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The beads in the Golgi complex-endoplasmic reticulum region.

The region between the rough endoplasmic reticulum (ER) and the Golgi complex has been studied in a variety of insect cell types in an attempt to find a marker for the exit gate or gates from the ER. We have found that the smooth surface of the rough endoplasmic reticulum near Golgi complex transitional elements has beadlike structures arranged in rings at the base of transition vesicles. They occur in all insect cell types and a variety of other organisms. The beads can be seen only after staining in bismuth salts. They are 10-12 nm in diameter and are separated from the membrane and one another by a clear halo giving them a center to center spacing of about 27 nm. The beads are not sensitive to nucleases under conditions which disrupt ribosomes or remove all Feulgen staining material from the nucleus. Under conditions similar to those used to stain tissue, bismuth does not react in vitro with nucleic acids. The component of the beads that stains preferentially with bismuth is therefore probably not nucleic acid.

Bismuth

Trace elements in man.

It is likely that most, if not all, of the elements found to be essential in animals will be shown to be so for man, and the clinical picture produced by deficiency of the elements in the human patient will differ little from that seen in the animal, although this has been established for only five elements (I, Fe, Cu, Co and Zn). However, the link between lack of a given element in the soil and a human patient is far less direct and much more complex than that met with in the animal grazing on deficient pastures, except in isolated primitive communitis. Zn is the most protean of the trace elements and has been chosen to illustrate this in human practice. Excesses of essential elements (both trace and major) give rise to toxic effects and the importance of a proper balance especially of the transitional elements in the human diet is discussed with special reference to Cu, Zn and Fe. Certain non-essential trace elements are individual and community hazards: Cd, Pb and Hg are the principal offenders for humans. Mankind is now largely dependent on grassland products, cereals and livestock with increasing dominance of the former in human nutrition. This has reduced the bioavailability of trace elements so that study of trace metals, especially Zn and Cu, in skeletal and dental remains at human burial and occupation sites should prove useful in assessing the consequences of this striking change in dietary habits.

Biological Evolution

A review of macromolecular transport and secretion at the cellular level.

This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role.

Animals

Symbionticism revisited: a discussion of the evolutionary impact of intracellular symbioses.

Wallin (1927) first published the notion that the fusion of bacteria with host cells was the principal source of genetic novelty for speciation. He suggested that mitochondria are transitional elements in this process. While the significance that he attributed to symbiosis now seem excessive, he was one of the first authors to be aware of the evolutionary potential of symbiotic events and his view of mitochondria may not seem strange to many cell biologist today. The most significant evolutionary development which has been attributed to intracellular symbiosis is the origin of eukaryotic cellular organization. The current status of the 'serial endosymbiosis hypothesis' is briefly review. The case for the symbiotic origin of the chloroplast, based principally on 16 S RNA oligonucleotide cataloguing, is very strong. Mitochondrial origins are more obscure but also appear to be symbiotic due to recent 18 S cataloguing from wheat embryos. The probablility of the multiple origin of some eukaryotic organelles is also examined, the processes in question being the acquisition of distinct stocks of chloroplasts from disparate photosynthetic prokaryotes and the secondary donation of organelles from degenerate eukaryotic endosymbionts to their hosts, with specific reference to the dinoflagellates Peridinium balticum, Kryptoperidinium foliaceum and the ciliate Mesodinium rubrum. It is concluded that the evolutionary potential of intracellular symbiosis ('cytobiosis': a term introduced in this paper) is great, with the best established influence being on the origin of eukaryotic chloroplasts. Together with the potential effects of viral vectors, symbiosis serves as a supplementary speciation mechanism capable of producing directed evolutionary changes. It is likely that these processes will explain some of the apparent anomalies in evolutionary rates and direction which are not readily explicable by the conventional synthetic theory of evolution.

Animals

The response of cell walls of Bacillus subtilis to metals and to electron-microscopic stains.

Purified cell walls of Bacillus subtilis were subjected to solutions of 40 independent metals and the metal uptake, the electron-scattering power of thin sections, and the type of staining response evaluated. This was repeated for six typical electron-microscopic stains (uranyl acetate, uranyl magnesium acetate, osmium tetroxide, Os-meth, osmium-dimethylethylenediamine, and ruthenium red) and one new staining reagent (a potassium platinum chloride - dimethylsulfoxide complex) whose specificity is for amine functions. The reaction of select metals can be specific in terms of both uptake and staining response. Of the metals studied most transition elements had a high affinity for the wall fabric and some (i.e., Sc III, most lanthanides, UIV, ZrIV,HfIV, Fe III, Pd II, Ru III, and In III) may be suitable as contrasting agents for electron microscopy. Furthermore, when the thickness of metal-reacted walls was compared to freeze-each and ultracryotomy data, statistical-dimensional differences were commonly seen, which indicates that wall ultrastructure can be profoundly affected by the type of metal and (or) staining reagent.

Bacillus subtilis

Aggregation-induced Electrochemiluminescence of AgNCs Enhanced with AuNPs@MXene Composites for Ultrasensitive Detection of microRNA.

MXene, a two-dimensional nanomaterial, has metal conductivity, high electronegativity, functionalized with surface groups, which make it widely applicable in catalysis and biosensing. However, studies on the principle of enhanced electrochemiluminescence (ECL) by MXene composites and the improvement of their performance in catalyzing the ECL reaction are still in their infancy. In this study, gold nanoparticles (AuNPs) are obtained by mild reductive reduction and loaded in situ on the Ti3C2Tx MXene surface to form the composites (AuNPs@MXene). In oxygenated PBS test buffer, AuNPs@MXene enhance the ECL emission of silver nanoclusters (AgNCs) with aggregation-induced electrochemiluminescence (AIECL) properties as luminophore. Approximately 7.5-fold enhancement of ECL signals is obtained by using two ECL enhancement strategies: an efficient AIECL emitter and a co-reaction accelerator. The special nucleic acid structure with "Three Way Junction (TWJ)" enables an ultra-sensitive detection of microRNA, providing an efficient and ultra-sensitive method for microRNA detection. The biosensor achieves a wide detection range of microRNA-21 from 100 aM to 1 nM, with a low detection limit of 31 aM, and exhibits excellent stability, selectivity and high reproducibility in real samples.

MicroRNAs

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals

Comparative analysis of conserved non-coding elements identifies gene regulatory networks rewired during the water-to-land transition in vertebrates.

The conquest of land by vertebrates has been a pivotal moment in evolutionary history. Adapting to the new habitats necessitated numerous changes in vertebrate anatomy and physiology, creating an enduring imprint on the developmental gene regulatory networks (GRNs) of tetrapods. The increase of high-quality genomic resources over the past decade has made it possible to study the genomic legacy of the water-to-land transition. While much attention has been given to the highly conserved non-coding elements (CNEs) of the genome that share high levels of similarity across evolutionarily diverged clades, recent evidence suggests that perhaps comparable attention should be given to "missing" CNE-s, conserved sequence patches present in extant stem gnathostomes and actinopterygian fishes that have become undetectable in tetrapods during the adaptation to terrestrial life, whether through true sequence loss or divergence beyond alignability. These sequences could help us reveal the relaxation of certain developmental constraints, related to the aquatic lifestyle, that made reaching new adaptive peaks in the developmental landscape possible. In this paper, we search for such CNEs and characterize them in comparison with pan-Gnathostome CNEs, using the zebrafish (Danio rerio) genome as a reference. Our results suggest that the rewiring of developmental networks related to pigmentation and muscle structure formation has left the largest genomic imprint. We also find that components of canonical Wnt and Hedgehog signalling, are enriched among CNEs retained in fish.

cis-regulatory evolution

Progress in the use of elemental diets in infants and children.

The clinical use of elemental diets to provide adequate nutrition in the infant or child in a catabolic state will, undoubtedly, increase as experience confirms the effectiveness and safety of this technique. The value of total parenteral nutrition and nutrition given through the peripheral vein should, in no way, be underestimated, since many infants and children will still require this form of nutrition during periods when the intestine is not available for alimentation. The use of elemental diets in the transitional period between total parenteral nutrition and more conventional feedings as well as in providing nutritional support when the intestine is totally or partially available provides a method of earlier discontinuance of parenteral nutrition and, hence, decreases the incidence of mechanical, metabolic and septic complications associated with intravenously administered nutrition. Each patient should be considered individually and a decision made as to whether or not enteral hyperalimentation can be used in place of, or in conjunction with, parenteral nutrition.

Amino Acids

Acral arteriovenous tumor.

A unique, superficial, lobulated, benign vascular tumor of the skin, found in the acral areas of adult males, is described. The combination of three different elements--arterial, venous, and transitional vascular channels--make up the predominant histologic features of this tumor. The transition of fibromuscular channels indicates a venous lesion, but the acral location of the lesions and the structure and staining characteristics suggest that the lesion is a hamartomatous proliferation of the Sucquet-Hoyer canal of the true glomus.

Adult

The effect of evolution on homologous proteins: a comparison between the chromophore microenvironments of Italian water buffalo (Bos bubalus, L.) and sperm whale apomyoglobin.

The perturbing effect of guanidium hydrochloride and pH on the molecular structure of water buffalo apomyoglobin has been investigated by circular dichroism in the far and near ultraviolet and by fluorescence. In the wavelength region between 320 and 260 nm the circular dichroic spectrum of the globin is highly structured and the contributions of the aromatic chromophores have been resolved. Buffalo apomyoglobin undergoes a structural transition at neutral pH which involves elements of the secondary and tertiary structure, as indicated by changes of dichroic activity of the peptide and aromatic chromophores and the fluorescence of the two tryptophanyl residues. The possibility of charge-transfer complex between indole and imidazole is discussed. A major structural transition with abrupt unfolding takes place in the pH region between 5.6 and 4.3. Below pH 4.3 the peptide helical residues, which survive the acid transition, appear to be resistent to further acidification to pH 2.0 while tryptophanyl emission is quenched and shifted to longer wavelengths. A structural transition occurs also in alkali above pH 10, which has been detected by the same techniques. The relationships between buffalo and sperm whale apomyoglobin are discussed.

Animals

Exploring Regulatory Roles of Transposable Elements in EMT and MET through Data-Driven Analysis: Insights from regulaTER.

Gene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in a given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded from https://github.com/karakulahg/regulaTER.

DNA Transposable Elements

Transition of Staphylococcus aureus tetracycline resistance plasmid pT181 from independent multicopy replicon to predominantly integrated chromosomal element over 65 years.

Mobile genetic elements (MGEs), including plasmids, phages and genome islands, are major sources of bacterial genetic diversity. The small plasmid pT181 confers tetracycline resistance in bacterial pathogen Staphylococcus aureus via an efflux pump, TetK. pT181 was one of the earliest sequenced S. aureus plasmids, and has been isolated in both clinical and livestock-associated strains for decades, both as an independent replicon and integrated in the chromosome as part of staphylococcal cassette chromosome mec (SCCmec). Bacterial genome analysis tools and high-quality sequences with metadata are publicly available, but these resources remain underleveraged for examining historical data, especially when studying the spread of MGEs across a species and over time. Using publicly available reads and metadata, we explored the evolution of pT181 over almost seven decades of samples to identify temporal trends in sequence evolution, copy number changes, and spread across S. aureus and beyond. pT181 was prevalent across S. aureus (found in 9.5% of 83,366 genomes tested), with a conserved sequence outside of three hypervariable regions. The history of pT181 since 1954 is characterized by spread across strains, significant variation in plasmid copy number of the independent replicon, and increasing frequency of integration of the plasmid into the S. aureus chromosome. We have identified multiple chromosomal integration locations of the plasmid, including outside of the previously characterized SCCmec. We find that pT181 has been transferred across staphylococcaceae and into a Gram-negative species. The repeated integration of pT181 into the chromosome may indicate co-evolution of the plasmid and the host, potentially to facilitate increased antibiotic resistance.

Journal Article

Ultrastructure of cerebellar hemangioblastoma.

Light and ultrastructural features of a cerebellar hemangioblastoma in a 56-year-old man are described in detail. The neoplasm was composed of three major cell types: endothelial cells, pericytes, and stromal cells. The endothelial cells lined the fenestrated vascular channels. The pericytes were ensheathed by their own basal lamina which separated them from the basal lamina covering the endothelium. The stromal cells contained, in addition to the conventional organelles, numerous membrane-bound lipid inclusions, annulate lamellae, and nuclear bodies. There were also present transitional cells which shared the fine structure of all the three major cell types. Histogenetically, the tumor was considered to be of vascular origin. The stromal cells represented the stem cells which, under the neoplastic influence, continued to proliferate and differentiate into "vasoformative" elements (pericytes and endothelium) which formed new blood vessels. The transitional forms between the stromal cells and the "vasoformative" elements suggested that the cellular components of a hemangioblastoma shared a common ancestry, most likely of an angioblastic lineage.

Cell Nucleus

Primary non-urachal adenocarcinoma of the bladder.

The clinical course of 34 patients with non-urachal adenocarcinoma of the bladder was reviewed and compared to the world experience. The 5-year survivorship was 19 per cent, with only 1 patient being free of disease. Metaplasia with formation of glandular elements reflects the unstable potential of the transitional cell and may be associated with the biologic aggressiveness of the tumor.

Adenocarcinoma

Characterization of the apolipoprotein B polypeptide of human plasma low density lipoprotein in detergent and denaturation solutions.

Apolipoprotein B, the polypeptide moiety of human serum low density lipoprotein, is subject to degradation (as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) both in the intact particle and after delipidation. Protease inhibitors, sodium azide, and nitrogen saturation did not influence the rate or degree of degradation. Lipid-free apolipoprotein B prepared by gel exclusion chromatography in sodium dodecyl sulfate bound a limited number of detergent molecules (up to 300) in monomeric sodium dodecyl sulfate solutions; circular dichroic spectra of this complex were similar to spectra of the intact lipoprotein. Near the critical micelle concentrations, a large, cooperative increase in detergent binding occurred, accompanied by circular dichroic changes indicating increased alpha helicity. By sucrose density centrifugation, lysopalmitoyl phosphatidylcholine could be substituted for the anionic detergent; about 300 mol of lysolipid were bound to the polypeptide. Replacement of detergent with guanidine hydrochloride by dialysis produced a soluble polypeptide with no ordered structure at denaturant concentrations above 7 M. At lower guanidine hydrochloride concentrations, structural elements were regained in a broad, reversible transition. It appears that apolipoprotein B is an easily degraded polypeptide with regions resembling water-soluble proteins but other regions which interact with lipid (or synthetic amphiphiles) and produce an overall insolubility in aqueous solution in the absence of amphiphilic ligands.

Apolipoproteins

Molecular properties of a major cell surface protein from chick embryo fibroblasts.

The molecular structure of chick embryo fibroblast cell surface protein has been investigated by ultracentrifugation, circular dichroism, and fluorescence. Most measurements were restricted to alkaline solutions because of the limited solubility of this protein at more neutral pH values. A very high frictional ratio for the protein suggests an asymmetric structure. However, there are elements of organized structure since typical thermal transition curves were found by several methods. Consequently, a model in which ordered domains are connected by flexible polypeptide chains seems to account for all the hydrodynamic and optical data.

Animals

Database-guided thermodynamic-kinetic regulation for PtNi-based intermetallic electrocatalysts.

Pt-Ni alloys exhibit outstanding oxygen reduction reaction (ORR) activity, yet achieving structural ordering to enhance stability remains a persistent challenge. Here, we propose a database-guided screening strategy to identify promoter elements (X) that facilitate ordering. By screening the critical disorder-to-order transition temperature ([Formula: see text]), solid solubility ([Formula: see text]), and diffusion pre-exponential factor ([Formula: see text]) of candidate elements from material databases, six sets of L10-Pt(NiX) nanoparticles were synthesized. The developed L10-PtNiFe catalysts demonstrated a high mass activity (MA) of 4.38 A mgPt-1, retaining 82.1% after 50,000 cycles of accelerated durability testing (ADT) in half-cells, and retaining 79% of its initial MA of 1.1 A mgPt-1 after 30,000 cycles in membrane electrode assembly (MEA). Theoretical calculations reveal that X incorporation broadens the annealing temperature ([Formula: see text]) window by forming Pt(NiX) with higher [Formula: see text] and lowering the kinetic threshold temperature ([Formula: see text]) via enhanced atom mobility. This work establishes a database-guided framework that enables phase transitions previously difficult to access by creating an effective annealing window through coordinated thermodynamic-kinetic regulation, thereby facilitating the formation of ordered PtNi-based intermetallic structures toward durable electrocatalysts.

Journal Article