168 research outputs found
Lack of functional GABA receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4
Background/Aims: Adult mice lacking functional GABAB receptors (GABAB1KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABAB1KO mice. Methods: PND4 wild-type (WT) and GABAB1KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males < females), but this sex difference was lost in GABAB1KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females. Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males. Serum LH and gonadal estradiol content were also increased in GABAB1KOs. Conclusion: We demonstrate that GABABRs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis. (c) 2013 S. Karger AG, Basel
Identification and characterization of a Ross River virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon
Alphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish an in vitro model of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRV PERS found several nucleotide differences in the nonstructural protein (nsP) region of the RRV PERS genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRV PERS showed significantly enhanced resistance to beta interferon (IFN-β)-stimulated antiviral activity. RRV PERS infection of RAW 264.7 macrophages induced lower levels of IFN-β expression and production than infection with RRV-T48. RRV PERS was also able to inhibit type I IFN signaling. Mice infected with RRV PERS exhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-α/β).Facultad de Ciencias Exacta
Hormonal Regulation of Follicle-Stimulating Hormone Glycosylation in Males
The Follicle-Stimulating Hormone plays an important role in the regulation of gametogenesis. It is synthesized and secreted as a family of glycoforms with differing oligosaccharide structure, biological action, and half-life. The presence of these oligosaccharides is absolutely necessary for the full expression of hormone bioactivity at the level of the target cell. The endocrine milieu modulates the glycosylation of this hormone. During male sexual development a progressive increase in FSH sialylation and in the proportion of glycoforms bearing complex oligosaccharides are the main features in this physiological condition. In late puberty, FSH oligosaccharides are largely processed in the medial- and trans-Golgi cisternae of the gonadotrope and remain without changes throughout adult life. In experimental models, the absence of gonads severely affects FSH sialylation; androgen administration is able to restore the characteristics observed under physiological conditions. The expression of ST6 beta-galactoside alpha-2,6-sialyltransferase 1 is hormonally regulated in the male rat; it decreases after short periods of castration but increases markedly at longer periods of androgen deprivation. Although ST3 beta-galactoside alpha-2,3-sialyltransferase 3 is expressed in the male rat pituitary it is not influenced by changes in the endocrine milieu. The oligosaccharide structure of FSH has an impact on the Sertoli cell endocrine activity. In more advanced stages of Sertoli cell maturation, both sialylation and complexity of the oligosaccharides are involved in the regulation of inhibin B production; moreover, FSH glycoforms bearing incomplete oligosaccharides may enhance the stimulatory effect exerted by gonadal growth factors. In this review, we discuss available information on variation of FSH glycosylation and its hormonal regulation under different physiological and experimental conditions, as well as the effect on Sertoli cell endocrine activity
PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics.
Quantum discord evolution of three-qubit states under noisy channels
We investigated the dissipative dynamics of quantum discord for correlated
qubits under Markovian environments.
The basic idea in the present scheme is that quantum discord is more general,
and possibly more robust and fundamental, than entanglement. We provide three
initially correlated qubits in pure Greenberger-Horne-Zeilinger (GHZ) or W
state and analyse the time evolution of the quantum discord under various
dissipative channels such as:
Pauli channels , , and , as well as
depolarising channels. Surprisingly, we find that under the action of Pauli
channel , the quantum discord of GHZ state is not affected by
decoherence. For the remaining dissipative channels, the W state is more robust
than the GHZ state against decoherence. Moreover, we compare the dynamics of
entanglement with that of the quantum discord under the conditions in which
disentanglement occurs and show that quantum discord is more robust than
entanglement except for phase flip coupling of the three qubits system to the
environment.Comment: 17 pages, 4 figures, accepted for publication in EPJ
Timing of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI)
Background: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. Material and methods: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. Results: Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97\u20130.99, p < 0.001) and OS (aHR 0.98, 95% CI 0.97\u20130.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63\u20130.79, p < 0.001) and OS (aHR 0.69, 95%CI 0.61\u20130.78, p < 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84\u20131.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81\u20131.08, p = 0.374) were not significantly different in patients with early or delayed SNB. Conclusions: Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals
Dynamics of multipartite quantum correlations under decoherence
Quantum discord is an optimal resource for the quantification of classical
and non-classical correlations as compared to other related measures. Geometric
measure of quantum discord is another measure of quantum correlations.
Recently, the geometric quantum discord for multipartite states has been
introduced by Jianwei Xu [arxiv:quant/ph.1205.0330]. Motivated from the recent
study [Ann. Phys. 327 (2012) 851] for the bipartite systems, I have
investigated global quantum discord (QD) and geometric quantum discord (GQD)
under the influence of external environments for different multipartite states.
Werner-GHZ type three-qubit and six-qubit states are considered in inertial and
non-inertial settings. The dynamics of QD and GQD is investigated under
amplitude damping, phase damping, depolarizing and flipping channels. It is
seen that the quantum discord vanishes for p>0.75 in case of three-qubit GHZ
states and for p>0.5 for six qubit GHZ states. This implies that multipartite
states are more fragile to decoherence for higher values of N. Surprisingly, a
rapid sudden death of discord occurs in case of phase flip channel. However,
for bit flip channel, no sudden death happens for the six-qubit states. On the
other hand, depolarizing channel heavily influences the QD and GQD as compared
to the amplitude damping channel. It means that the depolarizing channel has
the most destructive influence on the discords for multipartite states. From
the perspective of accelerated observers, it is seen that effect of environment
on QD and GQD is much stronger than that of the acceleration of non-inertial
frames. The degradation of QD and GQD happens due to Unruh effect. Furthermore,
QD exhibits more robustness than GQD when the multipartite systems are exposed
to environment.Comment: 15 pages, 4 figures, 4 table
The sudden change phenomenon of quantum discord
Even if the parameters determining a system's state are varied smoothly, the
behavior of quantum correlations alike to quantum discord, and of its classical
counterparts, can be very peculiar, with the appearance of non-analyticities in
its rate of change. Here we review this sudden change phenomenon (SCP)
discussing some important points related to it: Its uncovering,
interpretations, and experimental verifications, its use in the context of the
emergence of the pointer basis in a quantum measurement process, its appearance
and universality under Markovian and non-Markovian dynamics, its theoretical
and experimental investigation in some other physical scenarios, and the
related phenomenon of double sudden change of trace distance discord. Several
open questions are identified, and we envisage that in answering them we will
gain significant further insight about the relation between the SCP and the
symmetry-geometric aspects of the quantum state space.Comment: Lectures on General Quantum Correlations and their Applications, F.
F. Fanchini, D. O. Soares Pinto, and G. Adesso (Eds.), Springer (2017), pp
309-33
Identification and characterization of a Ross River virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon
Alphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish an in vitro model of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRV PERS found several nucleotide differences in the nonstructural protein (nsP) region of the RRV PERS genome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRV PERS showed significantly enhanced resistance to beta interferon (IFN-β)-stimulated antiviral activity. RRV PERS infection of RAW 264.7 macrophages induced lower levels of IFN-β expression and production than infection with RRV-T48. RRV PERS was also able to inhibit type I IFN signaling. Mice infected with RRV PERS exhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-α/β).Facultad de Ciencias Exacta
Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss
Persistent polyarthritis, which occurs in 30–40% of alphavirus-infected patients, has been proposed to be caused by proinflammatory mediators such as IL-6. In the present study we investigated the susceptibility and response of primary human osteoblasts to Ross River virus (RRV) infection and determined whether infection could result in bone pathology. RRV infection of osteoblasts resulted in increased receptor activator of nuclear factor-kappaB ligand (RANKL) but decreased osteoprotegerin (OPG). We are the first to report that alphavirus infection results in bone loss in an established RRV murine model and that this bone loss is prevented by IL-6 inhibition. These findings reveal that RRV can disrupt bone homeostasis and that osteoblasts play an important role in alphavirus-induced arthritis by regulating IL-6 and contribute to bone loss by disrupting the RANKL/OPG balance
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