High levels of Notch signaling down-regulate Numb and Numblike

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development

Physical workload and psychosocial working conditions in Swedish pig transport drivers

Working conditions of 20 Swedish pig transport drivers (PTD) were assessed by a questionnaire, a workshop, and recorded postures and movements during on-farm loading, driving, unloading at abattoir and vehicle cleaning. High arm positions and high frequencies of shoulder problems indicated an excessive physical load on shoulders. Extreme crouching postures inside vehicles and high frequencies of lower back problems indicated high load on the back of PTDs. Inadequate design of on-farm loading areas was associated with knee discomfort. Observed variation in workload between PTDs could be explained by differences in physical working environment and pig handling practices. PTDs reported high job satisfaction and commitment although conflicts with farmers and official veterinarians, as well as regulatory conflicts were emphasized. We conclude that issues of inadequate farm and abattoir facilities, stakeholder conflicts and insufficient training in animal handling need to be addressed to ensure sustainable PTD working conditions

Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

BACKGROUND: Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. METHODS: Uterine isthmic biopsies were collected from non-pregnant (n = 7), term pregnant women not in labour (n = 14), in normal labour (n = 7) and in prolonged labour (n = 7). mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. RESULTS: In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p < 0.05). In term-pregnant tissue, the expression of syndecan 3 and connexin 43 did not differ significantly compared to non-pregnant and normal labour. The immunoreactivity of syndecan 3 was strong at normal labour, in contrast to prolonged labour, where both a weaker expression and an irregular distribution were detected. The immunoreactivity of connexin 43 increased until term and further stronger staining occurred at normal labour. At prolonged labour, the immunoreactivity was weaker and more unevenly distributed. At labour, a co-localization of syndecan 3 and connexin 43 could be demonstrated in the smooth muscle by confocal microscopy. CONCLUSION: The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility

Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3

The Notch and transforming growth factor-β (TGF-β) signaling pathways play critical roles in the control of cell fate during metazoan development. However, mechanisms of cross-talk and signal integration between the two systems are unknown. Here, we demonstrate a functional synergism between Notch and TGF-β signaling in the regulation of Hes-1, a direct target of the Notch pathway. Activation of TGF-β signaling up-regulated Hes-1 expression in vitro and in vivo. This effect was abrogated in myogenic cells by a dominant-negative form of CSL, an essential DNA-binding component of the Notch pathway. TGF-β regulated transcription from the Hes-1 promoter in a Notch-dependent manner, and the intracellular domain of Notch1 (NICD) cooperated synergistically with Smad3, an intracellular transducer of TGF-β signals, to induce the activation of synthetic promoters containing multimerized CSL- or Smad3-binding sites. NICD and Smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and Smad3 could be recruited to CSL-binding sites on DNA in the presence of CSL and NICD. These findings indicate that Notch and TGF-β signals are integrated by direct protein–protein interactions between the signal-transducing intracellular elements from both pathways

Cross-sectional associations between occupational factors and musculoskeletal pain in women teachers, nurses and sonographers

A. Technical measurements of the physical workload. (DOCX 18 kb

Improving technical methods for assessment of workplace ergonomic exposure

AbstractBackground: Repetitive work, work performed in awkward and constrained postures and work with excessive or sustained muscular load is common in many occupational settings. Such work is known to be risk factors for developing musculoskeletal disorders in the neck/shoulder region and in arms and hands. One method that can be used to assess the exposure to these risk factors is technical recordings that rely on sensors attached directly to a subject. However, there is a commonly held belief that the methods are time consuming, require expensive equipment and also demand technical knowledge to perform and are therefore not suitable for all. Aims: To simplify the inclinometry method in order to make it easier to use for different actors in the work environment field, and to refine the surface electromyography (sEMG) method of the forearm extensor muscles for more accurate estimates of recorded muscular load. Methods: For the inclinometry method in the laboratory, one model of the new generation of triaxial accelerometers with integrated data loggers (GC inclinometer) were validated against traditional ones (LT inclinometer). Also the deviation angles of two simplified reference postures for upper arms from a standard reference posture were evaluated. For the field study, self-recordings of upper arm elevations were evaluated by analysing each recording twice; once with a simplified reference posture and once with a standard reference posture. For the sEMG method in the laboratory, the electrical activity of right forearm extensor muscles was recorded from four electrode pair positions during two maximal voluntary contractions (MVC; hand grip and resisted wrist extension). In the field study, the electrical activity was recorded using two electrode pair positions and the two MVCs during one working day of hotel room cleaning. Each recording was analysed twice; once with hand grip as reference contraction and once with resisted wrist extension as reference. Results: For the inclinometry method in the laboratory, all group mean absolute differences of simulated work tasks and body parts between the two inclinometers were less than 2.5°. In the field study, the upper arm elevations during work (50th percentile) were almost identical (group mean difference of 0.2°) for the two analyses using different reference postures. For sEMG in the laboratory, resisted wrist extension showed 1.2 – 1.7 times higher EMG amplitudes and lower coefficient of variation than hand grip. In the field study, the workload during cleaning was lower when using resisted wrist extension as the reference than when using hand grip. The workload (99th percentile) was overestimated in two subjects when hand grip was used as reference contraction. Conclusions: For the inclinometry method, the obtained data from the GC inclinometers were fully comparable to the data from the LT inclinometers. The simplified reference posture deviated somewhat from the standard reference, but the effect of this deviation on group recordings of work was negligible. The hotel room cleaners managed to perform self-recordings of upper arm elevations and velocities. For the sEMG, the use of resisted wrist extension may be a more accurate maximal effort of forearm extensor contraction than using hand grip. Problems associated with poorly activated forearm extensors can be overcome by using resisted wrist extension as reference

Ikääntyneen asukkaan osallistaminen yhteisöllisessä asumisessa : työkalu osallisuuden vahvistamiseksi

Opinnäytetyön tarkoituksena oli luoda työelämäkumppanilleni eli Länsi-Uudenmaan hyvinvointialueen Marianmäen palvelukeskuksen henkilökunnalle kyselymuotoinen työkalu yhteisöllisen asumisen asukkaiden mielipiteiden ja toiveiden selvittämiseen. Opinnäytetyön tavoitteena oli mahdollistaa jokaisen asukkaan tasapuolinen tilaisuus ilmaista mielipiteensä toiminnan ja hoivan sisällöstä ja siten vahvistaa asukkaiden osallisuutta yhteisöllisessä asumisessa. Työkalun avulla asukkaat ja henkilökunta yhdessä kehittivät ja voivat myös jatkossa kehittää yhteisöllisen asumisen toimintaa. Tietoperustan tässä opinnäytetyössä muodosti teoriatieto ikääntyneistä Suomessa, ikääntymisen vaikutuksesta toimintakykyyn ja sosiaaliseen verkostoon, ikääntyneiden yhteisöllisestä asumisesta ja yhteisöllisen asumisen toiminnasta ja osallisuudesta. Kehittämistyön toteutuksessa käytettiin konstruktiivisen tutkimuksen menetelmiä. Kehittämistyötä tehtiin opinnäytetyön tietoperustaan pohjautuvan aivoriihen avulla. Henkilökunnan aivoriihen tuloksena syntyivät työkalun kysymykset. Työkalu sisälsi sekä valmiita vastausvaihtoehtoja sisältäviä kysymyksiä että avoimia kysymyksiä. Asukkaat vastasivat työkalun kysymyksiin ja vastausten perusteella pidettiin asukkaiden ja henkilökunnan yhteisöllinen kokous. Kokous oli osa opin-näytetyön kehittämisprosessia ja johti toiminnan kehittämiseen. Kokouksen jälkeen työkalu muovautui lopulliseen muotoonsa henkilökunnan antaman palautteen myötä. Kehittämistyön tuloksena oli työkalu yhteisöllisen asumisen asukkaiden osallisuuden vahvistamiseen. Työkalun avulla henkilökunta saa tietoa asukkaiden toiveista toiminnan kehittämiseen. Työkalu ohjaa yhteisöllisten kokouksien sisältöä ja on käytössä kokouksien sisällön pohjana noin kaksi kertaa vuodessa. Työkalu on muokattavissa tarpeen mukaan vastaamaan tulevaisuuden tarpeita

Validity of a small low-cost triaxial accelerometer with integrated logger for uncomplicated measurements of postures and movements of head, upper back and upper arms

Repetitive work and work in constrained postures are risk factors for developing musculoskeletal disorders. Low-cost, user-friendly technical methods to quantify these risks are needed. The aims were to validate inclination angles and velocities of one model of the new generation of accelerometers with integrated data loggers against a previously validated one, and to compare meaurements when using a plain reference posture with that of a standardized one. All mean (n = 12 subjects) angular RMS-differences in 4 work tasks and 4 body parts were <2.5° and all mean median angular velocity differences <5.0 °/s. The mean correlation between the inclination signal-pairs was 0.996. This model of the new generation of triaxial accelerometers proved to be comparable to the validated accelerometer using a data logger. This makes it well-suited, for both researchers and practitioners, to measure postures and movements during work. Further work is needed for validation of the plain reference posture for upper arms