Importance Of Extrinsic Factors Research Articles

Movement patterns and activity levels are shaped by the neonatal environment in Antarctic fur seal pups

Tracking studies of juveniles are rare compared to those of adults, and consequently little is known about the influence of intrinsic and extrinsic factors on activity during this critical life stage. We used hourly GPS data, collected from 66 Antarctic fur seal pups from birth until moulting, to investigate the explanatory power of multiple individual-based and environmental variables on activity levels. Pups were sampled from two nearby breeding colonies of contrasting density during two subsequent years, and a two-state hidden Markov model was used to identify modalities in their movement behaviour, specifically ‘active’ and ‘inactive’ states. We found that movement was typified by central place exploration, with active movement away from and subsequent return to a location of inactivity. The probability of such directed exploration was unaffected by several factors known to influence marine mammal movement including sex, body condition, and temperature. Compared to pups born at the high-density colony, pups at low-density were more active, increased their activity with age, and transitioned earlier into the tussock grass, which offers protection from predators and extreme weather. Our study illustrates the importance of extrinsic factors, such as colony of birth, to early-life activity patterns and highlights the adaptive potential of movement.

Abstract 926: Extrinsic and intrinsic activation of RAS/MAPK signaling enables resistance to FLT3 inhibitor, gilteritinib, in acute myeloid leukemia

Abstract Acute Myeloid Leukemia (AML) remains a highly fatal disease due to the development of drug resistance. Mutational activation of kinases is a frequent event in leukemia, driving malignant cell growth. The most commonly mutated kinase in AML is the FMS-like tyrosine kinase 3 (FLT3) receptor. Internal tandem duplication (ITD) events in the juxtamembrane domain of FLT3 have been reported in ~ 20% of patients and lead to constitutive activation of FLT3. Previous work from our laboratory has shown that fibroblast growth factor 2 (FGF2) secreted by mesenchymal stromal cells protects FLT3-ITD AML cells from quizartinib, a FLT3 inhibitor (Cancer Research, 2016). FGF2 binds the FGFR1 receptor and activates MAPK signaling, enabling leukemia cells to become drug resistant. Over months of treatment, FGF2-protected leukemia cells acquired FLT3 resistance mutations. This two-step mechanism of resistance in vitro mirrors what happens in patients treated with quizartinib. Newer FLT3 inhibitors, such as gilteritinib, have been developed that have activity against both ITD and kinase domain mutations that impart resistance to quizartinib. We used a similar approach and treated the FLT3-ITD+ AML cell line, MOLM-14, with 100 nM of gilteritinib in media alone (n=4), or supplemented with 10 ng/ml FGF2 (n=4) or FLT3 ligand (FL, n=4). After 7 weeks, all cultures supplemented with FGF2 or FL eventually resumed growth. In contrast, no MOLM-14 cells cultured in gilteritinib alone resumed growth even after 16 weeks, suggesting the importance of extrinsic factors in facilitating early drug resistance. Selective pressure was then put on the ligand-dependent cultures by removal of FGF2 and FL. This transiently restored sensitivity to gilteritinib, however within a month the cultures resumed exponential growth. To further explore the mechanism of resistance, we performed immunoblots of kinase signaling pathways on MOLM-14 resistant cultures pre- and post-withdrawal of ligands. We saw robust activation of FLT3 receptor in resistant cultures with FL. FGF2 activated the MAPK pathway, circumventing inhibition by gilteritinib. After removal of extrinsic FGF2 and FL, there was re-activation of MAPK signaling but FLT3 itself remained inhibited. Whole Exome Sequencing of resistant cells identified NRAS mutations as the source of MAPK signaling after ligand withdrawal. Two of the four FGF2-supplemented cultures also developed novel FLT3 point mutations, although there was no clear re-activation of FLT3 signaling in these cultures. Our in vitro results suggest that extrinsic signals from the microenvironment can re-activate MAPK pathways enough to keep cells alive but continued selective pressure eventually leads to direct activation of MAPK through RAS mutations. As such, there is a need to consider rational inhibitor combinations early in disease therapy to prevent the emergence of resistance. Citation Format: Sunil K. Joshi, Stephen Christy, Renata Scopim Ribeiro, Shannon McWeeney, Jeffrey W. Tyner, Cristina E. Tognon, Brian J. Druker, Elie Traer. Extrinsic and intrinsic activation of RAS/MAPK signaling enables resistance to FLT3 inhibitor, gilteritinib, in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 926.

The Impact of Extrinsic Motivation on Employees’ Performance: A Comparative Analysis of Food and Textile Industries in Sindh, Pakistan

The purpose of present study is to examine the effects of external motivational factors on employees. Current study is employed Herzberg’s two-factor theory to investigate the effects of extrinsic factors on employees’ performance.in food and textile industries of Sindh, Pakistan. Seven point Likert scale is used for survey purpose. Reliability test is conducted for knowing the internal consistency of extrinsic factors as independent variables and employees’ performance as dependent variable. Pearson correlation, Analysis Of Variance (ANOVA), t test and multiple regression techniques are employed for data analysis.The results found that all extrinsic factors have positive and significant effects on employees. This study provides good amount of knowledge on the importance of extrinsic factors for improving the employees’ performance.

The importance of extrinsic factors in the development of cancers

ABSTRACTThere was recently a debate on the relative importance of intrinsic versus extrinsic factors in cancer risk. We reported that extrinsic risk factors contribute substantially (more than 70–90%) to most common cancers. This finding promotes further research into the causes of cancer and how they could be prevented.

Functions of neurotrophins and growth factors in neurogenesis and brain repair

The identification and isolation of multipotent neural stem and progenitor cells in the brain, giving rise to neurons, astrocytes, and oligodendrocytes initiated many studies in order to understand basic mechanisms of endogenous neurogenesis and repair mechanisms of the nervous system and to develop novel therapeutic strategies for cellular regeneration therapies in brain disease. A previous review (Trujillo et al., Cytometry A 2009;75:38-53) focused on the importance of extrinsic factors, especially neurotransmitters, for directing migration and neurogenesis in the developing and adult brain. Here, we extend our review discussing the effects of the principal growth and neurotrophic factors as well as their intracellular signal transduction on neurogenesis, fate determination and neuroprotective mechanisms. Many of these mechanisms have been elucidated by in vitro studies for which neural stem cells were isolated, grown as neurospheres, induced to neural differentiation under desired experimental conditions, and analyzed for embryonic, progenitor, and neural marker expression by flow and imaging cytometry techniques. The better understanding of neural stem cells proliferation and differentiation is crucial for any therapeutic intervention aiming at neural stem cell transplantation and recruitment of endogenous repair mechanisms.

Skin ageing

AbstractSimilar to the entire organism, skin is subject to an unpreventable intrinsic ageing process. Additionally, skin ageing is also influenced by exogenous factors. Ultraviolet radiation in particular results in premature skin ageing, also referred to as extrinsic skin ageing or photoageing, which is the main cause of the changes associated with the ageing process in sun‐exposed areas. Despite their morphological and pathophysiological differences, intrinsic and extrinsic ageing share several molecular similarities. The formation of reactive oxygen species and the induction of matrix metalloproteinases reflect the central aspects of skin ageing. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for the further degradation of the extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin ageing and the detection of its mechanisms have furthered the development of various therapeutic and preventive strategies.

Hautalterung

Like the entire human organism, the skin is subject to an intrinsic unpreventable aging process. But exogenous factors also influence skin aging. Ultraviolet radiation in particular results in premature skin aging, also referred to as extrinsic skin aging or photo aging, causing in large part aging-associated changes in sun-exposed areas. Intrinsic and extrinsic aging share several molecular similarities despite morphological and pathophysiological differences. The formation of reactive oxygen species and the induction of metalloproteinases reflect central aspects of skin aging. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for further degradation of extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin aging and the detection of its mechanisms has given rise to development of various therapeutic and preventive strategies.

PREFERENCE–PERFORMANCE RELATIONSHIPS AND EFFECTS OF HOST PLANT CHOICE IN AN HERBIVOROUS MARINE AMPHIPOD

The fitness of herbivores that have limited mobility as juveniles or larvae may often depend on the host choice behavior of adults. For such herbivores, selection should favor adults that choose plants that maximize the performance of their offspring, resulting in positive correlations across host plants among adult preferences, offspring performance (growth, survival, etc.), and for herbivores that are restricted to living on host plants, population-level parameters such as abundance on different hosts. We tested this hypothesis for the marine, nest-building amphipod Peramphithoe parmerong, using a series of behavioral and performance assays and relevant field data. Adults displayed strong preferences among eight species of brown algae in habitat choice assays, with Sargassum linearifolium and S. vestitum highly preferred; Colpomenia peregrina and Padina crassa of lower preference; and Dictyopteris acrostichoides, Dictyota dichotoma, Dilophus marginata, and Zonaria diesingiana consistently avoided. Juvenile amphipods were relatively immobile and, thus, mostly constrained to the host alga selected by their mother. Differences in the growth and survival of juvenile amphipods raised on single-species diets were consistent with adult nest-building preferences among algae, with the best performance on the two high-preference species of Sargassum. Thus, adult preferences for host plants largely determined juvenile performance due to (1) restricted movement by juveniles and (2) differences among algal species in their effects on growth, survival, and onset of reproduction. In contrast to host plant preferences by adults, feeding rates on different algae were not as clearly correlated with juvenile performance. In particular, the low-preference C. peregrina was consumed at a high rate, but survivorship on this alga was relatively poor. Differences in abundances of P. parmerong on different host algae in the field were consistent with laboratory preferences and not related to relative algal abundance or epiphyte loads, supporting the hypothesis that there were population-level consequences of host plant choice in this species. With regard to mechanisms underlying host use, amphipod preferences were closely (negatively) correlated with the presence of nonpolar secondary metabolites. Nonpolar crude extracts from nonhost species, all of which contain secondary metabolites, affected amphipod host acceptance behavior, whereas extracts from host species, all of which lack such metabolites, did not. Overall, host plant use was unrelated to the nutritional value of the algal species, but one low-preference host, C. peregrina, was notably nutritionally poor. These observations, and the correlations among adult preferences, offspring performance, and field densities for P. parmerong, are consistent with intrinsic host plant qualities determining host plant range for this species. This contrasts with previous studies that emphasized the importance of extrinsic factors, particularly predation, in determining amphipod host use.

Extrinsic factors affecting the reproduction of Nippostrongylus brasiliensis.

Experiments to study the effect of extrinsic factors on the copulation of normal adultNippostrongylus brasiliensisare described. Worms copulated when in contact with the rat small intestine, whether it was ligatured, maintained inside or outside the peritoneal cavity, slit open or its lumen obstructed, provided that the blood supply remained intact and the temperature was within a few degrees of normal. Copulation did not occur in the colon, pleural cavity, peritoneal cavity, pregnant or non-pregnant uterus of the live rat or under a variety ofin vitroconditions. These results indicate the importance of extrinsic factors for successful copulation since all the worms used in the experiments were intrinsically ready for immediate copulation in their normal environment. Worms observed duringin vitroexperiments were more vigorous and erratic in their movements than worms in their normal environment. The possible significance of this observation is discussed both in the context ofin vitroreproduction experiments andin vitroexperiments to study the physiology and biochemistry of the worm.