The organizational effects of oxytocin on the central expression of estrogen receptor α and oxytocin in adulthood

Background: Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor alpha (ER alpha) and the central production of oxytocin observed in juveniles ( at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles ( Microtus ochrogaster) received one of three doses of OT (High, 3 mu g; Med, 0.3 mu g; Low, 0.03 mu g), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERa or OT using immunocytochemistry. Results: In females, treatment with OT increased the expression of ERa immunoreactivity in the ventral lateral septum (0.03 mu g) and the ventromedial nucleus of the hypothalamus and central amygdala ( 0.3 g). In males, OT antagonist increased ERa expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus. Conclusion: The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ERa in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ERa patterns were sexually dimorphic, dose-dependent, and site-specific

Parents’ differential susceptibility to the effects of marital quality on sensitivity across the first year

The current investigation examined the differential susceptibility of parents to the effects of marital quality on changes in parenting. We predicted that parents who were high on the personality constructs Negative Affect and Constraint would be more susceptible to the effects of marital quality on their level of sensitivity. Sensitivity was assessed at 3.5 and 13 months for both mothers and fathers during a triadic interaction. Consistent with the differential susceptibility theory, results suggested that when mothers were high on Negative Affect and when fathers were high on Constraint, their marital quality was associated with changes in sensitivity. This investigation suggests that personality factors may create “vulnerabilities” in parents that make them differentially susceptible to the effects of the family environment on parentin

Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model.

With the increasing prevalence of artemisinin-resistant malaria parasites, a highly efficacious and durable vaccine for malaria is urgently required. We have developed an experimental virus-vectored vaccine platform based on an envelope-modified baculovirus dual-expression system (emBDES). Here, we show a conceptually new vaccine platform based on an adenovirus-prime/emBDES-boost heterologous immunization regimen expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). A human adenovirus 5-prime/emBDES-boost heterologous immunization regimen consistently achieved higher sterile protection against transgenic P. berghei sporozoites expressing PfCSP after a mosquito-bite challenge than reverse-ordered or homologous immunization. This high protective efficacy was also achieved with a chimpanzee adenovirus 63-prime/emBDES-boost heterologous immunization regimen against an intravenous sporozoite challenge. Thus, we show that the adenovirus-prime/emBDES-boost heterologous immunization regimen confers sterile protection against sporozoite challenge by two individual routes, providing a promising new malaria vaccine platform for future clinical use

Membrane Potential-Dependent Inactivation of Voltage-Gated Ion Channels in α-Cells Inhibits Glucagon Secretion From Human Islets

OBJECTIVE: To document the properties of the voltage-gated ion channels in human pancreatic alpha-cells and their role in glucagon release. RESEARCH DESIGN AND METHODS: Glucagon release was measured from intact islets. [Ca(2+)](i) was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated alpha-cells identified by immunocytochemistry. RESULT: Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl(2). Glucose remained inhibitory in the presence of ZnCl(2) and after blockade of type-2 somatostatin receptors. Human alpha-cells are electrically active at 1 mmol/l glucose. Inhibition of K(ATP)-channels with tolbutamide depolarized alpha-cells by 10 mV and reduced the action potential amplitude. Human alpha-cells contain heteropodatoxin-sensitive A-type K(+)-channels, stromatoxin-sensitive delayed rectifying K(+)-channels, tetrodotoxin-sensitive Na(+)-currents, and low-threshold T-type, isradipine-sensitive L-type, and omega-agatoxin-sensitive P/Q-type Ca(2+)-channels. Glucagon secretion at 1 mmol/l glucose was inhibited by 40-70% by tetrodotoxin, heteropodatoxin-2, stromatoxin, omega-agatoxin, and isradipine. The [Ca(2+)](i) oscillations depend principally on Ca(2+)-influx via L-type Ca(2+)-channels. Capacitance measurements revealed a rapid (<50 ms) component of exocytosis. Exocytosis was negligible at voltages below -20 mV and peaked at 0 mV. Blocking P/Q-type Ca(2+)-currents abolished depolarization-evoked exocytosis. CONCLUSIONS: Human alpha-cells are electrically excitable, and blockade of any ion channel involved in action potential depolarization or repolarization results in inhibition of glucagon secretion. We propose that voltage-dependent inactivation of these channels underlies the inhibition of glucagon secretion by tolbutamide and glucose

Vibrational energy redistribution during donor-acceptor electronic energy transfer: criteria to identify subsets of active normal modes

Photoinduced electronic energy transfer in conjugated donor-acceptor systems is naturally accompanied by intramolecular vibrational energy redistributions accepting an excess of electronic energy. Herein, we simulate these processes in a covalently linked donor-acceptor molecular dyad system by using nonadiabatic excited state molecular dynamics simulations. We analyze different complementary criteria to systematically identify the subset of vibrational normal modes that actively participate on the donoracceptor (S2S1) electronic relaxation. We analyze energy transfer coordinates in terms ofstate-specific normal modes defined according to the different potential energy surfaces (PESs) involved. On one hand, we identify those vibrations that contribute the most to the direction of the main driving force on the nuclei during electronic transitions, represented by the non-adiabatic derivative coupling vector between donor and acceptor electronic states. On the other hand, we monitor normal mode transient accumulations of excess energy and their intramolecular energy redistribution fluxes. We observe that the subset of active modes varies according to the PES on which they belong and these modes experience the most significant rearrangements and mixing. Whereas the nuclear motions that promote donoracceptor energy funneling can be localized mainly on one or two normal modes of the S2 state, they become spread out across multiple normal modes of the S1 state following the energy transfer eventThis work was partially supported by CONICET, UNQ, ANPCyT (PICT-2018-2360), the Universidad Carlos III de Madrid, the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 600371, el Ministerio de Economía, Industria y Competitividad (COFUND2014-51509), el Ministerio de Educación, cultura y Deporte (CEI-15-17), Banco Santander and el Ministerio de Ciencia, Innovación y Universidades (RTI2018-101020-B-I00). We also acknowledge support from the Bavarian University Centre for Latin America (BAYLAT). The work at Los Alamos National Laboratory (LANL) was supported by the Laboratory Directed Research and Development Funds (LDRD) program. This work was done in part at the Center for Nonlinear Studies (CNLS) and the Center for Integrated Nanotechnologies (CINT), a U.S. Department of Energy and Office of Basic Energy Sciences user facility, at LANL. This research used resources provided by the LANL Institutional Computing Program. Los Alamos National Laboratory is operated by Triad National Security, LLC, for the National Nuclear Security Administration of the U.S. Department of Energy. This work has received finantial support provided by the Spanish Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE) under Project CTQ2016-79345-P and by the Funda-ción Séneca under Project 20789/PI/18

Creation and annihilation of topological meron pairs in in-plane magnetized films

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction

Monitoring Alaskan Arctic shelf ecosystems through collaborative observation networks

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Danielson, S. L., Grebmeier, J. M., Iken, K., Berchok, C., Britt, L., Dunton, K. H., Eisner, L., V. Farley, E., Fujiwara, A., Hauser, D. D. W., Itoh, M., Kikuchi, T., Kotwicki, S., Kuletz, K. J., Mordy, C. W., Nishino, S., Peralta-Ferriz, C., Pickart, R. S., Stabeno, P. S., Stafford. K. M., Whiting, A. V., & Woodgate, R. Monitoring Alaskan Arctic shelf ecosystems through collaborative observation networks. Oceanography, 35(2), (2022): 52, https://doi.org/10.5670/oceanog.2022.119.Ongoing scientific programs that monitor marine environmental and ecological systems and changes comprise an informal but collaborative, information-rich, and spatially extensive network for the Alaskan Arctic continental shelves. Such programs reflect contributions and priorities of regional, national, and international funding agencies, as well as private donors and communities. These science programs are operated by a variety of local, regional, state, and national agencies, and academic, Tribal, for-profit, and nongovernmental nonprofit entities. Efforts include research ship and autonomous vehicle surveys, year-long mooring deployments, and observations from coastal communities. Inter-program coordination allows cost-effective leveraging of field logistics and collected data into value-added information that fosters new insights unattainable by any single program operating alone. Coordination occurs at many levels, from discussions at marine mammal co-management meetings and interagency meetings to scientific symposia and data workshops. Together, the efforts represented by this collection of loosely linked long-term monitoring programs enable a biologically focused scientific foundation for understanding ecosystem responses to warming water temperatures and declining Arctic sea ice. Here, we introduce a variety of currently active monitoring efforts in the Alaskan Arctic marine realm that exemplify the above attributes.Funding sources include the following: ALTIMA: BOEM M09PG00016, M12PG00021, and M13PG00026; AMBON: NOPP-NA14NOS0120158 and NOPP-NA19NOS0120198; Bering Strait moorings: NSF-OPP-AON-PLR-1758565, NSF-OPP-PLR-1107106; BLE-LTER: NSF-OPP-1656026; CEO: NPRB-L36, ONR N000141712274 and N000142012413; DBO: NSF-AON-1917469 and NOAA-ARP CINAR-22309.07; HFR, AOOS Arctic glider, and Passive Acoustics at CEO and Bering Strait: NA16NOS0120027; WABC: NSF-OPP-1733564. JAMSTEC: partial support by ArCS Project JPMXD1300000000 and ArCS II Project JPMXD1420318865; Seabird surveys: BOEM M17PG00017, M17PG00039, and M10PG00050, and NPRB grants 637, B64, and B67. This publication was partially funded by the Cooperative Institute for Climate, Ocean, & Ecosystem Studies (CICOES) under NOAA Cooperative Agreement NA20OAR4320271, and represents contribution 2021-1163 to CICOES, EcoFOCI-1026, and 5315 to PMEL. This is NPRB publication ArcticIERP-43

Liver-Directed AAV8 Booster Vaccine Expressing Plasmodium falciparum Antigen Following Adenovirus Vaccine Priming Elicits Sterile Protection in a Murine Model

Hepatocyte infection by malaria sporozoites is a bottleneck in the life-cycle of Plasmodium spp. including P. falciparum, which causes the most lethal form of malaria. Therefore, developing an effective vaccine capable of inducing the strong humoral and cellular immune responses necessary to block the pre-erythrocytic stage has potential to overcome the spatiotemporal hindrances pertaining to parasite biology and hepatic microanatomy. We recently showed that when combined with a human adenovirus type 5 (AdHu5)-priming vaccine, adeno-associated virus serotype 1 (AAV1) is a potent booster malaria vaccine vector capable of inducing strong and long-lasting protective immune responses in a rodent malaria model. Here, we evaluated the protective efficacy of a hepatotropic virus, adeno-associated virus serotype 8 (AAV8), as a booster vector because it can deliver a transgene potently and rapidly to the liver, the organ malaria sporozoites initially infect and multiply in following sporozoite injection by the bite of an infected mosquito. We first generated an AAV8-vectored vaccine expressing P. falciparum circumsporozoite protein (PfCSP). Intravenous (i.v.) administration of AAV8-PfCSP to mice initially primed with AdHu5-PfCSP resulted in a hepatocyte transduction rate ~2.5 times above that seen with intramuscular (i.m.) administration. This immunization regimen provided a better protection rate (100% sterile protection) than that of the i.m. AdHu5-prime/i.m. AAV8-boost regimen (60%, p &lt; 0.05), i.m. AdHu5-prime/i.v. AAV1-boost (78%), or i.m. AdHu5-prime/i.m. AAV1-boost (80%) against challenge with transgenic PfCSP-expressing P. berghei sporozoites. Compared with the i.m. AdHu5-prime/i.v. AAV1-boost regimen, three other regimens induced higher levels of PfCSP-specific humoral immune responses. Importantly, a single i.v. dose of AAV8-PfCSP recruited CD8+ T cells, especially resident memory CD8+ T cells, in the liver. These data suggest that boost with i.v. AAV8-PfCSP can improve humoral and cellular immune responses in BALB/c mice. Therefore, this regimen holds great promise as a next-generation platform for the development of an effective malaria vaccine