Minor versus major mergers: the stellar mass growth of massive galaxies from z=3 using number density selection techniques

We present a study on the stellar mass growth of the progenitors of local massive galaxies with a variety of number density selections with n≤1×10−4 Mpc−3 (corresponding to M*=1011.24 M⊙ at z=0.3) in the redshift range 0.3<z<3.0. We select the progenitors of massive galaxies using a constant number density selection, and one which is adjusted to account for major mergers. We find that the progenitors of massive galaxies grow by a factor of 4 in total stellar mass over this redshift range. On average the stellar mass added via the processes of star formation, major and minor mergers account for 24±8, 17±15 and 34±14per cent, respectively, of the total galaxy stellar mass at z=0.3. Therefore 51±20per cent of the total stellar mass in massive galaxies at z=0.3 is created externally to their z=3 progenitors. We explore the implication of these results on the cold gas accretion rate and size evolution of the progenitors of most massive galaxies over the same redshift range. We find an average gas accretion rate of∼66±32 M⊙ yr−1 over the redshift range of 1.5<z<3.0. We find that the size evolution of a galaxy sample selected this way is on average lower than the findings of other investigation

The evolution of galaxies at constant number density: a less biased view of star formation, quenching, and structural formation

Due to significant galaxy contamination and impurity in stellar mass selected samples (up to 95 per cent from z = 0–3), we examine the star formation history, quenching time-scales, and structural evolution of galaxies using a constant number density selection with data from the United Kingdom Infra-Red Deep Sky Survey Ultra-Deep Survey field. Using this methodology, we investigate the evolution of galaxies at a variety of number densities from z= 0–3. We find that samples chosen at number densities ranging from 3 × 10−4 to 10−5 galaxies Mpc−3 (corresponding to z ∼ 0.5 stellar masses of M∗ = 1010.95−11.6 M0) have a star-forming blue fraction of ∼50 per cent at z ∼ 2.5, which evolves to a nearly 100 per cent quenched red and dead population by z ∼ 1. We also see evidence for number density downsizing, such that the galaxies selected at the lowest densities (highest masses) become a homogeneous red population before those at higher number densities. Examining the evolution of the colours for these systems furthermore shows that the formation redshift of galaxies selected at these number densities is zform > 3. The structural evolution through size and S´ersic index fits reveal that while there remains evolution in terms of galaxies becoming larger and more concentrated in stellar mass at lower redshifts, the magnitude of the change is significantly smaller than for a mass-selected sample. We also find that changes in size and structure continues at z < 1, and is coupled strongly to passivity evolution.We conclude that galaxy structure is driving the quenching of galaxies, such that galaxies become concentrated before they become passive

Hexapeptides from mammalian inhibitory hormone hunt activate and inactivate nematode reproduction

© 2022 Hart et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Background: Biopurification has been used to disclose an evolutionarily conserved inhibitory reproductive hormone involved in tissue mass determination. A (rat) bioassay-guided physicochemical fractionation using ovine materials yielded via Edman degradation a 14-residue amino acid (aa) sequence. As a 14mer synthetic peptide (EPL001) this displayed antiproliferative and reproduction-modulating activity, while representing only a part of the native polypeptide. Even more unexpectedly, a scrambled-sequence control peptide (EPL030) did likewise. Methods: Reproduction has been investigated in the nematode Steinernema siamkayai, using a fermentation system supplemented with different concentrations of exogenous hexapeptides. Peptide structure-activity relationships have also been studied using prostate cancer and other mammalian cells in vitro, with peptides in solution or immobilized, and via the use of mammalian assays in vivo and through molecular modelling. Results: Reproduction increased (x3) in the entomopathogenic nematode Steinernema siamkayai after exposure to one synthetic peptide (IEPVFT), while fecundity was reduced (x0.5) after exposure to another (KLKMNG), both effects being dose-dependent. These hexamers are opposite ends of the synthetic peptide KLKMNGKNIEPVFT (EPL030). Bioactivity is unexpected as EPL030 is a control compound, based on a scrambled sequence of the test peptide MKPLTGKVKEFNNI (EPL001). EPL030 and EPL001 are both bioinformatically obscure, having no convincing matches to aa sequences in the protein databases. EPL001 has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Peptides up to a 20mer have also been shown to inhibit the proliferation of human cancer and other mammalian cells in vitro, with reproductive upregulation demonstrated previously in fish and frogs, as well as nematodes. EPL001 encodes the sheep neuroendocrine prohormone secretogranin II (sSgII), as deduced on the basis of immunoprecipitation using an anti-EPL001 antibody, with bespoke bioinformatics. Six sSgII residues are key to EPL001’s bioactivity: MKPLTGKVKEFNNI. A stereospecific bimodular tri-residue signature is described involving simultaneous accessibility for binding of the side chains of two specific trios of amino acids, MKP & VFN. An evolutionarily conserved receptor is conceptualised having dimeric binding sites, each with ligand-matching bimodular stereocentres. The bioactivity of the 14mer control peptide EPL030 and its hexapeptide progeny is due to the fortuitous assembly of subsets of the novel hormonal motif, MKPVFN, a default reproductive and tissue-building OFF signal.Peer reviewe

Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

&lt;br&gt;Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.&lt;/br&gt; &lt;br&gt;Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.&lt;/br&gt; &lt;br&gt;Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).&lt;/br&gt;&lt;br&gt;Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.&lt;/br&gt

Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity

Background: Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety. Methods: We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test. Results: In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05). Limitations: The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires. Conclusions: Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder

546 Results from Phase Ib study of tebentafusp (tebe) in combination with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM)

BackgroundTebe, a T cell receptor fused to an anti-CD3 effector, can redirect T cells to target gp100+ cells and in Ph3, demonstrated overall survival (OS) benefit as monotherapy in metastatic uveal melanoma. In Ph2, any tumor shrinkage (44% of patients) was a better predictor of OS than response rate. In Ph1, Tebe had monotherapy activity in mCM, also a gp100+ tumor, with 1-year OS ~74% in PD-1 naïve mCM. A Ph1 dose escalation of tebe with durva (anti-PD-L1) and/or treme (anti-CTLA4) was conducted in pre-treated mCM [NCT02535078], with nearly all patients having prior PD1-treatment, and where recently reported therapies have 1-yr OS of ~55%.MethodsHeavily pre-treated HLA-A2+ mCM patients received weekly IV tebe alone (Arm 4) or with increasing doses of durva and/or treme (Arm 1–3) administered IV monthly starting day 15 of each cycle. Primary objective was to identify RP2D of combination therapy. Secondary objectives included adverse events (AE) and efficacy.Results112 pts received ≥1 tebe dose. Median age was 59, 77% were ECOG 0, and 37% were BRAFm (of which 71% received prior BRAFi/MEKi). 91% of pts were 2L+, while 74% were 3L+. 103 (92%) received prior PD-1 inhibitor, of which 87% also received prior ipilimumab. 43 pts received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 29 received triplet therapy (Arm 3), and 27 received tebe alone (Arm 4). Maximum target doses of tebe (68 mcg) + durva (20 mg/kg) and treme (1 mg/kg) were tolerated. MTD was not formally identified for any arm. Two DLTs occurred: prolonged grade 3 rash (Arm 1) and grade 2 diarrhea leading to treatment delay (Arm 2). Related AEs that were Grade ≥3 or led to discontinuations were: 44%/0% (Arm 1), 23%/0% (Arm2), 38%/7% (Arm3), 26%/4% (Arm 4). There were no treatment-related deaths.In prior PD-1 pts, tumor shrinkage occurred in 36% and 1-yr OS was 68%. Of 51 evaluable PD-1 resistant pts (best response CR/PR/SD to prior PD1), tumor shrinkage occurred in 28% and 1-yr OS was 73% (figure 1). In 35 evaluable PD-1 refractory pts (prior best response PD), tumor shrinkage occurred in 49% and 1-yr OS was 61%. For 38 prior PD-1 pts who received ≥10mg/kg durva, 1-yr OS was 81%.Abstract 546 Figure 1% tumor change from baseline in evaluable patients with known response to prior PD1 exposureConclusionsTebe with anti-PD-L1 and/or anti-CTLA4 had an acceptable safety profile. Tebe + durva demonstrated durable tumor shrinkage and promising 1-yr OS rates in prior-PD1 treated mCM relative to recent reports.Trial RegistrationNCT02535078Ethics ApprovalThe institutional review board or independent ethics committee at each center approved the trial. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines

The seeding of ice algal blooms in Arctic pack ice: The multiyear ice seed repository hypothesis

Source at http://dx.doi.org/10.1002/2016JG003668 During the Norwegian young sea ICE expedition (N-ICE2015) from January to June 2015 the pack ice in the Arctic Ocean north of Svalbard was studied during four drifts between 83° and 80°N. This pack ice consisted of a mix of second year, fi rst year, and young ice. The physical properties and ice algal community composition was investigated in the three different ice types during the winter-spring-summer transition. Our results indicate that algae remaining in sea ice that survived the summer melt season are subsequently trapped in the upper layers of the ice column during winter and may function as an algal seed repository. Once the connectivity in the entire ice column is established, as a result of temperature-driven increase in ice porosity during spring, algae in the upper parts of the ice are able to migrate toward the bottom and initiate the ice algal spring bloom. Furthermore, this algal repository might seed the bloom in younger ice formed in adjacent leads. This mechanism was studied in detail for the dominant ice diatom Nitzschia frigida . The proposed seeding mechanism may be compromised due to the disappearance of older ice in the anticipated regime shift toward a seasonally ice-free Arctic Ocean