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Emotional stress is a constant companion of tinnitus patients, since this phantom sound can unfortunately be a very effective stressor. However, the mechanism of stress contribution to the onset or progression of tinnitus remains unknown. Here, we review the pathways induced by emotional stress and the outcome of their induction: corticosteroid-dependent changes in gene expression, epigenetic modulations, and impact of stress on neuronal plasticity and neurotransmission. Using clinical examples, we demonstrate the presence of emotional stress among tinnitus patients and we present methods to measure the degree of stress. The evidence causally linking emotional stress with tinnitus is still indirect-the main difficulty lies in the inaccessibility of human auditory tissues and the inability to directly measure tinnitus-induced psychological distress in animal models. However, we believe that translational research is the future way of filling this gap, finding the answers, and thereby improving both the diagnosis and treatment of tinnitus patients.
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Percepção Auditiva , Encéfalo/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia , Zumbido/fisiopatologia , Humanos , Modelos Neurológicos , Estresse Psicológico/psicologia , Zumbido/diagnóstico , Zumbido/psicologiaRESUMO
[Purpose] This study aimed to evaluate the anti-inflammatory and analgesic effects of intraoral application of low-level laser therapy (660â nm) to control pain, swelling and interincisal opening following the extraction of mandibular third molars. [Subjects and Methods] Ten patients underwent removal of lower third molars using the same surgical protocol and pharmacological approach. In the postoperative period, all patients received four consecutive daily sessions of low-level laser therapy, beginning 24 hours after the surgery. Intraoral applications using the diode laser with 660â nm wavelength in the continuous scan mode were performed covering the entire surgical area, which was divided into four quadrants, each of 1â cm(2) area at a distance of 1â cm. The energy applied at each point was 5â J/cm(2) during 8 seconds. [Results] The swelling and interincisal opening returned to normal 24 hours after the first low-level laser therapy application (Friedman test). Moreover, the pain intensity was reduced on the third postoperative day, according to the Friedman test. [Conclusion] Low-level laser therapy (660â nm), at the dosimetry used in this study, was effective in reducing postoperative pain and swelling following oral surgery.
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An efficient synthesis route is proposed to obtain single phase powder ceramic of CaFe5O7. This complex structure can be described as an intergrowth between one CaFe2O4 unit and n = 3 slices of FeO Wüstite-type structure. A detailed structural study has been carried out at room temperature combining transmission electron microscopy (TEM) observations (ED, HREM), scanning transmission electron microscopy (STEM-HAADF), and X-ray diffraction data. The analysis of these data has revealed an unexpected supercell with a monoclinic symmetry. From the hkl conditions deduced from the electron diffraction study and the analysis of X-ray diffraction data by simulated annealing, a structural model considering the centrosymmetric P21/m setting can be proposed. In addition the first magnetic and electrical transport measurements are reported showing a sharp peak in magnetic susceptibility and a strong localization around 360 K, associated to a structural change from monoclinic setting to orthorhombic one.
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AIMS/HYPOTHESIS: We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2ß. We also identified miR-153 target genes that correlated with IA-2ß localisation and function. METHODS: A bioinformatics approach was used to identify miR-153's genomic organisation. To analyse the co-regulation of miR-153 and IA-2ß, quantitative PCR analysis of miR-153 and Ia-2ß (also known as Ptprn2) was performed after a glucose stimulation assay in MIN6B cells and isolated murine pancreatic islets, and also in wild-type Ia-2 (also known as Ptprn), Ia-2ß single knockout and Ia-2/Ia-2ß double knockout mouse brain and pancreatic islets. Bioinformatics identification of miR-153 target genes and validation via luciferase reporter assays, western blotting and quantitative PCR were also carried out. RESULTS: Two copies of miR-153, miR-153-1 and miR-153-2, are localised in intron 19 of Ia-2 and Ia-2ß, respectively. In rodents, only miR-153-2 is conserved. We demonstrated that expression of miR-153-2 and Ia-2ß in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2ß knockout and Ia-2/Ia-2ß double knockout mice. miR-153 levels were unaffected in Ia-2 knockout mice. In addition, glucose stimulation, which increases Ia-2 and Ia-2ß expression, also significantly increased expression of miR-153. Several predicted targets of miR-153 were reduced after glucose stimulation in vitro, correlating with the increase in miR-153 levels. CONCLUSIONS/INTERPRETATION: This study suggests the involvement of miR-153, IA-2ß and miR-153 target genes in a regulatory network, which is potentially relevant to insulin and neurotransmitter release.
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Encéfalo/metabolismo , MicroRNAs/genética , Pâncreas/metabolismo , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Masculino , Camundongos , Camundongos Knockout , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The oxycarbonate Sr7Co4(CO3)O11.36 exhibits a peculiar structure that has been characterized by combining transmission electron microscopy analyses and neutron diffraction. It consists of a regular intergrowth between the m = 2 and carbonated m = 3 members of the Sr(m+1)Co(m)O3(m+1) Ruddlesden-Popper (RP) series, Sr3Co2O5.87 and Sr4Co2(CO3)O5.49, respectively. A description of the structure is proposed to provide identification of the different building blocks. This material is semiconducting and presents a complex magnetic behavior, characteristic of what is observed for the RP(2) or RP(3) series, with a cobalt valency close to 2.7.
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An original Ruddlesden-Popper phase, La(0.77)Sr(3.23)Co(2.75)C(0.25)O(8.40+δ), was isolated and studied by electron, X-ray, and neutron diffraction. This structure has complex crystal chemistry resulting from a high degree of flexibility in the structure, comprising the disordered introduction of carbonates into a cobalt layer and an important oxygen deficiency with a preferential repartition of vacancies along the layers stacking sequence. The former is necessary for the stabilization of the system, while the latter can be tuned by postsynthetic treatment, yielding in a large variety of cobalt species formal oxidation states ranging from Co(2+)/Co(3+) in the as-made phase to Co(3+)/Co(4+) when annealed under oxygen pressure. The potential richness deriving from this flexibility is illustrated in terms of the magnetotransport properties and includes a resistivity that varies within a range of 5 orders of magnitude after modulation of the oxygen content with the appearance of negative magnetoresistance and ferromagnetic interactions due to Co(3+)/Co(4+) mixed-valence state.
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Carbono/química , Cobalto/química , Lantânio/química , Óxidos/química , Oxigênio/química , Estrôncio/química , Difração de NêutronsRESUMO
Defects in the human Ca(2+)-sensing receptor gene have recently been shown to cause familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. We now demonstrate that a missense mutation (Glu128Ala) in this gene causes familial hypocalcaemia in affected members of one family. Xenopus oocytes expressing the mutant receptor exhibit a larger increase in inositol 1,4,5-triphosphate in response to Ca2+ than oocytes expressing the wild-type receptor. We conclude that this extracellular domain mutation increases the receptor's activity at low Ca2+ concentrations, causing hypocalcaemia in patients heterozygous for such a mutation.
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Cálcio/sangue , Genes Dominantes , Hipocalcemia/genética , Mutação Puntual , Receptores de Superfície Celular/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , DNA Complementar/genética , Feminino , Heterozigoto , Homeostase , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Escore Lod , Masculino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Oócitos , Linhagem , Receptores de Detecção de Cálcio , Proteínas Recombinantes de Fusão/metabolismo , Tetania/genética , Xenopus laevisRESUMO
The aim of this work is to evaluate and discuss river water quality trends over the last decade in ten watersheds where diffuse pollution represents more than half of the annual load of phosphorus (P) and nitrogen (N). Trend analyses taking into account flow data indicate a significant reduction of total P in eight rivers, of ammonia N in five rivers, of nitrate + nitrite in four rivers, of total filtered N in three rivers and of suspended solids in two rivers. An increase of turbidity was observed in four rivers and, for fecal coliforms, no trends. P decrease can be explained by reduced mineral P inputs on cropped lands related to means such as agro-environmental fertilization plans and addition of phytase in pig and poultry feed. However, for seven of them, median P concentrations remain at least two times greater than the Québec water quality guideline for protection of rivers against eutrophication. Concentrations of other parameters remain problematic in some rivers too. These results indicate the need to continue the efforts for further diffuse pollution reduction. Future work should better quantify actions taken at the watershed scale to reduce diffuse pollution.
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Microbiologia da Água/normas , Poluição da Água , Abastecimento de Água/normas , Água/química , Agricultura , Enterobacteriaceae/isolamento & purificação , Fezes/microbiologia , Nitrogênio/química , Fósforo/química , Quebeque , Fatores de TempoRESUMO
The importance of intracellular calcium in regulating cell function is well recognized. No less important, but less well understood (and probably appreciated), is the fundamental role played by extracellular calcium, Ca2+o, in the modulation of cell function. The recent cloning of Ca2+o-sensing, G-protein-coupled receptors from bovine (and human) parathyroid and rat kidney (and brain) has clearly demonstrated that Ca2+o can function as a traditional 'first messenger'. The identification of 'inactivating' and 'activating' mutations in this Ca2+o-sensing receptor in two hypercalcemic disorders and in an autosomal dominant form of hypocalcemia, respectively, has underscored the physiological relevance of this receptor in Ca2+ homeostasis in man. These advances have significantly enhanced our understanding of the molecular mechanisms involved in extracellular calcium sensing in parathyroid and kidney. Moreover, the localization of the Ca2+o-sensing receptor in tissues previously not known to have Ca2+o-sensing capability has suggested novel and potentially quite important roles for Ca2+o in regulating the function of cells not apparently directly involved in Ca2+ homeostasis.
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Proteínas de Ligação ao Cálcio/metabolismo , Animais , Encéfalo/metabolismo , Bovinos , Clonagem Molecular , Humanos , Hipercalcemia/genética , Rim/metabolismo , Mutação , Ratos , Sistemas do Segundo Mensageiro/fisiologiaRESUMO
To enhance equity and diversity in undergraduate biology, recent research in biology education focuses on best practices that reduce learning barriers for all students and improve academic performance. However, the majority of current research into student experiences in introductory biology takes place at large, predominantly White institutions. To foster contextual knowledge in biology education research, we harnessed data from a large research coordination network to examine the extent of academic performance gaps based on demographic status across institutional contexts and how two psychological factors, test anxiety and ethnicity stigma consciousness, may mediate performance in introductory biology. We used data from seven institutions across three institution types: 2-year community colleges, 4-year inclusive institutions (based on admissions selectivity; hereafter, inclusive), and 4-year selective institutions (hereafter, selective). In our sample, we did not observe binary gender gaps across institutional contexts, but found that performance gaps based on underrepresented minority status were evident at inclusive and selective 4-year institutions, but not at community colleges. Differences in social psychological factors and their impacts on academic performance varied substantially across institutional contexts. Our findings demonstrate that institutional context can play an important role in the mechanisms underlying performance gaps.
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Desempenho Acadêmico , Estudantes , Humanos , Aprendizagem , Grupos Minoritários , UniversidadesRESUMO
Previous angle-resolved photoemission spectroscopy experiments in NaxCoO2 reported both a strongly renormalized bandwidth near the Fermi level and moderately renormalized Fermi velocities, leaving it unclear whether the correlations are weak or strong and how they could be quantified. We explain why this situation occurs and solve the problem by extracting clearly the coherent and incoherent parts of the band crossing the Fermi level. We show that one can use their relative weight to estimate self-consistently a quasiparticle weight Z=0.15+/-0.05. We suggest this method could be a reliable way to study the evolution of correlations in cobaltates and for comparison with other strongly correlated systems.
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BACKGROUND: Cytokine release storm (CRS) is a potentially fatal, hyperinflammatory condition common to both coronavirus disease 2019 (COVID-19) and reactive hemophagocytic lymphohistiocytosis (rHLH). We present our experience with the use of a diagnostic score, developed for rHLH, in a kidney transplant recipient hospitalized with COVID-19. METHODS: We applied the H-Score to risk-stratify our patient to help predict his hospital course. This study was exempt from requiring specific Institutional Review Board approval, but met all the criteria required by our institution for this type of study and report including consent from the patient. RESULTS: The calculated H-Score for our patient fell below the diagnostic cut-off value for rHLH. Because rHLH is characterized by CRS, we expected him to have a milder hospital course with COVID-19. Correlating with his below cut-off H-score, the patient had a more benign than expected hospital course. CONCLUSIONS: Because this is only a single case, we plan to retrospectively review a series of patients to validate our initial experience-that a low H-Score may correlate with a milder hospital course in kidney transplant patients with COVID-19.
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Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Hospedeiro Imunocomprometido , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Índice de Gravidade de Doença , Betacoronavirus , COVID-19 , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/etiologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , Estudos Retrospectivos , SARS-CoV-2RESUMO
We have synthesized single crystals of the misfit-layered cobalt oxide, [Bi(1.5)Pb(0.5)Sr(2)O(4-δ)][CoO(2)](1.86), with quadruple NaCl-type layers, using a flux method, and measured their transport properties. From structural refinements, it is found that the modulation in the BiO layer observed in [Bi(1.74)Sr(2)O(4-δ)](RS)[CoO(2)](1.82) is suppressed by Pb substitution. The in-plane resistivity, thermopower, and Hall coefficient are 4.3 mΩ cm, 101 µV K(-1), and 1 × 10(-2) cm(3) C(-1) at 300 K, respectively; these are consistent with those of the misfit-layered cobalt oxides. All of these values are smaller than those of [Bi(1.74)Sr(2)O(4)][CoO(2)](1.82), indicating that the carrier concentration is larger than that of the undoped crystal. Moreover, the low T upturn of resistivity observed for most of the cobalt misfit oxides is replaced by a metallic behavior, following a T(2) dependence, indicating strong correlations in the Pb-doped crystal. Also, the magnetoresistance, usually negative for misfit oxides, is replaced by a small positive magnetoresistance. Doping with Pb is thus an efficient way to suppress the low T localized behavior usually observed for misfits.
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The search for multifunctional materials as multiferroics to be applied in microelectronic or for new, chemically stable and nontoxic, thermoelectric materials to recover waste heat is showing a common interest in the oxides whose structures contain a triangular network of transition-metal cations. To illustrate this point, two ternary systems, Ba-Co-O and Ca-Co-O, have been chosen. It is shown that new phases with a complex triangular structure can be discovered, for instance, by introduction of Ga (3+) into the Ba-Co-O system to stabilize Ba 6Ga 2Co 11O 26 and Ba 2GaCo 8O 14, which both belong to a large family of compounds with formula [Ba(Co,Ga)O 3-delta] n [BaCo 8O 11]. In the latter, both sublattices contain triangular networks derived from the hexagonal perovskite and the spinel structure. Among the hexagonal perovskite, the Ca 3Co 2O 6 crystals give clear evidence where the coupling of charges and spins is at the origin of a magnetocapacitance effect. In particular, the ferrimagnetic to ferromagnetic transition, with a one-third plateau on the M( H) curve characteristic of triangular magnetism, is accompanied by a peak in the dielectric constant. A second class of cobaltites is the focus of much interest. Their 2D structure, containing CoO 2 planes isostructural to a CdI 2 slice that are stacked in an incommensurate way with rock salt type layers, is referred to misfit cobaltite. The 2D triangular network of edge-shared CoO 6 octahedra is believed to be responsible for large values of the Seebeck coefficient and low electrical resistivity. A clear relationship between the structuresincommensurability ratiosand the electronic properties is evidenced, showing that the charge carrier concentration can be tuned via the control of the ionic radius of the cations in the separating layers.
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This study investigates the effect of variations in mineralocorticoid as well as cell sodium delivery and uptake on Na-K-ATPase activity in the mouse medullary thick ascending limb of Henle (mTALH). Pharmacologic doses of the mineralocorticoid deoxycorticosterone acetate (DOCA) resulted in a 28% increase of Na-K-ATPase activity. Furosemide-induced inhibition of sodium uptake by the mTALH cell also resulted in Na-K-ATPase activity reduction (45%). Sodium deprivation did not cause a clear change in enzyme activity, either at 3 d or 2 wk, likely reflecting the result of the opposing influences of decreased sodium delivery and increased endogenous aldosterone. Finally, the behavior of Na-K-ATPase activity at 3 d of sodium deprivation in the mTALH contrasted with a 60% increase in activity observed in the cortical collecting tubule, a nephron segment known to be responsive to mineralocorticoid, and this heterogeneity of response may suggest an important role for the mTALH in maintaining salt homeostasis.
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Desoxicorticosterona/farmacologia , Túbulos Renais/enzimologia , Alça do Néfron/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Sódio/farmacologia , Aldosterona/sangue , Animais , ATPase de Ca(2+) e Mg(2+)/metabolismo , Desoxicorticosterona/administração & dosagem , Dieta Hipossódica , Furosemida/administração & dosagem , Túbulos Renais Coletores/enzimologia , Túbulos Renais Coletores/metabolismo , Alça do Néfron/efeitos dos fármacos , Alça do Néfron/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Sódio/administração & dosagem , Fatores de TempoRESUMO
Na-K-Cl cotransport plays an important role in the kidney in NaCl reabsorption in the thick ascending limb of Henle and a less well defined role in the inner medullary collecting duct (IMCD). Two Na-K-Cl cotransporters encoded by different genes have been identified in the mammalian kidney: BSC1/NKCC2 which localizes to the apical thick ascending limb of Henle and BSC2/NKCC1 which was isolated from a mouse IMCD cell line (mIMCD-3) but its localization has not been determined. In this study we generated a polyclonal antibody (anti-mBSC2) against the mouse BSC2/NKCC1 protein in order to characterize and localize this protein in mouse kidney. Western blot analysis with affinity-purified anti-mBSC2 showed a protein doublet of 140 and 150 kD which was most abundant in the renal papilla but also seen in cortex and outer medulla. The 140-150-kD bands were not seen with preimmune serum or with anti-mBSC2 preabsorbed with specific antigen. Immunolocalization confirmed expression of mBSC2 protein on the basolateral surface of terminal IMCD segments and demonstrated expression in the papillary surface epithelium. Immunofluorescence also revealed the unexpected presence of the BSC2 protein at the juxtaglomerular afferent arteriole, in a juxtaglomerular structure probably representing the extraglomerular mesangium, and throughout the glomerular mesangium.
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Proteínas de Transporte/análise , Cloretos/metabolismo , Glomérulos Renais/química , Medula Renal/química , Túbulos Renais Coletores/química , Potássio/metabolismo , Sódio/metabolismo , Animais , Arteríolas/química , Glomérulos Renais/irrigação sanguínea , Túbulos Renais Distais/química , Masculino , Camundongos , Simportadores de Cloreto de Sódio-PotássioRESUMO
During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (> or = 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C. Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.
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Cálcio/fisiologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Túbulos Renais Coletores/fisiologia , Receptores de Superfície Celular/fisiologia , Vasopressinas/farmacologia , Água/metabolismo , Animais , Cátions , Epitélio/química , Epitélio/fisiologia , Espaço Extracelular/fisiologia , Immunoblotting , Imuno-Histoquímica , Medula Renal/química , Medula Renal/fisiologia , Túbulos Renais Coletores/química , Ratos , Ratos Sprague-Dawley , Receptores de Detecção de Cálcio , Receptores de Superfície Celular/químicaRESUMO
Recent data suggest that sex hormones affect the thiazide-sensitive NaCl cotransporter (TSC) density or binding capacity (Chen, Z., D.A. Vaughn, and D.D. Fanestil. 1994. J. Am. Soc. Nephrol. 5:1112-1119). Thus, we determined the effect of ovariectomy (OVX) and estrogen replacement on the ultrastructural localization of TSC in rat kidney using immunocytochemistry. Kidneys of intact female (CON) and OVX rats fed ad libitum for 6 and 9 wk or pair-fed for 9 wk were processed for transmission electron microscopy. Immunogold localization of rat TSC (rTSC1) demonstrated intense label in the apical plasma membrane of CON distal convoluted tubule (DCT). In OVX DCT, rTSC1 label and apical plasma membrane microprojections were decreased. Western blots of renal membrane protein from pair-fed CON and OVX revealed bands at 129-135 kD, but the OVX signal was reduced. Morphometric analyses demonstrated that injecting 10 microg/ kg body weight 17beta-estradiol subcutaneously 4x/wk in OVX rats restored DCT apical microprojections and label density for rTSC1. Thus, in OVX rats (a) rTSC1 immunoreactive renal membrane protein is reduced; (b) apical plasma membrane complexity and immunogold label for rTSC1 in DCT is decreased; and (c) estradiol replacement restores DCT ultrastructure and rTSC1 label to normal. We conclude that estrogen enhances the density of rTSC1 in the DCT, and may alter renal Na transport by this mechanism.
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Benzotiadiazinas , Proteínas de Transporte/metabolismo , Estradiol/farmacologia , Túbulos Renais Distais/efeitos dos fármacos , Túbulos Renais Distais/metabolismo , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Simportadores , Animais , Membrana Celular/metabolismo , Cloretos/metabolismo , Diuréticos , Feminino , Túbulos Renais Distais/ultraestrutura , Microscopia Imunoeletrônica , Ovariectomia , Ovário/metabolismo , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Simportadores de Cloreto de SódioRESUMO
Samples of the low-doped manganite La(0.875)Sr(0.125-x)Ca(x)MnO(3) (0≤x≤0.125) have been synthesized and the effect on the structural, magnetic and transport properties of decreasing the tolerance factor by replacing larger Sr(2+) ions with smaller Ca(2+) ions are reported. For samples with x≥0.0625, a concentration (x) dependent structural transition (rhombohedral ([Formula: see text]) to orthorhombic (Pnma)) has been detected at room temperature and the Curie temperature T(C) is found to decrease with increased Ca doping level. For samples with x≤0.0625, a narrow metallic region exists and the corresponding insulator to metal transition temperature T(MI) decreases with increasing Ca content, i.e. decreasing tolerance factor. In the paramagnetic region, x dependent crossover from Mott variable range hopping (Mott-VRH) to Shklovskii-Efros variable range hopping (SE-VRH) occurs as the Ca content increases. The thermoelectric power (TEP) of the samples increases substantially, varying inversely with the tolerance factor. These results are analysed from the consideration of increased bending of the Mn-O-Mn bond with the decrease of the average ionic radius of the A-site element [Formula: see text] and the tolerance factor t, which causes narrowing of the bandwidth, decrease of mobility of e(g) electrons and weakening of the double exchange (DE) interaction associated with the substitution of Ca.