Serotonin Receptor 1A (HTR1A), a Novel Regulator of GnRH Neuronal Migration in Chick Embryo

The hypothalamic GnRH neurons are a small group of cells that regulate the reproductive axis. These neurons are specified within the olfactory placode, delaminate from this structure, and then migrate to enter the forebrain before populating the hypothalamus. We have used microarray technology to analyze the transcriptome of the olfactory placode at a number of key time points for GnRH ontogeny using the chick embryo. This resulted in the identification of a large number of genes whose expression levels change significantly over this period. This repertoire includes those genes that are known to be important for GnRH neuronal development as well as many novel genes, such as the serotonin receptor 1A, HTR1A. We find that HTR1A is expressed in the region of the olfactory placode that generates GnRH neurons. We further show that when this receptor is inactivated using a selective HTR1A antagonist as well as a gene knockdown approach using RNAi, this resulted in delayed migration causing the GnRH neurons to stall just outside the forebrain. These findings implicate HTR1A as being important for GnRH neuronal migration from the olfactory placode to the forebrain. Our study thus extends the repertoire of genes involved in GnRH neuron biology and thus identifies new candidate genes that can be screened for in patients who do not show mutations in any of the previously identified hypogonadotrophic hypogonadism/Kallmann syndrome genes

Magnetic Susceptibility for CaV4O9CaV_4O_9

We examine experimental magnetic susceptibility $\chi^{tot}(T)$ for CaV$_4$O$_9$ by fitting with fitting function $\alpha \chi^{mag}(T) + c$. The function $\chi^{mag}(T)$ is a power series of 1/T and the lowest order term is fixed as $C/T$, where $C$ is the Curie constant as determined by the experimental $g$-value (g=1.96). Fitting parameters are $\alpha$, $c$ and expansion coefficients except for the first one in $\chi^{mag}(T)$. We determine $\alpha$ and $c$ as $\alpha \simeq$ 0.73 and $c\simeq$ 0 for an experimental sample. We interpret $\alpha$ as the volume fraction of CaV$_4$O$_9$ in the sample and $\chi^{mag}(T)$ as the susceptibility for the pure CaV$_4$O$_9$. The result of $\alpha \ne 1$ means that the sample includes nonmagnetic components. This interpretation consists with the result of a perturbation theory and a neutron scattering experiment.Comment: 4pages, 4figure

NaV_2O_5 as a quarter-filled ladder compound

A new X-ray diffraction study of the one-dimensional spin-Peierls compound \alpha-NaV_2O_5 reveals a centrosymmetric (Pmmn) crystal structure with one type of V site, contrary to the previously postulated non-centrosymmetric P2_1mn structure with two types of V sites (V^{+4} and V^{+5}). Density functional calculations indicate that NaV_2O_5 is a quarter-filled ladder compound with the spins carried by V-O-V molecular orbitals on the rungs of the ladder. Estimates of the charge-transfer gap and the exchange coupling agree well with experiment and explain the insulating behavior of NaV_2O_5 and its magnetic properties.Comment: Final version for PRL, value of U correcte

Ab Initio Calculation of Spin Gap Behavior in CaV4O9

Second neighbor dominated exchange coupling in CaV4O9 has been obtained from ab initio density functional (DF) calculations. A DF-based self-consistent atomic deformation model reveals that the nearest neighbor coupling is small due to strong cancellation among the various superexchange processes. Exact diagonalization of the predicted Heisenberg model yields spin-gap behavior in good agreement with experiment. The model is refined by fitting to the experimental susceptibility. The resulting model agrees very well with the experimental susceptibility and triplet dispersion.Comment: 4 pages; 3 ps figures included in text; Revte

Phase Diagram of the S = 1/2 Frustrated Coupled Ladder System

We present a theoretical study of the magnetic phase diagram of the frustrated coupled ladder structure realized recently in several materials. This system displays a nondegenerate spin-gap state in the dimer limit and an infinitely degenerate spin-gap state in the regime of weakly-coupled zig-zag chains. Between these we demonstrate the existence of gapless, magnetically ordered regions whose order is antiferromagnetic close to the honeycomb lattice limit, and incommensurate along the chains when all three magnetic interactions compete.Comment: 5 pages, RevTeX; 5 .eps figure

Spin-Peierls states of quantum antiferromagnets on the CaV4O9Ca V_4 O_9 lattice

We discuss the quantum paramagnetic phases of Heisenberg antiferromagnets on the 1/5-depleted square lattice found in $Ca V_4 O_9$. The possible phases of the quantum dimer model on this lattice are obtained by a mapping to a quantum-mechanical height model. In addition to the ``decoupled'' phases found earlier, we find a possible intermediate spin-Peierls phase with spontaneously-broken lattice symmetry. Experimental signatures of the different quantum paramagnetic phases are discussed.Comment: 9 pages; 2 eps figure

Home administration of lanreotide Autogel® by patients with acromegaly, or their partners, is safe and effective

Summary. Objective The introduction of ready-to-use lanreotide Autogel® has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. Design Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel® at their established dose. Effects were monitored for up to 40 weeks. Patients Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel® (60, 90 or 120 mg) for ≥ 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. Results All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%–99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. Conclusions Patients with acromegaly or their partners were able to administer lanreotide Autogel® injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients

Dysnatremia is a predictor for morbidity and mortality in hospitalized patients with COVID-19

Context: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19). Objective: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19. Methods: This retrospective longitudinal cohort study, including all adult patients who presented with COVID-19 to 2 hospitals in London over an 8-week period, evaluated the association of dysnatremia (serum sodium  145 mmol/L, hyponatremia, and hypernatremia, respectively) at several time points with inpatient mortality, need for advanced ventilatory support, and AKI. Results: The study included 488 patients (median age, 68 years). At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% hypernatremic. Hypernatremia 2 days after admission and exposure to hypernatremia at any time point during hospitalization were associated with a 2.34-fold (95% CI, 1.08-5.05; P = .0014) and 3.05-fold (95% CI, 1.69-5.49; P < .0001) increased risk of death, respectively, compared to normonatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support (95% CI, 1.34-3.45, P = .0011). Hyponatremia was not a risk factor for in-hospital mortality, except for the subgroup of patients with hypovolemic hyponatremia. Sodium values were not associated with the risk for AKI and length of hospital stay. Conclusion: Abnormal sodium levels during hospitalization are risk factors for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively. Serum sodium values could be used for risk stratification in patients with COVID-19

Sr2V3O9 and Ba2V3O9: quasi one-dimensional spin-systems with an anomalous low temperature susceptibility

The magnetic behaviour of the low-dimensional Vanadium-oxides Sr2V3O9 and Ba2V3O9 was investigated by means of magnetic susceptibility and specific heat measurements. In both compounds, the results can be very well described by an S=1/2 Heisenberg antiferromagnetic chain with an intrachain exchange of J = 82 K and J = 94 K in Sr2V3O9 and Ba2V3O9, respectively. In Sr2V3O9, antiferromagnetic ordering at T_N = 5.3 K indicate a weak interchain exchange of the order of J_perp ~ 2 K. In contrast, no evidence for magnetic order was found in Ba2V3O9 down to 0.5 K, pointing to an even smaller interchain coupling. In both compounds, we observe a pronounced Curie-like increase of the susceptibility below 30 K, which we tentatively attribute to a staggered field effect induced by the applied magnetic field. Results of LDA calculations support the quasi one-dimensional character and indicate that in Sr2V3O9, the magnetic chain is perpendicular to the structural one with the magnetic exchange being transferred through VO4 tetrahedra.Comment: Submitted to Phy. Rev.

Neuroendocrine abnormalities in Parkinson's disease.

Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research