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Background Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum. Methods Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal and db/db , ob/ob and wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum. Results Development : Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α was high in ITf but decreased in STf. Glucose escalated in db/db and ob/ob sera. Glucose doubled in ITf while being halved in STf in db/db mice. Glucose significantly dropped in db/db and ob/ob mice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf in db/db and ob/ob mice. One hundred ten kDa IR-β and 135 kDa IR-α decreased in db/db and ob/ob ITf. Only 110 kDa IR-β dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-β fell in db/db and ob/ob SPZ. One hundred ten kDa s IR-α rose in the db/db and ob/ob mouse sera. Conclusion Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α in the db/db and ob/ob interstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased in db/db and ob/ob mice.

Hyaluronan (HA) has gained significant attention in cancer research for its role in modulating chemoresistance. This review aims to elucidate the mechanisms by which HA contributes to chemoresistance, focusing on its interactions within the tumor microenvironment. HA is abundantly present in the extracellular matrix (ECM) and binds to cell-surface receptors such as CD44 and RHAMM. These interactions activate various signaling pathways, including PI3K/Akt, MAPK, and NF-κB, which are implicated in cell survival, proliferation, and drug resistance. HA also influences the physical properties of the tumor stroma, enhancing its density and reducing drug penetration. Additionally, HA-mediated signaling contributes to the epithelial–mesenchymal transition (EMT), a process associated with increased metastatic potential and resistance to apoptosis. Emerging therapeutic strategies aim to counteract HA-induced chemoresistance by targeting HA synthesis, degradation, metabolism, or its binding to CD44. This review underscores the complexity of HA’s role in chemoresistance and highlights the potential for HA-targeted therapies to improve the efficacy of conventional chemotherapeutics.

The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.

Recent studies of plant-animal mutualistic networks have assumed that interaction frequency between mutualists predicts species impacts (population-level effects), and that field estimates of interaction strength (per-interaction effects) are unnecessary. Although existing evidence supports this assumption for the effect of animals on plants, no studies have evaluated it for the reciprocal effect of plants on animals. We evaluate this assumption using data on the reproductive effects of pollinators on plants and the reciprocal reproductive effects of plants on pollinators. The magnitude of species impacts of plants on pollinators, the reciprocal impacts of pollinators on plants, and their asymmetry were well predicted by interaction frequency. However, interaction strength was a key determinant of the sign of species impacts. These results underscore the importance of quantifying interaction strength in studies of mutualistic networks. We also show that the distributions of interaction strengths and species impacts are highly skewed, with few strong and many weak interactions. This skewed distribution matches the pattern observed in food webs, suggesting that the community-wide organization of species interactions is fundamentally similar between mutualistic and antagonistic interactions. Our results have profound ecological implications, given the key role of interaction strength for community stability.

UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.

The pelagic larval phase represents a critical period in the early life history of fishes, since larval growth and development can contribute substantially to patterns of survival, dispersal and connectivity. The microstructure of otoliths was examined to investigate events during the early life history of the bridled monocle bream Scolopsis bilineatus (Nemipteridae) on the Great Barrier Reef. We validated a distinct settlement mark, characterized by a rapid transition from wide to narrow increments. The time fish spent in the plankton (Pelagic Larval Duration; PLD) ranged from 17 to 27 days (mean = 21.3 days), which is similar to many other fish families. Three distinct early life history stages occurred: pre-settlers (larvae), newly settled fish, and settled juveniles. Increment width (a proxy for growth) was sequentially narrower with each life history stage; pre-settlers>newly settled>settled juveniles, and growth was reduced as fish approached and underwent settlement to reef habitats. Evidence is provided for a “search phase”, whereby growth was reduced in the three to four days preceding settlement; this pattern may be indicative of changes in the behaviour of larvae immediately prior to settling. Two manipulative experiments investigated the effects of diet ration on otolith increment widths. Reduced food intake resulted in significantly narrower increment widths, with a possible lag effect of at least six days. Experiment results indicated that increment widths can be a reliable proxy of somatic growth, and results from this study overall highlight the utility of otoliths as a tool for investigating the early life history of fishes.

The response of crops to changing climate and atmospheric CO2 concentration ([CO2]) could have large effects on food production, and impact carbon, water, and energy fluxes, causing feedbacks to the climate. To simulate the response of temperate crops to changing climate and [CO2], which accounts for the specific phenology of crops mediated by management practice, we describe here the development of a process-oriented terrestrial biogeochemical model named ORCHIDEE-CROP (v0), which integrates a generic crop phenology and harvest module, and a very simple parameterization of nitrogen fertilization, into the land surface model (LSM) ORCHIDEEv196, in order to simulate biophysical and biochemical interactions in croplands, as well as plant productivity and harvested yield. The model is applicable for a range of temperate crops, but is tested here using maize and winter wheat, with the phenological parameterizations of two European varieties originating from the STICS agronomical model. We evaluate the ORCHIDEE-CROP (v0) model against eddy covariance and biometric measurements at seven winter wheat and maize sites in Europe. The specific ecosystem variables used in the evaluation are CO2 fluxes (net ecosystem exchange, NEE), latent heat, and sensible heat fluxes. Additional measurements of leaf area index (LAI) and aboveground biomass and yield are used as well. Evaluation results revealed that ORCHIDEE-CROP (v0) reproduced the observed timing of crop development stages and the amplitude of the LAI changes. This is in contrast to ORCHIDEEv196 where, by default, crops have the same phenology as grass. A halving of the root mean square error for LAI from 2.38 ± 0.77 to 1.08 ± 0.34 m2 m−2 was obtained when ORCHIDEEv196 and ORCHIDEE-CROP (v0) were compared across the seven study sites. Improved crop phenology and carbon allocation led to a good match between modeled and observed aboveground biomass (with a normalized root mean squared error (NRMSE) of 11.0–54.2 %), crop yield, daily carbon and energy fluxes (with a NRMSE of  ∼  9.0–20.1 and  ∼  9.4–22.3 % for NEE), and sensible and latent heat fluxes. The simulated yields for winter wheat and maize from ORCHIDEE-CROP (v0) showed a good match with the simulated results from STICS for three sites with available crop yield observations, where the average NRMSE was  ∼  8.8 %. The model data misfit for energy fluxes were within the uncertainties of the measurements, which themselves showed an incomplete energy balance closure within the range 80.6–86.3 %. The remaining discrepancies between the modeled and observed LAI and other variables at specific sites were partly attributable to unrealistic representations of management events by the model. ORCHIDEE-CROP (v0) has the ability to capture the spatial gradients of carbon and energy-related variables, such as gross primary productivity, NEE, and sensible and latent heat fluxes across the sites in Europe, which is an important requirement for future spatially explicit simulations. Further improvement of the model, with an explicit parameterization of nutritional dynamics and management, is expected to improve its predictive ability to simulate croplands in an Earth system model.

The PCSK9 contribution to cholesterol and immunotolerance homeostasis and response to glucose, and insulin in testis and hypophysis were studied using Pcsk9 -deficient ( −/− ) and transgenic [Tg (PCSK9)] mice, and diabetic, obese ob/ob and db/db mice. The spermatids/spermatozoa acrosome, peritubular vessels, and epididymal adipocytes were PCSK9- and LDL-R-positive. The pro-PCSK9/PCSK9 ratio was high in interstitial tissue-fractions (ITf) and spermatozoa and low in seminiferous tubule-fractions (STf) in normal adult mice. This ratio decreased in ITf in ob/ob and db/db mice but increased in tubules in ob/ob mice. Deleting pcsk9 lowered cholesterol in serum but increased testicular cholesterol. Furthermore, HMGCoA-red, ACAT-2 and LDL-R turnover increased whereas SR-BI decreased in ITf; in tubules, ABCA1 decreased and 160 kDa LDL-R increased in Pcsk9 −/− mice. Excess testicular cholesterol could result from increased cholesterol synthesis and uptake with reduction in SR-BI-mediated efflux in ITf and from the overload of apoptotic cells, lowered ABCA1-mediated efflux and stimulated LDL-R protein synthesis in tubules in Pcsk9 −/− mice. Concomitantly with the cholesterol accumulation, tubules showed infiltrates of immune cells, elevated IL-17A and IL-17RA, and changes in the immunotolerance homeostasis. PCSK9 deficiency decreased glucose in tubules and spermatozoa while increasing insulin2 in ITf and tubules not serum. Moreover, IR-α, and IR-β augmented in tubules but decreased in the anterior pituitary; IR-α increased whereas IR-β decreased in ITf. The histology and cholesterol levels were normal in Tg (PCSK9) mouse testis. The excess cholesterol creates a milieu favorable to the action of high IL-17A and IL-17RA, the development of inflammatory conditions and self-tolerance breakdown in testis.

Eurocentric music education is not a \"one size fits all\" approach to teaching and learning, particularly since many students do not relate nor connect with such formal and prescribed pedagogy. Hence, classroom music teachers have a responsibility to investigate and explore non-Western methods of musical practices, particularly since many classrooms in Canada are culturally diverse. This article does not debase traditional methods of music education but instead seeks to foster new and novel pedagogical techniques that are more inclusive and diverse, ultimately cultivating the growth of music programs while simultaneously inspiring more students to value and appreciate music as a lifelong endeavour. The principal goal of this article, therefore, is to provide eight rationales that collectively address the following question: Would music education acutely benefit from dispensing with traditional Eurocentric pedagogies rooted in the reading of standard musical notation?

This year marks a milestone for me - 40 years of playing the electric bass. As a veteran performer and music teacher educator, I would like to offer my professional and personal perspectives on all things electric bass. Specifically, I would like to address the following four questions: (i) Why have electric bass players garnered such an undesirable reputation?(ii) What function does the electric bass serve in pop music? (Hi) Does the electric bass have a role in Concert Band? and (iv) What are some practical tips for beginner bass players?