Background

Depression is a debilitating and difficult-to-treat condition in people with HIV (PWH) despite viral suppression on antiretroviral therapy (ART). Depression is associated with activation of the PKR-like ER kinase (PERK) pathway, which regulates protein synthesis in response to metabolic stress. We evaluated common PERK haplotypes that influence PERK expression in relation to depressed mood in PWH.

Methods

PWH from 6 research centers were enrolled in the study. Genotyping was conducted using targeted sequencing with TaqMan. The major PERK haplotypes A, B, and D were identified. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II). Covariates including genetically-defined ancestry, demographics, HIV disease/treatment parameters and antidepressant treatments were assessed. Data were analyzed using multivariable regression models.

Results

A total of 287 PWH with a mean (SD) age of 57.1±7.8 years were enrolled. Although the largest ethnic group was non-Hispanic white (n=129, 45.3%), African-American (n=124, 43.5%) and Hispanic (n=30, 10.5%) made up over half the sample. 20.3% were female and 96.5% were virally suppressed. Mean BDI-II was 9.6±9.5, and 28.9% scored above the cutoff for mild depression (BDI-II>13). PERK haplotype frequencies were AA57.8%, AB25.8%, AD 10.1%, and BB4.88%. PERK haplotypes were differentially represented according to genetic ancestry (p=6.84e-6). BDI-II scores were significantly higher in participants with the AB haplotype (F=4.45, p=0.0007).This finding was robust to consideration of potential confounds.

Conclusion

PERK haplotypes were associated with depressed mood in PWH.Consequently, pharmacological targeting of PERK-related pathways might amelioratedepression in PWH.

We present the first full-sky analysis of the cosmic ray arrival direction distribution with data collected by the High-Altitude Water Cherenkov and IceCube observatories in the northern and southern hemispheres at the same median primary particle energy of 10 TeV. The combined sky map and angular power spectrum largely eliminate biases that result from partial sky coverage and present a key to probe into the propagation properties of TeV cosmic rays through our local interstellar medium and the interaction between the interstellar and heliospheric magnetic fields. From the map, we determine the horizontal dipole components of the anisotropy δ 0h = 9.16 ×10-4 and δ 6h = 7.25 ×10-4 (±0.04 × 10-4). In addition, we infer the direction (229.°2 ± 3.°5 R.A., 11.°4 ± 3.°0 decl.) of the interstellar magnetic field from the boundary between large-scale excess and deficit regions from which we estimate the missing corresponding vertical dipole component of the large-scale anisotropy to be δN ∼ -3.97+1.0-2.0 × 10-4.

The High Altitude Water Cerenkov (HAWC) and IceCube observatories, through the Astrophysical Multimessenger Observatory Network (AMON) framework, have developed a multimessenger joint search for extragalactic astrophysical sources. This analysis looks for sources that emit both cosmic neutrinos and gamma rays that are produced in photohadronic or hadronic interactions. The AMON system is running continuously, receiving subthreshold data (i.e., data that are not suited on their own to do astrophysical searches) from HAWC and IceCube, and combining them in real time. Here we present the analysis algorithm, as well as results from archival data collected between 2015 June and 2018 August, with a total live time of 3.0 yr. During this period we found two coincident events that have a false-alarm rate (FAR) of <1 coincidence yr-1, consistent with the background expectations. The real-time implementation of the analysis in the AMON system began on 2019 November 20 and issues alerts to the community through the Gamma-ray Coordinates Network with an FAR threshold of <4 coincidences yr-1.