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"Jacques, H"
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Investigation of Ion Irradiation Effects in Silicon and Graphite Produced by 23 MeV I Beam
Both silicon and graphite are radiation hard materials with respect to swift heavy ions like fission fragments and cosmic rays. Recrystallisation is considered to be the main mechanism of prompt damage anneal in these two materials, resulting in negligible amounts of damage produced, even when exposed to high ion fluences. In this work we present evidence that these two materials could be susceptible to swift heavy ion irradiation effects even at low energies. In the case of silicon, ion channeling and electron microscopy measurements reveal significant recovery of pre-existing defects when exposed to a swift heavy ion beam. In the case of graphite, by using ion channeling, Raman spectroscopy and atomic force microscopy, we found that the surface of the material is more prone to irradiation damage than the bulk.
Journal Article
Pediatric Bipolar Disorder: Challenges in Diagnosis and Treatment
Despite an opportunity to prevent adult psychopathology associated with bipolar disorder through early diagnosis in children, there is insufficient information and awareness among healthcare providers about the unique features and treatment of mania and its comorbid conditions in children. Converging evidence from disparate sites describe a developmentally distinct presentation of bipolar disorder in youth that is highly morbid, persistent and responds to treatment with the mood stabilizer medications used in the treatment of adult bipolar disorder, such as divalproex sodium and carbamazepine. Some are additionally approved for use in pediatric populations including, for manic or mixed states, risperidone, aripiprazole, and asenapine for those aged 10–17 years and also including lithium and olanzapine for ages 13–17 years. Quetiapine is approved as monotherapy or as adjunct to lithium or divalproex sodium for manic states in those aged 10–17 years. Delayed or missed diagnosis, inappropriate treatment, worsening course, and treatment resistance unfortunately still occur. While an array of mood-stabilizing medications is available for treatment, such as second-generation antipsychotics, lithium, and anticonvulsants, these can be only partially effective and fraught with annoying and serious side effects. This article will review current practice in the diagnosis and treatment of pediatric bipolar disorder and its comorbid conditions, highlighting areas of need for future research.
Journal Article
Small-scale field evaluation of the efficacy and residual effect of Fludora® Fusion (mixture of clothianidin and deltamethrin) against susceptible and resistant Anopheles gambiae populations from Benin, West Africa
Background
In recognition of the threat of insecticide resistance in vectors of malaria, the WHO Global Malaria Programme recommends the development of an appropriate and comprehensive response to insecticide resistance. In principle, good resistance management practice requires the application of multiple insecticides of different modes of action, for example, in rotations and mixtures. Insecticides recommended by the World Health Organization for indoor residual spraying and long-lasting insecticide nets are limited. It is, therefore, judicious to prevent the rapid spread of insecticide resistance by evaluating new insecticides formulations with different modes of action and long residual effect.
Methods
Fludora
®
Fusion, a new neonicotinoid IRS formulation (a mixture of 500 g/kg clothianidin and 62.5 g/kg deltamethrin applied 200 mg ai/sqm + 25 mg ai/sqm, respectively) was tested. Small scale field evaluation of this product was conducted in the district of Dangbo in Benin, to compare its efficacy and residual effect on cement and mud walls against those of clothianidin 200 mg ai/sqm (WG 70) alone, and of deltamethrin 25 mg ai/sqm (WG 250) alone. WHO wall cone bioassays were conducted monthly with laboratory susceptible Anopheles “Kisumu” and wild
Anopheles gambiae
sensu stricto (s.s.) population from Dangbo. The induced mortality by each treatment per wall substrate for 24 h, 48 h, and 72 h post exposure were recorded every month and analysed.
Results
Fludora
®
Fusion and clothianidin WG 70 showed mortality rates over 80% WHO bio-efficacy threshold on cement walls either with susceptible or resistant
An. gambiae
s.s. over a period of 10 and 9 months, respectively. Treatment with Fludora
®
Fusion and clothianidin WG 70 on the mud walls showed residual effect for 6 months and 5 months respectively against both susceptible and resistant mosquitoes. During the whole evaluation period, deltamethrin WG 250 showed mortality rates below 80% against resistant Anopheles population. Furthermore, the knock down rates observed with the Fludora
®
Fusion combination were significantly higher (p < 5%) than those induced by Clothiandin WG 70.
Conclusion
Both the Fludora
®
Fusion combination and clothianidin alone showed very good and lasting efficacy for IRS against resistant Anopheles with some residual benefit provided by the combination. The residual efficacy of the Fludora
®
Fusion combination evaluated at 10 months shows this product is a good candidate for IRS interventions.
Journal Article
A review and perspective paper: Ras oncogene gets modest, from kingpin to mere henchman
The concomitant activation of both the YAP1 co-transcription factor and RAS GTPases is a hallmark of several aggressive cancers, though the intricacies of their relationship and implications for oncogenesis are still poorly understood. This review has presented a cooperative model where YAP1 and RAS are not independently acting oncogenes but rather interdependently acting ones, with each fulfilling an essential role within the oncogenic process. YAP1 is responsible for initiating the expression of key proteins that contribute to various cancer traits. However, these proteins must often be transported into the cytoplasm to exert their effects. We suggest that oncogenic RAS actually facilitates this transport, enabling the phosphorylation and subsequent activation of the nuclear transporter XPO1 (aka Exportin1). This mechanism is particularly crucial for anti-apoptotic proteins. Instead of being sequestered within the nucleus in an ineffective state, these proteins are rather shuttled into the cytoplasm. Within the cytoplasm, they can effectively inhibit apoptosis, undermining by these means the efficacy of chemotherapeutic agents designed to induce cell death in cancer cells. Therefore, a clearer understanding of the oncogenic partnership between RAS and YAP1 will likely provide new insights into the molecular underpinnings of cancer and highlight as well potential targets for therapeutic interventions designed to disrupt this pernicious interaction.
Graphical Abstract
I. YAP1 triggers expression of its target genes, some of which encode cargoes with a nuclear export signal. In response to physiological signals, some cargoes are shuttled into the cytoplasm. Exportin1 serves as the transfer vehicle from the nucleus into the cytoplasm (not shown). For functional nuclear proteins, this shuttling terminates their function, whereas for cytoplasmic proteins, it does initiate their function. In this drawing, the topology within the nucleus is not depicted.
II. Oncogenic RAS leads to Exportin1 activation and subsequent unwarranted nuclear-cytoplasmic shuttling of cargoes [
17
,
35
]. The cascade from RAS to Exportin1 is not depicted for the sake of clarity. Some of the cargoes are oncoproteins, cytoplasmic GTPases regulators, or antiapoptotic proteins (example shown: BIRC5 aka Survivin). These latter proteins are now empowered to hinder apoptosis, as expected upon anti-cancer therapies. Of course, the BIRC5 is not the only aberrantly shuttled protein. Another example is Beclin1 (BECN1), which is subjected to the same fate; once in the cytoplasm, it does initiate autophagy in the absence of any autophagic clue [
35
].
Journal Article
Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis
A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB.
Significance The infectious disease tuberculosis (TB) is a major public health problem that affects millions of people worldwide. TB treatment consists of a multidrug regimen that needs to be taken for a minimum of 6 mo, and lack of adherence to this regimen is associated with treatment failure and emergence of drug resistance. In a mouse model of TB chemotherapy, we have found that inclusion of the antileprosy drug clofazimine in the first-line regimen for TB reduces the duration of treatment necessary to achieve relapse-free cure from 6 mo to 3 mo. Our data suggest that clofazimine, a drug already known to be safe for long-term administration to patients with leprosy, has the potential to significantly shorten the duration of TB treatment.
Journal Article
Characterizing diversity of food systems in view of sustainability transitions. A review
Dominant food systems are configured from the productivist paradigm, which focuses on producing large amounts of inexpensive and standardized foods. Although these food systems continue being supported worldwide, they are no longer considered fit-for-purpose as they have been proven unsustainable in environmental and social terms. A large body of scientific literature argues that a transition from the dominant food systems to alternative ones built around the wider principles of sustainable production and rural development is needed. Promoting such a sustainability transition would benefit from a diagnosis of food system types to identify those systems that may harbor promising characteristics for a transition to sustainable food systems. While research on food system transitions abounds, an operational approach to characterize the diversity of food systems taking a system perspective is still lacking. In this paper we review the literature on how transitions to sustainable food systems may play out and present a framework based on the Multi-Level Perspective on Socio-Technical Transitions, which builds upon conceptual developments from social and natural science disciplines. The objectives of the framework are to (i) characterize the diversity of existing food systems at a certain geographical scale based on a set of structural characteristics and (ii) classify the food systems in terms of their support by mainstream practices, i.e., dominant food systems connected to regimes; deviate radically from them, niche food systems such as those based on grassroots innovation; or share elements of dominant and niche food systems, i.e., hybrid food systems. An example is given of application of our framework to vegetable food systems with a focus on production, distribution, and consumption of low-or-no pesticide vegetables in Chile. Drawing on this illustrative example we reflect on usefulness, shortcomings, and further development and use of the diagnostic framework.
Journal Article
Efficacy of a novel mode of action of an indoor residual spraying product, SumiShield® 50WG against susceptible and resistant populations of Anopheles gambiae (s.l.) in Benin, West Africa
Background
Scale-up of the distribution of long-lasting insecticide-treated bed nets and indoor residual spraying with insecticides over the last decade have contributed to the considerable decrease of malaria morbidity and mortality in sub-Saharan Africa. Due to the increasing pyrethroid resistance intensity and the spread of carbamate resistance in
Anopheles gambiae
(
s.s.
) mosquitoes and the limited number of insecticides recommended by the WHO for vector control, alternative insecticide formulations for IRS with long-lasting residual activity are required to sustain the gains obtained in most malaria-endemic countries.
Methods
SumiShield 50WG (clothianidin 300 mg ai/m
2
) developed by Sumitomo Chemical was evaluated alongside deltamethrin 25 mg ai/m
2
(K-Othrine 250 WG) against a pyrethroid resistant
Anopheles gambiae
(
s.l.
) population in experimental huts in Covè, Benin. Residual activity was also tested in cone bioassays with the susceptible
An. gambiae
“Kisumu” strain and the local wild resistant population.
Results
The results showed very low toxicity from deltamethrin (mortality rates ranged between 1–40%) against host-seeking resistant
Anopheles
populations. SumiShield in contrast gave an overall mean mortality of 91.7% at the 120 h observation across the eight- month observation period following spraying. The residual activity measured using cone tests was over the 80% WHO threshold for 24 weeks for resistant wild
Anopheles
population and 32 weeks for the susceptible strain “Kisumu” after the spraying.
Conclusions
SumiShield is a good candidate for IRS in areas of permanent malaria transmission and where
Anopheles
populations are resistant to other conventional insecticides such as pyrethroids. It would be interesting to complete experimental huts studies by assessing the efficacy and residual effect of SumiShield 50WG at community level (small-scale field testing) in an area where vectors are highly resistant to insecticides.
Journal Article