usable for tendon regeneration. Controlled laboratory study. Human tendon samples from the supraspinatus and the long head of the biceps were collected during rotator cuff tendon surgeries from 26 patients, washed with phosphate-buffered saline, cut into small pieces, and digested with collagenase type I and dispase. After centrifugation, cell pellets were resuspended in appropriate culture medium and plated. Adherent cells were cultured, phenotypically characterized, and then compared with human bone marrow stromal cells (BMSCs), as an example of adult stem cells, and human dermal fibroblasts, as normal proliferating cells with no stem cell properties. Two new adult stem cell populations from the supraspinatus and long head of the biceps tendons were isolated, characterized, and cultured in vitro. Cells showed adult stem cell characteristics (ie, they were self-renewing in vitro, clonogenic, and multipotent), as they could be induced to differentiate into different cell types--namely, osteoblasts, adipocytes, and skeletal muscle cells. This work demonstrated that human rotator cuff tendon stem cells and human long head of the biceps tendon stem cells can be isolated and possess a high regenerative potential, which is comparable with that of BMSCs. Moreover, comparative analysis of the sphingolipid pattern of isolated cells with that of BMSCs and fibroblasts revealed the possibility of using this class of lipids as new possible markers of the cell differentiation status. Rotator cuff and long head of the biceps tendons contain a stem cell population that can proliferate in vitro and could constitute an easily accessible stem cell source to develop novel therapies for tendon regeneration.

Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors.

PubMed

Kraus, Theo F J; Globisch, Daniel; Wagner, Mirko; Eigenbrod, Sabina; Widmann, David; Münzel, Martin; Müller, Markus; Pfaffeneder, Toni; Hackner, Benjamin; Feiden, Wolfgang; Schüller, Ulrich; Carell, Thomas; Kretzschmar, Hans A

2012-10-01

5-Methylcytosine (5 mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology. 5-Hydroxymethylcytosine (5 hmC) is generated from 5 mC by the action of the TET (Ten-Eleven-Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5 mC. We have used immunohistochemistry (IHC) and isotope-based liquid chromatography mass spectrometry (LC-MS) to investigate the presence and distribution of 5 hmC in human brain and brain tumors. In the normal adult brain, IHC identified 61.5% 5 hmC positive cells in the cortex and 32.4% 5 hmC in white matter (WM) areas. In tumors, positive staining of cells ranged from 1.1% in glioblastomas (GBMs) (WHO Grade IV) to 8.9% in Grade I gliomas (pilocytic astrocytomas). In the normal adult human brain, LC-MS also showed highest values in cortical areas (1.17% 5 hmC/dG [deoxyguanosine]), in the cerebral WM we measured around 0.70% 5 hmC/dG. levels were related to tumor differentiation, ranging from lowest values of 0.078% 5 hmC/dG in GBMs (WHO Grade IV) to 0.24% 5 hmC/dG in WHO Grade II diffuse astrocytomas. 5 hmC measurements were unrelated to 5 mC values. We find that the number of 5 hmC positive cells and the amount of 5 hmC/dG in the genome that has been proposed to be related to pluripotency and lineage commitment in embryonic stem cells is also associated with brain tumor differentiation and anaplasia. Copyright © 2012 UICC.

Growth hormone distribution kinetics are markedly reduced in adults with growth hormone deficiency.

PubMed

Catalina, Pablo F; Páramo, Concepción; Andrade, Maria Amalia; Mallo, Federico

2007-03-01

Growth hormone (GH) circulating levels are highly dependent not only on GH secretion rate from the pituitary, but also on the hormone distribution in the compartments of the body and elimination phenomena. In adult GH-deficient patients these factors become critical nowadays, especially when recombinant human GH (rhGH) is available for replacement therapy. In the present study, we assess the influence of both distribution and elimination phenomena on GH pharmacokinetics in adult GH-deficient patients. We used a four-step methodology following a compartmental approach after an intravenous bolus of recombinant GH in adult GH-deficient patients. We found that GH kinetics are clearly explained by a bi-exponential, two-compartmental model in GH-deficient patients, similarly than in normal or diabetic subjects, as previously shown. We have also observed a marked delay in the whole GH elimination process in GH-deficient patients compared to normal adult subjects, as revealed by metabolic clearance ratio (MCR), elimination constant from central compartment (k(10)), and mean resident time in the body (MRT). Interestingly, such a delay appear to be caused by deep changes in the distribution phase (Mtt(1)- mean transit time-1; T(1/2alpha)- GH half-life at distribution phase), while the elimination phenomenon remains unaltered. Our results emphasize the relevance of distribution phenomena in GH pharmacokinetics, and indicates that studies avoiding data from the GH distribution phase, such as those carried out in steady-state conditions, or those using noncompartmental models, could easily miss relevant information. Our data should be taken into consideration when establishing the appropriate dosage for GH replacement treatments in GH-deficient patients, and calculations should include GH distribution kinetics.

Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis.

PubMed

Sheanon, Nicole M; Backeljauw, Philippe F

2015-01-01

Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome. Turner syndrome effects 1 in every 2000 live births. Short stature is a cardinal feature of Turner Syndrome and the standard treatment is recombinant human growth hormone. When growth hormone is started at an early age a normal adult height can be achieved. With delayed diagnosis young women with Turner Syndrome may not reach a normal height. Adjuvant therapy with oxandrolone is used but there is no consensus on the optimal timing of treatment, the duration of treatment and the long term adverse effects of treatment. The objective of this review and meta-analysis is to examine the effect of oxandrolone on adult height in growth hormone treated Turner syndrome patients. Eligible trials were identified by a literature search using the terms: Turner syndrome, oxandrolone. The search was limited to English language randomized-controlled trials after 1980. Twenty-six articles were reviewed and four were included in the meta-analysis. A random effects model was used to calculate an effect size and confidence interval. The pooled effect size of 2.0759 (95 % CI 0.0988 to 4.0529) indicates that oxandrolone has a positive effect on adult height in Turner syndrome when combined with growth hormone therapy. In conclusion, the addition of oxandrolone to growth hormone therapy for treatment of short stature in Turner syndrome improves adult height. Further studies are warranted to investigate if there is a subset of Turner syndrome patients that would benefit most from growth hormone plus oxandrolone therapy, and to determine the optimal timing and duration of such therapy.

Apical Plasma Membrane Mispolarization of NaK-ATPase in Polycystic Kidney Disease Epithelia Is Associated with Aberrant Expression of the β2 Isoform

PubMed Central

Wilson, Patricia D.; Devuyst, Olivier; Li, Xiaohong; Gatti, Laura; Falkenstein, Doris; Robinson, Shawn; Fambrough, Douglas; Burrow, Christopher R.

2000-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical 22Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of α1, α3, β1, and β2 subunits of NaK-ATPase. High levels of expression of α1 and β1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas β2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against α1 and β1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle’s loop. In ADPKD kidneys, α1 and β2 subunits were localized to the apical epithelial cell membranes, whereas β1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken β1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken β2 or human β2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which endogenously expressed α1 and β2 NaK-ATPase subunits, showed colocalization at the apical cell surface and coassociation by immunoprecipitation analysis. These results are consistent with a model in which the additional transcription and translation of the β2 subunit of NaK-ATPase may result in the apical mislocalization of NaK-ATPase in ADPKD cystic epithelia. PMID:10623674

Effects of Elicitation Procedures on the Narratives of Normal and Closed Head-Injured Adults.

ERIC Educational Resources Information Center

Liles, Betty Z.; And Others

1989-01-01

Twenty-three normal adults and four closed head-injured (CHI) adults with a high level of language recovery retold and generated stories. The two tasks differentially influenced the performance of both groups. The two groups differed in measures of cohesiveness and story grammar only in the story generation task. (Author/JDD)

Tongue Palate Contact Patterns of Velar Stops in Normal Adult English Speakers

ERIC Educational Resources Information Center

Liker, Marko; Gibbon, Fiona E.

2008-01-01

This paper provides a more detailed description of normal tongue palate contact patterns for the occlusion phase of velar stops than currently exists. The study used electropalatography (EPG) to record seven normally speaking adults' contact patterns of voiceless velar stops in nine VkV contexts. A variety of EPG indices measured: per cent…

Stability of the Medial Olivocochlear Reflex as Measured by Distortion Product Otoacoustic Emissions

ERIC Educational Resources Information Center

Mishra, Srikanta K.; Abdala, Carolina

2015-01-01

Purpose: The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)-based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Method: Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing…

Real-time feedback enhances forward propulsion during walking in old adults.

PubMed

Franz, Jason R; Maletis, Michela; Kram, Rodger

2014-01-01

Reduced propulsive function during the push-off phase of walking plays a central role in the deterioration of walking ability with age. We used real-time propulsive feedback to test the hypothesis that old adults have an underutilized propulsive reserve available during walking. 8 old adults (mean [SD], age: 72.1 [3.9] years) and 11 young adults (age: 21.0 [1.5] years) participated. For our primary aim, old subjects walked: 1) normally, 2) with visual feedback of their peak propulsive ground reaction forces, and 3) with visual feedback of their medial gastrocnemius electromyographic activity during push-off. We asked those subjects to match a target set to 20% and 40% greater propulsive force or push-off muscle activity than normal walking. We tested young subjects walking normally only to provide reference ground reaction force values. Walking normally, old adults exerted 12.5% smaller peak propulsive forces than young adults (P<0.01). However, old adults significantly increased their propulsive forces and push-off muscle activities when we provided propulsive feedback. Most notably, force feedback elicited propulsive forces that were equal to or 10.5% greater than those of young adults (+20% target, P=0.87; +40% target, P=0.02). With electromyographic feedback, old adults significantly increased their push-off muscle activities but without increasing their propulsive forces. Old adults with propulsive deficits have a considerable and underutilized propulsive reserve available during level walking. Further, real-time propulsive feedback represents a promising therapeutic strategy to improve the forward propulsion of old adults and thus maintain their walking ability and independence. © 2013.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

PubMed Central

Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

2016-01-01

Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

Development of preference for conspecific faces in human infants.

PubMed

Sanefuji, Wakako; Wada, Kazuko; Yamamoto, Tomoka; Mohri, Ikuko; Taniike, Masako

2014-04-01

Previous studies have proposed that humans may be born with mechanisms that attend to conspecifics. However, as previous studies have relied on stimuli featuring human adults, it remains unclear whether infants attend only to adult humans or to the entire human species. We found that 1-month-old infants (n = 23) were able to differentiate between human and monkey infants' faces; however, they exhibited no preference for human infants' faces over monkey infants' faces (n = 24) and discriminated individual differences only within the category of human infants' faces (n = 30). We successfully replicated previous findings that 1-month-old infants (n = 42) preferred adult humans, even adults of other races, to adult monkeys. Further, by 3 months of age, infants (n = 55) preferred human faces to monkey faces with both infant and adult stimuli. Human infants' spontaneous preference for conspecific faces appears to be initially limited to conspecific adults and afterward extended to conspecific infants. Future research should attempt to determine whether preference for human adults results from some innate tendency to attend to conspecific adults or from the impact of early experiences with adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer

PubMed Central

Wilber, Andrew; Hargrove, Phillip W.; Kim, Yoon-Sang; Riberdy, Janice M.; Sankaran, Vijay G.; Papanikolaou, Eleni; Georgomanoli, Maria; Anagnou, Nicholas P.; Orkin, Stuart H.; Nienhuis, Arthur W.

2011-01-01

β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α2β2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34+ cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34+ cells demonstrated levels of HbF up to 21% per vector copy. For β-thalassemic CD34+ cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with β-globin deficiency. PMID:21156846

The Effects of Acoustic Bandwidth on Simulated Bimodal Benefit in Children and Adults with Normal Hearing.

PubMed

Sheffield, Sterling W; Simha, Michelle; Jahn, Kelly N; Gifford, René H

2016-01-01

The primary purpose of this study was to examine the effect of acoustic bandwidth on bimodal benefit for speech recognition in normal-hearing children with a cochlear implant (CI) simulation in one ear and low-pass filtered stimuli in the contralateral ear. The effect of acoustic bandwidth on bimodal benefit in children was compared with the pattern of adults with normal hearing. Our hypothesis was that children would require a wider acoustic bandwidth than adults to (1) derive bimodal benefit, and (2) obtain asymptotic bimodal benefit. Nineteen children (6 to 12 years) and 10 adults with normal hearing participated in the study. Speech recognition was assessed via recorded sentences presented in a 20-talker babble. The AzBio female-talker sentences were used for the adults and the pediatric AzBio sentences (BabyBio) were used for the children. A CI simulation was presented to the right ear and low-pass filtered stimuli were presented to the left ear with the following cutoff frequencies: 250, 500, 750, 1000, and 1500 Hz. The primary findings were (1) adults achieved higher performance than children when presented with only low-pass filtered acoustic stimuli, (2) adults and children performed similarly in all the simulated CI and bimodal conditions, (3) children gained significant bimodal benefit with the addition of low-pass filtered speech at 250 Hz, and (4) unlike previous studies completed with adult bimodal patients, adults and children with normal hearing gained additional significant bimodal benefit with cutoff frequencies up to 1500 Hz with most of the additional benefit gained with energy below 750 Hz. Acoustic bandwidth effects on simulated bimodal benefit were similar in children and adults with normal hearing. Should the current results generalize to children with CIs, these results suggest pediatric CI recipients may derive significant benefit from minimal acoustic hearing (<250 Hz) in the nonimplanted ear and increasing benefit with broader bandwidth. Knowledge of the effect of acoustic bandwidth on bimodal benefit in children may help direct clinical decisions regarding a second CI, continued bimodal hearing, and even optimizing acoustic amplification for the nonimplanted ear.

Social-cognitive deficits in normal aging

PubMed Central

Moran, Joseph M.; Jolly, Eshin; Mitchell, Jason P.

2012-01-01

A sizeable number of studies have implicated the default network (e.g., medial prefrontal and parietal cortices) in tasks that require participants to infer the mental states of others—that is, to mentalize. Parallel research has demonstrated that default network function declines over the lifespan, suggesting that older adults may show impairments in social-cognitive tasks that require mentalizing. Older and younger human adults were scanned using functional magnetic resonance imaging (fMRI) while performing three different social-cognitive tasks. Across three mentalizing paradigms, younger and older adults viewed animated shapes in brief social vignettes, stories about a person's moral actions and false belief stories. Consistent with predictions, older adults responded less accurately to stories about others' false beliefs and made less use of actors' intentions to judge the moral permissibility of behavior. These impairments in performance during social-cognitive tasks were accompanied by age-related decreases across all three paradigms in the BOLD response of a single brain region—dorsomedial prefrontal cortex. These findings suggest specific, task-independent age-related deficits in mentalizing that are localizeable to changes in circumscribed subregions of the default network. PMID:22514317

Psychological adjustment in Spanish young adult domestic adoptees: Mental health and licit substance consumption.

PubMed

Sánchez-Sandoval, Yolanda; Melero, Sandra

2018-05-24

Although adoptive families have been shown to provide a protective context for human development, some adopted children and adolescents are at increased risk for psychological adjustment problems. On the other hand, little is known about psychological adjustment of young adult adoptees. The aim of this study is to analyze the mental health and legal substance consumption (tobacco and alcohol) of young adults (n = 134) who were domestically adopted by Spanish families. Young adults showed significantly worse scores on the Symptom Check-List-90-R (Derogatis, 1975) and also more substance use than did the Spanish general population, but fewer difficulties than did the clinical population. On the Global Severity Index (GSI), 65.7% of adoptees were within the normal range, 24.6% were at risk, and 9.7% were within the clinical range. Male adoptees scored higher than expected for the general population on all subscales, whereas female adoptees did not. Age at adoption was not found to have a significant impact on adjustment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Behavioral and biochemical adjustments of the zebrafish Danio rerio exposed to the β-blocker propranolol.

PubMed

Mitchell, Kimberly M; Moon, Thomas W

2016-09-01

Propranolol (PROP) is a β-blocker prescribed mainly to treat human cardiovascular diseases and as a result of its wide usage and persistence, it is reported in aquatic environments. This study examined whether PROP alters developmental patterns and catecholamine (CA)-regulated processes in the zebrafish (Danio rerio) and if exposure during early life alters the stress response and behaviors of adults. The calculated 48h larva LC50 was 21.6mg/L, well above reported environmental levels (0.01-0.59μg/L). Stressed and PROP-exposed adult zebrafish had reduced testosterone and estradiol levels and exhibited behaviors indicating less anxiety than control fish. Furthermore, adults previously PROP-exposed as embryos/larvae had decreased growth in terms of body length and mass. Finally, these adults showed increased cholesterol and a dose-dependent decrease in testosterone levels compared with unexposed zebrafish. Thus PROP-exposure of zebrafish embryos/larvae alters developmental patterns and CA-regulated processes that may affect normal behaviors and responses to stressors, and at least some of these changes persist in the adult zebrafish. Copyright © 2015 Elsevier Inc. All rights reserved.

NHLH2: At the intersection of obesity and fertility

PubMed Central

Good, Deborah J.; Braun, Thomas

2013-01-01

Nescient helix loop helix 2 (NSCL2/NHLH2) is a neuronal transcription factor originally thought to be involved in neuronal development and childhood neuroblastomas. Accumulating evidence has since identified roles for NHLH2 in adult phenotypes of obesity and fertility. Here, we summarize these findings, and attempt to link genotype with phenotype in mouse models and humans. In particular, NHLH2 (Nhlh2 in mice) is one of only two genes that are genetically linked to physical activity levels. Nhlh2 also controls obesity and fertility, with strong sexual dimorphism displayed for both phenotypes by Nhlh2 mutant animals. We propose that Nhlh2 might function as a molecular sensor in different adult hypothalamic neurons to regulate energy balance, leading to normal body weight and reproduction. PMID:23684566

Aerobic Exercise Effects on Ocular Dominance Plasticity with a Phase Combination Task in Human Adults

PubMed Central

Reynaud, Alexandre; Hess, Robert F.

2017-01-01

Several studies have shown that short-term monocular patching can induce ocular dominance plasticity in normal adults, in which the patched eye becomes stronger in binocular viewing. There is a recent study showing that exercise enhances this plasticity effect when assessed with binocular rivalry. We address one question, is this enhancement from exercise a general effect such that it is seen for measures of binocular processing other than that revealed using binocular rivalry? Using a binocular phase combination task in which we directly measure each eye's contribution to the binocularly fused percept, we show no additional effect of exercise after short-term monocular occlusion and argue that the enhancement of ocular dominance plasticity from exercise could not be demonstrated with our approach. PMID:28357142

DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.

PubMed

Fish, Trevor J; Benninghoff, Abby D

2017-11-01

Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo [def,p]chrysene (DBC) or benzo [a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array. Lung tumor incidence in 45-week old mice initiated with BaP was 32%, much lower than that of the DBC-exposed offspring at 96%. Also, male offspring appeared more susceptible to BaP as compared to females. Distinct patterns of DNA methylation were associated with non-exposed, normal adjacent and adenocarcinoma lung tissues, as determined by principal components, hierarchical clustering and gene ontology analyses. From these methylation profiles, a set of genes of interest was identified that includes potential important targets for epigenetic modification during the process of lung tumorigenesis in animals exposed to environmental PAHs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Audibility-based predictions of speech recognition for children and adults with normal hearing.

PubMed

McCreery, Ryan W; Stelmachowicz, Patricia G

2011-12-01

This study investigated the relationship between audibility and predictions of speech recognition for children and adults with normal hearing. The Speech Intelligibility Index (SII) is used to quantify the audibility of speech signals and can be applied to transfer functions to predict speech recognition scores. Although the SII is used clinically with children, relatively few studies have evaluated SII predictions of children's speech recognition directly. Children have required more audibility than adults to reach maximum levels of speech understanding in previous studies. Furthermore, children may require greater bandwidth than adults for optimal speech understanding, which could influence frequency-importance functions used to calculate the SII. Speech recognition was measured for 116 children and 19 adults with normal hearing. Stimulus bandwidth and background noise level were varied systematically in order to evaluate speech recognition as predicted by the SII and derive frequency-importance functions for children and adults. Results suggested that children required greater audibility to reach the same level of speech understanding as adults. However, differences in performance between adults and children did not vary across frequency bands. © 2011 Acoustical Society of America

Optical aberrations, retinal image quality and eye growth: Experimentation and modeling

NASA Astrophysics Data System (ADS)

Tian, Yibin

2007-12-01

Retinal image quality is important for normal eye growth. Optical aberrations are of interest for two reasons: first, they degrade retinal images; second, they might provide some cues to defocus. Higher than normal ocular aberrations have been previously associated with human myopia. However, these studies were cross-sectional in design, and only reported aberrations in terms of root mean square (RMS) errors of Zernike coefficients, a poor metric of optical quality. This dissertation presents results from investigations of ocular optical aberrations, retinal image quality and eye growth in chicks and humans. A number of techniques were utilized, including Shack-Hartmann aberrometry, high-frequency A-scan ultrasonography, ciliary nerve section (CNX), photorefractive keratectomy (PRK) as well as computer simulations and modeling. A technique to extract light scatter information from Shack-Hartmann images was also developed. The main findings of the dissertation are summarized below. In young chicks, most ocular aberrations decreased with growth in both normal and CNX eyes, and there were diurnal fluctuations in some aberrations. Modeling suggested active reduction in higher order aberrations (HOAs) during early development. Although CNX eyes manifested greater than normal HOAs, they showed near normal growth. Retinal image degradation varied greatly among individual eyes post-PRK in young chicks. Including light scatter information into analyses of retinal image quality better estimated the latter. Albino eyes showed more severe retinal image degradation than normal eyes, due to increased optical aberrations and light scatter, but their growth was similar to those of normal eyes, implying that they are relatively insensitive to retina image quality. Although the above results questioned the influence of optical aberrations on early ocular growth, some optical quality metrics, derived from optical aberrations data, could predict how much the eyes of young chicks subsequently elongated. The performance of some focus measures was very poor when non-defocus aberrations exceeded a certain level; presumably, these non-defocus aberrations might interfere with the eye's ability to interpret defocus. In anisomyopic human adults, more myopic eyes had larger anterior and vitreous chambers, greater astigmatism, and more positive spherical aberration. However, compared to isometropes, only interocular differences in spherical equivalent refractive errors were significantly increased.

Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

ERIC Educational Resources Information Center

Cobb, Kensi M.; Stuart, Andrew

2016-01-01

Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

Judgments of Emotion in Clear and Conversational Speech by Young Adults with Normal Hearing and Older Adults with Hearing Impairment

ERIC Educational Resources Information Center

Morgan, Shae D.; Ferguson, Sarah Hargus

2017-01-01

Purpose: In this study, we investigated the emotion perceived by young listeners with normal hearing (YNH listeners) and older adults with hearing impairment (OHI listeners) when listening to speech produced conversationally or in a clear speaking style. Method: The first experiment included 18 YNH listeners, and the second included 10 additional…

Motivation to Address Self-Reported Hearing Problems in Adults with Normal Hearing Thresholds

ERIC Educational Resources Information Center

Alicea, Carly C. M.; Doherty, Karen A.

2017-01-01

Purpose: The purpose of this study was to compare the motivation to change in relation to hearing problems in adults with normal hearing thresholds but who report hearing problems and that of adults with a mild-to-moderate sensorineural hearing loss. Factors related to their motivation were also assessed. Method: The motivation to change in…

The Influence of Averageness on Adults' Perceptions of Attractiveness: The Effect of Early Visual Deprivation.

PubMed

Vingilis-Jaremko, Larissa; Maurer, Daphne; Rhodes, Gillian; Jeffery, Linda

2016-08-03

Adults who missed early visual input because of congenital cataracts later have deficits in many aspects of face processing. Here we investigated whether they make normal judgments of facial attractiveness. In particular, we studied whether their perceptions are affected normally by a face's proximity to the population mean, as is true of typically developing adults, who find average faces to be more attractive than most other faces. We compared the judgments of facial attractiveness of 12 cataract-reversal patients to norms established from 36 adults with normal vision. Participants viewed pairs of adult male and adult female faces that had been transformed 50% toward and 50% away from their respective group averages, and selected which face was more attractive. Averageness influenced patients' judgments of attractiveness, but to a lesser extent than controls. The results suggest that cataract-reversal patients are able to develop a system for representing faces with a privileged position for an average face, consistent with evidence from identity aftereffects. However, early visual experience is necessary to set up the neural architecture necessary for averageness to influence perceptions of attractiveness with its normal potency. © The Author(s) 2016.

Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice

PubMed Central

Nakai, Nobuhiro; Nagano, Masatoshi; Saitow, Fumihito; Watanabe, Yasuhito; Kawamura, Yoshinobu; Kawamoto, Akiko; Tamada, Kota; Mizuma, Hiroshi; Onoe, Hirotaka; Watanabe, Yasuyoshi; Monai, Hiromu; Hirase, Hajime; Nakatani, Jin; Inagaki, Hirofumi; Kawada, Tomoyuki; Miyazaki, Taisuke; Watanabe, Masahiko; Sato, Yuka; Okabe, Shigeo; Kitamura, Kazuo; Kano, Masanobu; Hashimoto, Kouichi; Suzuki, Hidenori; Takumi, Toru

2017-01-01

Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms. PMID:28691086

Microbiomes of the normal middle ear and ears with chronic otitis media.

PubMed

Minami, Shujiro B; Mutai, Hideki; Suzuki, Tomoko; Horii, Arata; Oishi, Naoki; Wasano, Koichiro; Katsura, Motoyasu; Tanaka, Fujinobu; Takiguchi, Tetsuya; Fujii, Masato; Kaga, Kimitaka

2017-10-01

The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. Prospective multicenter cohort study. All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan). In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears. The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation. 2b. Laryngoscope, 127:E371-E377, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Reaffirming normal: the high risk of pathologizing healthy adults when interpreting the MMPI-2-RF.

PubMed

Odland, Anthony P; Lammy, Andrew B; Perle, Jonathan G; Martin, Phillip K; Grote, Christopher L

2015-01-01

Monte Carlo simulations were utilized to determine the proportion of the normal population expected to have scale elevations on the MMPI-2-RF when multiple scores are interpreted. Results showed that when all 40 MMPI-2-RF scales are simultaneously considered, approximately 70% of normal adults are likely to have at least one scale elevation at or above 65 T, and as many as 20% will have five or more elevated scales. When the Restructured Clinical (RC) Scales are under consideration, 34% of normal adults have at least one elevated score. Interpretation of the Specific Problem Scales and Personality Psychopathology Five Scales--Revised also yielded higher than expected rates of significant scores, with as many as one in four normal adults possibly being miscategorized as having features of a personality disorder by the latter scales. These findings are consistent with the growing literature on rates of apparently abnormal scores in the normal population due to multiple score interpretation. Findings are discussed in relation to clinical assessment, as well as in response to recent work suggesting that the MMPI-2-RF's multiscale composition does not contribute to high rates of elevated scores.

Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

PubMed

Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

2012-01-01

Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated growth of CRF.

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

PubMed Central

Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C.; Rasskin-Gutman, Diego

2015-01-01

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual’s survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts—their topological patterns relative to each other—using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures. PMID:26452269

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy.

PubMed

Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C; Rasskin-Gutman, Diego

2015-01-01

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures.

The ergonomic relevance of anthropometrical proportions. Part I: body length measures.

PubMed

Küchmeister, Gerd; Behrenbruch, Kay; Ursula, Pieper; Leyk, Dieter

2009-06-01

Anthropometrical findings about proportions of the human body have a long tradition; most of them, however, are rather theoretical. To improve this situation a pragmatic and applicable definition of proportions, normal as well as deviating, is needed. The purpose of this paper is to set up three proportion types for body length measures: leggy-normal-stocky, and their rate in the population of adults in an industrial society (Germany). Based on queries of an actual anthropometrical database metrical limits for these three types are suggested regarding their influence on the most important body length measures in standing and sitting positions. The number of cases with normal proportions is about 60%, leggy and stocky types both reaching up to 20%. The metrical limits are proposed in order to account for differences between those proportion types which are relevant for ergonomics. When solving complex multidimensional design tasks (e.g. workplaces, vehicle interior design, personal equipment) users of anthropometrical data who do not have the opportunity to work with multivariate databases need supplementary information about the proportions of the human body. For this reason such supplementary information concerning proportions is being given here by physiological anthropologists. The application of the findings presented is exemplified in scenarios of ergonomic relevance.

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

On the classification of normally distributed neurons: an application to human dentate nucleus.

PubMed

Ristanović, Dušan; Milošević, Nebojša T; Marić, Dušica L

2011-03-01

One of the major goals in cellular neurobiology is the meaningful cell classification. However, in cell classification there are many unresolved issues that need to be addressed. Neuronal classification usually starts with grouping cells into classes according to their main morphological features. If one tries to test quantitatively such a qualitative classification, a considerable overlap in cell types often appears. There is little published information on it. In order to remove the above-mentioned shortcoming, we undertook the present study with the aim to offer a novel method for solving the class overlapping problem. To illustrate our method, we analyzed a sample of 124 neurons from adult human dentate nucleus. Among them we qualitatively selected 55 neurons with small dendritic fields (the small neurons), and 69 asymmetrical neurons with large dendritic fields (the large neurons). We showed that these two samples are normally and independently distributed. By measuring the neuronal soma areas of both samples, we observed that the corresponding normal curves cut each other. We proved that the abscissa of the point of intersection of the curves could represent the boundary between the two adjacent overlapping neuronal classes, since the error done by such division is minimal. Statistical evaluation of the division was also performed.

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

PubMed

Javaid, J I; Notorangelo, M P; Pandey, S C; Reddy, P L; Pandey, G N; Davis, J M

1994-07-01

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Calorie restriction increases cigarette use in adult smokers.

PubMed

Cheskin, Lawrence J; Hess, Judith M; Henningfield, Jack; Gorelick, David A

2005-05-01

Cigarette smokers weigh less than nonsmokers, and smokers often gain weight when they quit. This is a major barrier to smoking cessation, especially among women. However, strict dieting is not recommended during smoking cessation out of concern that it might promote relapse. This concern derives, in part, from the observation that calorie restriction increases self-administration of drugs of abuse in animals. This relationship has never been experimentally demonstrated in humans. To evaluate whether calorie restriction increases cigarette smoking in humans. Seventeen (nine males, eight females) healthy, normal-weight smokers not attempting to quit were cycled in partially counterbalanced order, double-blind, through four diets-normal calorie (2,000-2,800 kcal/day), low calorie (700 kcal/day deficit), low-carbohydrate (CHO)/normal-calorie, and low-CHO/low-calorie-for 6 days per diet in an inpatient research ward. Smoking was assessed by cigarette counts, breath carbon monoxide (CO) levels, and cigarette craving. Compared with the normal-calorie diet, while on the low-calorie diet, subjects smoked 8% more cigarettes (P<0.02) and had 11% higher breath CO levels (P<0.01). The low-CHO/normal-calorie diet showed no significant effect on either variable, but there was a 15% increase in breath CO levels (P<0.05) on the low-CHO/low-calorie diet. There were no changes in self-reported cigarette craving or mood. Consistent with animal studies, moderate calorie restriction was associated with a small but statistically significant increase in cigarette smoking, with no independent effect of CHO deprivation. These findings suggest that dieting may increase smoking behavior and could impede smoking-cessation attempts.

How close should a student with unilateral hearing loss stay to a teacher in a noisy classroom?

PubMed

Noh, Heil; Park, Yong-Gyu

2012-06-01

To determine the optimal seating position in a noisy classroom for students with unilateral hearing loss (UHL) without any auditory rehabilitation as compared to normal-hearing adults and student peers. Speech discrimination scores (SDS) for babble noise at distances of 3, 4, 6, 8, and 10 m from a speaker were measured in a simulated classroom measuring 300 m3 (reverberation time = 0.43 s). Students with UHL (n = 25, 10-19 years old), normal-hearing students (n = 25), and normal-hearing adults (n = 25). The SDS for the normal-hearing adults at the 3, 4, 6, 8, and 10 m distances were 90.0±6.4%, 84.7±7.9%, 80.6±10.0%, 75.5±12.6%, and 68.8±13.0%, respectively. Those for the normal-hearing students were 90.1±6.2%, 78.1±9.4%, 66.4±10.7%, 61.8±11.2%, and 60.8±10.9%. Those for the UHL group were 81.7±9.0%, 70.2±12.4%, 62.1±17.2%, 52.4±17.1%, and 48.9±17.9%. The UHL group needed a seating position of 4.35 m to achieve an equivalent mean SDS as those for normal-hearing adults seated at 10 m. Likewise, the UHL group needed to be seated at 6.27 m to have an equivalent SDS as the normal-hearing students seated at 10 m. Students with UHL in noisy classrooms require seating ranging from 4.35 m to no further than 6.27 m away from a teacher to obtain a SDS comparable to normal hearing adults and student peers.

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

PubMed

Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

2014-02-01

Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

The dog factor in brown dog tick Rhipicephalus sanguineus (Acari: Ixodidae) infestations in and near human dwellings.

PubMed

Uspensky, Igor; Ioffe-Uspensky, Inna

2002-06-01

Three cases of the tick Rhipicephalus sanguineus infiltration in or near human dwellings caused by dogs, and their influence on epidemiological features of human habitats have been investigated. (a) The observation of dogs kept indoors proved that single tick females could engorge and oviposit inside apartments followed by the development of subadults. (b) Abundant micropopulations of ticks were formed in small yards or gardens near the dwellings where dogs lived in kennels. (c) A huge field population of R. sanguineus was observed on a farm where watchdogs constantly patrolled along the farm perimeter. Tick abundance near the kennels and in the permanent resting sites of the dogs reached more than 30 adults per 10 min of collecting, while the number of adults on a dog reached 100. Unfed adult females under conditions of constant dog availability had a larger scutal index than females collected in the control field site. On the basis of circumstantial evidence it is possible to conclude that under the above conditions tick development may change from the normal 3-host cycle to a 2-host cycle. Ticks in the field had one complete generation per year. Ticks on the farm, as well as ticks in kennels, developed faster and a significant part of their population had two complete generations per year. R. sanguineus is the main vector and reservoir of a pathogen from the Rickettsia conorii complex, the causative agent of Israeli tick typhus. The described conglomerations of R. sanguineus create a great risk to humans who can be attacked by infected ticks in and around their homes, even in large towns. Such a feature of the tick life history most likely exists not only in Israel but in other countries as well.

Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

PubMed

Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

2018-02-01

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Autologous blood cell therapies from pluripotent stem cells

PubMed Central

Lengerke, Claudia; Daley, George Q.

2010-01-01

Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

Acute human herpes virus 7 (HHV-7) encephalitis in an immunocompetent adult patient: a case report and review of literature.

PubMed

Riva, Nicoletta; Franconi, Iacopo; Meschiari, Marianna; Franceschini, Erica; Puzzolante, Cinzia; Cuomo, Gianluca; Bianchi, Alessandro; Cavalleri, Francesca; Genovese, Maurilio; Mussini, Cristina

2017-06-01

We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.

Distribution of apolipoprotein E alleles in a Scottish healthy newborn population.

PubMed

Becher, J-C; Bell, J E; McIntosh, N; Keeling, J W

2005-01-01

The different alleles of the human apolipoprotein E polymorphism, ApoE epsilon2, epsilon3, epsilon4, have important implications for systemic lipid metabolism, immunological function and for the brain in maintenance and in response to injury. Few studies have focussed on their role in early life. The ApoE alleles and genotypes were ascertained in the cord blood of 371 full-term and normal Scottish newborn infants using PCR methodology. The results were compared to previously published data for Scottish adults in late middle age. There was a marginally significant over-representation of epsilon4 and under-representation of epsilon3 alleles in healthy infants as compared with adults. Inspection of the individual genotypes confirms the over-representation of ApoE 4/4 and 2/4 with a reduction in ApoE 2/3 and 3/3 when compared with Scottish adults. Although these results may have occurred by chance, the ApoE epsilon4 allele may confer an increased risk of premature death. Copyright (c) 2005 S. Karger AG, Basel.

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

PubMed Central

Wharton, J; Anderson, R H; Springall, D; Power, R F; Rose, M; Smith, A; Espejo, R; Khaghani, A; Wallwork, J; Yacoub, M H

1988-01-01

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:2973340

Cloning and expression of sheep DNA methyltransferase 1 and its development-specific isoform.

PubMed

Taylor, Jane; Moore, Hannah; Beaujean, Nathalie; Gardner, John; Wilmut, Ian; Meehan, Richard; Young, Lorraine

2009-05-01

Unlike the mouse embryo, where loss of DNA methylation in the embryonic nucleus leaves cleavage stage embryos globally hypomethylated, sheep preimplantation embryos retain high levels of methylation until the blastocyst stage. We have cloned and sequenced sheep Dnmt1 and found it to be highly conserved with both the human and mouse homologues. Furthermore, we observed that the transcript normally expressed in adult somatic tissues is highly abundant in sheep oocytes. Throughout sheep preimplantation development the protein is retained in the cytoplasm whereas Dnmt1 transcript production declines after the embryonic genome activation at the 8-16 cell stage. Attempts to clone oocyte-specific 5' regions of Dnmt1, known to be present in the mouse and human gene, were unsuccessful. However, a novel ovine Dnmt1 exon, theoretically encoding 13 amino acids, was found to be expressed in sheep oocytes, preimplantation embryos and early fetal lineages, but not in the adult tissue. RNAi-mediated knockdown of this novel transcript resulted in embryonic developmental arrest at the late morula stage, suggesting an essential role for this isoform in sheep blastocyst formation. (c) 2008 Wiley-Liss, Inc.

Empty Sella Syndrome

MedlinePlus

... hormone prolactin, which can interfere with the normal function of the testicles and ovaries. Primary ESS is most common in adults and women, ... hormone prolactin, which can interfere with the normal function of the testicles and ovaries. Primary ESS is most common in adults and women, ...

A Novel Marker for Purkinje Cells, Ribosomal Protein MPS1/S27: Expression of MPS1 in Human Cerebellum.

PubMed

Fernandez-Pol, J Alberto

2016-01-01

The ribosomal protein metallopanstimulin-1 (MPS1/S27) serves critical survival purposes in cell division, in normal and cancerous cells; for this reason, selective pressures of evolution have conserved the DNA sequences encoding MPS1/S27 in Archaea and Eukariotic cells. The expression of MPS1/S27 protein in human adult cerebellum has not been established. The presence of MPS1/S27, was screened in paraffin-embedded human adult brain specimens processed for tissue inmunohistochemistry. Affinity-purified specific antibodies were directed against the N-terminus of MPS1. The antibodies to MPS1 detected Purkinje cells (PC) and their dendrites. In PC, MPS1 antigen-positive staining was found in: the nucleolus, which was strongly stained; ribosomes attached to the external nuclear membrane; cytoplasm of PC, with strong staining in a punctuate fashion; the soma-attached large dendrite trunks of PC, which were MPS1 antigen-positive; and the granular cell layer, where cellular staining in a few cells that appeared to resemble smaller PC was observed. Since MPS1 is involved in cell division, DNA repair, and ribosomal biogenesis, it may be a useful antigen for studying processes such as protein synthesis, oncogenesis, regeneration, aging, and perhaps diseases of the human cerebellum. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Pasteurella multocida meningitis in an adult: case report.

PubMed

Armstrong, G R; Sen, R A; Wilkinson, J

2000-03-01

Pasteurella multocida is known to form part of the normal flora in the nasopharynx or gastrointestinal tract in many domestic and wild animals. Most human P multocida infections are soft tissue infections caused by dog or cat bites. Less commonly this bacterium is associated with infections affecting other organ systems of man. A case of fatal P multocida meningitis discovered at the necropsy of a 52 year old man is described. P multocida is an unusual causative agent of meningitis which tends to affect those at the extremes of age.

Age and Gender Effects on Wideband Absorbance in Adults With Normal Outer and Middle Ear Function.

PubMed

Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

2015-08-01

This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance (EA) data were collected at 30 frequencies using a prototype commercial instrument developed by Interacoustics. Results showed that the young adult group had significantly lower EA (between 400 and 560 Hz) than the middle-aged group. However, the middle-aged group showed significantly lower EA (between 2240 and 5040 Hz) than the young adult group. In addition, the older adult group had significantly lower EA than the young adult group (between 2520 and 5040 Hz). No significant difference in EA was found at any frequency between middle-aged and older adults. Across age groups, gender differences were found with men having significantly higher EA values than women at lower frequencies, whereas women had significantly higher EA at higher frequencies. This study provides evidence of the influence of gender and age on EA in adults with normal outer and middle ear function. These findings support the importance of establishing age- and gender-specific EA norms for the adult population.

Normal anatomy and histology of the adult zebrafish.

PubMed

Menke, Aswin L; Spitsbergen, Jan M; Wolterbeek, Andre P M; Woutersen, Ruud A

2011-08-01

The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.

Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

PubMed

Colas, Damien; Chuluun, Bayarsaikhan; Garner, Craig C; Heller, H Craig

2017-04-01

Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABA A receptor (GABA A R) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABA A R antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS. Copyright © 2017. Published by Elsevier Inc.

Evaluation of [18F]Mefway biodistribution and dosimetry based on whole-body PET imaging of mice.

PubMed

Constantinescu, Cristian C; Sevrioukov, Evgueni; Garcia, Adriana; Pan, Min-Liang; Mukherjee, Jogeshwar

2013-04-01

[(18)F]Mefway is a novel radiotracer specific to the serotonin 5-HT1A receptor class. In preparation for using this tracer in humans, we have performed whole-body PET studies in mice to evaluate the biodistribution and dosimetry of [(18)F]Mefway. Six mice (three females and three males) received IV injections of [(18)F]Mefway and were scanned for 2 h in an Inveon-dedicated PET scanner. Each animal also received a high-resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest on the following organs: the brain, large intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus, gallbladder, uterus, and urinary bladder. All organ time-activity curves without decay correction were normalized to the injected activity. The area under the normalized curves was then used to compute the residence times in each organ. Data were analyzed using PMOD and Matlab software. The absorbed doses in mouse organs were computed using the RAdiation Dose Assessment Resource animal models for dose assessment. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both female and male phantoms. The highest mouse residence times were found in the liver, urinary bladder, and kidneys. The largest doses in mice were found in the urinary bladder (critical organ), kidney, and liver for both females and males, indicating primary elimination via urinary system. The projected human effective doses were 1.21E - 02 mSv/MBq for the adult female model and 1.13E - 02 mSv/MBq for the adult male model. The estimated human biodistribution of [(18)F]Mefway was similar to that of [(11)C]WAY 100,635, a 5-HT1A tracer for which dosimetry has been evaluated in humans. The elimination of radiotracer was primarily via the kidney and urinary bladder with the urinary bladder being the critical organ. Whole-body mouse imaging can be used as a preclinical tool to provide initial estimates of the absorbed doses of [(18)F]Mefway in humans.

Region-specific reduction of auditory sensory gating in older adults.

PubMed

Cheng, Chia-Hsiung; Baillet, Sylvain; Lin, Yung-Yang

2015-12-01

Aging has been associated with declines in sensory-perceptual processes. Sensory gating (SG), or repetition suppression, refers to the attenuation of neural activity in response to a second stimulus and is considered to be an automatic process to inhibit redundant sensory inputs. It is controversial whether SG deficits, as tested with an auditory paired-stimulus protocol, accompany normal aging in humans. To reconcile the debates arising from event-related potential studies, we recorded auditory neuromagnetic reactivity in 20 young and 19 elderly adult men and determined the neural activation by using minimum-norm estimate (MNE) source modeling. SG of M100 was calculated by the ratio of the response to the second stimulus over that to the first stimulus. MNE results revealed that fronto-temporo-parietal networks were implicated in the M100 SG. Compared to the younger participants, the elderly showed selectively increased SG ratios in the anterior superior temporal gyrus, anterior middle temporal gyrus, temporal pole and orbitofrontal cortex, suggesting an insufficient age-related gating to repetitive auditory stimulation. These findings also highlight the loss of frontal inhibition of the auditory cortex in normal aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus

PubMed Central

di Pietro, Massimiliano; Lao-Sirieix, Pierre; Boyle, Shelagh; Cassidy, Andy; Castillo, Dani; Saadi, Amel; Eskeland, Ragnhild; Fitzgerald, Rebecca C.

2012-01-01

Barrett esophagus (BE) is a human metaplastic condition that is the only known precursor to esophageal adenocarcinoma. BE is characterized by a posterior intestinal-like phenotype in an anterior organ and therefore it is reminiscent of homeotic transformations, which can occur in transgenic animal models during embryonic development as a consequence of mutations in HOX genes. In humans, acquired deregulation of HOX genes during adulthood has been linked to carcinogenesis; however, little is known about their role in the pathogenesis of premalignant conditions. We hypothesized that HOX genes may be implicated in the development of BE. We demonstrated that three midcluster HOXB genes (HOXB5, HOXB6, and HOXB7) are overexpressed in BE, compared with the anatomically adjacent normal esophagus and gastric cardia. The midcluster HOXB gene signature in BE is identical to that seen in normal colonic epithelium. Ectopic expression of these three genes in normal squamous esophageal cells in vitro induces markers of intestinal differentiation, such as KRT20, MUC2, and VILLIN. In BE-associated adenocarcinoma, the activation midcluster HOXB gene is associated with loss of H3K27me3 and gain of AcH3, compared with normal esophagus. These changes in histone posttranslational modifications correlate with specific chromatin decompaction at the HOXB locus. We suggest that epigenetically regulated alterations of HOX gene expression can trigger changes in the transcriptional program of adult esophageal cells, with implications for the early stages of carcinogenesis. PMID:22603795

Alterations in gene expression and DNA methylation during murine and human lung alveolar septation.

PubMed

Cuna, Alain; Halloran, Brian; Faye-Petersen, Ona; Kelly, David; Crossman, David K; Cui, Xiangqin; Pandit, Kusum; Kaminski, Naftali; Bhattacharya, Soumyaroop; Ahmad, Ausaf; Mariani, Thomas J; Ambalavanan, Namasivayam

2015-07-01

DNA methylation, a major epigenetic mechanism, may regulate coordinated expression of multiple genes at specific time points during alveolar septation in lung development. The objective of this study was to identify genes regulated by methylation during normal septation in mice and during disordered septation in bronchopulmonary dysplasia. In mice, newborn lungs (preseptation) and adult lungs (postseptation) were evaluated by microarray analysis of gene expression and immunoprecipitation of methylated DNA followed by sequencing (MeDIP-Seq). In humans, microarray gene expression data were integrated with genome-wide DNA methylation data from bronchopulmonary dysplasia versus preterm and term lung. Genes with reciprocal changes in expression and methylation, suggesting regulation by DNA methylation, were identified. In mice, 95 genes with inverse correlation between expression and methylation during normal septation were identified. In addition to genes known to be important in lung development (Wnt signaling, Angpt2, Sox9, etc.) and its extracellular matrix (Tnc, Eln, etc.), genes involved with immune and antioxidant defense (Stat4, Sod3, Prdx6, etc.) were also observed. In humans, 23 genes were differentially methylated with reciprocal changes in expression in bronchopulmonary dysplasia compared with preterm or term lung. Genes of interest included those involved with detoxifying enzymes (Gstm3) and transforming growth factor-β signaling (bone morphogenetic protein 7 [Bmp7]). In terms of overlap, 20 genes and three pathways methylated during mouse lung development also demonstrated changes in methylation between preterm and term human lung. Changes in methylation correspond to altered expression of a number of genes associated with lung development, suggesting that DNA methylation of these genes may regulate normal and abnormal alveolar septation.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, Shawn M.; Lockhart, Samuel N.; Baker, Suzanne L.

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore » associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.« less

Increased height standard deviation scores in response to growth hormone therapy to near-adult height in older children with delayed skeletal maturation: results from the ANSWER Program.

PubMed

Ross, Judith L; Lee, Peter A; Gut, Robert; Germak, John

2015-01-01

A primary goal of recombinant human growth hormone therapy (GHT) in children is attaining normal adult height. In this study, children with growth hormone deficiency (GHD) (including isolated idiopathic growth hormone deficiency [IGHD] and multiple pituitary hormone deficiency [MPHD]), idiopathic short stature (ISS), and Turner syndrome (TS) were evaluated for near-adult height (NAH) and percent achieving NAH within the normal range after approximately 4 years of GHT. Data from the American Norditropin® Web-Enabled Research (ANSWER) Program were analyzed for NAH from age at treatment start (ATS) (i.e., referral age as defined by age at enrollment in the study) to last clinic visit using one of the following two criteria: 1) age ≥18 years, or 2) if male: ≥16 years and height velocity (HV) <2 cm/year; if female: ≥15 years and HV <2 cm/year. All patients had a baseline height standard deviation score (HSDS) ≤ -2, and either GHD (n = 201), ISS (n = 19), or TS (n = 41). The main outcome measures included HSDS and corrected HSDS (HSDS-target HSDS) in response to GH treatment, and correlation of ATS with NAH HSDS. Mean (± SD) chronological and bone ages at baseline were 14.0 ± 2.1 years and 11.7 ± 2.0 years, respectively, and mean GHT duration was 4.0 ± 1.6 years. Mean HSDS (baseline to NAH; GHD: -2.7 to -1.0; ISS: -2.8 to -1.4; TS: -3.0 to -1.8) and mean corrected HSDS (baseline to NAH; GHD: -2.1 to -0.3; ISS: -2.1 to -0.6; TS: -1.8 to -0.6) increased across diagnostic indications. Percentages of patients reaching near-adult HSDS > -2 were GHD: 87.6%; ISS: 78.9%; TS: 65.8%. Significant negative correlations were found between ATS and NAH HSDS when analyzed by sex. Despite a relatively advanced childhood age, the majority of GH-treated patients attained mean near-adult HSDS within the normal range (HSDS > -2). Negative correlations of ATS with near-adult HSDS indicate that an earlier age at treatment start would likely have resulted in greater adult height achieved in both male and female patients.

Metabolic brain networks in aging and preclinical Alzheimer's disease.

PubMed

Arnemann, Katelyn L; Stöber, Franziska; Narayan, Sharada; Rabinovici, Gil D; Jagust, William J

2018-01-01

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults.

PubMed

Johnson, W; Stovitz, S D; Choh, A C; Czerwinski, S A; Towne, B; Demerath, E W

2012-04-01

To estimate differences in skeletal maturity and stature from birth to age 18 years between individuals who are overweight vs normal weight in young adulthood. Weight, length and height, and relative skeletal age (skeletal-chronological age) were assessed annually from birth to age 18 years in 521 subjects (255 women) in the Fels Longitudinal Study who were overweight or obese (body mass index (BMI) >25 kg m(-2), n=131) or normal weight (n=390) in young adulthood (18-30 years). Generalized estimating equations were used to test for skeletal maturity and stature differences by young adult BMI status. Differences in height increased during puberty, being significant for girls at ages 10 to 12 years, and for boys at ages 11 to 13 years (P-values<0.001), with overweight or obese adults being ∼3 cm taller at those ages than normal weight adults. These differences then diminished so that by age 18 years, overweight or obese adults were not significantly different in stature to their normal weight peers. Differences in skeletal maturity were similar, but more pervasive; overweight or obese adults were more skeletally advanced throughout childhood. Skeletal maturity differences peaked at chronological age 12 in boys and 14 in girls (P-values<0.001), with overweight or obese adults being ∼1 year more advanced than normal weight adults. This descriptive study is the first to track advanced skeletal maturity and linear growth acceleration throughout infancy, childhood and adolescence in individuals who become overweight, showing that differences occur primarily around the time of the pubertal growth spurt. Increased BMI in children on a path to becoming overweight adults precedes an advancement in skeletal development and subsequently tall stature during puberty. Further work is required to assess the predictive value of accelerated pubertal height growth for assessing obesity risk in a variety of populations.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice.

PubMed

Seney, Marianne L; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-05-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice

PubMed Central

Seney, Marianne L.; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-01-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. PMID:22394611

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes.

PubMed

Köhler, Eleonore S; Sankaranarayanan, Selvakumari; van Ginneken, Christa J; van Dijk, Paul; Vermeulen, Jacqueline L M; Ruijter, Jan M; Lamers, Wouter H; Bruder, Elisabeth

2008-11-10

Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS), ornithine aminotransferase (OAT), argininosuccinate synthetase (ASS), arginase-1 (ARG1), arginase-2 (ARG2), and nitric-oxide synthase (NOS) were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

PubMed Central

Köhler, Eleonore S; Sankaranarayanan, Selvakumari; van Ginneken, Christa J; van Dijk, Paul; Vermeulen, Jacqueline LM; Ruijter, Jan M; Lamers, Wouter H; Bruder, Elisabeth

2008-01-01

Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS), ornithine aminotransferase (OAT), argininosuccinate synthetase (ASS), arginase-1 (ARG1), arginase-2 (ARG2), and nitric-oxide synthase (NOS) were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants. PMID:19000307

Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

PubMed

Griffiths, R R; Chausmer, A L

2000-11-01

Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

A pediatric brain structure atlas from T1-weighted MR images

NASA Astrophysics Data System (ADS)

Shan, Zuyao Y.; Parra, Carlos; Ji, Qing; Ogg, Robert J.; Zhang, Yong; Laningham, Fred H.; Reddick, Wilburn E.

2006-03-01

In this paper, we have developed a digital atlas of the pediatric human brain. Human brain atlases, used to visualize spatially complex structures of the brain, are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1 weighted MR data set of a 9 year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. Higher curvature surfaces were simplified with more reference points; lower curvature surfaces, with fewer. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/BrainAtlas) can be used to plan treatment, to conduct knowledge and modeldriven segmentation, and to analyze the shapes of brain structures in pediatric patients.

Validation of the ADAMO Care Watch for step counting in older adults.

PubMed

Magistro, Daniele; Brustio, Paolo Riccardo; Ivaldi, Marco; Esliger, Dale Winfield; Zecca, Massimiliano; Rainoldi, Alberto; Boccia, Gennaro

2018-01-01

Accurate measurement devices are required to objectively quantify physical activity. Wearable activity monitors, such as pedometers, may serve as affordable and feasible instruments for measuring physical activity levels in older adults during their normal activities of daily living. Currently few available accelerometer-based steps counting devices have been shown to be accurate at slow walking speeds, therefore there is still lacking appropriate devices tailored for slow speed ambulation, typical of older adults. This study aimed to assess the validity of step counting using the pedometer function of the ADAMO Care Watch, containing an embedded algorithm for measuring physical activity in older adults. Twenty older adults aged ≥ 65 years (mean ± SD, 75±7 years; range, 68-91) and 20 young adults (25±5 years, range 20-40), wore a care watch on each wrist and performed a number of randomly ordered tasks: walking at slow, normal and fast self-paced speeds; a Timed Up and Go test (TUG); a step test and ascending/descending stairs. The criterion measure was the actual number of steps observed, counted with a manual tally counter. Absolute percentage error scores, Intraclass Correlation Coefficients (ICC), and Bland-Altman plots were used to assess validity. ADAMO Care Watch demonstrated high validity during slow and normal speeds (range 0.5-1.5 m/s) showing an absolute error from 1.3% to 1.9% in the older adult group and from 0.7% to 2.7% in the young adult group. The percentage error for the 30-metre walking tasks increased with faster pace in both young adult (17%) and older adult groups (6%). In the TUG test, there was less error in the steps recorded for older adults (1.3% to 2.2%) than the young adults (6.6% to 7.2%). For the total sample, the ICCs for the ADAMO Care Watch for the 30-metre walking tasks at each speed and for the TUG test were ranged between 0.931 to 0.985. These findings provide evidence that the ADAMO Care Watch demonstrated highly accurate measurements of the steps count in all activities, particularly walking at normal and slow speeds. Therefore, these data support the inclusion of the ADAMO Care Watch in clinical applications for measuring the number of steps taken by older adults at normal, slow walking speeds.

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

PubMed Central

Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

2013-01-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau

PubMed Central

Klein, Ronald L.; Lin, Wen-Lang; Dickson, Dennis W.; Lewis, Jada; Hutton, Michael; Duff, Karen; Meyer, Edwin M.; King, Michael A.

2004-01-01

Neurofibrillary pathology was produced in the brains of adult rats after localized gene transfer of human tau carrying the P301L mutation, which is associated with frontotemporal dementia with parkinsonism. Within 1 month of in situ transfection of the basal forebrain region of normal rats, tau-immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions had features of neurofibrillary tangles and tau immunoreactivity at light and electron microscopic levels. In addition to neurofibrillary tangles, other tau pathology, including pretangles and neuropil threads, was abundant and widespread. Tau gene transfer to the hippocampal region of amyloid-depositing transgenic mice produced pretangles and threads, as well as intensely tau-immunoreactive neurites in amyloid plaques. The ability to produce neurofibrillary pathology in adult rodents makes this a useful method to study tau-related neurodegeneration. PMID:14695347

A basal stem cell signature identifies aggressive prostate cancer phenotypes

PubMed Central

Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

Amnion-derived stem cells: in quest of clinical applications

PubMed Central

2011-01-01

In the promising field of regenerative medicine, human perinatal stem cells are of great interest as potential stem cells with clinical applications. Perinatal stem cells could be isolated from normally discarded human placentae, which are an ideal cell source in terms of availability, the fewer number of ethical concerns, less DNA damage, and so on. Numerous studies have demonstrated that some of the placenta-derived cells possess stem cell characteristics like pluripotent differentiation ability, particularly in amniotic epithelial (AE) cells. Term human amniotic epithelium contains a relatively large number of stem cell marker-positive cells as an adult stem cell source. In this review, we introduce a model theory of why so many AE cells possess stem cell characteristics. We also describe previous work concerning the therapeutic applications and discuss the pluripotency of the AE cells and potential pitfalls for amnion-derived stem cell research. PMID:21596003

Lag threads organize the brain’s intrinsic activity

PubMed Central

Mitra, Anish; Snyder, Abraham Z.; Blazey, Tyler; Raichle, Marcus E.

2015-01-01

It has been widely reported that intrinsic brain activity, in a variety of animals including humans, is spatiotemporally structured. Specifically, propagated slow activity has been repeatedly demonstrated in animals. In human resting-state fMRI, spontaneous activity has been understood predominantly in terms of zero-lag temporal synchrony within widely distributed functional systems (resting-state networks). Here, we use resting-state fMRI from 1,376 normal, young adults to demonstrate that multiple, highly reproducible, temporal sequences of propagated activity, which we term “lag threads,” are present in the brain. Moreover, this propagated activity is largely unidirectional within conventionally understood resting-state networks. Modeling experiments show that resting-state networks naturally emerge as a consequence of shared patterns of propagation. An implication of these results is that common physiologic mechanisms may underlie spontaneous activity as imaged with fMRI in humans and slowly propagated activity as studied in animals. PMID:25825720

Report of two paediatric cases of central line infections caused by species of the genus Kocuria

PubMed Central

Hamula, Camille L.; Dingle, Tanis C.

2016-01-01

Introduction: Species of the genus Kocuria are Gram-positive cocci of the family Micrococcacceae that are ubiquitous in the environment and part of the normal skin and oral flora in humans. A paucity of cases have been reported of Kocuria as human pathogens and there are currently no evidence-based guidelines for managing these uncommon infections. Case presentation: We present two paediatric cases of central line infections with species of the genus Kocuria that required line removal despite antimicrobial therapy. Conclusion: Species of the genus Kocuria are uncommon human pathogens that have rarely been reported to cause opportunistic infections in both adult and paediatric populations. The cases presented here add to the growing body of literature documenting the pathogenicity of these organisms and the possible need for line removal to achieve clinical cure in central line-associated bacteraemia caused by species of the genus Kocuria. PMID:28348760

The efficacy of ultrasound treatment as a reversible male contraceptive in the rhesus monkey.

PubMed

VandeVoort, Catherine A; Tollner, Theodore L

2012-09-12

The use of therapeutic ultrasound as a contraceptive approach has involved nonhuman primates as well as rats and dogs. The current study was undertaken to determine whether this treatment could be a method for reversible contraception, using a model with testes size similar to adult humans. Two methods of ultrasound exposure were used, either the transducer probe at the bottom of a cup filled with saline (Cup) or direct application to the surface of the scrotum (Direct). Four adult rhesus (Macaca mulatta) males with normal semen parameters were treated with therapeutic ultrasound at 2.5 W/cm(2) for 30 min. Treatment was given 3 times, one every other day on a Monday-Wednesday-Friday schedule. For each male, semen quality was evaluated a minimum of three times over several months prior to ultrasound exposure and weekly for two months following ultrasound treatment. Semen samples from all males, regardless of exposure method, exhibited a decrease in the percentage of motile sperm following ultrasound treatment. There was an average reduction in motility of 40% the week following treatment. Similarly, curvilinear velocity and the percentage of sperm with a normally shaped flagellum were also reduced in all males following ultrasound treatment. A significant reduction in the total number of sperm in an ejaculate (total sperm count) was only observed in males that received ultrasound via the cup method. Following treatment via the cup method, males exhibited up to a 91.7% decrease in average total sperm count (n = 2). Sperm count did not approach pre-treatment levels until 8 weeks following ultrasound exposure. The sustained reduction in sperm count, percent motility, normal morphology, and sperm vigor with the cup exposure method provides proof of principle that testicular treatment with ultrasound can be an effective contraceptive approach in humans.

Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats.

PubMed

Wainstein, Julio; Ganz, Tali; Boaz, Mona; Bar Dayan, Yosefa; Dolev, Eran; Kerem, Zohar; Madar, Zecharia

2012-07-01

Olive tree (Olea europaea L.) leaves have been widely used in traditional remedies in European and Mediterranean countries as extracts, herbal teas, and powder. They contain several potentially bioactive compounds that may have hypoglycemic properties. To examine the efficacy of 500 mg oral olive leaf extract taken once daily in tablet form versus matching placebo in improving glucose homeostasis in adults with type 2 diabetes (T2DM). In this controlled clinical trial, 79 adults with T2DM were randomized to treatment with 500 mg olive leaf extract tablet taken orally once daily or matching placebo. The study duration was 14 weeks. Measures of glucose homeostasis including Hba1c and plasma insulin were measured and compared by treatment assignment. In a series of animal models, normal, streptozotocin (STZ) diabetic, and sand rats were used in the inverted sac model to determine the mechanism through which olive leaf extract affected starch digestion and absorption. In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group. In the animal models, normal and STZ diabetic rats exhibited significantly reduced starch digestion and absorption after treatment with olive leaf extract compared with intestine without olive leaf treatment. Reduced digestion and absorption was observed in both the mucosal and serosal sides of the intestine. Though reduced, the decline in starch digestion and absorption did not reach statistical significance in the sand rats. Olive leaf extract is associated with improved glucose homeostasis in humans. Animal models indicate that this may be facilitated through the reduction of starch digestion and absorption. Olive leaf extract may represent an effective adjunct therapy that normalizes glucose homeostasis in individuals with diabetes.

1H and 31P nuclear magnetic resonance investigation of the interaction between 2,3-diphosphoglycerate and human normal adult hemoglobin.

PubMed

Russu, I M; Wu, S S; Bupp, K A; Ho, N T; Ho, C

1990-04-17

High-resolution 1H and 31P nuclear magnetic resonance spectroscopy has been used to investigate the binding of 2,3-diphosphoglycerate to human normal adult hemoglobin and the molecular interactions involved in the allosteric effect of the 2,3-diphosphoglycerate molecule on hemoglobin. Individual hydrogen ion NMR titration curves have been obtained for 22-26 histidyl residues of hemoglobin and for each phosphate group of 2,3-diphosphoglycerate with hemoglobin in both the deoxy and carbonmonoxy forms. The results indicate that 2,3-diphosphoglycerate binds to deoxyhemoglobin at the central cavity between the two beta chains and the binding involves the beta 2-histidyl residues. Moreover, the results suggest that the binding site of 2,3-diphosphoglycerate to carbonmonoxyhemoglobin contains the same (or at least some of the same) amino acid residues responsible for binding in the deoxy form. As a result of the specific interactions with 2,3-diphosphoglycerate, the beta 2-histidyl residues make a significant contribution to the alkaline Bohr effect under these experimental conditions (up to 0.5 proton/Hb tetramer). 2,3-Diphosphoglycerate also affects the individual hydrogen ion equilibria of several histidyl residues located away from the binding site on the surface of the hemoglobin molecule, and, possibly, in the heme pockets. These results give the first experimental demonstration that long-range electrostatic and/or conformational effects of the binding could play an important role in the allosteric effect of 2,3-diphosphoglycerate on hemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)

Subsystems of sensory attention for skilled reaching: vision for transport and pre-shaping and somatosensation for grasping, withdrawal and release.

PubMed

Sacrey, Lori-Ann R; Whishaw, Ian Q

2012-06-01

Skilled reaching is a forelimb movement in which a subject reaches for a piece of food that is placed in the mouth for eating. It is a natural movement used by many animal species and is a routine, daily activity for humans. Its prominent features include transport of the hand to a target, shaping the digits in preparation for grasping, grasping, and withdrawal of the hand to place the food in the mouth. Studies on normal human adults show that skilled reaching is mediated by at least two sensory attention processes. Hand transport to the target and hand shaping are temporally coupled with visual fixation on the target. Grasping, withdrawal, and placing the food into the mouth are associated with visual disengagement and somatosensory guidance. Studies on nonhuman animal species illustrate that shared visual and somatosensory attention likely evolved in the primate lineage. Studies on developing infants illustrate that shared attention requires both experience and maturation. Studies on subjects with Parkinson's disease and Huntington's disease illustrate that decomposition of shared attention also features compensatory visual guidance. The evolutionary, developmental, and neural control of skilled reaching suggests that associative learning processes are importantly related to normal adult attention sharing and so can be used in remediation. The economical use of sensory attention in the different phases of skilled reaching ensures efficiency in eating, reduces sensory interference between sensory reference frames, and provides efficient neural control of the advance and withdrawal components of skilled reaching movements. Copyright © 2011 Elsevier B.V. All rights reserved.

Premorbid determinants of left ventricular dysfunction in a novel model of gradually induced pressure overload in the adult canine

NASA Technical Reports Server (NTRS)

Koide, M.; Nagatsu, M.; Zile, M. R.; Hamawaki, M.; Swindle, M. M.; Keech, G.; DeFreyte, G.; Tagawa, H.; Cooper, G. 4th; Carabello, B. A.

1997-01-01

BACKGROUND: When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. METHODS AND RESULTS: We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96 +/- 9 kdyne/cm2; dys group, 156 +/- 7 kdyne/cm2; P < .0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1 +/- 0.36; dys group, 3.9 +/- 0.26; P < .02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm2. Eighteen of 20 dogs with baseline mean systolic stress > 115 kdyne/cm2 developed dysfunction whereas 6 of 8 dogs with resting stress < or = 115 kdyne/cm2 maintained normal function. CONCLUSIONS: We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.

Mitochondrial apoptotic pathway activation in the atria of heart failure patients due to mitral and tricuspid regurgitation.

PubMed

Chang, Jen-Ping; Chen, Mien-Cheng; Liu, Wen-Hao; Lin, Yu-Sheng; Huang, Yao-Kuang; Pan, Kuo-Li; Ho, Wan-Chun; Fang, Chih-Yuan; Chen, Chien-Jen; Chen, Huang-Chung

2015-08-01

Apoptosis occurs in atrial cardiomyocytes in mitral and tricuspid valve disease. The purpose of this study was to examine the respective roles of the mitochondrial and tumor necrosis factor-α receptor associated death domain (TRADD)-mediated death receptor pathways for apoptosis in the atrial cardiomyocytes of heart failure patients due to severe mitral and moderate-to-severe tricuspid regurgitation. This study comprised eighteen patients (7 patients with persistent atrial fibrillation and 11 in sinus rhythm). Atrial appendage tissues were obtained during surgery. Three purchased normal human left atrial tissues served as normal controls. Moderately-to-severely myolytic cardiomyocytes comprised 59.7±22.1% of the cardiomyocytes in the right atria and 52.4±12.9% of the cardiomyocytes in the left atria of mitral and tricuspid regurgitation patients with atrial fibrillation group and comprised 58.4±24.8% of the cardiomyocytes in the right atria of mitral and tricuspid regurgitation patients with sinus rhythm. In contrast, no myolysis was observed in the normal human adult left atrial tissue samples. Immunohistochemical analysis showed expression of cleaved caspase-9, an effector of the mitochondrial pathways, in the majority of right atrial cardiomyocytes (87.3±10.0%) of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial cardiomyocytes (90.6±31.4%) and left atrial cardiomyocytes (70.7±22.0%) of mitral and tricuspid regurgitation patients with atrial fibrillation. In contrast, only 5.7% of cardiomyocytes of the normal left atrial tissues showed strongly positive expression of cleaved caspase-9. Of note, none of the atrial cardiomyocytes in right atrial tissue in sinus rhythm and in the fibrillating right and left atria of mitral and tricuspid regurgitation patients, and in the normal human adult left atrial tissue samples showed cleaved caspase-8 expression, which is a downstream effector of TRADD of the death receptor pathway. Immunoblotting of atrial extracts showed that there was enhanced expression of cytosolic cytochrome c, an effector of the mitochondrial pathways, but no expression of membrane TRADD and cytosolic caspase-8 in the right atrial tissue of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial and left atrial tissues of mitral and tricuspid regurgitation patients with atrial fibrillation. Taken together, this study showed that mitochondrial pathway for apoptosis was activated in the right atria in sinus rhythm and in the left and right atria in atrial fibrillation of heart failure patients due to mitral and tricuspid regurgitation, and this mitochondrial pathway activation may contribute to atrial contractile dysfunction and enlargement in this clinical setting. Copyright © 2015. Published by Elsevier Inc.

Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

PubMed

O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

2013-12-01

Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (p<0.05 for all). The other driving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

PubMed

Turco, Margherita Y; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G E; Brosens, Jan J; Critchley, Hilary O; Simons, Benjamin D; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J

2017-05-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically-defined medium

PubMed Central

Turco, Margherita Y.; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J.; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G.E.; Brosens, Jan J.; Critchley, Hilary O.; Simons, Benjamin D.; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J.

2017-01-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem cell-derived organoid cultures to generate 3D cultures of normal and decidualised human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation. PMID:28394884

Immunohistochemical Localization of Periostin in Human Gingiva

PubMed Central

Cobo, T.; Obaya, A.; Cal, S.; Solares, L.; Cabo, R.; Vega, J.A.; Cobo, J.

2015-01-01

The periostin is a matricellular protein expressed in collagen-rich tissues including some dental and periodontal tissues where it is regulated by mechanical forces, growth factors and cytokines. Interestingly the expression of this protein has been found modified in different gingival pathologies although the expression of periostin in normal human gingiva was never investigated. Here we used Western blot and double immunofluorescence coupled to laser-confocal microscopy to investigated the occurrence and distribution of periostin in different segments of the human gingival in healthy subjects. By Western blot a protein band with an estimated molecular mass of 94 kDa was observed. Periostin was localized at the epithelial-connective tissue junction, or among the fibers of the periodontal ligament, and never co-localized with cytokeratin or vimentin thus suggesting it is an extracellular protein. These results demonstrate the occurrence of periostin in adult human gingiva; its localization suggests a role in the bidirectional interactions between the connective tissue and the epithelial cells, and therefore in the physiopathological conditions in which these interactions are altered. PMID:26428890

Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

PubMed

Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

2011-06-01

Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear

PubMed Central

Kilpatrick, Lauren A.; Li, Qian; Yang, John; Goddard, John C; Fekete, Donna M.; Lang, Hainan

2010-01-01

Murine models are ideal for studying cochlear gene transfer as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, due to its small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAV) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear and allows for near-complete preservation of low and middle frequency hearing. In the present study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6, and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus (CMV) promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells (IHCs) were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness. PMID:21209625

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth

PubMed Central

Kimball, Todd; Rasmussen, Tara L.; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R.; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O.; Vondriska, Thomas M.

2016-01-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID:27663768

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.

PubMed

Franklin, Sarah; Kimball, Todd; Rasmussen, Tara L; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O; Vondriska, Thomas M

2016-11-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. Copyright © 2016 the American Physiological Society.

Physical exercise and cognitive performance in the elderly: current perspectives

PubMed Central

Kirk-Sanchez, Neva J; McGough, Ellen L

2014-01-01

In an aging population with increasing incidence of dementia and cognitive impairment, strategies are needed to slow age-related decline and reduce disease-related cognitive impairment in older adults. Physical exercise that targets modifiable risk factors and neuroprotective mechanisms may reduce declines in cognitive performance attributed to the normal aging process and protect against changes related to neurodegenerative diseases such as Alzheimer’s disease and other types of dementia. In this review we summarize the role of exercise in neuroprotection and cognitive performance, and provide information related to implementation of physical exercise programs for older adults. Evidence from both animal and human studies supports the role of physical exercise in modifying metabolic, structural, and functional dimensions of the brain and preserving cognitive performance in older adults. The results of observational studies support a dose-dependent neuroprotective relationship between physical exercise and cognitive performance in older adults. Although some clinical trials of exercise interventions demonstrate positive effects of exercise on cognitive performance, other trials show minimal to no effect. Although further research is needed, physical exercise interventions aimed at improving brain health through neuroprotective mechanisms show promise for preserving cognitive performance. Exercise programs that are structured, individualized, higher intensity, longer duration, and multicomponent show promise for preserving cognitive performance in older adults. PMID:24379659

Theory of forward and reverse middle-ear transmission applied to otoacoustic emissions in infant and adult ears

PubMed Central

Keefe, Douglas H.; Abdala, Carolina

2008-01-01

The purpose of this study is to understand why otoacoustic emission (OAE) levels are higher in normal-hearing human infants relative to adults. In a previous study, distortion product (DP) OAE input/output (I/O) functions were shown to differ at f2=6 kHz in adults compared to infants through 6 months of age. These DPOAE I/O functions were used to noninvasively assess immaturities in forward/reverse transmission through the ear canal and middle ear [Abdala, C., and Keefe, D. H., (2006). J. Acoust Soc. Am. 120, 3832–3842]. In the present study, ear-canal reflectance and DPOAEs measured in the same ears were analyzed using a scattering-matrix model of forward and reverse transmission in the ear canal, middle ear, and cochlea. Reflectance measurements were sensitive to frequency-dependent effects of ear-canal and middle-ear transmission that differed across OAE type and subject age. Results indicated that DPOAE levels were larger in infants mainly because the reverse middle-ear transmittance level varied with ear-canal area, which differed by more than a factor of 7 between term infants and adults. The forward middle-ear transmittance level was −16 dB less in infants, so that the conductive efficiency was poorer in infants than adults. PMID:17348521

Regional nonuniformity of normal adult human left ventricle.

PubMed

Bogaert, J; Rademakers, F E

2001-02-01

Regional nonuniformity is a feature of both diseased and normal left ventricles (LV). With the use of magnetic resonance (MR) myocardial tagging, we performed three-dimensional strain analysis on 87 healthy adults in local cardiac and fiber coordinate systems (radial, circumferential, longitudinal, and fiber strains) to characterize normal nonuniformities and to test the validity of wall thickening as a parameter of regional function. Regional morphology included wall thickness and radii of curvature measurements. With respect to transmural nonuniformity, subendocardial strains exceeded subepicardial strains. Going from base to apex, wall thickness and circumferential radii of curvature decreased, whereas longitudinal radii of curvature increased. All of the strains increased from LV base to apex, resulting in a higher ejection fraction (EF) at the apex than at the base (70.9 +/- 0.4 vs. 62.4 +/- 0.4%; means +/- SE, P < 0.0001). When we looked around the circumference of the ventricle, the anterior part of the LV was the flattest and thinnest and showed the largest wall thickening (46.6 +/- 1.2%) but the lowest EF (64.7 +/- 0.5%). The posterior LV wall was thicker, more curved, and showed a lower wall thickening (32.8 +/- 1.0%) but a higher EF (71.3 +/- 0.5%). The regional contribution of the LV wall to the ejection of blood is thus highly variable and is not fully characterized by wall thickening alone. Differences in regional LV architecture and probably local stress are possible explanations for this marked functional nonuniformity.

Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder.

PubMed

Althaus, M; Groen, Y; Wijers, A A; Noltes, H; Tucha, O; Hoekstra, P J

2015-12-01

The study investigated the effects of nasally administered oxytocin on neurophysiological orienting to empathy-evoking pictures in normally intelligent male adults with and without an autism spectrum disorder (ASD). It further investigated whether these effects might be moderated by the individual's approach and avoidance tendencies. All subjects participated in a randomised double-blind placebo controlled crossover trial where either oxytocin (OXT) or placebo was administered preceding the viewing of affective pictures.The pictures, selected from the International Affective Picture System (IAPS), represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. Both cardiac (ECR) and cortical (LPP) evoked orienting responses were measured and both were enhanced for the pictures with humans, in particular for the unpleasant ones. No significant group differences were found, nor were there any treatment effects. Moderator analysis, however, demonstrated that OXT did enhance orienting to affective pictures with humansin male adults with ASD who are easily distressed when seeing others in stressful situations and in healthy males who are highly sensitive to anticipated punishment and criticism or have a low drive for goal achievement. Individual differences in stress-related avoidance tendencies should be taken into account when considering OXT as a treatment of social deficiencies in autism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection.

PubMed

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2007-02-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

PubMed Central

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques. PMID:17047153

Sexual dichotomy of gonadal function in Prader-Willi syndrome from early infancy through the fourth decade.

PubMed

Hirsch, H J; Eldar-Geva, T; Bennaroch, F; Pollak, Y; Gross-Tsur, V

2015-11-01

At what age does the type of hypogonadism, namely hypothalamic or primary gonadal defect, become established in men and women with Prader-Willi syndrome (PWS)? The type of hypogonadism becomes established only in late adolescence and early adulthood. The etiology of hypogonadism in PWS is heterogeneous and the clinical expression is variable. Primary testicular failure is common in PWS men, while combinations of ovarian dysfunction and gonadotrophin deficiency are seen in women. This is a prospective study of a cohort of 106 PWS patients followed for a mean duration of 4.5 years. Serial blood samples were obtained and assayed for gonadotrophins, inhibin B, anti-Mullerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), testosterone (males), and estradiol (females). Results were compared with normal reference values obtained from the literature. For the purpose of this study, we defined the following age groups: infants <1 year; children 1-10 years; adolescents 11-20 years and adults >20 years. Study participants were 49 males (aged 2 months to 36 years) and 57 females (aged 1 month to 37 years) with genetically confirmed diagnoses of PWS (deletions 60, uniparental disomy 54, imprinting center defect 2) followed in the Israel national multidisciplinary PWS clinic. Serum LH levels were in the normal range (1.0-6.0 mIU/ml) for 7/10 adult men, and high in 3, while FSH (normal range 1.0-6.1 mIU/ml) was elevated (34.4 ± 11.5 mIU/ml) in 6 and normal (3.5 ± 1.6 mIU/ml) in 4 men. Testosterone was low (5.7 ± 3.4 nmol/l) compared with the normal range of 12.0-34.5 nmol/l in the reference population in all men >20 years. AMH showed a normal decrease with age, despite low testosterone levels. Inhibin B was normal (241 ± 105 pg/ml) in infant boys, but low or undetectable in most adult men. Hormonal profiles were more heterogeneous in women than in men. Estradiol was consistently detectable in only 7/13 adult women. Inhibin B was low or undetectable in all PWS females although occasional samples showed levels within the normal range of 15-95 pg/ml. Vaginal bleeding was reported to occur for the first time in eight women at a median age of 20 years (13-34 years), but only one had regular monthly menses. The type of hypogonadism (primary or secondary) in PWS can be determined only after age 20 years. The study cohort was heterogeneous, showing variability in BMI, cognitive disability and medical treatment. Demonstration of the natural history of reproductive hormone development in PWS suggests that androgen replacement may be indicated for most PWS boys in mid-adolescence. Recommendations for hormone replacement in PWS women need to be individually tailored, serial measurements of inhibin B should be performed, and contraception should be considered in those women who may have the potential for fertility. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; Lu, Guang-Ming; Zuo, Xi-Nian

2015-10-01

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reference ranges of lymphocyte subsets balanced for age and gender from a population of healthy adults in Chongqing District of China.

PubMed

Zhang, Kejun; Wang, Feng; Zhang, Mingxu; Cao, Xinglu; Yang, Shaojun; Jia, Shuangrong; Wang, Lixin; Luo, Jie; Deng, Shaoli; Chen, Ming

2016-11-01

The enumeration of lymphocyte subsets plays an essential role in the monitoring of immunological disorders. Immunophenotyping values have been found to be influenced by race, age, gender, and environmental conditions. Therefore, it is important to establish reference ranges for healthy adults from the local population for clinical decision-making. The current study aimed to establish a normal reference range for peripheral blood lymphocyte subsets in healthy adults from the Chongqing District of China by using single-platform flow cytometry. Age- and gender-specific reference ranges were established in 268 healthy adult males and females between 21 and 60 years of age. The CD8+ cell counts decreased with age, CD4+ cell percentages and counts increased with age, and total T cell percentages were higher in the female population. Our results are similar to those reported from other parts of China but different from some results reported from other countries; this further stresses the need to establish local reference ranges by region. Our results will help in the management of patients with human immunodeficiency virus and other immunological disorders in Chongqing District. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

Similarities and Differences for Swimming in Larval and Adult Lampreys.

PubMed

McClellan, Andrew D; Pale, Timothée; Messina, J Alex; Buso, Scott; Shebib, Ahmad

2016-01-01

The spinal locomotor networks controlling swimming behavior in larval and adult lampreys may have some important differences. As an initial step in comparing the locomotor systems in lampreys, in larval animals the relative timing of locomotor movements and muscle burst activity were determined and compared to those previously published for adults. In addition, the kinematics for free swimming in larval and adult lampreys was compared in detail for the first time. First, for swimming in larval animals, the neuromechanical phase lag between the onsets or terminations of muscle burst activity and maximum concave curvature of the body increased with increasing distance along the body, similar to that previously shown in adults. Second, in larval lampreys, but not adults, absolute swimming speed (U; mm s(-1)) increased with animal length (L). In contrast, normalized swimming speed (U'; body lengths [bl] s(-1)) did not increase with L in larval or adult animals. In both larval and adult lampreys, U' and normalized wave speed (V') increased with increasing tail-beat frequency. Wavelength and mechanical phase lag did not vary significantly with tail-beat frequency but were significantly different in larval and adult animals. Swimming in larval animals was characterized by a smaller U/V ratio, Froude efficiency, and Strouhal number than in adults, suggesting less efficient swimming for larval animals. In addition, during swimming in larval lampreys, normalized lateral head movements were larger and normalized lateral tail movements were smaller than for adults. Finally, larval animals had proportionally smaller lateral surface areas of the caudal body and fin areas than adults. These differences are well suited for larval sea lampreys that spend most of the time buried in mud/sand, in which swimming efficiency is not critical, compared to adults that would experience significant selection pressure to evolve higher-efficiency swimming to catch up to and attach to fish for feeding as well as engage in long-distance migration during spawning. Finally, the differences in swim efficiency for larval and adult lampreys are compared to other animals employing the anguilliform mode of swimming.

American College of Sports Medicine position stand. Exercise and physical activity for older adults.

PubMed

Chodzko-Zajko, Wojtek J; Proctor, David N; Fiatarone Singh, Maria A; Minson, Christopher T; Nigg, Claudio R; Salem, George J; Skinner, James S

2009-07-01

The purpose of this Position Stand is to provide an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The Position Stand is divided into three sections: Section 1 briefly reviews the structural and functional changes that characterize normal human aging, Section 2 considers the extent to which exercise and physical activity can influence the aging process, and Section 3 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on health and functional capacity. Although no amount of physical activity can stop the biological aging process, there is evidence that regular exercise can minimize the physiological effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults. Ideally, exercise prescription for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. The evidence reviewed in this Position Stand is generally consistent with prior American College of Sports Medicine statements on the types and amounts of physical activity recommended for older adults as well as the recently published 2008 Physical Activity Guidelines for Americans. All older adults should engage in regular physical activity and avoid an inactive lifestyle.

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

PubMed Central

Seals, Douglas R.

2016-01-01

Abstract Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well‐known benefits of chronic CR, long‐term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular ‘energy‐ and nutrient‐sensing’ mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long‐term CR. PMID:27641062

Dietary exposure estimates of twenty-one trace elements from a Total Diet Study carried out in Pavia, Northern Italy.

PubMed

Turconi, Giovanna; Minoia, Claudio; Ronchi, Anna; Roggi, Carla

2009-04-01

The significant role of trace elements in human health is well documented. Trace elements are those compounds that need to be present in the human diet to maintain normal physiological functions. However, some microelements may become harmful at high levels of exposure, or, on the other hand, may give rise to malnutrition, when their exposure is too low. The aim of the present study was to provide a reliable estimate of the dietary exposure of twenty-one trace elements in a Northern Italian area. For this purpose, trace element analyses were undertaken on total diet samples collected from a university cafeteria in Pavia, Northern Italy. The average daily exposure for the adult people was calculated on the basis of food consumption frequency, portion size and trace element levels in foodstuffs. The mean exposure values satisfy the Italian RDA for all the essential trace elements, except for Fe exposure in females, and are well below the Provisional Tolerable Daily Intake for all the toxic compounds, showing that the probability of dietary exposure to health risks is overall small. As far as Fe exposure is concerned, a potential risk of anaemia in the female adult population should be considered, then studies aimed at evaluating the Fe nutritional status of adult Italian women should be addressed. In conclusion, while not excluding the possibility that the daily exposure determined in the present study may not be representative of the population as a whole, this study provides a good estimate of the Italian adult consumer exposure to twenty-one trace elements.

Probability of Regenerating a Normal Limb After Bite Injury in the Mexican Axolotl (Ambystoma mexicanum).

PubMed

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L; Voss, S Randal

2014-06-01

Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls ( Ambystoma mexicanum ) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary-housed males and group-housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury likely explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury.

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

PubMed

Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

1975-12-01

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

ERP C250 Shows the Elderly (Cognitively Normal, Alzheimer’s Disease) Store More Stimuli in Short-Term Memory than Young Adults Do

PubMed Central

Chapman, Robert M.; Gardner, Margaret N.; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P.; Dupree, Haley M.; Antonsdottir, Inga M.; Kamalyan, Lily

2016-01-01

Objective To determine how aging and dementia affect the brain’s initial storing of task-relevant and irrelevant information in short-term memory. Methods We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. Results In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in intratrial parts 1–3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Conclusions Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. Significance C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. PMID:27178862

Negative psychosocial and heavy physical workloads associated with musculoskeletal pain interfering with normal life in older adults: cross-sectional analysis.

PubMed

Lilje, Stina C; Skillgate, Eva; Anderberg, Peter; Berglund, Johan

2015-07-01

Pain is one of the most frequent reasons for seeking health care, and is thus a public health problem. Although there is a progressive increase in pain and impaired physical function with age, few studies are performed on older adults. The aim of this study was to investigate if there are associations between musculoskeletal pain interfering with normal life in older adults and physical and psychosocial workloads through life. The association of heavy physical workload and negative psychosocial workload and musculoskeletal pain interfering with normal life (SF 12) was analyzed by multiple logistic regression. The model was adjusted for eight background covariates: age, gender, growing-up environment, educational level, if living alone or not, obesity, smoking, and leisure physical activity. Negative psychosocial and heavy physical workloads were independently associated with musculoskeletal pain interfering with normal life (adjusted OR: 4.44, 95% CI: 2.84-6.92), and (adjusted OR: 1.88, 95% CI: 1.20-2.93), respectively. The background covariates female gender and higher education were also associated with musculoskeletal pain interfering with normal life, and physical leisure activity was inversely associated. The findings suggest that negative psychosocial and heavy physical workloads are strongly associated with musculoskeletal pain interfering with normal life in older adults. © 2015 the Nordic Societies of Public Health.

Assessment of the effects of glutamic acid decarboxylase antibodies and trace elements on cognitive performance in older adults.

PubMed

Alghadir, Ahmad H; Gabr, Sami A; Al-Eisa, Einas S

2015-01-01

Homeostatic imbalance of trace elements such as iron (Fe), copper (Cu), and zinc (Zn) demonstrated adverse effects on brain function among older adults. The present study aimed to investigate the effects of trace elements and the presence of anti-glutamic acid decarboxylase antibodies (GADAs) in human cognitive abilities among healthy older adults. A total of 100 healthy subjects (65 males, 35 females; age range; 64-96 years) were recruited for this study. Based on Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score, the participants were classified according to cognitive performance into normal (n=45), moderate (n=30), and severe (n=25). Cognitive functioning, leisure-time physical activity (LTPA), serum trace elements - Fe, Cu, Zn, Zn/Cu, and GADAs were assessed using LOTCA battery, pre-validated physical activity (PA) questionnaire, atomic absorption, and immunoassay techniques, respectively. Approximately 45% of the study population (n=45) had normal distribution of cognitive function and 55% of the study population (n=55) had abnormal cognitive function; they were classified into moderate (score 62-92) and severe (score 31-62). There was a significant reduction in the level of Zn and Zn/Cu ratio along with an increase in the level of Fe, Cu, and anti-GADAs in subjects of severe (P=0.01) and moderate (P=0.01) cognitive performance. LOTCA-cognitive scores correlated positively with sex, HbA(1c), Fe, Cu, Zn, and Zn/Cu ratio, and negatively with age, PA, body mass index, and anti-GADAs. Significant inter-correlation was reported between serum trace element concentrations and anti-GADAs which suggest producing a cognitive decline via oxidative and neural damage mechanism. This study found significant associations among trace elements, anti-GADAs, and cognitive function in older adults. The homeostatic balance of trace elements should be recommended among older adults for better cognitive performance.

The sebaceous gland antigen defined by the OM-1 monoclonal antibody is expressed at high density on the surface of ovarian carcinoma cells.

PubMed

de Kretser, T A; Thorne, H J; Jacobs, D J; Jose, D G

1985-09-01

A monoclonal antibody, designated OM-1, was raised against ovarian serous papillary cystadenocarcinoma (stage IV) cells. This antibody was found to react strongly with primary and metastatic ovarian serous cystadenocarcinomas and endometrioid carcinomas but the antigen detected was either absent or at very low levels in ovarian mucinous adenocarcinomas, clear cell carcinomas, benign serous and mucinous cystadenomas and Brenner tumours. The OM-1 antibody gave no detectable reaction with 93 other human tumours, including examples of breast and colon adenocarcinomas. In normal tissues the OM-1 antibody reacted with normal sebaceous gland cells, lung type II pneumocytes and placental syncytial trophoblasts. In the normal ovary OM-1 reactivity was confined to extremely weak staining of the surface epithelium. No reaction with any other ovarian cell type could be detected. No evidence of reaction with other normal cell populations present in 24 adult and seven foetal tissues was found. The antigen detected is compared with other ovarian tumour-associated antigens. The OM-1 antibody is likely to prove of value in the detection and diagnosis of ovarian carcinoma.

Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation

PubMed Central

Lee, Myoung-Hwa; Amin, Niranjana D.; Venkatesan, Arun; Wang, Tongguang; Tyagi, Richa; Pant, Harish C.; Nath, Avindra

2013-01-01

Human immunodeficiency virus (HIV) infection associated neurocognitive disorders (HAND) is accompanied with brain atrophy. In these patients, impairment of adult neurogenesis and neurite outgrowth in the hippocampus may contribute to the cognitive dysfunction. Although running exercises can enhance neurogenesis and normalize neurite outgrowth, the underlying molecular mechanisms are not well understood. The HIV envelope protein, gp120, has been shown to impair neurogenesis. Using a gp120 transgenic mouse model, we demonstrate that exercise stimulated neural progenitor cell (NPC) proliferation in the hippocampal dentate gyrus and increased the survival rate and generation of newborn cells. However sustained exercise activity was necessary since the effects were reversed by detraining. Exercise also normalized dendritic outgrowth of neurons. Furthermore, it also increased the expression of hippocampal brainderived neurotrophic factor (BDNF) and normalized hyperactivation of cyclin-dependent kinase 5 (Cdk5). Hyper-activated Cdk5 or gp120 treatment led to aberrant neurite outgrowth and BDNF treatment normalized the neurite outgrowth in NPC cultures. These results suggest that sustained exercise has trophic activity on the neuronal lineage which is mediated by Cdk5 modulation of the BDNF pathway. PMID:23982957

Sex-dependent differences in voluntary physical activity.

PubMed

Rosenfeld, Cheryl S

2017-01-02

Numbers of overweight and obese individuals are increasing in the United States and globally, and, correspondingly, the associated health care costs are rising dramatically. More than one-third of children are currently considered obese with a predisposition to type 2 diabetes, and it is likely that their metabolic conditions will worsen with age. Physical inactivity has also risen to be the leading cause of many chronic, noncommunicable diseases (NCD). Children are more physically inactive now than they were in past decades, which may be due to intrinsic and extrinsic factors. In rodents, the amount of time engaged in spontaneous activity within the home cage is a strong predictor of later adiposity and weight gain. Thus, it is important to understand primary motivators stimulating physical activity (PA). There are normal sex differences in PA levels in rodents and humans. The perinatal environment can induce sex-dependent differences in PA disturbances. This Review considers the current evidence for sex differences in PA in rodents and humans. The rodent studies showing that early exposure to environmental chemicals can shape later adult PA responses are discussed. Next, whether there are different motivators stimulating exercise in male vs. female humans are examined. Finally, the brain regions, genes, and pathways that modulate PA in rodents, and possibly by translation in humans, are described. A better understanding of why each sex remains physically active through the life span could open new avenues for preventing and treating obesity in children and adults. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inhibition of gonadotropin and prostaglandin stimulation of testicular steroidogenesis in malnourished rats.

PubMed

Nduka, E U; Dada, O A

1984-01-01

The effect of human chorionic gonadotropin (hCG) and prostaglandin E1 (PGE1) on testicular steroidogenesis in protein-deficient and refed rats was studied in vitro. The malnourished, refed, and control rats were found to secret testosterone in response to hCG and PGE1 stimulation. There was a significant reduction in the basal level of secretion in the malnourished rat testis (1.0 +/- 0.4 nMol/3 hr./Testis). Malnourished rats refed with adequate protein diet responded to hCG and PGE1 stimulation in a similar manner to normally-fed adult rats.

Association of dioxins, furans and dioxin-like PCBs in human blood with nephropathy among US teens and young adults.

PubMed

Everett, Charles J; Thompson, Olivia M

2016-06-01

We assessed the association of three chlorinated dibenzo-p-dioxins, a chlorinated dibenzofuran, and four dioxin-like polychlorinated biphenyls (PCBs) in human blood with nephropathy (microalbuminuria or macroalbuminuria) among teens and young adults (12-30 years old) having normal glycohemoglobin (A1c <5.7%). The data were derived from the 1999-2004 National Health and Nutrition Examination Survey (unweighted n=1504, population estimate=38,806,338). In this paper, nephropathy refers to normal A1c with nephropathy. In an all-adult sample (Everett CJ, Thompson OM. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy? Environ Res 2014;132:126-31), the cut-offs for these chemicals being considered elevated, were defined as the 75th percentile. Using these same cut-offs again, the proportion of those with one or more of the eight dioxin-like compounds elevated was 9.9%. The four chemicals associated with nephropathy were 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin, PCB 126, PCB 169, and PCB 156. The proportion with one or more of these four dioxin-like chemicals elevated was 3.9% (unweighted n=46) and the odds ratio (OR) for nephropathy was 7.1 [95% confidence interval (CI) 1.8-28.1]. The association was strong among females (OR 17.4, 95% CI 3.4-88.6), but among males there were no cases of nephropathy when one or more of the four dioxin-like chemicals were elevated, and therefore no association. In a separate analysis, elevated toxic equivalency, defined using the eight dioxin-like chemicals (TEQ8), was associated with nephropathy. TEQ8 ≥50.12 fg/g included 2.6% of the sample (unweighted n=28) and had an OR of 5.8 (95% 1.3-25.9) for nephropathy. As found in the analysis of one or more of four dioxin-like chemicals elevated, TEQ8 ≥50.12 fg/g was associated with nephropathy among females (OR 11.9, 95% CI 1.6-87.2), but not males. Trends for least-squares means also differed by gender, but there were no significant differences in mean TEQ8 between normal subjects and those having nephropathy in either males or females. We also evaluated pre-diabetes (A1c 5.7-6.4%) without nephropathy and found no associations when one or more of four dioxin-like compounds were elevated, or when TEQ8 was ≥50.12 fg/g. In this study, associations of dioxin-like chemicals with nephropathy were found among females at an early age. Prospective studies are needed to determine if dioxin-like compounds cause nephropathy, or if these relationships are cases of reverse causation.

Binaural Advantage for Younger and Older Adults with Normal Hearing

ERIC Educational Resources Information Center

Dubno, Judy R.; Ahlstrom, Jayne B.; Horwitz, Amy R.

2008-01-01

Purpose: Three experiments measured benefit of spatial separation, benefit of binaural listening, and masking-level differences (MLDs) to assess age-related differences in binaural advantage. Method: Participants were younger and older adults with normal hearing through 4.0 kHz. Experiment 1 compared spatial benefit with and without head shadow.…

Effect of virtual reality exercise using the nintendo wii fit on muscle activities of the trunk and lower extremities of normal adults.

PubMed

Park, Jungseo; Lee, Daehee; Lee, Sangyong

2014-02-01

[Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults.

Effect of Virtual Reality Exercise Using the Nintendo Wii Fit on Muscle Activities of the Trunk and Lower Extremities of Normal Adults

PubMed Central

Park, Jungseo; Lee, Daehee; Lee, Sangyong

2014-01-01

[Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults. PMID:24648647

Working memory training using EEG neurofeedback in normal young adults.

PubMed

Xiong, Shi; Cheng, Chen; Wu, Xia; Guo, Xiaojuan; Yao, Li; Zhang, Jiacai

2014-01-01

Recent studies have shown that working memory (WM) performance can be improved by intensive and adaptive computerized training. Here, we explored the WM training effect using Electroencephalography (EEG) neurofeedback (NF) in normal young adults. In the first study, we identified the EEG features related to WM in normal young adults. The receiver operating characteristic (ROC) curve showed that the power ratio of the theta-to-alpha rhythms in the anterior-parietal region, accurately classified a high percentage of the EEG trials recorded during WM and fixation control (FC) tasks. Based on these results, a second study aimed to assess the training effects of the theta-to-alpha ratio and tested the hypothesis that up-regulating the power ratio can improve working memory behavior. Our results demonstrated that these normal young adults succeeded in improving their WM performance with EEG NF, and the pre- and post-test evaluations also indicated that WM performance increase in experimental group was significantly greater than control groups. In summary, our findings provided preliminarily evidence that WM performance can be improved through learned regulation of the EEG power ratio using EEG NF.

Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.

PubMed

Streck, R J; Helinski, E H; Ovak, G M; Pauly, J L

1990-09-01

Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.

Human Endometrial DNA Methylome Is Cycle-Dependent and Is Associated With Gene Expression Regulation

PubMed Central

Houshdaran, Sahar; Zelenko, Zara; Irwin, Juan C.

2014-01-01

Human endometrium undergoes major gene expression changes, resulting in altered cellular functions in response to cyclic variations in circulating estradiol and progesterone, largely mediated by transcription factors and nuclear receptors. In addition to classic modulators, epigenetic mechanisms regulate gene expression during development in response to environmental factors and in some diseases and have roles in steroid hormone action. Herein, we tested the hypothesis that DNA methylation plays a role in gene expression regulation in human endometrium in different hormonal milieux. High throughput, genome-wide DNA methylation profiling of endometrial samples in proliferative, early secretory, and midsecretory phases revealed dynamic DNA methylation patterns with segregation of proliferative from secretory phase samples by unsupervised cluster analysis of differentially methylated genes. Changes involved different frequencies of gain and loss of methylation within or outside CpG islands. Comparison of changes in transcriptomes and corresponding DNA methylomes from the same samples revealed association of DNA methylation and gene expression in a number of loci, some important in endometrial biology. Human endometrial stromal fibroblasts treated in vitro with estradiol and progesterone exhibited DNA methylation changes in several genes observed in proliferative and secretory phase tissues, respectively. Taken together, the data support the observation that epigenetic mechanisms are involved in gene expression regulation in human endometrium in different hormonal milieux, adding endometrium to a small number of normal adult tissues exhibiting dynamic DNA methylation. The data also raise the possibility that the interplay between steroid hormone and methylome dynamics regulates normal endometrial functions and, if abnormal, may result in endometrial dysfunction and associated disorders. PMID:24877562

Effects of Noise Level and Cognitive Function on Speech Perception in Normal Elderly and Elderly with Amnestic Mild Cognitive Impairment.

PubMed

Lee, Soo Jung; Park, Kyung Won; Kim, Lee-Suk; Kim, HyangHee

2016-06-01

Along with auditory function, cognitive function contributes to speech perception in the presence of background noise. Older adults with cognitive impairment might, therefore, have more difficulty perceiving speech-in-noise than their peers who have normal cognitive function. We compared the effects of noise level and cognitive function on speech perception in patients with amnestic mild cognitive impairment (aMCI), cognitively normal older adults, and cognitively normal younger adults. We studied 14 patients with aMCI and 14 age-, education-, and hearing threshold-matched cognitively intact older adults as experimental groups, and 14 younger adults as a control group. We assessed speech perception with monosyllabic word and sentence recognition tests at four noise levels: quiet condition and signal-to-noise ratio +5 dB, 0 dB, and -5 dB. We also evaluated the aMCI group with a neuropsychological assessment. Controlling for hearing thresholds, we found that the aMCI group scored significantly lower than both the older adults and the younger adults only when the noise level was high (signal-to-noise ratio -5 dB). At signal-to-noise ratio -5 dB, both older groups had significantly lower scores than the younger adults on the sentence recognition test. The aMCI group's sentence recognition performance was related to their executive function scores. Our findings suggest that patients with aMCI have more problems communicating in noisy situations in daily life than do their cognitively healthy peers and that older listeners with more difficulties understanding speech in noise should be considered for testing of neuropsychological function as well as hearing.

In vivo delineation of subdivisions of the human amygdaloid complex in a high-resolution group template

PubMed Central

Tyszka, J. Michael; Pauli, Wolfgang M.

2016-01-01

The nuclei of the human amygdala remain difficult to distinguish in individual subject structural magnetic resonance images. However, interpretation of the amygdala’s role in whole brain networks requires accurate localization of functional activity to a particular nucleus or subgroup of nuclei. To address this, we constructed high spatial resolution, three-dimensional templates, using joint high accuracy diffeomorphic registration of T1- and T2-weighted structural images from 168 typical adults between 22 and 35 years old released by the Human Connectome Project. Several internuclear boundaries are clearly visible in these templates, which would otherwise be impossible to delineate in individual subject data. A probabilistic atlas of major nuclei and nuclear groups was constructed in this template space and mapped back to individual spaces by inversion of the individual diffeomorphisms. Group level analyses revealed a slight (approximately 2%) bias towards larger total amygdala and nuclear volumes in the right hemisphere. No substantial sex or age differences were found in amygdala volumes normalized to total intracranial volume, or subdivision volumes normalized to amygdala volume. The current delineation provides a finer parcellation of the amygdala with more accurate external boundary definition than current histology-based atlases when used in conjunction with high accuracy registration methods, such as diffeomorphic warping. These templates and delineation are intended to be an open and evolving resource for future functional and structural imaging studies of the human amygdala. PMID:27354150

Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.

PubMed

Lentes, K U; Hinney, A; Ziegler, A; Rosenkranz, K; Wurmser, H; Barth, N; Jacob, K; Coners, H; Mayer, H; Grzeschik, K H; Schäfer, H; Remschmidt, H; Pirke, K M; Hebebrand, J

1997-01-01

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.

Knockout of Foxp2 disrupts vocal development in mice.

PubMed

Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

2016-03-16

The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control.

Lessons learned from studying syndromic autism spectrum disorders.

PubMed

Sztainberg, Yehezkel; Zoghbi, Huda Y

2016-10-26

Syndromic autism spectrum disorders represent a group of childhood neurological conditions, typically associated with chromosomal abnormalities or mutations in a single gene. The discovery of their genetic causes has increased our understanding of the molecular pathways critical for normal cognitive and social development. Human studies have revealed that the brain is particularly sensitive to changes in dosage of various proteins from transcriptional and translational regulators to synaptic proteins. Investigations of these disorders in animals have shed light on previously unknown pathogenic mechanisms leading to the identification of potential targets for therapeutic intervention. The demonstration of reversibility of several phenotypes in adult mice is encouraging, and brings hope that with novel therapies, skills and functionality might improve in affected children and young adults. As new research reveals points of convergence between syndromic and nonsyndromic autism spectrum disorders, we believe there will be opportunities for shared therapeutics for this class of conditions.

Static and dynamic postural control in low-vision and normal-vision adults.

PubMed

Tomomitsu, Mônica S V; Alonso, Angelica Castilho; Morimoto, Eurica; Bobbio, Tatiana G; Greve, Julia M D

2013-04-01

This study aimed to evaluate the influence of reduced visual information on postural control by comparing low-vision and normal-vision adults in static and dynamic conditions. Twenty-five low-vision subjects and twenty-five normal sighted adults were evaluated for static and dynamic balance using four protocols: 1) the Modified Clinical Test of Sensory Interaction on Balance on firm and foam surfaces with eyes opened and closed; 2) Unilateral Stance with eyes opened and closed; 3) Tandem Walk; and 4) Step Up/Over. The results showed that the low-vision group presented greater body sway compared with the normal vision during balance on a foam surface (p≤0.001), the Unilateral Stance test for both limbs (p≤0.001), and the Tandem Walk test. The low-vision group showed greater step width (p≤0.001) and slower gait speed (p≤0.004). In the Step Up/Over task, low-vision participants were more cautious in stepping up (right p≤0.005 and left p≤0.009) and in executing the movement (p≤0.001). These findings suggest that visual feedback is crucial for determining balance, especially for dynamic tasks and on foam surfaces. Low-vision individuals had worse postural stability than normal-vision adults in terms of dynamic tests and balance on foam surfaces.

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population.

PubMed

Rosler, Ariel

2006-08-01

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.

Lack of Association of Mutations in Optineurin With Disease in Patients With Adult-onset Primary Open-angle Glaucoma

PubMed Central

Wiggs, Janey L.; Auguste, Josette; Allingham, R. Rand; Flor, Jason D.; Pericak-Vance, Margaret A.; Rogers, Kathryn; LaRocque, Karen R.; Graham, Felicia L.; Broomer, Bob; Del Bono, Elizabeth; Haines, Jonathan L.; Hauser, Michael

2005-01-01

Objective: To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma. Methods: The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography. Results: The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found. Conclusion: The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance: Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma. PMID:12912697

Varieties of numerical abilities.

PubMed

Dehaene, S

1992-08-01

This paper provides a tutorial introduction to numerical cognition, with a review of essential findings and current points of debate. A tacit hypothesis in cognitive arithmetic is that numerical abilities derive from human linguistic competence. One aim of this special issue is to confront this hypothesis with current knowledge of number representations in animals, infants, normal and gifted adults, and brain-lesioned patients. First, the historical evolution of number notations is presented, together with the mental processes for calculating and transcoding from one notation to another. While these domains are well described by formal symbol-processing models, this paper argues that such is not the case for two other domains of numerical competence: quantification and approximation. The evidence for counting, subitizing and numerosity estimation in infants, children, adults and animals is critically examined. Data are also presented which suggest a specialization for processing approximate numerical quantities in animals and humans. A synthesis of these findings is proposed in the form of a triple-code model, which assumes that numbers are mentally manipulated in an arabic, verbal or analogical magnitude code depending on the requested mental operation. Only the analogical magnitude representation seems available to animals and preverbal infants.

Neurovascular coupling and energy metabolism in the developing brain

PubMed Central

Kozberg, M.; Hillman, E.

2016-01-01

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

Mutations in the growth hormone releasing hormone receptor: a new form of dwarfism in humans.

PubMed

Baumann, G

1999-06-01

We describe a recently identified new form of dwarfism due to isolated growth hormone (GH) deficiency, secondary to inactivating mutations in the GH-releasing hormone receptor (GHRHR) gene. The identical nonsense mutations in the extracellular domain of the GHRHR (E72X or E50X, depending on whether the signal peptide is included in the numbering) has been independently described in three families residing on or originating from the Indian subcontinent (Pakistan, the Bombay region, and Delft near Sri Lanka). Another inactivating mutation, involving the donor splice site of intron 1, has been identified in a population in north-eastern Brazil. Genetic transmission is autosomal recessive; the gene is located on the short arm of chromosome 7. Affected subjects have severe isolated GH deficiency and postnatal growth failure, with a mean adult height of 130 cm for men and 114 cm for women (7-8 standard deviations below the norm). Dwarfism is proportional; a characteristic feature is relative microcephaly, which results in a 'miniaturized adult', eumorphic aspect. Bone age and puberty are delayed, but fertility appears normal. This new syndrome corresponds to the human homologue of the previously identified 'little mouse'.

Conspecific Interactions in Adult Laboratory Rodents: Friends or Foes?

PubMed

Lukas, Michael; de Jong, Trynke R

2017-01-01

Interactions between adult conspecifics, including sexual behaviors, affiliation, and aggression are crucial for the well-being, survival, and reproduction of mammals. This holds true for any mammalian species, but certainly for humans: An inability to optimally navigate the social system can have a strong negative impact on physical and mental health. Translational rodent models have been used for decades to unravel the neural pathways and substrates involved in normal and abnormal conspecific interactions. Researchers in the field of translational social neuroscience face a double challenge: Not only do they need to pay considerable attention to the behavioral ecology of their model species or their ancestors, they also have to expect a relatively large variability in behavior and adjust their experimental design accordingly. In this chapter, we will lay out traditional and novel rodent models and paradigms to study sexual, affiliative, and aggressive interactions among adult conspecifics. We will discuss the merits and main findings and briefly consider the most promising novel directions. Finally, we review the modulatory involvement of two major players in mammal social interaction: the central oxytocin and vasopressin system.

Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

PubMed

Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

2017-04-01

Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

PubMed Central

Cardin, Velia

2016-01-01

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects.

PubMed

Yamazaki, Yuji; Imura, Akihiro; Urakawa, Itaru; Shimada, Takashi; Murakami, Junko; Aono, Yukiko; Hasegawa, Hisashi; Yamashita, Takeyoshi; Nakatani, Kimihiko; Saito, Yoshihiko; Okamoto, Nozomi; Kurumatani, Norio; Namba, Noriyuki; Kitaoka, Taichi; Ozono, Keiichi; Sakai, Tomoyuki; Hataya, Hiroshi; Ichikawa, Shoji; Imel, Erik A; Econs, Michael J; Nabeshima, Yo-Ichi

2010-07-30

Alpha-Klotho (alphaKl) regulates mineral metabolism such as calcium ion (Ca(2+)) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation. The aims of this study were: (1) to establish a sandwich ELISA system enabling detection of circulating serum salphaKl, and (2) to determine reference values for salphaKl serum levels and relationship to indices of renal function, mineral metabolism, age and sex in healthy subjects. We successively developed an ELISA to measure serum salphaKl in healthy volunteers (n=142, males 66) of ages (61.1+/-18.5year). The levels (mean+/-SD) in these healthy control adults were as follows: total calcium (Ca; 9.46+/-0.41mg/dL), Pi (3.63+/-0.51mg/dL), blood urea nitrogen (BUN; 15.7+/-4.3mg/dL), creatinine (Cre; 0.69+/-0.14mg/dL), 1,25 dihydroxyvitamin D (1,25(OH)(2)D; 54.8+/-17.7pg/mL), intact parathyroid hormone (iPTH; 49.2+/-20.6pg/mL), calcitonin (26.0+/-12.3pg/mL) and intact fibroblast growth factor (FGF23; 43.8+/-17.6pg/mL). Serum levels of salphaKl ranged from 239 to 1266pg/mL (mean+/-SD; 562+/-146pg/mL) in normal adults. Although salphaKl levels were not modified by gender or indices of mineral metabolism, salphaKl levels were inversely related to Cre and age. However, salphaKl levels in normal children (n=39, males 23, mean+/-SD; 7.1+/-4.8years) were significantly higher (mean+/-SD; 952+/-282pg/mL) than those in adults (mean+/-SD; 562+/-146, P<0.001). A multivariate linear regression analysis including children and adults in this study demonstrated that salphaKl correlated negatively with age and Ca, and positively with Pi. Finally, we measured a serum salphaKl from a patient with severe tumoral calcinosis derived from a homozygous missense mutation of alpha-klotho gene. In this patient, salphaKl level was notably lower than those of age-matched controls. We established a detection system to measure human serum salphaKl for the first time. Age, Ca and Pi seem to influence serum salphaKl levels in a normal population. This detection system should be an excellent tool for investigating salphaKl functions in mineral metabolism. Copyright 2010 Elsevier Inc. All rights reserved.

A MEG investigation of somatosensory processing in the rhesus monkey

PubMed Central

Wilson, Tony W.; Godwin, Dwayne W.; Czoty, Paul W.; Nader, Michael A.; Kraft, Robert A.; Buchheimer, Nancy C.; Daunais, James B.

2009-01-01

The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole-head MEG instrumentation to record neuromagnetic responses in adult rhesus monkeys. Nonhuman primate models of human disease provide the closest phylogenetic link to humans. The present, non-invasive imaging study could promote exciting links between invasive animal studies and non-invasive human studies, allowing experimentally induced deficits and pharmacological treatments to be interpreted in light of resulting brain network interactions. PMID:19306931

Flies without centrioles.

PubMed

Basto, Renata; Lau, Joyce; Vinogradova, Tatiana; Gardiol, Alejandra; Woods, C Geoffrey; Khodjakov, Alexey; Raff, Jordan W

2006-06-30

Centrioles and centrosomes have an important role in animal cell organization, but it is uncertain to what extent they are essential for animal development. The Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for centriole replication in flies. DSas-4 mutants start to lose centrioles during embryonic development, and, by third-instar larval stages, no centrioles or centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and approximately 30% of the asymmetric divisions of larval neuroblasts are abnormal. Nevertheless, mutant flies develop with near normal timing into morphologically normal adults. These flies, however, have no cilia or flagella and die shortly after birth because their sensory neurons lack cilia. Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development.

Transient visual pathway critical for normal development of primate grasping behavior.

PubMed

Mundinano, Inaki-Carril; Fox, Dylan M; Kwan, William C; Vidaurre, Diego; Teo, Leon; Homman-Ludiye, Jihane; Goodale, Melvyn A; Leopold, David A; Bourne, James A

2018-02-06

An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar, which is thought to relay information to the middle temporal (MT) area during early life and then swiftly withdraws. Small MRI-guided lesions to a subdivision of the inferior pulvinar subnucleus (PIm) in the infant marmoset monkey led to permanent deficits in reaching-and-grasping behavior in the adult. This functional loss coincided with the abnormal anatomical development of multiple cortical areas responsible for the guidance of actions. Our study reveals that the transient retino-pulvinar-MT pathway underpins the development of visually guided manual behaviors in primates that are crucial for interacting with complex features in the environment.

Two dimensional microcirculation mapping with real time spatial frequency domain imaging

NASA Astrophysics Data System (ADS)

Zheng, Yang; Chen, Xinlin; Lin, Weihao; Cao, Zili; Zhu, Xiuwei; Zeng, Bixin; Xu, M.

2018-02-01

We present a spatial frequency domain imaging (SFDI) study of local hemodynamics in the human finger cuticle of healthy volunteers performing paced breathing and the forearm of healthy young adults performing normal breathing with our recently developed Real Time Single Snapshot Multiple Frequency Demodulation - Spatial Frequency Domain Imaging (SSMD-SFDI) system. A two-layer model was used to map the concentrations of deoxy-, oxy-hemoglobin, melanin, epidermal thickness and scattering properties at the subsurface of the forearm and the finger cuticle. The oscillations of the concentrations of deoxy- and oxy-hemoglobin at the subsurface of the finger cuticle and forearm induced by paced breathing and normal breathing, respectively, were found to be close to out-of-phase, attributed to the dominance of the blood flow modulation by paced breathing or heartbeat. Our results suggest that the real time SFDI platform may serve as one effective imaging modality for microcirculation monitoring.

Extracommunicative functions of language: verbal interference causes selective categorization impairments.

PubMed

Lupyan, Gary

2009-08-01

In addition to its communicative functions, language has been argued to have a variety of extracommunicative functions, as assessed by its causal involvement in putatively nonlinguistic tasks. In the present work, I argue that language may be critically involved in the ability of human adults to categorize objects on a specific dimension (e.g., color) while abstracting over other dimensions (e.g., size). This ability is frequently impaired in aphasic patients. The present work demonstrates that normal participants placed under conditions of verbal interference show a pattern of deficits strikingly similar to that of aphasic patients: impaired taxonomic categorization along perceptual dimensions, and preserved thematic categorization. A control experiment using a visuospatial-interference task failed to find this selective pattern of deficits. The present work has implications for understanding the online role of language in normal cognition and supports the claim that language is causally involved in nonverbal cognition.

Defective enamel ultrastructure in diabetic rodents.

PubMed

Atar, M; Atar-Zwillenberg, D R; Verry, P; Spornitz, U M

2004-07-01

We investigated six different types of diabetic rodents. Four expressed a genetic obesity resulting in diabetes. One developed diabetes induced by a diet-dependent obesity, and one with genetic diabetes received anti-diabetic medication. The tooth samples were examined under a scanning electron microscope and with an energy dispersive microanalysis (EDX). The electron micrographs showed severe, varying degrees of damage within the six different diabetic animal types, such as irregular crystallite deposition and prism perforations in genetically obese animals compared to less-disordered prism structures in diet-dependent obesity. Anti-diabetic medication resulted in normal enamel ultrastructure. The EDX analysis revealed a reduction in the amount of calcium and phosphorus in all regions affected by diabetes. Based on these animal studies, we suggest that both juvenile diabetes type I (in infants) and adult diabetes type II (in pregnant mothers, affecting the developing foetus) may affect the normal development of teeth in humans.

Spatial frequency discrimination learning in normal and developmentally impaired human vision

PubMed Central

Astle, Andrew T.; Webb, Ben S.; McGraw, Paul V.

2010-01-01

Perceptual learning effects demonstrate that the adult visual system retains neural plasticity. If perceptual learning holds any value as a treatment tool for amblyopia, trained improvements in performance must generalise. Here we investigate whether spatial frequency discrimination learning generalises within task to other spatial frequencies, and across task to contrast sensitivity. Before and after training, we measured contrast sensitivity and spatial frequency discrimination (at a range of reference frequencies 1, 2, 4, 8, 16 c/deg). During training, normal and amblyopic observers were divided into three groups. Each group trained on a spatial frequency discrimination task at one reference frequency (2, 4, or 8 c/deg). Normal and amblyopic observers who trained at lower frequencies showed a greater rate of within task learning (at their reference frequency) compared to those trained at higher frequencies. Compared to normals, amblyopic observers showed greater within task learning, at the trained reference frequency. Normal and amblyopic observers showed asymmetrical transfer of learning from high to low spatial frequencies. Both normal and amblyopic subjects showed transfer to contrast sensitivity. The direction of transfer for contrast sensitivity measurements was from the trained spatial frequency to higher frequencies, with the bandwidth and magnitude of transfer greater in the amblyopic observers compared to normals. The findings provide further support for the therapeutic efficacy of this approach and establish general principles that may help develop more effective protocols for the treatment of developmental visual deficits. PMID:20832416

HOXB homeobox gene expression in cervical carcinoma.

PubMed

López, R; Garrido, E; Piña, P; Hidalgo, A; Lazos, M; Ochoa, R; Salcedo, M

2006-01-01

The homeobox (HOX) genes are a family of transcription factors that bind to specific DNA sequences in target genes regulating gene expression. Thirty-nine HOX genes have been mapped in four conserved clusters: A, B, C, and D; they act as master genes regulating the identity of body segments along the anteroposterior axis of the embryo. The role played by HOX genes in adult cell differentiation is unclear to date, but growing evidence suggests that they may play an important role in the development of cancer. To study the role played by HOX genes in cervical cancer, in the present work, we analyzed the expression of HOXB genes and the localization of their transcripts in human cervical tissues. Reverse transcription-polymerase chain reaction analysis and nonradioactive RNA in situ hybridization were used to detect HOXB expression in 11 normal cervical tissues and 17 cervical carcinomas. It was determined that HOXB1, B3, B5, B6, B7, B8, and B9 genes are expressed in normal adult cervical epithelium and squamous cervical carcinomas. Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was found only in tumor tissues. Our findings suggest that the new expression of HOXB2, HOXB4, and B13 genes is involved in cervical cancer.

Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

2009-01-01

Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

Human Streptococcus agalactiae strains in aquatic mammals and fish

PubMed Central

2013-01-01

Background In humans, Streptococcus agalactiae or group B streptococcus (GBS) is a frequent coloniser of the rectovaginal tract, a major cause of neonatal infectious disease and an emerging cause of disease in non-pregnant adults. In addition, Streptococcus agalactiae causes invasive disease in fish, compromising food security and posing a zoonotic hazard. We studied the molecular epidemiology of S. agalactiae in fish and other aquatic species to assess potential for pathogen transmission between aquatic species and humans. Methods Isolates from fish (n = 26), seals (n = 6), a dolphin and a frog were characterized by pulsed-field gel electrophoresis, multilocus sequence typing and standardized 3-set genotyping, i.e. molecular serotyping and profiling of surface protein genes and mobile genetic elements. Results Four subpopulations of S. agalactiae were identified among aquatic isolates. Sequence type (ST) 283 serotype III-4 and its novel single locus variant ST491 were detected in fish from Southeast Asia and shared a 3-set genotype identical to that of an emerging ST283 clone associated with invasive disease of adult humans in Asia. The human pathogenic strain ST7 serotype Ia was also detected in fish from Asia. ST23 serotype Ia, a subpopulation that is normally associated with human carriage, was found in all grey seals, suggesting that human effluent may contribute to microbial pollution of surface water and exposure of sea mammals to human pathogens. The final subpopulation consisted of non-haemolytic ST260 and ST261 serotype Ib isolates, which belong to a fish-associated clonal complex that has never been reported from humans. Conclusions The apparent association of the four subpopulations of S. agalactiae with specific groups of host species suggests that some strains of aquatic S. agalactiae may present a zoonotic or anthroponotic hazard. Furthermore, it provides a rational framework for exploration of pathogenesis and host-associated genome content of S. agalactiae strains. PMID:23419028

Sodium urine test

MedlinePlus

... or monitor many types of kidney diseases. Normal Results For adults, normal urine sodium values are generally ... meaning of your specific test result. What Abnormal Results Mean A higher than normal urine sodium level ...

Using open source accelerometer analysis to assess physical activity and sedentary behaviour in overweight and obese adults.

PubMed

Innerd, Paul; Harrison, Rory; Coulson, Morc

2018-04-23

Physical activity and sedentary behaviour are difficult to assess in overweight and obese adults. However, the use of open-source, raw accelerometer data analysis could overcome this. This study compared raw accelerometer and questionnaire-assessed moderate-to-vigorous physical activity (MVPA), walking and sedentary behaviour in normal, overweight and obese adults, and determined the effect of using different methods to categorise overweight and obesity, namely body mass index (BMI), bioelectrical impedance analysis (BIA) and waist-to-hip ratio (WHR). One hundred twenty adults, aged 24-60 years, wore a raw, tri-axial accelerometer (Actigraph GT3X+), for 3 days and completed a physical activity questionnaire (IPAQ-S). We used open-source accelerometer analyses to estimate MVPA, walking and sedentary behaviour from a single raw accelerometer signal. Accelerometer and questionnaire-assessed measures were compared in normal, overweight and obese adults categorised using BMI, BIA and WHR. Relationships between accelerometer and questionnaire-assessed MVPA (Rs = 0.30 to 0.48) and walking (Rs = 0.43 to 0.58) were stronger in normal and overweight groups whilst sedentary behaviour were modest (Rs = 0.22 to 0.38) in normal, overweight and obese groups. The use of WHR resulted in stronger agreement between the questionnaire and accelerometer than BMI and BIA. Finally, accelerometer data showed stronger associations with BMI, BIA and WHR (Rs = 0.40 to 0.77) than questionnaire data (Rs = 0.24 to 0.37). Open-source, raw accelerometer data analysis can be used to estimate MVPA, walking and sedentary behaviour from a single acceleration signal in normal, overweight and obese adults. Our data supports the use of WHR to categorise overweight and obese adults. This evidence helps researchers obtain more accurate measures of physical activity and sedentary behaviour in overweight and obese populations.

Automated Identification of Abnormal Adult EEGs

PubMed Central

López, S.; Suarez, G.; Jungreis, D.; Obeid, I.; Picone, J.

2016-01-01

The interpretation of electroencephalograms (EEGs) is a process that is still dependent on the subjective analysis of the examiners. Though interrater agreement on critical events such as seizures is high, it is much lower on subtler events (e.g., when there are benign variants). The process used by an expert to interpret an EEG is quite subjective and hard to replicate by machine. The performance of machine learning technology is far from human performance. We have been developing an interpretation system, AutoEEG, with a goal of exceeding human performance on this task. In this work, we are focusing on one of the early decisions made in this process – whether an EEG is normal or abnormal. We explore two baseline classification algorithms: k-Nearest Neighbor (kNN) and Random Forest Ensemble Learning (RF). A subset of the TUH EEG Corpus was used to evaluate performance. Principal Components Analysis (PCA) was used to reduce the dimensionality of the data. kNN achieved a 41.8% detection error rate while RF achieved an error rate of 31.7%. These error rates are significantly lower than those obtained by random guessing based on priors (49.5%). The majority of the errors were related to misclassification of normal EEGs. PMID:27195311

Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.

PubMed

Li, Ge; Millard, Steven P; Peskind, Elaine R; Zhang, Jing; Yu, Chang-En; Leverenz, James B; Mayer, Cynthia; Shofer, Jane S; Raskind, Murray A; Quinn, Joseph F; Galasko, Douglas R; Montine, Thomas J

2014-06-01

Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury). Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31). Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.

Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

PubMed

Yokoyama, Jennifer S; Lee, Allen K L; Takada, Leonel T; Busovaca, Edgar; Bonham, Luke W; Chao, Steven Z; Tse, Marian; He, Jing; Schwarz, Christopher G; Carmichael, Owen T; Matthews, Brandy R; Karydas, Anna; Weiner, Michael W; Coppola, Giovanni; DeCarli, Charles S; Miller, Bruce L; Rosen, Howard J

2015-01-01

Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations.

The Effect of Tinnitus on Listening Effort in Normal-Hearing Young Adults: A Preliminary Study

ERIC Educational Resources Information Center

Degeest, Sofie; Keppler, Hannah; Corthals, Paul

2017-01-01

Purpose: The objective of this study was to investigate the effect of chronic tinnitus on listening effort. Method: Thirteen normal-hearing young adults with chronic tinnitus were matched with a control group for age, gender, hearing thresholds, and educational level. A dual-task paradigm was used to evaluate listening effort in different…

Individual Variability in Delayed Auditory Feedback Effects on Speech Fluency and Rate in Normally Fluent Adults

ERIC Educational Resources Information Center

Chon, HeeCheong; Kraft, Shelly Jo; Zhang, Jingfei; Loucks, Torrey; Ambrose, Nicoline G.

2013-01-01

Purpose: Delayed auditory feedback (DAF) is known to induce stuttering-like disfluencies (SLDs) and cause speech rate reductions in normally fluent adults, but the reason for speech disruptions is not fully known, and individual variation has not been well characterized. Studying individual variation in susceptibility to DAF may identify factors…

Attitudes of Overweight and Normal Weight Adults Regarding Exercise at a Health Club

ERIC Educational Resources Information Center

Miller, Wayne C.; Miller, Todd A.

2010-01-01

Objective: To compare attitudes of overweight (OW) and normal weight (NW) adults regarding health club exercise. Design: A 46-item survey (23 pairs of attitude/value statements) measured attitudes toward exercising at a health club 30 minutes, twice a week, for a month. Setting: Survey posted on surveymonkey.com. Respondents (men = 730, women =…

1Interaction between serum BDNF and aerobic fitness predicts recognition memory in healthy young adults

PubMed Central

Whiteman, Andrew; Young, Daniel E.; He, Xuemei; Chen, Tai C.; Wagenaar, Robert C.; Stern, Chantal; Schon, Karin

2013-01-01

Convergent evidence from human and non-human animal studies suggests aerobic exercise and increased aerobic capacity may be beneficial for brain health and cognition. It is thought growth factors may mediate this putative relationship, particularly by augmenting plasticity mechanisms in the hippocampus, a brain region critical for learning and memory. Among these factors, glucocorticoids, brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), hormones that have considerable and diverse physiological importance, are thought to effect normal and exercise-induced hippocampal plasticity. Despite these predictions, relatively few published human studies have tested hypotheses that relate exercise and fitness to the hippocampus, and none have considered the potential links to all of these hormonal components. Here we present cross-sectional data from a study of recognition memory; serum BDNF, cortisol, IGF-1, and VEGF levels; and aerobic capacity in healthy young adults. We measured circulating levels of these hormones together with performance on a recognition memory task, and a standard graded treadmill test of aerobic fitness. Regression analyses demonstrated BDNF and aerobic fitness predict recognition memory in an interactive manner. In addition, IGF-1 was positively associated with aerobic fitness, but not with recognition memory. Our results may suggest an exercise adaptation-related change in the BDNF dose-response curve that relates to hippocampal memory. PMID:24269495

Development and aging of the healthy human brain uncinate fasciculus across the lifespan using diffusion tensor tractography.

PubMed

Hasan, Khader M; Iftikhar, Amal; Kamali, Arash; Kramer, Larry A; Ashtari, Manzar; Cirino, Paul T; Papanicolaou, Andrew C; Fletcher, Jack M; Ewing-Cobbs, Linda

2009-06-18

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

PubMed

McGough, Ellen L; Kelly, Valerie E; Weaver, Kurt E; Logsdon, Rebecca G; McCurry, Susan M; Pike, Kenneth C; Grabowski, Thomas J; Teri, Linda

2018-04-01

This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia. Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Neural control of the lips differs for young and older adults following a perturbation

PubMed Central

de Miranda Marzullo, Ana Carolina; Neto, Osmar Pinto; Ballard, Kirrie J.; Robin, Donald A.; Chaitow, Lauren

2011-01-01

Aging impairs the control of many skilled movements including speech. The purpose of this paper was to investigate whether young and older adults adapt to lower lip perturbations during speech differently. Twenty men (10 young, 26 ± 3 years of age; 10 older, 60 ± 9 years of age) were requested to repeat the word (“papa”) 300 times. In 15% of the trials, the subjects experienced a mechanical perturbation on the lower lip. Displacement and neural activation (EMG) of the upper and lower lips were evaluated. Perturbations to the lower lip caused a greater increase in the maximum displacement of the lower lip for older adults compared with young adults (34.7 ± 19% vs. 13.4 ± 17%; P = 0.017). Furthermore, young adults exhibited significantly greater 30–100 Hz normalized EMG power for the lower lip compared to the upper lip (P < 0.005). In young adults, changes from normal to perturbed trials in the 30–50 Hz frequency band of the EMG were negatively correlated to the changes from normal to perturbed trials in the lower lip maximum displacement (R2 = 0.48; P = 0.025). It is concluded that young adults adapt better to lower lip perturbations compared with older adults and that the associated neural activation strategy of the involved muscle is different for the two age groups. PMID:20852991

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

2008-01-01

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Thyroid Autoantibodies Are Rare in Nonhuman Great Apes and Hypothyroidism Cannot Be Attributed to Thyroid Autoimmunity

PubMed Central

Aliesky, Holly; Courtney, Cynthia L.; Rapoport, Basil

2013-01-01

The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. PMID:24092641

Mechanical behaviour of the human atria.

PubMed

Bellini, Chiara; Di Martino, Elena S; Federico, Salvatore

2013-07-01

This work was aimed at providing a local mechanical characterisation of tissues from the healthy human atria. Thirty-two tissue specimens were harvested from nine adult subjects whose death was not directly related to cardiovascular diseases. Tissues were kept in Tyrode's solution and tested using a planar biaxial device. Results showed that tissues from healthy human atria undergo large deformations under in-plane distributed tensions roughly corresponding to an in vivo pressure of 15 mmHg. The material was modelled as hyperelastic and a Fung-type elastic strain energy potential was chosen. This class of potentials is based on a function of a quadratic form in the components of the Green-Lagrange strain tensor, and it has been previously proved that the fourth-order tensor of this quadratic form is proportional to the linear elasticity tensor of the linearised theory. This has three important consequences: (i) the coefficients in Fung-type potentials have a precise physical meaning; (ii) whenever a microstructural description for the linear elasticity tensor is available, this is automatically inherited by the Fung-type potential; (iii) because of the presence of the linear elasticity tensor in the definition of a Fung-type potential, each of the three normal stresses is coupled with all three normal strains.We propose to include information on the microstructure of the atrium by writing the linear elasticity tensor as the volumetric-fraction-weighed sum of the linear elasticity tensors of the three constituents of the tissue: the ground matrix, the main fibre family and the secondary fibre family. To the best of our knowledge, this is the first time that a Fung-type potential is given a precise structural meaning, based on the directions and the material properties of the fibres. Because of the coupling between normal strains and normal stresses, this structurally-based Fung-type potential allows for discriminating among all testing protocols in planar biaxial stretch.

Major depressive and anxiety disorders in visually impaired older adults.

PubMed

van der Aa, Hilde P A; Comijs, Hannie C; Penninx, Brenda W J H; van Rens, Ger H M B; van Nispen, Ruth M A

2015-01-20

We assessed the prevalence of subthreshold depression and anxiety, and major depressive, dysthymic, and anxiety disorders (panic disorder, agoraphobia, social phobia, and general anxiety disorder) in visually impaired older adults and compared these estimates with those of normally sighted peers. Cross-sectional data were analyzed based on telephone interviews with visually impaired older adults aged ≥ 60 years (n = 615) with a visual acuity of ≥ 0.30 logMAR (20/40 Snellen) in the best eye from outpatient low vision rehabilitation centers, and face-to-face interviews with community-dwelling normally sighted peers (n = 1232). To determine prevalence rates, the normally sighted population was weighted on sex and age to fit the visually impaired population. Logistic regression analyses were used to compare the populations and to correct for confounders. The prevalence of major depressive disorder (5.4%) and anxiety disorders (7.5%), as well as the prevalence of subthreshold depression (32.2%) and subthreshold anxiety (15.6%), were significantly higher in visually impaired older adults compared to their normally sighted peers (P < 0.05). Agoraphobia and social phobia were the most prevalent anxiety disorders in visually impaired older adults. This study shows that depression and anxiety are major public health problems in visually impaired older adults. Research on psychotherapeutic and psychopharmacologic interventions to improve depression and anxiety in this population is warranted. (http://www.trialregister.nl number, NTR3296.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Evaluation of Mandarin Chinese Speech Recognition in Adults with Cochlear Implants Using the Spectral Ripple Discrimination Test

PubMed Central

Dai, Chuanfu; Zhao, Zeqi; Zhang, Duo; Lei, Guanxiong

2018-01-01

Background The aim of this study was to explore the value of the spectral ripple discrimination test in speech recognition evaluation among a deaf (post-lingual) Mandarin-speaking population in China following cochlear implantation. Material/Methods The study included 23 Mandarin-speaking adult subjects with normal hearing (normal-hearing group) and 17 deaf adults who were former Mandarin-speakers, with cochlear implants (cochlear implantation group). The normal-hearing subjects were divided into men (n=10) and women (n=13). The spectral ripple discrimination thresholds between the groups were compared. The correlation between spectral ripple discrimination thresholds and Mandarin speech recognition rates in the cochlear implantation group were studied. Results Spectral ripple discrimination thresholds did not correlate with age (r=−0.19; p=0.22), and there was no significant difference in spectral ripple discrimination thresholds between the male and female groups (p=0.654). Spectral ripple discrimination thresholds of deaf adults with cochlear implants were significantly correlated with monosyllabic recognition rates (r=0.84; p=0.000). Conclusions In a Mandarin Chinese speaking population, spectral ripple discrimination thresholds of normal-hearing individuals were unaffected by both gender and age. Spectral ripple discrimination thresholds were correlated with Mandarin monosyllabic recognition rates of Mandarin-speaking in post-lingual deaf adults with cochlear implants. The spectral ripple discrimination test is a promising method for speech recognition evaluation in adults following cochlear implantation in China. PMID:29806954

Evaluation of Mandarin Chinese Speech Recognition in Adults with Cochlear Implants Using the Spectral Ripple Discrimination Test.

PubMed

Dai, Chuanfu; Zhao, Zeqi; Shen, Weidong; Zhang, Duo; Lei, Guanxiong; Qiao, Yuehua; Yang, Shiming

2018-05-28

BACKGROUND The aim of this study was to explore the value of the spectral ripple discrimination test in speech recognition evaluation among a deaf (post-lingual) Mandarin-speaking population in China following cochlear implantation. MATERIAL AND METHODS The study included 23 Mandarin-speaking adult subjects with normal hearing (normal-hearing group) and 17 deaf adults who were former Mandarin-speakers, with cochlear implants (cochlear implantation group). The normal-hearing subjects were divided into men (n=10) and women (n=13). The spectral ripple discrimination thresholds between the groups were compared. The correlation between spectral ripple discrimination thresholds and Mandarin speech recognition rates in the cochlear implantation group were studied. RESULTS Spectral ripple discrimination thresholds did not correlate with age (r=-0.19; p=0.22), and there was no significant difference in spectral ripple discrimination thresholds between the male and female groups (p=0.654). Spectral ripple discrimination thresholds of deaf adults with cochlear implants were significantly correlated with monosyllabic recognition rates (r=0.84; p=0.000). CONCLUSIONS In a Mandarin Chinese speaking population, spectral ripple discrimination thresholds of normal-hearing individuals were unaffected by both gender and age. Spectral ripple discrimination thresholds were correlated with Mandarin monosyllabic recognition rates of Mandarin-speaking in post-lingual deaf adults with cochlear implants. The spectral ripple discrimination test is a promising method for speech recognition evaluation in adults following cochlear implantation in China.

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

PubMed

Amodeo, Valeria; A, Deli; Betts, Joanne; Bartesaghi, Stefano; Zhang, Ying; Richard-Londt, Angela; Ellis, Matthew; Roshani, Rozita; Vouri, Mikaella; Galavotti, Sara; Oberndorfer, Sarah; Leite, Ana Paula; Mackay, Alan; Lampada, Aikaterini; Stratford, Eva Wessel; Li, Ningning; Dinsdale, David; Grimwade, David; Jones, Chris; Nicotera, Pierluigi; Michod, David; Brandner, Sebastian; Salomoni, Paolo

2017-07-11

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Differences in taste detection thresholds between normal-weight and obese young adults.

PubMed

Park, Dong Choon; Yeo, Joon Hyung; Ryu, In Yong; Kim, Sang Hoon; Jung, Junyang; Yeo, Seung Geun

2015-05-01

Compared with normal-weight individuals, obese young adults exhibited a significantly higher taste threshold for salty taste. Smoking also affected taste functions in this population. The aim of this study was to investigate the differences in taste detection thresholds between normal-weight and obese young adults. Taste threshold was measured using electrogustometry (EGM) and chemically with sucrose, NaCl, citric acid, and quinine hydrochloride in 41 volunteers in their twenties, 23 with body mass index (BMI) <23 kg/m(2) (normal-weight group) and 18 with BMI >25 kg/m(2) (obese group). BMI was significantly higher in the obese than in the normal-weight group (p < 0.05). The obese group exhibited significantly higher EGM thresholds than the normal-weight group on the right (p < 0.05) and left (p < 0.05) posterior tongue. In chemical taste tests, the obese group had higher thresholds for sweet, salty, sour, and bitter tastes than the normal-weight group, although the difference in threshold was significant only for salty taste (p < 0.05). Smoking had an impact on taste threshold, with smokers having higher thresholds than non-smokers, with significantly higher EGM thresholds on the right anterior and posterior and the left anterior tongue (p < 0.05 each).

Echocardiography parameters of clinically normal adult captive chimpanzees (Pan troglodytes).

PubMed

Sleeper, Meg M; Drobatz, Ken; Lee, D Richard; Lammey, Michael L

2014-04-15

To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes). Retrospective cohort study. 88 clinically normal adult chimpanzees. Echocardiographic data obtained between 2002 and 2011 from chimpanzees at the Alamogordo Primate Facility were reviewed (263 echocardiograms obtained from 158 individuals). Data from clinically normal individuals (33 females and 55 males) were analyzed. Basic cardiac parameters measured in all individuals included aortic root diameter and left atrial diameter in the short and long axis during diastole. Left ventricular measurements included left ventricular internal diameter in systole and diastole and diastolic septal and posterior wall thickness. The E point to septal separation was also measured. Spectral Doppler measurements included the peak flow velocity of the pulmonary artery and aorta and diastolic transmitral flow. The presence of arrhythmias was also noted. Standard echocardiographic findings for a large group of adult female and male chimpanzees were obtained. Female and male chimpanzees were grouped by age in 10-year blocks, and echocardiographic findings were analyzed statistically by 10-year block. In male chimpanzees, cardiac arrhythmias were noted to increase with age. Cardiovascular disease is an important cause of morbidity and death in captive chimpanzees; however, basic echocardiographic measurements from a large cohort of clinically normal animals have not previously been reported. The number of animals in the present study was insufficient to generate reference ranges; however, data from a large cohort of clinically normal animals are presented. This information will be useful for veterinarians working in clinical and research settings with this species.

ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

PubMed

Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

2016-06-01

To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Association between Obesity and Serum 25(OH)D Concentrations in Older Mexican Adults.

PubMed

Rontoyanni, Victoria G; Avila, Jaqueline C; Kaul, Sapna; Wong, Rebeca; Veeranki, Sreenivas P

2017-01-31

Vitamin D is essential for maintaining bone mineralization and calcium homeostasis, and prevents falls and fractures in older adults. Mexico is undergoing an epidemiologic and demographic transition with increasing obesity rates. The study's aim was to determine the association of obesity with serum 25-hydroxyvitamin D [25(OH)D] concentrations in older Mexican adults. Data from 1772 Mexicans, aged ≥50 years, enrolled in a sub-sample of the 3rd wave of the Mexican Health and Aging Study, were included. Serum 25(OH)D concentrations were used to define vitamin D status, and were categorized into tertiles. Body mass index measures were used to categorize older adults into under/normal weight, overweight, and obese groups. Multinomial logistic regression models were used to assess the relationship, adjusting for potential confounders. Approximately 40% and 37% of older Mexican adults were either overweight or obese, respectively. Compared to under/normal weight older Mexicans, obese adults were 1.78 times (95% Confidence Interval (CI) 1.27-2.48) and 1.94 times (95% CI 1.40-2.68) more associated with the first and second tertile concentrations of serum 25(OH)D, respectively. Overweight adults were 1.52 times (95% CI 1.12-2.06) more associated with the second tertile of serum 25(OH)D concentration than under/normal weight adults. Overweight/Obesity was found to be significantly associated with low concentrations of serum 25(OH) in older Mexican adults.

Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

PubMed

Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

2018-02-01

Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success. Testes from 15 adult gender dysphoria patients (mean ± standard deviation age 35 ± 9.3 years) showing spermatogonial arrest became available for this study after sex-reassignment surgery. In vitro primary testicular somatic cell cultures were generated to explore the self-organizing ability of testicular somatic cells to form testis cords over a 2-week period. Morphological phenotype, protein marker expression and temporal dynamics of cell reassembly were analyzed. Cell suspensions obtained by two-step enzymatic digestion were plated onto glass coverslips in 24-well plates. To obtain adherent somatic cells, the supernatant was discarded on Day 2. The culture of the attached cell population was continued. Reassembly into cord-like structures was analyzed daily by microscopic observations. Endpoints were qualitative changes in morphology. Cell types were characterized by phase-contrast microscopy and immunohistochemistry. Dynamics of cord formation were recorded by time-lapse microscopy. Primary adult human testicular cells underwent sequential morphological changes including compaction and reaggregation resulting in round or elongated cord-like structures. Time-lapse video recordings within the first 4 days of culture revealed highly dynamic processes of migration and coalescence of reaggregated cells. The cellular movements were mediated by peritubular cells. Immunohistochemical analysis showed that both SRY-related high mobility box 9-positive Sertoli and α-smooth muscle actin-positive peritubular myoid cells interacted and contributed to cord-like structure formation. Not applicable. Owing to scarcity of normal human testicular tissue, testes from gender dysphoria patients were used in the study. The regressed status might influence the experimental responses of primary cells. We observed basic morphological features resembling in vivo testicular cords, however, the proof of functionality (e.g. support of germ cells) will need further studies. The proposed in vitro culture system may open opportunities for examination of testicular cell interactions during testicular tubulogenesis. Further refinement of our approach may enable initiation of ex vivo spermatogenesis. The work was supported by EU-FP7-PEOPLE-2013-ITN 603568: 'Growsperm'. No conflict of interests is declared. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Whole-body and local RF absorption in human models as a function of anatomy and position within 1.5T MR body coil.

PubMed

Murbach, Manuel; Neufeld, Esra; Kainz, Wolfgang; Pruessmann, Klaas P; Kuster, Niels

2014-02-01

Radiofrequency energy deposition in magnetic resonance imaging must be limited to prevent excessive heating of the patient. Correlations of radiofrequency absorption with large-scale anatomical features (e.g., height) are investigated in this article. The specific absorption rate (SAR), as the pivotal parameter for quantifying absorbed radiofrequency, increases with the radial dimension of the patient and therefore with the large-scale anatomical properties. The absorbed energy in six human models has been modeled in different Z-positions (head to knees) within a 1.5T bodycoil. For a fixed B1+ incident field, the whole-body SAR can be up to 2.5 times higher (local SAR up to seven times) in obese adult models compared to children. If the exposure is normalized to 4 W/kg whole-body SAR, the local SAR can well-exceed the limits for local transmit coils and shows intersubject variations of up to a factor of three. The correlations between anatomy and induced local SAR are weak for normalized exposure, but strong for a fixed B1+ field, suggesting that anatomical properties could be used for fast SAR predictions. This study demonstrates that a representative virtual human population is indispensable for the investigation of local SAR levels. Copyright © 2013 Wiley Periodicals, Inc.

Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

PubMed

Kearse, K P; Smith, N L; Semer, D A; Eagles, L; Finley, J L; Kazmierczak, S; Kovacs, C J; Rodriguez, A A; Kellogg-Wennerberg, A E

2000-12-15

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn. Copyright 2000 Wiley-Liss, Inc.

Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

PubMed

Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

2017-08-01

Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Rich-club organization of the newborn human brain

PubMed Central

Ball, Gareth; Aljabar, Paul; Zebari, Sally; Tusor, Nora; Arichi, Tomoki; Merchant, Nazakat; Robinson, Emma C.; Ogundipe, Enitan; Rueckert, Daniel; Edwards, A. David; Counsell, Serena J.

2014-01-01

Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a “rich club”—a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical–subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants. PMID:24799693

Cystic fibrosis transmembrane conductance regulator protein (CFTR) expression in the developing human brain: comparative immunohistochemical study between patients with normal and mutated CFTR.

PubMed

Marcorelles, Pascale; Friocourt, Gaëlle; Uguen, Arnaud; Ledé, Françoise; Férec, Claude; Laquerrière, Annie

2014-11-01

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein has recently been shown to be expressed in the human adult central nervous system (CNS). As CFTR expression has also been documented during embryonic development in several organs, such as the respiratory tract, the intestine and the male reproductive system, suggesting a possible role during development we decided to investigate the expression of CFTR in the human developing CNS. In addition, as some, although rare, neurological symptoms have been reported in patients with CF, we compared the expression of normal and mutated CFTR at several fetal stages. Immunohistochemistry was performed on brain and spinal cord samples of foetuses between 13 and 40 weeks of gestation and compared with five patients with cystic fibrosis (CF) of similar ages. We showed in this study that CFTR is only expressed in neurons and has an early and widespread distribution during development. Although we did not observe any cerebral abnormality in patients with CF, we observed a slight delay in the maturation of several brain structures. We also observed different expression and localization of CFTR depending on the brain structure or the cell maturation stage. Our findings, along with a literature review on the neurological phenotypes of patients with CF, suggest that this gene may play previously unsuspected roles in neuronal maturation or function. © The Author(s) 2014.

Expression of an Intestine-Specific Transcription Factor (CDX1) in Intestinal Metaplasia and in Subsequently Developed Intestinal Type of Cholangiocarcinoma in Rat Liver

PubMed Central

Ren, Ping; Silberg, Debra G.; Sirica, Alphonse E.

2000-01-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478–486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats. PMID:10666391

Expression of an intestine-specific transcription factor (CDX1) in intestinal metaplasia and in subsequently developed intestinal type of cholangiocarcinoma in rat liver.

PubMed

Ren, P; Silberg, D G; Sirica, A E

2000-02-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478-486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats.

Synthesis of elastic microfibrillar components fibrillin-1 and fibrillin-2 by human optic nerve head astrocytes in situ and in vitro.

PubMed

Pena, J D; Mello, P A; Hernandez, M R

2000-05-01

The purpose of this study was to identify elastic microfibrillar components fibrillin-1 and fibrillin-2 in optic nerve heads of adult normal and glaucomatous subjects, in cultured optic nerve head astrocytes (type 1B astrocytes), as well as fibrillin-1 in fetal optic nerve heads. To characterize synthesis and gene expression of microfibrillar proteins in human optic nerve heads and cultured type 1B astrocytes, light microscopy immunohistochemistry, in situ hybridization, and RT-PCR or Northern blots were performed. Our results demonstrated that fibrillin-1 was associated with blood vessels, astrocytes in the glial columns and cribriform plates, and with astrocyte processes in the nerve bundles in all samples. In glaucomatous optic nerves there was enhanced fibrillin-1 immunoreactivity, especially surrounding blood vessels. Fibrillin-2 was localized primarily to blood vessels in all samples, without qualitative differences between normal and glaucomatous samples. In fetal optic nerve heads fibrillin-1 mRNA was localized to glial cells and to the blood vessel walls. In adult optic nerve heads, there was little fibrillin-1 mRNA as detectable by in situ hybridization and RT-PCR. There was no detectable upregulation of fibrillin-1 mRNA in glaucoma. In cultured type 1B astrocytes, fibrillin-1 staining was mostly pericellular. There was little fibrillin-2 immunoreactivity. In conclusion, astrocytes from the optic nerve head deposit elastic microfibrillar components in situ and in vitro, with a predominance of fibrillin-1. Upregulation of fibrillin-1 mRNA was not observed in glaucoma, suggesting that increased transcription may occur early in the disease process. Cultures of type 1B astrocytes from the optic nerve head provides a useful model to study mechanisms regulating the interactions of elastin and the microfibrils in optic nerve head astrocytes.

Nintendo Wii remote controllers for head posture measurement: accuracy, validity, and reliability of the infrared optical head tracker.

PubMed

Kim, Jongshin; Nam, Kyoung Won; Jang, Ik Gyu; Yang, Hee Kyung; Kim, Kwang Gi; Hwang, Jeong-Min

2012-03-15

To evaluate the accuracy, validity, and reliability of a newly developed infrared optical head tracker (IOHT) using Nintendo Wii remote controllers (WiiMote; Nintendo Co. Ltd., Kyoto, Japan) for measurement of the angle of head posture. The IOHT consists of two infrared (IR) receivers (WiiMote) that are fixed to a mechanical frame and connected to a monitoring computer via a Bluetooth communication channel and an IR beacon that consists of four IR light-emitting diodes (LEDs). With the use of the Cervical Range of Motion (CROM; Performance Attainment Associates, St. Paul, MN) as a reference, one- and three-dimensional (1- and 3-D) head postures of 20 normal adult subjects (20-37 years of age; 9 women and 11 men) were recorded with the IOHT. In comparison with the data from the CROM, the IOHT-derived results showed high consistency. The measurements of 1- and 3-D positions of the human head with the IOHT were very close to those of the CROM. The correlation coefficients of 1- and 3-D positions between the IOHT and the CROM were more than 0.99 and 0.96 (P < 0.05, Pearson's correlation test), respectively. Reliability tests of the IOHT for the normal adult subjects for 1- and 3-D positions of the human head had 95% limits of agreement angles of approximately ±4.5° and ±8.0°, respectively. The IOHT showed strong concordance with the CROM and relatively good test-retest reliability, thus proving its validity and reliability as a head-posture-measuring device. Considering its high performance, ease of use, and low cost, the IOHT has the potential to be widely used as a head-posture-measuring device in clinical practice.

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

PubMed Central

Smith, Kiersten S.; Morrell, Joan I.

2010-01-01

The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli. PMID:21056059

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

PubMed

Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

2008-08-01

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

PubMed Central

Gumucio, D L; Rood, K L; Gray, T A; Riordan, M F; Sartor, C I; Collins, F S

1988-01-01

The molecular mechanisms responsible for the human fetal-to-adult hemoglobin switch have not yet been elucidated. Point mutations identified in the promoter regions of gamma-globin genes from individuals with nondeletion hereditary persistence of fetal hemoglobin (HPFH) may mark cis-acting sequences important for this switch, and the trans-acting factors which interact with these sequences may be integral parts in the puzzle of gamma-globin gene regulation. We have used gel retardation and footprinting strategies to define nuclear proteins which bind to the normal gamma-globin promoter and to determine the effect of HPFH mutations on the binding of a subset of these proteins. We have identified five proteins in human erythroleukemia cells (K562 and HEL) which bind to the proximal promoter region of the normal gamma-globin gene. One factor, gamma CAAT, binds the duplicated CCAAT box sequences; the -117 HPFH mutation increases the affinity of interaction between gamma CAAT and its cognate site. Two proteins, gamma CAC1 and gamma CAC2, bind the CACCC sequence. These proteins require divalent cations for binding. The -175 HPFH mutation interferes with the binding of a fourth protein, gamma OBP, which binds an octamer sequence (ATGCAAAT) in the normal gamma-globin promoter. The HPFH phenotype of the -175 mutation indicates that the octamer-binding protein may play a negative regulatory role in this setting. A fifth protein, EF gamma a, binds to sequences which overlap the octamer-binding site. The erythroid-specific distribution of EF gamma a and its close approximation to an apparent repressor-binding site suggest that it may be important in gamma-globin regulation. Images PMID:2468996

The Biological Role of Nestin(+)-Cells in Physiological and Pathological Cardiovascular Remodeling

PubMed Central

Calderone, Angelino

2018-01-01

The intermediate filament protein nestin was identified in diverse populations of cells implicated in cardiovascular remodeling. Cardiac resident neural progenitor/stem cells constitutively express nestin and following an ischemic insult migrate to the infarct region and participate in angiogenesis and neurogenesis. A modest number of normal adult ventricular fibroblasts express nestin and the intermediate filament protein is upregulated during the progression of reparative and reactive fibrosis. Nestin depletion attenuates cell cycle re-entry suggesting that increased expression of the intermediate filament protein in ventricular fibroblasts may represent an activated phenotype accelerating the biological impact during fibrosis. Nestin immunoreactivity is absent in normal adult rodent ventricular cardiomyocytes. Following ischemic damage, the intermediate filament protein is induced in a modest population of pre-existing adult ventricular cardiomyocytes bordering the peri-infarct/infarct region and nestin(+)-ventricular cardiomyocytes were identified in the infarcted human heart. The appearance of nestin(+)-ventricular cardiomyocytes post-myocardial infarction (MI) recapitulates an embryonic phenotype and depletion of the intermediate filament protein inhibits cell cycle re-entry. Recruitment of the serine/threonine kinase p38 MAPK secondary to an overt inflammatory response after an ischemic insult may represent a seminal event limiting the appearance of nestin(+)-ventricular cardiomyocytes and concomitantly suppressing cell cycle re-entry. Endothelial and vascular smooth muscle cells (VSMCs) express nestin and upregulation of the intermediate filament protein may directly contribute to vascular remodeling. This review will highlight the biological role of nestin(+)-cells during physiological and pathological remodeling of the heart and vasculature and discuss the phenotypic advantage attributed to the intermediate filament protein. PMID:29492403

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, L.R.

Much research has been devoted to measurement of total blood volume (TBV) and cardiac output (CO) in humans but not enough effort has been devoted to collection and reduction of results for the purpose of deriving typical or {open_quotes}reference{close_quotes} values. Identification of normal values for TBV and CO is needed not only for clinical evaluations but also for the development of biokinetic models for ultra-short-lived radionuclides used in nuclear medicine (Leggett and Williams 1989). The purpose of this report is to offer reference values for TBV and CO, along with estimates of the associated uncertainties that arise from intra- andmore » inter-subject variation, errors in measurement techniques, and other sources. Reference values are derived for basal supine CO and TBV in reference adult humans, and differences associated with age, sex, body size, body position, exercise, and other circumstances are discussed.« less

[Research advances in CKLF-like MARVEL transmembrane domain containing member 5].

PubMed

Yuan, Ye-qing; Xiao, Yun-bei; Liu, Zhen-hua; Zhang, Xiao-wei; Xu, Tao; Wang, Xiao-feng

2012-12-01

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.

Probability of regenerating a normal limb after bite injury in the Mexican axolotl (Ambystoma mexicanum)

PubMed Central

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L.

2014-01-01

Abstract Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls (Ambystoma mexicanum) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary‐housed males and group‐housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury probably explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury. PMID:25745564

A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults123

PubMed Central

Stote, Kim S; Baer, David J; Spears, Karen; Paul, David R; Harris, G Keith; Rumpler, William V; Strycula, Pilar; Najjar, Samer S; Ferrucci, Luigi; Ingram, Donald K; Longo, Dan L; Mattson, Mark P

2009-01-01

Background Although consumption of 3 meals/d is the most common pattern of eating in industrialized countries, a scientific rationale for this meal frequency with respect to optimal health is lacking. A diet with less meal frequency can improve the health and extend the lifespan of laboratory animals, but its effect on humans has never been tested. Objective A pilot study was conducted to establish the effects of a reduced-meal-frequency diet on health indicators in healthy, normal-weight adults. Design The study was a randomized crossover design with two 8-wk treatment periods. During the treatment periods, subjects consumed all of the calories needed for weight maintenance in either 3 meals/d or 1 meal/d. Results Subjects who completed the study maintained their body weight within 2 kg of their initial weight throughout the 6-mo period. There were no significant effects of meal frequency on heart rate, body temperature, or most of the blood variables measured. However, when consuming 1 meal/d, subjects had a significant increase in hunger; a significant modification of body composition, including reductions in fat mass; significant increases in blood pressure and in total, LDL-, and HDL-cholesterol concentrations; and a significant decrease in concentrations of cortisol. Conclusions Normal-weight subjects are able to comply with a 1 meal/d diet. When meal frequency is decreased without a reduction in overall calorie intake, modest changes occur in body composition, some cardiovascular disease risk factors, and hematologic variables. Diurnal variations may affect outcomes. PMID:17413096

Effects of aging on identifying emotions conveyed by point-light walkers.

PubMed

Spencer, Justine M Y; Sekuler, Allison B; Bennett, Patrick J; Giese, Martin A; Pilz, Karin S

2016-02-01

The visual system is able to recognize human motion simply from point lights attached to the major joints of an actor. Moreover, it has been shown that younger adults are able to recognize emotions from such dynamic point-light displays. Previous research has suggested that the ability to perceive emotional stimuli changes with age. For example, it has been shown that older adults are impaired in recognizing emotional expressions from static faces. In addition, it has been shown that older adults have difficulties perceiving visual motion, which might be helpful to recognize emotions from point-light displays. In the current study, 4 experiments were completed in which older and younger adults were asked to identify 3 emotions (happy, sad, and angry) displayed by 4 types of point-light walkers: upright and inverted normal walkers, which contained both local motion and global form information; upright scrambled walkers, which contained only local motion information; and upright random-position walkers, which contained only global form information. Overall, emotion discrimination accuracy was lower in older participants compared with younger participants, specifically when identifying sad and angry point-light walkers. In addition, observers in both age groups were able to recognize emotions from all types of point-light walkers, suggesting that both older and younger adults are able to recognize emotions from point-light walkers on the basis of local motion or global form. (c) 2016 APA, all rights reserved).

Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies

PubMed Central

Chi, Michael W.; Griffith, Leslie C.; Vecsey, Christopher G.

2014-01-01

Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of population densities throughout larval development, kept them isolated during early adulthood, and then tested their sleep patterns. Our findings reveal that flies that had been isolated as larvae had more fragmented sleep than those that had been raised at higher population densities. This effect was more prominent in females than in males. Larval population density did not affect sleep in female flies that were mutant for amnesiac, which has been shown to be required for normal memory consolidation, adult sleep regulation, and brain development. In contrast, larval population density effects on sleep persisted in female flies lacking the olfactory receptor or83b, suggesting that olfactory signals are not required for the effects of larval population density on adult sleep. These findings show that population density during early development can alter sleep behavior in adulthood, suggesting that genetic and/or structural changes are induced by this developmental manipulation that persist through metamorphosis. PMID:25116571

Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies.

PubMed

Chi, Michael W; Griffith, Leslie C; Vecsey, Christopher G

2014-08-11

Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of population densities throughout larval development, kept them isolated during early adulthood, and then tested their sleep patterns. Our findings reveal that flies that had been isolated as larvae had more fragmented sleep than those that had been raised at higher population densities. This effect was more prominent in females than in males. Larval population density did not affect sleep in female flies that were mutant for amnesiac, which has been shown to be required for normal memory consolidation, adult sleep regulation, and brain development. In contrast, larval population density effects on sleep persisted in female flies lacking the olfactory receptor or83b, suggesting that olfactory signals are not required for the effects of larval population density on adult sleep. These findings show that population density during early development can alter sleep behavior in adulthood, suggesting that genetic and/or structural changes are induced by this developmental manipulation that persist through metamorphosis.

Aging affects neural precision of speech encoding

PubMed Central

Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2012-01-01

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the auditory system’s temporal precision. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (ages 18 to 30) and older adult humans (60 to 67). Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Taken together, our results support the theory that older adults have a loss of temporal precision in subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception. PMID:23055485

Visual Attention in Deaf and Normal Hearing Adults: Effects of Stimulus Compatibility

ERIC Educational Resources Information Center

Sladen, Douglas P.; Tharpe, Anne Marie; Ashmead, Daniel H.; Grantham, D. Wesley; Chun, Marvin M.

2005-01-01

Visual perceptual skills of deaf and normal hearing adults were measured using the Eriksen flanker task. Participants were seated in front of a computer screen while a series of target letters flanked by similar or dissimilar letters was flashed in front of them. Participants were instructed to press one button when they saw an "H," and another…

Contributions of Language and Memory Demands to Verbal Memory Performance in Language-Learning Disabilities

ERIC Educational Resources Information Center

Isaki, Emi; Spaulding, Tammie J.; Plante, Elena

2008-01-01

The purpose of this study is to investigate the performance of adults with language-based learning disorders (L/LD) and normal language controls on verbal short-term and verbal working memory tasks. Eighteen adults with L/LD and 18 normal language controls were compared on verbal short-term memory and verbal working memory tasks under low,…

Glimpsing Speech in the Presence of Nonsimultaneous Amplitude Modulations from a Competing Talker: Effect of Modulation Rate, Age, and Hearing Loss

ERIC Educational Resources Information Center

Fogerty, Daniel; Ahlstrom, Jayne B.; Bologna, William J.; Dubno, Judy R.

2016-01-01

Purpose: This study investigated how listeners process acoustic cues preserved during sentences interrupted by nonsimultaneous noise that was amplitude modulated by a competing talker. Method: Younger adults with normal hearing and older adults with normal or impaired hearing listened to sentences with consonants or vowels replaced with noise…

Response Errors in Females' and Males' Sentence Lipreading Necessitate Structurally Different Models for Predicting Lipreading Accuracy

ERIC Educational Resources Information Center

Bernstein, Lynne E.

2018-01-01

Lipreaders recognize words with phonetically impoverished stimuli, an ability that varies widely in normal-hearing adults. Lipreading accuracy for sentence stimuli was modeled with data from 339 normal-hearing adults. Models used measures of phonemic perceptual errors, insertion of text that was not in the stimulus, gender, and auditory speech…

Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults

PubMed Central

Casaletto, Kaitlin B.; Ward, Michael E.; Baker, Nicholas S.; Bettcher, Brianne M.; Gelfand, Jeffrey M.; Li, Yaqiao; Chen, Robert; Dutt, Shubir; Miller, Bruce; Kramer, Joel H.; Green, Ari J.

2017-01-01

Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer’s disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study. Retinal nerve fiber thinning and reduced total macular and macular ganglion cell volumes were each associated with smaller MTL volumes (ps < 0.04). Notably, these markers of retinal structure were not associated with primary motor cortex or basal ganglia volumes (regions relatively unaffected in AD) (ps > 0.70), or frontal, precuneus, or temporoparietal volumes (regions affected in later AD Braak staging ps > 0.20). Retinal structure was not significantly associated with verbal or visual memory consolidation performances (ps > 0.14). Retinal structure was associated with MTL volumes, but not memory performances, in otherwise neurologically normal older adults. Given that MTL atrophy is a neuropathological hallmark of AD, retinal integrity may be an early marker of ongoing AD-related brain health. PMID:28068565

Typical and Atypical Development of Functional Connectivity in the Face Network.

PubMed

Song, Yiying; Zhu, Qi; Li, Jingguang; Wang, Xu; Liu, Jia

2015-10-28

Extensive studies have demonstrated that face recognition performance does not reach adult levels until adolescence. However, there is no consensus on whether such prolonged improvement stems from development of general cognitive factors or face-specific mechanisms. Here, we used behavioral experiments and functional magnetic resonance imaging (fMRI) to evaluate these two hypotheses. With a large cohort of children (n = 379), we found that the ability of face-specific recognition in humans increased with age throughout childhood and into late adolescence in both face memory and face perception. Neurally, to circumvent the potential problem of age differences in task performance, attention, or cognitive strategies in task-state fMRI studies, we measured the resting-state functional connectivity (RSFC) between the occipital face area (OFA) and fusiform face area (FFA) in human brain and found that the OFA-FFA RSFC increased until 11-13 years of age. Moreover, the OFA-FFA RSFC was selectively impaired in adults with developmental prosopagnosia (DP). In contrast, no age-related changes or differences between DP and normal adults were observed for RSFCs in the object system. Finally, the OFA-FFA RSFC matured earlier than face selectivity in either the OFA or FFA. These results suggest the critical role of the OFA-FFA RSFC in the development of face recognition. Together, our findings support the hypothesis that prolonged development of face recognition is face specific, not domain general. Copyright © 2015 the authors 0270-6474/15/3514624-12$15.00/0.

The role of auditory and cognitive factors in understanding speech in noise by normal-hearing older listeners

PubMed Central

Schoof, Tim; Rosen, Stuart

2014-01-01

Normal-hearing older adults often experience increased difficulties understanding speech in noise. In addition, they benefit less from amplitude fluctuations in the masker. These difficulties may be attributed to an age-related auditory temporal processing deficit. However, a decline in cognitive processing likely also plays an important role. This study examined the relative contribution of declines in both auditory and cognitive processing to the speech in noise performance in older adults. Participants included older (60–72 years) and younger (19–29 years) adults with normal hearing. Speech reception thresholds (SRTs) were measured for sentences in steady-state speech-shaped noise (SS), 10-Hz sinusoidally amplitude-modulated speech-shaped noise (AM), and two-talker babble. In addition, auditory temporal processing abilities were assessed by measuring thresholds for gap, amplitude-modulation, and frequency-modulation detection. Measures of processing speed, attention, working memory, Text Reception Threshold (a visual analog of the SRT), and reading ability were also obtained. Of primary interest was the extent to which the various measures correlate with listeners' abilities to perceive speech in noise. SRTs were significantly worse for older adults in the presence of two-talker babble but not SS and AM noise. In addition, older adults showed some cognitive processing declines (working memory and processing speed) although no declines in auditory temporal processing. However, working memory and processing speed did not correlate significantly with SRTs in babble. Despite declines in cognitive processing, normal-hearing older adults do not necessarily have problems understanding speech in noise as SRTs in SS and AM noise did not differ significantly between the two groups. Moreover, while older adults had higher SRTs in two-talker babble, this could not be explained by age-related cognitive declines in working memory or processing speed. PMID:25429266

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Baldwin, Kenneth M.

1995-01-01

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

PubMed

Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

2017-10-01

No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Neocortical glial cell numbers in human brains.

PubMed

Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

2008-11-01

Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

An integrated mathematical model of the human cardiopulmonary system: model development.

PubMed

Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

2016-04-01

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. Copyright © 2016 the American Physiological Society.

GRP-induced up-regulation of Hsp72 promotes CD16+/94+ natural killer cell binding to colon cancer cells causing tumor cell cytolysis.

PubMed

Taglia, Lauren; Matusiak, Damien; Benya, Richard V

2008-01-01

Gastrin-releasing peptide (GRP) and its receptor (GRPR) are not normally expressed by epithelial cells lining the adult human colon. However post malignant transformation both GRP and its receptor are aberrantly expressed in the colon where we have previously shown they act to retard metastasis by enhancing tumor cell attachment to the extracellular matrix. In the present study, we show that GRP signaling via its cognate receptor when both are aberrantly expressed in human colon cancer cells causes heat shock protein 72 (Hsp72) to be expressed. We show that GRP/GRPR induces expression of Hsp72 by signaling via focal adhesion kinase. When expressed, Hsp72 promotes the binding of CD16+ and CD94+ natural killer cells, resulting in tumor cell cytolysis. These findings demonstrate the presence of a novel mechanism whereby aberrantly expressed GRP/GRPR in human colorectal cancer attenuates tumor progression and may promote a favorable outcome.

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults

PubMed Central

Foley, J. M.; Gooding, A. L.; Thames, A. D.; Ettenhofer, M. L.; Kim, M. S.; Castellon, S. A.; Marcotte, T. D.; Sadek, J. R.; Heaton, R. K.; van Gorp, W. G.; Hinkin, C. H.

2013-01-01

Objectives To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. Methods Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 ≤ 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). Results Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = –0.40, P < .001; time: b = –0.40, P = .001) and attention (blocks: b = –0.49, P = .001; time: b = –0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. Conclusions Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline. PMID:23314403

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

PubMed Central

Walko, Gernot; Woodhouse, Samuel; Pisco, Angela Oliveira; Rognoni, Emanuel; Liakath-Ali, Kifayathullah; Lichtenberger, Beate M.; Mishra, Ajay; Telerman, Stephanie B.; Viswanathan, Priyalakshmi; Logtenberg, Meike; Renz, Lisa M.; Donati, Giacomo; Quist, Sven R.; Watt, Fiona M.

2017-01-01

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2. PMID:28332498

Pancreatic β-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human Diabetes.

PubMed

Dahan, Tehila; Ziv, Oren; Horwitz, Elad; Zemmour, Hai; Lavi, Judith; Swisa, Avital; Leibowitz, Gil; Ashcroft, Frances M; In't Veld, Peter; Glaser, Benjamin; Dor, Yuval

2017-02-01

β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin + cells, gastrin expression in humans with T2D occurs in both insulin + and somatostatin + cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated β-cells after exposure to severe hyperglycemia. Gastrin expression in adult β-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of β-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human β-cell reprogramming in diabetes. © 2017 by the American Diabetes Association.

Pancreatic β-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human Diabetes

PubMed Central

Dahan, Tehila; Ziv, Oren; Horwitz, Elad; Zemmour, Hai; Lavi, Judith; Swisa, Avital; Leibowitz, Gil; Ashcroft, Frances M.; In’t Veld, Peter

2017-01-01

β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated β-cells after exposure to severe hyperglycemia. Gastrin expression in adult β-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of β-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human β-cell reprogramming in diabetes. PMID:27864307

Prospective Isolation and Comparison of Human Germinal Matrix and Glioblastoma EGFR+ Populations with Stem Cell Properties.

PubMed

Tome-Garcia, Jessica; Tejero, Rut; Nudelman, German; Yong, Raymund L; Sebra, Robert; Wang, Huaien; Fowkes, Mary; Magid, Margret; Walsh, Martin; Silva-Vargas, Violeta; Zaslavsky, Elena; Friedel, Roland H; Doetsch, Fiona; Tsankova, Nadejda M

2017-05-09

Characterization of non-neoplastic and malignant human stem cell populations in their native state can provide new insights into gliomagenesis. Here we developed a purification strategy to directly isolate EGFR +/- populations from human germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF ligand ( LB EGFR + ), and uniquely compared their functional and molecular properties. LB EGFR + populations in both GM and GBM encompassed all sphere-forming cells and displayed proliferative stem cell properties in vitro. In xenografts, LB EGFR + GBM cells showed robust tumor initiation and progression to high-grade, infiltrative gliomas. Whole-transcriptome sequencing analysis confirmed enrichment of proliferative pathways in both developing and neoplastic freshly isolated EGFR + populations, and identified both unique and shared sets of genes. The ability to prospectively isolate stem cell populations using native ligand-binding capacity opens new doors onto understanding both normal human development and tumor cell biology. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Inca - interparietal bones in neurocranium of human skulls in central India

PubMed Central

Marathe, RR; Yogesh, AS; Pandit, SV; Joshi, M; Trivedi, GN

2010-01-01

Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. Objectives: To find the incidence of Inca variants in Central India. Materials and Methods: In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Results: Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the five observed Inca ossicles, two were fragmented. Conclusions: This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists. PMID:21799611

Inca - interparietal bones in neurocranium of human skulls in central India.

PubMed

Marathe, Rr; Yogesh, As; Pandit, Sv; Joshi, M; Trivedi, Gn

2010-01-01

Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. To find the incidence of Inca variants in Central India. In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the five observed Inca ossicles, two were fragmented. This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists.

Midline shift and lateral guidance angle in adults with unilateral posterior crossbite.

PubMed

Rilo, Benito; da Silva, José Luis; Mora, María Jesús; Cadarso-Suárez, Carmen; Santana, Urbano

2008-06-01

Unilateral posterior crossbite is a malocclusion that, if not corrected during infancy, typically causes permanent asymmetry. Our aims in this study were to evaluate various occlusal parameters in a group of adults with uncorrected unilateral posterior crossbite and to compare findings with those obtained in a group of normal subjects. Midline shift at maximum intercuspation, midline shift at maximum aperture, and lateral guidance angle in the frontal plane were assessed in 25 adults (ages, 17-26 years; mean, 19.6 years) with crossbites. Midline shift at maximum intercuspation was zero (ie, centric midline) in 36% of the crossbite subjects; the remaining subjects had a shift toward the crossbite side. Midline shift at maximum aperture had no association with crossbite side. Lateral guidance angle was lower on the crossbite side than on the noncrossbite side. No parameter studied showed significant differences with respect to the normal subjects. Adults with unilateral posterior crossbite have adaptations that compensate for the crossbite and maintain normal function.

Neural decoding of treadmill walking from noninvasive electroencephalographic signals

PubMed Central

Presacco, Alessandro; Goodman, Ronald; Forrester, Larry

2011-01-01

Chronic recordings from ensembles of cortical neurons in primary motor and somatosensory areas in rhesus macaques provide accurate information about bipedal locomotion (Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. Front Integr Neurosci 3: 3, 2009). Here we show that the linear and angular kinematics of the ankle, knee, and hip joints during both normal and precision (attentive) human treadmill walking can be inferred from noninvasive scalp electroencephalography (EEG) with decoding accuracies comparable to those from neural decoders based on multiple single-unit activities (SUAs) recorded in nonhuman primates. Six healthy adults were recorded. Participants were asked to walk on a treadmill at their self-selected comfortable speed while receiving visual feedback of their lower limbs (i.e., precision walking), to repeatedly avoid stepping on a strip drawn on the treadmill belt. Angular and linear kinematics of the left and right hip, knee, and ankle joints and EEG were recorded, and neural decoders were designed and optimized with cross-validation procedures. Of note, the optimal set of electrodes of these decoders were also used to accurately infer gait trajectories in a normal walking task that did not require subjects to control and monitor their foot placement. Our results indicate a high involvement of a fronto-posterior cortical network in the control of both precision and normal walking and suggest that EEG signals can be used to study in real time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function. PMID:21768121

Understanding Older Adult's Perceptions of Factors that Support Trust in Human and Robot Care Providers.

PubMed

Stuck, Rachel E; Rogers, Wendy A

2017-06-01

As the population of older adults increase so will the need for care providers, both human and robot. Trust is a key aspect to establish and maintain a successful older adult-care provider relationship. However, due to trust volatility it is essential to understand it within specific contexts. This proposed mixed methods study will explore what dimensions of trust emerge as important within the human-human and human-robot dyads in older adults and care providers. First, this study will help identify key qualities that support trust in a care provider relationship. By understanding what older adults perceive as needing to trust humans and robots for various care tasks, we can begin to provide recommendations based on user expectations for design to support trust.

Discourse changes in early Alzheimer disease, mild cognitive impairment, and normal aging.

PubMed

Chapman, Sandra Bond; Zientz, Jennifer; Weiner, Myron; Rosenberg, Roger; Frawley, William; Burns, Mary Hope

2002-01-01

The purpose of this study was to determine the sensitivity of discourse gist measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and in the preclinical stages. Differences in discourse abilities were examined in 25 cognitively normal adults, 24 adults with mild probable AD, and 20 adults with mild cognitive impairment (MCI) at gist and detail levels of discourse processing. The authors found that gist and detail levels of discourse processing were significantly impaired in persons with AD and MCI as compared with normal control subjects. Gist-level discourse processing abilities showed minimal overlap between cognitively normal control subjects and those with mild AD. Moreover, the majority of the persons with MCI performed in the range of AD on gist measures. These findings indicate that discourse gist measures hold promise as a diagnostic complement to enhance early detection of AD. Further studies are needed to determine how early the discourse gist deficits arise in AD.

Have you got any cholesterol? Adults' views of human nutrition

NASA Astrophysics Data System (ADS)

Schibeci, Renato; Wong, Khoon Yoong

1994-12-01

The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaoxia, E-mail: xiaoxia.yang@fda.hhs.gov; Doerge, Daniel R.; Teeguarden, Justin G.

A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d{sub 6}-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d{sub 6}-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult humanmore » model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d{sub 6}-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.« less

Higher fasting glucose is associated with poorer cognition among healthy young adults.

PubMed

Hawkins, Misty A W; Gunstad, John; Calvo, Dayana; Spitznagel, Mary Beth

2016-02-01

Obesity is associated with cognitive deficits; however, the mechanisms are unclear, especially among otherwise healthy adults. Our objectives were to examine (a) whether obesity is linked to elevations in fasting glucose and (b) whether these elevations are associated with cognitive impairment among otherwise healthy young adults. Participants were 35 normal weight adults and 35 young adults with obesity who completed a task from the Automated Neuropsychological Assessment Metrics-4 (ANAM-4). Measured body mass index (BMI) and fasting blood glucose levels (mg/dL) were examined. Persons with obesity had higher fasting glucose levels than normal weight persons (p = .03). After applying Bonferroni correction for multiple tests, higher fasting glucose predicted less accurate performance on tests of inhibitory control: Go/No-Go Commission Errors (β = .33, p = .004). No effects were observed for sustained attention or working memory (ps ≥. 049). Persons with glucose levels in the prediabetes range had nearly twice as many errors as those with normal glucose, a large effect that was independent of BMI. Young adults who were obese but otherwise healthy had higher fasting glucose levels compared with normal weight peers. Higher glucose levels were associated with poorer cognitive performance on tests of inhibitory control, especially among individuals with prediabetes levels. Thus, subclinical elevations in blood glucose may contribute to cognitive impairment and, ultimately, greater impulsivity-well in advance of the development of chronic disease states (e.g., insulin resistance or Type 2 diabetes) and independently of excess adiposity--though prospective studies are needed to determine directionality of this relationship. (c) 2016 APA, all rights reserved).

New insights into the development and differentiation of the human anorectal epithelia. Are there clinical consequences?

PubMed Central

Zehm, Sarah; Illig, Romana; Moser, Patrizia; Aigner, Felix

2010-01-01

Purpose The epithelial lining of the anorectum still raises discussions concerning the levels of transition between the various zones and leads to an incomplete understanding of the immmunoprofile of rectal carcinoma. Since the expression of cytokeratins depends on the epithelial cell-type and the parahox-gene CDX2 is important for the development of the colorectal epithelium, we investigated different cytokeratins and CDX2 in the anorectum of human prenatal stages and in adult normal and neoplastic anorecta. Materials and Methods The differentiation and spatiotemporal distribution of the epithelial zones were examined in 33 human embryos and fetuses, in a 2-year-old child and four adults. In comparison, 17 specimens of ultralow rectal adenocarcinoma and 4 specimens of anal carcinoma were investigated. Monoclonal antibodies were directed against cytokeratin (CK) 18, 20, 7 and 14 and CDX2. Results Due to the cytokeratin profile and to CDX2 expression, the different anorectal zones could already be differentiated in human prenatal life. We showed that anorectal epithelial differentiation including the squamous epithelia ran in a craniocaudal direction, and that the anorectal zone was a transitional zone between rectal zone and anal transitional zone where CK 7, 18, 20 and CDX2 are simultaneously expressed. All cases of rectal adenocarcinoma showed positivity for CK 18, 20 and CDX2, and three also labelled for CK 7, whereas CK 14 was only expressed in the cases of anal carcinoma. Conclusions Our results elucidate the connection between the prenatal pattern and the origin of the different types of anorectal carcinoma. PMID:20563874

New insights into the development and differentiation of the human anorectal epithelia. Are there clinical consequences?

PubMed

Fritsch, Helga; Zehm, Sarah; Illig, Romana; Moser, Patrizia; Aigner, Felix

2010-10-01

The epithelial lining of the anorectum still raises discussions concerning the levels of transition between the various zones and leads to an incomplete understanding of the immmunoprofile of rectal carcinoma. Since the expression of cytokeratins depends on the epithelial cell-type and the parahox-gene CDX2 is important for the development of the colorectal epithelium, we investigated different cytokeratins and CDX2 in the anorectum of human prenatal stages and in adult normal and neoplastic anorecta. The differentiation and spatiotemporal distribution of the epithelial zones were examined in 33 human embryos and fetuses, in a 2-year-old child and four adults. In comparison, 17 specimens of ultralow rectal adenocarcinoma and 4 specimens of anal carcinoma were investigated. Monoclonal antibodies were directed against cytokeratin (CK) 18, 20, 7 and 14 and CDX2. Due to the cytokeratin profile and to CDX2 expression, the different anorectal zones could already be differentiated in human prenatal life. We showed that anorectal epithelial differentiation including the squamous epithelia ran in a craniocaudal direction, and that the anorectal zone was a transitional zone between rectal zone and anal transitional zone where CK 7, 18, 20 and CDX2 are simultaneously expressed. All cases of rectal adenocarcinoma showed positivity for CK 18, 20 and CDX2, and three also labelled for CK 7, whereas CK 14 was only expressed in the cases of anal carcinoma. Our results elucidate the connection between the prenatal pattern and the origin of the different types of anorectal carcinoma.

Ureaplasma--Are you sitting comfortably?

PubMed

Gwee, Amanda; Curtis, Nigel

2014-01-01

The role of Ureaplasma spp. in human disease has been controversial, as these bacteria are commonly isolated as part of the normal genital tract flora. Ureaplasma has been shown to have a causal role in urogenital infections and is associated with significant foetal and neonatal morbidity and mortality when infection occurs during the perinatal period. Although rare, invasive Ureaplasma infection (meningitis, renal abscess, mediastinitis and arthritis) has also been reported in both adults and children. This review outlines the unique microbiological features and various clinical presentations of Ureaplasma infection. It also discusses the treatment options, which in the neonatal period can be particularly challenging. Copyright © 2013. Published by Elsevier Ltd.

Update on the Notochord Including its Embryology, Molecular Development, and Pathology: A Primer for the Clinician

PubMed Central

Ramesh, Tushar; Nagula, Sai V; Saker, Erfanul; Shoja, Mohammadali; Loukas, Marios; Oskouian, Rod J; Tubbs, R. Shane

2017-01-01

The notochord is a rod-like embryological structure, which plays a vital role in the development of the vertebrate. Though embryological, remnants of this structure have been observed in the nucleus pulposus of the intervertebral discs of normal adults. Pathologically, these remnants can give rise to slow-growing and recurrent notochord-derived tumors called chordomas. Using standard search engines, the literature was reviewed regarding the anatomy, embryology, molecular development, and pathology of the human notochord. Clinicians who interpret imaging or treat patients with pathologies linked to the notochord should have a good working knowledge of its development and pathology. PMID:28480155

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Penetration and aspiration in healthy older adults as assessed during endoscopic evaluation of swallowing.

PubMed

Butler, Susan G; Stuart, Andrew; Markley, Lisa; Rees, Catherine

2009-03-01

A previous article from our group presented data on normal swallowing as assessed during simultaneous manometry and flexible endoscopic evaluation of swallowing (FEES). Because penetration and aspiration events were identified in healthy adults, the question arose, could the presence of the manometric catheter confound normal FEES findings? Thus, a follow-up study was designed to address the effects of catheter condition on healthy older adults as assessed during FEES. Twenty older adults (mean, 78.9 years of age) participated. The participants each contributed 28 swallows, affording a study total of 560 swallows for analyses. The older adults demonstrated penetration on 82 (15%) and aspiration on 18 (3%) of 545 swallows. The numbers of participants who had penetration and aspiration during the study protocol were 75% and 30%, respectively. The older adults demonstrated both penetration and aspiration events irrespective of the presence of a catheter; whether they were drinking milk, water, or barium; whether the bolus was 5 or 10 mL; and whether they took the bolus via syringe or self-administered the bolus with a cup. However, significantly more aspiration was found on thin liquids than on puree or solids. Endoscopic data on normal swallowing physiology were generated. These may serve as an accurate benchmark for clinicians and researchers in the interpretation of dysphagia.

Variations in Velopharyngeal Structure in Adults With Repaired Cleft Palate.

PubMed

Perry, Jamie L; Kotlarek, Katelyn J; Sutton, Bradley P; Kuehn, David P; Jaskolka, Michael S; Fang, Xiangming; Point, Stuart W; Rauccio, Frank

2018-01-01

The purpose of this study was to examine differences in velopharyngeal structures between adults with repaired cleft palate and normal resonance and adults without cleft palate. Thirty-six English-speaking adults, including 6 adults (2 males and 4 females) with repaired cleft palate (M = 32.5 years of age, SD = 17.4 years) and 30 adults (15 males and 15 females) without cleft palate (M = 23.3 years of age, SD = 4.1 years), participated in the study. Fourteen velopharyngeal measures were obtained on magnetic resonance images and compared between groups (cleft and noncleft). After adjusting for body size and sex effects, there was a statistically significant difference between groups for 10 out of the 14 velopharyngeal measures. Compared to those without cleft palate, participants with repaired cleft palate had a significantly shorter hard palate height and length, shorter levator muscle length, shorter intravelar segment, more acute levator angles of origin, shorter and thinner velum, and greater pharyngeal depth. Although significant differences were evident in the cleft palate group, individuals displayed normal resonance. These findings suggest that a wide variability in velopharyngeal anatomy can occur in the presence of normal resonance, particularly for those with repaired cleft palate. Future research is needed to understand how anatomic variability impacts function, such as during speech.

The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

PubMed

Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

How Does Reading Performance Modulate the Impact of Orthographic Knowledge on Speech Processing? A Comparison of Normal Readers and Dyslexic Adults

ERIC Educational Resources Information Center

Pattamadilok, Chotiga; Nelis, Aubéline; Kolinsky, Régine

2014-01-01

Studies on proficient readers showed that speech processing is affected by knowledge of the orthographic code. Yet, the automaticity of the orthographic influence depends on task demand. Here, we addressed this automaticity issue in normal and dyslexic adult readers by comparing the orthographic effects obtained in two speech processing tasks that…

THE THERAPEUTIC EFFECT OF ENVIRONMENT ON EMOTIONALLY DISTURBED AND MENTALLY SUBNORMAL CHILDREN. A KAUFMANN INTERNATIONAL DESIGN AWARD STUDY, 1964-66.

ERIC Educational Resources Information Center

BAYES, KENNETH

CURRENT RESEARCH AND THOUGHT ON THE EFFECTS OF ARCHITECTURAL FORM AND COLOR IN THE TREATMENT OF EMOTIONALLY DISTURBED AND RETARDED CHILDREN ARE SURVEYED IN THIS PUBLICATION. TO A LESSER EXTENT, IT COVERS THE RELATIONSHIP OF THERAPY TO BEHAVIOR, NORMAL CHILDREN TO HANDICAPPED CHILDREN, NORMAL ADULTS TO MENTAL PATIENTS, AND CHILDREN TO ADULTS.…

The in vitro MIMIC® platform reflects age-associated changes in immunological responses after influenza vaccination.

PubMed

Dauner, Allison; Agrawal, Pankaj; Salvatico, Jose; Tapia, Tenekua; Dhir, Vipra; Shaik, S Farzana; Drake, Donald R; Byers, Anthony M

2017-10-04

Increasing research and development costs coupled with growing concerns over healthcare expenditures necessitate the generation of pre-clinical testing models better able to predict the efficacy of vaccines, drugs and biologics. An ideal system for evaluating vaccine immunogenicity will not only be reliable but also physiologically relevant, able to be influenced by immunomodulatory characteristics such as age or previous exposure to pathogens. We have previously described a fully autologous human cell-based MIMIC® (Modular IMmune In vitro Construct) platform which enables the evaluation of innate and adaptive immunity in vitro, including naïve and recall responses. Here, we establish the ability of this module to display reduced antibody production and T cell activation upon in vitro influenza vaccination of cells from elderly adults. In the MIMIC® system, we observe a 2.7-4.2-fold reduction in strain-specific IgG production to seasonal trivalent influenza vaccine (TIV) in the elderly when compared to adults, as well as an age-dependent decline in the generation of functional antibodies. A parallel decline in IgG production with increasing age was detected via short-term ex vivo stimulation of B cells after in vivo TIV vaccination in the same cohort. Using MIMIC®, we also detect a reduction in the number but not proportion of TIV-specific multifunctional CD154 + IFNγ + IL-2 + TNFα + CD4 + T cells in elderly adults. Inefficient induction of multifunctional helper T cells with TIV stimulation in MIMIC® despite a normalized number of initial CD4 + T cells suggests a possible mechanism for an impaired anti-TIV IgG response in elderly adults. The ability of the MIMIC® system to recapitulate differential age-associated responses in vitro provides a dynamic platform for the testing of vaccine candidates and vaccine enhancement strategies in a fully human model including the ability to interrogate specific populations, such as elderly adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does Central Vision Loss Impair Visual Search Performance of Adults More than Children?

PubMed

Satgunam, PremNandhini; Luo, Gang

2018-05-01

In general, young adults with normal vision show the best visual search performance when compared with children and older adults. Through our study, we show that this trend is not observed in individuals with vision impairment. An interaction effect of vision impairment with visual development and aging is observed. Performance in many visual tasks typically shows improvement with age until young adulthood and then declines with aging. Using a visual search task, this study investigated whether a similar age effect on performance is present in people with central vision loss. A total of 98 participants, 37 with normal sight (NS) and 61 with visual impairment (VI) searched for targets in 150 real-world digital images. Search performance was quantified by an integrated measure combining speed and accuracy. Participant ages ranged from 5 to 74 years, visual acuity from -0.14 (20/14.5) to 1.16 logMAR (20/290), and log contrast sensitivity (CS) from 0.48 to 2.0. Data analysis was performed with participants divided into three age groups: children (aged <14 years, n = 25), young adults (aged 14 to 45 years, n = 47), and older adults (aged >45 years, n = 26). Regression (r = 0.7) revealed CS (P < .001) and age (P = .003) were significant predictors of search performance. Performance of VI participants was normalized to the age-matched average performance of the NS group. In the VI group, it was found that children's normalized performance (52%) was better than both young (39%, P = .05) and older (40%, P = .048) adults. Unlike NS participants, young adults in the VI group may not have search ability superior to children with VI, despite having the same level of visual functions (quantified by visual acuity and CS). This could be because of vision impairment limiting the developmental acquisition of the age dividend for peak performance. Older adults in the VI group had the worst performance, indicating an interaction of aging.

A comparison of vestibular evoked myogenic potential (VEMP) between definite Meniere's disease patients and normal healthy adults.

PubMed

Jariengprasert, Chanchai; Tiensuwan, Montip; Euasirirattanapaisan, Khongpol

2013-12-01

To compare the results of VEMP between unilateral definite Meniere's disease patients and normal healthy adults. Thirty-two patients with unilateral definite Meniere's disease patients and 32 age-matched normal healthy adults (control) underwent VEMP tests with short tone burst of 500 Hz at 90 dBnHL. Student-t test was used for comparison of means of all parameters between two groups. Absent VEMP response was found in 14 MD patients and abnormal asymmetry ratio (AR) was found in five MD patients. Normal responses were found in all subjects of the control group. The mean P1 and N1 latencies, VEMP amplitude between unilateral MD, and control were not significantly different between two groups. However the difference between the mean AR of both groups showed statistically significant (p-value < 0.05). The upper limit of normal AR was calculated to be of 35.15%. The absence of VEMP response and AR of VEMP were more dominant than other parameters such as P1 and N1 latencies or VEMP amplitude in the detection of saccular dysfunction in MD. The results suggested that AR should be used as a tool in interpretation of VEMP response for the diagnostic batteries in MD. The upper limit of normal AR of < or = 35% should be recommended.

Induction of human embryonic and induced pluripotent stem cells into urothelium.

PubMed

Osborn, Stephanie L; Thangappan, Ravikumar; Luria, Ayala; Lee, Justin H; Nolta, Jan; Kurzrock, Eric A

2014-05-01

In vitro generation of human urothelium from stem cells would be a major advancement in the regenerative medicine field, providing alternate nonurologic and/or nonautologous tissue sources for bladder grafts. Such a model would also help decipher the mechanisms of urothelial differentiation and would facilitate investigation of deviated differentiation of normal progenitors into urothelial cancer stem cells, perhaps elucidating areas of intervention for improved treatments. Thus far, in vitro derivation of urothelium from human embryonic stem cells (hESCs) or human induced pluripotent stem (hiPS) cells has not been reported. The goal of this work was to develop an efficient in vitro protocol for the induction of hESCs into urothelium through an intermediary definitive endoderm step and free of matrices and cell contact. During directed differentiation in a urothelial-specific medium ("Uromedium"), hESCs produced up to 60% urothelium, as determined by uroplakin expression; subsequent propagation selected for 90% urothelium. Alteration of the epithelial and mesenchymal cell signaling contribution through noncell contact coculture or conditioned media did not enhance the production of urothelium. Temporospatial evaluation of transcription factors known to be involved in urothelial specification showed association of IRF1, GET1, and GATA4 with uroplakin expression. Additional hESC and hiPS cell lines could also be induced into urothelium using this in vitro system. These results demonstrate that derivation and propagation of urothelium from hESCs and hiPS cells can be efficiently accomplished in vitro in the absence of matrices, cell contact, or adult cell signaling and that the induction process appears to mimic normal differentiation.

Induction of Human Embryonic and Induced Pluripotent Stem Cells Into Urothelium

PubMed Central

Osborn, Stephanie L.; Thangappan, Ravikumar; Luria, Ayala; Lee, Justin H.; Nolta, Jan

2014-01-01

In vitro generation of human urothelium from stem cells would be a major advancement in the regenerative medicine field, providing alternate nonurologic and/or nonautologous tissue sources for bladder grafts. Such a model would also help decipher the mechanisms of urothelial differentiation and would facilitate investigation of deviated differentiation of normal progenitors into urothelial cancer stem cells, perhaps elucidating areas of intervention for improved treatments. Thus far, in vitro derivation of urothelium from human embryonic stem cells (hESCs) or human induced pluripotent stem (hiPS) cells has not been reported. The goal of this work was to develop an efficient in vitro protocol for the induction of hESCs into urothelium through an intermediary definitive endoderm step and free of matrices and cell contact. During directed differentiation in a urothelial-specific medium (“Uromedium”), hESCs produced up to 60% urothelium, as determined by uroplakin expression; subsequent propagation selected for 90% urothelium. Alteration of the epithelial and mesenchymal cell signaling contribution through noncell contact coculture or conditioned media did not enhance the production of urothelium. Temporospatial evaluation of transcription factors known to be involved in urothelial specification showed association of IRF1, GET1, and GATA4 with uroplakin expression. Additional hESC and hiPS cell lines could also be induced into urothelium using this in vitro system. These results demonstrate that derivation and propagation of urothelium from hESCs and hiPS cells can be efficiently accomplished in vitro in the absence of matrices, cell contact, or adult cell signaling and that the induction process appears to mimic normal differentiation. PMID:24657961

Electrophysiological gap detection thresholds: effects of age and comparison with a behavioral measure.

PubMed

Palmer, Shannon B; Musiek, Frank E

2014-01-01

Temporal processing ability has been linked to speech understanding ability and older adults often complain of difficulty understanding speech in difficult listening situations. Temporal processing can be evaluated using gap detection procedures. There is some research showing that gap detection can be evaluated using an electrophysiological procedure. However, there is currently no research establishing gap detection threshold using the N1-P2 response. The purposes of the current study were to 1) determine gap detection thresholds in younger and older normal-hearing adults using an electrophysiological measure, 2) compare the electrophysiological gap detection threshold and behavioral gap detection threshold within each group, and 3) investigate the effect of age on each gap detection measure. This study utilized an older adult group and younger adult group to compare performance on an electrophysiological and behavioral gap detection procedure. The subjects in this study were 11 younger, normal-hearing adults (mean = 22 yrs) and 11 older, normal-hearing adults (mean = 64.36 yrs). All subjects completed an adaptive behavioral gap detection procedure in order to determine their behavioral gap detection threshold (BGDT). Subjects also completed an electrophysiologic gap detection procedure to determine their electrophysiologic gap detection threshold (EGDT). Older adults demonstrated significantly larger gap detection thresholds than the younger adults. However, EGDT and BGDT were not significantly different in either group. The mean difference between EGDT and BGDT for all subjects was 0.43 msec. Older adults show poorer gap detection ability when compared to younger adults. However, this study shows that gap detection thresholds can be measured using evoked potential recordings and yield results similar to a behavioral measure. American Academy of Audiology.

GDNF and NGF family members and receptors in human fetal and adult spinal cord and dorsal root ganglia.

PubMed

Josephson, A; Widenfalk, J; Trifunovski, A; Widmer, H R; Olson, L; Spenger, C

2001-11-12

We describe the expression of mRNA encoding ligands and receptors of members of the GDNF family and members of the neurotrophin family in the adult human spinal cord and dorsal root ganglia (DRG). Fetal human spinal cord and ganglia were investigated for the presence of ligands and receptors of the neurotrophin family. Tissues were collected from human organ donors and after routine elective abortions. Messenger RNA was found encoding RET, GFR alpha-1, BDNF, trkB, and trkC in the adult human spinal cord and BDNF, NT-3, p75, trkB, and trkC in the fetal human spinal cord. The percentage of adult human DRG cells expressing p75, trkA, trkB, or trkC was 57, 46, 29, and 24%, respectively, and that of DRG cells expressing RET, GFR alpha-1, GFR alpha-2, or GFR alpha-3 was 79, 20, 51, and 32%, respectively. GFR alpha-2 was expressed selectively in small, GFR alpha-3 principally in small and GFR alpha-1 and RET in both large and small adult human DRG neurons. p75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons. Fetal DRG cells were positive for the same probes as adult DRG cells except for NT-3, which was only found in fetal DRG cells. Messenger RNA species only expressed at detectable levels in fetal but not adult spinal cord tissues included GDNF, GFR alpha-2, NT-3, and p75. Notably, GFR alpha-2, which is expressed in the adult rat spinal cord, was not found in the adult human spinal cord. Copyright 2001 Wiley-Liss, Inc.

Can performance of daily activities discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment?

PubMed Central

Rodakowski, Juleen; Skidmore, Elizabeth R.; Reynolds, Charles F.; Dew, Mary Amanda; Butters, Meryl A.; Holm, Margo B.; Lopez, Oscar L.; Rogers, Joan C.

2014-01-01

OBJECTIVES Our primary aim was to examine whether preclinical disability in performance of cognitively-focused instrumental activities of daily living (C-IADL) tasks can discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment (MCI). The secondary purpose was to determine the two tasks with the strongest psychometric properties and assess their discriminative ability. Our goal was to generate diagnosis-relevant information about cognitive changes associated with MCI and DSM-5 Mild Neurocognitive Disorder. DESIGN Secondary analyses of cross-sectional data from a cohort of individuals diagnosed with normal cognitive function or MCI. SETTING Private home locations in Pittsburgh, PA. PARTICIPANTS Older adults with remitted major depression (N=157). MEASUREMENTS Diagnosis of cognitive status was made by the Alzheimer’s Disease Research Center at the University of Pittsburgh. Performance of 8 C-IADL was measured using the criterion-referenced, observation-based Performance Assessment of Self-Care Skills (PASS). RESULTS A total of 96 older adults with normal cognitive function (mean age=72.5, SD=5.9) and 61 older adults with MCI (mean age=75.5, SD=6.3) participated. The 8 C-IADL demonstrated 81% accuracy in discriminating cognitive status (area under curve 0.81, p<0.001). Two tasks (shopping and checkbook balancing) were the most discriminating (area under curve 0.80, p<0.001); they demonstrated similar ability, as the 8 C-IADL, to discriminate cognitive status. Assessing performance on these two C-IADL takes 10–15 minutes. CONCLUSION This is the first demonstration of the discriminative ability of preclinical disability in distinguishing MCI from cognitively normal older adults. These findings highlight potential tasks, when measured with the observation-based PASS, which demonstrate increased effort for individuals with MCI. These tasks may be considered when attempting to diagnose MCI or Mild Neurocognitive Disorder in clinical practice and research. PMID:24890517

Impact of diastolic and systolic blood pressure on mortality: implications for the definition of "normal".

PubMed

Taylor, Brent C; Wilt, Timothy J; Welch, H Gilbert

2011-07-01

The National Heart, Lung and Blood Institute currently defines a blood pressure under 120/80 as "normal." To examine the independent effects of diastolic (DBP) and systolic blood pressure (SBP) on mortality and to estimate the number of Americans affected by accounting for these effects in the definition of "normal." DESIGN, PARTICIPANTS AND MEASURES: Data on adults (age 25-75) collected in the early 1970s in the first National Health and Nutrition Examination Survey were linked to vital status data through 1992 (N = 13,792) to model the relationship between blood pressure and mortality rate adjusting for age, sex, race, smoking status, BMI, cholesterol, education and income. To estimate the number of Americans in each blood pressure category, nationally representative data collected in the early 1960s (as a proxy for the underlying distribution of untreated blood pressure) were combined with 2008 population estimates from the US Census. The mortality rate for individuals over age 50 began to increase in a stepwise fashion with increasing DBP levels of over 90. However, adjusting for SBP made the relationship disappear. For individuals over 50, the mortality rate began to significantly increase at a SBP ≥ 140 independent of DBP. In individuals ≤ 50 years of age, the situation was reversed; DBP was the more important predictor of mortality. Using these data to redefine a normal blood pressure as one that does not confer an increased mortality risk would reduce the number of American adults currently labeled as abnormal by about 100 million. DBP provides relatively little independent mortality risk information in adults over 50, but is an important predictor of mortality in younger adults. Conversely, SBP is more important in older adults than in younger adults. Accounting for these relationships in the definition of normal would avoid unnecessarily labeling millions of Americans as abnormal.

Appearance is a function of the face.

PubMed

Borah, Gregory L; Rankin, Marlene K

2010-03-01

Increasingly, third-party insurers deny coverage to patients with posttraumatic and congenital facial deformities because these are not seen as "functional." Recent facial transplants have demonstrated that severely deformed patients are willing to undergo potentially life-threatening surgery in search of a normal physiognomy. Scant quantitative research exists that objectively documents appearance as a primary "function" of the face. This study was designed to establish a population-based definition of the functions of the human face, rank importance of the face among various anatomical areas, and determine the risk value the average person places on a normal appearance. Voluntary adult subjects (n = 210) in three states aged 18 to 75 years were recruited using a quota sampling technique. Subjects completed study questionnaires of demography and bias using the Gamble Chance of Death Questionnaire and the Rosenberg Self-Esteem Scale. The face ranked as the most important anatomical area for functional reconstruction. Appearance was the fifth most important function of the face, after breathing, sight, speech, and eating. Normal facial appearance was rated as very important for one to be a functioning member of American society (p = 0.01) by 49 percent. One in seven subjects (13 percent) would accept a 30 to 45 percent risk of death to obtain a "normal" face. Normal appearance is a primary function of the face, based on a large, culturally diverse population sample across the lifespan. Normal appearance ranks above smell and expression as a function. Restoration of facial appearance is ranked the most important anatomical area for repair. Normal facial appearance is very important for one to be a functional member of American society.

Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg

2005-04-15

Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent withmore » the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.« less

Fitness but not weight status is associated with projected physical independence in older adults.

PubMed

Sardinha, Luis B; Cyrino, Edilson S; Santos, Leandro Dos; Ekelund, Ulf; Santos, Diana A

2016-06-01

Obesity and fitness have been associated with older adults' physical independence. We aimed to investigate the independent and combined associations of physical fitness and adiposity, assessed by body mass index (BMI) and waist circumference (WC) with the projected ability for physical independence. A total of 3496 non-institutionalized older adults aged 65 and older (1167 male) were included in the analysis. BMI and WC were assessed and categorized according to established criteria. Physical fitness was evaluated with the Senior Fitness Test and individual test results were expressed as Z-scores. Projected ability for physical independence was assessed with the 12-item composite physical function scale. Logistic regression was used to estimate the odds ratio (OR) for being physically dependent. A total of 30.1 % of participants were classified as at risk for losing physical independence at age 90 years. Combined fitness and fatness analysis demonstrated that unfit older adults had increased odds ratio for being physically dependent in all BMI categories (normal: OR = 9.5, 95 %CI = 6.5-13.8; overweight: OR = 6.0, 95 %CI = 4.3-8.3; obese: OR = 6.7, 95 %CI = 4.6-10.0) and all WC categories (normal: OR = 10.4, 95%CI = 6.5-16.8; middle: OR = 6.2, 95 %CI = 4.1-9.3; upper: OR = 7.0, 95 %CI = 4.8-10.0) compared to fit participants that were of normal weight and fit participants with normal WC, respectively. No increased odds ratio was observed for fit participants that had increased BMI or WC. In conclusion, projected physical independence may be enhanced by a normal weight, a normal WC, or an increased physical fitness. Adiposity measures were not associated with physical independence, whereas fitness is independently related to physical independence. Independent of their weight and WC status, unfit older adults are at increased risk for losing physical independence.

Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

PubMed Central

Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

2011-01-01

Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

Effects of infrasound on cell proliferation in the dentate gyrus of adult rats.

PubMed

Liu, Juanfang; Lin, Tian; Yan, Xiaodong; Jiang, Wen; Shi, Ming; Ye, Ruidong; Rao, Zhiren; Zhao, Gang

2010-06-02

Adult rats were used to identify the effects of infrasound on neurogenesis in the hippocampal dentate gyrus. After 7 consecutive days' exposure to infrasound of 16 Hz at 130 dB, immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) was preformed. Compared with those in normal groups, the numbers of BrdU+ and DCX+/BrdU+ cells in the subgranular zone in infrasound groups were significantly decreased at 3, 6, 10 and 14 days and returned to normal at 18 days. The percentage of BrdU+ cells that were co-labeled with DCX showed no significant differences between the infrasound and normal groups. These data suggest that infrasound inhibits the cell proliferation in adult rat dentate gyrus but has no effects on early migration and differentiation of these newborn cells.