Many bacterial type I toxin mRNAs possess a long 5΄ untranslated region (UTR) that serves as the target site of the corresponding antitoxin sRNA. This is the case for the zorO-orzO type I system where the OrzO antitoxin base pairs to the 174-nucleotide zorO 5΄ UTR. Here, we demonstrate that the full-length 5΄ UTR of the zorO type I toxin hinders its own translation independent of the sRNA whereas a processed 5΄ UTR (zorO Δ28) promotes translation. The full-length zorO 5΄ UTR folds into an extensive secondary structure sequestering the ribosome binding site (RBS). Processing of the 5΄ UTR does not alter the RBS structure, but opens a large region (EAP region) located upstream of the RBS. Truncation of this EAP region impairs zorO translation, but this defect can be rescued upon exposing the RBS. Additionally, the region spanning +35 to +50 of the zorO mRNA is needed for optimal translation of zorO. Importantly, the positive and negative effects on translation imparted by the 5΄ UTR can be transferred onto a reporter gene, indicative that the 5΄ UTR can solely drive regulation. Moreover, we show that the OrzO sRNA can inhibit zorO translation via base pairing to the of the EAP region.
Chromosomally encoded toxin-antitoxin systems have been increasingly identified and characterized across bacterial species over the past two decades. Overproduction of the toxin gene results in cell growth stasis or death for the producing cell, but co-expression of its antitoxin can repress the toxic effects. For the subcategory of type I toxin-antitoxin systems, many of the described toxin genes encode a small, hydrophobic protein with several charged residues distributed across the sequence of the toxic protein. Though these charged residues are hypothesized to be critical for the toxic effects of the protein, they have not been studied broadly across different type I toxins. Herein, we mutated codons encoding charged residues in the type I toxin zorO, from the zor-orz toxin-antitoxin system, to determine their impacts on growth inhibition, membrane depolarization, ATP depletion, and the localization of this small protein. The non-toxic variants of ZorO accumulated both in the membrane and cytoplasm, indicating that membrane localization alone is not sufficient for its toxicity. While mutation of a charged residue could result in altered toxicity, this was dependent not only on the position of the amino acid within the protein but also on the residue to which it was converted, suggesting a complex role of charged residues in ZorO-mediated toxicity. A previous study indicated that additional copies of the zor-orz system improved growth in aminoglycosides: within, we note that this improved growth is independent of ZorO toxicity. By increasing the copy number of the zorO gene fused with a FLAG-tag, we were able to detect the protein expressed from its native promoter elements: an important step for future studies of toxin expression and function.
Type I toxin-antitoxin loci consist of two genes: a small, hydrophobic, potentially toxic protein, and a small RNA (sRNA) antitoxin. The sRNA represses toxin gene expression by base pairing to the toxin mRNA. A previous bioinformatics search predicted a duplicated type I locus within Escherichia coli O157:H7 (EHEC), which we have named the gene pairs zorO-orzO and zorP-orzP. We show that overproduction of the zorO gene is toxic to E. coli; co-expression of the sRNA OrzO can neutralize this toxicity, confirming that the zorO-orzO pair is a true type I toxin-antitoxin locus. However, OrzO is unable to repress zorO in a strain deleted for RNase III, indicating that repression requires cleavage of the target mRNA. Sequence analysis and mutagenesis studies have elucidated a nucleotide sequence region (V1) that allows differential recognition of the zorO mRNA by OrzO and not OrzP, and a specific single nucleotide within the V1 of OrzO that is critical for repression of zorO. Although there are 18 nt of complementarity between the OrzO sRNA and the zorO mRNA, not all base pairing interactions are needed for repression; however, the amount needed is dependent on whether there is continuous or discontinuous complementarity to the target mRNA.
Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in Escherichia coli O157:H7 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. However, little is known about its inhibitory mechanism. In this study, we demonstrate that the ZorO localized in the inner membrane affects the plasma membrane integrity and potential when expressed in E. coli cells, which triggers the production of cytotoxic hydroxyl radicals. We further show that five internal amino acids (Ala-Leu-Leu-Arg-Leu; ALLRL) of ZorO are necessary for its toxicity. This result prompted us to address the potential of the synthetic ALLRL peptide as an antimicrobial. Exogenously-added ALLRL peptide to Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a fungus, Candida albicans, trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, E. coli. The ALLRL peptide retains its activity under the physiological salt concentrations, which is in contrast to natural antimicrobial peptides. Importantly, this peptide has no toxicity against mammalian cells. Taken together, an effective and short peptide, ALLRL, would be an attractive antimicrobial to Gram-positive bacteria and C. albicans.
In an open, prospective study in 27 Swiss neurological practices and polyclinics, the fastmelt formulation of zolmitriptan was tested in 113 migraine patients as a therapeutic agent for migraine attacks (ZORO [= Zomig oro] Studie). A total of 311 attacks with and without aura were analyzed. With the help of a structured diary, the patients documented each attack in detail by recording the time of onset of the migraine, the intensity, when the medication was taken, the duration of the migraine, concomitant symptoms, concurrent medication and adverse effects. The subjective onset of effect was reached within 60 minutes in 56% of the cases, and within two hours in 73%. The pain intensity was determine with a visual analog pain scale from 1 to 10. The effect, defined by a decline in pain of two or more levels, was achieved within two hours in 68% of the attacks (ITT population). An average of 34% of the ITT patients achieved complete freedom from pain within 120 minutes. The meaningful migraine relief (MMR), defined as a marked improvement in well-being, was achieved within 120 minutes in 59% of all attacks, and after > 2 hours another 34% achieved this state. A decline of approximately 50% in intensity of the concomitant symptoms of nausea, photophobia and phonophobia within two hours was measured on a 10-point visual analog scale (0 = no symptoms; 10 = extremely severe symptoms). After the initial therapeutic effect, migraine recurrences occurred within 4-24 hours after intake of medication in 22% of the cases on the average. The known adverse effects caused by triptan were reported by 17% of the patients. Most of them did not lead to termination of treatment, and none of the more severe adverse effects were reported. In the patient diary, the study participants were also asked about the time of onset of the migraine and the time of taking the medication, in the assumption that this interval would be relatively short from the standpoint of ideal fabrication of the preparation. Surprisingly, despite the fact that patients were instructed by the study neurologists to take the medication as promptly as possible at the onset of an attack, the patients waited a median of 90 minutes after the onset of the migraine (n = 308 attacks) before taking the triptan. In the visual 10-point scale, this time increased the average pain intensity from a median of 5.0 to 6.0. There are various reasons that may explain this unexpected behavior (the experience of many migraine patients that attacks often subside spontaneously within a short period of time; the difficulty of distinguishing an incipient migraine from a tension headache, etc.). Further research will be necessary to clarify this situation. With regard to efficacy in headaches, concomitant autonomic symptoms, rapid onset of effect, and acceptance, this fastmelt triptan formulation represents real competition with the other triptans in the usual tablet formulation. It is especially suitable for active migraine patients who would like to have an effective therapeutic agent available for rapid use in all life situations.
Observational studies suggested that luteinizing hormone-releasing hormone agonists (LHRHa) might prevent premature ovarian failure resulting from adjuvant chemotherapy in premenopausal patients. We aimed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer. In a prospective, randomized, open-label, controlled multicenter study, 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide (with or without taxane) -based neoadjuvant chemotherapy with or without goserelin. The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle, continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle. The primary objective was the reappearance of normal ovarian function, defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy. Fifty-three patients (88.3%) experienced temporary amenorrhea (93.3% with v 83.3% without goserelin). No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy (70.0% with v 56.7% without goserelin; difference of 13.3%; 95% CI, -10.85 to 37.45; P = .284). All but one evaluable patient reported regular menses at 2 years after chemotherapy. Time to restoration of menstruation was 6.8 months (95% CI, 5.2 to 8.4) with goserelin and 6.1 months (95% CI, 5.3 to 6.8) without goserelin (P = .304). Chemotherapy resulted in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up, supporting the other findings. Premenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone.
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Charcoal rot, a disease caused by the soilborne fungus Macrophomina phaseolina, affects a broad range of host plants globally. The disease has been reported on soybean in New York (NY) (Cummings et al. 2013), however, there have been no previous reports of M. phaseolina infecting dry bean (Phaseolus vulgaris) in NY. In August 2024, dry bean roots were collected from a research plot at Musgrave Research Farm in Aurora, NY (42.73422° N, 76.65898° W) to identify potential root rot pathogens. Affected roots showed characteristic symptoms of charcoal rot, including dark lesions on the lower stem and root tissue and a dry rot of the cortex. Signs of fungal growth were also present on the diseased roots including numerous black microsclerotia. Symptomatic root tissues were surface sterilized (10% sodium hypochlorite for one minute), rinsed three times with sterile distilled water and placed on Petri plates with 2% water agar with ampicillin (1 mg/l), then incubated at 18°C. After three to four days, hyphal tips were transferred to potato dextrose agar (PDA) and incubated at room temperature in the dark for 10 days. Colonies were initially hyaline, later developing a gray to black pigmentation. Microsclerotia were abundant, globose to oblong, consistent with morphological descriptions of M. phaseolina (Smith and Wyllie, 1999). Three isolates (2024_34, 2024_38, and 2024_40) were selected for further characterization. The internal transcribed spacer (ITS) region was amplified using primers ITS1/ITS4 (White et al. 1990), and calmodulin (CAL) and translation elongation factor (TEF1-α) genes were amplified using M. phaseolina-specific primers MpCalF/MpCalR and MpTefF/MpTefR, respectively (Santos et al. 2020). BLASTn analysis revealed 100% identity with reference M. phaseolina sequences in the NCBI GenBank database. The sequences of the three isolates were deposited in GenBank under the following accession numbers: Isolate 2024_34 - PV605619 (ITS), PV626632 (CAL), PV613809 (TEF1-α); Isolate 2024_38 - PV605620 (ITS), PV640550 (CAL), PV613810 (TEF1-α); Isolate 2024_40 - PV605624 (ITS), PV640551 (CAL), PV613811 (TEF1-α). A maximum likelihood tree based on concatenated ITS, CAL, and TEF1-α sequences constructed using RAxML v.8.2.11 with the GTR + gamma substitution model (Stamatakis, 2014) placed the three isolates within the M. phaseolina clade. Pathogenicity tests were conducted using dry bean cv. 'Zoro'. Four seeds per 15-20 cm pot were planted, with five replicates for each treatment: inoculated and non-inoculated control. Inoculum consisted of 10 g of a macerated, 12-day-old M. phaseolina culture grown on PDA, applied using an inoculum layering technique. The non-inoculated control plots received the same amount of sterile and noncolonized PDA. Plants were maintained in a greenhouse at 28/17°C (day/night), with a 13-h light/11-h dark cycle and 70% relative humidity. Inoculated plants showed symptoms (root browning, dry rot) within five to six weeks post-inoculation, while non-inoculated controls remained asymptomatic. The pathogen was reisolated and confirmed as M. phaseolina based on morphology, completing Koch's postulates. Pathogenicity tests were repeated twice for all three isolates. This report confirms the occurrence of charcoal rot caused by M. phaseolina on dry bean in NY and highlights the need for surveillance and integrated disease management to mitigate its potential impact in the northeastern region of the United States.
Bacterial chromosomal type I toxin-antitoxin systems consist of a small protein, typically under 60 amino acids, and a small RNA (sRNA) that represses toxin translation. These gene pairs have gained attention over the last decade for their contribution to antibiotic persistence and phage tolerance in bacteria. However, biological functions for many remain elusive as gene deletions often fail to produce an observable phenotype. For many pairs, it is still unknown when the toxin and/or antitoxin gene are natively expressed within the bacterium. We examined sequence conservation of three type I toxin-antitoxin systems, tisB/istR-1, shoB/ohsC, and zor/orz, in over 2,000 Escherichia coli strains, including pathogenic and commensal isolates. Using our custom database, we found that these gene pairs are widespread across E. coli and have expression potential via BLASTn. We identified an alternative, dominant sequence variant of TisB and confirmed that it is toxic upon overproduction. Additionally, analyses revealed a highly conserved sequence in the zorO mRNA untranslated region that is required for full toxicity. We further noted that over 30% of E. coli genomes contain an orz antitoxin gene only and confirmed its expression in a representative strain: the first confirmed report of a type I antitoxin without its cognate toxin. Our results add to our understanding of these systems, and our methodology is applicable for other type I loci to identify critical regulatory and functional features.IMPORTANCEChromosomal type I toxin-antitoxins are a class of genes that have gained increasing attention over the last decade for their roles in antibiotic persistence which may contribute to therapeutic failures. However, the control of many of these genes and when they function have remained elusive. We demonstrate that a simple genetic conservation-based approach utilizing free, publicly available data yields known and novel insights into the regulation and function of three chromosomal type I toxin-antitoxins in Escherichia coli. This study also provides a framework for how this approach could be applied to other genes of interest.
Type I toxin-antitoxin systems consist of a small protein (under 60 amino acids) whose overproduction can result in cell growth stasis or death, and a small RNA that represses translation of the toxin mRNA. Despite their potential toxicity, type I toxin proteins are increasingly linked to improved survival of bacteria in stressful environments and antibiotic persistence. While the interaction of toxin mRNAs with their cognate antitoxin sRNAs in some systems are well characterized, additional translational control of many toxins and their biological roles are not well understood. Using an ectopic overexpression system, we show that the efficient translation of a chromosomally encoded type I toxin, ZorO, requires mRNA processing of its long 5' untranslated region (UTR; Δ28 UTR). The severity of ZorO induced toxicity on growth inhibition, membrane depolarization, and ATP depletion were significantly increased if expressed from the Δ28 UTR versus the full-length UTR. ZorO did not form large pores as evident via a liposomal leakage assay, in vivo morphological analyses, and measurement of ATP loss. Further, increasing the copy number of the entire zor-orz locus significantly improved growth of bacterial cells in the presence of kanamycin and increased the minimum inhibitory concentration against kanamycin and gentamycin; however, no such benefit was observed against other antibiotics. This supports a role for the zor-orz locus as a protective measure against specific stress agents and is likely not part of a general stress response mechanism. Combined, these data shed more insights into the possible native functions for type I toxin proteins. IMPORTANCE Bacterial species can harbor gene pairs known as type I toxin-antitoxin systems where one gene encodes a small protein that is toxic to the bacteria producing it and a second gene that encodes a small RNA antitoxin to prevent toxicity. While artificial overproduction of type I toxin proteins can lead to cell growth inhibition and cell lysis, the endogenous translation of type I toxins appears to be tightly regulated. Here, we show translational regulation controls production of the ZorO type I toxin and prevents subsequent negative effects on the cell. Further, we demonstrate a role for zorO and its cognate antitoxin in improved growth of E. coli in the presence of aminoglycoside antibiotics.
The root-knot nematodes (Meloidogyne spp.) are considered one of the most destructive diseases in the world. In Egypt, farmers primarily rely on chemical nematicides, which have become costly to control. Currently, abamectin is a bio-based pesticide used as an alternative tool against Meloidogyne spp. on cucumber plants (Cucumis sativus L.). During the current research, four tested abamectin formulations were DIVA (1.8% EW), RIOMECTIN (5% ME), AGRIMEC GOLD (8.4% SC) and ZORO (3.6% EC) compared with two reference nematicides namely, CROP NEMA (5% CS) and TERVIGO (2% SC). The main results showed that, in vitro study elucidated that the most effective formulations of abamectin as a larvicidal were EW with LC50 value of 21.66 µg ml-1. However, in the egg hatching test, the formulations of abamectin SC (2%) and EW were the most effective in reducing egg hatching, with LC50 values of 12.83 and 13.57 µg ml-1. The calculated relative potency values showed diversity depending on the two referenced nematicides. On the other hand, in vivo study, the results indicated that, all tested formulations of abamectin recorded general mean reductions in root galls (23.05-75.23%), egg masses (14.46-65.63%). Moreover, the total population density declined by 39.24-87.08%. Furthermore, the influence of abamectin formulations, in the presence of root-knot nematodes, on the growth of cucumber plants parameters, such as root dry weight, root length, root radius, root surface area, shoot dry weight and shoot height, as well as the content of macro-elements (N, P and K) exhibited varying levels of response.
Sixty chemical immobilizations of red deer (Cervus elaphus hippelaphus) have been carried out during an etho-ecological study from August 1994 to December 1996 in a 35 ha pen in the district of Nitra (Slovac Republic). Our objective was to determine the efficacy and standard dosages of Zoletil and Rompun for the immobilization of adult red deer in feral conditions as an alternative to the use of the highly toxic opioids. We therefore compared an Immobilon-Rompun combination (ImRo) with a 1:1 mixture of Zoletil and Rompun (ZoRo) as an injectable solution. Use of both combinations led to the immobilization of >92% of deer with an injection volume <3 ml. Mean (SD) dose to achieve immobilization was 35 (14) microg/kg ethorphine + 0.14 (0.056) mg/kg acepromazine + 0.36 (0.14) mg/kg xylazine compared to 1.2 (0.8) mg/kg tiletamine + 1.2 (0.8) mg/kg zolazepam + 2.3 (1.6) mg/kg xylazine. This corresponds to a volume of 1.8 (0.7) ml/100 kg body mass (BM) for ImRo (range = 1.0 to 4.6) and to 2.3 (1.6) ml/100 kg BM for ZoRo (range = 0.7 to 4.0), respectively. Heart rate, respiratory rate and oxyhaemoglobin saturation values did not differ significantly between the two groups during immobilization. Three deer (5%) died during immobilization, but fatalities could not be directly associated with the drug effect. Mean (SD) time from darting to complete immobilization was 5.5 (4.2) min for ImRo and 7.5 (6.1) min for ZoRo, respectively. Differences were not statistically significant. Anesthesia with both combinations of immobilizing agents could be reversed within 2 min using sarmazenile-yohimbine for ZoRo and diprenorphine-yohimbine for ImXy immobilizations, respectively. We conclude that the 1:1 combination of Zoletil and xylazine is a valuable alternative to the use of opioids for the immobilization of adult red deer including feral adult animals.
Currently, no single best primary endpoint exists for measuring the efficacy of treatments in seriously ill patients with respiratory infections, such as influenza, who require hospitalization. The Hospital Recovery Scale is an ordinal endpoint used to evaluate treatment outcomes in clinical studies of hospitalized patients infected with influenza. To determine whether Hospital Recovery Scale outcomes correspond to those for other clinical endpoints in patients hospitalized due to influenza, data from the phase 3 randomized, double-blind ZORO clinical trial (NCT01231620) were analyzed. Randomized influenza-infected patients were divided into subgroups of interest based on prespecified baseline and infection-related characteristics, as well as randomized treatment arms (intravenous zanamivir 300 mg or 600 mg, or oral oseltamivir 75 mg). Clinical endpoints relevant to this population were included to analyze differences in outcomes between the subgroups, and correspondence of these endpoints and hospital recovery endpoint was evaluated. Data from 488 patients were analyzed. There were strong correlations (ρs > 0.8) between the Hospital Recovery Scale assessed on the day after completion of a 5-day antiviral therapy (Day 6) and both time to hospital discharge and time to intensive care unit discharge, and moderate to strong correlations (0.6 < ρs < 0.8) between the Hospital Recovery Scale on Day 6 and several other relevant clinical endpoints. The Hospital Recovery Scale is applicable as a primary endpoint in trials to evaluate new therapies for severely ill patients hospitalized due to influenza, and may have utility in other severe respiratory illnesses such as COVID-19.
Recently reported data from the German ZORO trial and the Italian PROMISE-GIM6 trial have come to different conclusions. The AGO Breast Commission does not recommend the general use of luteinizing hormone-releasing hormone (LHRH) analogues for the preservation of ovarian function. Instead, we distinguish between patients with hormone receptor-negative and hormone receptor-positive disease. This article reviews the AGO recommendations in light of the ZORO and PROMISE-GIM6 data. In conclusion, separate recommendations are needed for the prevention of ovarian failure and for fertility preservation because the trials did not investigate fertility rate as a primary outcome measure. The results from not yet published trials such as OPTION and POEM may shed new light on the role of LHRH analogues. Kürzlich publizierte Daten der deutschen ZORO-Studie und der italienischen PROMISE-GIM6-Studie kommen zu unterschiedlichen Ergebnissen. In den aktuellen Leitlinien der AGO Kommission Mamma wird die generelle Gabe eines GnRH (gonadotropin-releasing hormone)-Analogons zum Erhalt der Ovarfunktion nicht empfohlen. Es wird aber unterschieden, ob die Patientin ein hormonrezeptorpositives oder -negatives Mammakarzinom hat. Der vorliegende Artikel beleuchtet die Empfehlungen noch einmal im Licht der aktuellen Daten. Zusammenfassend kann man sagen, dass der Erhalt der Ovarfunktion nicht mit dem Erhalt der Fertilität gleichgesetzt werden darf und es daher auch unterschiedliche Vorgehensweisen geben sollte. Daten aus anderen Studien wie OPTION und POEM werden sicherlich noch einmal die Rolle der GnRH-Analoga anders beurteilen.
In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation.
Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.
Hepatitis B infection and disease are highly endemic in South America. Prevalences of positivity are particularly high in Amazonia, and among Amerindian peoples in particular. This paper reports the results of a seroepidemiological survey for hepatitis B virus (HBV) carried out among four Amerindian populations from the Brazilian Amazon region: Gavião, Surui, Zoro and Navate. Rates of positivity to HBV serological markers (HBsAg, anti-HBs and or anti-HBc) are very high for the four groups, ranging from 62.8 to 95.7%. It is argued that the high rates of positivity in the Amerindian groups dealt with in this study, as well as for other Amazonian populations, are related to a complex of cultural practices which enhance the likelihood of HBV transmission (bloodletting, scarification, tattooing and orally processed food, among others). The authors suggest that, due to unique patterns of interaction between sociocultural and environmental factors. HBV infection assumes a specific profile in native Amazonian societies.
This work presents the Protein Association Analyzer (PRASA) (http://zoro.ee.ncku.edu.tw/prasa/) that predicts protein interactions as well as interaction types. Protein interactions are essential to most biological functions. The existence of diverse interaction types, such as physically contacted or functionally related interactions, makes protein interactions complex. Different interaction types are distinct and should not be confused. However, most existing tools focus on a specific interaction type or mix different interaction types. This work collected 7234058 associations with experimentally verified interaction types from five databases and compiled individual probabilistic models for different interaction types. The PRASA result page shows predicted associations and their related references by interaction type. Experimental results demonstrate the performance difference when distinguishing between different interaction types. The PRASA provides a centralized and organized platform for easy browsing, downloading and comparing of interaction types, which helps reveal insights into the complex roles that proteins play in organisms.
In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. This work presents the CCProf platform, which provides conformational changes of entire proteins, named conformational change profile (CCP) in the context. CCProf aims to be a platform where users can study potential causes of novel conformational changes. It provides 10 biological features, including conformational change, potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view, so that researchers can capture important relevance between different biological features visually. The CCProf contains 986,187 protein structure pairs for 3123 proteins. In addition, CCProf provides a 3D view in which users can see the protein structures before and after conformational changes as well as binding targets that induce conformational changes. All information (e.g. CCP, binding targets and protein structures) shown in CCProf, including intermediate data are available for download to expedite further analyses. Database URL:http://zoro.ee.ncku.edu.tw/ccprof/.
The Malagasy ponerine Pachycondyla sikorae-group is revised and a worker-based key to species is presented. Fourteen species are recognised, of which 13 are described as new. The species group is redefined and divided into two species complexes: the sikorae-complex (P. gorogota sp. n., P. haratsingy sp. n., P. ivolo sp. n., P. maeva sp. n., P. mialy sp. n., P nosy sp. n. and P. sikorae Forel) and the vohitravo-complex (P. agnivo sp. n., P. antsiraka sp. n., P. daraina sp. n., P. rovana sp. n., P. tahary sp. n., P. vohitravo sp. n. and P. zoro sp. n.). All 14 species are endemic to Madagascar and distributed across the rainforests in the east and the transitional humid habitats in the northwest of Madagascar. Distribution maps of each species are included.