Biodegradation of polystyrene nanoplastics by Achromobacter xylosoxidans M9 offers a mealworm gut-derived solution for plastic pollution.

Nanoplastics pose significant environmental problems due to their high mobility and increased toxicity. These particles can cause infertility and inflammation in aquatic organisms, disrupt microbial signaling and act as pollutants carrier. Despite extensive studies on their harmful impact on living organisms, the microbial degradation of nanoplastics is still under research. This study investigated the degradation of nanoplastics by isolating bacteria from the gut microbiome of Tenebrio molitor larvae fed various plastic diets. Five bacterial strains capable of degrading polystyrene were identified, with Achromobacter xylosoxidans M9 showing significant nanoplastic degradation abilities. Within 6 days, this strain reduced nanoplastic particle size by 92.3%, as confirmed by SEM and TEM analyses, and altered the chemical composition of the nanoplastics, indicating a potential for enhanced bioremediation strategies. The strain also caused a 7% weight loss in polystyrene film over 30 days, demonstrating its efficiency in degrading nanoplastics faster than polystyrene film. These findings might enhance plastic bioremediation strategies.

Multiplex PCR-based genotyping of Salmonella Enteritidis and Salmonella Typhimurium from food sources and assessment of their antimicrobial resistance profiles in Egypt.

BACKGROUND: Salmonellosis is a widespread zoonotic disease that poses a significant threat to livestock and public health. This study aimed to serotype 20 Salmonella isolates obtained from sixty retail chicken meats, assess Salmonella contamination from eggs, and evaluate antibiotic resistance profiles. METHODS AND RESULTS: Twenty eggs were randomly collected in the new Borg El Arab market. Bacterial isolation was carried out utilizing both traditional culture, biochemical, and PCR methods. Among the twenty eggs analyzed, three (15%) tested positive for Salmonella, while the remaining seventeen (85%) were confirmed as negative. Genotyping through multiplex PCR revealed the presence of two S. Enteritidis and other serovar, with the use of three specific gene sets: a random sequence for Salmonella spp., sdfI gene for S. Enteritidis, and flagellin (fliC gene) for S. Typhimurium. Out of the 20 isolates obtained from chicken meat, five (25%) were identified as S. Typhimurium, and three (15%) were classified as S. Enteritidis. All isolates sourced from chicken meat exhibited resistance to Rifampicin and Amoxicillin, with 90% displaying sensitivity to cefotaxime, gemifloxacin, and Erythromycin. Importantly, S. Blegdam, identified via serological methods, displayed resistance to all tested antibiotics. For the three isolates obtained from eggs, 66.6% showed sensitivity to cefotaxime, erythromycin, cefuraxime, and cefaclor, while displaying complete resistance (100%) to Amoxicillin, rifampicin, clarithromycin, and cefadroxil. Notably, one serovar exhibited absolute resistance to all tested drugs. CONCLUSION: Stakeholders must implement strict control measures and rationalize antibiotic use in veterinary and human medicine due to the rise of antibiotic-resistant strains.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expression of oncogenic proteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agents for NSCLC. We used structure-based virtual screening to evaluate 66 antiviral drugs thoroughly. The top 6 antiviral drugs exhibiting impressive binding energies  (i.e. surpassing a threshold of -8.5 kcalmol-1) were identified. Subsequent bioactivity analysis and ADMET profiling were performed to select the most promising candidates, followed by a molecular dynamic simulation. Among the selected antiviral regimens, dolutegravir demonstrated the highest docking score (-9.8 kcalmol-1), followed by rilpivirine and ensitrelvir, surpassing other candidates and our reference EGFR TKI. Further molecular dynamics simulations revealed promising dynamic interactions of dolutegravir, ensitrelvir, and rilpivirine with the EGFR target as compared with afatinib. Our findings highlight the repositioning potential of antiviral drugs for anti-EGFR drug discovery, supported by their robust docking scores, ADMET profiles, dynamic interactions, and binding free energies. The results open up new avenues for advanced NSCLC therapy. Further in vitro investigations are warranted to evaluate their efficacy and safety.

Dual phytoremediation and biochar production by Eichhornia crassipes in hydroponic system receiving different 1,4-dioxane dosages.

This study focuses on applying phytoremediation as a low-effective and simple process to treat wastewater laden with 1,4 dioxane (DIOX). A floating macrophyte (Eichhornia crassipes) was cultivated under hydroponic conditions (relative humidity 50-67%, photoperiod cycle 18:6 h light/dark, and 28-33 °C) and subjected to different DIOX loads between 0.0 (control) and 11.5 mg/g fresh mass (FM). The aquatic plant achieved DIOX and chemical oxygen demand (COD) removal efficiencies of 76-96% and 67-94%, respectively, within 15 days. E. crassipes could tolerate elevated DIOX-associated stresses until a dose of 8.2 mg DIOX/g, which highly influenced the oxidative defense system. Malondialdehyde (MDA) content, hydrogen peroxide (H2O2), and total phenolic compounds (TPC) increased by 7.3, 8.4, and 4.5-times, respectively, in response to operating the phytoremediation unit at a DIOX load of 11.5 mg/g. The associated succulent value, proteins, chlorophyll-a, chlorophyll-b, and pigments dropped by 39.6%, 45.8%, 51.5%, 80.8%, and 55.5%, respectively. The suggested removal mechanism of DIOX by E. crassipes could be uptake followed by phytovolatilization, whereas direct photodegradation from sunlight contributed to about 19.36% of the total DIOX removal efficiencies. Recycling the exhausted E. crassipes for biochar production was a cost-efficient strategy, making the payback period of the phytoremediation project equals to 6.96 yr.

Eichhornia crassipes could be used in phytoremediation of 1,4 dioxane (DIOX)-laden water at DIOX load< 8.2 mg/g FM. E. crassipes removed 77­97% DIOX via uptake and phytovolatilization. Recycling exhausted-plant to produce biochar was cost-efficient with 7 yr-payback period.

Phycoremediation of 1,4 dioxane-laden wastewater: A Techno-economic and sustainable development approach.

Microalgal tolerance to emerging contaminants (ECs) such as 1,4 dioxane (DXN) and its impact on phycoremediation performance, algal growth, biomolecules generated, and recycling the produced biomass for biochar production has been rarely reported. Hence, Chlorella vulgaris was cultivated in DXN-free wastewater (WW1) and 100 mg L-1 DXN-laden wastewater (WW2) in 1-liter photobioreactors with an operating volume of 800 ml under controlled conditions: temperature (25 ± 1 °C), light intensity (351 µmol m-2s-1), and photoperiod (12 h light:12 h dark). Interestingly, this microalgal-based system achieved up to 32.79% removal efficiency of DXN in WW2. In addition, there was no significant difference in the removal of COD (90.6% and 86.8%) and NH4-N (74.5% and 76.8%) between WW1 and WW2, respectively. Moreover, the variation in C. vulgaris growth, pigments, lipid, and carbohydrate contents between the two applied wastewaters was negligible. However, there was a significant increase in the protein yield upon exposure to DXN, suggesting the ability of C. vulgaris to secrete various antioxidant and degrading enzymes to detoxify the contaminant. These results were validated by FTIR, SEM, and EDX analysis of C. vulgaris biomass with and without DXN exposure. The harvested biomass was thermally treated at 350 °C for 60 min in an oxygen-free environment. The biochars generated from both algal systems were characterized by comparable morphologies and elemental profiles with sufficient C and N contents, indicating their applicability to enhance the soil properties. The economic evaluation of the combined phycoremediation/pyrolysis system demonstrated a net profit of 596 USD⋅y-1 with a payback period of 6.2 years and fulfilled the objectives of several sustainable development goals (SDGs). This is the first study to point to C. vulgaris as a robust microalgal strain in remediating DXN-laden wastewater accompanied by the potential recyclability of the biomass produced for biochar production.

Impacts of kinetin implementation on leaves, floral and root-related traits during seed production in hybrid rice under water deficiency.

BACKGROUND: Water deficit is one of the most significant abiotic factors affecting rice and agricultural production worldwide. In hybrid rice, cytoplasmic male sterility (CMS) is an important technique for creating high-yielding crop based on heterosis. The phytohormone kinetin (Kin) regulates cell division in plant during the early stages of grain formation, as well as flow assimilation and osmotic regulation under water stress. The present study performed to estimate the effects of irrigation intervals (irrigation each six days (I6), nine days (I9), twelve days (I12) and fifteen days (I15) against continuous flooding (CF, each three days)) and kinetin exogenously application (control, 15 mg L-1 and 30 mg L-1) on hybrid rice (L1, IR69625A; L2, G46A and R, Giza 178 R) seed production. RESULTS: Leaves traits (Chlorophyll content (CHC), relative water content (RWC), stomatal conductance (SC), Leaf temperature (LT) and transpiration rate (TR)), floral traits such as style length (SL) and total stigma length (TSL), in addition to root traits (i.e., root length (RL), root volume (RV), root: shoot ratio (RSR), root thickness (RT), root xylem vessels number (RXVN) and root xylem vessel area (RXVA) were evaluated and a significant enhancement in most traits was observed. Applying 30 mg L-1 kinetin significantly and positively enhanced all growth, floral and roots traits (RV and RXVA recorded the most increased values by 14.8% and 23.9%, respectively) under prolonging irrigation intervals, in comparison to non-treated plants. CONCLUSIONS: Subsequently, spraying kinetin exogenously on foliar could be an alternative method to reduce the harmful influences of water deficiency during seed production in hybrid rice.

Retention strength of monolithic zirconia crowns cemented with different primer-cement systems.

BACKGROUND: The purpose of this in vitro study was to assess the influence of different cement systems with different ceramic primers on the retention strength of zirconia crowns. METHODS: Thirty extracted molars were prepared with flat occlusal surfaces, 20 degrees taper, and 3 mm axial wall height. A zirconia crown with an occlusal bar was fabricated for each tooth. All specimens were divided (n = 10) into; Group M: Multilink Speed/Monobond N, Group P: Panavia V5/Clearfil Ceramic Primer Plus, Group D: Duo-Link universal/Z-Prime Plus. The intaglio surfaces of crowns were air-abraded using 50 µm alumina at 2.5 bar for 10 s. Then each crown was cemented onto its corresponding tooth. All specimens were thermocycled for 10,000 cycles between 5 and 55 °C. Each crown was subjected to gradually increasing vertical load along the path of insertion through hooks engaging the occlusal bar using a universal testing machine until failure. The force at dislodgment was recorded and retention strength was calculated for each specimen. The failure modes were recorded for each specimen. The data were statistically analyzed using one way ANOVA test followed by Tukey HSD test (α = .05). RESULTS: Group D showed lowest strength (1.42 ± 0.23 MPa) and differed significantly (P < .001) from Group M (2.71 ± 0.45 MPa) and Group P (2.47 ± 0.41 MPa). There was no significant difference (P = .34) between Group M and Group P. The failure modes for Groups M and Group P were mainly cohesive, while Group D showed adhesive failure. CONCLUSIONS: The retention strength of zirconia crowns was improved with Multilink Speed and Panavia V5 cement systems, while the use of the Duo-Link Universal cement system only showed half of those retention strength values.

Clinical and radiographic prospective study of customized one-piece titanium and one-piece fusion-sputtered zirconia implants: five-year mean follow-up.

BACKGROUND: To evaluate the clinical and radiographic assessment of customized fusion-sputtered one-piece zirconia implants. METHODS: Twenty-eight patients received either fusion sputtered one-piece zirconia implants (n = 14) or one-piece titanium implants (n = 14). All implants were one-piece designs. After 4 months of immediate loading, all implants were restored with a monolithic zirconia crown. All implants were evaluated at baseline, 6 months, 1 year, 2 years, and 5 years. Implant mobility, plaque index, and gingival index evaluations were performed. The measurements of marginal bone level were calculated radiographically. RESULTS: All implants were well maintained through the evaluation period with a 100% survival rate without any clinical complications. Regarding gingival index, there was no statistically significant difference (P = .364) between zirconia (3.3 ± 0.7 mm) and titanium (3.5 ± 0.6 mm) implants, after 5 years. There was no statistically significant difference (P = .470) between zirconia (1.77 ± 0.039 mm) and titanium (1.80 ± 0.28 mm) implants regarding marginal bone loss, after 5 years. CONCLUSIONS: One-piece fusion-sputtered zirconia implant represents a reliable treatment modality in replacing a missing tooth in the esthetic zone.

Utilization of genetic diversity and marker-trait to improve drought tolerance in rice (Oryza sativa L.).

Drought stress is one of the main problems for the rice crop, as it reduces the production and productivity of the grain yield significantly. In Egypt, many restrictions were made on the cultivation of rice due to its high-water demand. Producing promising drought-tolerant rice cultivars combined with high yielding is one of the main targets for rice breeders. A set of 22 highly diverse rice genotypes were evaluated under normal and drought conditions. Morphological, physiological, and yield traits were recorded on each genotype. Drought susceptibility index (DSI) was estimated for six yield traits to identify the most drought-tolerant rice genotypes. A high genetic variation was found among genotypes tested in the experiment. Under normal conditions, the highest phenotypic correlation was found between grain yield (GY) and sterility percentage (SP) (- 0.73**), while it was among GY and chlorophyll content (CC) (0.82**) under drought conditions. To identify quantitative trait loci (QTL) controlling yielding traits under drought and normal, a single marker analysis was performed between all yield traits under both conditions and a set of 106 simple sequence repeat (SSR) marker alleles. The genetic association analysis revealed 14 and 17 QTL under drought and normal conditions, respectively. The most drought-tolerant genotypes were selected based on phenotypic traits, the number of QTL in each selected genotype, and the level of genetic diversity existed among the genotypes. As a result, five genotypes (Giza 178, IET1444, GZ1368-S-5-4, Nahda, Giza 14) were identified as the most promising drought-tolerant rice genotypes. Eight QTL controlling drought tolerance were identified in Giza 178, Nahda, and GZ1368-S-5-4, while four QTL were found in IET1444. The number of different QTLs were estimated among the five selected genotypes. Giza 178 and GZ1368-S-5-4 shared the same QTLs. Seven different QTLs were found among Nahda, IET1444, GZ1368-S-5-4, and Giza 14. Combining information from phenotypic traits, genetic diversity analysis, and QTL analysis was very useful in identifying the true drought-tolerant rice genotypes that can be used for crossing in the future breeding program.

Clinical and radiographic evaluations of implant-supported cantilever fixed partial dentures replacing maxillary anterior teeth: A randomized clinical trial.

STATEMENT OF PROBLEM: Replacing maxillary or mandibular anterior teeth with implant-supported prostheses is challenging because of the small mesiodistal and buccolingual dimensions, which can affect the number and position of implants and thus the definitive prosthetic design. PURPOSE: The purpose of this randomized clinical trial was to assess the clinical and radiographic outcomes of patients treated with implant-supported cantilever fixed partial dentures (ICFPDs) compared with implant-supported conventional fixed partial dentures to replace maxillary anterior teeth. MATERIAL AND METHODS: Fourteen participants missing 2 central incisors and 1 lateral incisor (6 men and 8 women) with a mean age of 40 years (range, 30 to 50 years) were divided equally into 2 groups, the IFF group (n=7; implant-supported FPD design) and the ICF group (n=7; ICFPD). Each participant received 2 implants (13×3.75) according to the fixed partial denture design. All participants were evaluated in terms of the implant stability, peri-implant sulcus depth, marginal bone loss, gingival index, and plaque index at the baseline and after 6, 12, 18, and 24 months. RESULTS: The clinical results revealed no significant difference between the 2 groups in the implant stability, gingival index, or plaque index over the follow-up period. However, regarding the average peri-implant sulcus depth, the implant adjacent to the cantilever showed a significant difference compared with the other implants after 24 months, with an average peri-implant sulcus depth of 2 mm, which was still within the typical range. The average marginal bone loss for implants near the cantilever was significantly higher than that for the other implants in the 2 designs, with a value of 1.8 mm at the 2-year follow-up examination, which was also within the typical range of bone loss per year. CONCLUSIONS: Under the conditions of this randomized clinical trial, implant-supported cantilever fixed dental prostheses can be used successfully to replace maxillary anterior teeth.

Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing.

Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-ß clamp complex. This complex contains two pairs of Hda dimers sandwiched between two ß clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the ß clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-ß clamp complex indicate that the interaction of the ß clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-ß clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function.

Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma.

Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

Pattern of Vascular Involvement in Egyptian Patients with Budd-Chiari Syndrome: Relation to Etiology and Impact on Clinical Presentation.

INTRODUCTION AND AIM: Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction. This work aims to analyze the pattern of vascular involvement in Egyptian patients with BCS, demonstrates its relation to etiology and shows its impact on clinical presentation. MATERIAL AND METHODS: The current retrospective study was conducted at The Tropical Medicine Department, Ain Shams University on one hundred Egyptian patients with confirmed diagnosis of primary BCS who were presented to the Budd-Chiari Study Group (BCSG) from April 2014 to May 2016 by collecting clinical, laboratory and radiological data from their medical records. RESULTS: Isolated hepatic vein occlusion (HVO) was the most common pattern of vascular involvement (43%), followed by combined HVO and inferior vena cava (IVC) compression by enlarged caudate lobe (32%), then combined HVO and IVC stenosis/webs (21%), and lastly isolated IVC occlusion (4%). Ascites was more significantly encountered in BCS patients with HVO than in those with isolated inferior vena cava (IVC) occlusion and patent HVs (P = 0.005). Abdominal pain was significantly encountered in patients with occluded three major HVs (P = 0.044). Behcet's disease was significantly detected in isolated IVC occlusion. Protein C deficiency was significantly detected in patients with combined HVO and IVC compression. CONCLUSION: Isolated HVs occlusion was the most common pattern of vascular involvement in Egyptian patients with primary BCS. Vascular pattern of involvement affected the clinical presentation and was related to the underlying thrombophilia in those patients.

Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation.

The yeast THO complex and the associated RNA helicase Sub2p are important mRNP maturation factors. Transcripts produced in THO/sub2 mutants are subject to degradation by a surveillance mechanism that involves the nuclear RNA exosome. Here we show that inefficient polyadenylation forms the basis of this accelerated mRNA decay. A genetic screen reveals extensive interactions between deletions of THO subunits and mRNA 3' end processing mutants. Nuclear run-ons strengthen this link by showing premature transcription termination close to polyadenylation sites in THO/sub2 mutants in vivo. Moreover, in vitro, pre-mRNA substrates are poorly polyadenylated and consequently unstable in extracts from THO/sub2 mutant strains. Decreased polyadenylation correlates with a specific downregulation of the poly(A)-polymerase cofactor Fip1p by the ubiquitin/proteasome pathway. Both polyadenylation defects and Fip1p instability depend on the nuclear exosome component Rrp6p and its activator Trf4p. We suggest that removal of aberrant mRNA is facilitated by direct regulation of polyadenylation activity.

Acute Beta Blockade at Peak Stress: Will It Alter the Sensitivity of Dobutamine Stress Echocardiography in Patients with Normal Resting Wall Motion?

BACKGROUND: We compared the accuracy of recovery phase images following administration of intravenous propranolol with peak stress images, for detection of coronary artery disease in patients with no resting wall motion abnormalities undergoing dobutamine stress echocardiography. METHODS: We enrolled 100 consecutive patients with no resting wall motion abnormalities who underwent dobutamine stress echocardiography. Propranolol was injected after termination of dobutamine infusion. Positive peak stress images were defined as the induction of wall motion abnormalities at any stage before propranolol injection. Positive recovery phase images were defined as maintenance or worsening of wall motion abnormalities induced at peak stress, or the appearance of new wall motion abnormalities during recovery phase. Significant coronary stenosis was defined as ≥ 50% obstruction of ≥ 1 sizable artery by coronary angiography. RESULTS: Seventy-two patients (72%) had significant coronary artery disease. Analysis of peak stress images revealed sensitivity, specificity, positive and negative predictive values of 80.6%, 85.7%, 93.5%, and 63.2%; the overall accuracy was 82%. Analysis of the recovery phase images revealed sensitivity, specificity, positive and negative predictive values of 91.7%, 75%, 90.4%, and 77.8%; here, the overall accuracy was 87%. CONCLUSIONS: In patients with no resting wall motion abnormalities, acute beta blockade during dobutamine stress echocardiography improved the sensitivity of recovery phase images for detection of significant coronary artery disease versus peak stress images, but with reduced specificity. KEY WORDS: Accuracy; Beta blocker; Coronary artery disease; Dobutamine stress echocardiography; Recovery phase images.

A novel mercuric reductase from the unique deep brine environment of Atlantis II in the Red Sea.

A unique combination of physicochemical conditions prevails in the lower convective layer (LCL) of the brine pool at Atlantis II (ATII) Deep in the Red Sea. With a maximum depth of over 2000 m, the pool is characterized by acidic pH (5.3), high temperature (68 °C), salinity (26%), low light levels, anoxia, and high concentrations of heavy metals. We have established a metagenomic dataset derived from the microbial community in the LCL, and here we describe a gene for a novel mercuric reductase, a key component of the bacterial detoxification system for mercuric and organomercurial species. The metagenome-derived gene and an ortholog from an uncultured soil bacterium were synthesized and expressed in Escherichia coli. The properties of their products show that, in contrast to the soil enzyme, the ATII-LCL mercuric reductase is functional in high salt, stable at high temperatures, resistant to high concentrations of Hg(2+), and efficiently detoxifies Hg(2+) in vivo. Interestingly, despite the marked functional differences between the orthologs, their amino acid sequences differ by less than 10%. Site-directed mutagenesis and kinetic analysis of the mutant enzymes, in conjunction with three-dimensional modeling, have identified distinct structural features that contribute to extreme halophilicity, thermostability, and high detoxification capacity, suggesting that these were acquired independently during the evolution of this enzyme. Thus, our work provides fundamental structural insights into a novel protein that has undergone multiple biochemical and biophysical adaptations to promote the survival of microorganisms that reside in the extremely demanding environment of the ATII-LCL.

Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex immunological disease with multiple pathological features that is primarily induced by smoking together with additional genetic risk factors. COPD is frequently underdiagnosed; forced expiratory volume in the first second (FEV1) is considered to be the main diagnostic measure for COPD, yet it is insufficiently sensitive to monitor disease progression. Biomarkers capable of monitoring COPD progression and severity are needed. In this report, we evaluated matrix metalloproteinase-9 (MMP-9) as an early marker for the detection and staging of COPD, by assessing the mRNA levels of MMP-9 in peripheral blood samples collected from 22 COPD patients, 6 asymptomatic smokers, and 5 healthy controls. Our results demonstrate that the mRNA levels of MMP-9 increased more than two-fold in severe COPD relative to non-COPD smokers or moderate COPD groups. Moreover, in the very severe COPD group, MMP-9 mRNA levels showed a 4-fold increase relative to the non-COPD smokers or the moderate COPD groups, while there was a mild increase (∼40%) when compared to the severe COPD group. Taken together, our results suggest that MMP-9 serves as a biomarker for the grade and severity of COPD.

Therapeutic superiority of combined propranolol with short steroids course over propranolol monotherapy in infantile hemangioma.

UNLABELLED: Infantile hemangiomas are the most common benign childhood tumor that may have functional and/or cosmetic complications. We aimed to compare the clinical efficacy of propranolol alone and propranolol primed with systemic corticosteroids on the outcome of infantile hemangioma. A prospective randomized study included 40 infants aged less than 9 months with cutaneous hemangiomas. Patients were randomly assigned into two groups: group A were given oral prednisolone for the initial 2 weeks combined with oral propranolol, while group B were given oral propranolol alone for 6 months. The median age of the studied patients was 4.5 months (ranged 4 weeks-8 months). Sequential determination of the dimensions of the hemangiomas based on direct measurement and photographic analysis were performed. A significant reduction in the size of the lesions was found in group A in the 2-, 4-, and 8-week evaluation compared to group B (p < 0.001) with no statistical difference in the ultimate 6 month response (p = 0.134). Multiple logistic regression showed that early treatment before 6 months of age (OR 9.82, p = 0.007) and combined treatment with propranolol and prednisolone (OR 10.71, p = 0.006) were the predictors of best response. CONCLUSION: Combining propranolol with corticosteroids gives a faster response and should be considered in treating life- or function-threatening hemangiomas.

Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

The interaction of Pcf11 and Clp1 is needed for mRNA 3'-end formation and is modulated by amino acids in the ATP-binding site.

Polyadenylation of eukaryotic mRNAs contributes to stability, transport and translation, and is catalyzed by a large complex of conserved proteins. The Pcf11 subunit of the yeast CF IA factor functions as a scaffold for the processing machinery during the termination and polyadenylation of transcripts. Its partner, Clp1, is needed for mRNA processing, but its precise molecular role has remained enigmatic. We show that Clp1 interacts with the Cleavage-Polyadenylation Factor (CPF) through its N-terminal and central domains, and thus provides cross-factor connections within the processing complex. Clp1 is known to bind ATP, consistent with the reported RNA kinase activity of human Clp1. However, substitution of conserved amino acids in the ATP-binding site did not affect cell growth, suggesting that the essential function of yeast Clp1 does not involve ATP hydrolysis. Surprisingly, non-viable mutations predicted to displace ATP did not affect ATP binding but disturbed the Clp1-Pcf11 interaction. In support of the importance of this interaction, a mutation in Pcf11 that disrupts the Clp1 contact caused defects in growth, 3'-end processing and transcription termination. These results define Clp1 as a bridge between CF IA and CPF and indicate that the Clp1-Pcf11 interaction is modulated by amino acids in the conserved ATP-binding site of Clp1.