imagine (Institute of molecular genetics and genetic engineering)
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    The effect of live and inert feed treatment with lactobacilli on weaning success in intensively reared pike-perch larvae

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    Weaning to inert diet in intensively reared pike-perch larvae is confronted with significant fish loss, which prevents successful commercialization of pike-perch production. Achievement of satisfactory feed quality and effective assimilation of nutrients by larval fish is the major challenge in larval production process. Aim of this study was to evaluate whether treatment of live and inert feed with lactobacilli could alleviate growth retardation associated with early weaning of pike-perch reared in recirculating system. Weaning started on 18th day post-hatching (DPH) either as sudden weaning (SW) or by co-administration of Anemia for six days (gradual weaning, GW). Prior to administration to fish, Anemia was treated with Lactobacillus salivarius BGHO1/Lb. reuteri BGGO6-55, while inert feed was treated with Lb. paracasei subsp. paracasei BGHN14/Lb. rhamnosus BGT10. Treatment with lactobacilli slightly raised neutral lipid level in Anemia nauplii, but significantly reduced their content in dry feed. Fish were sampled on the 24th DPH. Survival, morphometric indices, skeleton differentiation, digestive enzyme activity and opportunistic pathogenic bacteria level were assessed in whole fish specimens. GW fish were presented with better survival, body growth and phospholipase A2 (PLA2) activity. Alongside, Vibrio spp. growth was suppressed in these fish and skeleton development was improved, according to Alizarin Red staining and ColIA1/Sparc mRNA expression data. Lactobacilli application in GW fish correlated with an increase of survival, condition factor and growth rate, according to trypsin and chymotrypsin activities, indicating better utilization of dietary proteins for muscle building. In SW fish, lactobacilli elevated chymotrypsin activity, PLA2 to lipase activity ratio and improved survival and ossification, as evident from Alizarin Red staining and ColIA1/Sparc mRNA expression. This indicated improved fatty acid absorption and control of metamorphosis process. Furthermore, lactobacilli suppressed Vibrio spp. growth in SW fish. Aside from demonstrating the ability of lactobacilli to aid weaning in pike-perch larvae, this study indicated that different types of food treatment may direct fish growth in a predictable manner, allowing further cost-effective improvements of larval pike-perch rearing in intensive system

    Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood

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    Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised

    Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors

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    Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay

    A call for global action for rare diseases in Africa

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    The 11(th) International Conference on Rare Diseases and Orphan Drugs (ICORD), South Africa, included the Africa-Rare initiative launch and facilitated multi-stakeholder engagement in the challenges facing, and opportunities for, Africans living with rare diseases. The following ICORD Global Call to Action, developed in collaboration with the International Rare Diseases Research Consortium, synthesizes the outcomes of the deliberations and emphasizes the international collaborative efforts required to address the global effects of rare diseases on public health

    Special Issue on Environmental Biocatalysis

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    The influence of coating with aminopropyl triethoxysilane and CuO/Cu2O nanoparticles on antimicrobial activity of cotton fabrics under dark conditions

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    A novel impregnation process for the fabrication of cotton nanocomposite with strong antimicrobial activity against antibiotics-resistant bacteria and yeast was developed. The impregnation process includes the sol-gel treatment of fabric with (3-aminopropyl)triethoxysilane in the first step, and synthesis of the CuO/Cu2O nanoparticles (NPs) on the fabric surface in the second step. The in situ synthesis of the CuO/Cu2O NPs was based on the adsorption of Cu2+-ions by the introduced amino groups of the sol-gel coating. The adsorbed Cu2+-ions are subsequently reduced in the alkaline solution of NaBH4. X-ray diffraction measurements confirmed the formation of CuO/Cu2O NPs. Scanning electron microscopy and atomic absorption spectrometry analyses indicate that the particle size, agglomeration, and amounts of synthesized NPs were highly affected by the initial concentration of CuSO(4)solution. The toxicity of nanocomposites to human keratinocytes (HaCaT) and antimicrobial activity against Gram-negativeEscherichia coliATCC 25922,E. coliATCC BAA 2469, andKlebsiella pneumoniaeATCC BAA 2146, and Gram-positive bacteriaStaphylococcus aureusATCC 25923,S. aureusATCC 43300 and yeastCandida albicansATCC 24433 strongly depended on the copper content. In addition to excellent antimicrobial activity, controlled release of Cu2+-ions from the fabrics into physiological saline solution was obtained

    Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells

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    The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene

    The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS

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    The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1(G93A) mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1(G93A) and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies

    Understanding bioplastic materials - Current state and trends

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    Plastic pollution is now considered one of the largest environmental threats facing humans and animals globally. Development of bioplastic materials may offer part of the solution as bioplastics include both nondegradable and biodegradable materials with both being important for sustainability. Bioplastic materials are currently being designed to encompass minimal carbon footprint, high recycling value and complete biodegradability. This review examines recent developments and trends in the field of bioplastic materials. A range of the most utilized bioplastic materials is presented (poly(lactic acid) (PLA), polyhydroxyalkanoate (PHA), starch, cellulose, bio-based poly(butylene succinate) (bio-PBS) and bio-polyethylene (bio-PE)) including their production, application and degradation options

    Genomic Characteristics of Colistin-Resistant Salmonella enterica subsp. enterica Serovar Infantis from Poultry Farms in the Republic of Serbia

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    The antimicrobial susceptibility testing was conducted on 174 single isolates from poultry farms in Serbia and it was determined that seven Salmonella spp. were multidrug resistant. Sixteen serotypes were detected, but only serotype Infantis confirmed reduced susceptibility to colistin. Seven colistin resistant Salmonella Infantis were studied in detail using the WGS approach. Three sequence types were identified corresponding to different epizootiology region. The isolate from the Province of Vojvodina 3842 and isolates from Jagodina (92 and 821) are represented by the sequence type ST413 and ST11, respectively. Four isolates from Kraljevo are ST32, a common S. Infantis sequence type in humans, poultry and food. The fosfomycin resistance gene fosA7 in isolate 3842 and the vgaA gene in isolate 8418/2948 encoding resistance to pleuromutilins were reported for the first time in serovar Infantis. The changes in relative expression of the phoP/Q, mgrB and pmrA/B genes were detected. Single nucleotide polymorphisms of the pmrB gene, including transitions Val164Gly or Val164Met, and Arg92Pro are described. Analyses of quinolone resistance determining region revealed substitutions Ser83Tyr in GyrA protein and Thr57Ser and Ser80Arg in ParC protein. Based on WGS data, there are two major clusters among analyzed Salmonella Infantis isolates from central Serbia

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