Intestinal microbiota diversity from broilers with runting and stunting syndrome performed by metagenomics.

RESEARCH HIGHLIGHTS: RSS causes dysbiosis of the gut microbiota of the ilea of chicks.A difference was found in gut microbiota between chicks with or without RSS.Candidatus Arthromitus was predominant in chicks with RSS.Clostridium sensu stricto 1 was strictly associated with chicks with RSS.

Effects of in ovo injection of bacterial peptides and CpG-ODN on Salmonella enterica serovar Heidelberg infection in specific pathogen-free (SPF) chicks.

RESEARCH HIGHLIGHTS: Peptides + CpG-ODN reduced SH in caeca at the first week post-infection.Administered formulations did not reduce SH-faecal excretion.Levels of intestinal IgA were similar between all groups.CpG-ODN improved some parameters associated with chick intestinal health.

Effects of cold stress on physiologic metabolism in the initial phase and performance of broiler rearing.

This study aimed to investigate the effects of 8 h of cold stress (18 °C) every day in broiler chicks during the first 7 days of rearing on crop filling analysis, yolk sac consumption, digestive and immune organs weights, and physiological metabolism at seven days and performance between 1 and 35 days. Cobb500 male broiler chickens (n = 274) were randomly assigned to two treatments. The treatments consisted of varying environmental temperatures during the first week post-housing. Chicks were reared at a thermoneutral temperature (32 °C) or under cold stress (18 °C) for 8 h/day during the first week, and both groups were subsequently reared at a thermoneutral temperature for 8-35 days. The thermoneutral group reached 90% full crop after 48 h of housing (P < 0.05), while the cold-stressed group had more empty crops at 2 h and 48 h after housing (P < 0.05). The chick cloacal temperature was not affected by the treatments (P > 0.05). Additionally, the treatment did not affect serum amylase and corticosterone levels, feed intake, body weight gain, or feed conversion ratio (P > 0.05, while the cold-stressed group had elevated heterophil/lymphocyte count at day 7 (P < 0.05). The thermoneutral group showed higher viability (%) at 7 and 35 days and a higher production factor at 35 days (P < 0.05). Broiler chickens under cyclic cold stress experienced decreased yolk sac absorption during the first week and increased feed intake and feed conversion ratio after 35 days of rearing. Viability was also lower in the cold-stressed group. An appropriate strategy to minimize these adverse effects is to rear the chicks in a thermoneutral environment during the first week.

Antitrypanosomal Activity of 1,2,3-Triazole-Based Hybrids Evaluated Using In Vitro Preclinical Translational Models.

Chagas disease therapy still relies on two nitroderivatives, nifurtimox and benznidazole (Bz), which have important limitations and serious adverse effects. New therapeutic alternatives for this silent disease, which has become a worldwide public health problem, are essential for its control and elimination. In this study, 1,2,3-triazole analogues were evaluated for efficacy against T. cruzi. Three triazole derivatives, 1d (0.21 µM), 1f (1.23 µM), and 1g (2.28 µM), showed potent activity against trypomastigotes, reaching IC50 values 10 to 100 times greater than Bz (22.79 µM). Promising candidates are active against intracellular amastigotes (IC50 ≤ 6.20 µM). Treatment of 3D cardiac spheroids, a translational in vitro model, significantly reduced parasite load, indicating good drug diffusion and efficacy. Oral bioavailability was predicted for triazole derivatives. Although infection was significantly reduced without drug pressure in a washout assay, the triazole derivatives did not inhibit parasite resurgence. An isobologram analysis revealed an additive interaction when 1,2,3-triazole analogs and Bz were combined in vitro. These data indicate a strengthened potential of the triazole scaffold and encourage optimization based on an analysis of the structure-activity relationship aimed at identifying new compounds potentially active against T. cruzi.

Synthesis by Microwave Irradiation, Molecular Structural Analysis and Trypanocidal Activity of Novel Pyrazole-tetrahydropyrimidine Derivatives.

BACKGROUND: A series of new eight 2-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1,4,5,6-tetrahydropyrimidines 1(a-h) were synthesized by microwave irradiation technique. In vitro phenotypic screening was performed to evaluate the effect of these compounds on intracellular amastigotes forms of Trypanosoma cruzi, the etiological agent of Chagas disease. METHODS: Compounds 1(a-h) were synthesized from pyrazole-carbonitriles 2(a-h) employing microwave irradiation (50W) for 10-20 minutes. Physicochemical properties were calculated using OSIRIS DataWarrior. The toxic effect on mammalian cells (Vero Cells) and the trypanocidal activity against Trypanosoma cruzi (Dm28c-Luc) were also evaluated. RESULTS: Compounds 1(a-h) were obtained in 24-94% yields. They were completely characterized by Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS) analyses. The derivatives showed low trypanocidal activity, with IC50 ranging from 47.16 to > 100 µM, with lower activity than benznidazole (1.93 µM) used as reference drug. CONCLUSION: The attractive features of this synthetic methodology are mild conditions, short reaction time, and low power. All derivatives showed low toxicity in mammalian cells, good oral bioavailability, and did not violate Lipinski´s rule of 5.

Floor eggs: Hatchability, microbiological analysis, and effects of post-hatch use of ceftiofur on performance of broiler chicks.

The present study aimed to determine the effects of egg type (nest clean or floor eggs) on eggshell microbiological, hatching performance, chick quality, yolk sac microbiology, and the interaction between egg type and post-hatch use of ceftiofur on broiler performance at 7, 14, 21, 28 and 35 days. A total of 2500 fertile eggs were obtained from a commercial flock of Cobb Slow® broiler breeders. Half of the eggs were collected directly from the floor, and the other half were collected from the nests. Microbiological evaluation of eggshells was performed before and after sanitization. After hatching, 420 male chicks were randomly selected and distributed in a completely randomized design in a 2 × 2 factorial scheme, separated by the type of egg (clean nest or floor) and the inclusion or not of subcutaneous ceftiofur, totaling four treatments. Egg type did not influence hatchability although the contamination level was 1.3% higher. The body weight and body weight gain of chicks at seven days were greater for chicks from nest eggs that received ceftiofur than chicks from floor eggs that also received ceftiofur. There was no interaction between the studied factors or individual effects for performance at 14, 21, 28, and 35 days. It is concluded that incubation of floor eggs, after standard sanitization, does not influence the hatch results and chick quality. Furthermore, it has been proven that the use of ceftiofur is unnecessary when there is correct management during broiler rearing.

Bioactivity of Novel Pyrazole-Thiazolines Scaffolds against Trypanosoma cruzi: Computational Approaches and 3D Spheroid Model on Drug Discovery for Chagas Disease.

Chagas disease, a century-old disease that mainly affects the impoverished population in Latin America, causes high morbidity and mortality in endemic countries. The available drugs, benznidazole (Bz) and nifurtimox, have limited effectiveness and intense side effects. Drug repurposing, and the development of new chemical entities with potent activity against Trypanosoma cruzi, are a potential source of therapeutic options. The present study describes the biological activity of two new series of pyrazole-thiazoline derivatives, based on optimization of a hit system 5-aminopyrazole-imidazoline previously identified, using structure−activity relationship exploration, and computational and phenotype-based strategies. Promising candidates, 2c, 2e, and 2i derivatives, showed good oral bioavailability and ADMET properties, and low cytotoxicity (CC50 > 100 µM) besides potent activity against trypomastigotes (0.4−2.1 µM) compared to Bz (19.6 ± 2.3 µM). Among them, 2c also stands out, with greater potency against intracellular amastigotes (pIC50 = 5.85). The selected pyrazole-thiazoline derivatives showed good permeability and effectiveness in the 3D spheroids system, but did not sustain parasite clearance in a washout assay. The compounds' mechanism of action is still unknown, since the treatment neither increased reactive oxygen species, nor reduced cysteine protease activity. This new scaffold will be targeted to optimize in order to enhance its biological activity to identify new drug candidates for Chagas disease therapy.

Feed form and nutritional level for rearing growing broilers in thermoneutral or heat stress environments.

The present study aimed to investigate the effects of different physical forms of feed and feeding programs on nutrient digestibility and performance of grower-finisher broilers under thermoneutrality or thermal stress. Three experiments were conducted using male broiler chickens (n = 720) aged 19-42 d. The design of two of the experiments was fully randomized in a 2 × 2 factorial arrangement with two forms of feed (mash and pellet) and two nutritional levels (13.19 MJ/kg and 194.8 g/kg CP - normal level and 13.61 MJ/kg and 210.3 g/kg CP - high level). The experiments took place in a climate-controlled room: Experiment 1 at thermoneutrality (21-23 °C and 58-60% relative humidity) for 24 h/day; Experiment 2 under thermal stress cycle (31-32 °C and 63-65% relative humidity), for 6h/day and thermoneutrality (21-23 °C, 58-60% relative humidity) for 18h/day. The nutrient digestibility and performance was analyzed. The design of the third experiment was fully randomized with two ambient condition treatments (thermoneutral and thermal stress) on heat production, caloric increment and net energy. Pellet feed obtained higher digestibility of dry matter, digestibility of crude protein, AME and AMEn (P < 0.05) than mash feed for broilers reared in the thermoneutral environment. At the high nutritional level there was no effect of treatments on the coefficient of dry matter and crude protein (DCCP) (P > 0.05), while the highest digestibility of AME and AMEn were obtained by the high nutritional level diet (P < 0.05). Pellet feed had higher DCCP (P < 0.05) than mash feed for broilers reared under cyclic heat stress. Broiler chickens under cyclic stress experienced increased caloric increment, rectal temperature and respiratory rate. The appropriate strategy to minimize these effects in both ambient conditions is to pellet feed.

Short communication: Effects of breeder age and pre-placement feed on IgY concentration in egg yolk and chick serum.

Breeder age and pre-placement feed are factors that can affect broiler performance during grow out. This study evaluated the effects of breeder age (29 and 55 weeks old) on IgY transference to egg yolk in addition to the effects of breeder age (29 and 55 weeks old) and pre-placement feed (with or without), in a factorial arrangement, on IgY concentration in chick serum. Forty-eight eggs were collected from a breeder flock and considered the experimental units. Eighteen chicks from each breeder age were randomly selected to determine IgY at pulling. After 48 h of placement, old breeders had greater egg weight and yolk weight (p ≤ 0.05) than the young ones. Breeder age (p > 0.05) had no effect on IgY concentration of egg yolk. Breeder age (p > 0.05) had no effect on IgY concentration of chick serum at pulling. There was no interaction (p > 0.05) between breeder age and pre-placement feed for IgY concentration of chick serum at housing. There was also no effect of breeder age or pre-placement feed during placement time (48 h) on IgY concentration of chick serum at housing (p > 0.05). In conclusion, 48 h of fasting had no effect on IgY concentration in chick serum despite breeder age. It appears that the immunoglobulins from the residual yolk sac are not used as a protein source during the period between hatching and housing.

Structural Optimization and Biological Activity of Pyrazole Derivatives: Virtual Computational Analysis, Recovery Assay and 3D Culture Model as Potential Predictive Tools of Effectiveness against Trypanosoma cruzi.

Chagas disease, a chronic and silent disease caused by Trypanosoma cruzi, is currently a global public health problem. The treatment of this neglected disease relies on benznidazole and nifurtimox, two nitroheterocyclic drugs that show limited efficacy and severe side effects. The failure of potential drug candidates in Chagas disease clinical trials highlighted the urgent need to identify new effective chemical entities and more predictive tools to improve translational success in the drug development pipeline. In this study, we designed a small library of pyrazole derivatives (44 analogs) based on a hit compound, previously identified as a T. cruzi cysteine protease inhibitor. The in vitro phenotypic screening revealed compounds 3g, 3j, and 3m as promising candidates, with IC50 values of 6.09 ± 0.52, 2.75 ± 0.62, and 3.58 ± 0.25 µM, respectively, against intracellular amastigotes. All pyrazole derivatives have good oral bioavailability prediction. The structure-activity relationship (SAR) analysis revealed increased potency of 1-aryl-1H-pyrazole-imidazoline derivatives with the Br, Cl, and methyl substituents in the para-position. The 3m compound stands out for its trypanocidal efficacy in 3D microtissue, which mimics tissue microarchitecture and physiology, and abolishment of parasite recrudescence in vitro. Our findings encourage the progression of the promising candidate for preclinical in vivo studies.

Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury.

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to -29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model.

Experimental ethology of intensively reared lowland pacas (Cuniculus paca).

The objective of this study was to evaluate and to describe the main behaviors of family groups of lowland pacas (Cuniculus paca) raised in a commercial breeding facility. We used 24 adult pacas, 16 females and 8 males, with a mean live weight of 8.2 kg and age ranging from 2 to 4 years. The animals were kept in groups of two females and one male per enclosure. Cameras were used to monitor the animals. The behaviors identified were divided into five categories (maintenance, exploratory, social interaction, reproductive, and environmental interaction). A completely randomized design in a split-split plot arrangement with three treatment factors was used: sex, period of the day, and season. The frequencies of the maintenance and environmental interaction behavioral categories were significantly higher during the day compared to the nocturnal period (P < 0.05). The duration of each behavioral category differed significantly (P < 0.05) between day and night. The frequencies of the maintenance and reproductive behavioral categories were significantly higher during the dry season compared to the rainy season (P < 0.05) and the relative duration of behaviors of the environmental interaction category was shorter during the dry season (P < 0.05). Females exhibited a significantly higher frequency of maintenance and environmental interaction than males (P < 0.05) and the duration of environmental interaction was shorter (P < 0.05) in females. The present results add to the existing knowledge on the behavior of lowland pacas raised in captivity for production of this wild species which is in the stage of domestication.

Optimization of 1,4-Naphthoquinone Hit Compound: A Computational, Phenotypic, and In Vivo Screening against Trypanosoma cruzi.

Chagas disease (CD) still represents a serious public health problem in Latin America, even after more than 100 years of its discovery. Clinical treatments (nifurtimox and benznidazole) are considered inadequate, especially because of undesirable side effects and low efficacy in the chronic stages of the disease, highlighting the urgency for discovering new effective and safe drugs. A small library of compounds (1a-i and 2a-j) was designed based on the structural optimization of a Hit compound derived from 1,4-naphthoquinones (C2) previously identified. The biological activity, structure-activity relationship (SAR), and the in silico physicochemical profiles of the naphthoquinone derivatives were analyzed. Most modifications resulted in increased trypanocidal activity but some substitutions also increased toxicity. The data reinforce the importance of the chlorine atom in the thiophenol benzene ring for trypanocidal activity, highlighting 1g, which exhibit a drug-likeness profile, as a promising compound against Trypanosoma cruzi. SAR analysis also revealed 1g as cliff generator in the structure-activity similarity map (SAS maps). However, compounds C2 and 1g were unable to reduce parasite load, and did not prevent mouse mortality in T. cruzi acute infection. Phenotypic screening and computational analysis have provided relevant information to advance the optimization and design of new 1,4-naphthoquinone derivatives with a better pharmacological profile.

Runting and Stunting Syndrome in Broiler Chickens: Histopathology and Association With a Novel Picornavirus.

Runting stunting syndrome (RSS) in commercial chickens has been reported worldwide, and although several studies have attempted to clarify the cause and describe the lesions, there are gaps in knowledge of the epidemiology, pathogenesis, and etiology. The study objective was to use commercial chicks naturally affected by RSS to describe the histologic changes of RSS in all segments of the small intestine in chicks of different ages and to identify viral gene sequences in affected chicks and their association with histologic lesions. Chicks lacking clinical signs but from the same houses and from unaffected houses were used as controls. The average weight of affected chicks was significantly lower than expected for their flocks. Macroscopically, the small intestines had paler serosa, with watery, mucoid, or foamy contents and poorly digested food. Histologic lesions were characterized by necrotic crypts, crypt dilation, and flattening of the crypt epithelium. Histomorphometry of the intestines revealed villous atrophy especially in the jejunum and ileum. Histologic changes in other organs were not observed. Random next-generation sequencing of total RNA extracted from formalin-fixed paraffin-embedded tissues detected avian nephritis virus, avian rotavirus, and picornavirus in jejunal segments from 7-day-old chicks. No viruses were detected in the jejunum of 1-day-old chicks. Detection of picornaviral reads was significantly associated (P < .05) with histologic lesions of RSS. Sequence analysis of the picornavirus revealed genetic similarity with the genus Gallivirus. Using in situ hybridization for galliviral nucleic acid sequences, the signal was associated with crypt lesion severity, although signal was detected both in chicks with and without RSS.

Relative bioavailability of manganese in relation to proteinate and sulfate sources for broiler chickens from one to 20 d of age.

The objective of this study was to evaluate the relative bioavailability (RB) of manganese (Mn) proteinate compared to Mn sulfate for broilers fed a diet based on corn and soybean meal for 20 d. The diets of 1,350 male Cobb broilers were supplemented with 0, 35, 70, 105, or 140 mg of Mn/kg of feed in the form of Mn sulfate or Mn proteinate. Weight gain, feed intake, feed conversion, bone strength, and Mn concentration in the tibia and liver, as well as the concentration of type I collagen in the tibia, were evaluated. No differences were observed for performance variables (P > 0.05) or for type I collage concentration in broiler tibia (P > 0.05), regardless of the source and level of supplementation used. Relative bioavailability was determined using bone strength values and Mn concentration in the tibia and liver, assuming Mn sulfate as the standard source (100%) by the slope-ratio method. The RB of Mn proteinate based on bone strength was 111%, based on liver Mn concentration was 128%, and based on tibia Mn concentration was 105%. Manganese proteinate was more bioavailable than Mn sulfate; it can be an important source of supplementation to improve bone quality in broilers.

Effects of Caffeine on Egg Quality and Performance of Laying Hens.

This study's objective was to determine the effects of caffeine intake at various levels, incorporated in the layers' food, on performance and egg quality of hens. A total of 576 hens, aged 56 weeks, were used. The layers were fed rations containing 0 (control), 150, 300, or 450 ppm of caffeine for 12 weeks. During the experimental period, performance parameters (weight, feed consumption, and livability) and egg production and quality (weight, Haugh unit, percentages of yolk, albumen and eggshell, yolk color, eggshell thickness, and resistance, and calcium and phosphorus eggshell contents) were evaluated. The highest concentration of caffeine in the diet (450 ppm) promoted a significant increase in the mortality of hens (1.45% per week) compared to controls (0.23%). There was a reduction in feed consumption by hens, decreased egg production, and reduced eggshell thickness and percentage, with the increase of caffeine. The egg yolk percentage was increased, and the eggshell percentage was reduced in the groups treated with 300 and 450 ppm of caffeine. Furthermore, reduced eggshell thickness was found in all groups that received caffeine. However, it was found that 150 ppm of caffeine in the food did not cause significant changes in most egg production and quality parameters. In summary, caffeine consumption by laying hens increased mortality rate and promoted deleterious effects on chicken production and egg quality at concentrations of 300 and 450 ppm.

Dopamine depletion induces neuron-specific alterations of GABAergic transmission in the mouse striatum.

Lack of dopamine (DA) in the striatum and the consequential dysregulation of thalamocortical circuits are major causes of motor impairments in Parkinson's disease. The striatum receives multiple cortical and subcortical afferents. Its role in movement control and motor skills learning is regulated by DA from the nigrostriatal pathway. In Parkinson's disease, DA loss affects striatal network activity and induces a functional imbalance of its output pathways, impairing thalamocortical function. Striatal projection neurons are GABAergic and form two functionally antagonistic pathways: the direct pathway, originating from DA receptor type 1-expressing medium spiny neurons (D1 R-MSN), and the indirect pathway, from D2 R-MSN. Here, we investigated whether DA depletion in mouse striatum also affects GABAergic function. We recorded GABAergic miniature IPSCs (mIPSC) and tonic inhibition from D1 R- and D2 R-MSN and used immunohistochemical labeling to study GABAA R function and subcellular distribution in DA-depleted and control mice. We observed slower decay kinetics and increased tonic inhibition in D1 R-MSN, while D2 R-MSN had increased mIPSC frequency after DA depletion. Perisomatic synapses containing the GABAA R subunits α1 or α2 were not affected, but there was a strong decrease in non-synaptic GABAA Rs containing these subunits, suggesting altered receptor trafficking. To broaden these findings, we also investigated GABAA Rs in GABAergic and cholinergic interneurons and found cell type-specific alterations in receptor distribution, likely reflecting changes in connectivity. Our results reveal that chronic DA depletion alters striatal GABAergic transmission, thereby affecting cellular and circuit activity. These alterations either result from pathological changes or represent a compensatory mechanism to counteract imbalance of output pathways.

N-Nitrosulfonamides as Carbonic Anhydrase Inhibitors: A Promising Chemotype for Targeting Chagas Disease and Leishmaniasis.

Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, respectively, responsible of the neglected tropical disorders (NTDs) Chagas disease and leishmaniasis. The present pharmacotherapy is often ineffective and exhibits serious side effects. The metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1) recently identified in these protozoans (α-TcCA and ß-LdcCA) are novel promising targets for chemotherapeutic interventions. Herein, we report a series of N-nitrosulfonamides, as a novel chemotype to yield the target CA isoform selective inhibition over ubiquitous human isozymes. Two derivatives selected among the most active and selective ones for TcCA/LdcCA over off-target CAs were progressed as silver salts to in vitro studies with various developmental forms and spp of Trypanosoma cruzi and leishmania. Excellent values of parasites growth inhibition (IC50) were observed, with some selectivity index (over cytotoxicity for macrophages and Vero cells) being comparable or better than reference drugs. These findings make N-nitrosulfonamides and their salts promising lead compounds for a rational optimization of innovative agents for the treatment of Chagas disease and leishmaniasis based on CA inhibition.

Cell type-specific distribution of GABAA receptor subtypes in the mouse dorsal striatum.

The striatum is the main input nucleus of the basal ganglia, mediating motor and cognitive functions. Striatal projection neurons are GABAergic medium spiny neurons (MSN), expressing either the dopamine receptor type 1 (D1 -R MSN) and forming the direct, movement-promoting pathway, or dopamine receptor type 2 (D2 -R MSN), forming the indirect movement-suppressing pathway. Locally, activity and synchronization of MSN are modulated by several subtypes of GABAergic and cholinergic interneurons. Overall, GABAergic circuits in the striatum remain poorly characterized, and little is known about the intrastriatal connectivity of interneurons and the distribution of GABAA receptor (GABAA R) subtypes, distinguished by their subunit composition, in striatal synapses. Here, by using immunofluorescence in mouse tissue, we investigated the distribution of GABAA Rs containing the α1 , α2 , or α3 subunit in perisomatic synapses of striatal MSN and interneurons, as well as the innervation pattern of D1 R- and D2 R-MSN soma and axonal initial segment (AIS) by GABAergic and cholinergic interneurons. Our results show that perisomatic GABAergic synapses of D1 R- and D2 R-MSN contain the GABAA R α1 and/or α2 subunits, but not the α3 subunit; D2 R-MSN have significantly more α1 -GABAA Rs on their soma than D1 R-MSN. Further, interneurons have few perisomatic synapses containing α2 -GABAA Rs, whereas α3 -GABAA Rs (along with the α1 -GABAA Rs) are abundant in perisomatic synapses of CCK+ , NPY+ /SOM+ , and vAChT+ interneurons. Each MSN and interneuron population analyzed received a distinct pattern of GABAergic and cholinergic innervation, complementing this postsynaptic heterogeneity. In conclusion, intra-striatal GABAergic circuits are distinguished by cell-type specific innervation patterns, differential expression and postsynaptic targeting of GABAA R subtypes.

Trypanosoma cruzi infection of human induced pluripotent stem cell-derived cardiomyocytes: an in vitro model for drug screening for Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, is an important global public health problem which, despite partial efficacy of benznidazole (Bz) in acute phase, urgently needs an effective treatment. Cardiotoxicity is a major safety concern for conduction of more accurate preclinical drug screening platforms. Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are a reliable model to study genetic and infectious cardiac alterations and may improve drug development. Herein, we introduce hiPSC-CM as a suitable model to study T. cruzi heart infection and to predict the safety and efficacy of anti-T. cruzi drugs.