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The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses. E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice. The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.

Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all cells of an individual. They are normally transcriptionally silenced and transmitted only vertically. Enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed in tumor patients and HIV-infected individuals. As HERV-K is usually not expressed and immunological tolerance development is unlikely, it is an appropriate target for the development of immunotherapies. We generated a recombinant vaccinia virus (MVA-HKenv) expressing the HERV-K envelope glycoprotein (ENV), based on the modified vaccinia virus Ankara (MVA), and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) or the HERV-K ENV gene (RLZ-HKenv cells). Intravenous injection of RLZ-HKenv cells into syngenic BALB/c mice led to the formation of pulmonary metastases, which were detectable by X-gal staining. A single vaccination of tumor-bearing mice with MVA-HKenv drastically reduced the number of pulmonary RLZ-HKenv tumor nodules compared to vaccination with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the formation of RLZ-HKenv tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to metastasis. Protection from tumor formation correlated with enhanced HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for the first time that HERV-K ENV is a useful target for vaccine development and might offer new treatment opportunities for diverse types of cancer.

The radio-emitting neutron star population encompasses objects with spin periods ranging from milliseconds to tens of seconds. As they age and spin more slowly, their radio emission is expected to cease. We present the discovery of an ultra-long-period radio-emitting neutron star, PSR J0901-4046, with spin properties distinct from the known spin- and magnetic-decay-powered neutron stars. With a spin period of 75.88 s, a characteristic age of 5.3 Myr and a narrow pulse duty cycle, it is uncertain how its radio emission is generated and challenges our current understanding of how these systems evolve. The radio emission has unique spectro-temporal properties, such as quasi-periodicity and partial nulling, that provide important clues to the emission mechanism. Detecting similar sources is observationally challenging, which implies a larger undetected population. Our discovery establishes the existence of ultra-long-period neutron stars, suggesting a possible connection to the evolution of highly magnetized neutron stars, ultra-long-period magnetars and fast radio bursts. Using the MeerKAT radio telescope, the authors have discovered a neutron star with an ultra-long spin period of 76 s. Though it resides in the neutron star graveyard, it emits radio waves and challenges our understanding of neutron star evolution.

New radio telescope arrays offer unique opportunities for large-scale commensal SETI surveys. Ethernet-based architectures are allowing multiple users to access telescope data simultaneously by means of multicast Ethernet subscriptions. Breakthrough Listen will take advantage of this by conducting a commensal SETI survey on the MeerKAT radio telescope in South Africa. By subscribing to raw voltage data streams, Breakthrough Listen will be able to beamform commensally anywhere within the field of view during primary science observations. The survey will be conducted with unprecedented speed by forming and processing 64 coherent beams simultaneously, allowing the observation of several million objects within a few years. Both coherent and incoherent observing modes are planned. We present the list of desired sources for observation and explain how these sources were selected from the Gaia DR2 catalog. Given observations planned by MeerKAT’s primary telescope users, we discuss their effects on the commensal survey and propose a commensal observing strategy in response. Finally, we outline our proposed approach toward observing one million nearby stars and analyze expected observing progress in the coming years.

The Vela pulsar, like many other young pulsars, undergoes occasional sudden “spin-ups” in rotational frequency known as glitches. These glitches are characterised by a sudden (less than 30s) rise in the rotation frequency accompanied by a jump in the spin-down. This is generally followed by rapidly decaying transients in the spin-down and a gradual linear recovery. This recovery provides insight into the internal structure of the neutron star. The telescopes at HartRAO was been used to monitor the Vela pulsar almost daily from 1985 in order to monitor these glitches. The vast majority of these observations were made using the 26m antenna at 1.6 GHz and 2.3 Ghz. When the 26m antenna was offline due to a bearing failure for two years from 2008 the 15m MeerKAT prototype antenna was used to observe Vela. During the entire monitoring campaign 10 large glitches have been observed. The majority of the glitches show a similar recovery pattern. We discuss the characteristics of this common recovery. We compare the standard glitch recovery to that predicted by a hydrodynamic model of the neutron star interior. An exception to the standard glitch are the two glitches which occurred in 1994 separated by 32 days. This “double” glitch is unique amongst Vela glitches. The event is accompanied by typical transients in rotation frequency derivative but all of the long-term offset occurs at the first event and the rapidly-decaying transient is only seen with the second spin-up.

New radio telescope arrays offer unique opportunities for large-scale commensal SETI surveys. Ethernet-based architectures are allowing multiple users to access telescope data simultaneously by means of multicast Ethernet subscriptions. Breakthrough Listen will take advantage of this by conducting a commensal SETI survey on the MeerKAT radio telescope in South Africa. By subscribing to raw voltage data streams, Breakthrough Listen will be able to beamform commensally anywhere within the field of view during primary science observations. The survey will be conducted with unprecedented speed by forming and processing 64 coherent beams simultaneously, allowing the observation of several million objects within a few years. Both coherent and incoherent observing modes are planned. We present the list of desired sources for observation and explain how these sources were selected from the Gaia DR2 catalog. Given observations planned by MeerKAT’s primary telescope users, we discuss their effects on the commensal survey and propose a commensal observing strategy in response. Finally, we outline our proposed approach toward observing one million nearby stars and analyze expected observing progress in the coming years.

The radio-emitting neutron star population encompasses objects with spin periods ranging from milliseconds to tens of seconds. As they age and spin more slowly, their radio emission is expected to cease. We present the discovery of an ultra-long period radio-emitting neutron star, PSR J0901-4046, with spin properties distinct from the known spin and magnetic-decay powered neutron stars. With a spin-period of 75.88 s, a characteristic age of 5.3 Myr, and a narrow pulse duty-cycle, it is uncertain how radio emission is generated and challenges our current understanding of how these systems evolve. The radio emission has unique spectro-temporal properties such as quasi-periodicity and partial nulling that provide important clues to the emission mechanism. Detecting similar sources is observationally challenging, which implies a larger undetected population. Our discovery establishes the existence of ultra-long period neutron stars, suggesting a possible connection to the evolution of highly magnetized neutron stars, ultra-long period magnetars, and fast radio bursts.

Hepatitis B virus (HBV) causes severe liver disease but the underlying mechanisms are incompletely understood. During chronic HBV infection, the liver is recurrently injured by immune cells in the quest for viral elimination. To compensate tissue injury, liver regeneration represents a vital process which requires proliferative insulin receptor signaling. This study aims to investigate the impact of HBV on liver regeneration and hepatic insulin receptor signaling. After carbon tetrachloride-induced liver injury, liver regeneration is delayed in HBV transgenic mice. These mice show diminished hepatocyte proliferation and increased expression of fibrosis markers. This is in accordance with a reduced activation of the insulin receptor although HBV induces expression of the insulin receptor via activation of NF-E2-related factor 2. This leads to increased intracellular amounts of insulin receptor in HBV expressing hepatocytes. However, intracellular retention of the receptor simultaneously reduces the amount of functional insulin receptors on the cell surface and thereby attenuates insulin binding in vitro and in vivo. Intracellular retention of the insulin receptor is caused by elevated amounts of α-taxilin, a free syntaxin binding protein, in HBV expressing hepatocytes preventing proper targeting of the insulin receptor to the cell surface. Consequently, functional analyses of insulin responsiveness revealed that HBV expressing hepatocytes are less sensitive to insulin stimulation leading to delayed liver regeneration. This study describes a novel pathomechanism that uncouples HBV expressing hepatocytes from proliferative signals and thereby impedes compensatory liver regeneration after liver injury.

Recently, PSR J0738-4042 has grown a bright new emission component in its average pulse profile. Using data from Parkes and HartRAO, spanning back to the early 1980s, and applying statistical techniques to model the pulse profile shape with time, we have uncovered unexpected long-term variability, which is very well correlated with changes in the spin-down rate. We present these findings in the context of a growing population of radio-variable pulsars with correlated timing irregularities, including the intermittent pulsars, state-changing pulsars and other individual examples.

Background The mosquito-borne Chikungunya virus (CHIKV) causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses. Methodology/Principal Findings E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) and surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice. Conclusions/Significance The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.