The alignments between galaxies, their underlying matter structures, and the cosmic web constitute vital ingredients for a comprehensive understanding of gravity, the nature of matter, and structure formation in the Universe. We provide an overview on the state of the art in the study of these alignment processes and their observational signatures, aimed at a non-specialist audience. The development of the field over the past one hundred years is briefly reviewed. We also discuss the impact of galaxy alignments on measurements of weak gravitational lensing, and discuss avenues for making theoretical and observational progress over the coming decade.

Recent findings support the hypothesis that the CD34+-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133+ cells from granulocyte colony-stimulating factor–mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133+ progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulexeuropaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133+-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.

We demonstrate the high level expression of integral membrane proteins (IMPs) in a cell-free coupled transcription/translation system using a modified Escherichia coli S30 extract preparation and an optimized protocol. The expression of the E. coli small multidrug transporters EmrE and SugE containing four transmembrane segments (TMS), the multidrug transporter TehA with 10 putative TMS, and the cysteine transporter YfiK with six putative TMS, were analysed. All IMPs were produced at high levels yielding up to 2.7 mg of protein per mL of reaction volume. Whilst the vast majority of the synthesized IMPs were precipitated in the reaction mixture, the expression of a fluorescent EmrE-sgGFP fusion construct showed evidence that a small part of the synthesized protein 'remained soluble and this amount could be significantly increased by the addition of E. coli lipids into the cell-free reaction. Alternatively, the majority of the precipitated IMPs could be solubilized in detergent micelles, and modifications to the solubilization procedures yielded proteins that were almost pure. The folding induced 1 by formation of the proposed a-helical secondary structures of the IMPs after solubilization in various micelles was monitored by CD spectroscopy. Furthermore, the reconstitution of EmrE, SugE and TehA into proteoliposomes was demonstrated by freeze-fracture electron microscopy, and the function of EmrE was additionally analysed by the specific transport of ethidium. The cell-free expression technique allowed efficient amino acid specific labeling of the IMPs with 15 N isotopes, and the recording of solution NMR spectra of the solubilized EmrE, SugE and YfiK proteins further indicated a correctly folded conformation of the proteins.

Protein dynamics plays an important role in protein function. Many functionally important motions occur on the microsecond and low millisecond time scale and can be characterized by nuclear magnetic resonance relaxation experiments. We describe the different states of a peptidyl carrier protein (PCP) that play a crucial role in its function as a peptide shuttle in the nonribosomal peptide synthetases of the tyrocidine A system. Both apo-PCP (without the bound 4'-phosphopantetheine cofactor) and holo-PCP exist in two different stable conformations. We show that one of the apo conformations and one of the holo conformations are identical, whereas the two remaining conformations are only detectable by nuclear magnetic resonance spectroscopy in either the apo or holo form. We further demonstrate that this conformational diversity is an essential prerequisite for the directed movement of the 4'-PP cofactor and its interaction with externally acting proteins such as thioesterases and 4'-PP transferase.

SummaryTAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Remarkably, already undamaged oocytes express high levels of the protein, suggesting that TAp63α's activity is under tight control of an inhibitory mechanism. Biochemical studies have proposed that inhibition requires the C-terminal transactivation inhibitory domain. However, the structural mechanism of TAp63α inhibition remains unknown. Here, we show that TAp63α is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with ∼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. Furthermore, we show that a helix in the oligomerization domain of p63 is crucial for tetramer stabilization and competes with the transactivation domain for the same binding site. Our results demonstrate how TAp63α is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.

The shapes of galaxies are not randomly oriented on the sky. During the galaxy formation and evolution process, environment has a strong influence, as tidal gravitational fields in the large-scale structure tend to align nearby galaxies. Additionally, events such as galaxy mergers affect the relative alignments of both the shapes and angular momenta of galaxies throughout their history. These "intrinsic galaxy alignments" are known to exist, but are still poorly understood. This review will offer a pedagogical introduction to the current theories that describe intrinsic galaxy alignments, including the apparent difference in intrinsic alignment between early-and late-type galaxies and the latest efforts to model them analytically. It will then describe the ongoing efforts to simulate intrinsic alignments using both N-body and hydrodynamic simulations. Due to the relative youth of this field, there is still much to be done to understand intrinsic galaxy alignments and this review summarises the current state of the field, providing a solid basis for future work.

The survival rate of cancer patients is steadily increasing, owing to more efficient therapies. Understanding the molecular mechanisms of chemotherapy-induced premature ovarian insufficiency (POI) could identify targets for prevention of POI. Loss of the primordial follicle reserve is the most important cause of POI, with the p53 family member p63 being responsible for DNA-damage-induced apoptosis of resting oocytes. Here, we provide the first detailed mechanistic insight into the activation of p63, a process that requires phosphorylation by both the priming kinase CHK2 and the executioner kinase CK1 in mouse primordial follicles. We further describe the structural changes induced by phosphorylation that enable p63 to adopt its active tetrameric conformation and demonstrate that previously discussed phosphorylation by c-Abl is not involved in this process. Inhibition of CK1 rescues primary oocytes from doxorubicin and cisplatin-induced apoptosis, thus uncovering a new target for the development of fertoprotective therapies.

Galaxy shapes are not randomly oriented, rather they are statistically aligned in a way that can depend on formation environment, history and galaxy type. Studying the alignment of galaxies can therefore deliver important information about the physics of galaxy formation and evolution as well as the growth of structure in the Universe. In this review paper we summarise key measurements of galaxy alignments, divided by galaxy type, scale and environment. We also cover the statistics and formalism necessary to understand the observations in the literature. With the emergence of weak gravitational lensing as a precision probe of cosmology, galaxy alignments have taken on an added importance because they can mimic cosmic shear, the effect of gravitational lensing by large-scale structure on observed galaxy shapes. This makes galaxy alignments, commonly referred to as intrinsic alignments, an important systematic effect in weak lensing studies. We quantify the impact of intrinsic alignments on cosmic shear surveys and finish by reviewing practical mitigation techniques which attempt to remove contamination by intrinsic alignments.