Interactions of N- and C-terminal parts of Ana1 permitting centriole duplication but not elongation.

The conserved process of centriole duplication requires establishment of a Sas6-centred cartwheel initiated by Plk4's phosphorylation of Ana1/STIL. Subsequently the centriole undergoes conversion to a centrosome requiring its radial expansion and elongation, mediated by a network requiring interactions between Cep135, Ana1/Cep295, and Asterless/Cep152. Here we show that mutant alleles encoding overlapping N- and C-terminal parts of Ana1 are capable of intragenic complementation to rescue radial expansion.

Greatwall-Endos-PP2A/B55 network regulates translation and stability of maternal transcripts in the oocyte-to-embryo transition.

The transition from oocyte to embryo requires translation of maternally provided transcripts that in is activated by Pan Gu kinase to release a rapid succession of 13 mitotic cycles. Mitotic entry is promoted by several protein kinases that include Greatwall/Mastl, whose Endosulfine substrates antagonize Protein Phosphatase 2A (PP2A), facilitating mitotic Cyclin-dependent kinase 1/Cyclin B kinase activity. Here we show that hyperactive can not only be suppressed by mutants in its Endos substrate but also by mutants in Pan Gu kinase subunits.

9-fold symmetry is not essential for centriole elongation and formation of new centriole-like structures.

As daughter centrioles assemble during G2, they recruit conserved Ana3/RTTN followed by its partner Rcd4/PPP1R35. Together, this contributes to the subsequent recruitment of Ana1/CEP295, required for the centriole's conversion to a centrosome. Here, we show that Rcd4/PPP1R35 is also required to maintain 9-fold centriole symmetry in the Drosophila male germline; its absence causes microtubule triplets to disperse into a reduced number of doublet or singlet microtubules.

Protocol for preparing Drosophila genomic DNA to create chromosome-level de novo genome assemblies.

De novo genome assemblies are common tools for examining novel biological phenomena in non-model organisms. Here, we present a protocol for preparing Drosophila genomic DNA to create chromosome-level de novo genome assemblies. We describe steps for high-molecular-weight DNA preparation with phenol or Genomic-tips, quality control, long-read nanopore sequencing, short-read DNA library preparation, and sequencing.

Protocol for screening facultative parthenogenesis in Drosophila.

Most species of sexually reproducing Drosophila are capable of some degree of facultative parthenogenesis, which involves the initiation of development in an unfertilized egg. Here, we present an optimized protocol to screen facultative parthenogenesis in Drosophila. We describe steps for the collection and maintenance of virgin flies.

A genetic basis for facultative parthenogenesis in Drosophila.

Facultative parthenogenesis enables sexually reproducing organisms to switch between sexual and asexual parthenogenetic reproduction. To gain insights into this phenomenon, we sequenced the genomes of sexually reproducing and parthenogenetic strains of Drosophila mercatorum and identified differences in the gene expression in their eggs. We then tested whether manipulating the expression of candidate gene homologs identified in Drosophila mercatorum could lead to facultative parthenogenesis in the non-parthenogenetic species Drosophila melanogaster.

Mob4 is essential for spermatogenesis in Drosophila melanogaster.

Gamete formation is essential for sexual reproduction in metazoans. Meiosis in males gives rise to spermatids that must differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of interconnected spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles.

Can the UK 'Netflix' Payment Model Boost the Antibacterial Pipeline?

The silent pandemic of antimicrobial resistance (AMR) is a global issue needing prompt attention. A comprehensive one-health approach across human and animal health, agriculture and the environment is needed to solve this, addressing overuse of antibacterials, and of course, optimising measures for preventing and controlling infection. We also need a robust pipeline of new antibacterials.

Behind the developing brains and beating hearts of stem cell-derived embryo models.

Studies over the past decade have shown how stem cells representing embryonic and extra-embryonic tissues of the mouse can self-assemble in the culture dish to recapitulate an astonishing part of early embryonic development. A systematic analysis has demonstrated how pluripotent embryonic stem cells can be induced to behave like the implanting epiblast; how they can interact with trophectoderm stem cells to form a patterned structure resembling the implanting embryo prior to gastrulation; and how the third stem cell type-extra-embryonic endoderm cells-can be incorporated to generate structures that undergo the cell movements and gene expression patterns of gastrulation. Moreover, such stem cell-derived embryo models can proceed to neurulation and establish progenitors for all parts of the brain and neural tube, somites, beating heart structures and gut tube.

Targeting Drosophila Sas6 to mitochondria reveals its high affinity for Gorab.

The ability to relocalize proteins to defined subcellular locations presents a powerful tool to examine protein-protein interactions that can overcome a tendency of non-targeted exogenous proteins to form inaccessible aggregates. Here, we show that a 24-amino-acid sequence from the Drosophila proapoptotic protein Hid's tail anchor (HTA) domain can target exogenous proteins to the mitochondria in Drosophila cells. We use this HTA tag to target the Drosophila centriole cartwheel protein Sas6 to the mitochondria, and show that both exogenous and endogenous Gorab can be co-recruited from the Golgi to the new mitochondrial site.

Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension.

Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis.

Embryo model completes gastrulation to neurulation and organogenesis.

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization.

Bereavement in the Time of COVID-19: Learning from Experiences of those Bereaved as a Result of Deaths in an Acute Hospital Setting in 2020.

The COVID-19 pandemic has resulted in many people experiencing bereavement in challenging circumstances. In April 2020 at a large London Trust, a "Bereavement Welfare Hub" was established to offer support and advice by telephone to relatives and carers of all adults who died as inpatients. Data from BWH call records regarding 809 adults who died at the Trust in March, April and May 2020 were collated.

Phase II, Double-Blind, Vehicle-Controlled Study to Determine the Cantharidin Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects with External Genital Warts.

Background: External genital warts are caused by various subtypes of the human papilloma virus and spread through direct skin-to-skin contact. Approximately 1% of the US population have external genital warts. Although cantharidin has been used to treat external genital warts for decades, there are no US Food and Drug Administration-approved cantharidin products and no reliable or controlled sources of cantharidin available.

COVE-1: A Phase 2, Open-Label Study to Evaluate Efficacy and Safety and the Optimal Regimen of VP-102, a Proprietary Drug-Device Product Containing Topical Cantharidin (0.7% w/v) Under Occlusion for the Treatment of Common Warts.

Introduction: Verrucae vulgaris, or common warts, is a common skin condition for which there is no US Food and Drug Administration-approved treatment. Compounded cantharidin has been used to treat warts for years but lacks a controlled formulation, consistent application schedule and methods, and robust safety and efficacy studies. VP-102 is a proprietary drug-device combination product containing a topical formulation of 0.

The careful control of Polo kinase by APC/C-Ube2C ensures the intercellular transport of germline centrosomes during oogenesis.

A feature of metazoan reproduction is the elimination of maternal centrosomes from the oocyte. In animals that form syncytial cysts during oogenesis, including and human, all centrosomes within the cyst migrate to the oocyte where they are subsequently degenerated. The importance and the underlying mechanism of this event remain unclear.

Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins.

Lysosome-related organelles (LROs) are endosomal compartments carrying tissue-specific proteins, which become enlarged in Chediak-Higashi syndrome (CHS) due to mutations in LYST. Here, we show that Drosophila Mauve, a counterpart of LYST, suppresses vesicle fusion events with lipid droplets (LDs) during the formation of yolk granules (YGs), the LROs of the syncytial embryo, and opposes Rab5, which promotes fusion. Mauve localizes on YGs and at spindle poles, and it co-immunoprecipitates with the LDs' component and microtubule-associated protein Minispindles/Ch-TOG.

The dimeric Golgi protein Gorab binds to Sas6 as a monomer to mediate centriole duplication.

The duplication and ninefold symmetry of the centriole requires that the cartwheel molecule, Sas6, physically associates with Gorab, a trans-Golgi component. How Gorab achieves these disparate associations is unclear. Here, we use hydrogen-deuterium exchange mass spectrometry to define Gorab's interacting surfaces that mediate its subcellular localization.

Pooled Results of Two Randomized Phase III Trials Evaluating VP-102, a Drug-Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum.

Background: Compounded cantharidin has been used for decades to treat molluscum contagiosum but lacks rigorous clinical evidence to support its safety and efficacy. VP-102 is a shelf-stable drug-device combination product that contains topical cantharidin (0.7% weight/volume [w/v]) and is being evaluated for the treatment of molluscum.

Novel perspectives of target-binding by the evolutionarily conserved PP4 phosphatase.

Protein phosphatase 4 (PP4) is an evolutionarily conserved and essential Ser/Thr phosphatase that regulates cell division, development and DNA repair in eukaryotes. The major form of PP4, present from yeast to human, is the PP4c-R2-R3 heterotrimeric complex. The R3 subunit is responsible for substrate-recognition via its EVH1 domain.

Interaction interface in the C-terminal parts of centriole proteins Sas6 and Ana2.

The centriole is a ninefold symmetrical structure found at the core of centrosomes and, as a basal body, at the base of cilia, whose conserved duplication is regulated by Plk4 kinase. Plk4 phosphorylates a single serine residue at the N-terminus of Ana2 to promote Ana2's loading to the site of procentriole formation. Four conserved serines in Ana2's STAN motif are then phosphorylated by Plk4, enabling Sas6 recruitment.

Expression of SARS-CoV-2 receptor and the protease suggests susceptibility of the human embryo in the first trimester.

While initially recognized as causing respiratory disease, the SARS-CoV-2 virus also affects many other organs leading to other complications. It has emerged that advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered. Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes , encoding the SARS-CoV-2 receptor, and , encoding a protease that cleaves both the viral spike protein and the ACE2 receptor to facilitate infection.