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1.
J Neurosci ; 44(13)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38050126

RESUMO

Dynamic microtubules critically regulate synaptic functions, but the role of microtubule severing in these processes is barely understood. Katanin is a neuronally expressed microtubule-severing complex regulating microtubule number and length in cell division or neurogenesis; however, its potential role in synaptic functions has remained unknown. Studying mice from both sexes, we found that katanin is abundant in neuronal dendrites and can be detected at individual excitatory spine synapses. Overexpression of a dominant-negative ATPase-deficient katanin subunit to functionally inhibit severing alters the growth of microtubules in dendrites, specifically at premature but not mature neuronal stages without affecting spine density. Notably, interference with katanin function prevented structural spine remodeling following single synapse glutamate uncaging and significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation. Furthermore, katanin inhibition reduced the invasion of microtubules into fully developed spines. Our data demonstrate that katanin-mediated microtubule severing regulates structural and functional plasticity at synaptic sites.


Assuntos
Microtúbulos , Neurônios , Animais , Camundongos , Katanina/genética , Katanina/metabolismo , Microtúbulos/metabolismo , Neurônios/fisiologia , Neurogênese , Plasticidade Neuronal
2.
Pflugers Arch ; 476(8): 1235-1247, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38856775

RESUMO

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.


Assuntos
Estimulação Elétrica , Laringe , Substância Cinzenta Periaquedutal , Proteínas Proto-Oncogênicas c-fos , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Substância Cinzenta Periaquedutal/metabolismo , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Elétrica/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Laringe/fisiologia , Laringe/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Pressão , Bulbo/metabolismo , Bulbo/fisiologia , Ácido Glutâmico/metabolismo
3.
J Phys Chem A ; 128(18): 3596-3603, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38656804

RESUMO

The vibrational and electronic spectroscopy of the radical cations of two nucleobases (NB) (uracil and thymine) was studied by cryogenic ion photodissociation spectroscopy. The radical cations have been generated from the photodissociation of NB-Ag+ complexes. A charge transfer process from the NB to Ag+ governs the deactivation mechanism, leading to the formation of the radical cation without further tautomerization. Single- and double-resonance spectroscopy allows for structural assignments of both the silver complexes and the radical cations by comparison with DFT-based calculations. Interestingly, a tautomer-dependent fragmentation is observed in the thymine enol form that involves the loss of NCO, a fragment which was never reported before for this NB. This selective photodissociation of silver complexes containing aromatic chromophore greatly expands the current technique to produce isomer-selected radical cations in the gas phase providing benchmark experimental data to assess calculations of open-shell species.

4.
Alzheimers Dement ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212313

RESUMO

INTRODUCTION: Cellular prion protein (PrPC) was implicated in amyloid beta (Aß)-induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear. METHODS: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics. RESULTS: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aß levels. Light-sheet microscopy showed that PrPC influenced Aß-plaque burden but not the distribution of those plaques. Interestingly, caveolin-1 (Cav-1) KO neurons significantly reduced intracellular Aß-oligomer (Aßo) uptake when compared to wild-type neurons. DISCUSSION: The findings shed new light on the relevance of intracellular Aßo, suggesting that PrPC and Cav-1 modulate intracellular Aß levels and the Aß-plaque load. HIGHLIGHTS: PrPC expression adversely affects lifespan and behavior in 5xFAD mice. PrPC increases Aß1-40 and Aß1-42 levels and Aß-plaque load in 5xFAD mice. Cav-1 interacts with both PrPC and Aß peptides. Knocking out Cav-1 leads to a significant reduction in intracellular Aß levels.

5.
Pflugers Arch ; 475(4): 505-516, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36543918

RESUMO

Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20-50 µA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5-10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (p < 0,001) and tachycardia (p < 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (p < 0,01, p < 0,001, p < 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (p < 0,01; p < 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.


Assuntos
Ácido Cinurênico , Taquicardia , Ratos , Animais , Ácido Cinurênico/farmacologia , Frequência Cardíaca/fisiologia , Substância Cinzenta Periaquedutal , Ácido Glutâmico/farmacologia , Transmissão Sináptica , Taquipneia
6.
Chemphyschem ; 24(1): e202200324, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36000956

RESUMO

The photodetachment and stability of R-Mandelate, the deprotonated form of the R-Mandelic acid, was investigated by observing the neutral species issued from either simple photodetachment or dissociative photodetachment in a cold anions set-up. R-Mandalate has the possibility to form an intramolecular ionic hydrogen-bond between adjacent hydroxyl and carboxylate groups. The potential energy surface along the proton transfer (PT) coordinate between both groups (O- …H+ …- OCO) features a single local minima, with the proton localized on the O- group (OH…- OCO). However, the structure with the proton localized on the - OCO group (O- …HOCO) is also observed because it falls within the extremity of the vibrational wavefunction of the OH…- OCO isomer along the PT coordinate. The stability of the corresponding radicals, produced upon photodetachment, is strongly dependent on the position of the proton in the anion: the radicals produced from the OH…- OCO isomer decarboxylate without barrier, while the radicals produced from the O- …HOCO isomer are stable.


Assuntos
Hidrogênio , Prótons , Isomerismo , Ácidos Mandélicos , Ânions/química
7.
PLoS Biol ; 18(8): e3000820, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866173

RESUMO

Mutations in the gene encoding the microtubule-severing protein spastin (spastic paraplegia 4 [SPG4]) cause hereditary spastic paraplegia (HSP), associated with neurodegeneration, spasticity, and motor impairment. Complicated forms (complicated HSP [cHSP]) further include cognitive deficits and dementia; however, the etiology and dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working and associative memory deficits upon spastin depletion in mice. Loss of spastin-mediated severing leads to reduced synapse numbers, accompanied by lower miniature excitatory postsynaptic current (mEPSC) frequencies. At the subcellular level, mutant neurons are characterized by longer microtubules with increased tubulin polyglutamylation levels. Notably, these conditions reduce kinesin-microtubule binding, impair the processivity of kinesin family protein (KIF) 5, and reduce the delivery of presynaptic vesicles and postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Rescue experiments confirm the specificity of these results by showing that wild-type spastin, but not the severing-deficient and disease-associated K388R mutant, normalizes the effects at the synaptic, microtubule, and transport levels. In addition, short hairpin RNA (shRNA)-mediated reduction of tubulin polyglutamylation on spastin knockout background normalizes KIF5 transport deficits and attenuates the loss of excitatory synapses. Our data provide a mechanism that connects spastin dysfunction with the regulation of kinesin-mediated cargo transport, synapse integrity, and cognition.


Assuntos
Ácido Glutâmico/metabolismo , Cinesinas/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo , Neurônios/metabolismo , Espastina/deficiência , Tubulina (Proteína)/metabolismo , Potenciais de Ação , Animais , Membrana Celular/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Potenciais Pós-Sinápticos Excitadores , Hipocampo/patologia , Hipocampo/fisiopatologia , Camundongos Knockout , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Atividade Motora , Neurônios/patologia , Neurônios/ultraestrutura , Transporte Proteico , Espastina/metabolismo , Sinapses/metabolismo , Sinapses/ultraestrutura , Vesículas Sinápticas/metabolismo
8.
Nature ; 546(7658): 406-410, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28538727

RESUMO

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.


Assuntos
Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Zika virus/isolamento & purificação , América/epidemiologia , Número Básico de Reprodução , Brasil/epidemiologia , Variação Genética , Genoma Viral/genética , Humanos , Microcefalia/epidemiologia , Microcefalia/virologia , Epidemiologia Molecular , Filogeografia , Análise Espaço-Temporal , Zika virus/genética , Infecção por Zika virus/epidemiologia
9.
Res Sports Med ; : 1-11, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695507

RESUMO

The purpose of this protocol was to adapt and validate the English version of the Short Musculoskeletal Function Assessment (SMFA) into Chilean Spanish according to the World Health Organisation guidelines. This is a cross-sectional study of 897 surveys of patients with non-traumatic surgical orthopaedic pathologies. We analysed internal consistency, validity, and acceptability, including correlation with the short form 36 (SF-36) medical score. The validation included 900 participants with a response rate of 99,66%, with excellent internal consistency (Cronbach's α = 0.962). The Dysfunction and Bother Index items showed a value of 0.952 and 0.884 respectively, eliminating one item in the Dysfunction sub-scale. The principal component analysis was forced to four factors explaining 55.5% of the variance. SMFA-CL sub-scales are significantly correlated with SF-36 components and subcomponents. The first version of the SMFA-CL version (Spanish-Chilean) scale is reported. This culturally adapted score demonstrated a high rate of reliability, validity, and ability to objectively evaluate foot and ankle pathologies.

10.
Br Poult Sci ; 63(2): 108-114, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34404284

RESUMO

1. The study was carried out to evaluate the effect of stocking density on performance, litter moisture, Eimeria oocyst shedding, intestinal and foot lesions in broilers.2. A total of 192 1-d-old male Cobb broilers were distributed with three different stocking densities (6, 8 or 10 chickens/m2) with outdoor access and eight replicates in a completely randomised design over two periods. Productive parameters were measured from 3 to 7 weeks of age.3. Oocyst counts (OPG) in both excreta and litter were performed at 3, 4 and 5 weeks of age. Intestinal and foot pad lesions were evaluated at 7 weeks old. The stocking density of 6 birds/m2 had the highest body weights (P < 0.05) (2129 ± 37.67, 2759 ± 50.82 and 3167 ± 75.64 g at weeks 5, 6 and 7 of age, respectively).4. Feed intake decreased with increasing stocking density at week 3 (r = -0.57), 4 (r = -0.48), 5 (r = -0.84), 6 (r = -0.68) and 7 (r = -0.65) of age (P < 0.05). Birds with stocking densities of 8 and 10/m2 consumed, respectively, up to 11% and 19.5% less feed than the lower stocking density groups.5. Stocking density affected (P < 0.05) feed conversion (1.61, 1.49 and 1.46) and litter moisture (40.88, 52.60 and 56.19%) at 3 weeks of age. Neither carcase yield nor mortality was different between densities (P > 0.05). Likewise, there was no effect of stocking density on OPG neither in excreta nor in litter, intestinal lesions, or foot pad and hock injuries (P > 0.05).6. In conclusion, the higher stocking density decreased both the feed intake and the live weight in broilers, but there were no effects in the number of Eimeria OPG in excreta or litter, neither intestinal lesions nor in foot pad injuries.


Assuntos
Galinhas , Eimeria , Criação de Animais Domésticos , Animais , Abrigo para Animais , Masculino , Clima Tropical
11.
Neth Heart J ; 30(6): 328-334, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34910278

RESUMO

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up.

12.
Br Poult Sci ; 62(5): 632-637, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33870809

RESUMO

1. The effects of housing system and stocking density on growth performance and carcase yield of a commercial strain of broiler chickens reared under tropical environmental conditions may differ from temperate conditions.2. In two experimental periods, carried out during two contrasting seasons of the year (winter and summer), 240 Cobb 500 male chickens were randomly assigned in groups of 60 to 1 of 4 treatments, with 6 replicates in each, low stocking density with outdoor access (LO, 5 birds/m2); high stocking density with outdoor access (HO, 10 birds/m2); low stocking density indoors (LI, 5 birds/m2); high stocking density indoors (HI, 10 birds/m2). From 21 to 42 d old, body weight (BW) and feed intake (FI) were weekly recorded. Mortality was measured daily and carcase weight at slaughter. Indoor and outdoor temperature and relative humidity were measured daily.3. There was a tendency for chickens raised in the outdoor access to be heavier than those raised in the indoor treatments. Chickens raised in the low-density treatments in the first experimental period were significantly heavier, gained more weight and had lower value for feed conversion ratio (FCR) than those reared at high density. In the second experimental period mortality significantly increased on week 4 due to heat stress. Birds raised with outdoor access had an increased carcase yield compared to those raised exclusively indoors.4. In conclusion, low stocking density in combination with low environmental temperatures had enhancing effects on BW, BWG, FI and FCR, and the effects of housing system depended on stocking density. Low stocking density and outdoor access had positive effects on carcase yield.


Assuntos
Criação de Animais Domésticos , Galinhas , Animais , Abrigo para Animais , Masculino , Estações do Ano , Clima Tropical
13.
Phys Chem Chem Phys ; 22(29): 16813-16821, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32662468

RESUMO

Ligand-free atomic silver nanoclusters (AgNCs) were successfully synthesized following the electrochemical procedure developed by Lopez-Quintela and col. (D. Buceta, N. Busto, G. Barone, J. M. Leal, F. Domínguez, L. J. Giovanetti, F. G. Requejo, B. García and M. A. López-Quintela, Angew. Chem., Int. Ed., 2015, 54, 7612-7616), who have identified the presence of Ag2 and Ag3 AgNCs. The goal of this work was to get information on the photophysics of these AgNCs, which was achieved by combining information from excitation/emission matrix (EEM) and time resolved emission spectroscopy (TRES) along with DFT/TD-DFT calculations. This procedure allowed deconvolving the emission and excitation spectra of the AgNC mixture, with further assignment of each transition and lifetime associated to Ag2, Ag3+ and Ag42+ clusters. This deconvolution together with theoretical calculations allowed suggesting for the first time the radiative and non-radiative excited state deactivation mechanism for these clusters.

14.
Nucleic Acids Res ; 46(W1): W323-W328, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29905875

RESUMO

Correlated mutations between residue pairs in evolutionarily related proteins arise from constraints needed to maintain a functional and stable protein. Identifying these inter-related positions narrows down the search for structurally or functionally important sites. MISTIC is a server designed to assist users to calculate covariation in protein families and provide them with an interactive tool to visualize the results. Here, we present MISTIC2, an update to the previous server, that allows to calculate four covariation methods (MIp, mfDCA, plmDCA and gaussianDCA). The results visualization framework has been reworked for improved performance, compatibility and user experience. It includes a circos representation of the information contained in the alignment, an interactive covariation network, a 3D structure viewer and a sequence logo. Others components provide additional information such as residue annotations, a roc curve for assessing contact prediction, data tables and different ways of filtering the data and exporting figures. Comparison of different methods is easily done and scores combination is also possible. A newly implemented web service allows users to access MISTIC2 programmatically using an API to calculate covariation and retrieve results. MISTIC2 is available at: https://mistic2.leloir.org.ar.


Assuntos
Biologia Computacional , Internet , Proteínas/genética , Software , Mutação , Conformação Proteica , Proteínas/química , Alinhamento de Sequência , Análise de Sequência de Proteína
15.
Risk Anal ; 40(11): 2462-2477, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32579752

RESUMO

The increasing need to manage biosecurity threats, such as diseases, zoonoses, and biological weapons, poses serious challenges for risk analysts and policymakers. These threats are large in number, can occur concurrently, and may cause multiple tangible and intangible impacts. They often have an emerging nature, exacerbated by incomplete evidence about their probability of occurrence and potential impacts. There is also a limited amount of time and resources available to evaluate the risks posed by each threat, and it is difficult to learn from past projects. On the other hand, there is also a need to provide policymakers with transparent and consistent threat prioritizations, together with evidence-based recommendations. In response to these challenges, we propose a risk analysis framework for the prioritization and management of biosecurity threats. The framework encompasses key design choices that analysts may use in risk analysis projects along three dimensions: risk support, risk group, and risk organization. The framework has prescriptive value, as a design tool to inform risk analysis projects in this context, along with descriptive value, as a learning tool to understand past projects. We applied the framework prescriptively in two biosecurity threat prioritization projects for the UK Department for Environment, Food and Rural Affairs, and illustrate its descriptive value by reporting our experience of these projects as in-depth case studies. Overall, the proposed framework provides important insights into the impact of different design choices on the success of risk analysis projects for biosecurity threat prioritizations.


Assuntos
Medição de Risco , Medidas de Segurança/organização & administração , Animais , Humanos , Probabilidade
16.
Proc Biol Sci ; 286(1902): 20190369, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31039715

RESUMO

Competition plays a central role in the maintenance of biodiversity. A backbone of classic niche theory is that local coexistence of competitors is favoured by the contraction or divergence of species' niches. However, this effect should depend on the diversity of resources available in the local environment, particularly when resources vary in multiple ecological dimensions. Here, we investigated how available resource breadth (i.e. prey diversity) and competition together shape multidimensional niche variation (between and within individuals) and interspecific niche overlap in 42 populations of congeneric tropical frog species. We modelled realized niches in two key trophic dimensions (prey size and carbon stable isotopes) and sampled available food resources to quantify two-dimensional resource breadth. We found a 14-fold variation in multidimensional population niche width across populations, most of which was accounted for by within-individual diet variation. This striking variation was predicted by an interaction whereby individual niche breadth increased with resource breadth and decreased with the number of congeneric competitors. These ecological gradients also interact to influence the degree of niche overlap between species, which surprisingly decreased with population total niche width, providing novel insights on how similar species can coexist in local communities. Together, our results emphasize that patterns of exploitation of resources in multiple dimensions are driven by both competitive interactions and extrinsic factors such as local resource breadth.


Assuntos
Anuros/fisiologia , Dieta , Meio Ambiente , Cadeia Alimentar , Animais , Brasil , Isótopos de Carbono/análise , Modelos Biológicos
17.
PLoS Comput Biol ; 14(12): e1006615, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30533007

RESUMO

Protein-DNA interactions play important roles in regulations of many vital cellular processes, including transcription, translation, DNA replication and recombination. Sequence variants occurring in these DNA binding proteins that alter protein-DNA interactions may cause significant perturbations or complete abolishment of function, potentially leading to diseases. Developing a mechanistic understanding of impacts of variants on protein-DNA interactions becomes a persistent need. To address this need we introduce a new computational method PremPDI that predicts the effect of single missense mutation in the protein on the protein-DNA interaction and calculates the quantitative binding affinity change. The PremPDI method is based on molecular mechanics force fields and fast side-chain optimization algorithms with parameters optimized on experimental sets of 219 mutations from 49 protein-DNA complexes. PremPDI yields a very good agreement between predicted and experimental values with Pearson correlation coefficient of 0.71 and root-mean-square error of 0.86 kcal mol-1. The PremPDI server could map mutations on a structural protein-DNA complex, calculate the associated changes in binding affinity, determine the deleterious effect of a mutation, and produce a mutant structural model for download. PremPDI can be applied to many tasks, such as determination of potential damaging mutations in cancer and other diseases. PremPDI is available at http://lilab.jysw.suda.edu.cn/research/PremPDI/.


Assuntos
Algoritmos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Biologia Computacional , DNA/genética , Proteínas de Ligação a DNA/química , Bases de Dados Genéticas , Humanos , Modelos Lineares , Simulação de Dinâmica Molecular , Ligação Proteica/genética , Termodinâmica
18.
Trop Anim Health Prod ; 51(6): 1591-1599, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30827004

RESUMO

This study validated a protocol to identify the nutraceutical value of Gymnopodium floribundum (GF) foliage based on its effects on sheep nutrition, production and health and its impact on adult Haemonchus contortus. Thirty animals (17.8 ± 3.44 kg BW) were distributed into five experimental groups (n = 6). Groups T1-T3 received feed including 20%, 30% and 40% GF content, respectively, and group T4 received feed with 0% GF. Groups T1-T4 were all infected with 6000 H. contortus infective larvae (L3). Group T5 included six worm-free lambs fed a diet without GF. Feed intake, dry matter digestibility (DMD) and organic matter digestibility (OMD) were measured, in addition to the faecal excretion of eggs per gram (EPG) and total faecal egg count (TFEC) of H. contortus. On day 39 post-infection, lambs were humanely slaughtered to recover and count adult parasites and assess the length and fecundity of female worms. Higher levels of GF in the diet reduced DMD and OMD (P < 0.05), with the lowest values in T3 (40% GF) (P < 0.05). Body weight gain was similar for all groups (0.18 to 0.2 kg/day; P > 0.05). EPG and TFEC were lower in T1 and T3 than in T4 (P < 0.05), and the number of adult female worms was lowest in T3 (P < 0.05). In conclusion, GF leaf meal can be considered a nutraceutical when included at 40% (T3) in the diet of lambs, based on its ability to decrease the EPG and TFEC of H. contortus by reducing the female worm burden. A 40% inclusion level had no negative impact on lamb diet intake, production and health, although a reduction of digestibility was observed.


Assuntos
Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais , Hemoncose/veterinária , Haemonchus , Doenças dos Ovinos/parasitologia , Animais , Fezes/parasitologia , Feminino , Hemoncose/prevenção & controle , Masculino , Contagem de Ovos de Parasitas/veterinária , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/prevenção & controle
19.
Am Nat ; 192(4): E139-E149, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30205026

RESUMO

Ecologists have long searched for a universal size-scaling constant that governs trophic interactions. Although this is an appealing theoretical concept, predator-prey size ratios (PPSRs) vary strikingly across and within natural food webs, meaning that predators deviate from their optimal prey size by consuming relatively larger or smaller prey. Here we suggest that this unexpected variation in allometric scaling of trophic interactions can be predicted by gradients of prey limitation consistent with predictions from optimal foraging theory. We analyzed >6,000 trophic interactions of 52 populations from four tropical frog species along a gradient of prey limitation. The mean of PPSR and its variance differed up to two orders of magnitude across and within food webs. Importantly, as prey availability decreased across food webs, PPSR and its variance became more size dependent. Thus, trophic interactions did not follow a fixed allometric scaling but changed predictably with the strength of prey limitation. Our results emphasize the importance of ecological contexts in arranging food webs and the need to incorporate ecological drivers of PPSR and its variance in food web and community models.


Assuntos
Anuros/fisiologia , Tamanho Corporal , Comportamento Predatório/fisiologia , Animais , Brasil , Cadeia Alimentar , Clima Tropical
20.
J Anim Ecol ; 87(5): 1452-1464, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29938791

RESUMO

Although neglected by classic niche theory, individual variation is now recognized as a prevalent phenomenon in nature with evolutionary and ecological relevance. Recent theory suggests that differences in individual variation across competitors can affect species coexistence and community patterns. However, the degree of individual variation is flexible across wild populations and we still know little about the ecological drivers of this variation across populations of single species and, especially, across coexisting species. Here, we aimed to (a) elucidate the major drivers of individual niche variation in natural communities and (b) to determine how consistent this variation is across coexisting species and communities. We analysed natural patterns of individual-level niche variation in four species of coexisting generalist frogs across a wide range of tropical communities. Specifically, we used gut contents and stable isotopes (δ13 C and δ15 N) from frog species and their prey to quantify individual niche specialization. Then, we combined data on local community structure, availability of prey, phylogenetic relationships and predator-prey size models to test how this variation is related to four ecological factors which are predicted to be key drivers of individual specialization: intraspecific competition, interspecific competition, ecological opportunity (i.e., diversity of resources) and predation. We found that the degree of individual trophic specialization varied by up to ninefold across populations within the same species. This sizable variation in trophic specialization across populations was at least partially explained by gradients of density of competitors (both conspecifics and heterospecifics) and intraguild predation. However, the specific relationships between individual specialization and these ecological gradients were strongly species-specific. As consequences, the identity of the species with more individual variation changed among sites and there was typically no spatial correlation in the degree of individual specialization across coexisting species. Our results show that individual niche specialization within and across species can be strongly context-dependent and that hierarchies of individual variation among coexisting species are not necessarily consistent across communities. Recent theory suggests that this pattern could lead to concurrent changes in competitive interactions across sites and thereby could play a key role in species coexistence at the landscape level. Our results suggest that individual variation across and within coexisting species has the potential to affect not only species coexistence at local communities, but also regional diversity patterns.


Assuntos
Ecologia , Comportamento Predatório , Animais , Evolução Biológica , Filogenia , Especificidade da Espécie
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