Biodeterioration of Mayan buildings at uxmal and tulum,Mexico

Uxmal and Tulum are two important Mayan sites in the Yucatan peninsula. The buildings are mainly composed of limestone and grey/black discoloration is seen on exposed walls and copious greenish biofilms on inner walls. The principal microorganisms detected on interior walls at both Uxmal and Tulum were cyanobacteria; heterotrophic bacteria and filamentous fungi were also present. A dark‐pigmented mitosporic fungus and Bacillus cereus, both isolated from Uxmal, were shown to be acidogenic in laboratory cultures. Cyanobacteria belonging to rock‐degrading genera Synechocystis and Gloeocapsa were identified at both sites. Surface analysis previously showed that calcium ions were present in the biofilms on buildings at Uxmal and Tulum, suggesting the deposition of biosolubilized stone. Apart from their potential to degrade the substrate, the coccoid cyanobacteria supply organic nutrients for bacteria and fungi, which can produce organic acids, further increasing stone degradation.     

Dose-response effect of chlorhexidine on a multispecies oral biofilm formed on pure titanium and on a titanium-zirconium alloy

Abstract

This study aimed to test the dose-response effect of chlorhexidine on multispecies biofilms formed on commercially pure titanium (cpTi) and titanium-zirconium (TiZr) alloy. Biofilms were formed on cpTi and TiZr discs and treated two times per day with five different chlorhexidine concentrations (0.12, 0.20, 0.50, 1, 2%). The biofilms were collected for microbiological, biochemical and microscopic analyses. The significance of differences among groups was evaluated by linear regression, ANOVA, Bonferroni and Tukey tests. The mean number of colony-forming units decreased as the chlorhexidine concentration increased for both cpTi and TiZr (p?<?0.05). The maximum effect was observed with the 0.5% concentration. Confocal microscopy images suggested an increase in the number of dead bacterial cells with increased chlorhexidine concentration. The biofilm pH increased after chlorhexidine exposure (p?<?0.05). Chlorhexidine showed an antimicrobial dose-response effect in controlling biofilm on cpTi and TiZr. 0.5% chlorhexidine can be used to achieve the maximum antimicrobial effect on both materials.     

Multiscale simulation of flow-induced texture formation in polymer liquid crystals and carbonaceous mesophases

This paper presents theory and simulation of flow-induced structures in liquid crystalline materials, useful to the creation of synthetic material structures and to the biomimetics of natural fibers. A multiscale theory and simulation of hydrodynamic texture formation is presented; it provides fundamental principles for control and optimization of structures in liquid crystal polymers and carbonaceous mesophases. In thermotropic flow-aligning nematic polymers it is found that as the shear-rate increases, the pathway between an oriented non-planar state and an oriented planar state is through meso-texture formation and coarsening, with temperature and shear rate being efficient fields to control the grain size of the texture. For capillary flow of carbonaceous mesophases, the simulations predict the emergence of macroscopic ring patterns whose thickness and density can be controlled by the applied pressure drops. The results provide insight on microstructure formation and control in liquid crystalline materials.     

Computational study of conformational changes in human 3-hydroxy-3-methylglutaryl coenzyme reductase induced by substrate binding

Abstract

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is mainly involved in the regulation of cholesterol biosynthesis. HMGR catalyses the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate at the expense of two NADPH molecules in a two-step reversible reaction. In the present study, we constructed a model of human HMGR (hHMGR) to explore the conformational changes of HMGR in complex with HMG-CoA and NADPH. In addition, we analysed the complete sequence of the Flap domain using molecular dynamics (MD) simulations and principal component analysis (PCA). The simulations revealed that the Flap domain plays an important role in catalytic site activation and substrate binding. The apo form of hHMGR remained in an open state, while a substrate-induced closure of the Flap domain was observed for holo hHMGR. Our study also demonstrated that the phosphorylation of Ser872 induces significant conformational changes in the Flap domain that lead to a complete closure of the active site, suggesting three principal conformations for the first stage of hHMGR catalysis. Our results were consistent with previous proposed models for the catalytic mechanism of hHMGR.

Communicated by Ramaswamy H. Sarma     

Depression in Medical School: The Influence of Morningness‐Eveningness

Medical students are at higher risk for depression, affecting not only their lives but also patient care. This article studied a population of medical students engaged in lecture‐based learning regarding the presence of depressive symptoms and its relation to morningness‐eveningness. Depressive symptoms were assessed by the Beck Depressive Inventory scale (BDI>10), and diurnal preference was assessed by the Horne & Östberg Morningness/Eveningness Questionnaire (MEQ). Family history of depression and involvement in regular physical activity were also investigated. A total of 161 students, 77 (47.8%) males, aged 19 to 30 yrs (22.1±2.1) living in a city close to the equator were evaluated. Fifty‐three individuals (32.9%) had depressive symptoms. Depressive individuals showed a trend to be female (p=0.07). Also, female gender showed a non‐significant shift toward morningness. Fifty‐eight (36.0%) subjects participated in regular physical activity. In 57 cases (35.4%), there was a history of depression in the family. Fifteen individuals (9.3%) were definitely evening type, 42 (26.1%) were moderately evening type, 44 (27.3%) were indifferent, 42 (26.1%) were moderately morning type, and 18 (11.2%) were definitely morning type. Family history of depression (OR=0.29, 95% CI=1.37–6.12) and sedentary life (OR=0.28, 95% CI=0.12–0.65) were associated with depressive symptoms. Eveningness was associated with depressive symptoms (OR=0.66, 95% CI=0.50–0.88), and this association remained significant after adjusting for the presence of familial depression and physical activity (OR=0.71, 95% CI=0.52–0.95). In conclusion, depressive symptoms are independently associated with “eveningness” in medical students. These results should be confirmed by future studies involving a larger number of subjects.     

Photosynthetic characteristics and quality of five passion fruit varieties under field conditions

Due to photosynthetic mechanisms respond very quickly to most stressors and due to strong concerns regarding the impact of climate change on future plant productivity, the purpose of this study was to perform a comparative analysis of in vivo photosynthetic efficiencies and fruit quality of five cultivars of passion fruit (Passiflora edulis Sims. f. flavicarpa Degener). The experiments were conducted in the northern region of Espírito Santo State using cultivars FB 200, FB 300, BRS Gigante Amarelo, BRS Sol do Cerrado, and BRS Ouro Vermelho. Analyses were performed 6 months after planting, when the plants were beginning reproduction and were repeated two times during the next 4 months until fruit ripening. Chlorophyll a fluorescence transient, total chlorophyll content, and gas exchange were measured in the leaves. Physical and chemical fruit attributes were also assessed. The lowest fluorescence rates were identified in the FB 300, BRS Sol do Cerrado, and BRS Ouro Vermelho cultivars, which exhibited better capacities for quinone A (Q_A) reoxidation and better electron transfer efficiencies from Photosystem II to Photosystem I acceptors. Better photochemical performances (PI_total) and CO₂ assimilations (A) resulted in higher fruit pulp yields, demonstrating the superior quality of the FB 300, BRS Sol do Cerrado, and BRS Ouro Vermelho cultivars.     

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Alzheimer′s disease (AD) is the most common form of dementia in the elderly. Memory loss in AD is increasingly attributed to soluble oligomers of the amyloid‐β peptide (AβOs), toxins that accumulate in AD brains and target particular synapses. Glutamate receptors appear to be centrally involved in synaptic targeting by AβOs. Once bound to neurons, AβOs dysregulate the activity and reduce the surface expression of both N‐methyl‐d ‐aspartate (NMDA) and 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid (AMPA) types of glutamate receptors, impairing signaling pathways involved in synaptic plasticity. In the extracellular milieu, AβOs promote accumulation of the excitatory amino acids, glutamate and d ‐serine. This leads to overactivation of glutamate receptors, triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking AβOs to deregulated glutamate neurotransmission and implicating this as a primary mechanism of synapse failure in AD. We also discuss strategies to counteract the impact of AβOs on excitatory neurotransmission. In particular, we review evidence showing that inducing neuronal hyperpolarization via activation of inhibitory GABA_A receptors prevents AβO‐induced excitotoxicity, suggesting that this could comprise a possible therapeutic approach in AD.     

Identification of Serpin Determinants of Specificity and Selectivity for Furin Inhibition through Studies of α1PDX (α1-Protease Inhibitor Portland)-Serpin B8 and Furin Active-site Loop Chimeras

α₁-Protease inhibitor Portland (α₁PDX) is an engineered serpin family inhibitor of the proprotein convertase (PC), furin, that exhibits high specificity but limited selectivity for inhibiting furin over other PC family proteases. Here, we characterize serpin B8, a natural inhibitor of furin, together with α₁PDX-serpin B8 and furin-PC chimeras to identify determinants of serpin specificity and selectivity for furin inhibition. Replacing reactive center loop (RCL) sequences of α₁PDX with those of serpin B8 demonstrated that both the P4–P1 RXXR recognition sequence as well as the P1′–P5′ sequence are critical determinants of serpin specificity for furin. Alignments of PC catalytic domains revealed four variable active-site loops whose role in furin reactivity with serpin B8 was tested by engineering furin-PC loop chimeras. The furin(298–300) loop but not the other loops differentially affected furin reactivity with serpin B8 and α₁PDX in a manner that depended on the serpin RCL-primed sequence. Modeling of the serpin B8-furin Michaelis complex identified serpin exosites in strand 3C close to the 298–300 loop whose substitution in α₁PDX differentially affected furin reactivity depending on the furin loop and serpin RCL-primed sequences. These studies demonstrate that RCL-primed residues, strand 3C exosites, and the furin(298–300) loop are critical determinants of serpin reactivity with furin, which may be exploited in the design of specific and selective α₁PDX inhibitors of PCs.     

Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids

We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR) assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.     

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.