Studying Millisecond Pulsars in X-rays

Millisecond pulsars represent an evolutionarily distinct group among rotation-powered pulsars. Outside the radio band, the soft X-ray range ($\sim 0.1$--10 keV) is most suitable for studying radiative mechanisms operating in these fascinating objects. X-ray observations revealed diverse properties of emission from millisecond pulsars. For the most of them, the bulk of radiation is of a thermal origin, emitted from small spots (polar caps) on the neutron star surface heated by relativistic particles produced in pulsar acceleration zones. On the other hand, a few other very fast rotating pulsars exhibit almost pure nonthermal emission generated, most probably, in pulsar magnetospheres. There are also examples of nonthermal emission detected from X-ray nebulae powered by millisecond pulsars, as well as from pulsar winds shocked in binary systems with millisecond pulsars as companions. These and other most important results obtained from X-ray observations of millisecond pulsars are reviewed in this paper, as well as results from the search for millisecond pulsations in X-ray flux of the radio-quite neutron star RX J1856.5-3754

The Role of Oestrogen Receptor Beta (ERβ) in the Aetiology and Treatment of Type 2 Diabetes Mellitus

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary.

OBJECTIVE: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. RESULTS: We found TR isoforms to be expressed most prominently in gonadotropes and - although to a lesser extent - in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. CONCLUSIONS: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T(4)).

Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus.

CONTEXT: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. OBJECTIVE: The aim of this study was to report the distribution of type II and type III deiodinase (D2 and D3) as well as the recently identified T(3) transporter, monocarboxylate transporter 8 (MCT8), in the human hypothalamus. DESIGN: The study included enzyme activity assays, immunocytochemical studies, and mRNA in situ hybridizations in postmortem human hypothalamus (n = 9). RESULTS: D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence, blood vessels, and cells lining the third ventricle. By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN). In support of these immunocytochemical data, D2 and D3 enzyme activities are detectable in the mediobasal human hypothalamus. Combined D2, D3, MCT8, and thyroid hormone receptor immunohistochemistry and TRH mRNA in situ hybridization clearly showed that D3, MCT8, and thyroid hormone receptor isoforms are all expressed in TRH neurons of the PVN, whereas D2 is not. CONCLUSIONS AND IMPLICATIONS: Based on these findings, we propose three possible routes for thyroid hormone feedback on TRH neurons in the human PVN: 1) local thyroid hormone uptake from the vascular compartment within the PVN, 2) thyroid hormone uptake from the cerebrospinal fluid in the third ventricle followed by transport to TRH neurons in the PVN or IFN neurons projecting to TRH neurons in the PVN, and 3) thyroid hormone sensing in the IFN of the mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN.