Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

BACKGROUND Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. FINDINGS A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. CONCLUSION The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.This work was funded by the Royal Society of Tropical Medicine and Hygiene through a Dennis Burkitt Fellowship to JJM. ARD is supported by the Economic and Social Research Council. JJM is supported by a Wellcome Trust Research Training Fellowship (GR074833MA)

Translin and Trax differentially regulate telomere-associated transcript homeostasis

Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1(+) (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere-specific fashion

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

Table of cancer data sets analyzed. (DOCX 14 kb

Traditional and Health-Related Philanthropy: The Role of Resources and Personality

I study the relationships of resources and personality characteristics to charitable giving, postmortem organ donation, and blood donation in a nationwide sample of persons in households in the Netherlands. I find that specific personality characteristics are related to specific types of giving: agreeableness to blood donation, empathic concern to charitable giving, and prosocial value orientation to postmortem organ donation. I find that giving has a consistently stronger relation to human and social capital than to personality. Human capital increases giving; social capital increases giving only when it is approved by others. Effects of prosocial personality characteristics decline at higher levels of these characteristics. Effects of empathic concern, helpfulness, and social value orientations on generosity are mediated by verbal proficiency and church attendance.

New insights into the manual activities of individuals from the Phaleron cemetery (Archaic Athens, Greece)

Until the early 5th century BC, Phaleron Bay was the main port of ancient Athens (Greece). On its shore, archaeologists have discovered one of the largest known cemeteries in ancient Greece, including a range of burial forms, simple pits, cremations, larnaces (clay tubs), and series of burials of male individuals who appear to have died violent deaths, referred to here as “atypical burials”. Reconstructing the osteobiographies of these individuals will help create a deeper understanding of the socio-political conditions preceding the rise of Classical Athens. Here, we assess the habitual manual behavior of the people of Archaic Phaleron (ca. 7th – 6th cent. BC), relying on a new and precise three-dimensional method for reconstructing physical activity based on hand muscle attachment sites. This approach has been recently validated on laboratory animal samples as well as on recent human skeletons with a detailed level of long-term occupational documentation (i.e., the mid-19th century Basel Spitalfriedhof sample). Our Phaleron sample consists of 48 adequately preserved hand skeletons, of which 14 correspond to atypical burials. Our results identified consistent differences in habitual manual behaviors between atypical burials and the rest. The former present a distinctive power-grasping tendency in most skeletons, which was significantly less represented in the latter (p-values of <0.01 and 0.03). Based on a comparison with the uniquely documented Basel sample (45 individuals), this entheseal pattern of the atypical burials was exclusively found in long-term heavy manual laborers. These findings reveal an important activity difference between burials typical for the Phaleron cemetery and atypical burials, suggesting that the latter were likely involved in distinctive, strenuous manual activities. The results of this pilot study comprise an important first step towards reconstructing the identity of these human skeletal remains. Future research can further elucidate the occupational profiles of these individuals through the discovery of additional well-preserved hand skeletons and by extending our analyses to other anatomical regions

Propuesta de rediseño del sistema de abastecimiento de agua potable, para el Barrio Camilo Ortega, Municipio de Managua, en el período 2011-2031

El agua es el principal elemento para la supervivencia humana, por eso existe una gran relación entre el agua y la salud, los que son dos elementos que contribuyen al sostenimiento y a la calidad de la vida. La disponibilidad y calidad del agua determinan el grado de salud e higiene en cualquiera sociedad. La presente Tesis Monográfica titulada “Propuesta de rediseño del Abastecimiento de agua potable, para el Bo. Camilo Ortega, Municipio de Managua, Mayo 2011 a Mayo 2031” para optar por la titulación de Ingeniero Civil. Del 100% de las aguas, sólo un 2% equivalen a agua dulce, las cuales al pasar por un corto proceso de tratamiento y cloración puede ser consumida, lo que provoca una disputa por el vital líquido, debido a que cada comunidad por muy pequeña que sea, requiere de un servicio mínimo de abastecimiento de agua potable. El mayor aporte de las aguas dulces, lo hacen las aguas subterráneas las cuales eran relativamente libres de contaminación y particularmente útiles para uso doméstico. Hoy, salvo en raros casos, el agua como se encuentra en la naturaleza, no puede ser utilizada directamente para el consumo humano ni para usos industriales, dado que no es lo suficientemente pura biológicamente ni químicamente, debido a residuos y sustancias contaminantes arrojados por el ser humano a diario

Targeting of the Tumor Suppressor GRHL3 by a miR-21-Dependent Proto-Oncogenic Network Results in PTEN Loss and Tumorigenesis

SummaryDespite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC

Rugby Fans in Training New Zealand (RUFIT-NZ): protocol for a randomized controlled trial to assess the effectiveness and cost-effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs in New Zealand

Background A healthy lifestyle program that appeals to, and supports, obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. In Scotland, Football Fans in Training (FFIT), a weight management and healthy lifestyle program for overweight and obese men aged 35–65 years , delivered by community coaching staff at professional football clubs, has been shown to be beneficial and cost-effective. A pilot program inspired by FFIT but delivered by professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, improved physiological outcomes, and adherence to healthy lifestyle behaviors in overweight and obese men. The objective of this trial is to determine the effectiveness and cost-effectiveness of the Rugby Fans in Training New Zealand (RUFIT-NZ) program. Methods A pragmatic, two-arm, multi-center, randomized controlled trial involving 308 overweight and obese men aged 30–65 years, randomized to either an intervention group (n = 154) or a wait-list control group (n = 154). The intervention-group participated in the 12-week RUFIT-NZ program, a gender-sensitized, healthy lifestyle intervention adapted to the environment and cultural diversity of NZ and delivered through professional rugby clubs. Participants in the intervention group undergo physical training sessions, in addition to workshop-based sessions to learn about nutrition, physical activity, sleep, sedentary behavior, and a range of behavior-change strategies for sustaining a healthier lifestyle. The control group receives the program after 52 weeks. The primary outcome is change in body weight from baseline to 52 weeks. Secondary outcomes include change in body weight at 12 weeks; waist circumference, blood pressure, fitness, and lifestyle behaviors at 12 and 52 weeks; and cost-effectiveness. A process evaluation informed by the RE-AIM framework will evaluate potential implementation of RUFIT-NZ as an ongoing program in NZ after the trial. Discussion This trial will investigate the effectiveness and cost-effectiveness of the RUFIT-NZ program in overweight and obese NZ men

COVID-19: Fernunterricht aus Sicht der Mitarbeitenden von Schulen in Deutschland, Österreich und der Schweiz

Im Zuge der Corona-Pandemie wurden weltweit temporären Schulschließungen vorgenommen. Wie funktioniert(e) Bildung in dieser Kri­se? Daten des Schul-Barometers von insgesamt 5.167 Mitarbeitenden an Schulen aus Deutschland, Österreich und der Schweiz ermöglichen einen Einblick in die Rahmenbedingungen von Digitalisierung während des Lehrens und Lernens während der Schulschließung. Die Daten bestätigen den „digital divide“ in den Kompetenzen und Erfahrungen der Lehrkräfte. Lehrkräfte in Österreich und der Schweiz schätzen ihre digitalen Kompetenzen höher ein als deutsche Mitarbeitende. Die technische Ausstattung wird von Befragten aus Österreich und der Schweiz ebenfalls besser eingeschätzt als in Deutschland. Die Kooperation zwischen Mitarbeitenden der Schule selbst sowie mit Eltern und ein stärkerer Fokus auf die Beziehungsebene zu Schüler*innen wird in Zeiten der Krise trotz und wegen der Distanz noch bedeutsamer für Lehre und Lernen. Perspektivisch können aus den Daten des Schul-Barometers Empfehlungen für die „Schule von morgen“ abgeleitet werden

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the ‘burden of hypoxia and hyperoxia’ expressed in ‘%hours’. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. Trial registration: ClinicalTrial.gov, NCT0159031