Vaccination of Holstein heifers with Mycobacterium bovis BCG strain induces protection against bovine tuberculosis and higher milk production yields in a natural transmission setting.

Bovine tuberculosis (TB) is a chronic disease caused mainly by Mycobacterium bovis, a zoonotic pathogen that has a worldwide distribution causing serious economic losses for milk and meat producers. In Chile, the disease in dairy cattle has a heterogeneous distribution, where the Metropolitan Region concentrates the highest animal prevalence and the main challenge for the national control and eradication programme. In this epidemiological context, vaccination with the M. bovis Bacillus Calmette-Guerin (BCG) vaccine might be a useful strategy for disease prevention and control. The objective of this study was to assess the efficacy and impacts on productivity and fertility of vaccination with the BCG Russia strain in 11 month-old heifers from a dairy farm, under a natural transmission condition. Sixty-two animals were vaccinated via the subcutaneous route with the equivalent of one human dose of BCG, and 60 control animals received saline. Subsequently, blood sampling was performed at 3, 6, 9, 12, 15 and 18 months post-inoculation, and infection status was determined using the IFNγ release assay (IGRA) with the DIVA (differentiate infected from vaccinated animals) antigens ESAT-6, CFP-10 and Rv3615c. Efficacy was calculated as the percentage of reduction in the incidence of infection attributable to vaccination, which showed a statistically significant level of overall protection of 66.5%. No adverse effects on fertility and production were recorded. In contrast, we observed beneficial effects of vaccination on several milk production parameters, with the milk yield in the first 100 days after calving in the BCG group significantly higher compared to unvaccinated heifers (p < .05). These results suggest that BCG vaccination of heifers in a natural transmission setting might result in both sanitary and productive benefits, supporting its implementation as a new strategy for TB prevention in a high prevalence area of Chile.

Wild Blonde Capuchins (Sapajus flavius) Perform Anointing Behaviour Using Toxic Secretions of a Millipede (Spirobolida: Rhinocricidae).

Defensive secretions of millipedes are remarkable for containing toxic quinones known to efficiently repell hematophagous arthropods. Here we show that Endangered blonde capuchin monkeys make use of such secretions. We (i) describe the anointing behavior performed by the monkeys (ii) identify the millipede species used in the process (iii) describe the volatile chemical composition of its secretion. The blonde capuchin monkeys selectively searched for millipedes hidden under the ground. We observed three bouts of anointing behavior, performed by 13 individuals of all age classes (from adults to independent infants), both solitarily (1 event) and socially (10 events). The only millipede species used by the monkeys is an undescribed species of the genus Poecilocricus (Spirobolida, Rhinocricidae). The volatile chemical composition of the secretions was predominantly comprised of a mixture of benzoquinones and hydroquinones. The social nature of the behavior and time of the observations (mosquito season), suggest that social bonding and mosquito avoidance is linked to the anointing behavior of the monkeys.

Small but wise: Common marmosets (Callithrix jacchus) use acoustic signals as cues to avoid interactions with blonde capuchin monkeys (Sapajus flavius).

Vocalizations are often used by animals to communicate and mediate social interactions. Animals may benefit from eavesdropping on calls from other species to avoid predation and thus increase their chances of survival. Here we use both observational and experimental evidence to investigate eavesdropping and how acoustic signals may mediate interactions between two sympatric and endemic primate species (common marmosets and blonde capuchin monkeys) in a fragment of Atlantic Rainforest in Northeastern Brazil. We observed 22 natural vocal encounters between the study species, but no evident visual or physical contact over the study period. These two species seem to use the same area throughout the day, but at different times. We broadcasted alarm and long distance calls to and from both species as well as two control stimuli (i.e., forest background noise and a loud call from an Amazonian primate) in our playback experiments. Common marmosets showed anti-predator behavior (i.e., vigilance and flight) when exposed to blonde capuchin calls both naturally and experimentally. However, blonde capuchin monkeys showed no anti-predator behavior in response to common marmoset calls. Blonde capuchins uttered long distance calls and looked in the direction of the speaker following exposure to their own long distance call, whereas they fled when exposed to their own alarm calls. Both blonde capuchin monkeys and common marmosets showed fear behaviors in response to the loud call from a primate species unknown to them, and showed no apparent response to the forest background noise. Common marmoset responses to blonde capuchin calls suggests that the latter is a potential predator. Furthermore, common marmosets appear to be eavesdropping on calls from blonde capuchin monkeys to avoid potentially costly encounters with them.

BCR-ABL1-induced downregulation of WASP in chronic myeloid leukemia involves epigenetic modification and contributes to malignancy.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR-ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR-ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Wiskott-Aldrich syndrome protein (WASP) is an important regulator of signaling transduction in hematopoietic cells and was shown to be an endogenous inhibitor of the c-ABL TK. Here, we show that the expression of WASP decreases with the progression of CML, inversely correlates with the expression of BCR-ABL1 and is particularly low in blast crisis. Enforced expression of BCR-ABL1 negatively regulates the expression of WASP. Decreased expression of WASP is partially due to DNA methylation of the proximal WASP promoter. Importantly, lower levels of WASP in CML advanced phase patients correlate with poorer overall survival (OS) and is associated with TKI response. Interestingly, enforced expression of WASP in BCR-ABL1-positive K562 cells increases the susceptibility to apoptosis induced by TRAIL or chemotherapeutic drugs and negatively modulates BCR-ABL1-induced tumorigenesis in vitro and in vivo. Taken together, our data reveal a novel molecular mechanism that operates in BCR-ABL1-induced tumorigenesis that can be used to develop new strategies to help TKI-resistant, CML patients in blast crisis (BC).

Analgesia for patients undergoing shockwave lithotripsy for urinary stones – a systematic review and meta-analysis

ABSTRACT Background Shock wave lithotripsy (SWL) is the first line treatment modality for a significant proportion of patients with upper urinary tracts stones. Simple analgesics, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are all suitable agents but the relative efficacy and tolerability of these agents is uncertain. Objectives To determine the efficacy of the different types of analgesics used for the control of pain during SWL for urinary stones. Materials and Methods We searched the Cochrane Renal Group’s Specialised Register, MEDLINE, EMBASE and also hand-searched reference lists of relevant articles (Figure-1). Randomised controlled trials (RCT’s) comparing the use of any opioid, simple analgesic or NSAID during SWL were included. These were compared with themselves, each-other or placebo. We included any route or form of administration (bolus, PCA). We excluded agents that were used for their sedative qualities. Data were extracted and assessed for quality independently by three reviewers. Meta-analyses have been performed where possible. When not possible, descriptive analyses of variables were performed. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Results Overall, we included 9 RCTs (539 participants from 6 countries). Trial agents included 7 types of NSAIDs, 1 simple analgesic and 4 types of opioids. There were no significant differences in clinical efficacy or tolerability between a simple analgesic (paracetamol) and an NSAID (lornoxicam). When comparing the same simple analgesic with an opioid (tramadol), both agents provided safe and effective analgesia for the purpose of SWL with no significant differences. There were no significant differences in pain scores between NSAIDs or opioids in three studies. Adequate analgesia could be achieved more often for opioids than for NSAIDs (RR 0.358; 95% CI 043 to 0.77, P=0.0002) but consumed doses of rescue analgesia were similar between NSAIDs and opioids in two studies (P=0.58, >0.05). In terms of tolerability, there is no difference in post-operative nausea and vomiting (PONV) between the groups (RR 0.72, 95% CI 0.24 to 2.17, P=0.55). One study compared outcomes between two types of NSAIDs (diclofenac versus dexketoprofen). There were no significant differences in any of our pre-defined outcomes measures. Conclusion Simple analgesics, NSAIDs and opioids can all reduce the pain associated with shock wave lithotripsy to a level where the procedure is tolerated. Whilst there are no compelling differences in safety or efficacy of simple analgesics and NSAIDs, analgesia is described as adequate more often for opioids than NSAIDs.

Analgesia for patients undergoing shockwave lithotripsy for urinary stones - a systematic review and meta-analysis.

BACKGROUND: Shock wave lithotripsy (SWL) is the first line treatment modality for a significant proportion of patients with upper urinary tracts stones. Simple analgesics, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are all suitable agents but the relative efficacy and tolerability of these agents is uncertain. OBJECTIVES: To determine the efficacy of the different types of analgesics used for the control of pain during SWL for urinary stones. MATERIALS AND METHODS: We searched the Cochrane Renal Group's Specialised Register, MEDLINE, EMBASE and also hand-searched reference lists of relevant articles (Figure-1). Randomised controlled trials (RCT's) comparing the use of any opioid, simple analgesic or NSAID during SWL were included. These were compared with themselves, each-other or placebo. We included any route or form of administration (bolus, PCA). We excluded agents that were used for their sedative qualities. Data were extracted and assessed for quality independently by three reviewers. Meta-analyses have been performed where possible. When not possible, descriptive analyses of variables were performed. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. RESULTS: Overall, we included 9 RCTs (539 participants from 6 countries). Trial agents included 7 types of NSAIDs, 1 simple analgesic and 4 types of opioids. There were no significant differences in clinical efficacy or tolerability between a simple analgesic (paracetamol) and an NSAID (lornoxicam). When comparing the same simple analgesic with an opioid (tramadol), both agents provided safe and effective analgesia for the purpose of SWL with no significant differences. There were no significant differences in pain scores between NSAIDs or opioids in three studies. Adequate analgesia could be achieved more often for opioids than for NSAIDs (RR 0.358; 95% CI 043 to 0.77, P=0.0002) but consumed doses of rescue analgesia were similar between NSAIDs and opioids in two studies (P=0.58, >0.05). In terms of tolerability, there is no difference in post-operative nausea and vomiting (PONV) between the groups (RR 0.72, 95% CI 0.24 to 2.17, P=0.55). One study compared outcomes between two types of NSAIDs (diclofenac versus dexketoprofen). There were no significant differences in any of our pre-defined outcomes measures. CONCLUSION: Simple analgesics, NSAIDs and opioids can all reduce the pain associated with shock wave lithotripsy to a level where the procedure is tolerated. Whilst there are no compelling differences in safety or efficacy of simple analgesics and NSAIDs, analgesia is described as adequate more often for opioids than NSAIDs.

Vocal Repertoire of Wild Blonde Capuchins (Sapajus flavius) and Contextual Use of Calls.

Despite advances in the study of capuchin monkeys (Cebus and Sapajus), there is fairly limited information on their vocal communication systems. The present study focused on investigating the structure and use of vocalizations by wild blonde capuchin monkeys, Sapajus flavius. The study subjects produced 29 different call types, which we grouped into 10 categories according to their behavioral context. The number of call types per context varied from one to six. Some of the call types in the vocal repertoire were only produced by individuals of specific age classes. The "nhan" call, for instance, was only emitted by infants, whereas the "ghrr" call was specific to adults. Other call types had no age-specificity and were produced by animals of two or more age categories. Discriminant Function Analysis correctly classified 77.4% of calls to type (n = 14 types). The "huh" and "huh-1var" calls, which are food-associated calls, were most commonly used, together representing approximately 52% of recorded vocalizations. Information on the vocal repertoire of blonde capuchins increases our knowledge of this very little known and Critically Endangered species. Ultimately, it may be used as a tool to help survey these animals in the wild and to assess welfare in captivity.

Propagation of the loud "tchó" call of golden-backed uakaris, Cacajao melanocephalus, in the black-swamp forests of the upper Amazon.

Arboreal primates use loud vocalisations to transmit information in densely vegetated habitats. These vocalisations are likely to show adaptations to increase their propagation and to transmit information. Golden-backed uakaris, Cacajao melanocephalus, emit a loud vocalization termed the "tchó" call, which seems to function as a contact call and encodes information on the individual signaler and behavioural context. Because the call is often used for communication over relatively large distances, we were interested in its propagation in the wild. The aim of the present study was to investigate the degradation patterns of the tchó call in the flooded igapó forest. We examined via playback experiments how the acoustic parameters of this call changed with increasing distance from the playback speaker. We broadcast 12 tchó calls and rerecorded them along a transect at distances of 10, 20, 40, 80 and 160 m from the speaker in two igapó forest patches in Jaú National Park, Amazonas, Brazil. At 160 m from the speaker, the tchó call degraded in both patches and was barely recordable. Up to a distance of 80 m, the bandwidth and number of harmonics in the call decreased with increasing distance, while the lowest frequency increased. The highest frequency (HF) did not gradually decrease with increasing distance. However, when we compared the HF at distances of 10 and 80 m, we could see a clear decrease in this parameter. Call duration increased compared with the broadcast signal up to 40 m because of reverberation, but decreased at 80 m as the weaker echoes of the call attenuated. These changes may reveal information about the signaler's distance during signal transmission. The frequency of maximum energy (FME) of the tchó call decreased significantly when comparing recordings made at 10 and 80 m. Nevertheless, it did not show a consistent and gradual decrease with increasing rerecording distance (at least up to 80 m). FME remained relatively stable (±50 Hz on average, at least up to 80 m) when compared to the other call parameters, suggesting that the tchó call may be adapted to transmit information with some efficiency throughout the igapó forest.

Cytopathological effects of Bacillus sphaericus Cry48Aa/Cry49Aa toxin on binary toxin-susceptible and -resistant Culex quinquefasciatus larvae.

The Cry48Aa/Cry49Aa mosquitocidal two-component toxin was recently characterized from Bacillus sphaericus strain IAB59 and is uniquely composed of a three-domain Cry protein toxin (Cry48Aa) and a binary (Bin) toxin-like protein (Cry49Aa). Its mode of action has not been elucidated, but a remarkable feature of this protein is the high toxicity against species from the Culex complex, besides its capacity to overcome Culex resistance to the Bin toxin, the major insecticidal factor in B. sphaericus-based larvicides. The goal of this work was to investigate the ultrastructural effects of Cry48Aa/Cry49Aa on midgut cells of Bin-toxin-susceptible and -resistant Culex quinquefasciatus larvae. The major cytopathological effects observed after Cry48Aa/Cry49Aa treatment were intense mitochondrial vacuolation, breakdown of endoplasmic reticulum, production of cytoplasmic vacuoles, and microvillus disruption. These effects were similar in Bin-toxin-susceptible and -resistant larvae and demonstrated that Cry48Aa/Cry49Aa toxin interacts with and displays toxic effects on cells lacking receptors for the Bin toxin, while B. sphaericus IAB59-resistant larvae did not show mortality after treatment with Cry48Aa/Cry49Aa toxin. The cytopathological alterations in Bin-toxin-resistant larvae provoked by Cry48Aa/Cry49Aa treatment were similar to those observed when larvae were exposed to a synergistic mixture of Bin/Cry11Aa toxins. Such effects seemed to result from a combined action of Cry-like and Bin-like toxins. The complex effects caused by Cry48Aa/Cry49Aa provide evidence for the potential of these toxins as active ingredients of a new generation of biolarvicides that conjugate insecticidal factors with distinct sites of action, in order to manage mosquito resistance.

Translocation and insecticidal activity of Bacillus thuringiensis living inside of plants.

The major biological pesticide for the control of insect infestations of crops, Bacillus thuringiensis was found to be present naturally within cotton plants from fields that had never been treated with commercial formulations of this bacterium. The ability of B. thuringiensis to colonize plants as an endophyte was further established by the introduction of a strain marked by production of green fluorescent protein (GFP). After inoculation of this preparation close to the roots of cotton and cabbage seedlings, GFP-marked bacteria could be re-isolated from all parts of the plant, having entered the roots and migrated through the xylem. Leaves taken from the treated plants were able to cause toxicity when fed to the Lepidoptera Spodoptera frugiperda (cotton) and Plutella xylostella (cabbage). These results open up new horizons for understanding the natural ecology and evolution of B. thuringiensis and use of B. thuringiensis in insect control.