Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons

Studies m hum ins and rodents indicate that a minimum amount of stored energy is required for normal pubertal development The adipocyte-derived hormone leptin is a key metabolic signal to the neuroendocrine reproductive axis Humans and mice lacking leptin or the leptin receptor (LepR) (ob/ob and db/db mice, respectively) are infertile and fail to enter puberty Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility, but the exact site or sites of leptin action are unclear Here, we found that genetic deletion of LepR selectively from hypothalamic Kiss1 neurons m mice had no effect on puberty or fertility, indicating that direct leptin signaling m Kiss1 neurons is not required for these processes However, bilateral lesions of the ventral premammillary nucleus (PMV) of ob/ob mice blunted the ability of exogenous leptin to induce sexual maturation Moreover, unilateral reexpression of endogenous LepR m PMV neurons was sufficient to induce puberty and improve fertility m female LepR-null mice This LepR reexpression also normalized the increased hypothalamic GnRH content characteristic of leptin-signaling deficiency These data suggest that the PMV is a key site for leptin's permissive action at the onset of puberty and support the hypothesis that the multiple actions of leptin to control metabolism and reproduction at e anatomically dissociated

Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 mg/kg) or B2 receptor (HOE140, 200 mg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism ( R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1b transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI.

Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Background: Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Methodology/Principal Findings: BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5 +/- 0.7) in control untreated animals to 10(5.0 +/- 0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5 +/- 0.5) parasites were quantified from untreated animals, as opposed to 10(5.1 +/- 0.1) parasites detected in treated mice. Conclusions/Significance: Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.

Hepatitis B Infection Is Associated with Asymptomatic Malaria in the Brazilian Amazon

Background: Areas that are endemic for malaria are also highly endemic for hepatitis B virus (HBV) infection. Nevertheless, it is unknown whether HBV infection modifies the clinical presentation of malaria. This study aimed to address this question. Methodology and Findings: An observational study of 636 individuals was performed in Rondonia, western Amazon, Brazil between 2006 and 2007. Active and passive case detections identified Plasmodium infection by field microscopy and nested Polymerase Chain Reaction (PCR). HBV infections were identified by serology and confirmed by real-time PCR. Epidemiological information and plasma cytokine profiles were studied. The data were analyzed using adjusted multinomial logistic regression. Plasmodium-infected individuals with active HBV infection were more likely to be asymptomatic (OR: 120.13, P < 0.0001), present with lower levels of parasitemia and demonstrate a decreased inflammatory cytokine profile. Nevertheless, co-infected individuals presented higher HBV viremia. Plasmodium parasitemia inversely correlated with plasma HBV DNA levels (r=-0.6; P=0.0003). Conclusion: HBV infection diminishes the intensity of malaria infection in individuals from this endemic area. This effect seems related to cytokine balance and control of inflammatory responses. These findings add important insights to the understanding of the factors affecting the clinical outcomes of malaria in endemic regions.

Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. Methods and Findings: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. Conclusion: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

Gold is not a Faradaic-Efficient Borohydride Oxidation Electrocatalyst: An Online Electrochemical Mass Spectrometry Study

Direct borohydride fuel cells are promising high energy density portable generators. However, their development remains limited by the complexity of the anodic reaction: The borohydride oxidation reaction (BOR) kinetics is slow and occurs at high overvoltages, while it may compete with the heterogeneous hydrolysis of BH(4)(-). Nevertheless, one usually admits that gold is rather inactive toward the heterogeneous hydrolysis of BH(4)(-) and presents some activity regarding the BOR, therefore yielding to the complete eight-electron BOR. In the present paper, by coupling online mass spectrometry to electrochemistry, we in situ monitored the H(2) yield during BOR experiments on sputtered gold electrodes. Our results show non-negligible H(2) generation on Au on the whole BOR potential range (0-0.8 V vs reversible hydrogen electrode), thus revealing that gold cannot be considered as a faradaic-efficient BOR electrocatalyst. We further propose a relevant reaction pathway for the BOR on gold that accounts for these findings.

The mitochondrial genome of the phytopathogenic basidiomycete Moniliophthora perniciosa is 109 kb in size and contains a stable integrated plasmid

We present here the sequence of the mitochondrial genome of the basidiomycete phytopathogenic hemibiotrophic fungus Moniliophthora perniciosa, causal agent of the Witches` Broom Disease in Theobroma cacao. The DNA is a circular molecule of 109103 base pairs, with 31.9 % GC, and is the largest sequenced so far. This size is due essentially to the presence of numerous non-conserved hypothetical ORFs. It contains the 14 genes coding for proteins involved in the oxidative phosphorylation, the two rRNA genes, one ORF coding for a ribosomal protein (rps3), and a set of 26 tRNA genes that recognize codons for all amino acids. Seven homing endonucleases are located inside introns. Except atp8, all conserved known genes are in the same orientation. Phylogenetic analysis based on the cox genes agrees with the commonly accepted fungal taxonomy. An uncommon feature of this mitochondrial genome is the presence of a region that contains a set of four, relatively small, nested, inverted repeats enclosing two genes coding for polymerases with an invertron-type structure and three conserved hypothetical genes interpreted as the stable integration of a mitochondrial linear plasmid. The integration of this plasmid seems to be a recent evolutionary event that could have implications in fungal biology. This sequence is available under GenBank accession number AY376688. (c) 2008 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Forest-related partnerships in Brazilian Amazonia: There is more to sustainable forest management than reduced impact logging

There is more to sustainable forest management than reduced impact logging. Partnerships between multiple actors are needed in order to create the institutional context for good forest governance and sustainable forest management and stimulate the necessary local community involvement. The idea behind this is that the parties would be able to achieve more jointly than on their own by combining assets, knowledge, skills and political power of actors at different levels of scale. This article aims to demonstrate by example the nature and variety of forest-related partnerships in Brazilian Amazonia. Based on the lessons learned from these cases and the authors` experience, the principal characteristics of successful partnerships are described, with a focus on political and socioeconomic aspects. These characteristics include fairly negotiated partnership objectives, the active involvement of the public sector as well as impartial brokers, equitable and cost-effective institutional arrangements, sufficient and equitably shared benefits for all the parties involved, addressing socioeconomic drawbacks, and taking measures to maintain sustainable exploitation levels. The authors argue that, in addition to product-oriented partnerships which focus on sustainable forest management, there is also a need for politically oriented partnerships based on civil society coalitions. The watchdog function of these politically oriented partnerships, their awareness-raising campaigns regarding detrimental policies and practices, and advocacy for good forest governance are essential for the creation of the appropriate legal and political framework for sustainable forest management. (C) 2008 Elsevier B.V. All rights reserved.

The queen is dead-long live the workers: intraspecific parasitism by workers in the stingless bee Melipona scutellaris

Insect societies are well known for their high degree of cooperation, but their colonies can potentially be exploited by reproductive workers who lay unfertilized, male eggs, rather than work for the good of the colony. Recently, it has also been discovered that workers in bumblebees and Asian honeybees can succeed in entering and parasitizing unrelated colonies to produce their own male offspring. The aim of this study was to investigate whether such intraspecific worker parasitism might also occur in stingless bees, another group of highly social bees. Based on a large-scale genetic study of the species Melipona scutellaris, and the genotyping of nearly 600 males from 45 colonies, we show that similar to 20% of all males are workers` sons, but that around 80% of these had genotypes that were incompatible with them being the sons of workers of the resident queen. By tracking colonies over multiple generations, we show that these males were not produced by drifted workers, but rather by workers that were the offspring of a previous, superseded queen. This means that uniquely, workers reproductively parasitize the next-generation workforce. Our results are surprising given that most colonies were sampled many months after the previous queen had died and that workers normally only have a life expectancy of similar to 30 days. It also implies that reproductive workers greatly outlive all other workers. We explain our results in the context of kin selection theory, and the fact that it pays workers more from exploiting the colony if costs are carried by less related individuals.

Enrollment in Physical Education Is Associated With Health-Related Behavior Among High School Students

METHODS: A total of 4210 students attending public high schools in Pernambuco (northeast of Brazil) were selected using random 2-stage cluster sampling. Data were collected by using the Global School-based Student Health Survey. The independent variable was the frequency of participation in PE classes, whereas physical activity, television viewing, smoking, and alcohol, fruit, vegetables and soda consumption were dependent variables. Logistic regressions were carried out to perform crude and adjusted analysis of the association between enrollment in PE classes and health-related behaviors. RESULTS: Sixty-five percent of students do not take part in PE classes, with a significantly higher proportion among females (67.8%). It was observed that enrollment in PE classes was positively associated with physical activity, TV viewing, and fruit consumption, but was negatively associated with soda drinking. The likelihood of reporting being active and eating fruit on a daily basis was 27% and 45% higher, respectively, among those who participate in at least 2 classes per week in comparison with those who do not. Students who participate in PE classes had 28-30% higher likelihood of reporting lower TV viewing during week days. CONCLUSIONS: Findings suggest that higher levels of enrollment in PE classes could play a role in the promotion of health-related behaviors among high school students.

Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice

Lacchini S, Heimann AS, Evangelista FS, Cardoso L, Silva GJ, Krieger JE. Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice. Physiol Genomics 37: 225-230, 2009. First published March 3, 2009; doi:10.1152/physiolgenomics.90288.2008.-We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.4 +/- 4.3% and 45.7 +/- 6.5%, respectively) compared with 1- and 2-copy mice (8.3 +/- 1.3% and 8.5 +/- 0.9%, respectively). Femoral ACE levels from control and injured vessels were assessed in 1- and 3-copy Ace mice, which represent the extremes of the observed response. ACE vascular activity was higher in 3- vs. 1-copy Ace mice (2.4-fold, P < 0.05) in the control uninjured vessel. Upon injury, ACE activity significantly increased in both groups [2.41-fold and 2.14-fold (P < 0.05) for 1- and 3-copy groups, respectively] but reached higher levels in 3- vs. 1-copy Ace mice (P < 0.05). Pharmacological interventions were then used as a counterproof and to indirectly assess the role of angiotensin II (ANG II) on this response. Interestingly, ACE inhibition (enalapril) and ANG II AT(1) receptor blocker (losartan) reduced intima thickening in 3-copy mice to 1-copy mouse values (P < 0.05) while ANG II treatment significantly increased intima thickening in 1-copy mice to 3-copy mouse levels (P < 0.05). Together, these data indicate that small physiologically relevant changes in ACE, not associated with basal vascular abnormalities or blood pressure levels, do influence the magnitude of cuff-induced neointima thickening in mice.

Is there a connection between long airplane flight, venous thromboembolism, and sleep-disordered breathing?

Commercial passenger flights have been increasing around the world. The effect of these flights on health is unclear. Venous thromboembolism has been noted after recent long-distance airplane flight, even in the absence of other risk factors. Hypoxia caused by the low ambient pressure during flights could contribute, and individuals with obstructive sleep apnea may be particularly vulnerable. The association between the effects of long airplane travel and sleep-disordered breathing deserves further study. (C) 2008 Elsevier B.V. All rights reserved.

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1 IS INVOLVED IN DIFFERENTIATION OF REGENERATING MYOFIBERS IN VIVO

This work was undertaken to provide further insight into the role of mammalian target of rapamycin complex 1 (mTORC1) in skeletal muscle regeneration, focusing on myofiber size recovery. Rats were treated or not with rapamycin, an mTORC1 inhibitor. Soleus muscles were then subjected to cryolesion and analyzed 1, 10, and 21 days later. A decrease in soleus myofiber cross-section area on post-cryolesion days 10 and 21 was accentuated by rapamycin, which was also effective in reducing protein synthesis in these freeze-injured muscles. The incidence of proliferating satellite cells during regeneration was unaltered by rapamycin, although immunolabeling for neonatal myosin heavy chain (MHC) was weaker in cryolesion+rapamycin muscles than in cryolesion-only muscles. In addition, the decline in tetanic contraction of freeze-injured muscles was accentuated by rapamycin. This study indicates that mTORC1 plays a key role in the recovery of muscle mass and the differentiation of regenerating myofibers, independently of necrosis and satellite cell proliferation mechanisms. Muscle Nerve 42: 778-787,2010

Chronic Stress Is Associated with High Cortisol Levels and Emotional Coping Mechanisms in Amnestic Mild Cognitive Impairment

Background/Aims: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). Methods: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. Results: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). Conclusion: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory deficit awareness constitutes an additional potential factor involved in high stress severity. Copyright (C) 2009 S. Karger AG, Basel

IS ORDINARY ELECTRIC DRILLS` VENTING PORT A POTENTIAL SOURCE OF SURGICAL INFECTION?

Objective: To evaluate the potential risk of surgical contamination by the venting port of ordinary electric drills (ED) employed in orthopaedic surgeries. Materials and Methods: an experimental laboratory, randomized study was developed to analyze EDs in surgical practice and new cleaned and sterilized equipment, which were contaminated with Bacillus atrophaeus spores at a concentration of 84 X 10(6) UFC. The air generated by the engine of each drill was collected and cultivated on sterile agar plates. Results: Positive culture was identified in two ED in surgical practice, as well as a positive culture to Bacillus atrophaeus with 1 CFU growth (1, 19 X 10(-8)). Conclusion: In the conditions of the experiment, the air generated by the venting port of the ED`s engine does not consist of a source of contamination for the surgical site.