Population dynamics of Achatina fulica in a peri-urban area adjacent to the Fiocruz Atlantic Forest Biological Station (EFMA), in Rio de Janeiro, Brazil, with report on Angiostrongylus cantonensis infection.

Achatina fulica is a species native to East Africa, considered one of the 100 worst invasive alien species in the world. The present study investigated the population of the snail, A. fulica, in a peri-urban area adjacent to the Fiocruz Atlantic Forest Biological Station (EFMA), in Jacarepaguá, Rio de Janeiro state, Brazil, focusing on population dynamics and the nematodes associated with this species. To this end, specimens were collected during four climatic seasons of the years 2021 and 2022 in three fixed 20 m × 10 m plots. The abundance of A. fulica in these areas was evaluated in relation to a set of environmental variables (temperature, relative humidity air, and soil pH and calcium). The abundance of snails infected by nematodes was also evaluated in relation to the season and body size of the specimens. The molluscs were found by active search, and standardized (15 minutes/three collections). Nematode larvae were extracted from the specimens by artificial digestion and identified by their external morphology and the sequencing of molecular markers. A total of 280 specimens of A. fulica were collected, with the highest abundances being recorded in the autumn and summer, although no significant relationship was found between the number of specimens collected and the environmental variables. Overall, 192 snails were infected by nematodes: Angiostrongylus cantonensis, Cruzia tentaculata and free-living nematodes, including Caenorhabditis briggsae. These findings demonstrate the epidemiological importance of the study area and the need to implement educational measures in the community, with the aim of controlling the local A. fulica population, thereby minimizing the risk of parasitic infection in the local human population.

Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Aqueous extract OF Moringa oleifera Lam leaves added to freezing extenders damages goat sperm membranes.

BACKGROUND: Semen cryopreservation is a biotechnology used frequently in animal production; however, there are some obstacles, such as those caused by high levels of reactive oxygen species (ROS). Moringa oleifera (MO) is known as a potent source of antioxidants and might be an important adjuvant. OBJECTIVE: The objective of this study was to determine the effect of different concentrations of MO extract supplementation on goat semen cryopreservation efficiency. MATERIALS AND METHODS: Ejaculates (n=6) from four goat breeders were pooled and diluted in skimmed milk (SM) or Tris-egg yolk (TEY)-based extenders and supplemented with different concentrations of MO extract (0, 1, 2 and 5 mg/mL). After the freeze-thaw cycle, sperm kinetics and viability were assessed. RESULTS: With the SM extender, straightness, wobble and plasma membrane integrity were lower than in the control group (P < 0.05). With the TEY extender, wobble was lower in with 5 mg/mL MO extract than in the control group (P < 0.05). As regards sperm ultrastructure, evaluated by SEM, the MO extract, regardless of the diluent used, damaged the membrane of sperm cells in a dose-dependent manner. CONCLUSION: The addition of aqueous extract of MO leaves in both diluents at all concentrations tested affects the parameters of sperm progressivity and damages the plasma membrane in a dose-dependent manner. DOI: 10.54680/fr23310110712.

Parental report of dental pain and discomfort in preschool children is associated with sleep disorders: a cross-sectional study in Brazilian families.

PURPOSE: To evaluate the prevalence of sleep disorders in Brazilian preschool children and its associations with parental report of dental pain and discomfort. METHODS: This cross-sectional study involved 604 Brazilian preschoolers (4-5 years old). Sleep disorders (SD) and the parental report of dental pain and discomfort (DPD) were evaluated using the Brazilian versions of the Sleep Disturbance Scale for Children (SDSC) and the Dental Discomfort Questionnaire (DDQ-B), respectively. Bivariate and multivariate Poisson regression analyses with robust variance were performed to analyze the association between SDSC and DP. RESULTS: Prevalence of SD ranged from 7 to 21%. 7.9% of the children had DPD indicating the need for more invasive dental procedures (DDQ-B ≥ 5). Significant associations were found between DPD and the following SDSC domains: sleep hyperhidrosis (p = 0.024; PRa = 1.38; 95% CI: 1.04-1.83), disorders of initiating and maintaining sleep (p < 0.001; PRa = 1.41; 95% CI: 1.15-1.73), parasomnias (p < 0.001; PRa = 1.82; 95% CI: 1.39-2.37), and sleep-wake transition disorders (p = 0.018; PRa = 1.28; 95% CI: 1.04-1.58). Children with higher prevalence of DPD presented 20% higher prevalence of SD than children lower prevalence of DPD (p = 0.039; PRa = 1.20; 95% CI: 1.01-1.44). CONCLUSION: Preschool children with higher prevalence of DPD are more likely to have SD, such as hyperhidrosis, disorders of initiating and maintaining sleep, parasomnias, and sleep-wake transition.

Increasing levels of calcium salts of palm fatty acids affect production responses during the immediate postpartum and carryover periods in dairy cows.

Our objective was to determine the dose-response effects of calcium salts of palm fatty acids (CSPF) on nutrient digestibility and production responses of early-lactation dairy cows grazing on tropical pastures and to evaluate carryover effects throughout mid and late lactation. Forty multiparous dairy cows (Jersey × Holstein) with (mean ± standard error of the mean) 20 ± 1.69 kg of milk/d and 20 ± 5.0 d in milk were used in a randomized complete block design. During the treatment period, all cows were kept in a grazing system. The treatments were offered for 90 d (treatment period) and consisted of 4 increasing levels of CSPF: 0 (0 kg/d), 0.2 (0.2 kg/d), 0.4 (0.4 kg/d), and 0.6 (0.6 kg/d). Each treatment had 10 animals. Increasing CSPF from 0 to 0.6 kg/d replaced an equivalent amount of a corn-based concentrate supplement offered at 10 kg/d on an as-fed basis (8.96 kg/d as a dry matter basis). All cows were housed and received a diet without fat inclusion fed as total mixed ration once a day from 91 to 258 d of the experiment (carryover period). During the treatment period, increasing CSPF linearly decreased dry matter intake (1.20 kg/d), linearly increased neutral detergent fiber digestibility (3.90 percentage units), and quadratically increased total fat digestibility (6.30 percentage units at 0.4 kg/d CSPF). Increasing CSPF linearly increased the yields of milk (4.10 kg/d), milk fat (0.11 kg/d), milk lactose (0.19 kg/d), energy-corrected milk (ECM; 3.30 kg/d), and feed efficiency (ECM/dry matter intake, 0.34 kg/kg), and linearly decreased milk protein content (0.38 g/100 g), body weight change (0.05 kg/d), and body condition score (0.37). We observed interactions between CSPF and time during the carryover period. Overall, CSPF supplementation linearly increased or tended to increase milk yield until 202 d of the experiment with a similar pattern observed for all the other yield variables. In conclusion, supplementing CSPF from 0 to 0.6 kg/d during 90 d increased neutral detergent fiber and total fat digestibility and the yields of milk, milk fat, and ECM in early-lactation dairy cows grazing on tropical pastures. Most production measurements linearly increased during the treatment period, indicating that 0.6 kg/d CSPF was the best dose. Also, supplementing CSPF from 0 to 0.6 kg/d for 90 d during early lactation had positive carryover effects across mid and late lactation.

Agonistic Behavior Is Affected by Memory in the Dusky Damselfish Stegastes fuscus.

The ability to discriminate familiar from unfamiliar conspecifics has been demonstrated in several species of fish. Agonistic interactions are among the most frequent behaviors exhibited by territorial species and could offer useful information for the individual recognition process. In agonistic situations, memory may modulate the behavioral response and affect social dynamics, but few studies have explored the memory retention acquired during aggressive encounters. The present study investigated the memory retention of an agonistic encounter in the dusky damselfish Stegastes fuscus. The experimental procedure was divided into three parts: (1) Familiarization; (2) Recognition test; and (3) Memory test. During the familiarization phase, the fish were visually exposed to the same conspecific for 5 days (10 min per day) and the behavior was recorded. On the following day (conspecific recognition test), half of the animals were paired with the same conspecific and the other half with a different conspecific for 10 min, and the behavior was recorded. The fish were retested 5, 10, and 15 days after the test to evaluate memory retention. In the memory test, they were exposed to the same conspecific as before or to a different conspecific. We found that the damselfish reduced their agonistic displays when the stimulus fish was familiar, but when it was unfamiliar, the animals were more aggressive and only reduced their mnemonic response after 10 days. These results suggest that the recognition ability of damselfish can be affected by time and that it modulates agonistic response.

Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders.

Circular RNA (circRNA) is an unusual class of RNA-like structures composed by exonic and/or intronic sequences that are regulated by the backsplicing mechanism and by the spliceosome-mediated machinery. These circular transcripts tend to accumulate during aging in several human tissues, especially in the mammalian brain, and their expression is correlated with the occurrence of several human pathologies, including a broad spectrum of neurological disorders. Previous findings have also shown that circRNAs are significantly present in the neuronal tissue and are up-regulated during neurogenesis, with a significant number been derived from neural genes, suggesting these circular molecules are involved in the cellular and molecular phenotype of our brain. However, the complete biogenesis, the many types of circRNA molecules, and their involvement with neuronal phenotype and with the occurrence of pathologies are still a challenging avenue for researchers. In this updated review, we discuss the current findings of the biogenesis and the diversity of cirRNAs and their molecular involvement in neurological tissue phenotype. We also discuss how some circRNAs can act as sponge molecules, regulating the activity of microRNA expression over gene translation. Finally, we also show the correlation of altered circRNA expression in neurological disorders.

Isoniazid and verapamil modulatory activity and efflux pump gene expression in Mycobacterium tuberculosis.

INTRODUCTION: Resistance to first-line anti-tuberculosis drugs is a major concern in the treatment of the disease. New strategies, such as the use of efflux pump inhibitors (EPIs), are being investigated to improve the outcome of the treatment. Verapamil (VP), one such inhibitor, was shown to inhibit several efflux pump (EP) Mycobacterium tuberculosis proteins and demonstrate synergic activity with anti-TB drugs.OBJECTIVE: To evaluate the combinatory effect of isoniazid (INH) and VP in M. tuberculosis.METHODS: Minimal inhibitory concentrations and combinatory effects of INH+VP were determined using respectively resazurin microtitre assay plate (REMA) and resazurin drugs combination microtitre assay (REDCA). From the results, we selected three bacilli with different susceptibility profiles and assessed their expression of 10 EP genes through quantitative reverse transcription polymerase chain reaction after exposure to INH, VP and INH + VP for 48 h.RESULTS: A significant reduction of INH MIC was observed in INH-susceptible isolates upon combination with VP. In brief, gene expression assays revealed expression patterns that could be correlated with each resistance profile, presence or absence of gene mutations and combinatory effect with VP.CONCLUSION: Combining VP with INH showed important results in drug-susceptible strains, and clinical trials on combined VP + anti-TB drugs should be discussed.

Thermoluminescence emission on lead oxychloroborate glasses under UV exposure.

Glassy materials were prepared using two different systems: 50B2 O3 - (50 - x)PbO - xPbCl2, with x = 0, 2 and 5 in mol % (System BPCl-I) and 50BO1.5 - (50 - x)PbO - xPbCl2 with x = 0, 2, 5 and 7 in cationic % (System BPCl-II). Structural and optical characterization showed that PbCl when substituted for PbO changed the structure of the glass network by replacing nonbridging oxygens for chlorine ions. This substitution also caused a change in the number of defects responsible for thermoluminescence (TL) emission (electrons and hole trap centres). Thermoluminescence emissions were observed for the first time in lead oxychloroborate glasses after exposure to UV radiation. Sample BPCl-I-2 (x = 2 from System I) demonstrated better TL emission compared with other glass samples. One intense peak in the glow curve, centred at ~122°C followed by a shoulder at ~180°C, was highly sensitive to UV radiation. There were also good linear responses at dose range ~0.4 to ~2 J/cm2 for the first peak (low temperature) and ~0.4 to ~4 J/cm2 for the second peak (high temperature).

Alendronate induces postnatal maxillary bone growth by stimulating intramembranous ossification and preventing premature cartilage mineralization in the midpalatal suture of newborn rats.

Cleft palate is a common malformation of craniofacial development, and postnatal deficiencies in palate formation may occur. The aim of this study was to determine whether alendronate treatment could induce maxillary mineralization and thus reduce the need for surgical procedures. The effects of alendronate on maxillary bone development, the midpalatal suture, and the levels of transforming growth factor beta-1 (TGF-ß1), bone morphogenetic protein 2 (BMP-2), collagen I and II, and V-ATPase were evaluated in newborn rats. Thirty newborn rats were placed in a control group and 30 in a group that received intraperitoneal alendronate (2.5 mg/kg/day). The animals were euthanized on day 7 or 12, and the heads were subjected to histological and immunohistochemical analyses. Specimens from rats that received alendronate presented larger bone matrix deposition in areas of intramembranous ossification of the maxillary bone when compared to controls. Furthermore, higher levels of TGF-ß1, BMP-2, and collagen I were observed, whereas osteoclasts showed no V-ATPase. The alendronate group also showed higher levels of TGF-ß1 and collagen II in the midpalatal suture, whereas BMP-2 levels were lower than in controls. These results coincided with an expansion of the chondroid. In conclusion, alendronate increased the intramembranous ossification in the maxillary bone in association with increased expression of TGF-ß1, BMP-2, and collagen I and decreased V-ATPase. The drug induced an expansion of chondrocytes and a decrease in mineral bone deposition despite the high levels of TGF-ß1 in this area. Alendronate may therefore be useful in the treatment of diseases affecting bone growth.

First detection of bovine papillomavirus type 2 in cutaneous wart lesions from ovines.

This study diagnosed cutaneous wart lesions excised from three rams from a sheep farm in São Paulo State, Brazil. Histopathologically, these cases were diagnosed as papilloma. The amplification by PCR, sequencing and bioinformatics analysis showed that all the lesions presented DNA sequences of bovine papillomavirus type 2. This is the first report confirming the detection of BPV2 in papilloma warts from ovines.

Treatment with ascorbic acid and α-tocopherol modulates oxidative-stress markers in the spinal cord of rats with neuropathic pain.

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.

Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain.

N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain.

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.

Graphene Oxide as Scaffolds for Stem Cells: An Overview.

Graphene and graphene oxide topography have an effect on the fate of stem cells such as adhesion, differentiation, and proliferation. This overview clearly shows that a new design and manipulation of associated graphene oxide stem cell culture platforms are of paramount importance as a focus in stem cell to tissue engineering applications. This overview also proposes that a film of graphene oxide is an efficient platform to modulate structure and function of multipotent mesenchymal stem/stromal cells (MSCs) and in special human adipose tissue derived mesenchymal stromal/stem cells (AT-MSCs). The implication of graphene oxide on osteogenesis, neurogenesis, oligodendrogenesis, adipogenic and epithelial differentiation is also discussed. Graphene oxide toxicity on stem cells and the importance of GO application on ATMSCs differentiation and proliferation are final topics that are being discussed.

Invasion status of the common carp Cyprinus carpio in inland waters of Argentina.

This study documents the presence of Cyprinus carpio in 119 natural environments and 49 artificial habitats in Argentina, showing an exponential increment of invaded locations over time since it was introduced in the nineteenth century. Geographic expansion patterns revealed that since its initial introduction, species records demonstrate an increment in the central portion of the country only after 1970 and subsequent expansion after 1990 to the north, west and south. Using an environmental similarity index it was determined that more than half the country offers good conditions for C. carpio establishment. Environmental factors and anthropogenic impacts are relevant drivers that can account for the current and future distribution of C. carpio in Argentina.

Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population.

OBJECTIVES: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population. SUBJECTS AND METHODS: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms. RESULTS: A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry. CONCLUSIONS: The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population.

Hyperproliferative action of bovine papillomavirus: genetic and histopathological aspects.

The bovine papillomavirus (BPV) causes papillomas that regress spontaneously, but can also progress to malignancy. This study evaluated the role of BPV in oncogenesis. Twenty-four samples from uninfected calves and the papillomas of BPV infected cattle were subjected to molecular diagnosis, as well as histopathological and immunohistochemical analyses. The comet assay (CA) was used to evaluate the clastogenic potential of BPV. The results confirmed the presence of BPV-2, 3, 5, and 9 in infected samples. Histopathological analysis revealed acanthosis, koilocytosis, hypergranulosis, hyperkeratosis, and transformed fibroblasts.E7 and L1 BPV proteins were detected in the epithelium, as well as in the connective tissues, indicating productive infection at different sites. CA results showed that BPV-2, 5, and 9 exhibit the same level of clastogenicity. These findings support the oncogenic action of BPV in establishing a favorable microenvironment for oncogenesis.

Developmental ecdysteroid titers and DNA puffs in larvae of two sciarid species, Rhynchosciara americana and Rhynchosciara milleri (Diptera: Sciaridae).

Ecdysteroid titers, developmental landmarks and the presence of prominent amplifying regions (DNA puffs) have been compared during late larval to pupal development in four groups of Rhynchosciara americana larvae and in R. americana and Rhynchosciara milleri. Three prominent DNA puffs (B2, C3 and C8) expand and regress sequentially on the rising phase of the 20-hydroxyecdysone (20E) titer in R. americana as a firm, cellular cocoon is being constructed. A sharp rise in 20E coincides with the regression of these puffs. The shape of the 20E curve is similar in R. milleri, a species that does not construct a massive cocoon, but the behavior of certain DNA puffs and their temporal relationship to the curve differs. Regions corresponding to B2 and C3 can be identified in R. milleri by banding pattern similarity with R. americana chromosomes and, in the case of B2, by hybridization to an R. americana probe. A B2 puff appears in R. milleri as the 20E titer rises but remains small in all gland regions. A puff similar to the R. americana C3 puff occurs in posterior gland cells of R. milleri (C3(Rm)) after the B2 puff, but this site did not hybridize to R. americana C3 probes. C3(Rm) incorporated (3)H-thymidine above background, but showed less post-puff DNA accumulation than C3 of R. americana. R. americana C8 probes hybridized to a more distal region of the R. milleri C chromosome that did not appear to amplify or form a large puff. These differences can be related to developmental differences, in particular differences in cocoon construction between the two species.

The mGluR5 positive allosteric modulator, CDPPB, ameliorates pathology and phenotypic signs of a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin protein (htt), leading to motor dysfunction, cognitive decline, psychiatric alterations, and death. The metabotropic glutamate receptor 5 (mGluR5) has been implicated in HD and we have recently demonstrated that mGluR5 positive allosteric modulators (PAMs) are neuroprotective in vitro. In the present study we demonstrate that the mGluR5 PAM, CDPPB, is a potent neuroprotective drug, in vitro and in vivo, capable of delaying HD-related symptoms. The HD mouse model, BACHD, exhibits many HD features, including neuronal cell loss, htt aggregates, motor incoordination and memory impairment. However, chronic treatment of BACHD mice with CDPPB 1.5 mg/kg s.c. for 18 weeks increased the activation of cell signaling pathways important for neuronal survival, including increased AKT and ERK1/2 phosphorylation and augmented the BDNF mRNA expression. CDPPB chronic treatment was also able to prevent the neuronal cell loss that takes place in the striatum of BACHD mice and decrease htt aggregate formation. Moreover, CDPPB chronic treatment was efficient to partially ameliorate motor incoordination and to rescue the memory deficit exhibited by BACHD mice. Importantly, no toxic effects or stereotypical behavior were observed upon CDPPB chronic treatment. Thus, CDPPB is a potential drug to treat HD, preventing neuronal cell loss and htt aggregate formation and delaying HD symptoms.