Hasil untuk "Biology (General)"

Società Italiana di Biologia Sperimentale

Lake Faro is a unique coastal meromictic ecosystem characterized by a permanent density stratification that prevents complete vertical mixing, resulting in a stable oxic-anoxic interface (chemocline). This study aims to characterize microbial diversity and community assembly along the water column, thanks also to the measure of the environmental parameters of the water nutrients which gave us great support to understand how steep environmental gradients shape niche partitioning. Microbial community composition was investigated using Illumina MiSeq sequencing of the 16S rRNA (using cDNA), revealing interesting insights on taxonomic and functional transitions from surface waters to the reduced bottom layers. The highlighted a pronounced vertical zonation of microbial communities, tightly coupled to sulfur and nitrogen biogeochemical cycles. The monimolimnion (0–12m) is dominated by typical marine aerobic groups, including oxygenic Cyanobacteria (mainly Synechococcus spp.), followed by Bacteroidota and Proteobacteria, which collectively sustain primary production in the nutrient-limited upper layers. Chemocline (12-15m) and Ipolimnion (15–25m), represent a metabolic hotspot where a shift in community composition occurs. Here, bacterial communities are dominated by Desulfobacterota, the second most abundant phylum after Bacteroidota, with Dissulfuribacteraceae, Desulfobulbaceae, Desulfuromonadaceae as most representative families, well adapted to low-light and high-sulfide conditions. Overall, the findings of this study suggests that below 15m depth a complex anaerobic food web develops, primarily structured by dissolved oxygen, sulfide concentration, and redox potential. This study provides a comprehensive baseline for understanding microbial dark matter in meromictic lagoons and highlights the chemocline as a critical ecological filter regulating carbon and sulfur cycling in coastal Mediterranean environments.

Huynh Hoang Khanh Thu, Yulia V. Ostankova, Alexander N. Shchemelev et al.

Vietnam faces a hyperendemic burden of hepatitis B virus (HBV) infection, but the prevalence of occult HBV infection (OBI) and its underlying molecular mechanisms in healthy populations remain poorly understood. This study aimed to characterize the serological and molecular HBV profile of a healthy Vietnamese adult cohort in Southern Vietnam. We assessed the prevalence of occult HBV infection (OBI) and HBsAg-positivity (serving as a proxy for probable chronic infection). In this cross-sectional study, 397 healthy adults from Southern Vietnam underwent serological screening for HBsAg, anti-HBs, and anti-HBc. All participants were screened for HBV DNA using a high-sensitivity PCR assay (LOD ≥ 5 IU/mL). For all viremic cases, the full Pre-S/S region was sequenced to determine genotype and characterize escape mutations. We uncovered a high prevalence of both HBsAg-positivity (17.6%) and OBI (9.3% HBsAg-negative, HBV DNA-positive). Serological analysis revealed a massive, age-dependent reservoir of past exposure (63.7% anti-HBc) characterized by a high and increasing prevalence of the anti-HBc only profile (31.5%), a key serological marker for OBI. This trend contrasted sharply with a steep age-related decline in protective anti-HBs. The viral landscape was dominated by genotypes B (73.8%) and C (26.2%), with sub-genotypes B4 and C1 being the most prevalent. Critically, individuals with OBI carried a significantly higher burden of S gene escape mutations compared to those with HBsAg-positivity (<i>p</i> < 0.001). Canonical escape variants, including sG145R (21.6%), sK141R/T/E/Q (24.3%), and sT116N/A/I/S (18.9%), were exclusively or highly enriched in the OBI group. A LASSO-logistic model based on this mutational profile successfully predicted occult infection with high accuracy (AUC = 0.83). A substantial hidden reservoir of occult HBV infection exists within the healthy adult population of Vietnam, driven by a high burden of S gene escape mutations. These findings highlight the significant limitations of conventional HBsAg-only screening. They also underscore the need for comprehensive molecular surveillance to address the true scope of HBV viremia, hopefully enabling a reduction in hidden transmission of clinically significant viral variants.

WANG Jiawei(王佳薇), GONG Shuying(龚淑英), FAN Fangyuan(范方媛) et al.

Granular green tea is a significant category of famous high-quality green tea in Zhejiang Province. In this study, we conducted comparative experiments on key technical parameters, including moisture resurgence, second fixation and stir-frying techniques, during the primary processing of granular green tea and systematically analyzed their effects on sensory quality and chemical composition. The results indicated that appropriately controlling the rehumidification time (1.5 h), reducing the moisture content of the second fixed leaves (40%), decreasing the amount of tea leaves per frying pan (4 kg/pan), and selecting a frying pan with better air permeability (60-type) effectively enhanced the dry tea appearance and the emerald color of the tea liquor and improved the freshness of the aroma and taste. Moderate rehumidification and a lower moisture content in the second fixed leaves increased the content of catechins and some key umami amino acids, whereas a lower loading amount of tea leaves per frying pan increased the total amino acid content; a higher moisture content in the second fixed leaves increased the water extract content. Higher-quality samples with superior aroma and freshness had higher levels of floral compounds such as linalool, geraniol, and α-terpineol. Conversely, a longer rehumidification time, greater moisture content in the second fixed leaves, more tea leaves per frying pan, and lower air permeability of the stir-frying machine led to higher temperatures and moisture and increased the relative content of compounds such as n-hexadecanoic acid, heptanoic acid, and 6, 10, 14-trimethyl-2-pentadecanone in the aroma profile. In conclusion, this study identifies an optimal processing combination for improving the overall quality of granular green tea and provides a theoretical basis for refining its processing technology.(颗粒形绿茶是浙江省名优绿茶的重要品类。本研究针对颗粒形绿茶初制中回潮、二青、炒制等工序的关键技术参数开展对比试验，系统分析不同技术参数对颗粒形绿茶感官品质及化学组分的影响。结果表明，适当控制回潮时间（1.5 h）、降低二青叶含水率（40%）、适当减少炒制投叶量（4 kg/小锅）及选用透气性能较好的炒锅（60型），能够提升颗粒形绿茶外形及茶汤的翠绿色泽，并提高香气滋味的鲜爽性。适度回潮和较低的二青叶含水率有助于提升儿茶素含量及部分对鲜味具有重要贡献的氨基酸含量；较低的炒制投叶量可提升氨基酸总量；而较高的二青叶含水率则有利于提升水浸出物含量。在香气鲜爽性高、品质较优的样品中，芳樟醇、香叶醇、α-松油醇等具有花香特征的化合物的相对含量较高；而长时间回潮、较高的二青叶含水率、较高的炒制投叶量及较低透气性的锅型所引起的较高温度及含水率，则会促进正十六烷酸、庚酸、6，10，14-三甲基-2-十五烷酮等香气组分的积累。本研究明确了提升颗粒形绿茶综合品质的适宜工艺组合，为优化其加工技术提供了理论依据。)

Abdulrahman Alrumayh, Khaled Alhassoon, Fahd Alsaleem et al.

This paper presents a novel design of a continuum robot driven by electromagnets and springs, offering enhanced precision in multi-degree-of-freedom bending for diverse applications. Traditional continuum robots, while effective in navigating constrained environments, often face limitations in actuation methods, such as wire-based systems or pre-curved tubes. Our design overcomes these challenges by utilizing electromagnetically driven actuation, which allows each segment of the robot to bend independently at any angle, providing unprecedented flexibility and control. The technical challenges discussed emphasize the goals of this work, with the main aim being to develop a motion control system that uses electromagnets and springs to improve the accuracy and consistency of the robot’s movements. By balancing magnetic and spring forces, our system ensures predictable and stable motion in 3D space. The integration of this mechanism into multi-segmented robots opens up new possibilities in fields such as medical devices, search and rescue operations, and industrial inspection. Finite element method (FEM) simulations validate the efficiency of the proposed approach, demonstrating the precise control of the robot’s motion trajectory and enhancing its operational reliability in complex scenarios.

Chuanzhe Wang, Jie Lv, Mengyi Yang et al.

Cardiovascular diseases (CVD) are the leading global threat to human health. The clinical application of vascular stents improved the survival rates and quality of life for patients with cardiovascular diseases. However, despite the benefits stents bring to patients, there are still notable complications such as thrombosis and in-stent restenosis (ISR). Surface modification techniques represent an effective strategy to enhance the clinical efficacy of vascular stents and reduce complications. This paper reviews the development strategies of vascular stents based on surface functional coating technologies aimed at addressing the limitations in clinical application, including the inhibition of intimal hyperplasia, promotion of re-endothelialization. These strategies have improved endothelial repair and inhibited vascular remodeling, thereby promoting vascular healing post-stent implantation. However, the pathological microenvironment of target vessels and the lipid plaques are key pathological factors in the development of atherosclerosis (AS) and impaired vascular repair after percutaneous coronary intervention (PCI). Therefore, restoring normal physiological environment and removing the plaques are also treatment focuses after PCI for promoting vascular repair. Unfortunately, research in this area is limited. This paper reviews the advancements in vascular stents based on surface engineering technologies over the past decade, providing guidance for the development of stents.

Chizoba M. Enemchukwu, Christiana Nwabueze, Oluchi J. Osuala et al.

Background: The adult human vagina hosts a complex biota containing diverse communities of microorganisms. The occurrence of multi-drug-resistant strains of these microorganisms has persistently increased due to poor hygiene and misuse or abuse of antibiotics. The vaginal microflora may exhibit patterns of growth, biochemical expression, or response to the standard drugs which consequently lead to answer the complex questions of antimicrobial resistance. Aim: The study aimed to quantify the susceptibility profile of microorganisms isolated from vaginal discharge and evaluate the minimum inhibitory concentration of diverse antimicrobial drugs. Methods: Fifty vaginal swabs were collected from female students of Madonna University, Nigeria while two samples were collected each from a pregnant and a non-pregnant woman at the university’s tertiary care teaching hospital. The isolates were grown in selective media and identified through Gram-staining and biochemical physiology for identification. The Kirby-Bauer disc diffusion method was used for microbial susceptibility testing, and the agar dilution method was used to determine the minimum inhibitory concentration of commonly prescribed antibiotics at the teaching hospital. Results: Sixty-eight microorganisms comprising 17 Gram-positive (Staphylococcus sp.) and 31 Gram-negative (Escherichia coli and others) bacteria and 20 fungi (Candida sp.) were isolated. The bacteria showed a high resistance (>80%) to amoxicillin, cefuroxime, and cefixime but were relatively susceptible (35–100%) to levofloxacin and ofloxacin. Cefepime showed high activity with a minimum inhibitory concentration range of 25–50 µg/mL against the studied bacteria. The isolated fungi were susceptible to amphotericin B (35–40%) but resistant (>85%) to other antifungal drugs tested. Conclusion: The study suggests that bacterial vaginosis prevalence at the university could best be treated with ofloxacin (second generation- fluoroquinlone), levofloxacin (third generation- fluoroquinolone), and cefepime (fourth generation- cephalosporin) due to their greater sensitivity, while candidiasis could best be treated with amphotericin B (a pyolene).

Ciro Gargiulo Isacco, Mario G. Balzanelli, Stefania Garzone et al.

<i>Chlamydia trachomatis</i> and human papillomavirus (HPV) are the most common pathogens found in sexually transmitted infections (STIs), and both are known to increase the risk of cervical cancer (CC) and infertility. HPV is extremely common worldwide, and scientists use it to distinguish between low-risk and high-risk genotypes. In addition, HPV transmission can occur via simple contact in the genital area. From 50 to 80% of sexually active individuals become infected with both <i>C. trachomatis</i> and HPV viruses during their lifetime, and up to 50% become infected with an HPV oncogenic genotype. The natural history of this coinfection is strongly conditioned by the balance between the host microbiome and immune condition and the infecting agent. Though the infection often regresses, it tends to persist throughout adult life asymptomatically and silently. The partnership between HPV and <i>C. trachomatis</i> is basically due to their similarities: common transmission routes, reciprocal advantages, and the same risk factors. <i>C. trachomatis</i> is a Gram-negative bacteria, similar to HPV, and an intracellular bacterium, which shows a unique biphasic development that helps the latter continue its steady progression into the host throughout the entire life. Indeed, depending on the individual’s immune condition, the <i>C. trachomatis</i> infection tends to migrate toward the upper genital tract and spread to the uterus, and the fallopian tubes open up a pathway to HPV invasion. In addition, most HPV and <i>C. trachomatis</i> infections related to the female genital tract are facilitated by the decay of the first line of defense in the vaginal environment, which is constituted by a healthy vaginal microbiome that is characterized by a net equilibrium of all its components. Thus, the aim of this paper was to highlight the complexity and fragility of the vaginal microenvironment and accentuate the fundamental role of all elements and systems involved, including the <i>Lactobacillus</i> strains (<i>Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus crispatus</i>) and the immune–endocrine system, in preserving it from oncogenic mutation. Therefore, age, diet, and genetic predisposition together with an unspecific, persistent low-grade inflammatory state were found to be implicated in a high frequency and severity grade of disease, potentially resulting in pre-cancerous and cancerous cervical lesions.

Timothy Sands

Infrastructure monitoring, inspection, repair, and replacement in space is crucial for continued usage and safety, yet it is expensive, time-consuming, and technically very challenging. New robotics technologies and artificial intelligence algorithms are potentially novel approaches that may alleviate such demanding operations using existing or novel sensing technologies. Space structures must necessarily be very light weight due to the high costs of placing robots in space. Several methods are proposed and compared to control highly flexible space robotics, where a key challenge is the presence of flexible resonant modes at frequencies so low as to reside inside typical feedback controller bandwidths. Such conditions imply the very action of sending control signals to the ultra-light weight robotics will cause structural resonance. Implementations of incrementally increasing order are offered, achieving an over ninety percent performance improvement in trajectory tracking errors, while improvement using unshaped methods merely achieve a twenty-four percent improvement in direct comparison (where the only modification is the proposed control methodology). Based on superior performance, single-sinusoidal trajectory shaping is recommended, with a corollary benefit of preparing future research into applying deterministic artificial intelligence whose current instantiation relies on single-sinusoidal, autonomous trajectory generation.

Huifang Lian, Huifang Lian, Huifang Lian et al.

PurposeFungal keratitis is a sight-threatening corneal infection caused by fungal pathogens, and the pathogenic mechanisms have not been fully elucidated. The aim of this study was to determine whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis contributes to Candida albicans (C. albicans) keratitis and explore the underlying mechanism.MethodsAn in vivo mouse model of C. albicans keratitis and an in vitro culture model of human corneal epithelial cells (HCECs) challenged with heat-killed C. albicans (HKCA) were established in this study. The degree of corneal infection was evaluated by clinical scoring. Gene expression was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis or immunofluorescence staining was performed to evaluate protein expression. TdT-mediated dUTP nick end labeling (TUNEL) staining was performed to examine the pyroptotic cell death. A lactate dehydrogenase (LDH) release assay was performed to assess cytotoxicity.ResultsCompared with the mock-infected group, we observed that the mRNA levels of NLRP3, caspase-1 (CASP1), interleukin (IL)−1β and gasdermin-D (GSDMD) in C. albicans-infected mice cornea was significantly increased. Our data also demonstrated that the protein expression of NLRP3 and the pyroptosis-related markers apoptosis-associated speck-like protein containing a CARD (ASC), cleaved CASP1, N-GSDMD, cleaved IL-1β and cleaved IL-18 as well as pyroptotic cell death were dramatically elevated in the mouse model of C. albicans keratitis. More importantly, NLRP3 knockdown markedly alleviated pyroptosis and consequently reduced corneal inflammatory reaction in C. albicans keratitis. In vitro, the presence of activated NLRP3 inflammasome and pyroptotic cell death were validated in HCECs exposed to HKCA. Furthermore, the potassium (K+) channel inhibitor glyburide decreased LDH release and suppressed NLRP3 inflammasome activation and pyroptosis in HCECs exposed to HKCA.ConclusionIn conclusion, the current study revealed for the first time that NLRP3 inflammasome activation and pyroptosis occur in C. albicans-infected mouse corneas and HCECs. Moreover, NLRP3 inflammasome-mediated pyroptosis signaling is involved in the disease severity of C. albicans keratitis. Therefore, This NLRP3 inflammasome-dependent pathway may be an attractive target for the treatment of fungal keratitis.

Tong Zhou, Yong-Hua Sang, Shang Cai et al.

Abstract POLRMT (RNA polymerase mitochondrial) is responsible for the transcription of mitochondrial genome encoding key components of oxidative phosphorylation. This process is important for cancer cell growth. The current study tested expression and potential functions of POLRMT in non-small cell lung cancer (NSCLC). TCGA cohorts and the results from the local lung cancer tissues showed that POLRMT is overexpressed in human lung cancer tissues. In both primary human NSCLC cells and A549 cells, POLRMT silencing (by targeted lentiviral shRNAs) or knockout (through CRSIPR/Cas9 gene editing method) potently inhibited cell viability, proliferation, migration, and invasion, and induced apoptosis activation. On the contrast, ectopic overexpression of POLRMT using a lentiviral construct accelerated cell proliferation and migration in NSCLC cells. The mtDNA contents, mRNA levels of mitochondrial transcripts, and subunits of respiratory chain complexes, as well as S6 phosphorylation, were decreased in POLRMT-silenced or -knockout NSCLC cells, but increased after ectopic POLRMT overexpression. In vivo, intratumoral injection of POLRMT shRNA adeno-associated virus (AAV) potently inhibited NSCLC xenograft growth in severe combined immune deficiency mice. The mtDNA contents, mRNA levels of mitochondria respiratory chain complex subunits, and S6 phosphorylation were decreased in POLRMT shRNA AAV-injected NSCLC xenograft tissues. These results show that POLRMT is a novel and important oncogene required for NSCLC cell growth in vitro and in vivo.

Roni O Maimon-Mor, Tamar R Makin

The potential ability of the human brain to represent an artificial limb as a body part (embodiment) has been inspiring engineers, clinicians, and scientists as a means to optimise human-machine interfaces. Using functional MRI (fMRI), we studied whether neural embodiment actually occurs in prosthesis users' occipitotemporal cortex (OTC). Compared with controls, different prostheses types were visually represented more similarly to each other, relative to hands and tools, indicating the emergence of a dissociated prosthesis categorisation. Greater daily life prosthesis usage correlated positively with greater prosthesis categorisation. Moreover, when comparing prosthesis users' representation of their own prosthesis to controls' representation of a similar looking prosthesis, prosthesis users represented their own prosthesis more dissimilarly to hands, challenging current views of visual prosthesis embodiment. Our results reveal a use-dependent neural correlate for wearable technology adoption, demonstrating adaptive use-related plasticity within the OTC. Because these neural correlates were independent of the prostheses' appearance and control, our findings offer new opportunities for prosthesis design by lifting restrictions imposed by the embodiment theory for artificial limbs.

Guy Karlebach, Peter Hansen, Diogo FT Veiga et al.

Abstract We present Hierarchical Bayesian Analysis of Differential Expression and ALternative Splicing (HBA-DEALS), which simultaneously characterizes differential expression and splicing in cohorts. HBA-DEALS attains state of the art or better performance for both expression and splicing and allows genes to be characterized as having differential gene expression, differential alternative splicing, both, or neither. HBA-DEALS analysis of GTEx data demonstrated sets of genes that show predominant DGE or DAST across multiple tissue types. These sets have pervasive differences with respect to gene structure, function, membership in protein complexes, and promoter architecture.

Gábor Valcz, Edit I. Buzás, Ágnes Kittel et al.

Small extracellular vesicles (EVs) are membrane enclosed structures that are usually released from cells upon exocytosis of multivesicular bodies (MVBs) as a collection of separate, free EVs. In this study, we analysed paraffin embedded sections of archived human colorectal cancer samples. We studied 3D reconstructions of confocal microscopic images complemented by HyVolution and STED imaging. Unexpectedly, we found evidence that large, MVB-like aggregates of ALIX/CD63 positive EV clusters were released en bloc by migrating tumour cells. These structures were often captured with partial or complete extra-cytoplasmic localization at the interface of the plasma membrane of the tumour cell and the stroma. Their diameter ranged between 0.62 and 1.94 μm (mean±S.D.: 1.17 ± 0.34 μm). High-resolution 3D reconstruction showed that these extracellular MVB-like EV clusters were composed of distinguishable internal particles of small EV size (mean±S.D.: 128.96 ± 16.73 nm). In vitro, HT29 colorectal cancer cells also showed the release of similar structures as confirmed by immunohistochemistry and immune electron microscopy. Our results provide evidence for an en bloc transmission of MVB-like EV clusters through the plasma membrane. Immunofluorescent-based detection of the MVB like small EV clusters in archived pathological samples may represent a novel and unique opportunity which enables analysis of EV release in situ in human tissues.

Julianna Bozler, Balint Z Kacsoh, Giovanni Bosco

Rapid or even anticipatory adaptation to environmental conditions can provide a decisive fitness advantage to an organism. The memory of recurring conditions could also benefit future generations; however, neuronally-encoded behavior isn’t thought to be inherited across generations. We tested the possibility that environmentally triggered modifications could allow ‘memory’ of parental experiences to be inherited. In Drosophila melanogaster, exposure to predatory wasps leads to inheritance of a predisposition for ethanol-rich food for five generations. Inhibition of Neuropeptide-F (NPF) activates germline caspases required for transgenerational ethanol preference. Further, inheritance of low NPF expression in specific regions of F1 brains is required for the transmission of this food preference: a maternally derived NPF locus is necessary for this phenomenon, implicating a maternal epigenetic mechanism of NPF-repression. Given the conserved signaling functions of NPF and its mammalian NPY homolog in drug and alcohol disorders, these observations raise the intriguing possibility of NPY-related transgenerational effects in humans.

Jason Liang, Bin-Zhong Li, Alexander P Tan et al.

Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.

L.B. CARVALHO, M.D.C. PEREIRA, P.E.V. BORGES et al.

RESUMO A adubação fosfatada pode influenciar a resposta das culturas tolerantes ao glyphosate em razão de a absorção ativa do herbicida ser mediada por carreadores de fosfato. O objetivo desta pesquisa foi analisar características de crescimento de plantas de milho RR e soja RR quando submetidas à aplicação de glyphosate e de adubo fosfatado. O primeiro experimento foi realizado variando as doses de glyphosate (720 a 1.440 g e.a. ha-1) e de superfosfato triplo (54 a 162 kg ha-1 de P2O5) adicional à adubação recomendada. O segundo experimento foi realizado variando as mesmas doses de glyphosate e com adubação fosfatada (162 kg ha-1 de P2O5) ou não, mantendo-se a testemunha sem aplicação do herbicida e do adubo. Para ambas as culturas, altura e massa seca foram influenciadas pelos tratamentos, e o número de folhas não foi afetado. A resposta das plantas de milho e soja, quanto à altura e à massa seca, foi contrária com a aplicação de glyphosate e de superfosfato triplo; enquanto o crescimento das plantas de soja foi afetado negativamente, plantas de milho aumentaram seu crescimento quando expostas ao glyphosate em substrato com elevada adubação fosfatada (162 kg ha-1 de P2O5).

Sofia M. da Silva, Catarina Amaral, Susana S. Neves et al.

Desulfovibrio gigas belongs to the group of sulfate reducing bacteria (SRB). These ubiquitous and metabolically versatile microorganisms are often exposed to reactive nitrogen species (RNS). Nonetheless, the mechanisms and regulatory elements involved in nitrosative stress protection are still poorly understood. The transcription factor HcpR has emerged as a putative regulator of nitrosative stress response among anaerobic bacteria. HcpR is known to orchestrate the expression of the hybrid cluster protein gene,hcp, proposed to be involved in cellular defense against RNS. According to phylogenetic analyses, the occurrence ofhcpR paralog genes is a common feature among severalDesulfovibrio species. Within theD. gigas genome we have identified two HcpR‐related sequences. One of these sequences,hcpR1, was found in the close vicinity of thehcp gene and this finding prompted us to proceed with its functional characterization. We observed that the growth of aD. gigas strain lackinghcpR1 is severely impaired under nitrosative stress. Anin silico search revealed several putative targets of HcpR1 that were experimentally validated. The fact that HcpR1 regulates several genes encoding proteins involved in nitrite and nitrate metabolism, together with the sensitive growth phenotype to NO displayed by anhcpR1 mutant strain, strongly supports a relevant role of this factor under nitrosative stress. Moreover, the finding that severalDesulfovibrio species possess HcpR paralogs, which have been transmitted vertically in the evolution and diversification of the genus, suggests that these sequences may confer adaptive or survival advantage to these organisms, possibly by increasing their tolerance to nitrosative stress.

L.G.S. Assunção, S.M. Eloi-Santos, S.V. Peixoto

The measurement of the serum concentration of the acute-phase reactant C-reactive protein (CRP) provides a useful marker in clinical practice. However, the distribution of CRP is not available for all age and population groups. This study assessed the distribution of high sensitivity-CRP (hs-CRP) by gender and age in 1470 elderly individuals from a Brazilian community that participates in the Bambuí Cohort Study. Blood samples were collected after 12 h of fasting and serum samples were stored at -70°C. Measurements were made with a commercial hs-CRP immunonephelometric instrument. More than 50% of the results were above 3.0 mg/L for both genders. Mean hs-CRP was higher in women (3.62 ± 2.58 mg/L) than in men (3.03 ± 2.50 mg/L). This difference was observed for all ages, except for the over-80 age group. This is the first population-based study to describe hs-CRP values in Latin American elderly subjects. Our results indicate that significant gender differences exist in the distribution of hs-CRP, and suggest that gender-specific cut-off points for hs-CRP would be necessary for the prediction of cardiovascular risks.

Auriemma Lauren B, Shah Shaili, Linden Lara M et al.

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor menin (<it>MEN1</it>) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (<it>IRF1)</it>, and is further recruited when <it>IRF1 </it>transcription is triggered by interferon-γ signaling.</p> <p>Results</p> <p>RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at <it>IRF1</it>. While MEN1 knockdown does not impact the rate of transcription, <it>IRF1 </it>heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the <it>IRF1 </it>promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with <it>IRF1</it>, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.</p> <p>Conclusions</p> <p>Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.</p>

Larsson Ola, Sandberg Rickard

<p>Abstract</p> <p>Background</p> <p>Microarrays enable high throughput detection of transcript expression levels. Different investigators have recently introduced updated probe set definitions to more accurately map probes to our current knowledge of genes and transcripts.</p> <p>Results</p> <p>We demonstrate that updated probe set definitions provide both better precision and accuracy in probe set estimates compared to the original Affymetrix definitions. We show that the improved precision mainly depends on the increased number of probes that are integrated into each probe set, but we also demonstrate an improvement when the same number of probes is used.</p> <p>Conclusion</p> <p>Updated probe set definitions does not only offer expression levels that are more accurately associated to genes and transcripts but also improvements in the estimated transcript expression levels. These results give support for the use of updated probe set definitions for analysis and meta-analysis of microarray data.</p>