OscoNet: Inferring oscillatory gene networks

Background: Oscillatory genes, with periodic expression at the mRNA and/or protein level, have been shown to play a pivotal role in many biological contexts. However, with the exception of the circadian clock and cell cycle, only a few such genes are known. Detecting oscillatory genes from snapshot single-cell experiments is a challenging task due to the lack of time information. Oscope is a recently proposed method to identify co-oscillatory gene pairs using single-cell RNA-seq data. Although promising, the current implementation of Oscope does not provide a principled statistical criterion for selecting oscillatory genes. Results: We improve the optimisation scheme underlying Oscope and provide a wellcalibrated non-parametric hypothesis test to select oscillatory genes at a given FDR threshold. We evaluate performance on synthetic data and three real datasets and show that our approach is more sensitive than the original Oscope formulation, discovering larger sets of known oscillators while avoiding the need for less interpretable thresholds. We also describe how our proposed pseudo-time estimation method is more accurate in recovering the true cell order for each gene cluster while requiring substantially less computation time than the extended nearest insertion approach. Conclusions: OscoNet is a robust and versatile approach to detect oscillatory gene networks from snapshot single-cell data addressing many of the limitations of the original Oscope method

Stop stereotyping.

Restraining the expression of stereotypes is a necessary requirement for harmonious living, yet surprisingly little is known about the efficacy of this process. Accordingly, in two experiments, here we used a stop-signal task to establish how effectively stereotype-related responses can be inhibited. In Experiment 1, following the presentation of gender-typed occupational contexts, participants reported the sex of target faces (i.e., Go trials) unless an occasional auditory tone indicated they should withhold their response (i.e., Stop trials). In Experiment 2, following the presentation of male and female faces, participants made either stereotypic or counter-stereotypic judgments, unless a stop signal was presented. Regardless of whether stereotyping was probed indirectly (Experiment 1) or directly (Experiment 2), a consistent pattern of results was observed; inhibition was faster for stereotypic compared with counter-stereotypic responses. These findings demonstrate that stopping stereotyping may be less challenging than has widely been assumed

Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation.

Recent studies suggest that cells make stochastic choices with respect to differentiation or division. However, the molecular mechanism underlying such stochasticity is unknown. We previously proposed that the timing of vertebrate neuronal differentiation is regulated by molecular oscillations of a transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR-9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR-9 oscillator as a consequence of low molecular numbers of interacting species, determined experimentally. We report that increased stochasticity spreads the timing of differentiation in a population, such that initially equivalent cells differentiate over a period of time. Surprisingly, inherent stochasticity also increases the robustness of the progenitor state and lessens the impact of unequal, random distribution of molecules at cell division on the temporal spread of differentiation at the population level. This advantageous use of biological noise contrasts with the view that noise needs to be counteracted

GFI1 proteins regulate stem cell formation in the AGM

In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothelial-to-haematopoietic transition (EHT). Here, we establish the absolute requirement of the transcriptional repressors GFI1 and GFI1B (growth factor independence 1 and 1B) in this unique trans-differentiation process. We first demonstrate that Gfi1 expression specifically defines the rare population of HE that generates emerging HSCs. We further establish that in the absence of GFI1 proteins, HSCs and haematopoietic progenitor cells are not produced in the AGM, revealing the critical requirement for GFI1 proteins in intra-embryonic EHT. Finally, we demonstrate that GFI1 proteins recruit the chromatin-modifying protein LSD1, a member of the CoREST repressive complex, to epigenetically silence the endothelial program in HE and allow the emergence of blood cells.We thank the staff at the Advanced Imaging, animal facility, Molecular Biology Core facilities and Flow Cytometry of CRUK Manchester Institute for technical support and Michael Lie-A-Ling and Elli Marinopoulou for initiating the DamID-PIP bioinformatics project. We thank members of the Stem Cell Biology group, the Stem Cell Haematopoiesis groups and Martin Gering for valuable advice and critical reading of the manuscript. Work in our laboratory is supported by the Leukaemia and Lymphoma Research Foundation (LLR), Cancer Research UK (CRUK) and the Biotechnology and Biological Sciences Research Council (BBSRC). SC is the recipient of an MRC senior fellowship (MR/J009202/1).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncb327

Selectively varying the number of active quantum wells in integrated devices using only one growth step

The phenomenon of indium migration off the sidewalls of features on patterned GaAs substrates during MBE growth has been studied. The level of migration depends strongly on the arsenic flux and the growth temperature. Modulating the arsenic flux during the growth of multilayer structures allows the number of active quantum wells to vary from one region of a device to another.NRC publication: Ye

Extremely low threshold current density InGaAs/GaAs/AlGaAs strained SQW laser grown by MBE with As2

In this report, we present data on an InGaAs/GaAs strained single quantum well laser with the lowest reported threshold current density to date, namely 44\u2002A\u2002cm 122 for a 3\u2002mm cavity length. This was grown by solid-source molecular-beam epitaxy with the arsenic dimer, As2. The structure is that of a graded-index, separate-confinement heterostructure with a single strained InGaAs quantum well, sandwiched between GaAs barrier layers and AlGaAs cladding layers. The wavelength of the lasers was around 985\u2002nm, and the internal efficiency and losses were 69% and 0.70\u2002cm 121, respectively. In addition, data on the uniformity of our lasers, which are grown on rotating 2 in substrates (1 in\u2002=\u20022.54\u2002cm), show drops in photoluminescence emission wavelength and layer thickness of less than 4\u2002nm and 4%, respectively, from the centre to the edge of the wafer and very little compositional change.Peer reviewed: YesNRC publication: Ye

A study of the evolution of the third COVID-19 pandemic wave in the Athens metropolitan area, Greece, through two cross-sectional seroepidemiological surveys: March, June 2021

We studied the third coronavirus disease 2019 (COVID-19) pandemic wave in Athens metropolitan area (3 738 901 inhabitants) through two seroepidemiological surveys. Persons presenting in 12 healthcare facilities across Athens in March and June 2021 were studied (764 and 901, respectively). Immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein were measured by a chemiluminescent microparticle immunoassay. In March the seroprevalence rate was 11.6%, meaning that 435 208 residents of Athens had evidence of immunity. The respective values in June were 55.7% and 2 082 568 residents. The highest seroprevalence rates attributed to SARS-CoV-2 infection were recorded in persons <18 years (16.3% in March and 31.6% in June), while immunity was mainly vaccine-induced in persons 18–64 years and >65 years. Infection-attributed immunity also increased in older-age groups. Wide ranges in seroprevalence rates were noted across areas in March and June. The highest seroprevalence rates were recorded in Piraeus (47.2%) and West Attica (37.5%). However, the highest increase (>5 times) occurred in Piraeus and the South Section of Athens, which are among the most densely populated areas in Athens. In both study periods, history of COVID-19 or febrile episode, and having a cohabitant with COVID-19 were associated with increased risk for seropositivity among unvaccinated persons (p values <0.001 for all). Residing in Piraeus, the South Section or West Attica was associated with increased risk for seropositivity in June (p values <0.001). Wide heterogeneity in seroprevalence rates was found across areas in Athens, which is mainly attributed to population density. The impact of population mobility and socioeconomic status should be explored. © 2021 Wiley Periodicals LLC