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Search results are presented for physics beyond the standard model in final states with two opposite-charge, same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb(-1) of proton-proton collisions at root s = 13TeV collected with the CMS detector at the LHC in 2016. The analysis uses the invariant mass of the lepton pair, searching for a kinematic edge or a resonant-like excess compatible with the Z boson mass. The search for a kinematic edge targets production of particles sensitive to the strong force, while the resonance search targets both strongly and electroweakly produced new physics. The observed yields are consistent with the expectations from the standard model, and the results are interpreted in the context of simplified models of supersymmetry. In a gauge mediated supersymmetry breaking (GMSB) model of gluino pair production with decay chains including Z bosons, gluino masses up to 1500-1770 GeV are excluded at the 95% confidence level depending on the lightest neutralino mass. In a model of electroweak chargino-neutralino production, chargino masses as high as 610 GeV are excluded when the lightest neutralino is massless. In GMSB models of electroweak neutralino-neutralino production, neutralino masses up to 500-650 GeV are excluded depending on the decay mode assumed. Finally, in a model with bottom squark pair production and decay chains resulting in a kinematic edge in the dilepton invariant mass distribution, bottom squark masses up to 980-1200 GeV are excluded depending on the mass of the next-to-lightest neutralino.

The transverse momentum balance of pairs of back-to-back b quark jets in PbPb and pp collisions recorded with the CMS detector at the LHC is reported. The center-of-mass energy in both collision systems is 5.02 TeV per nucleon pair. Compared to the pp collision baseline, b quark jets have a larger imbalance in the most central PbPb collisions, as expected from the jet quenching effect. The data are also compared to the corresponding measurement with inclusive dijets. In the most central collisions, the imbalance of b quark dijets is comparable to that of inclusive dijets.

A recent report described a new PCOS-like phenotype in lean older infertile women, and was characterized by high age-specific anti-Mullerian hormone (AMH) but hypo- rather than the expected hyper-androgenism. The hypo-androgenism was, furthermore, characterized of, likely, adrenal origin and autoimmune etiology. We extracted data on 708 consecutive infertility patients, and separated them into three age-strata, < 35, 36-42, and > 42 years. In each stratum, we investigated how levels of anti-Mullerian hormone (AMH) and testosterone (T) interrelate between high-AMH (AMH ae 75th quantile) and normal AMH (25th-75th quantile) and low-T (total testosterone ae19.0 ng/dL), normal-T (19.0-29.0 ng/dL) and high-T (> 29.0 ng/dL). High-AMH cycles were presumed to reflect PCOS-like patients. Routine in vitro fertilization (IVF) cycle outcomes and clinical phenotypes of patients were then compared between groups with AMH and T as statistical variables. This hypo-androgenic PCOS-like phenotype already exists in age stratum < 35 years. It appears to arise from a lean, at very young ages hyper-androgenic PCOS phenotype that develops in comparison to controls (likely autoimmune-induced) insufficiency of the adrenal zona reticularis (low-T and low-DHEAS) and zona fasciculata (low-C), and is characterized by frequent evidence of autoimmunity. A degree of adrenal insufficiency, thus, concomitantly appears to affect adrenal androgen and, to lesser degrees, glucocorticoid production (mineralocorticoids were not investigated). Here investigated new PCOS-like phenotype demonstrates features compatible with what under Rotterdam criteria has been referred to as PCOS phenotype-D. If confirmed, the observation that the ontogeny of this phenotype already at young ages is, likely, driven by adrenal autoimmunity, supports the position of the androgen excess and PCOS society that the etiology of phenotype-D differs from that of classical hyper-androgenic PCOS of mostly ovarian etiology.

Derepression of chromatin-mediated transcriptional repression of paternal and maternal genomes is considered the first major step that initiates zygotic gene expression after fertilization. The histone variant H3.3 is present in both male and female gametes and is thought to be important for remodeling the paternal and maternal genomes for activation during both fertilization and embryogenesis. However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA-tagged mouse model, engineered to report H3.3 expression in live animals and to distinguish different sources of H3.3 protein in embryos, we show here that sperm-derived H3.3 (sH3.3) protein is removed from the sperm genome shortly after fertilization and extruded from the zygotes via the second polar bodies (PBII) during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is incorporated into the paternal genome as early as 2 h postfertilization and is detectable in the paternal genome until the morula stage. Knockdown of maternal H3.3 resulted in compromised embryonic development both of fertilized embryos and of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in oocytes impairs both activation of the Oct4 pluripotency marker gene and global de novo transcription from the paternal genome important for early embryonic development. Our results suggest that H3.3-mediated paternal chromatin remodeling is essential for the development of preimplantation embryos and the activation of the paternal genome during embryogenesis.

Background: Highly Individualized Egg Retrieval (HIER), defined as age-specific early oocyte retrieval (ER), has been demonstrated to avoid premature luteinization in women >= 43. We here investigated whether HIER also applies to younger women with premature ovarian aging (POA), and what best lead follicle size should be for administration of ovulation-triggers. Methods: Fifty-six women >= 43, and 37 POA patients underwent IVF cycles. Granulosa cells (GCs) were isolated, cultures were established, RNA was extracted and real-time PCR analyses performed, with gene expressions at mRNA level investigated for FSH receptor (FSHR), luteinizing hormone receptor (LHCPR), P450 aromatase (CYP19a1) and progesterone receptor (PGR). POA was defined by age < 40, FSH above 95%CI and/or AMH below 95%CI for age. Women >= 43 years were divided into very early retrieval (VER), with human chorionic gonadotropin (hCG) trigger at 13. 5-15.5 mm, ER at 16.0-18.0 mm or standard retrievel (SR) at 18.5-20.5 mm; POA patients were divided into ER and SR. Pregnancy rates and and molecular markers of premature luteinization (PL) were main outcome measures. Results: ER resulted in a significantly higher clinical pregnancy rate (16.7%) than VER (5.9%) or SR (6.7%; both P < 0.05). Molecular markers of PL were highest with SR and lowest with VER. In POA, ER improved pregnancy chances even more than in women >= 43 (7.7% with SR vs. 41.7% with ER), while also reducing molecular markers of PL. With low ovarian reserve (LOR), by avoiding PL, ER with hCG trigger at 16.0-18.0 mm, thus, improves clinical pregnancy rates at all ages. As VER demonstrated lowest molecular PL marker but equally poor pregnancy rates as SR, too early ovulation triggers, likely, result in cytoplasmatic immaturity. Conclusions: HIER is even more effective in POA patients than women above age 43, demonstrating that HIER should be further investigated going into even more advanced ages.

IntroductionObesity is a risk factor for adverse physical health outcomes during pregnancy. Much less is known about the association between obesity and maternal mental health. Evidence suggests that prenatal depression is associated with excessive weight gain during pregnancy and that this relationship may vary according to pregravid body mass index (BMI). Young women may be particularly vulnerable to postpartum depression. The objective of this study is to examine the association between prepregnancy BMI, gestational weight gain, and postpartum depressive symptoms among adolescents. MethodsParticipants were 505 pregnant adolescents aged 14 to 21 years followed during pregnancy and 6 months postpartum. Data were collected via interviews and medical record abstraction. Multilevel linear mixed models were used to test the association between excessive gestational weight gain as defined by National Academy of Medicine Guidelines and postpartum depressive symptoms measured via the validated Center for Epidemiologic Studies Depression (CES-D) scale. Analyses controlled for sociodemographic factors (maternal age, race, ethnicity, relationship status), health behaviors (nutrition, physical activity), prenatal depressive symptoms, and postpartum weight retention. ResultsPrepregnancy BMI was classified as follows: 11% underweight, 53% healthy weight, 19% overweight, and 18% obese. One-half (50%) of participants exceeded recommended guidelines for gestational weight gain. Adolescents with excessive gestational weight gain who entered pregnancy overweight or obese had significantly higher postpartum depressive symptoms (, 2.41; SE, 1.06 vs , 2.58; SE, 1.08, respectively; both P < .05) compared with those with healthy prepregnancy BMI and appropriate gestational weight gain. Adolescents who gained gestational weight within clinically recommended guidelines were not at risk for increased depressive symptoms. DiscussionAdolescents who enter pregnancy overweight or obese and experience excessive weight gain may be at increased risk for postpartum depressive symptoms. Health care providers should offer preventive interventions during pregnancy and the interconceptional period to support healthy weight gain and safeguard women's mental health.

Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycantargeting antibodies showed differences of only 3-to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMCderived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Envpseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMCderived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of these in vitro neutralization assays to in vivo antibody performance. IMPORTANCE Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Antibodies with exceptional neutralizing activity against HIV-1 may provide several advantages to traditional HIV drugs, including an improved side-effect profile, a reduced dosing frequency, and immune enhancement. The activity of these antibodies has been established in vitro by utilizing HIV-1 Envpseudotyped viruses derived from circulating viruses but produced in 293T cells by pairing Env proteins with a backbone vector. We tested PBMC-produced circulating viruses against five anti-HIV-1 antibodies currently in clinical development. We found that the activity of these antibodies against PBMC isolates is significantly less than that against 293T Env-pseudotyped viruses. This decline varied among the antibodies tested, with some demonstrating moderate reductions in activity and others showing an almost 100-fold reduction. As the development of these antibodies progresses, it will be critical to determine how the results of different in vitro tests correspond to performance in the clinic.

Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of proton proton collision data collected at root s = 13 TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1). The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simplified models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180 GeV and 1150 GeV are excluded at 95% CL. These results significantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations.

Glia have been suggested to regulate sleep-like states in vertebrates and invertebrates alike. In the nematode Caenorhabditis elegans, sleep is associated with molting between larval stages. To understand if glia modulate neural circuits driving sleep in C. elegans larvae, we ablated the astrocyte-like CEPsh glia. We found that glia-ablated animals exhibit episodes of immobility preceding sleep, prolonged sleep, molting-independent short-duration locomotory pausing, and delayed development. CEPsh glia ensheath synapses between the sleep-associated ALA neuron and its postsynaptic partner AVE, a major locomotion interneuron. While AVE calcium transients normally correlate with head retraction, glia ablation results in prolonged calcium transients that are uncoupled from movement. Strikingly, all these glia ablation defects are suppressed by the ablation of ALA. Our results suggest that glia attenuate sleep-promoting inhibitory connections between ALA and AVE, uncovering specific roles for glia in sleep behavior. We propose that similar mechanisms may underlie glial roles in sleep in other animals.