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World Journal of Gastroenterology Apr 2020Colorectal cancer (CRC) is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union. While the incidence and... (Review)
Review
Colorectal cancer (CRC) is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union. While the incidence and mortality rates in western, high developed countries are declining, reflecting the success of screening programs and improved treatment regimen, a rise of the overall global CRC burden can be observed due to lifestyle changes paralleling an increasing human development index. Despite a growing insight into the biology of CRC and many therapeutic improvements in the recent decades, preclinical models are still indispensable for the development of new treatment approaches. Since the development of carcinogen-induced rodent models for CRC more than 80 years ago, a plethora of animal models has been established to study colon cancer biology. Despite tenuous invasiveness and metastatic behavior, these models are useful for chemoprevention studies and to evaluate colitis-related carcinogenesis. Genetically engineered mouse models (GEMM) mirror the pathogenesis of sporadic as well as inherited CRC depending on the specific molecular pathways activated or inhibited. Although the vast majority of CRC GEMM lack invasiveness, metastasis and tumor heterogeneity, they still have proven useful for examination of the tumor microenvironment as well as systemic immune responses; thus, supporting development of new therapeutic avenues. Induction of metastatic disease by orthotopic injection of CRC cell lines is possible, but the so generated models lack genetic diversity and the number of suited cell lines is very limited. Patient-derived xenografts, in contrast, maintain the pathological and molecular characteristics of the individual patient's CRC after subcutaneous implantation into immunodeficient mice and are therefore most reliable for preclinical drug development - even in comparison to GEMM or cell line-based analyses. However, subcutaneous patient-derived xenograft models are less suitable for studying most aspects of the tumor microenvironment and anti-tumoral immune responses. The authors review the distinct mouse models of CRC with an emphasis on their clinical relevance and shed light on the latest developments in the field of preclinical CRC models.
Topics: Animals; Colorectal Neoplasms; Disease Models, Animal; Female; Male; Mice
PubMed: 32308343
DOI: 10.3748/wjg.v26.i13.1394 -
Medicine Sep 2022The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis.
BACKGROUND
The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE.
METHODS
A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes.
RESULTS
Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P = .04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated.
CONCLUSION
In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea.
Topics: Bacillus clausii; Child; Diarrhea; Gastroenteritis; Humans; Probiotics; Saccharomyces boulardii
PubMed: 36086703
DOI: 10.1097/MD.0000000000030500 -
Perspectives on Behavior Science Jun 2023In the history of the field, behavior analysts have used the operant chamber as an apparatus for both teaching and experimental investigations. In the early days of the...
In the history of the field, behavior analysts have used the operant chamber as an apparatus for both teaching and experimental investigations. In the early days of the field, students spent significant time in the animal laboratory, using operant chambers to conduct hands-on experiments. These experiences allowed students to see behavior change as an orderly process and drew many students toward careers in behavior analysis. Today, most students no longer have access to animal laboratories. However, the Portable Operant Research and Teaching Lab (PORTL) can fill this void. PORTL is a table-top game that creates a free-operant environment for studying the principles of behavior and their application. This article will describe how PORTL works and the parallels between PORTL and the operant chamber. Examples will illustrate how PORTL can be used to teach concepts such as differential reinforcement, extinction, shaping, and other basic principles. In addition to its use as a teaching tool, PORTL provides a convenient and inexpensive way for students to replicate research studies and even conduct their own research projects. As students use PORTL to identify and manipulate variables, they gain a deeper understanding for how behavior works.
PubMed: 37425989
DOI: 10.1007/s40614-023-00369-y -
Frontiers in Neural Circuits 2022The interest in studying the neural circuits related to mating behavior and mate choice in monogamous species lies in the parallels found between human social structure... (Review)
Review
The interest in studying the neural circuits related to mating behavior and mate choice in monogamous species lies in the parallels found between human social structure and sexual behavior and that of other mammals that exhibit social monogamy, potentially expanding our understanding of human neurobiology and its underlying mechanisms. Extensive research has suggested that social monogamy, as opposed to non-monogamy in mammals, is a consequence of the neural encoding of sociosensory information from the sexual partner with an increased reward value. Thus, the reinforced value of the mate outweighs the reward value of mating with any other potential sexual partners. This mechanism reinforces the social relationship of a breeding pair, commonly defined as a pair bond. In addition to accentuated prosocial behaviors toward the partner, other characteristic behaviors may appear, such as territorial and partner guarding, selective aggression toward unfamiliar conspecifics, and biparental care. Concomitantly, social buffering and distress upon partner separation are also observed. The following work intends to overview and compare known neural and functional circuits that are related to mating and sexual behavior in monogamous mammals. We will particularly discuss reports on Cricetid rodents of the and genus, and New World primates (NWP), such as the subfamily of the titi monkey and the marmoset (). In addition, we will mention the main factors that modulate the neural circuits related to social monogamy and how that modulation may reflect phenotypic differences, ultimately creating the widely observed diversity in social behavior.
Topics: Animals; Humans; Mammals; Pair Bond; Primates; Sexual Behavior, Animal; Social Behavior
PubMed: 36247729
DOI: 10.3389/fncir.2022.978344 -
Communications Biology Sep 2023Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on... (Review)
Review
Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on surface-attached formations, but detached aggregates have received increasing attention in the past decade due to their pivotal role in chronic infections. Understanding their nature sparked fervent discussions in biofilm conferences and scientific literature. This review consolidates current insights on non-attached aggregates, offering examples of their occurrence in nature and diseases. We discuss their formation and dispersion mechanisms, resilience to antibiotics and immune-responses, drawing parallels to surface-attached biofilms. Moreover, we outline available in vitro models for studying non-attached aggregates.
Topics: Anti-Bacterial Agents; Biofilms; Molecular Weight
PubMed: 37658117
DOI: 10.1038/s42003-023-05281-4 -
Cells May 2022plays a pivotal role as a model system in understanding the biochemistry and molecular biology of mammals including humans. A considerable portion of our knowledge on... (Review)
Review
plays a pivotal role as a model system in understanding the biochemistry and molecular biology of mammals including humans. A considerable portion of our knowledge on the genes and pathways involved in cellular growth, resistance to toxic agents, and death has in fact been generated using this model organism. The yeast chronological lifespan (CLS) is a paradigm to study age-dependent damage and longevity. In combination with powerful genetic screening and high throughput technologies, the CLS has allowed the identification of longevity genes and pathways but has also introduced a unicellular "test tube" model system to identify and study macromolecular and cellular damage leading to diseases. In addition, it has played an important role in studying the nutrients and dietary regimens capable of affecting stress resistance and longevity and allowing the characterization of aging regulatory networks. The parallel description of the pro-aging roles of homologs of RAS, S6 kinase, adenylate cyclase, and Tor in yeast and in higher eukaryotes in chronological survival studies is valuable to understand human aging and disease. Here we review work on the chronological lifespan with a focus on the genes regulating age-dependent macromolecular damage and longevity extension.
Topics: Aging; Animals; Cell Cycle; Genes, Regulator; Humans; Longevity; Mammals; Saccharomyces cerevisiae
PubMed: 35626750
DOI: 10.3390/cells11101714 -
Orthopaedics & Traumatology, Surgery &... Oct 2021Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the parallelism of screws remains controversial.
MATERIALS AND METHODS
MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before June 2, 2020, that compared the use of parallel and non-parallel screw fixation for the treatment of FNF. The pooled analysis was designed to identify differences between the two groups and focused on postoperative complications, including fracture nonunion and osteonecrosis of the femoral head (ONFH).
RESULTS
Over four studies, we enrolled 445 patients, including 195 patients with fixed FNF with parallel trajectory screws and 250 patients with fixed FNF with non-parallel screws. The pooled analysis showed no difference in the nonunion rates (odds ratio (OR)=0.91; 95% confidence interval (CI), 0.24-3.44; p=0.89) and no significant difference in the incidence of ONFH between parallel and non-parallel screw fixation (OR=0.74; 95% CI: 0.21-2.63; p=0.64).
CONCLUSIONS
The results of this meta-analysis reveal that screw parallelism in multiple cannulated screw fixation of FNF has no relationship with either the fracture nonunion rate or the incidence of postoperative ONFH.
LEVEL OF EVIDENCE
III; meta-analysis.
Topics: Bone Screws; Femoral Neck Fractures; Fracture Fixation, Internal; Fractures, Ununited; Humans; Postoperative Complications
PubMed: 34217865
DOI: 10.1016/j.otsr.2021.103005 -
Wiley Interdisciplinary Reviews. RNA Jul 2020Recent cryo-EM structures of a group II intron caught in the process of invading DNA have given new insight into the mechanisms of both splicing and retrotransposition.... (Review)
Review
Recent cryo-EM structures of a group II intron caught in the process of invading DNA have given new insight into the mechanisms of both splicing and retrotransposition. Conformational dynamics involving the branch-site helix domain VI are responsible for substrate exchange between the two steps of splicing. These structural rearrangements have strong parallels with the movement of the branch-site helix in the spliceosome during catalysis. This is strong evidence for the spliceosome evolving from a group II intron ancestor. We observe other topological changes in the overall structure of the catalytic domain V that may occur in the spliceosome as well. Therefore, studying group II introns not only provides us with insight into the evolutionary origins of the spliceosome, but also may inform the design of experiments to further probe structure-function relationships in this eukaryotic splicing apparatus. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.
Topics: Introns; Nucleic Acid Conformation; RNA Precursors; RNA Splicing; Retroelements
PubMed: 32045511
DOI: 10.1002/wrna.1589 -
Journal of Evolutionary Biology Jun 2021Research on the genomics of adaptation is rapidly changing. In the last few decades, progress in this area has been driven by methodological advances, not only in the...
Research on the genomics of adaptation is rapidly changing. In the last few decades, progress in this area has been driven by methodological advances, not only in the way increasingly large amounts of molecular data are generated (e.g. with high-throughput sequencing), but also in the way these data are analysed. This includes a growing appreciation and quantitative treatment of covariation among units within the same data type (e.g. genes) or across data types (e.g. genes and phenotypes). The development and adoption of more and more integrative tools have resulted in richer and more interesting empirical work. This special issue - comprising methodological, empirical, and review papers - aims to capture a 'snapshot' of this rapidly evolving field. We discuss in particular three important themes in the study of adaptation: the genetic architecture of adaptive variation, protein-coding and regulatory changes, and parallel evolution. We highlight how more traditional key themes in the study of genetic architecture (e.g. the number of loci underlying adaptive traits and the distribution of their effects) are now being complemented by other factors (e.g. how patterns of linkage and number of loci interact to affect the ability to adapt). Similarly, apart from addressing the relative importance of protein-coding and regulatory changes, we now have the tools to look in-depth at specific types of regulatory variation to gain a clearer picture of regulatory networks. Finally, parallel evolution has always been central to the study of adaptation, but now we are often able to address the question of whether - and to what extent - parallelism at the organismal or phenotypic level is matched by parallelism at the genetic level. Perhaps most importantly, we can now determine what mechanisms are driving parallelism (or lack thereof) across levels of biological organization. All these recent methodological developments open up new directions for future studies of adaptive changes across traits, levels of biological organization, demographic contexts and time scales.
Topics: Adaptation, Biological; Biological Evolution; Genetic Variation; Genomics
PubMed: 34145685
DOI: 10.1111/jeb.13871 -
RSC Advances May 2022G-Quadruplex (G4), as a non-canonical nucleic acid secondary structure, has been proved to be prevalent in genomes and plays important roles in many biological...
G-Quadruplex (G4), as a non-canonical nucleic acid secondary structure, has been proved to be prevalent in genomes and plays important roles in many biological processes. Ligands targeting G4, especially small-molecular fluorescent light-up probes with selectivity for special conformations, are essential for studying the relationship between G4 folding and the cellular response. However, their development still remains challenging but is attracting massive attention. Here, we synthesized a new tetraphenylethene derivative, namely TPE-B, as a parallel G4 probe. Fluorescence experiments showed that TPE-B could give out a strong fluorescence response to the G4 structure. Moreover, it gave a much higher fluorescence intensity response to parallel G4s than anti-parallel ones, which indicated that TPE-B could serve as a special tool for probing parallel G4s. The circular dichroism (CD) spectra and melting curves showed that TPE-B could selectively bind and stabilize parallel G4s without changing their topology. ESI-MS studies showed that TPE-B could bind to parallel G4 with a 1 : 1 stoichiometry. The gel staining results showed that TPE-B was a good candidate for probing parallel G4s. Altogether, the TPE-B molecule may serve as a promising new probe that can discriminate parallel G4s.
PubMed: 35702216
DOI: 10.1039/d2ra01433e