The Tully-Fisher Relation for 25,000 SDSS Galaxies as Function of Environment

We construct Tully-Fisher relationships (TFRs) in the $u$, $g$, $r$, $i$ and $z$ bands and stellar mass TFRs (smTFRs) for a sample of $25,698$ late spiral type galaxies (with $0.045<z<0.085$) from the Sloan Digital Sky Survey (SDSS) and study the effects of environment on the relation. We use SDSS-measured Balmer emission line widths, $v_{\rm FWHM}$, as a proxy for disc circular velocity, $v_{\rm circ}$. A priori it is not clear whether we can construct accurate TFRs given the small $3"$ diameter of the fibres used for SDSS spectroscopic measurements. However, we show by modelling the H$\alpha$ emission profile as observed through a $3"$ aperture that for galaxies at appropriate redshifts ($z>0.045$) the fibres sample enough of the disc to obtain a linear relationship between $v_{\rm FWHM}$ and $v_{\rm circ}$, allowing us to obtain a TFR and to investigate dependence on other variables. We also develop a methodology for distinguishing between astrophysical and sample bias in the fibre TFR trends. We observe the well-known steepening of the TFR in redder bands in our sample. We divide the sample of galaxies into four equal groups using projected neighbour density ($\Sigma$) quartiles and find no significant dependence on environment, extending previous work to a wider range of environments and a much larger sample. Having demonstrated that we can construct SDSS-based TFRs is very useful for future applications because of the large sample size available.Comment: accepted for publication in MNRAS. 15 pages, 12 figure

Interaction of pregnancy-specific glycoprotein 1 with integrin Α5β1 is a modulator of extravillous trophoblast functions

Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin α5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to α5β1 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to α5β1 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy

The Resolved Structure and Dynamics of an Isolated Dwarf Galaxy: A VLT and Keck Spectroscopic Survey of WLM

We present spectroscopic data for 180 red giant branch stars in the isolated dwarf irregular galaxy WLM. Observations of the Calcium II triplet lines in spectra of RGB stars covering the entire galaxy were obtained with FORS2 at the VLT and DEIMOS on Keck II allowing us to derive velocities, metallicities, and ages for the stars. With accompanying photometric and radio data we have measured the structural parameters of the stellar and gaseous populations over the full galaxy. The stellar populations show an intrinsically thick configuration with $0.39 \leq q_{0} \leq 0.57$. The stellar rotation in WLM is measured to be $17 \pm 1$ km s$^{-1}$, however the ratio of rotation to pressure support for the stars is $V/\sigma \sim 1$, in contrast to the gas whose ratio is seven times larger. This, along with the structural data and alignment of the kinematic and photometric axes, suggests we are viewing WLM as a highly inclined oblate spheroid. Stellar rotation curves, corrected for asymmetric drift, are used to compute a dynamical mass of $4.3\pm 0.3\times10^{8}$M$_{\odot}$ at the half light radius ($r_{h} = 1656 \pm 49$ pc). The stellar velocity dispersion increases with stellar age in a manner consistent with giant molecular cloud and substructure interactions producing the heating in WLM. Coupled with WLM's isolation, this suggests that the extended vertical structure of its stellar and gaseous components and increase in stellar velocity dispersion with age are due to internal feedback, rather than tidally driven evolution. These represent some of the first observational results from an isolated Local Group dwarf galaxy which can offer important constraints on how strongly internal feedback and secular processes modulate SF and dynamical evolution in low mass isolated objects.Comment: 14 Pages, 17 figures, 3 tables. Accepted for publication in Ap

Storage globulins pass through the Golgi apparatus and multivesicular bodies in the absence of dense vesicle formation during early stages of cotyledon development in mung bean

During seed development and maturation, large amounts of storage proteins are synthesized and deposited in protein storage vacuoles (PSVs). Multiple mechanisms have been proposed to be responsible for transporting storage proteins to PSVs in developing seeds. In this study, a specific antibody was raised against the mung bean (Vigna radiata) seed storage protein 8S globulin and its deposition was followed via immunogold electron microscopy in developing mung bean cotyledons. It is demonstrated that non-aggregated 8S globulins are present in multivesicular bodies (MVBs) in early stages of cotyledon development where neither dense vesicles (DVs) nor a PSV were recognizable. However, at later stages of cotyledon development, condensed globulins were visible in both DVs and distinct MVBs with a novel form of partitioning, with the internal vesicles being pushed to one sector of this organelle. These distinct MVBs were no longer sensitive to wortmannin. This study thus indicates a possible role for MVBs in transporting storage proteins to PSVs during the early stage of seed development prior to the involvement of DVs. In addition, wortmannin treatment is shown to induce DVs to form aggregates and to fuse with the plasma membrane

PATH-10. Accelerating comprehensive CNS tumor molecular diagnostics with Rapid-CNS2 and MNP-flex: a prospective multi-center validation [Abstract]

BACKGROUND The 2021 WHO classification update highlights the necessity of integrating molecular alterations for precise central nervous system (CNS) tumor diagnoses. However, current molecular reporting methods are hindered by significant initial investment, labor-intensive protocols, and lengthy turnaround times. Methylation-based classification has emerged as a pivotal diagnostic tool but is currently limited to array-based techniques. This necessitates exploration of novel technologies to streamline molecular analysis. METHODS We implemented Rapid-CNS2 - our adaptive sampling-based nanopore sequencing workflow- on 190 adult and pediatric samples at University Hospital Heidelberg and University of Nottingham. Intraoperative potential was assessed through real-time analysis followed by 24-hour sequencing for comprehensive genomic insights. Additionally, we developed MNP-Flex, a platform-agnostic version of the Heidelberg methylation classifier covering 184 CNS tumor classes. We evaluated MNP-flex on a global cohort of over 78,000 samples from methylation arrays, whole genome bisulfite sequencing, nanopore whole genome sequencing, methylation panels and Rapid-CNS2. RESULTS Rapid-CNS2 validation yielded accurate integrated diagnoses in all 190 samples. Within a crucial 30-minute timeframe, we reported accurate methylation families and arm-level copy number profiles followed by next-day reporting of fine-grained methylation classification, SNVs, focal CNVs, MGMT status, fusions and novel structural variants. Moreover, MNP-Flex achieved 92% accuracy over the validation dataset spanning over 78,000 samples from five different technologies. CONCLUSIONS The adoption of Rapid-CNS2 and MNP-Flex enables rapid intraoperative broad methylation classification and copy number alteration reporting within 30 minutes, with additional clinically relevant, fine-grained molecular insights available the following day. It offers clinicians rapid access to comprehensive molecular information critical for treatment decisions. Furthermore, MNP-Flex extends the utility of the Heidelberg methylation classifier to diverse sequencing-based data. By overcoming the limitations of currently available methods, our workflow represents a paradigm shift in the field, promising improved management of CNS tumor patients. Rapid-CNS2 can be executed with a single command, while MNP-Flex is publicly available as a web service, enhancing accessibility and usability for clinical applications

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

A General Model for the CO-H2 Conversion Factor in Galaxies with Applications to the Star Formation Law

The most common means of converting an observed CO line intensity into a molecular gas mass requires the use of a conversion factor (Xco). While in the Milky Way this quantity does not appear to vary significantly, there is good reason to believe that Xco will depend on the larger-scale galactic environment. Utilising numerical models, we investigate how varying metallicities, gas temperatures and velocity dispersions in galaxies impact the way CO line emission traces the underlying H2 gas mass, and under what circumstances Xco may differ from the Galactic mean value. We find that, due to the combined effects of increased gas temperature and velocity dispersion, Xco is depressed below the Galactic mean in high surface density environments such as ULIRGs. In contrast, in low metallicity environments, Xco tends to be higher than in the Milky Way, due to photodissociation of CO in metal-poor clouds. At higher redshifts, gas-rich discs may have gravitationally unstable clumps which are warm (due to increased star formation) and have elevated velocity dispersions. These discs tend to have Xco values ranging between present-epoch gas-rich mergers and quiescent discs at low-z. This model shows that on average, mergers do have lower Xco values than disc galaxies, though there is significant overlap. Xco varies smoothly with the local conditions within a galaxy, and is not a function of global galaxy morphology. We combine our results to provide a general fitting formula for Xco as a function of CO line intensity and metallicity. We show that replacing the traditional approach of using one constant Xco for starbursts and another for discs with our best-fit function produces star formation laws that are continuous rather than bimodal, and that have significantly reduced scatter.Comment: Accepted by MNRAS; major revision includes moving the bulk of the equations to an appendi