Electric dipole moments and the search for new physics

Static electric dipole moments of nondegenerate systems probe mass scales for physics beyond the Standard Model well beyond those reached directly at high energy colliders. Discrimination between different physics models, however, requires complementary searches in atomic-molecular-and-optical, nuclear and particle physics. In this report, we discuss the current status and prospects in the near future for a compelling suite of such experiments, along with developments needed in the encompassing theoretical framework.Comment: Contribution to Snowmass 2021; updated with community edits and endorsement

Rhegmatogenous Retinal Detachment in Children: Clinical Factors Predictive of Successful Surgical Repair

To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). Retrospective interventional case series. Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. Patients were divided into 3 age groups (0-6 years, 7-12 years, and 13-18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. Complete reattachment of the retina at final follow-up. Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22-0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2-4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5-8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12-0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1-4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1-5.1) compared with PPV alone (51%). Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV

Phosphorylation of Eukaryotic Initiation Factor-2α during Stress and Encystation in <i>Entamoeba</i> Species

<div><p><i>Entamoeba histolytica</i> is an enteric pathogen responsible for amoebic dysentery and liver abscess. It alternates between the host-restricted trophozoite form and the infective environmentally-stable cyst stage. Throughout its lifecycle <i>E</i>. <i>histolytica</i> experiences stress, in part, from host immune pressure. Conversion to cysts is presumed to be a stress-response. In other systems, stress induces phosphorylation of a serine residue on eukaryotic translation initiation factor-2α (eIF2α). This inhibits eIF2α activity resulting in a general decline in protein synthesis. Genomic data reveal that <i>E</i>. <i>histolytica</i> possesses eIF2α (<i>Eh</i>eIF2α) with a conserved phosphorylatable serine at position 59 (Ser⁵⁹). Thus, this pathogen may have the machinery for stress-induced translational control. To test this, we exposed cells to different stress conditions and measured the level of total and phospho-<i>Eh</i>eIF2α. Long-term serum starvation, long-term heat shock, and oxidative stress induced an increase in the level of phospho-<i>Eh</i>eIF2α, while short-term serum starvation, short-term heat shock, or glucose deprivation did not. Long-term serum starvation also caused a decrease in polyribosome abundance, which is in accordance with the observation that this condition induces phosphorylation of <i>Eh</i>eIF2α. We generated transgenic cells that overexpress wildtype <i>Eh</i>eIF2α, a non-phosphorylatable variant of eIF2α in which Ser⁵⁹ was mutated to alanine (<i>Eh</i>eIF2α-S59A), or a phosphomimetic variant of eIF2α in which Ser⁵⁹ was mutated to aspartic acid (<i>Eh</i>eIF2α-S59D). Consistent with the known functions of eIF2α, cells expressing wildtype or <i>Eh</i>eIF2α-S59D exhibited increased or decreased translation, respectively. Surprisingly, cells expressing <i>Eh</i>eIF2α-S59A also exhibited reduced translation. Cells expressing <i>Eh</i>eIF2α-S59D were more resistant to long-term serum starvation underscoring the significance of <i>Eh</i>eIF2α phosphorylation in managing stress. Finally, phospho-eIF2α accumulated during encystation in <i>E</i>. <i>invadens</i>, a model encystation system. Together, these data demonstrate that the eIF2α-dependent stress response system is operational in <i>Entamoeba</i> species.</p></div

Western blot analysis confirming exogenous protein expression in transgenic cell lines.

<p>Trophozoites were transfected with plasmids encoding luciferase (209-Luc), wildtype eIF2α (<i>Eh</i>eIF2α-S59), the non-phosphorylatable variant (<i>Eh</i>eIF2α-S59A), or the phosphomimetic variant (<i>Eh</i>eIF2α-S59D). All exogenous versions of eIF2α were FLAG-tagged at the N-terminus. Protein expression was induced using 5 μg mL^-1 tetracycline for 24 hours. Western blots of cell lysates were performed using antibodies specific for total <i>Eh</i>eIF2α, phospho-<i>Eh</i>eIF2α, the FLAG tag, or luciferase. Tetracycline induces expression of exogenous proteins.</p

Analysis of eukaryotic translation initiation factor 2α amino acid sequences.

<p>Protein identity (A) and similarity (B) matrices were generated using BLOSUM 62 algorithm and Protein Blast. (C) The amino acids around the key serine residue, occurring at position 59 in <i>E</i>. <i>histolytica</i> were aligned using a Standard Protein BLAST. The key serine residue that becomes phosphorylated is indicated by shading. Fully conserved resides are noted by an asterisk (*) below the residues. Residues showing strongly similar properties are indicated by a colon (:). Amino acid sequences were identified using UniProtKB; UniProtKB accession number identified. Eh, <i>Entamoeba histolytica</i> (accession no. C4M0A4); Ei, <i>E</i>. <i>invadens</i> (accession no. S0AZW3); Tg, <i>Toxoplasma gondii</i> (accession no. S8GC56); Pf, <i>Plasmodium falciparum</i> (accession no. Q8IBH7); Sc, <i>Saccharomyces cerevisiae</i> (accession no. P20459); Dm, <i>Drosophila melanogaster</i> (accession no. P41374); Hs, <i>Homo sapiens</i> (accession no. P05198)</p

Polyribosome abundance in control and stressed cells.

<p>Total RNA from control (A), serum-starved (B), or glucose-starved (C) cells were resolved by sucrose gradient (15–45%) ultracentrifugation, which separates free ribosomes and monosomes (light fractions) from polysomes (dense fractions). The gradients were fractionated and the fractions were analyzed by UV spectrometry (254 nm). Representative profiles of at least 3 separate trials are shown. Long-term serum starvation led to a decrease in large polysome abundance.</p

SUnSET analysis of active protein biosynthesis in control and transgenic cell lines.

<p>(A) Wildtype cells were incubated in normal growth medium with 100 μg mL^-1 cycloheximide (Cyclo), 10 μg mL^-1 puromycin (Puro), or both (Cyclo + Puro). Cell lysates were subjected to SDS-PAGE and Western blotting using antibody specific for puromycin. Trophozoites readily incorporated puromycin into proteins (Puro). The incorporation was authentic since it was blocked by cycloheximide treatment (Cyclo + Puro). This confirms the utility of the SUnSET procedure for assessing protein synthesis in <i>E</i>. <i>histolytica</i>. (B) Protein expression was induced in the four transgenic cell lines by tetracycline for 72 h and SUnSET was performed. Cell overexpressing the wildtype <i>Eh</i>eIF2α showed the highest level of puromycin incorporation, and thus, the highest level of protein synthesis. As expected, cells expressing the phosphomimetic protein (EheIF2α-S59D) exhibited the lowest level of puromycin incorporation in accordance with the known function of phosphorylated versions of eIF2α. Equal protein loads are demonstrated by Coomassie staining of gels (lower panels). Representative data for at least 3 separate trials are shown. Molecular weight (kDa) is shown.</p

Levels of phospho-eIF2α and total eIF2α levels in control and stressed cells.

<p>Control or stressed cells were subjected to Western blot analysis using antibodies specific total eIF2α or phospho-eIF2α. The ratio of phospho-eIF2α to total eIF2α was determined by scanning densitometry and image analysis (Image J, NCBI). The data represent the mean (± standard error) of at least 3 separate trials. All densitometry values were corrected for load using actin and the ratio of phospho-eIF2α to total eIF2α in control unstressed cells was arbitrarily set to 100%. Representative Western blots shown below each stress condition. Only long-term serum starvation, long-term heat shock, and oxidative stress induced a statistically significant increase in the level of phospho-eIF2α (*<i>P</i><0.05, ***<i>P</i><0.001). Due to the lability of phospho-eIF2α, it was necessary to perform Western blots for the various conditions at different times. As such, differences in the intensities of bands representing total eIF2α are due to variations in exposure to film from trial to trial.</p