The effects of sleep restriction on executive inhibitory control and affect in young adults

Purpose: Young adults regularly experience restricted sleep due to a range of social, educational and vocational commitments. Evidence suggests that extended periods of sleep deprivation negatively impact affective and inhibitory control mechanisms leading to behavioural consequences such as increased emotional reactivity and impulsive behaviour. It is less clear whether acute periods of restricted sleep produce the same behavioural consequences. Methods: Nineteen young adults (m = 8, f = 12) with habitual late bed-time (after 22:30 h) and wake-time (after 06:30 h) completed a range of objective and subjective measures assessing sleepiness (Psychomotor Vigilance Task, Karolinska Sleepiness Scale), inhibitory control (Emotional Go/No-go Task and a Balloon Analog Risk Task) and affect (Positive and Negative Affective Schedule). Testing was counterbalanced across participants, and occurred on two occasions once following restricted sleep and once following habitual sleep one week apart. Results: Compared to habitual sleep, sleep restriction produced significantly slower performance on the Psychomotor Vigilance Task, and higher subjective ratings of sleepiness on the Karolinska Sleepiness Scale. Sleep restriction also caused a significant decrease in positive affect, but no change in negative affect on the Affective Schedule. Inhibitory control efficiency was significantly differentiated, with participants showing an increase in risk taking on the Balloon Analog Risk Task, but there was no evidence of increased reactivity to negative stimuli on the Emotional Go/No-go task. Conclusions: Results suggest that even acute periods of sleep loss may cause deficits in affective experiences and increase impulsive and potentially high risk behaviour in young adults.

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

Mesenchymal stem cells as mediators of the neuronal cell niche

This study examined the role of heparan sulfate proteoglycans (HSPGs) in neural lineage differentiation of human mesenchymal stem cells (hMSCs). Several HSPGs were identified as potential new targets controlling neural fate specification and may be applied to the development of improved models to examine and repair brain damage. hMSCs were characterised throughout extended in vitro expansion for neural lineage potential (neurons, astrocytes, oligodendrocytes) and differentiated using terminal differentiation and intermediate sphere formation. Brain damage and neurological disorders caused by injury or disease affect a large number of people often resulting in lifelong disabilities. Multipotent mesenchymal stem cells have a large capacity for self-renewal and provide an excellent model to examine the regulation and contribution of both stem cells and their surrounding microenvironment to the repair of neural tissue damage.

Social media and niche sports: The netball ANZ championship and commonwealth games on twitter

This article analyses and compares Twitter activity for the niche sport of netball over the 2013 trans-Tasman ANZ Championship competition and the international Commonwealth Games event in 2014. Patterns within the Twitter data that were discovered through an analysis of the 2013 ANZ Championship season are considered in terms of the Commonwealth Games, and thus compared between a quasi-domestic and an international context. In particular, we highlight the extent to which niche sports such as netball attempt to capitalise on the opportunities provided by social media, and the challenges involved in coordinating event-specific hashtags, such as the #netball2014 hashtag promoted by the Commonwealth Games Federation.

Stochastic dynamics of interacting haematopoietic stem cell niche lineages

Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.

Dissecting the prostate cancer stem cell niche inside the bone marrow

Prostate cancer frequently metastasizes to bone, which becomes incurable; yet how cancer cells manage to migrate and grow inside the bone remains unknown. In this study I have discovered that both bone and fat cells within the bone marrow actively promote the survival and expansion of prostate cancer cells, and have subsequently developed approaches that can effectively inhibit these processes. Therefore, my work offers opportunities for the development of new prognostic and therapeutic approaches against metastatic prostate cancer and have the potential for improving the treatment outcome of the patients.

Internationalizing school curriculum in Australasia: As niche, by test, or at heart?

Global citizenship has emerged as a pressing curricular priority which all educational systems are currently grappling with. The challenge is to negotiate how this orientation might sit alongside the more traditional mission of mass school curriculum in building collective ballast for a national identity through a common morality and shared narratives, or may conflict with efforts to protect and promote indigenous and minority identities. As a case study of how these agendas interact, this chapter will consider curricular responses to global imperatives in the variegated conditions across the Australasian region (defined as Australia, New Zealand and Papua New Guinea). The chapter will outline recent developments in the social, economic and political contexts surrounding curricular reforms in these settings, and demonstrate how these developments have changed the conditions of possibility and strength of purpose behind efforts to internationalise school curricula. Three types of systemic responses are then described: firstly, an appetite for globally branded curricula such as the International Baccalaureate, Montessori, and Cambridge University Certificates to distinguish some in a stratified market; secondly, convergence in curriculum to improve national performance on international standardised tests; and thirdly, the infusion of cosmopolitan sensibilities, regional identities and intercultural competencies as a core curricular goal for all. The chapter considers the various pragmatic interpretations of ‘internationalisation’ in these responses, and argues that the third response seems both the most difficult to enact, and the most vulnerable to political interference.

"America Would Lose Its Soul" : The Immigration Restriction Debate, 1920-1924

Vuosien 1830 ja 1924 välillä Yhdysvaltoihin muutti noin 35 miljoonaa eurooppalaista. Tämä niinkutsuttu "maahanmuuton vuosisata" päättyi varsin äkillisesti kun Yhdysvallat päätti rajoittaa maahanmuuttoa 1920-luvulla. Vuosina 1921 ja 1924 säädetyt lait asettivat kansallisuuteen perustuvat kiintiöt kaikille eurooppalaisille maahanmuuttajille; vuoden 1924 laki myös lopetti kokonaan japanilaisten maahanmuuton. Tämä työ tutkii näihin kiintiölakeihin johtanutta maahanmuuttajavastaisuuden kasvua sekä etenkin lakien ympärillä käytyä keskustelua. Pääpaino on kongressissa esitetyissä maahanmuuton vastaisissa argumenteissa. Nämä jakautuivat karkeasti ottaen kolmeen kategoriaan: maahanmuuton vastustajat sanoivat, että siirtolaisten vaikutus taloudelliseen tilanteeseen oli epäsuotuisa, siirtolaisten rodullinen ja kulttuurinen "laatu" oli huonontunut, ja siirtolaiset olivat radikaaleja ja bolshevismiin taipuvaisia. Erityistä huolta herätti maahanmuuttajien vaikutus Amerikan kulttuuriseen, rodulliseen ja poliittiseen yhtenäisyyteen. Huoli kansakunnan yhtenäisyydestä oli tulosta paitsi siirtolaisten määrästä myös amerikkalaisessa yhteiskunnassa tapahtuneista muutoksista. Erityisen tärkeitä olivat työväenliikkeen vaikutusvallan kasvu ja teollisuusjohtajien pyrkimys pysäyttää se. Maahanmuuttajien "bolshevismi" olikin käyttökelpoinen argumentti paitsi maahanmuuttajia myös amerikkalaisia työläisiä vastaan: teollisuusjohtajat painottivat että lakot ja työväenliike olivat tulosta siirtolaisten mukanaan tuomista "epäamerikkalaisista" ajatusmalleista, eivät yhteiskunnan epäoikeudenmukaisuudesta. Kongressin keskustelun lisäksi työssä käsitellään myös eri yhteiskunnallisten ryhmien ja vaikuttajien kantaa siirtolaisuuteen. Keskusteluun maahanmuutosta vaikuttivat etenkin eugenistit ja muut sosiaalitieteilijät, jotka väittivät itä- ja eteläeurooppalaisten olevan rodullisesti anglosakseja huonompia. Tämän väitteen vaikutusvaltaa lisäsivät yhteiskunnassa vallalla olleet ennakkoluulot, ja monet yhdistykset ja liikkeet (mm. Ku Klux Klan ja erilaiset isänmaalliset järjestöt) olivatkin tärkeitä rajoittamisen kannattajia. Keskustelu maahanmuutosta painottui ideologisiin ja tunteellisiin kysymyksiin, mutta rajoitusten taustalla oli myös konkreettisempia tekijöitä. Yhteiskunnan teollistuminen ja kaupungistuminen olivat pienentäneet siirtolaisista koituvaa taloudellista hyötyä: siirtolaisia ei enää tarvittu raivaamaan uusia viljelysmaita, kun taas tuotannon koneistuminen vähensi työvoiman tarvetta huomattavasti. Pitkän aikavälin taloudellisten tekijöiden roolin merkitys käy ilmeiseksi kun otetaan huomioon, että muut maahanmuuttomaat (esim. Kanada ja Australia) eivät juuri rajoittaneet siirtolaisuutta tänä aikana vaikka niissäkin esiintyi runsaasti rodullista ja kulttuurista maahanmuuttajavastaisuutta. Pääsyy rajoitusten vähäisyyteen näissä maissa oli juuri maahanmuuttajien tuoma taloudellinen hyöty, sekä teollisena työvoimana että maanviljelijöinä. Vaikka kiintiölakiehdotusten ympärillä käytiin kiivasta väittelyä, kongressi kuitenkin hyväksyi lait varsin suurella enemmistöllä. Siirtolaisia itseään lukuunottamatta varsin harvat näkivät lait haitallisina, kun taas useat erilaiset ryhmät katsoivat hyötyvänsä maahanmuuton rajoittamisesta. Avainsanat: siirtolaisuus, maahanmuutto, Yhdysvallat, 1920-luku, kiintiölait, maahanmuuton rajoittaminen

Mapping the carriage of flaA-restriction fragment length polymorphism Campylobacter genotypes on poultry carcasses through the processing chain and comparison to clinical isolates

Poultry are considered a major source for campylobacteriosis in humans. A total of 1866 Campylobacter spp. isolates collected through the poultry processing chain were typed using flaA-restriction fragment length polymorphism to measure the impact of processing on the genotypes present. Temporally related human clinical isolates (n = 497) were also typed. Isolates were obtained from whole chicken carcass rinses of chickens collected before scalding, after scalding, before immersion chilling, after immersion chilling and after packaging as well as from individual caecal samples. A total of 32 genotypes comprising at least four isolates each were recognised. Simpson's Index of Diversity (D) was calculated for each sampling site within each flock, for each flock as a whole and for the clinical isolates. From caecal collection to after packaging samples the D value did not change in two flocks, decreased in one flock and increased in the fourth flock. Dominant genotypes occurred in each flock but their constitutive percentages changed through processing. There were 23 overlapping genotypes between clinical and chicken isolates. The diversity of Campylobacter is flock dependant and may alter through processing. This study confirms that poultry are a source of campylobacteriosis in the Australian population although other sources may contribute.

Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1

The genome of the human pathogen Entamoeba histolytica, a primitive protist, contains non-long terminal repeat retrotransposable elements called EhLINEs. These encode reverse transcriptase and endonuclease required for retrotransposition. The endonuclease shows sequence similarity with bacterial restriction endonucleases. Here we report the salient enzymatic features of one such endonuclease. The kinetics of an EhLINE1-encoded endonuclease catalyzed reaction, determined under steady-state and single-turnover conditions, revealed a significant burst phase followed by a slower steady-state phase, indicating that release of product could be the slower step in this reaction. For circular supercoiled DNA the K-m was 2.6 x 10-8 m and the k(cat) was 1.6 x 10-2 sec-1. For linear E. histolytica DNA substrate the K-m and k(cat) values were 1.3 x 10-8 m and 2.2 x 10-4 sec-1 respectively. Single-turnover reaction kinetics suggested a noncooperative mode of hydrolysis. The enzyme behaved as a monomer. While Mg2+ was required for activity, 60% activity was seen with Mn2+ and none with other divalent metal ions. Substitution of PDX12-14D (a metal-binding motif) with PAX(12-14)D caused local conformational change in the protein tertiary structure, which could contribute to reduced enzyme activity in the mutated protein. The protein underwent conformational change upon the addition of DNA, which is consistent with the known behavior of restriction endonucleases. The similarities with bacterial restriction endonucleases suggest that the EhLINE1-encoded endonuclease was possibly acquired from bacteria through horizontal gene transfer. The loss of strict sequence specificity for nicking may have been subsequently selected to facilitate spread of the retrotransposon to intergenic regions of the E. histolytica genome.

Cardiac function before and after treatment for various types of loading conditions and in myocardial restriction : A prospective study on pediatric patients with two- and three-dimensional echocardiography and measurement of serum natriuretic peptides

Background: The incidence of all forms of congenital heart defects is 0.75%. For patients with congenital heart defects, life-expectancy has improved with new treatment modalities. Structural heart defects may require surgical or catheter treatment which may be corrective or palliative. Even those with corrective therapy need regular follow-up due to residual lesions, late sequelae, and possible complications after interventions. Aims: The aim of this thesis was to evaluate cardiac function before and after treatment for volume overload of the right ventricle (RV) caused by atrial septal defect (ASD), volume overload of the left ventricle (LV) caused by patent ductus arteriosus (PDA), and pressure overload of the LV caused by coarctation of the aorta (CoA), and to evaluate cardiac function in patients with Mulibrey nanism. Methods: In Study I, of the 24 children with ASD, 7 underwent surgical correction and 17 percutaneous occlusion of ASD. Study II had 33 patients with PDA undergoing percutaneous occlusion. In Study III, 28 patients with CoA underwent either surgical correction or percutaneous balloon dilatation of CoA. Study IV comprised 26 children with Mulibrey nanism. A total of 76 healthy voluntary children were examined as a control group. In each study, controls were matched to patients. All patients and controls underwent clinical cardiovascular examinations, two-dimensional (2D) and three-dimensional (3D) echocardiographic examinations, and blood sampling for measurement of natriuretic peptides prior to the intervention and twice or three times thereafter. Control children were examined once by 2D and 3D echocardiography. M-mode echocardiography was performed from the parasternal long axis view directed by 2D echocardiography. The left atrium-to-aorta (LA/Ao) ratio was calculated as an index of LA size. The end-diastolic and end-systolic dimensions of LV as well as the end-diastolic thicknesses of the interventricular septum and LV posterior wall were measured. LV volumes, and the fractional shortening (FS) and ejection fraction (EF) as indices of contractility were then calculated, and the z scores of LV dimensions determined. Diastolic function of LV was estimated from the mitral inflow signal obtained by Doppler echocardiography. In three-dimensional echocardiography, time-volume curves were used to determine end-diastolic and end-systolic volumes, stroke volume, and EF. Diastolic and systolic function of LV was estimated from the calculated first derivatives of these curves. Results: (I): In all children with ASD, during the one-year follow-up, the z score of the RV end-diastolic diameter decreased and that of LV increased. However, dilatation of RV did not resolve entirely during the follow-up in either treatment group. In addition, the size of LV increased more slowly in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides in patients treated percutaneously increased during the first month after ASD closure and normalized thereafter, but in patients treated surgically, they remained higher than in controls. (II): In the PDA group, at baseline, the end-diastolic diameter of LV measured over 2SD in 5 of 33 patients. The median N-terminal pro-brain natriuretic peptide (proBNP) concentration before closure measured 72 ng/l in the control group and 141 ng/l in the PDA group (P = 0.001) and 6 months after closure measured 78.5 ng/l (P = NS). Patients differed from control subjects in indices of LV diastolic and systolic function at baseline, but by the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV end-diastolic volume decreased significantly during follow-up. (III): Before repair, the size and wall thickness of LV were higher in patients with CoA than in controls. Systolic blood pressure measured a median 123 mm Hg in patients before repair (P < 0.001) and 103 mm Hg one year thereafter, and 101 mm Hg in controls. The diameter of the coarctation segment measured a median 3.0 mm at baseline, and 7.9 at the 12-month (P = 0.006) follow-up. Thicknesses of the interventricular septum and posterior wall of the LV decreased after repair but increased to the initial level one year thereafter. The velocity time integrals of mitral inflow increased, but no changes were evident in LV dimensions or contractility. During follow-up, serum levels of natriuretic peptides decreased correlating with diastolic and systolic indices of LV function in 2D and 3D echocardiography. (IV): In 2D echocardiography, the interventricular septum and LV posterior wall were thicker, and velocity time integrals of mitral inflow shorter in patients with Mulibrey nanism than in controls. In 3D echocardiography, LV end-diastolic volume measured a median 51.9 (range 33.3 to 73.4) ml/m² in patients and 59.7 (range 37.6 to 87.6) ml/m² in controls (P = 0.040), and serum levels of ANPN and proBNP a median 0.54 (range 0.04 to 4.7) nmol/l and 289 (range 18 to 9170) ng/l, in patients and 0.28 (range 0.09 to 0.72) nmol/l (P < 0.001) and 54 (range 26 to 139) ng/l (P < 0.001) in controls. They correlated with several indices of diastolic LV function. Conclusions (I): During the one-year follow-up after the ASD closure, RV size decreased but did not normalize in all patients. The size of the LV normalized after ASD closure but the increase in LV size was slower in patients treated surgically than in those treated with the percutaneous technique. Serum levels of ANPN and proBNP were elevated prior to ASD closure but decreased thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically. (II): Changes in LV volume and function caused by PDA disappeared by 6 months after percutaneous closure. Even the children with normal-sized LV benefited from the procedure. (III): After repair of CoA, the RV size and the velocity time integrals of mitral inflow increased, and serum levels of natriuretic peptides decreased. Patients need close follow-up, despite cessation of LV pressure overload, since LV hypertrophy persisted even in normotensive patients with normal growth of the coarctation segment. (IV): In children with Mulibrey nanism, the LV wall was hypertrophied, with myocardial restriction and impairment of LV function. Significant correlations appeared between indices of LV function, size of the left atrium, and levels of natriuretic peptides, indicating that measurement of serum levels of natriuretic peptides can be used in the clinical follow-up of this patient group despite its dependence on loading conditions.

Mulibrey nanism : Clinical characteristics and pathophysiologic features of growth restriction, insulin resistance and tumour development

Background: Mulibrey nanism (MUL; Muscle-liver-brain-eye nanism; OMIM 253250) is an autosomal recessive growth disorder more prevalent in Finland than elsewhere in the world. Clinical characteristics include severe prenatal onset growth restriction, cardiopathy, multiple organ manifestations but no major neurological handicap. MUL is caused by mutations in the TRIM37 gene on chromosome 17q22-23, encoding a peroxisomal protein TRIM37 with ubiquitin E3-ligase activity. Nineteen different mutations have been detected, four of them present in the Finnish patients. Objective: This study aimed to characterize clinical and histopathological features of MUL in the national cohort of Finnish patients. Patients and methods: A total of 92 Finnish patients (age 0.7 to 77 years) participated in the clinical follow-up study. Patients hospital records and growth charts were reviewed. Physical, radiographic and laboratory examinations were performed according to a clinical protocol. Thirty patients (18 females) were treated with recombinant human GH for a median period of 5.7 years. Biopsies and autopsy samples were used for the histopathological and immunohistochemical analyses. Results: MUL patients were born small for gestational age (SGA) with immature craniofacial features after prenatal-onset growth restriction. They experienced a continuous deceleration in both height SDS and weight-for-height (WFH) postnatally. In infancy feeding difficulties and frequent pneumonias were common problems. At the time of diagnosis (median age 2.1 years) characteristic craniofacial, radiological and ocular features were the most constant findings. MUL patients showed a dramatic change in glucose metabolism with increasing age. While the children had low fasting glucose and insulin levels, 90% of the adults were insulin resistant, half had type 2 diabetes and an additional 42% showed impaired glucose tolerance (IGT). Seventy percent fulfilled the National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria for metabolic syndrome as adults. GH therapy improved pre-pubertal growth but had only minor impact on adult height (+5 cm). Interestingly, treated subjects were slimmer and had less frequent metabolic concerns as young adults. MUL patients displayed histologically a disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours present in several internal organs. A total of 232 tumorous lesions were detected in our patient cohort. The majority of the tumours showed strong expression of endothelial cell marker CD34 as well as α-smooth muscle actin (α-SMA). Fifteen of the tumours were malignant and seven of them (five Wilms tumours) occurred in the kidney. Conclusions: MUL patients present a distinct postnatal growth pattern. Short-term response of GH treatment is substantial but the long-term impact remains modest. Although MUL patients form a distinct clinical and diagnostic entity, their clinical findings vary considerably from infancy to adulthood. While failure to thrive dominates early life, MUL adults develop metabolic syndrome and have a tendency for malignancies and vascular lesions in several organs. This speaks for a central role of TRIM37 in regulation of key cellular functions, such as proliferation, migration, angiogenesis and insulin signalling.

DNA looping and translocation provide an optimal cleavage mechanism for the type III restriction enzymes

EcoP15I is a type III restriction enzyme that requires two recognition sites in a defined orientation separated by up to 3.5 kbp to efficiently cleave DNA. The mechanism through which site- bound EcoP15I enzymes communicate between the two sites is unclear. Here, we use atomic force microscopy to study EcoP15I-DNA pre-cleavage complexes. From the number and size distribution of loops formed, we conclude that the loops observed do not result from translocation, but are instead formed by a contact between site- bound EcoP15I and a nonspecific region of DNA. This conclusion is confirmed by a theoretical polymer model. It is further shown that translocation must play some role, because when translocation is blocked by a Lac repressor protein, DNA cleavage is similarly blocked. On the basis of these results, we present a model for restriction by type III restriction enzymes and highlight the similarities between this and other classes of restriction enzymes.