Growth Advantage Research Articles

Effects of on-farm hatching versus hatchery hatching on growth performance, gut development, and intestinal health and function in broiler chickens.

An alternative hatching system known as hatch on-farm (HOF) provides early access to feed compared to hatch in hatchery (HH) system. Early feeding may promote favorable gut development, potentially improving intestinal health and broiler performance. Previous studies have assessed the effects of HOF on chick quality, welfare and performance, its impacts on gut health remain inconclusive. A total of 560 Ross 308 male chicks were reared until d 38, hatched either in a hatchery (n = 280) or on-farm (n = 280), with 14 replicates per system and 20 birds per pen. Production parameters were periodically monitored. Digestive and immune organ characteristics, intestinal permeability and histomorphology were assessed on d 7, 14, and 38. High-throughput qPCR analyzed 79 ileal genes regarding barrier integrity, immune function, nutrient transporters, gut hormones, metabolism, and oxidation. HOF chicks had higher d1 body weights than HH chicks (P < 001), but this advantage disappeared within first week, with no subsequent performance differences. HOF chickens demonstrated increased duodenal villus width on d 7 and 14, and increased ileal crypt depth and submucosal thickness on d 7 (P < 0.05). Relative bursal weight was higher on d 14 (P = 0.018) and tended to be higher on d 38 in HOF chickens (P = 0.094). Intestinal permeability remained unaffected (P > 0.05), while HH chicks showed upregulation of gut barrier genes such as MUC5ac on d 7 and CLDN2 and MUC2 on d 14 (P < 0.05). HH chicks also showed upregulation of nutrient transports including VDR on d 7 and SLC30A1 and SLC5A9 on d 38, and decreased expression of the appetite-suppressing hormone CCK on d 7 (P < 0.05). HOF chicks upregulated immune-related genes, including IL-8 on d 7, IL-6, IFN-γ, AVBD9 on d 14, and NOS2 on d 38 (P < 0.05), and the oxidation gene HIF1A on d 38 (P = 0.039). In conclusion, although the HOF showed only transient growth advantages, it enhanced mucosal morphology and modulated immunity, indicating improved intestinal health.

Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7.

The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC. The role of ADRM1-ΔEx9 in early liver carcinogenesis was studied using human liver-derived non-tumoral organoids and a murine model with hydrodynamic in vivo transfection. ADRM1-ΔEx9 biology in HCC and its potential as a biomarker for predicting Olaparib response were investigated using patient-derived tumor organoids and xenograft models. The underlying mechanism was delineated using the Proteome Profiler Human Ubiquitin Array. ADRM1-ΔEx9, not its full-length counterpart, conferred human liver organoids with pro-survival advantages and a more profound tumor formation in a hydrodynamic transfected murine model. Functional knockdown resulted in spontaneous apoptosis in cell lines and patient-derived organoids, highlighting a pivotal role for ADRM1-ΔEx9 in HCC oncogenicity. Mechanistically, the shortened C-terminus of ADRM1-ΔEx9 signified a specific deubiquitinase partner BAP1 and navigated proteasome specificity. The new exon 8-10 fusion in ADRM1-ΔEx9 created a de novo binding to tumor suppressor protein FBXW7, resulting in its selective proteasome-mediated degradation. The loss of FBXW7 protein in ADRM1-ΔEx9 expressing tumors underscores their sensitivity to PARP inhibitor Olaparib. Notably, findings on ADRM1-ΔEx9 in primary HCC tumors denote its overexpression in a subgroup of patients with inferior survival and a window of therapeutic opportunity through its synthetic lethality association with Olaparib. ADRM1-ΔEx9 redirects ubiquitin proteasome specificity to degrade the tumor suppressor protein FBXW7 selectively. This promotes HCC tumor formation and provides a synthetic lethal link for PARPi therapy. Reduced tumor suppressor protein FBXW7 expression is pivotal in HCC pathogenesis and other liver diseases. However, the regulatory mechanism governing FBXW7 protein expression remains elusive. Herein, we unveil a non-canonical spliced isoform of the ubiquitin receptor ADRM1 that selectively degrades FBXW7 protein, thereby promoting the premalignant transformation of hepatic cells and conferring growth advantages to HCC tumors. Furthermore, our results demonstrate that ADRM1-ΔEx9-expressing HCC tumors exhibited sensitivity to Olaparib in a dose-dependent manner, implicating the potential use of Olaparib in targeting ADRM1-ΔEx9-driven HCC growth.

The Dynamics of Training and Development Initiatives: Unraveling their Influence on Organizational Performance

The research proposed by this study explores the relationship between training and development (T&amp;D) and the organization's performance with special reference to the corporate sector of Karachi. The premise for this research, therefore, lies in the understanding that the subject of employee development has been accepted as a key factor in the promotion of organizational effectiveness and efficiency and the attainment of competitive advantage within the complex business environment of the modern world. The study employed quantitative and qualitative data. The quantitative data is collected through closed ended question questionnaire based on five-point Likert scale the respondent were selected though convenience sample and analysed through SPSS and Smart PLS. The qualitative data is collected from a review of past relevant research papers from repositories and open-access journals, 102 respondents were interviewed during a survey conducted electronically. The study reveals the substantial positive interaction between organizational performance and T&amp;D programs, highlighting the potential for significant improvement and instilling a sense of hope and optimism. According to the study, there is an urgent and compelling need for the corporate sector of Karachi to strategically focus on the training and development of people in order to support organizational growth and development. Training is a powerful tool and opens up several Seiten of learning and development besides increasing motivation and commitment to work that, in turn, has a direct impact on productivity. Further, to confirm the importance of T&amp;D programs in sustainable growth and competitive advantage strategy, this study is quite appropriate through better focus, attention and development of its human capital, which is likely to result in the sustainable growth of the organization in the complex business environment of Karachi and other areas of the world.

Eco-evolutionary dynamics of adapting pathogens and host immunity

As pathogens spread in a population of hosts, immunity is built up, and the pool of susceptible individuals are depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with rapid antigenic evolution and frequent emergence of immune evasive variants. However, the host’s immune systems adapt, and older immune responses wane, such that escape variants only enjoy a growth advantage for a limited time. If variant growth dynamics and reshaping of host-immunity operate on comparable time scales, viral adaptation is determined by eco-evolutionary interactions that are not captured by models of rapid evolution in a fixed environment. Here, we use a Susceptible/Infected model to describe the interaction between an evolving viral population in a dynamic but immunologically diverse host population. We show that depending on strain cross-immunity, heterogeneity of the host population, and durability of immune responses, escape variants initially grow exponentially, but lose their growth advantage before reaching high frequencies. Their subsequent dynamics follows an anomalous random walk determined by future escape variants and results in variant trajectories that are unpredictable. This model can explain the apparent contradiction between the clearly adaptive nature of antigenic evolution and the quasi-neutral dynamics of high-frequency variants observed for influenza viruses.

Eco-evolutionary dynamics of adapting pathogens and host immunity.

As pathogens spread in a population of hosts, immunity is built up, and the pool of susceptible individuals are depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with rapid antigenic evolution and frequent emergence of immune evasive variants. However, the host's immune systems adapt, and older immune responses wane, such that escape variants only enjoy a growth advantage for a limited time. If variant growth dynamics and reshaping of host-immunity operate on comparable time scales, viral adaptation is determined by eco-evolutionary interactions that are not captured by models of rapid evolution in a fixed environment. Here, we use a Susceptible/Infected model to describe the interaction between an evolving viral population in a dynamic but immunologically diverse host population. We show that depending on strain cross-immunity, heterogeneity of the host population, and durability of immune responses, escape variants initially grow exponentially, but lose their growth advantage before reaching high frequencies. Their subsequent dynamics follows an anomalous random walk determined by future escape variants and results in variant trajectories that are unpredictable. This model can explain the apparent contradiction between the clearly adaptive nature of antigenic evolution and the quasi-neutral dynamics of high-frequency variants observed for influenza viruses.

Establishment and Characterization of Bisexually Fertile Triploid Dwarf Surf Clam Mulinia lateralis.

Triploids are widely used to rapidly achieve genetic improvements of organisms due to their fast growth and enhanced environmental adaptability. Artificially induced triploids are generally considered to be infertile owing to the obvious inhibition of gonadal development. Recently, some fertile individuals with reduced advantages have been found in triploid bivalves, which is a notable deviation from the original intention of artificially inducing triploids. This study utilized dwarf surf clams (Mulinia lateralis), a promising model organism of bivalves, to develop a model for exploring the potential mechanism of triploid reproduction. The results showed that the optimal induction condition for triploid M. lateralis, determined by orthogonal experiments, was 0.5mg/L cytochalasin B (CB) to inhibit PB2 for 20min, resulting in a triploidy rate of 95.57% and a hatching rate of 60.25%. By tracking the development of M. lateralis, we found that the induced triploids could develop normally to maturity and exhibited significant growth and survival advantages post-metamorphosis. Although the triploidy rate exhibited a slight decline overtime, it remained high, with a ratio of 90.63% at 120 dpf. Histological observation confirmed that the gonadal development pattern of triploid M. laterali was similar to that of diploids, but it also showed characteristics such as developmental retardation, few mature gametes, and gamete gigantism. The dynamic expression of genes related to gonadal development provided further molecular evidence for this phenomenon. Additionally, 82.6% of triploid M. laterali exhibited normal spawning behavior, produced fewer but larger viable gametes, and could generate offspring with full developmental potential. Flow cytometry analysis revealed that sperm of triploid M. laterali was aneuploid, with a DNA content of about 1.5 times that of diploid sperm, and the ploidy levels of mating offspring were 2N (DD, diploid female × diploid male), 2.5N (DT, diploid female × triploid male), 2.5N (TD, triploid female × diploid male), and 3N (TT, triploid female × triploid male), respectively. Overall, the artificially induced triploid M. laterali has been confirmed to be bisexually fertile, which will provide a unique model for exploring the underlying mechanisms of advantageous trait formation and fertility regulation in triploids, and offer a valuable platform for the study of ploidy control and polyploidization in bivalves. Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary. Yes, i have checked and it is OK.

Wheat genotypes selected for their high early daytime stomatal conductance under elevated nocturnal temperatures maintain high yield and biomass

Abstract Global nighttime temperatures are increasing and correlate with a decline in crop yield. Various aspects of nocturnal physiology in plants are under-studied, one of which is the independent influence on daytime processes. Twelve elite wheat genotypes were field-grown in plots with artificially increased nighttime temperatures (+ 2°C). The stomatal conductance on the adaxial and abaxial leaf side was measured during the morning and the night, and stomatal morphological traits were assessed during the same period of plant growth. To determine whether an increase in early daytime stomatal conductance provides a growth and/or yield advantage under high temperature, the biomass, grain number, grain weight, and grain yield were measured. Genotypes exhibiting the highest early daytime stomatal conductance also showed higher biomass, grain number, and yield. An increase of 19 % in early daytime stomatal conductance led to a yield increase of 86 and 65 gm-2, in heated and control conditions respectively, translating to 43 and 35 % yield enhancement. Irrespective of the environment, the adaxial leaf side showed the highest diurnal and nocturnal conductance, mirroring direct stomatal aperture (SA) measurements. The high nighttime temperature treatment increased daytime stomatal conductance but reduced nocturnal conductance. SA varied with growing conditions; in the morning, plants under high nighttime temperatures showed larger SA than those from the control independently of the leaf side, conversely, the opposite trend was observed in the night. Stomata on the adaxial leaf side showed higher density (SD) and larger size (SL). Results from this study show that early daytime conductance increased productivity in hot-irrigated environments studied here. Previous studies showed that high pre-dawn conductance improves morning photosynthesis, and here we find that high nocturnal temperatures increased early morning conductance but reduced night time conductance and this may be a factor that contributed to minimize yield losses.

RISK MANAGEMENT AS A DETERMINING FACTOR IN THE EFFECTIVENESS OF INNOVATION MANAGEMENT

Innovations are a key factor in competitiveness but are accompanied by risks such as technological failures and unpredictable market reactions. Effective risk management helps organizations minimize threats, stimulate creativity, and maintain long-term success by ensuring a balance between innovation and risk. This study analyzes the relationship between risk management and innovation management effectiveness. By evaluating how organizations can balance innovative efforts with the need for risk management, the paper emphasizes the importance of implementing risk management strategies to enhance innovation outcomes. Special attention is given to how risk management helps companies make strategic decisions, build an innovation culture, and effectively cope with challenges in competitive and market instability conditions. Risk management in the context of innovation plays a crucial role in the successful implementation of innovation projects. Innovations, by nature, are associated with uncertainty and risks that can significantly affect their success. The risk management process includes identifying, assessing, mitigating, and monitoring various types of risks—technological, financial, market, and organizational. This process helps organizations not only minimize potential threats but also effectively leverage opportunities arising from these risks. The article discusses key stages of risk management and how they can be integrated into innovation processes to ensure the successful implementation of projects and achieve long-term growth and competitive advantages.

Rapid Sex Identification in Spotted Knifejaw (Oplegnathus punctatus) Using tmem88 Gene Structural Variation Markers.

Spotted knifejaw (Oplegnathus punctatus) is an economically important marine cultured species exhibiting a unique complex sex chromosome system (X1X1X2X2 in females and X1X2Y in males), with males possessing one fewer chromosome (2n = 47) than females (2n = 48) and an abnormally large Y chromosome. Additionally, males demonstrate significant growth advantages over females. Rapid and accurate sex identification is essential for effective culture management, selective breeding, and population control. In this study, we identified a homologous region of the tmem88 gene containing large DNA insertion markers on the X and Y chromosomes through whole-genome sequencing of O. punctatus. The X1 chromosome harbors a 278bp DNA fragment, whereas the Y chromosome contains a 1472bp fragment, resulting in a 1194bp size difference indicative of structural variation in the non-coding region of the tmem88 gene. We developed a rapid detection method based on this variation, utilizing a pair of primers that amplify two distinct bands (278bp and 1472bp) in male (X1X2Y) individuals and a single 278bp band in female (X1X1X2X2) individuals when analyzed by agarose gel electrophoresis. This method enables efficient and accurate sex differentiation in O. punctatus, significantly reducing the time required for identification and enhancing detection efficiency. This study provides a valuable tool for the rapid identification of sex in O. punctatus, facilitating improved breeding strategies and supporting the large-scale production of high-quality fry.

Bacterial microcompartment utilization in the human commensal Escherichia coli Nissle 1917.

The human gut is a complex environment of different bacterial species, nutrient sources, and changing conditions that are essential for human health. An imbalance can allow for the emergence of opportunistic pathogens. Bacterial microcompartments (BMCs) are utilized by bacteria to metabolize less common nutrients, conferring a growth advantage. Although widely studied in enteropathogens, there is limited research on BMC activity in commensal species. We demonstrate the formation of the eut BMC and utilization of ethanolamine as a carbon source in the human gut commensal Escherichia coli Nissle 1917 (EcN). Additionally, we found increased ammonium production when EcN utilized ethanolamine but did not see the same in Salmonella enterica, highlighting potential differences in how these species affect the wider microbial community.

A spheroid whole mount drug testing pipeline with machine-learning based image analysis identifies cell-type specific differences in drug efficacy on a single-cell level

BackgroundThe growth and drug response of tumors are influenced by their stromal composition, both in vivo and 3D-cell culture models. Cell-type inherent features as well as mutual relationships between the different cell types in a tumor might affect drug susceptibility of the tumor as a whole and/or of its cell populations. However, a lack of single-cell procedures with sufficient detail has hampered the automated observation of cell-type-specific effects in three-dimensional stroma-tumor cell co-cultures.MethodsHere, we developed a high-content pipeline ranging from the setup of novel tumor-fibroblast spheroid co-cultures over optical tissue clearing, whole mount staining, and 3D confocal microscopy to optimized 3D-image segmentation and a 3D-deep-learning model to automate the analysis of a range of cell-type-specific processes, such as cell proliferation, apoptosis, necrosis, drug susceptibility, nuclear morphology, and cell density.ResultsThis demonstrated that co-cultures of KP-4 tumor cells with CCD-1137Sk fibroblasts exhibited a growth advantage compared to tumor cell mono-cultures, resulting in higher cell counts following cytostatic treatments with paclitaxel and doxorubicin. However, cell-type-specific single-cell analysis revealed that this apparent benefit of co-cultures was due to a higher resilience of fibroblasts against the drugs and did not indicate a higher drug resistance of the KP-4 cancer cells during co-culture. Conversely, cancer cells were partially even more susceptible in the presence of fibroblasts than in mono-cultures.ConclusionIn summary, this underlines that a novel cell-type-specific single-cell analysis method can reveal critical insights regarding the mechanism of action of drug substances in three-dimensional cell culture models.

Identification of Three POMCa Genotypes in Largemouth Bass (Micropterus salmoides) and Their Differential Physiological Responses to Feed Domestication.

Diverse feeding habits in teleosts involve a wide range of appetite-regulating factors. As an appetite-suppressing gene, the polymorphisms of POMCa in largemouth bass (Micropterus salmoides) were validated via sequencing and high-resolution melting (HRM). The frequency distribution of different POMCa genotypes were analyzed in two populations, and physiological responses of different POMCa genotypes to feed domestication were investigated. The indel of an 18 bp AU-rich element (ARE) in the 3' UTR and four interlocked SNP loci in the ORF of 1828 bp of POMCa cDNA sequence were identified in largemouth bass and constituted three genotypes of POMC-A I, II, and III, respectively. POMC-A I and Allele I had increased frequencies in the selection population than in the non-selection population (p < 0.01), 63.55% vs. 43.33% and 0.7850 vs. 0.6778, respectively. POMC-A I possessed the lowest value of POMCa mRNA during fasting (p < 0.05) and exhibited growth and physiological advantages under food deprivation and refeeding according to the levels of body mass and four physiological indicators, i.e., cortisol (Cor), growth hormone (GH), insulin-like growth factor-1 (IGF-1), and glucose (Glu). The identification of three POMCa genotypes, alongside their varying physiological responses during feed domestication, suggests a selective advantage that could be leveraged in molecular marker-assisted breeding of largemouth bass that are adapted to feeding on formula diet.

Stem cell graft dose and composition could impact on the expansion of donor-derived clones after allogeneic hematopoietic stem cell transplantation - a virtual clinical trial.

Hematopoietic stem cell transplantation is a potentially curative intervention for a broad range of diseases. However, there is evidence that malignant or pre-malignant clones contained in the transplant can expand in the recipient and trigger donor-derived malignancies. This observation has gained much attention in the context of clonal hematopoiesis, a medical condition where significant amounts of healthy blood cells are derived from a small number of hematopoietic stem cell clones. In many cases the dominating clones carry mutations conferring a growth advantage and thus could undergo malignant transformation in the recipient. Since clonal hematopoiesis exists in a significant proportion of potential stem cell donors, a more detailed understanding of its role for stem cell transplantation is required. We propose mechanistic computational models and perform virtual clinical trials to investigate clonal dynamics during and after allogenic hematopoietic stem cell transplantation. Different mechanisms of clonal expansion are considered, including mutation-related changes of stem cell proliferation and self-renewal, aberrant response of mutated cells to systemic signals, and self-sustaining chronic inflammation triggered by the mutated cells. Model simulations suggest that an aberrant response of mutated cells to systemic signals is sufficient to explain the frequently observed quick expansion of the mutated clone shortly after transplantation which is followed by a stabilization of the mutated cell number at a constant value. In contrary, a mutation-related increase of self-renewal or self-sustaining chronic inflammation lead to ongoing clonal expansion. Our virtual clinical trials suggest that a low number of transplanted stem cells per kg of body weight increases the transplantation-related expansion of donor-derived clones, whereas the transplanted progenitor dose or growth factor support after transplantation have no impact on clonal dynamics. Furthermore, in our simulations the change of the donors' variant allele frequencies in the year before stem cell donation is associated with the expansion of donor-derived clones in the recipient. This in silico study provides insights in the mechanisms leading to clonal expansion and identifies questions that could be addressed in future clinical trials.

Growth Superiority and Genetic Characterization of the Hybrid from Female Ussuri Catfish (Pseudobagrus ussuriensis) and Male Longsnout Catfish (Leiocassis longirostris).

Crossbreeding is a traditional breeding technique and has been performed successfully in many fish species. However, distant hybridization between different genera is hard to be successful because of reproductive isolation. In this study, diploid hybrids (PL) were successfully derived from the hybridization of Ussuri catfish (Pseudobagrus ussuriensis, PU, ♀, 2n = 52) and longsnout catfish (Leiocassis longirostris, LL, ♂, 2n = 52). And the morphological data, external frame parameters, chromosomal karyotypes, DNA content measurement, mitochondrial DNA control region, and species-specific marker identification were applied to investigate the traits and genetic characterization of the PL hybrid offspring and their parents. Both quantifiable traits and shape frame parameters of the PL hybrid offspring were revealed to be intermediate between those of their parents; however, cluster analysis showed that their external morphology was more in favor of the maternal PU. The growth comparisons showed that the hybrids had significant growth advantages over maternal PU. Based on karyotype patterns, DNA contents and mitochondrial DNA, the hybrid origin and maternal inheritance of hybrid offspring were further confirmed. According to the sequence variations identified from the genome sequences of the two catfish species, one species-specific marker was developed to distinguish the PL hybrid offspring and their parents. Therefore, this study provides a successful case for intergeneric hybridization and hybrid superiority, and the PL hybrid shows promise for commercial application, pending further studies into its husbandry, health, and welfare with larger populations of fish.

Fast-track health technology assessment for in vitro diagnostics—a design thinking case study

The evolution of diagnostic technologies, combined with the urgent need for efficient healthcare delivery in challenging public health contexts, calls for agile and empathetic innovation. This is particularly relevant in...

RhlR-mediated cooperation in cystic fibrosis-adapted isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa uses quorum sensing (QS) to regulate the expression of dozens of genes, many of which encode shared products, called "public goods." P. aeruginosa possesses two complete acyl-homoserine lactone (AHL) QS circuits: the LasR-I and RhlR-I systems. Canonically, these systems are hierarchically organized: RhlR-I activity depends on LasR-I activation. However, in contrast to laboratory strains, isolates from people with cystic fibrosis can engage in AHL QS using only the transcription factor RhlR. In these isolates, RhlR regulates AHL QS and the production of secreted public goods, such as the exoprotease elastase, which are accessible to both producing and non-producing cells. When P. aeruginosa strains that use LasR to regulate elastase production are grown on casein as the sole carbon and energy source, LasR-null mutant "cheaters" commonly arise in populations due to a selective growth advantage. We asked if these social dynamics might differ in "RhlR cooperators": populations that use RhlR, not LasR, to regulate public goods. We passaged RhlR cooperators from several genetic backgrounds in casein broth. We found that cheaters emerged among most RhlR cooperators. However, in one isolate background, E90, RhlR-null mutants were dramatically outcompeted by RhlR cooperators. In this background, the mechanism by which RhlR mutants are outcompeted by RhlR cooperators is AHL-dependent and occurs in stationary phase but is not the same as previously described "policing" mechanisms. Our data suggest that cheating, or the lack thereof, does not explain the lack of RhlR mutants observed in most infection environments.IMPORTANCEQuorum sensing (QS) mutants arise in a variety of populations of bacteria, but mutants of the gene encoding the transcription factor RhlR in Pseudomonas aeruginosa appear to be infrequent. Our work provides insight on the mechanisms through which RhlR-mediated cooperation is maintained in a LasR-null population of P. aeruginosa. Characterizing the selective pressure(s) that disfavor mutations from occurring in RhlR may enhance our understanding of P. aeruginosa evolution in chronic infections and potentially guide the development of therapeutics targeting the RhlR-I QS circuit.

Origin of Chromosome 12 Trisomy Surge in Human Induced Pluripotent Stem Cells (iPSCs).

Cultured pluripotent stem cells are unique in being the only fully diploid immortal human cell lines. However, during continued culture they can acquire significant chromosome abnormalities. Chromosome 12 trisomy is the most common whole-chromosome abnormality found during culture of human induced pluripotent stem cells (iPSCs). The conventional paradigm is that trisomy 12 occurs very rarely but provides a proliferative advantage, enabling these cells to outcompete the diploid. Here, we challenge this prevailing model by demonstrating that trisomy 12 can arise simultaneously during mitosis in a high percentage (~2%) of diploid iPSCs. Using a single cell line that reproducibly undergoes transition from diploid to trisomy 12, we found that proliferation differences alone could not account for the rapid dominance of trisomic cells. Through careful mapping by fluorescent in-situ hybridization (FISH), we identified critical transition passages where trisomic cells first appeared and swiftly gained dominance. Remarkably, single trisomic cells repeatedly emerged de novo from diploid parents. Delving deeper, we discovered an extremely high incidence of chromosome 12 anaphase bridging exclusively during transition passages, along with overrepresentation of chromosome 12 chromatids in micronuclei. These micronuclei failed to replicate during S phase, leading to M phase cells containing two normal replicated copies of chromosome 12 and one unreplicated single chromatid. Consequently, we observed 1.5% of metaphase cells with an unpaired chromosome 12 chromatid positioned outside the metaphase plate, and 2% anaphase cells showing three chromosome 12 signals oriented to one pole and two to the other. Further analysis revealed that nearly 20% of subtelomeric repeats were eroded in the p arms but not q arms of chromosome 12 during transition passages. We found that p arm fusions were exclusively responsible for the chromosome 12 bridging observed in anaphase cells of transition passages. Our findings unveil a novel mechanism of whole-chromosome instability in iPSCs, where chromosome 12p arm-specific segregation errors occur simultaneously in a high percentage of cells rather than originating from single, rare events. The slight yet significant growth advantage of trisomy 12 cells allows them to persist and eventually dominate the population. This discovery has profound implications for pinpointing origins of chromosome instability during culture of iPSCs and helping to promote their effective use in research and regenerative medicine.

In vitro culture of Leucoagaricus gongylophorus (Agaricaceae), symbiont fungus of the leaf-cutting ant Atta mexicana (Hymenoptera, Formicidae), using solid and plant-supplemented culture media

Background and Aims: The mutualism between leaf-cutting ants and the fungus Leucoagaricus gongylophorus is a remarkable instance of insect-fungus symbiosis. In this study, we aimed to make a molecular identification of the L. gongylophorus strain obtained from the fungal garden of Atta mexicana, to compare the mycelial growth of the strain in several culture media and PDA medium enriched with foliar material from several plants and perform a cost analysis for the in vitro maintenance of the symbiont fungus.Methods: Seven solid culture media were compared for the in vitro growth of Leucoagaricus gongylophorus isolated from an Atta mexicana nest. In addition, we compared the fungal growth on Potato Dextrose Agar (PDA) medium enriched with selected foliar material from the leaves of six plants previously known to be either well-foraged or avoided by Atta mexicana.Key results: Higher mycelial growth percentages were obtained on compost extract added with a mineral mixture (CE) (27.3±12.7 mm) and PDA media (25.3±1.15 mm) at 28 days of growth. Furthermore, this is the first study reporting the growth of a fungal symbiont of Atta mexicana on CE, complete basic medium (CBM), Pagnocca A, and B media. PDA media enriched with some plants did not show advantages for fungus growth. Lower mycelial growth percentages were obtained on PDA media enriched with Rosa alba (0.0±0.0 mm), Coffea arabica (5.3±0.66 mm), Citrus reticulata (3.0±1.0 mm), and Psidium guajava (2.0±1.15 mm) leaves, in comparison with the control treatment (PDA medium).Conclusions: The use of culture media like CE and CBM might be a cost-effective alternative for in vitro culture of Leucoagaricus gongylophorus, even in the absence of ants. Leaves of some plant species inhibit in vitro growth of this fungus, in line with their status as plants avoided by Atta mexicana. The strong inhibition of the extract of Rosa alba, the best-foraged plant by Atta mexicana, suggests the existence of particularly effective detoxification mechanisms in natural conditions.

Pengaruh Influencer Marketing, Digital Marketing, dan Brand Image Pada Minat Beli Konsumen Tokopedia

This study aims to examine the influence of influencer marketing, digital marketing, and brand image on consumer purchase intention on the Tokopedia e-commerce platform. A quantitative research method with a replication approach was conducted in Batam City, Riau Islands, involving 204 Tokopedia users as respondents. Data were collected through questionnaires and analysed using SPSS version 26. The findings indicate that influencer marketing, digital marketing, and brand image significantly influence consumer purchase intention on Tokopedia. Data analysis shows good validity and reliability for all variables studied. Normality tests indicate that the data are normally distributed, and multicollinearity tests confirm no issues among the independent variables. These findings provide insights into the critical roles of digital marketing strategies and brand image management in influencing consumer purchasing behaviour on Tokopedia. Practical implications highlight the importance for Tokopedia to continually optimize digital marketing strategies and enhance brand image quality to support growth and competitive advantage in the competitive e-commerce market. Moreover, the study contributes to the existing literature by emphasizing the specific mechanisms through which influencer marketing and digital strategies shape consumer perceptions and behaviours in the online marketplace. Future research could explore additional variables or conduct longitudinal studies to further understand the evolving dynamics of consumer behaviour in the digital age.

Adoption of social media by small and medium sized (SMEs) enterprises of District Sargodha for promotion of Businesses

Social Media Marketing has become a key driver of growth and competitive advantage in many business enterprises in the developed world. Small and Medium Enterprises in District Sargodha, Punjab Pakistan are faced with numerous challenges which made mortality rate of small businesses very high. Social media marketing has the potential of enhancing the growth of SMEs in Pakistan. However, its adoption rate among SMEs is still low. The objective of this study therefore is to investigate the factors influencing Social Media Marketing adoption by SMEs in Sargodha using the Diffusion of Innovation framework. This study models the adoption social media marketing by SMEs in District Sargodha using Everett Rogers’ Diffusion of Innovation theory. The study adopts a cross-sectional survey research design using a structured questionnaire to collect data from 200 SMEs located in District Sargodha, Punjab Pakistan. Data were analysed using multiple regression Ordinary Least Squares Method. Results show that only complexity of social media for all SMEs are significantly determines social media adoption by SMEs. Other dependent factors do not have significant effect on social media adoption. As such, it was recommended that attention should be paid to these variables to drive the adoption social media marketing by SMEs.