Search

Targeted degradation of cell surface and extracellular proteins via lysosomal delivery is an important means to modulate extracellular biology. However, these approaches have limitations due to lack of modularity, ease of development, restricted tissue targeting and applicability to both cell surface and extracellular proteins. We describe a lysosomal degradation strategy, termed cytokine receptor-targeting chimeras (KineTACs), that addresses these limitations. KineTACs are fully genetically encoded bispecific antibodies consisting of a cytokine arm, which binds its cognate cytokine receptor, and a target-binding arm for the protein of interest. We show that KineTACs containing the cytokine CXCL12 can use the decoy recycling receptor, CXCR7, to target a variety of target proteins to the lysosome for degradation. Additional KineTACs were designed to harness other CXCR7-targeting cytokines, CXCL11 and vMIPII, and the interleukin-2 (IL-2) receptor-targeting cytokine IL-2. Thus, KineTACs represent a general, modular, selective and simple genetically encoded strategy for inducing lysosomal delivery of extracellular and cell surface targets with broad or tissue-specific distribution. KineTACs are modular bispecific antibodies for degradation of extracellular and cell-surface proteins. [ABSTRACT FROM AUTHOR]

Musical creativity is represented through the activity of "creation" in the curricula for music education in both Montenegrin and Slovenian primary schools. Starting from the assumption that this activity is insufficiently realised, a survey of the teaching practice of the specialist music teachers in the two countries was conducted (N = 154). The obtained results show that creative musical activities are moderately represented in teaching practice and that Slovenian teachers achieve programme-defined goals related to the activities through which pupils create their own music to a greater extent. The results also indicate the particular circumstances that, in real school conditions, make it difficult to systematically realise this activity within regular music classes. [ABSTRACT FROM AUTHOR]

The foundations of modern Slovene music teaching were laid in the experimental music education which was carried out as a longitudinal study in all eight grades of primary school. First introduced in the school year 1963/64, it aimed at thoroughly reforming music education and developing new teaching methods. The entire project was carried out by Breda Oblak who, in her written lesson plans and in the practical execution of lessons, developed the concept of active music learning, basing it on performing, listening and creating activities. At seminars for teachers, which included also observations of experimental lessons, she disseminated the new music teaching methods to the broadest pedagogic practice. She used the results of the study to develop didactic packs for all grades of primary schools. These materials were issued in two cycles: first for the eight-year and latter for the nine-year primary school. Breda Oblak transformed the music education teaching methods, upgrading them into modern music-teaching theory and practice. [ABSTRACT FROM AUTHOR]

Creativity is the focus of research in various areas. The present paper focuses on creativity in music and the role of the teacher in stimulating and developing it in an individual's musical development. It highlights the importance of evaluating musical ideas, the creative process and final products. The Music Olympiad involves a presentation of competitor's own compositions. In the research, we analysed the characteristics of the compositions written for and performed at the first three Slovene Music Olympiads. [ABSTRACT FROM AUTHOR]

We have previously deleted both endogenous copies of the clathrin heavy-chain gene in the chicken pre B-cell-line DT40 and replaced them with clathrin under the control of a tetracycline-regulatable promoter (Tet-Off). The originally derived cell-line DKO-S underwent apoptosis when clathrin expression was repressed. We have also described a cell-line DKO-R derived from DKO-S cells that was less sensitive to clathrin-depletion. Here we show that the restriction of transferrin uptake, resulting in iron deprivation, is responsible for the lethal consequence of clathrin-depletion. We further show that the DKO-R cells have up-regulated an anti-apoptotic survival pathway based on the chemokine SDF-1 and its receptor CXCR4. Our work clarifies several puzzling features of clathrin-depleted DT40 cells and reveals an example of how SDF-1/CXCR4 signalling can abrogate pro-apoptotic pathways and increase cell survival. We propose that the phenomenon described here has implications for the therapeutic approach to a variety of cancers. [ABSTRACT FROM AUTHOR]

Samo Vremšak dedicated part of his opus to children's and youth choirs. The present paper presents the publications of the compositions for these two ensembles, the composer's choice of texts and the characteristics of his musical expression. The analysis of 12 compositions for children's choir and 19 for youth choir from the composer's collection (1997) shows the rhythmical, melodic, harmonic and compositional characteristics of Vremšak's compositions and proves his command and creative use of various compositional techniques in forming an artistic musical language of his own. [ABSTRACT FROM AUTHOR]

Bodily movement plays an important role in musical production, reproduction and perception. Musical performance is linked to expressive movement of the musician which co-influences the perception by the audience. The performer's movements and gestures, which the audience can see during the performance, function as a special communicational means and intensify the whole musical experience. Research shows that musical performances which attract auditory and visual attention and intensify the listeners' focus cause in them physical, cognitive and emotional-experiential activities. This paper dedicates particular attention to bodily movements and gestures in piano playing. In connection with holistic learning and musical activities, it highlights the paradigm of embodied music cognition and its place in Émile Jaques-Dalcroze's eurhythmics. In dealing with creative musical expression, it focuses on improvisation, while also pointing out the connection of musical movement with musicality. [ABSTRACT FROM AUTHOR]

Molecular biology is a rapidly evolving field that has led to the development of increasingly sophisticated technologies to improve our capacity to study cellular processes in much finer detail. Transcription is the first step in protein expression and the major point of regulation of the components that determine the characteristics, fate and functions of cells. The study of transcriptional regulation has been greatly facilitated by the development of reporter genes and transcription factor expression vectors, which have become versatile tools for manipulating promoters, as well as transcription factors in order to examine their function. The understanding of promoter complexity and transcription factor structure offers an insight into the mechanisms of transcriptional control and their impact on cell behaviour. This review focuses on some of the many applications of molecular cut-and-paste tools for the manipulation of promoters and transcription factors leading to the understanding of crucial aspects of transcriptional regulation. [ABSTRACT FROM AUTHOR]

Despite its cultural significance, the oldest Slovene public radio show Veseli tobogan (Happy Toboggan) has not yet been thoroughly researched or evaluated. The article covers the history of the show and some figures that helped in building its reputation. Among them, the article focuses on the work of the composer Bojan Adamič. He was engaged in the show from the start, at first as a pianist and a member of the jury in auditions, then as an arranger (producing around 800 works) and the leader of the Bojan Adamič Ensemble. The period from 1982 (1983) to 1995 could be named Adamič's Period of Veseli tobogan. In addition to the show's production and its concept, the article highlights the musical and cultural values of the period. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis (PD) is one of the options for renal replacement therapy (RRT) in the end stage renal disease (ESRD) patients. Compared to hemodialysis (HD), patients on PD experience a greater sense of well-being, an improved steady state in terms of extracellular fluid volume shifts and hemodynamics and it is preferred method for patients with problematic vascular access, bleeding tendencies, heart failure and elderly patients. In order to perform PD, a tunneled catheter should be placed through the abdominal wall and into peritoneal space, with positioning of the catheter within the most dependent portion of pelvis. Currently, there are several techniques available for PD catheter placement: open surgery, laparoscopic and percutaneous. We present for the first time in our country a case of 65 year old male patient to whom percutaneous onsite insertion of peritoneal catheter was performed. The idea is to emphasize that sometimes this should be a method of choice for RRT, especially in patients where general anesthesia should be avoid. Compared to other methods, percutaneous insertion is a simple procedure with no need for general anesthesia, and the benefits of quick recovery, earlier ambulation, and less delay in catheter placement. [ABSTRACT FROM AUTHOR]

Some of the most valuable frescoes in the world can be found in the churches and monasteries in the Republic of Macedonia. Painted mostly in the Byzantine (eleventh to fifteenth centuries) and post-Byzantine periods (fifteenth to eighteenth centuries), these frescoes are now under threat, presumably due to the fact that the original roofs covering the churches were replaced by modern ones. The new roofs, made of aggressive materials such as cement mortar and reinforced concrete, have very low air permeability and do not allow sufficient drying of the fresco layers during the humid periods in winter and cause over-drying of the fresco layers during the hot and dry summer periods. This phenomenon is believed to be the main cause for the frescoes' degradation. This study examines some recent interventions to Macedonian church buildings and what appears to be consequential damage to the fresco paintings, which in some cases is already irreversible. It also proposes possible approaches which could help to save this important element of world heritage and preserve it for posterity. [ABSTRACT FROM AUTHOR]

The rat PC12 variant cell line, A35C, lacks regulated secretory organelles due to a selective transcriptional block. Hence, A35C may provide clues about the mechanisms that underlie control of neurosecretion. We used mRNA microarray profiling to examine gene expression in A35C. Genes for regulated secretory proteins were down-regulated, while other membrane trafficking pathways were unaffected. A subset of genes repressed in A35C contain binding sites for the neuronal transcriptional repressor, RE1-silencing transcription factor (REST), and REST is expressed in A35C but not normal PC12 cells. Blocking the activity of REST in A35C using a dominant-negative construct induced the reappearance of mRNAs for synaptophysin, chromogranin A, synaptotagmin IV and the β3 subunit of the voltage-gated sodium channel (Scn3b), all of which contain RE1 sites in their genes. In the case of Scn3b, the corresponding protein was also re-expressed. Granule and synaptic vesicle proteins were not re-expressed at the protein level, despite reactivation of their mRNA, suggesting the existence of additional post-transcriptional control for these proteins. Our work identifies one of the mechanisms underlying the phenotype of neurosecretory-deficient neuroendocrine cells, and begins to define the critical components that determine a key aspect of the neuroendocrine phenotype. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) produced by inducible nitric-oxide synthase (NOSII) is mainly regulated at the transcriptional level by the nuclear factor-κB (NF-κB). In the present study, we further analyzed the role of NF-κB in the in vivo transcriptional regulation of NOSII gene by comparing two clones isolated from the EMT-6 mouse mammary cancer cell line. In response to interleukin (IL)-1β or lipopolysaccharide (LPS), EMT-6 clone J (EMT-6J) cells produce 3-fold more NO than EMT-6 clone H (EMT-6H) cells, an effect correlated with enhanced activation of NF-κB in EMT-6J cells. In response to IL-1β, the kinetics of degradation of NF-κB inhibitors IκB-α and IκB-β, the nucleo-cytoplasmic shuttling of the transcription factor and its binding to a specific DNA sequence were similar in both clones. In contrast, an IL-1β-induced phosphorylation of serine residues in NF-κB p65 subunit was observed in EMT-6J, but not in EMT-6H, cells. This IL-1β-induced phosphorylation of p65 was specifically prevented by pretreatment of EMT-6J cells with the casein kinase II inhibitor DRB. Small interfering RNA-mediated depletion of casein kinase II-α subunit also decreased NF-κB transcriptional activity and NOSII gene transcription in IL-1β and LPS-stimulated EMT-6J cells to the levels observed in EMT-6H cells treated in the same conditions. Altogether, these data indicate that casein kinase II-mediated phosphorylation of p65 subunit can enhance the transcriptional activity of NF-κB in vivo. This post-translational modification of the transcription factor can be responsible for increased NOSII gene transcription and NO production in tumor cells exposed to either IL-1β or LPS. [ABSTRACT FROM AUTHOR]

A new photoactive monoclinic polymorph (γ-form) of 6-(2′,4′- dinitrobenzyl)-2,2′-bipyridine was obtained from an acetone- methanol solution. The crystal structure was compared with those of two polymorphs reported previously (photoactive orthorhombic α-form and photoinactive monoclinic β-form) and with structures of related nitrobenzylpyridines to explain the relation between the structure and photochromism. The comparison of the reaction cavities around the reactive pyridyl-benzyl-nitro fragment among the polymorphs and related nitrobenzylpyridines revealed that a crucial factor for photochromic activity is the rotational freedom of the ortho- nitro group in their crystals and its accessibility from the proton-donor and proton-acceptor sites. This is because the ortho-nitro group should rotate around the N--C bond to transfer a proton from the methylene group to the N atom of the pyridine ring. [ABSTRACT FROM AUTHOR]

Presents information on a study which reviewed the mechanisms of the antitumoral effects of lipopolysaccharide and lipid A. Mechanisms of lipid A antitumoral effect in animal models; Mechanisms of lipid antitumoral effects in patients; Conclusions.

A variant of the PC12 pheochromocytoma cell line (termed A35C) has been isolated that lacks regulated secretory organelles and several constituent proteins. Northern and Southern blot analyses suggested a block at the transcriptional level. The proprotein-converting enzyme carboxypeptidase H was synthesised in the A35C cell line but was secreted by the constitutive pathway. Transient transfection of A35C cells with cDNAs encoding the regulated secretory proteins dopamine β-hydroxylase and synaptotagmin I resulted in distinct patterns of mistargeting of these proteins. It is surprising that hybrid cells created by fusing normal PC12 cells with A35C cells exhibited the variant phenotype, suggesting that A35C cells express an inhibitory factor that represses neuroendocrine-specific gene expression. [ABSTRACT FROM AUTHOR]

Median arcuate ligament syndrome (MALS) is a rare condition that is often overlooked as a result of its nonspecific symptoms. It is usually presented with nausea, bloating, abdominal postprandial pain, and weight loss. The diagnosis of MALS is usually delayed and made by excluding other causes for the symptoms. The diagnosis of this syndrome is based on clinical presentation and radiological findings on computer tomography angiography (CTA) or magnetic resonance angiography (MRA). Surgery is treatment of choice, with promising results from laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Fabricates high-temperature superconducting arrays of Josephson junctions as millimeter-wave oscillators at 77 K. Detection of power levels in the microwatt range; Discussion on participating and cross junctions; Use of monolithic log-periodic spiral antennas to enable power coupling.

An abstract of the article "Early diagnostic ultrastructural features of Wilson's disease" by Pance Zdravkovski and others, is presented.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value. [ABSTRACT FROM AUTHOR]

Reduction of expression of E-cadherin in canine mammary tumors has been correlated with invasive behavior, lymph node metastases and shorter survival period after tumor removal. The aim of this study was to examine the expression of E-cadherin in canine benign and malignat mammary tumors with different grade of malignancy. 38 canine mammary tumors were studied. In general, the percentage of positive stained cells was bigger in benign neoplasia and carcinomas with grade of malignancy The expression of E-Cadherin decreased with growth of the grade of malignancy. Among the groups of tumors of different grade of malignancy, statistical significant loss of expression of E-Cadherin was detected between benign lesions and carcinomas grade of malignancy II (p< 0,01), and between benign lesions and carcinomas III grade of malignancy (p< 0,01). [ABSTRACT FROM AUTHOR]

The aim of this investigation was to determine the prevalence of feline mammary tumors, as well as it's pathohistological classification and prevalence in different breeds of cats. According obtained results, it is concluded that from total number of processed feline mammary tumors, 92,4% were malignant and 7,6 were benign, according to the World Health Organization criteria from 1999. The most common tumors in this investigation were tubulopapillary and solid carcinomas. Most of carcinomas were classified with grade III of malignancy. The most affected breeds were mixed breeds. [ABSTRACT FROM AUTHOR]

A novel solid oxovanadium(V) complex, monoaqua(8-hydroxyquinolinato)dioxovanadium(V), VO 2 (H 2 O)(Q) (Q = 8-hydroxyquinolinate ion) was synthesized and characterized by FTIR and UV/Vis spectroscopy, voltammetric measurements and Hartree-Fock ab initio calculations on the models of the ligand Q and the respective phenol QH. Electrochemical measurements in solution clearly showed complex formation between NH 4 VO 3 and 8-hydroxyquinoline, revealing an electrode reaction of the intermediate NH 4 [VO 2 (Q)OH] species on the mercury electrode in 0.1 M NH 3 /NH 4 Cl buffer (pH 9.85) as a reversible process at -0.700 V ( vs . Ag | AgCl | KCl sat reference electrode). The square-wave voltammogram of an aqueous solution of the VO 2 (H 2 O)(Q) complex obtained with thermal deamination of NH 4 [VO 2 (Q)OH] presented a new reversible peak at -0.720 V. [ABSTRACT FROM AUTHOR]

This review should provide more information about the importance of iodine in dairy cattle, since milk is considered as valuable source of iodine in newborn animal nutrition and in recent years in human nutrition. Iodine is an essential element for thyroid gland function and it is incorporated into the thyroid hormones, which play key role in energy metabolism, growth and brain development. Iodine also exert multiple and complex actions on many organs that capture it, not including its effects as part of thyroid hormones. Therefore, the adequate iodine bioavailability and optimal feed intake in dairy cattle is of pivotal importance for optimal iodine concentration in milk. Its concentrations in milk may be variable as it is influenced by many factors: iodine intake in feed, iodine forms used for feeding, iodine supplementation of feed, presence of goitrogenic substances and its ratio in animal feed, milk yield, seasonal fluctuations and also farm management. [ABSTRACT FROM AUTHOR]

Current serology tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies mainly take the form of enzyme-linked immunosorbent assays, chemiluminescent microparticle immunoassays or lateral flow assays, which are either laborious, expensive or lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost, solution-based assay to detect antibodies in serum, plasma, whole blood and to a lesser extent saliva, using rationally designed split luciferase antibody biosensors. This new assay, which generates quantitative results in 30 min, substantially reduces the complexity and improves the scalability of coronavirus disease 2019 (COVID-19) antibody tests. This assay is well-suited for point-of-care, broad population testing, and applications in low-resource settings, for monitoring host humoral responses to vaccination or viral infection. A rapid, split luciferase test for SARS-CoV-2 antibodies in blood and saliva compatible with lyophilization and use in low-resource settings. [ABSTRACT FROM AUTHOR]

Context: Bladder cancer (BC) is the sixth most common malignant neoplasm in men. Recently, great effort has been devoted to the study of BC variant histology (VH). Yet, the results from these studies have shown conflicting data and remain unclear whether their presence alters recurrence and survival rates after radical cystectomy (RC). Aims: We undertook this study aiming to test the effect on VH on recurrence-free survival (RFS) and overall survival (OS) in single-center RC patients. Settings and Design: We have retrospectively analyzed medical records and pathology reports from 331 patients who underwent RC with or without pelvic lymphadenectomy at University Urology Clinic-Skopje, North Macedonia, in the period between 2010 and 2018. Subjects and Methods: Microscopic analysis of the specimens involved the evaluation of histological tumor type, tumor grade, pathological tumor node metastasis stage, presence of lymphovascular invasion, and resection margin status. Statistical Analysis Used: Univariable and multivariable Cox regression models were applied to test the effect of VH on RFS and OS. Results: We found 185 patients who matched our inclusion criteria. At multivariable analyses, lymphovascular invasion and positive resection margins were associated with shorter RFS. Similarly, patients diagnosed with lymphovascular invasion, positive resection margins, and a pelvic lymph node metastasis had poorer OS. VH was not found to be an independent predictor of both RFS and OS (P > 0.05). Conclusions: The present study did not reveal prognostic effect of VH on RFS and OS. In our series, histomorphologic parameters including lymphovascular invasion, resection margins, and pelvic lymph node metastasis were the most relevant predictors on survival outcome after RC. [ABSTRACT FROM AUTHOR]

The recurrent emergence of drug resistance in Plasmodium falciparum increases the urgency to genetically validate drug resistance mechanisms and identify new targets. Reverse genetics have facilitated genome-scale knockout screens in Plasmodium berghei and Toxoplasma gondii, in which pooled transfections of multiple vectors were critical to increasing scale and throughput. These approaches have not yet been implemented in human malaria species such as P. falciparum and P. knowlesi, in part because the extent to which pooled transfections can be performed in these species remains to be evaluated. Here we use next-generation sequencing to quantitate uptake of a pool of 94 barcoded vectors. The distribution of vector acquisition allowed us to estimate the number of barcodes and DNA molecules taken up by the parasite population. Dilution cloning of P. falciparum transfectants showed that individual clones possess as many as seven episomal barcodes, revealing that an intake of multiple vectors is a frequent event despite the inefficient transfection efficiency. Transfection of three spectrally-distinct fluorescent reporters allowed us to evaluate different transfection methods and revealed that schizont-stage transfection limited the tendency for parasites to take up multiple vectors. In contrast to P. falciparum, we observed that the higher transfection efficiency of P. knowlesi resulted in near complete representation of the library. These findings have important implications for how reverse genetics can be scaled in culturable Plasmodium species. [ABSTRACT FROM AUTHOR]

As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests. [ABSTRACT FROM AUTHOR]

Nanotechnology presents a modern field of science that in the last twenty-five years plays a dominant role in the biomedicine. Different analytical methods are used for evaluation of the physico-chemical properties of nanoparticles including chromatography, electrophoresis, X-ray scattering, spectroscopy, mass spectrometry, zeta potential measurement and microscopy on which this article will focus. Herein, we present novel application of the long-established TEM technique that is focused on characterization and evaluation of various nanoparticles in development of drug delivery systems. Transmission electron microscopy images were taken of samples from native nanoparticles, nanoparticles labeled using stannous chloride labeling procedure, inorganic silica nanoparticles loaded with budesonide and native micelles and micelles carrier of anticancer drug camptothecin. In the case of radiolabeled nanoparticles, beside for nanoparticle characterization, TEM technique was used to confirm the stability of the nanoparticles after radiolabeling. Furthermore, the porous structure of hybrid silica particles loaded with budesonide was examined under TEM. Transmission electron microscopy technique offers exceptional benefits for nanoparticle characterization. Additionally, the necessity of ultrastructural analysis demonstrates the potential of TEM in the field of nanomedicine. Hence, the long-established and well-known TEM has been only partially exploited and offer researchers very detailed images of specimens at microscopic and nano scale. [ABSTRACT FROM AUTHOR]

Invasion of human erythrocytes is essential for Plasmodium falciparum parasite survival and pathogenesis, and is also a complex phenotype. While some later steps in invasion appear to be invariant and essential, the earlier steps of recognition are controlled by a series of redundant, and only partially understood, receptor-ligand interactions. Reverse genetic analysis of laboratory adapted strains has identified multiple genes that when deleted can alter invasion, but how the relative contributions of each gene translate to the phenotypes of clinical isolates is far from clear. We used a forward genetic approach to identify genes responsible for variable erythrocyte invasion by phenotyping the parents and progeny of previously generated experimental genetic crosses. Linkage analysis using whole genome sequencing data revealed a single major locus was responsible for the majority of phenotypic variation in two invasion pathways. This locus contained the PfRh2a and PfRh2b genes, members of one of the major invasion ligand gene families, but not widely thought to play such a prominent role in specifying invasion phenotypes. Variation in invasion pathways was linked to significant differences in PfRh2a and PfRh2b expression between parasite lines, and their role in specifying alternative invasion was confirmed by CRISPR-Cas9-mediated genome editing. Expansion of the analysis to a large set of clinical P. falciparum isolates revealed common deletions, suggesting that variation at this locus is a major cause of invasion phenotypic variation in the endemic setting. This work has implications for blood-stage vaccine development and will help inform the design and location of future large-scale studies of invasion in clinical isolates. [ABSTRACT FROM AUTHOR]

The purpose of this study is to identify Helicobacter species with 2 different morphology (Helicobacter-like organisms and Gastrospirillumlike organisms) in gastric imprint of pig stomach. A total of 120 gastric specimens, (60 from intensive and 60 from extensive pig production) were analyzed. The presence of Helicobacter species was detected in 9 of total 60 (15%) pigs from intensive production and 6.67% (4/60) belong to „Helicobacter pylori morphotype", while 8.33% (5/60) belong to „Gastrospirillum-morphotype". Helicobacter species in pigs from extensive production was found in 14 of total 60 (23.33%). „Helicobacterpylori morphotype" were present in 5 of total 60 samples (8.33%), while bacteria with spiral appearance (Gastrospirillum-morphotype) were identified in 9 of total 60 samples (15%). Also, semi-quantitative evaluation of bacterial density was performed. The gastric imprint is useful, fast, simple and inexpensive method, widely used for confirmation of presence of Helicobacter species. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. [ABSTRACT FROM AUTHOR]

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to determine the prevalence of canine mammary tumors in the region of Bitola and Prilep, as well as it's pathohistological classification and prevalence in different breeds of dogs. According obtained results, it is concluded that from total number of processed mammary tumors, 70% were malignant and 30% were benign. According to the World Health Organization criteria from 2011, the most common tumors in this investigation were complex and tubulopapilary carcinomas, less prevalent were spindle cell carcinomas while mixed carcinomas and sarcomas were absent. Most of the carcinomas (40%) were classified with I grade of malignancy. The most common breeds affected were cross breeds, poodles, cocker spaniels and German shepherds. [ABSTRACT FROM AUTHOR]

Photomechanical and photochromic activities are reported for single crystals of a new multiresponsive material, 2,4-di-tert-butyl-6-((e)-((4-((E)-phenyldiazenyl)phenyl)imino)methyl)phenol (Azim-1), with two photoactive groups that can undergo photoisomerization (azo and imine), and an ortho-hydroxy group that is capable of proton transfer. Upon irradiation with UV light, platy and needle-shaped crystals of Azim-1 rapidly bend towards the light source and return to their initial shape as soon as the irradiation is terminated. Upon prolonged exposure to UV light, the crystals change their color from yellow to red. The crystal structure of non-irradiated Azim-1 is reported, and the mechanisms of the photomechanical and photochromic responses are discussed. [ABSTRACT FROM AUTHOR]

We carried out photopolymerization by [2 + 2] dimerization of a photoreactive guest molecule in the channels of a photoreactive porous coordination polymer. The photoreactions of the guest and two host ligands were monitored by single-crystal X-ray crystallography, providing snapshots of the interplay between the reactive centers. By correlating the structures of these three photocenters, a strong synergism was discovered among three reaction (quasi)equilibria and three types of photochemical reactions (isomerization, dimerization, and polymerization). This result indicates a strong coupling and feedback mechanism among the photocenters moderated by the coordination backbone. [ABSTRACT FROM AUTHOR]

Considering the confusing biodistribution data through the literature and few reported alerts as well as our preliminary biodistribution results, we decided to evaluate the interaction and interference of the commonly present 99mTc (technetium-99m)-stannic oxide colloid during the direct stannous chloride 99mTc-labeling procedure and to assess its influence on the biodistribution pattern of amphiphilic poly(lactic-co-glycolic acid) nanoparticles. In order to confirm our thesis, beside stannous chloride, we employed two different reducing agents that don't form colloidal particles. The use of sodium borohydride was previously reported in the literature, whereas sodium dithionite was adapted for the first time in the 99mTc direct labeling procedure for nanoparticles. The results in our paper clearly differentiate among samples with and without colloidal impurities originating from the labeling procedure with a logical follow up of the radiochemical, physicochemical evaluation, and biodistribution studies clarifying previously reported data on stannic oxide colloidal interference. 99mTc-nanoparticle complex labeled with sodium dithionite as reducing agent illustrated appropriate labeling efficacy, stability, and potential for further use in biodistribution studies thus providing solution for the problem of low-complex stability when sodium borohydride is used and colloidal stannic oxide interference for stannous chloride procedure. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A paradigm shift from hard to flexible, organic-based optoelectronics requires fast and reversible mechanical response from actuating materials that are used for conversion of heat or light into mechanical motion. As the limits in the response times of polymer-based actuating materials are reached, which are inherent to the less-than-optimal coupling between the light/heat and mechanical energy in them, a conceptually new approach to mechanical actuation is required to leapfrog the performance of organic actuators. Herein, we explore single crystals of 1,2,4,5-tetrabromobenzene (TBB) as actuating elements and establish relations between their kinematic profile and mechanical properties. Centimeter-size acicular crystals of TBB are the only naturally twinned crystals out of about a dozen known materials that exhibit the thermosalient effect-an extremely rare and visually impressive crystal locomotion. When taken over a phase transition, crystals of this material store mechanical strain and are rapidly self-actuated to sudden jumps to release the internal strain, leaping up to several centimeters. To establish the structural basis for this colossal crystal motility, we investigated the mechanical profile of the crystals from macroscale, in response to externally induced deformation under microscope, to nanoscale, by using nanoindentation. Kinematic analysis based on high-speed recordings of over 200 twinned TBB crystals exposed to directional or nondirectional heating unraveled that the crystal locomotion is a kinematically complex phenomenon that includes at least six kinematic effects. The nanoscale tests confirm the highly elastic nature, with an elastic deformation recovery (60%) that is far superior to those of molecular crystals reported earlier. This property appears to be critical for accumulation of stress required for crystal jumping. Twinned crystals of TBB exposed to moderate directional heating behave as all-organic analogue of a bimetallic strip, where the lattice misfit between the two crystal components drives reversible deformation of the crystal. [ABSTRACT FROM AUTHOR]

While self-actuation and motility are habitual for humans and nonsessile animals, they are hardly intuitive for simple, lifeless, homogeneous objects. Among mechanically responsive materials, the few accidentally discovered examples of crystals that when heated suddenly jump, propelling themselves to distances that can reach thousands of times their own size in less than 1 ms, provide the most impressive display of the conversion of heat into mechanical work. Such thermosalient crystals are biomimetic, nonpolymeric self-actuators par excellence. Yet, due to the exclusivity and incongruity of the phenomenon, as well as because of the unavailability of ready analytical methodology for its characterization, the reasons behind this colossal self-actuation remain unexplained. Aimed at unraveling the mechanistic aspects of the related processes, herein we establish the first systematic assessment of the interplay among the thermodynamic, kinematic, structural, and macroscopic factors driving the thermosalient phenomenon. The collective results are consistent with a latent but very rapid anisotropic unit cell deformation in a two-stage process that ultimately results in crystal explosion, separation of debris, or crystal reshaping. The structural perturbations point to a mechanism similar to phase transitions of the martensitic family. [ABSTRACT FROM AUTHOR]