Hybrid mosquitoes? Evidence from rural Tanzania on how local communities conceptualize and respond to modified mosquitoes as a tool for malaria control.

BACKGROUND: Different forms of mosquito modifications are being considered as potential high-impact and low-cost tools for future malaria control in Africa. Although still under evaluation, the eventual success of these technologies will require high-level public acceptance. Understanding prevailing community perceptions of mosquito modification is, therefore, crucial for effective design and implementation of these interventions. This study investigated community perceptions regarding genetically-modified mosquitoes (GMMs) and their potential for malaria control in Tanzanian villages where no research or campaign for such technologies has yet been undertaken. METHODS: A mixed-methods design was used, involving: (i) focus group discussions (FGD) with community leaders to get insights on how they frame and would respond to GMMs, and (ii) structured questionnaires administered to 490 community members to assess awareness, perceptions and support for GMMs for malaria control. Descriptive statistics were used to summarize the findings and thematic content analysis was used to identify key concepts and interpret the findings. RESULTS: Nearly all survey respondents were unaware of mosquito modification technologies for malaria control (94.3%), and reported no knowledge of their specific characteristics (97.3%). However, community leaders participating in FGDs offered a set of distinctive interpretive frames to conceptualize interventions relying on GMMs for malaria control. The participants commonly referenced their experiences of cross-breeding for selecting preferred traits in domestic plants and animals. Preferred GMMs attributes included the expected reductions in insecticide use and human labour. Population suppression approaches, requiring as few releases as possible, were favoured. Common concerns included whether the GMMs would look or behave differently than wild mosquitoes, and how the technology would be integrated into current malaria control policies. The participants emphasised the importance and the challenge of educating and engaging communities during the technology development. CONCLUSIONS: Understanding how communities perceive and interpret novel technologies is crucial to the design and effective implementation of new vector control programmes. This study offers vital clues on how communities with no prior experience of modified mosquitoes might conceptualize or respond to such technologies when deployed in the context of malaria control programmes. Drawing upon existing interpretive frames and locally-resonant analogies when deploying such technologies may provide a basis for more durable public support in the future.

Ugandan stakeholder hopes and concerns about gene drive mosquitoes for malaria control: new directions for gene drive risk governance.

BACKGROUND: The African Union's High-Level Panel on Emerging Technologies identified gene drive mosquitoes as a priority technology for malaria elimination. The first field trials are expected in 5-10 years in Uganda, Mali or Burkina Faso. In preparation, regional and international actors are developing risk governance guidelines which will delineate the framework for identifying and evaluating risks. Scientists and bioethicists have called for African stakeholder involvement in these developments, arguing the knowledge and perspectives of those people living in malaria-afflicted countries is currently missing. However, few African stakeholders have been involved to date, leaving a knowledge gap about the local social-cultural as well as ecological context in which gene drive mosquitoes will be tested and deployed. This study investigates and analyses Ugandan stakeholders' hopes and concerns about gene drive mosquitoes for malaria control and explores the new directions needed for risk governance. METHODS: This qualitative study draws on 19 in-depth semi-structured interviews with Ugandan stakeholders in 2019. It explores their hopes for the technology and the risks they believed pertinent. Coding began at a workshop and continued through thematic analysis. RESULTS: Participants' hopes and concerns for gene drive mosquitoes to address malaria fell into three themes: (1) ability of gene drive mosquitoes to prevent malaria infection; (2) impacts of gene drive testing and deployment; and, (3) governance. Stakeholder hopes fell almost exclusively into the first theme while concerns were spread across all three. The study demonstrates that local stakeholders are able and willing to contribute relevant and important knowledge to the development of risk frameworks. CONCLUSIONS: International processes can provide high-level guidelines, but risk decision-making must be grounded in the local context if it is to be robust, meaningful and legitimate. Decisions about whether or not to release gene drive mosquitoes as part of a malaria control programme will need to consider the assessment of both the risks and the benefits of gene drive mosquitoes within a particular social, political, ecological, and technological context. Just as with risks, benefits-and importantly, the conditions that are necessary to realize them-must be identified and debated in Uganda and its neighbouring countries.

Construction and application of an HSP70 promoter-inducible genome editing system in transgenic silkworm to induce resistance to Nosema bombycis.

The microsporidian Nosema bombycis is an obligate intracellular parasitic fungus that causes devastating disease in sericulture. To date, no efficient biotechnological method to inhibit the proliferation of microspores has been established. Here, we developed a powerful genetic engineering technique involving microsporidia-inducible genome editing in transgenic silkworm that confers resistance to N. bombycis. This system includes an HSP70 promoter-induced expression of the Cas9 protein line and a target BmATAD3A gene line. The double-positive HSP70-Cas9(+)×sgATAD3A(+) lines were obtained by hybridization and activation of the CRISPR/Cas9 system under the condition of microsporidia infection, although it is silenced in uninfected individuals. Genome editing analysis showed that the system could efficiently edit the BmATAD3A gene and induce large deletions. It is notable that the HSP70-induced system could effectively improve the survival rate of transgenic silkworm after microsporidia infection and inhibit the expression of key microsporidia genes. Moreover, no significant developmental differences between the transgenic silkworms infected with microsporidia and normal individuals were observed. In this study, we effectively inhibited microsporidia proliferation in transgenic individuals through disruptive techniques, thereby providing a method for microsporidia treatment and prevention, paving the way for economically advantageous insect breeding.

Aggressive behavior in transgenic animal models: A systematic review.

Aggressive behavior is often core or comorbid to psychiatric and neurodegenerative disorders. Transgenic animal models are commonly used to study the neurobiological mechanisms underlying aggressive phenotypes and have led to new insights into aggression. This systematic review critically evaluates the available literature on transgenic animal models tested for aggression with the resident-intruder test. By combining the available literature on this topic, we sought to highlight effective methods for laboratory aggression testing and provide recommendations for study design as well as aggression induction and measurement in rodents that are translational to humans, taking into consideration possible confounding factors. In addition, we built a molecular landscape of interactions between the proteins encoded by the aggression-linked genes from our systematic search. Some molecular pathways within this landscape overlap with psychiatric and neurodegenerative disorders and the landscapes point towards a number of putative (drug) targets for aggression that need to be validated in future studies.

Students' knowledge of, and attitudes towards biotechnology revisited, 1995-2014: Changes in agriculture biotechnology but not in medical biotechnology.

Modern biotechnology is one of the most important scientific and technological revolutions in the 21st century, with an increasing and measurable impact on society. Development of biotechnology curriculum has become important to high school bioscience classrooms. This study has monitored high school students in Taiwan on their knowledge of and attitudes towards biotechnology for nearly two decades. Not surprisingly, knowledge of biotechnology of current students has increased significantly (p < 0.001) and most students have learned some definitions and examples of biotechnology. There was a positive correlation between biotechnology knowledge and attitudes toward biotechnology for current students who study Advanced Biology (AB). However, for current students who did not study AB, there was a negative correlation.The attitude results showed that students today expressed less favorable opinions toward agricultural biotechnology (p < 0.001) despite studying AB or not. However, there is no significant difference between students today and 18 years ago in opinions towards medical biotechnology. In addition, current students showed a greater concern involving environmental risks than former students. Interestingly, the high school curriculum did affect students' attitudes toward genetically engineered (GE) plants but not GE animals. Our current study also found that the students' attitude towards GE animals was influenced more by their limited knowledge than by their moral belief. On the basis of findings from this study, we suggest that more materials of emerging animal biotechnology should be included in high school curriculum and recommend that high school teachers and university faculty establish a collaborative framework in the near future. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):475-491, 2016.

Marmosets: A Neuroscientific Model of Human Social Behavior.

The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species' reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets' behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets' social behavior and cognition are more similar to that of humans. For example, marmosets are among only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this Primer, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and signaling. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in neuropsychiatric disorders.

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria.

BACKGROUND: The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria. METHODS: The sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered. RESULTS: All participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support. CONCLUSIONS: Although a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release.

The Roman High- and Low-Avoidance rat strains differ in fearpotentiated startle and classical aversive conditioning / Las cepas de ratas Roman de alta y baja evitación difieren en respuesta de sobresalto potenciada por miedo y en condicionamiento clásico aversivo

The Swiss sublines of Roman High-(RHA/Verh) and Low-(RLA/Verh) Avoidance rats have been genetically selected (and outbred) since 1972 because of their good versus extremely poor acquisition of two-way, active avoidance. Inbred strains (RHA-I and RLA-I), derived from those two lines, have been maintained at our laboratory since 1997. The RLA line/strain shows increased stress-induced endocrine responses and enhanced anxiety/fearfulness in a variety of unconditioned behavioural variables and tests. Thus far, however, the Roman rat strains have not been compared in procedures involving classical fear conditioning to cues or contexts. Therefore, the present work was aimed at comparing RHA-I and RLA-I rats in 1) two different procedures of fear-potentiated startle and 2) in a classical fear conditioning (i.e., conditioned freezing) paradigm. The results indicate that, compared to RHA-I rats, RLA-I animals display higher levels of conditioned fear (as measured either by startle responses or freezing behavior) across those different tasks (AU)

Las sublíneas suizas de ratas Romanas «High»-(RHA/Verh) y «Low»-(RLA/Verh) «Avoidance» han sido seleccionadas genéticamente, desde 1972, en función de su excelente (RHA) o extremadamente pobre adquisición de la tarea de evitación activa en dos sentidos. Cepas consanguíneas (RHA-I y RLA-I), derivadas de las dos líneas anteriores, se mantienen en nuestro laboratorio desde 1997. En comparación con la cepa RHA-I, la cepa RLA-I muestra incrementos en las respuestas hormonales al estrés, así como en conductas de ansiedad/miedo en una variedad de pruebas y variables conductuales incondicionadas. Hasta la fecha, las cepas de ratas Romanas no han sido comparadas en procedimientos de condicionamiento clásico de miedo a contextos o estímulos discretos. El presente trabajo tuvo como objetivo comparar ambas en 1) dos procedimientos de medida de la respuesta de sobresalto potenciada por miedo; y, 2) en un procedimiento de condicionamiento clásico de miedo (petrificación condicionada). Los resultados indican que las ratas RLA-I muestran niveles mayores de condicionamiento de miedo (respuesta de sobresalto y respuesta e petrificación) que las RHA-I, reforzando así los perfiles diferenciales de ansiedad/miedo de las dos cepas (AU)

Behavioral differences among C57BL/6 substrains: implications for transgenic and knockout studies.

Separate breeding colonies of C57BL/6 ("B6") mice maintained at the Jackson Laboratories ("J") and NIH ("N") have led to the emergence of two distinct substrains of C57BL/6 mice: C57BL/6J and C57BL/6N. Molecular genetic studies indicate simple sequence-length polymorphisms, single-nucleotide polymorphisms, and copy-number variants among B6 substrains that may contribute to phenotypic differences. We examined differences in motor coordination, pain sensitivity, and conditional fear in the C57BL/6J strain and three N strains: C57BL/6NCrl (Charles River), C57BL/6NTac (Taconic), and C57BL/6NHsd (Harlan Sprague Dawley). Male C57BL/6J mice demonstrated enhanced motor coordination, as measured by the rotarod assay, markedly enhanced pain sensitivity in two assays of acute thermal nociception (e.g., tail withdrawal and hot plate), and a reduced level of conditional fear. The tail withdrawal result was confirmed in a separate laboratory. We also provide a table reviewing previously reported behavioral differences among various B6 substrains and discuss the significance of environmental differences due to obtaining mice form different vendors. These data may be seen as a potential problem and as a potential opportunity. Great care must be taken when working with mice engineered by using B6 embryonic stem cell lines because control groups, backcrosses, and intercrosses could inadvertently introduce behaviorally significant polymorphic alleles or environmental confounds. On the other hand, deliberate crosses between B6 substrains may provide an opportunity to map polymorphic loci that contribute to variability in a trait on largely homogenous backgrounds, which has the potential to improve mapping resolution and aid in the selection of candidate genes.