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Superparamagnetic iron oxide nanoparticles (SPIONs) are emerging nanomaterials, in part due to their superparamagnetic property. At room temperature, they can be readily magnetized under the influence of an external magnetic field and yet return to an apparently nonmagnetic state in its absence, with closed (no hysteresis) magnetization curves resulting in zero magnetic remanence and coercivity. Their high surface to volume ratio due to the nanometer length scale and subsequent high surface area enables them to be used in a range of applications that includes targeted drug delivery, magnetic contrasting agents in MRI scans for medical diagnosis, and in localized heating induced by an alternating magnetic field (AMF) for targeted therapy with minimum side effects. In this chapter, we systematically introduce the concept of magnetic nanomaterials, superparamagnetic materials such as SPIONs, various syntheses routes, various core-shell SPIONs, surface functionalization of core-shell SPIONs, main characterization techniques, and application of SPIONs in medical diagnosis and therapy. We have also summarized the current state of commercially available SPIONs and their applications in nanomedicine including information of clinical trials. Finally, we have provided an overview of the potential theranostics application of SPIONs in various diseases.

Background Physiotherapy is indicated for treatment of a painful degenerative knee meniscus tear. Predicting the outcome remains uncertain. Objective The purpose of this systematic review was to identify which predictive factors are associated with the outcome of physiotherapy for degenerative knee meniscus tear. Methods A systematic electronic literature search was undertaken of PubMed, CINAHL, Medline with AMED and EMBASE via Ovid from inception to July 2021. Studies of adults receiving physiotherapy which presented data on the association of baseline variables and the treatment outcome were included. Study quality was assessed using CASP (Critical Appraisal Skills Programme) tools. Data were narratively analysed. Results 1051 titles were retrieved and screened for eligibility. Fifteen studies met the inclusion criteria. Nine studies investigated just degenerative tears. The evidence-base was of low/moderate quality. Across all studies, seven and five studies (100%) reported no association between mechanical symptoms or gender respectively (p > 0.05). There was no association with osteoarthritis in 80%, age in 71%, or body mass index in 60% of studies (p > 0.05). Four studies (80%) reported that higher baseline pain was associated with cross-over to surgery, greater improvement with surgery or less improvement in pain score (p > 0.05). Conclusion Patient demographic characteristics provide minimal association with outcome following physiotherapy for degenerative meniscus tear. The evidence-base is limited in size and quality. A large adequately powered prospective cohort study investigating a broad range of predictive factors is warranted to develop a predictive model to better stratify those most likely to benefit from physiotherapy.

The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.

Members of the crenarchaeal kingdom, such as Sulfolobus, divide by binary fission yet lack genes for the otherwise near-ubiquitous tubulin and actin superfamilies of cytoskeletal proteins. Recent work has established that Sulfolobus homologs of the eukaryotic ESCRT-III and Vps4 components of the ESCRT machinery play an important role in Sulfolobus cell division. In eukaryotes, several pathways recruit ESCRT-III proteins to their sites of action. However, the positioning determinants for archaeal ESCRT-III are not known. Here, we identify a protein, CdvA, that is responsible for recruiting Sulfolobus ESCRT-III to membranes. Overexpression of the isolated ESCRT-III domain that interacts with CdvA results in the generation of nucleoid-free cells. Furthermore, CdvA and ESCRT-III synergize to deform archaeal membranes in vitro. The structure of the CdvA/ESCRT-III interface gives insight into the evolution of the more complex and modular eukaryotic ESCRT complex.

Defects in chromosome replication can lead to translocations that are thought to result from recombination events at stalled DNA replication forks. The progression of forks is controlled by an essential DNA helicase, which unwinds the parental duplex and can stall on encountering tight protein–DNA complexes. Such pause sites are hotspots for recombination and it has been proposed that stalled replisomes disassemble, leading to fork collapse. However, in both prokaryotes and eukaryotes it now seems that paused forks are surprisingly stable, so that DNA synthesis can resume without recombination if the barrier protein is removed. Recombination at stalled forks might require other events that occur after pausing, or might be dependent on features of the surrounding DNA sequence. These findings have important implications for our understanding of the regulation of genome stability in eukaryotic cells, in which pausing of forks is mediated by specific proteins that are associated with the replicative helicase.

Lipase immobilized novel high surface area core-shell superparamagnetic nanoparticles have been fabricated and used as efficient reusable catalysts for the selective production of pharmaceutically important chiral isomers from meso-cyclopent-2-en-1,4-diacetate.

The proliferation of eukaryotic cells is a highly regulated process that depends on the precise duplication of chromosomal DNA in each cell cycle. Regulation of the replication licensing system, which promotes the assembly of complexes of proteins termed Mcm2-7 onto replication origins, is responsible for preventing re-replication of DNA in a single cell cycle. Recent work has shown how the licensing system is directly controlled by cyclin-dependent kinases (CDKs). Repression of origin licensing is emerging as a ubiquitous route by which the proliferative capacity of cells is lowered, and Mcm2-Mcm7 proteins show promise as diagnostic markers of early cancer stages. These results have prompted us to propose a functional distinction between the proliferative state and the non-proliferative state (including G0) depending on whether origins are licensed.

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., Targeted alteration of the genome lies at the heart of the exploitation of S. pombe as a model system. The rate of analysis is often determined by the efficiency with which a target locus can be manipulated. For most loci this is not a problem, however for some loci, such as fin1+, rates of gene targeting below 5% can limit the scope and scale of manipulations that are feasible within a reasonable time frame. We now describe a simple modification of transformation procedure for directing integration of genomic sequences that leads to a 5-fold increase in the transformation efficiency when antibiotic based dominant selection markers are used. We also show that removal of the pku70+ and pku80+ genes, which encode DNA end binding proteins required for the non-homologous end joining DNA repair pathway, increases the efficiency of gene targeting at fin1+ to around 75-80% (a 16-fold increase). We describe how a natMX6/rpl42+ cassette can be used for positive and negative selection for integration at a targeted locus. To facilitate the evaluation of the impact of a series of mutations on the function of a gene of interest we have generated three vector series that rely upon different selectable markers to direct the expression of tagged/untagged molecules from distinct genomic integration sites. pINTL and pINTK vectors use ura4+ selection to direct disruptive integration of leu1+ and lys1+ respectively, while pINTH vectors exploit nourseothricin resistance to detect the targeted disruption of a hygromycin B resistance conferring hphMX6 cassette that has been integrated on chromosome III. Finally, we have generated a series of multi-copy expression vectors that use resistance to nourseothricin or kanamycin/G418 to select for propagation in prototrophic hosts. Collectively these protocol modifications and vectors extend the versatility of this key model system., Swiss National Science Foundation (www.snf.ch). École polytechnique fédérale de Lausanne (www.epfl.ch). Cancer Research UK [CRUK] C147/A6058.

DNA repair pathways can enable tumour cells to survive DNA damage that is induced by chemotherapeutic treatments; therefore, inhibitors of specific DNA repair pathways might prove efficacious when used in combination with DNA-damaging chemotherapeutic drugs. In addition, alterations in DNA repair pathways that arise during tumour development can make some cancer cells reliant on a reduced set of DNA repair pathways for survival. There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects.

9 páginas, 5 figuras.-- et al., The Mrc1 and Tof1 proteins are conserved throughout evolution, and in budding yeast they are known to associate with the MCM helicase and regulate the progression of DNA replication forks. Previous work has shown that Mrc1 is important for the activation of checkpoint kinases in responses to defects in S phase, but both Mrc1 and Tof1 also regulate the normal process of chromosome replication. Here, we show that these two important factors control the normal progression of DNA replication forks in distinct ways. The rate of progression of DNA replication forks is greatly reduced in the absence of Mrc1 but much less affected by loss of Tof1. In contrast, Tof1 is critical for DNA replication forks to pause at diverse chromosomal sites where nonnucleosomal proteins bind very tightly to DNA, and this role is not shared with Mrc1., Acknowledge the support of Cancer Research U.K., from whom K.L. received a Senior Cancer Research Fellowship; the European Molecular Biology Organization Young Investigator Programme; and the Junta de Castilla y León and the Instituto de Salud “Carlos III”-Fondo de Investigaciones Sanitarias for providing A.C. with funding (grants PI031255 and PI061409).

Eukaryotic cells regulate the progression and integrity of DNA replication forks to maintain genomic stability and couple DNA synthesis to other processes. The budding yeast proteins Mrc1 and Tof1 associate with the putative MCM-Cdc45 helicase and limit progression of the replisome when nucleotides are depleted, and the checkpoint kinases Mec1 and Rad53 stabilize such stalled forks and prevent disassembly of the replisome. Forks also pause transiently during unperturbed chromosome replication, at sites where nonnucleosomal proteins bind DNA tightly. We describe a method for inducing prolonged pausing of forks at protein barriers assembled at unique sites on a yeast chromosome, allowing us to examine for the first time the effects of pausing upon replisome integrity. We show that paused forks maintain an intact replisome that contains Mrc1, Tof1, MCM-Cdc45, GINS, and DNA polymerases α and ε and that recruits the Rrm3 helicase. Surprisingly, pausing does not require Mrc1, although Tof1 and Csm3 are both important. In addition, the integrity of the paused forks does not require Mec1, Rad53, or recombination. We also show that paused forks at analogous barriers in the rDNA are regulated similarly. These data indicate that paused and stalled eukaryotic replisomes resemble each other but are regulated differently., This work was funded by Cancer Research U.K., from whom K.L. receives a Senior Cancer Research Fellowship, and by the Instituto de Salud Carlos III (F.I.S. grant no. 03-1255), together with a PGC grant awarded to A.B. by the Spanish science ministry. K.L. is supported by the EMBO Young Investigator program, and A.C. received a short-term fellowship from EMBO and is supported by the Sistema Nacional de Salud (grant no. 02-3059). M.K. is funded by a JSPS Post-Doctoral Fellowship for Research Abroad.

During late mitosis and early interphase, origins of replication become "licensed" for DNA replication by loading Mcm2-7 complexes [1–5]. Mcm2-7 complexes are removed from origins as replication forks initiate replication, thus preventing rereplication of DNA in a single cell cycle. Premature origin licensing is prevented in metaphase by the action of geminin, which binds and inhibits Cdt1/RLF-B, a protein that is required for the loading of Mcm2-7 [6–9]. Recombinant geminin that is added to Xenopus egg extracts is efficiently degraded upon exit from metaphase [10]. Here, we show that recombinant and endogenous forms of Xenopus geminin behave differently from one another, such that a significant proportion of endogenous geminin escapes proteolysis upon exit from metaphase. During late mitosis and early G1, the surviving population of endogenous geminin does not associate with Cdt1/RLF-B and does not inhibit licensing. Following nuclear assembly, geminin is imported into nuclei and becomes reactivated to bind Cdt1/RLF-B. This reactivated geminin provides the major nucleoplasmic inhibitor of origin relicensing during late interphase. Since the initiation of replication at licensed origins depends on nuclear assembly [11], our results suggest an elegant and novel mechanism for preventing rereplication of DNA in a single cell cycle.