HoxA cluster is haploinsufficient for activity of hematopoietic stem and progenitor cells

Functional compensation between homeodomain proteins has hindered the ability to unravel their role in hematopoiesis using single gene knockouts. Because HoxB genes are dispensable for hematopoiesis, and most HoxA genes are expressed an order of magnitude higher than other cluster genes in hematopoietic stem cell (HSC)-enriched populations, we hypothesize that maintenance of HoxA cluster expression is important for adult hematopoiesis and that global decrease of HoxA gene expression levels affects steady-state hematopoiesis.

Potentially Inappropriate Medications Defined by STOPP Criteria and the Risk of Adverse Drug Events in Older Hospitalized Patients

Background: Previous studies have not demonstrated a consistent association between potentially inappropriate medicines (PIMs) in older patients as defined by Beers criteria and avoidable adverse drug events (ADEs). This study aimed to assess whether PIMs defined by new STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions) criteria are significantly associated with ADEs in older people with acute illness.

Methods: We prospectively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval. Potentially inappropriate medicines were defined by both Beers and STOPP criteria. Adverse drug events were defined by World Health Organization–Uppsala Monitoring Centre criteria and verified by a local expert consensus panel, which also assessed whether ADEs were causal or contributory to current hospitalization. Hallas criteria defined ADE avoidability.Wecompared the proportions of patients taking Beers criteria PIMs
and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission.

Results: A total of 329 ADEs were detected in 158 of 600 patients (26.3%); 219 of 329 ADEs (66.6%) were considered causal or contributory to admission. Of the 219 ADEs, 151(68.9%)considered causal or contributory to admission were avoidable or potentially avoidable. After adjusting for age, sex, comorbidity, dementia, baseline activities of daily living function, and number of medications, the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed (odds ratio, 1.847; 95% confidence interval [CI], 1.506-2.264; P.001); prescription of Beers criteria PIMs did not significantly increase ADE risk (odds ratio, 1.276; 95% CI, 0.945-1.722; P=.11).

Conclusion: STOPP criteria PIMs,unlike Beers criteria PIMs, are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization.

The anonymity of the hunt: A critique of hunting as sharing

Hunter-gatherers are often ascribed a “monistic” worldview at odds with the nature-society dichotomy. The centerpiece of this claim is that they view hunting as similar to sharing within the band and prey animals as part of a common sphere of sociality. This article challenges this thesis. An examination of the work of its main proponents shows that it conflates two different senses of “animal”—the flesh-and-blood animals of the hunt and the animal Spirit that is said to control the animals. The sharing motif in hunting makes sense with respect to the anthropomorphic Spirit but not to the animals hunted. The conditions of the hunt as a spatiotemporal event provide further grounds for skepticism toward the idea of hunting-as-sharing. Drawing on biologist Robert Hinde’s model of relationships, I argue that hunting represents an anonymous one-off interaction that cannot develop into a personal relationship, in stark contrast to the durable forms of personalized sociality associated with the hunter-gatherer band. This is not to deny the possibility of human-animal cosociality in the form of personal relationships but rather to redirect the search away from the hunt to the interface with domesticated animals.

WASP-41b: A Transiting Hot Jupiter Planet Orbiting a Magnetically Active G8V Star

We report the discovery of a transiting planet with an orbital period of 3.05 days orbiting the star TYC 7247-587-1. The star, WASP-41, is a moderately bright G8 V star (V=11.6) with a metallicity close to solar ([Fe/H]=-0.08±0.09). The star shows evidence of moderate chromospheric activity, both from emission in the cores of the Ca ii H and K ines and photometric variability with a period of 18.4 days and an amplitude of about 1%. We use a new method to show quantitatively that this periodic signal has a low false-alarm probability. The rotation period of the star implies a gyrochronological age for WASP-41 of 1.8 Gyr with an error of about 15%. We have used a combined analysis of the available photometric and spectroscopic data to derive the mass and radius of the planet (0.92±0.06 M, 1.20±0.06 R). Further observations of WASP-41 can be used to explore the connections between the properties of hot Jupiter planets and the level of chromospheric activity in their host stars.

WASP-40b: Independent Discovery of the 0.6 M Transiting Exoplanet HAT-P-27b

From WASP photometry and SOPHIE radial velocities we report the discovery of WASP-40b (HAT-P-27b), a 0.6 M planet that transits its 12th magnitude host star every 3.04 days. The host star is of late G-type or early K-type and likely has a metallicity greater than solar ([Fe/H]=0.14±0.11). The planet's mass and radius are typical of the known hot Jupiters, thus adding another system to the apparent pileup of transiting planets with periods near 3-4 days. Our parameters match those of the recent HATnet announcement of the same planet, thus giving confidence in the techniques used. We report a possible indication of stellar activity in the host star.

Glacial Survival of Boreal Trees in Northern Scandinavia

It is commonly believed that trees were absent in Scandinavia during the last glaciation and first recolonized the Scandinavian Peninsula with the retreat of its ice sheet some 9000 years ago. Here, we show the presence of a rare mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with its highest frequency to the west—an area believed to sustain ice-free refugia during most of the last ice age. We further show the survival of DNA from this haplotype in lake sediments and pollen of Trøndelag in central Norway dating back ~10,300 years and chloroplast DNA of pine and spruce in lake sediments adjacent to the ice-free Andøya refugium in northwestern Norway as early as ~22,000 and 17,700 years ago, respectively. Our findings imply that conifer trees survived in ice-free refugia of Scandinavia during the last glaciation, challenging current views on survival and spread of trees as a response to climate changes.

Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and EAE severity in the absence of IL-12 receptor signaling

Intravenous (i.v.) administration of autoantigen effectively induces Ag-specific tolerance against experimental autoimmune encephalomyelitis (EAE). We and others have shown enhanced EAE severity in mice lacking IL-12 or its receptor, strongly suggesting an immunoregulatory effect of IL-12 signaling. To examine the role of IL-12 responsiveness in autoantigen-induced tolerance in EAE, we administered autoantigen i.v. in two distinct treatment regimes to wildtype and IL-12Rβ2(-/-) mice, immunized to develop EAE. Administration at the induction phase suppressed EAE in wildtype and IL-12Rβ2(-/-) mice however the effect was somewhat less potent in the absence of IL-12Rβ2. Expression of pro-inflammatory cytokines such as IFN-γ, IL-17 and IL-2, was inhibited in wild-type tolerized mice but less so in IL-12Rβ2(-/-) mice. I.v. antigen was also effective in suppressing disease in both genotypes when given during the clinical phase of disease with similar CNS inflammation, demyelination and peripheral inflammatory cytokine profiles observed in both genotypes. There was however a mild impact of a lack of IL-12 signaling on Treg induction during tolerance induction compared to WT mice in this treatment regime. These findings show that the enhanced severity of EAE that occurs in the absence of IL-12 signaling can be effectively overcome by i.v. autoantigen, indicating that this therapeutic effect is not primarily mediated by IL-12 and that i.v. tolerance could be a powerful approach in suppressing severe and aggressive MS.