Induced seismicity and fluid injection
House in central Oklahoma damaged in an earthquake on November 6, 2011. Image courtesy of Flickr/US Geological Survey.
Over the past decade, the central and eastern United States have experienced an increased number of earthquakes, which are mostly attributed to waste fluid disposal through subsurface injection of saltwater produced from oil/gas production. Guang Zhai et al. (pp. 16228–16233) combined data on fluid injection over time with a physics-based model of crustal stress to calculate pore pressure and poroelastic stresses, and estimate relative seismicity over time for central and western Oklahoma. The authors found that pore-pressure diffusion was the dominant determinant of seismicity rate. However, poroelastic stresses amplified the effect of pore pressure on seismicity by a factor of 2–6. The model reproduced the observed frequency and magnitude patterns of earthquakes of magnitude 3 or greater over time for the years 2008–2017. A mandatory reduction in injection volumes, imposed in 2016, substantially reduced the probability of an earthquake exceeding magnitude 5 in western Oklahoma, but not in central Oklahoma. Imposing a hypothetical injection shut-in in April 2017 led to a gradual decrease in earthquake probability, approaching background levels by approximately 2025. The results highlight the importance of fluid diffusion in determining earthquake risk, according to the authors. — B.D.
Smoking and peers’ genetic risk
Being surrounded by peers with a genetic predisposition to smoke may affect an individual’s smoking behavior. Image courtesy of Pixabay/realworkhard.
Studies have shown that the phenotype of nonhuman animals can be shaped by the genomes of surrounding individuals, but whether humans experience similar effects is unclear. To determine whether being surrounded by peers with a genetic predisposition to smoke affects an individual’s smoking behavior, Ramina Sotoudeh et al. (pp. 16302–16307) analyzed survey data collected between 1994 and 1995 from 3,895 middle school and high school students in the United States. Additionally, between 2008 and 2009, DNA samples were collected from the students. The genetic propensity to smoke in grade-mates and friends was each positively associated with an individual’s smoking behavior, although the correlation was stronger for individuals and their grade-mates. The authors also found that sharing a grade with even a small minority of peers who had a high genetic propensity to smoke greatly increased an individuals’ tendency to smoke. However, having peers with low genetic propensity to smoke did not reduce grade-mates’ tendency to smoke. The findings suggest that grade-mate smoking behavior may be a stronger predictor of individual smoking behavior than the individual’s own genetic propensity. Moreover, genes should be treated as an important part of an individual’s social environment, and social environments should be considered in the context of genetic influence, according to the authors. — M.S.
Inhibition of IRE1α as potential multiple myeloma therapy
In multiple myeloma (MM), a lethal human hematologic cancer, malignant plasma cells overloaded with unfolded proteins (UPs) disproportionately proliferate in bone marrow. Healthy cells mitigate excessive accumulation of UPs by activating the IRE1α–XBP1s biochemical pathway, an adaptive stress response in the endoplasmic reticulum that promotes protein folding and reestablishes homeostasis. Jonathan Harnoss et al. (pp. 16420–16429) demonstrate that the IRE1α–XBP1s pathway is critical for MM cell growth and suggest that IRE1α inhibition represents a promising MM therapeutic approach. Using strategies designed to disrupt IRE1α at the gene, transcript, and kinase levels, the authors show that different human MM cell lines growing in vitro in 3D, rather than 2D, exhibit higher IRE1α pathway activity and a stronger dependency on IRE1α. Furthermore, IRE1α disruption attenuated the ability of MM cells to form malignant subcutaneous and orthometastatic human xenograft tumors in mice, as well as reducing the viability of malignant plasma cells in bone marrow samples from MM patients. Along with additional evidence that IRE1α kinase inhibition spares viability and function of normal tissues, the study suggests that IRE1α-specific kinase-based inhibitors represent a potentially safe and effective therapeutic approach for MM, according to the authors. — T.J.
Stable in vitro transformation of peripheral B cells
Primary effusion lymphomas (PELs) are an aggressive form of non-Hodgkin’s lymphoma that are causally associated with Kaposi’s sarcoma-associated herpesvirus (KSHV). Infecting B cells with KSHV in vitro has so far been challenging, and even when infected, B cells are not transformed by KSHV, making it difficult to model the conditions necessary for the development of PELs. Because most PELs are coinfected with Epstein–Barr virus (EBV), Aurélia Faure et al. (pp. 16519–16528) investigated the role of EBV in coinfection by KSHV. The authors found that coinfection with EBV supported the optimal infection of peripheral B cells with KSHV, with the highest efficiency of KSHV infection occurring within 24 hours of EBV infection. The dually infected B cells were stably transformed and maintained both viruses for months in culture. Some transformed cells that grew to dominate the culture showed increased expression of most KSHV viral latent and lytic genes and shared multiple properties with PEL cells, including the differential expression of a subset of cellular genes similar to those of PEL cells. The authors suggest that the long-term infection and in vitro transformation of peripheral B cells by KSHV and EBV could enable detailed analyses of the viral and cellular genes involved in the development of PEL. — S.R.
Sex-specific gene exacerbates Parkinson’s disease in male mice
In Parkinson’s disease (PD), progressive degeneration of dopamine-producing neurons in the brain’s substantia nigra region leads to gradual decline of voluntary movement control. Males are twice as likely as females to develop PD, and men with PD progress more rapidly and experience greater neuronal degeneration than female counterparts. Joohyung Lee et al. (pp. 16577–16582) report that SRY, a Y-chromosome gene found only in males, may represent a genetic mechanism that exacerbates PD risk factors and disease progression in men. In contrast to the theory that sex differences in PD stem solely from estrogen’s neuroprotective role in females, the authors found using human cell cultures and mouse models that SRY is aberrantly up-regulated in male substantia nigra, where the gene mediates motor control via dopamine biosynthesis. In addition, the authors demonstrate that lowering SRY expression in male rats with PD mitigates key male biases, including neuronal degeneration and inflammation. The findings suggest that SRY represents a sex-specific mechanism for dopamine neuron death in men, according to the authors. — T.J.
Transitioning to middle school
During adolescence self-awareness and independence typically increase and sensitivity to social acceptance heightens. Transitioning to a new environment during adolescence may increase the risk of poor grades and behavioral problems in school. Geoffrey Borman, Christopher Rozek, et al. (pp. 16286–16291) recruited 1,304 middle school students in the midwestern United States to determine whether an intervention that included advice, reassurance that social and academic adversity in middle school was temporary, and confirmation that support was available at school could ease the transition from elementary to middle school. The authors surveyed the students at the beginning of the school year in September—2 weeks before starting the intervention—and at the end of the school year in May. Across the entire school district, the intervention increased students’ sense of social belonging, reduced disciplinary incidents by 34%, reduced the number of failing grades by 18%, and reduced class absences by 12%. The intervention was particularly successful for male students and underrepresented ethnic and racial minority students. The majority of long-term academic benefits of the intervention resulted from changes in students’ academic engagement and attitudes toward school, such as anxiety and social belonging, according to the authors. — M.S.