African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax , is a major problem in cattle and other livestocks ...in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12.
The nuclear envelope (NE) has a dual role of serving as a protective shell for the genome and a critical communication interface that compartmentalizes cells into cytoplasmic and nuclear domains. The ...NE is reinforced by the integrated scaffold of nuclear lamins, heterochromatin, nuclear pores, and other NE proteins with critical roles in regulating the three-dimensional architecture of the genome. Importantly, this interface is in the direct path of force transduction, emanating from the cell-extrinsic environment and generated by the cells themselves, leading to deformation of the nucleus. Alterations in the mechanical properties of NE components have profound implications for cellular dysfunction, aging, and disease. Here we discuss some of the recent findings on the biophysical properties of the nuclear periphery and how NE-derived signaling and nuclear remodeling serve as gatekeepers of genome integrity, normal ploidy, and cellular function.
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Adolescence is a critical period for circadian rhythm, with a strong shift toward eveningness around age 14. Also, eveningness in adolescence has been found to predict later onset of depressive ...symptoms. However, no previous study has investigated structural variations associated with chronotype in early adolescence and how this adds to the development of depressive symptoms.
Assessment of 128 community-based adolescents (51% girls) at age 14 and 19 years was performed. Using whole-brain voxel-based morphometry, baseline (at age 14) regional gray matter volumes (GMVs), follow-up (at age 19) regional GMVs, and longitudinal changes (between 14 and 19) associated with Morningness/Eveningness Scale in Children score and sleep habits at baseline were measured. The association of GMV with depressive symptoms at 19 years was studied, and the role of potential clinical and genetic factors as mediators and moderators was assessed.
Higher eveningness was associated with larger GMV in the right medial prefrontal cortex at ages 14 and 19 in the whole sample. GMV in this region related to depressive symptoms at age 19 in catechol-O-methyltransferase (COMT) Val/Val, but not in Met COMT, carriers. Larger GMV also was observed in the right fusiform gyrus at age 14, which was explained by later wake-up time during weekends.
In adolescence, eveningness and its related sleep habits correlated with distinct developmental patterns. Eveningness was specifically associated with GMV changes in the medial prefrontal cortex; this could serve as a brain vulnerability factor for later self-reported depressive symptoms in COMT Val/Val carriers.
BACKGROUND: Tsetse fly-transmitted African animal trypanosomosis causes annual losses that run into billions of dollars. The disease is assumed to cause hunger and poverty in most sub-Saharan ...countries since it represents a serious impediment to sustainable livestock production. Both a cross-sectional and a longitudinal study were carried out from November to December 2007 to evaluate trypanosomosis risk and susceptibility of trypanosomes to trypanocidal drug treatment in village cattle populations in south-east Mali. METHODS: Eight purposively selected villages participated in the study. In each village, eight traps deployed along drainage lines over 24hour duration were used to catch tsetse. One hundred systematically selected cattle in the study villages were examined for trypanosomes. All trypanosome-positive cattle were randomly allocated into two treatment groups: a group treated with 0.5 mg/kg bw. isometamidium chloride (ISMM) and a group treated with 3.5 mg/kg bw. diminazene aceturate (DIM). The cattle were monitored for trypanosomes at day 14 and 28 post-treatment. RESULTS: Of the 796 cattle examined, 125 (15.7%) were trypanosome-positive. Village trypanosome prevalences ranged between 11% and 19%. There were no significant (p > 0.05) differences in the village trypanosome prevalences. Trypanosoma congolense was the dominant trypanosome species accounting for 73% (91/125) of the infections and T. vivax the remainder. Twenty (31.7%) of the 63 cattle on 0.5 mg/kg bw. ISMM treatment were still positive14 days post-treatment. Of the 43 aparasitaemic cattle monitored to day 28, 25.6% (11) became parasitaemic, resulting in a cumulative failure rate of 49.2% (31/63). Trypanosoma congolense accounted for 77.4% (24/31) of failed ISMM treatments. The 62 cattle treated with 3.5 mg/kg bw. DIM resulted in 30.6% (19/62) failed treatments. Although 42.2% (19/45) of T. congolense positive cattle did not respond to DIM treatment, all T. vivax positive cattle responded positively to DIM treatment. CONCLUSIONS: The overreliance on trypanocides in the control of trypanosomosis will ultimately lead to multiple drug-resistant trypanosome populations as detected in villages in south-east Mali rendering the use of drugs doubtful. Effective alternative methods for trypanosomosis control ought to substitute chemotherapy to ensure sustainable cattle production in these villages. Since there is no single strategy for containing trypanocidal drug resistance, promotion of an integrated approach combining proven trypanosomosis control approaches in high trypanosomosis risk areas is most desirous. The best-bet strategy this study recommended for areas with multiple drug resistance included area-wide community tsetse control, control of co-infections to exploit self-cure against resistant trypanosome populations and the rational use of trypanocidal drugs which should be urgently promoted at all levels as a way of containing or reversing resistance.
Summary
Background Mallory–Weiss syndrome (MWS) with active bleeding at endoscopy may require endoscopic haemostasis the modalities of which are not well‐defined.
Aim To compare the efficacy of ...endoscopic band ligation vs. hemoclip plus epinephrine (adrenaline) in bleeding MWS.
Methods From 2001 to 2008, 218 consecutive patients with a MWS at endoscopy were hospitalized in our Gastrointestinal Bleeding Unit. In 56 patients (26%), an endoscopic haemostasis was required because of active bleeding. Band ligation was performed in 29 patients (Banding group), while hemoclip application plus epinephrine injection was performed in 27 patients (H&E group). Treatment efficacy and early recurrent bleeding were retrospectively compared between the two groups.
Results Primary endoscopic haemostasis was achieved in all patients. Recurrent bleeding occurred in 0% in Banding group vs. 18% in H&E group (P = 0.02). The use of hemoclips plus epinephrine (OR = 3; 95% CI = 1.15–15.8) and active bleeding at endoscopy (OR = 1.9; 95% CI = 1.04–5.2) were independent predictive factors of early recurrent bleeding.
Conclusions Haemostasis by hemoclips plus epinephrine was an independent predictive factor of rebleeding. This result suggests that band ligation could be the first choice endoscopic treatment for bleeding MWS, but requires further prospective assessment.
The steadily increasing luminosity of the LHC requires an upgrade with high-rate and high-resolution detector technology for the inner end cap of the ATLAS muon spectrometer: the New Small Wheels ...(NSW). In order to achieve the goal of precision tracking at a hit rate of about 15 kHz/cm2 at the inner radius of the NSW, large area Micromegas quadruplets with 100µm spatial resolution per plane have been produced. IRFU, from the CEA research center of Saclay, is responsible for the production and validation of LM1 Micromegas modules. The construction, production, qualification and validation of the largest Micromegas detectors ever built are reported here. Performance results under cosmic muon characterization will also be discussed.
Patients with obscure-overt gastrointestinal bleeding (OOGIB) are defined by overt hemorrhage and negative upper and lower endoscopy findings. At present, the place of emergency capsule enteroscopy ...in patients with severe OOGIB is unknown. The aim of this study was to assess the diagnostic yield and the impact of emergency capsule enteroscopy on further management in patients with severe OOGIB.
Between 2003 and 2010, we retrospectively included all patients with severe OOGIB who underwent emergency capsule enteroscopy in the 24-48 h following negative urgent upper and lower endoscopy. Severe OOGIB was defined by ongoing bleeding with hemodynamic instability and/or the need for significant red blood cell transfusion.
Out of 5744 patients hospitalized in our Gastrointestinal Bleeding Unit, 55 (1%) presented with severe OOGIB and underwent emergency capsule enteroscopy. Capsule enteroscopy showed blood in 41 patients (75%) and lesions in 37 patients (67%). Findings included small bowel angiodysplasia in 19 patients (35%), ulcers in 7 (13%), tumors in 5 (9%), small-bowel varices in 2 (3%), cecum angiodysplasia in 4 (7%), fresh blood in small bowel without identified lesion in 12 (22%). Specific diagnostic and therapeutic procedures were undertaken in 78 % of patients. Further management included endoscopy (54%), surgery (22%), and radiology (2%).
Emergency capsule enteroscopy identified bleeding lesions in 67 % of patients with severe OOGIB. Emergency capsule enteroscopy seems to be a promising diagnostic tool with a subsequent impact on clinical management in patients with severe OOGIB.
•We evaluated swine influenza A transmission virus in piglets with different MDA statuses after a single-dose vaccination.•The transmission rate of the challenge strain was found 3.6 time greater in ...MDA-positive than in MDA-negative pigs.•Estimated parameters were unsed to feed a mechanistic model of SwIAV transmission in a farrow-to-finish pig farm.•An extended SwIAV within-farm persistence was observed when both sows and piglets were batch-to-batch vaccinated.•Alternative vaccination schemes need to be tested, accounting for population dynamics and hosts’ immune statuses.
Swine influenza A virus (swIAV) is a major pathogen affecting pigs with a huge economic impact and potentially zoonotic. Epidemiological studies in endemically infected farms permitted to identify critical factors favoring on-farm persistence, among which maternally-derived antibodies (MDAs). Vaccination is commonly practiced in breeding herds and might be used for immunization of growing pigs at weaning. Althoughinterference between MDAs and vaccination was reported in young piglets, its impact on swIAV transmission was not yet quantified. To this aim, this study reports on a transmission experiment in piglets with or without MDAs, vaccinated with a single dose injection at four weeks of age, and challenged 17 days post-vaccination. To transpose small-scale experiments to real-life situation, estimated parameters were used in a simulation tool to assess their influence at the herd level.
Based on a thorough follow-up of the infection chain during the experiment, the transmission of the swIAV challenge strain was highly dependent on the MDA status of the pigs when vaccinated.
MDA-positive vaccinated animals showed a direct transmission rate 3.6-fold higher than the one obtained in vaccinated animals without MDAs, estimated to 1.2. Vaccination nevertheless reduced significantly the contribution of airborne transmission when compared with previous estimates obtained in unvaccinated animals.
The integration of parameter estimates in a large-scale simulation model, representing a typical farrow-to-finish pig herd, evidenced an extended persistence of viral spread when vaccination of sows and single dose vaccination of piglets was hypothesized. When extinction was quasi-systematic at year 5 post-introduction in the absence of sow vaccination but with single dose early vaccination of piglets, the extinction probability fell down to 33% when batch-to-batch vaccination was implemented both in breeding herd and weaned piglets.
These results shed light on a potential adverse effect of single dose vaccination in MDA-positive piglets, which might lead to longer persistence of the SwIAV at the herd level.
Each plant species has its own rhizobacteriome, whose activities determine both soil biological quality and plant growth. Little knowledge exists of the rhizosphere bacterial communities associated ...with opportunity crops with high economic potential such as Synsepalum dulcificum. Native to West Africa, this shrub is famous for its red berries representing the only natural source of miraculin, a glycoprotein, with sweetening properties, but also playing a role in the treatment of cancer and diabetes. This study aimed to characterize the structure and diversity of rhizobacterial communities associated with S. dulcificum and to identify the parameters determining this diversity. An initial sampling stage allowed the collection of rhizosphere soils from 29 S. dulcificum accessions, belonging to three distinct phenotypes, from 16 municipalities of Benin, located either on farms or in home gardens. The bacterial diversity of these rhizosphere soils was assessed by Illumina sequencing of the 16S rRNA gene after DNA extraction from these soils. Furthermore, an analysis of the physicochemical properties of these soils was carried out. All accessions combined, the most represented phylum appeared to be Actinobacteriota, with an average relative abundance of 43.5 %, followed by Proteobacteria (14.8 %), Firmicutes (14.3 %) and Chloroflexi (12.2 %), yet the relative abundance of dominant phyla varied significantly among accessions (p < 0.05). Plant phenotype, habitat, climate and soil physicochemical properties affected the bacterial communities, but our study pointed out that soil physicochemical parameters were the main driver of rhizobacterial communities' structure and diversity. Among them, the assimilable phosphorus, lead, potassium, arsenic and manganese contents, texture and cation exchange capacity of rhizosphere soils were the major determinants of the composition and diversity of rhizosphere bacterial communities. These results suggested the possibility of improving the growth conditions and productivity of S. dulcificum, by harnessing its associated bacteria of interest and better managing soil physicochemical properties.
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•Synsepalum dulcificum rhizobacterial community characterization using metabarcoding•Actinobacteriota, Proteobacteria, Firmicutes and Chloroflexi are the major phyla.•Plant phenotype, habitat, climate and soil parameters affect bacterial diversity.•Soil physicochemical parameters drive the rhizobacterial community diversity.
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•Particle size fraction C in a target set was predicted using a soil NIR library.•Models calibrated with the spectral library could accurately predict fraction C.•Spiking with ...extra-weighting systematically improved model accuracy.•Reference data uncertainty affected the assessment of NIRS prediction accuracy.
Particle size fractionation enables a better understanding of soil organic carbon (C) dynamics since it separates fractions that differ in composition, residence time and function. However, this method is time-consuming and tedious; thus, its use has been greatly limited. Our objective was to evaluate the ability of an existing soil spectral library (SSL) from different regions of West Africa to predict the C amount in the fractions (gCkg−1soil) of the samples in a new target set from Benin.
The SSL included 181samples from five countries, and the target set included 94samples (depth ≤ 40 cm), most of which were coarse-textured; near-infrared reflectance (NIR) spectra were collected for 2 mm sieved samples (non-fractionated samples). The predicted variables were the C amounts in the non-fractionated soil and in the < 20, 20–50, and > 50 µm fractions (F<20, F20–50, and F>50, respectively). Different methods were tested to optimize the predictions: (i)SSL enrichment with 10 or 15samples selected from the target set (spiking) and replicated six times (i.e. extra-weighted); (ii)locally weighted (local) partial least squares regression (PLSR), which is calibration by the spectral neighbours with the highest weights attributed to closest neighbours, and was compared to “global” (i.e., common) PLSR, where all calibration samples equally contribute; and (iii)spectrum pretreatments (e.g., smoothing, centring, derivatization). In addition, the intermediate precision of the conventional data (standard error of laboratory; SELint) was estimated through triplicate fractionation of three samples carried out by three operators (one per replicate).
When the SSL alone was used for calibration, the predictions were inaccurate for the C amounts in the non-fractionated soil and in F<20; however, the predictions were accurate for the C amounts in F20-50 and F>50, with minimal benefit from the local PLSR over the global PLSR in general. For the non-fractionated soil, F<20, F20–50 and F>50, the ratios of performance to the interquartile range in the validation set, RPIQVAL, were 1.6–1.8, 1.6–1.7, 1.9 and 1.9–2.1, respectively. Calibration with SSL spiked (i.e., completed with spiking samples) yielded an increase in RPIQVAL from 33 to 56% for the C amount in the non-fractionated soil and F<20 and from 0 to 20 % for F20-50 and F>50 (RPIQVAL reached 2.4–2.5, 2.2–2.3, 1.9–2.0 and 2.1–2.3, respectively), and the benefit of local PLSR was still limited. The SELint was based on a few samples and thus only provided a rough estimation; this estimate represented at least 65% of the prediction error for the C amounts in the fractions. Therefore, the SELint needs to be determined more extensively to both improve the model accuracy and refine the interpretation of the predictions based on NIR spectra. This library should be enriched with samples from other sites to represent other soil types.
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