Differential Effect Research Articles

Semiconductive-like Behaviour and Negative Differential Effect Observed in Self-Assembled Riboflavin Layer on Gold Electrodes

Riboflavin or vitamin B2 plays significant roles in metabolic reactions and energy production, establishing it as an important research subject in biology and medicine. While there are numerous riboflavin-related publications in these fields, interrogation of its electronic properties in relation to the physiological function at the cellular level remains obscure due to technological challenges. However, progress in molecular electronics and the discovery of the semiconductor-like behaviour of biomolecules in recent times have initiated growing interest in exploring the electronic properties of these materials for potential bioelectronic device applications. In this work, we demonstrate novel semiconductor-like behaviour in riboflavin within a gold/Riboflavin/gold Schottky junction. We observed the occurrence of two negative differential resistance peaks at low voltages of 1.5 and 2.0 V, probably the first-ever report of this effect in a biomolecule. Interestingly, the proposed mechanism simulates a single Schottky junction behaviour despite the physical existence of two junctions. Solid-state parameters such as turn-on voltage, shunt resistance, and ideality factor were also calculated using Conventional and Cheung and Cheung’s methods. The results were highly characteristic to the riboflavin studied when compared to previous works on biomolecules. This opens up the possibility of developing solid-state sensors for electronically characterising biomolecules like vitamins to help advance our understanding of the electronic properties of these essential nutrients.

Differential Asthmatic Effect Due to House Dust Mite Depending on Age and Exposure Duration

Differential Asthmatic Effect Due to House Dust Mite Depending on Age and Exposure Duration

IInduction of G2/M Phase Block and Apoptosis by Kaempferol in Human Sarcoma Cells

malignant cells has interested us to seek new strategies for the treatment of sarcoma. Flavonoids have been recently claimed to exert anti-cancer effects. We focused on the flavonoid kaempferol, to determine whether it induces apoptosis of sarcoma cells in vitro. Methods: We examined cell growth using a CCK-8 assay, morphology, cell cycle analysis, and the apoptosis or differentiation effects of kaempferol on cultured human osteosarcoma MG-63 cells. All experiments were performed at least three times in duplicates. The ANOVA and independent sample t-test were used for the comparison of the continuous variables Results: Kaempferol (50 μM), adversely affected the proliferation of MG-63 cells. Anti-proliferative action of kaempferol appeared to be linked to apoptotic cell death based on the morphological changes depicting nuclear fragmentation. Cell cycle analysis demonstrated the induction of G2/M phase arrest and an enhanced sub-G1 population. However, the intracellular alkaline phosphatase (ALP) activity was observed to have been stimulated. This apoptosis might be associated with cell differentiation of the cells in the early stage. Conclusions: This study demonstrates that kaempferol inhibited the growth of MG-63 cells in vitro. G2/M phase arrest and induction of intracellular ALP activities in the early phase are observed. These findings indicate that kaempferol may present as an additional pharmacological tool for the treatment of human sarcoma cells.

A Concept of Thermal Effort for Heat-Induced Metal Plasticity

This paper proposes a new concept of material effort that considers heat-induced plasticity for heat-resistant steels. These steels indicate a strength differential effect, a stress shearness effect, pressure sensitivity, and other features. Therefore, a three-parameter, temperature-dependent yield function was presented and, next, analytically and geometrically researched. To validate the accuracy of the formulated yield function, experiments were conducted with the designed specimens to characterize the heat-resistant steels St12T and 26H2MF, which underwent simple shear, uniaxial strain tension, and compression tests. The yield function was calibrated by using a simple analysis. Next, the calibrated constitutive equations were used to numerically determine the load–stroke responses of different tests. The numerical analysis showed that the proposed yield function based on three parameters could accurately describe the thermal effort in various loading conditions from the onset of yielding to the ultimate rupture. Accordingly, the proposed yield function is recommended to model material strength under various thermal loading conditions.

Comparative Analysis of Cystamine and Cysteamine as Radioprotectors and Antioxidants: Insights from Monte Carlo Chemical Modeling under High Linear Energy Transfer Radiation and High Dose Rates.

This study conducts a comparative analysis of cystamine (RSSR), a disulfide, and cysteamine (RSH), its thiol monomer, to evaluate their efficacy as radioprotectors and antioxidants under high linear energy transfer (LET) and high-dose-rate irradiation conditions. It examines their interactions with reactive primary species produced during the radiolysis of the aqueous ferrous sulfate (Fricke) dosimeter, offering insights into the mechanisms of radioprotection and highlighting their potential to enhance the therapeutic index of radiation therapy, particularly in advanced techniques like FLASH radiotherapy. Using Monte Carlo multi-track chemical modeling to simulate the radiolytic oxidation of ferrous to ferric ions in Fricke-cystamine and Fricke-cysteamine solutions, this study assesses the radioprotective and antioxidant properties of these compounds across a variety of irradiation conditions. Concentrations were varied in both aerated (oxygen-rich) and deaerated (hypoxic) environments, simulating conditions akin to healthy tissue and tumors. Both cystamine and cysteamine demonstrate radioprotective and strong antioxidant properties. However, their effectiveness varies significantly depending on the concentration employed, the conditions of irradiation, and whether or not environmental oxygen is present. Specifically, excluding potential in vivo toxicity, cysteamine substantially reduces the adverse effects of ionizing radiation under aerated, low-LET conditions at concentrations above ~1 mM. However, its efficacy is minimal in hypoxic environments, irrespective of the concentration used. Conversely, cystamine consistently offers robust protective effects in both oxygen-rich and oxygen-poor conditions. The distinct protective capacities of cysteamine and cystamine underscore cysteamine's enhanced potential in radiotherapeutic settings aimed at safeguarding healthy tissues from radiation-induced damage while effectively targeting tumor tissues. This differential effectiveness emphasizes the need for personalized radioprotective strategies, tailored to the specific environmental conditions of the tissue involved. Implementing such approaches is crucial for optimizing therapeutic outcomes and minimizing collateral damage in cancer treatment.

Understanding ‘understanding music’ in Proust

ABSTRACT Sonic events of various kinds (musical and otherwise) are often complex semiotic occasions in Proust’s Recherche. One of the ways we attest to the meaningfulness of sounds we hear, to our understanding of them, is by applying language to them. When we talk or write about sounds or react to them, we also produce social effects. This – by inducing us to react to them and then produce language about them – is one of the ways sounds make social meanings happen in Proust (and in general). By examining language produced about sounds from a couple different volumes of the Recherche, I investigate what Bourdieu calls the differential social effect of works of art. I consider how scenes of language production around sound and music in the novel are constructed to reveal the social effects of apprehending sound and reacting to it. Finally, I speculate on how all of this work the novel does is part of a larger project of understanding: understanding what it means to understand musical sounds.

Beta-Blocker in Heart Rate Control and Cardio Protection: The Role of ADRB1 Variants and HCN4 Regulation – A Systematic Review

Elevated heart rate is linked to adverse cardiovascular outcomes. Sinoatrial (SA) nodes, hyperpolarization-activated cyclic nucleotide-gated-4 (HCN4) channels, and beta1-adrenergic receptor (ADRB1) are responsible for generating the heart rate. Beta-blockers have a cardioprotective effect on heart failure, including controlling heart rate. However, the responses to beta-blockers can vary among individuals. ADRB1 genetic variability may be contributed to the differential beta-blocker effect in heart failure. HCN4 also performs a crucial function in the pacemaker cells of the heart. Exploring the effect of beta-blockers in pacemaker cells is expanding the view of their role and their therapeutic response in heart failure. The objectives of this study were to identify ADRB1 genetic variants affecting heart rate response in heart failure subjects with beta-blocker treatment and to explore the effect of beta-blockers on HCN4 channels and SA nodes. A systematic review was performed using three databases. Eight of 668 manuscripts were selected. The systematic review found that ADRB1 genetic variants (A145G (Ser49Gly) and C1165G (Arg389Gly)) can affect heart rate response in beta-blocker-treated heart failure. The study also found that the percentage of patients with the Ser49Ser-Gly389X haplotype achieved a heart rate target was higher than other haplotypes. Individuals with the Arg389Arg genotype necessitated a markedly increased amount of beta-blocker dose to reach the identical heart rate target compared to those with the Gly389X gene variation. In addition, the review found that carvedilol, a beta-blocker derivative, demonstrated beneficial effects in inhibiting HCN-gated channels. Bisoprolol and carvedilol improved channel regulation in the SA Node by reversing the downregulation of HCN4 and sodium channels. In general, this systematic review provides important insights into beta-blockers in treating heart failure, specifically concerning the genetic variability of ADRB1 and the beta-blockers effect on the SA node and HCN4 channels.

The differential effect of optogenetic serotonergic manipulation on sustained motor actions and waiting for future rewards in mice.

Serotonin is an essential neuromodulator that affects behavioral and cognitive functions. Previous studies have shown that activation of serotonergic neurons in the dorsal raphe nucleus (DRN) promotes patience to wait for future rewards. However, it is still unclear whether serotonergic neurons also regulate persistence to act for future rewards. Here we used optogenetic activation and inhibition of DRN serotonergic neurons to examine their effects on sustained motor actions for future rewards. We trained mice to perform waiting and repeated lever-pressing tasks with variable reward delays and tested effects of optogenetic activation and inhibition of DRN serotonergic neurons on task performance. Interestingly, in the lever-pressing task, mice tolerated longer delays as they repeatedly pressed a lever than in the waiting task, suggesting that lever-pressing actions may not simply be costly, but may also be subjectively rewarding. Optogenetic activation of DRN serotonergic neurons prolonged waiting duration in the waiting task, consistent with previous studies. However, its effect on lever presses was nuanced, and was detected only by focusing on the period before premature reward check and by subtracting the trends within and across sessions using generalized linear model. While optogenetic inhibition decreased waiting, it did not affect lever pressing time or numbers. These results revealed that the necessity of motor actions may increase motivation for delayed rewards and that DRN serotonergic neurons more significantly promote waiting rather than persistent motor actions for future rewards.

Disturbed function of TBL1X has a differential effect on T3-regulated gene expression in two human liver cell models.

Mutations in TBL1X, part of the NCOR1/SMRT corepressor complex, were identified in patients with hereditary X-linked central congenital hypothyroidism and associated hearing loss. The role of TBL1X in thyroid hormone (TH) action, however, is incompletely understood. The aim of the present study was to investigate the role of TBL1X on T3-regulated gene expression in two human liver cell models. A human hepatoma cell line (HepG2) wherein TBL1X was downregulated using siRNAs, and human-induced pluripotent stem cell-derived hepatocytes (iHeps) generated from individuals with a TBL1X N365Y mutation. Both cell types were treated with increasing concentrations of T3. The expression of T3-regulated genes was measured by qPCR. KLF9, CPT1A, and PCK1 mRNA expression were higher upon T3 stimulation in the HepG2 cells with decreased TBL1X expression compared to controls, while DIO1 mRNA expression was lower. Hemizygous TBL1X N365Y iHeps exhibited decreased expression of CPT1A, G6PC1, PCK1, FBP1, and ELOVL2 compared to cells with the heterozygous TBL1X N365Y allele, but KLF9 and HMGCS2 expression was unaltered. Downregulation of TBL1X in HepG2 cells and the TBL1X N365Y variant in iHeps have differential effects on T3-regulated gene expression. This suggests that TBL1X may play a gene context role in TH action.

Will I Be the Same? Enhancing Academic Tourism Through Transformative Tourism Experiences

The growing relevance of transformative tourism experiences calls for further empirical research across different contexts. This study tests a comprehensive conceptual model within international academic tourism, incorporating co-creation theory and experience economy framework. Data were collected through a questionnaire survey ( N = 704) and analyzed using structural equation modeling. The results substantiate the proposed conceptual model, revealing a positive influence of activating factors on perceived transformation outcomes. Additionally, transformative tourism experiences confirm a significant impact on place attachment and positive memories, influencing behavioral intentions. Notably, perceived safety influences solely behavioral change, as opposed to personal change, meriting further investigation into this differential effect on transformative tourism experience outcomes. This study enhances understanding of the interrelationships among academic transformative tourism experiences components, namely by exploring the intended achievements’ role. It also elucidates transformative tourism experiences’ impacts on students’ destination perceptions and attitudes. Findings highlight the need for educational and tourism stakeholders to promote stimulating environments and impactful programs that actively engage students, fostering memorable life-changing experiences, place attachment, and loyalty.

Using the Extended Theory of Planned Behavior to Explore the Effect of Farmer Differentiation on Their Intention to Revitalize Idle Homesteads: Empirical Evidence from Shaanxi, China

The revitalization of idle homesteads is an essential element in stimulating rural land resources and assets and promoting the integrated development of urban and rural areas. However, existing studies have paid less attention to the relationship between the differentiation of farm households and revitalization intention. Therefore, exploring the relationship between farmer differentiation and revitalization intention has become the key to improving the revitalization intention. The differentiation of farmers in the process of urbanization is an important factor affecting the intention of farmers to revitalize idle homesteads. This study defines “farmer differentiation” as a second-order factor and is based on the theoretical analysis framework of “farmer differentiation (FD)–farmer cognition (FC)–revitalization intention (RI)” to systematically reveal the relationship between FD and RI with a multi-dimensional perspective. At the same time, we analyze the mediating role of FC in the relationship between FD and RI. The data collected from 881 Shaanxi, China, farmers are analyzed through structural equation modeling (SEM). The results of the study show that (1) The dimensions of farmer differentiation (FD) are wealth capital differentiation (WCD) and reputation capital differentiation (RCD). (2) The formation of farmers’ intention to revitalize follows the logical relationship of “FC–RI” in the Extended Theory of Planned Behavior (ETPB), and subjective norms (SN) are the critical factor. (3) The logical relationship of “FD–FC–RI” in the ETPB has been confirmed. In addition to the direct positive effect of the WCD and RCD on farmers’ intention to revitalize idle homesteads, WCD will indirectly affect RI through the four sub-dimensions of behavioral attitudes (BA), subjective norms (SN), perceived behavioral control (PBC) and homestead dependence (HD) under the FC conception. Meanwhile, the chain mediating role of the WCD and FC sub-dimensions in the RCD effect on the intention to revitalize cannot be ignored. Therefore, to increase farmers’ intention to revitalize Idle homesteads, policymakers need to focus on increasing WCD and RCD and helping farmers establish proactive FC.

Tightening Blocks in Complementary Analyses of Observational Studies: Optimization Algorithm and Examples

An observational block design has I blocks matched for covariates and J individuals per block, but treatments were not randomly assigned to individuals within blocks, as would have been done in an experiment. Tightening an observational block design means selecting J ′ < J individuals from each block, and possibly I ′ ≤ I blocks, to construct a new observational block design that, in some way, addresses unmeasured biases from nonrandom treatment assignment. Tightening must preserve covariate balance while altering the design to achieve some additional objective. An optimization algorithm is introduced that achieves this while maintaining the block structure by finely balancing covariates across blocks and through optimal subset matching. An example is considered in detail, both to motivate and illustrate the tightening of an observational block design. Two tightened designs are built from a study of light daily alcohol consumption and its possible effects on HDL cholesterol. One tightened design adjusts for an outcome tentatively presuming it was unaffected by the treatment. The second tightened design uses a differential effect to remove bias from an unobserved general disposition that promotes several treatments. An R package tightenBlock implements the method, contains the data, and in that package the help-file for the function tighten reproduces the example.

Early markers of induced pluripotent stem cell hematopoietic development

The generation of immune cell populations from induced pluripotent stem cells (iPSCs) is a valuable model to study mechanisms that control hematopoietic development; it also is a promising approach to develop immunotherapeutic strategies to treat various diseases, including hereditary, oncological and infectious ones. To date, it has been demonstrated that iPSCs can differentiate into different immune cells, including macrophages, neutrophils, natural killer cells and T cells. However, the protocols suggested so far are experimental, and they require optimization, standardization and scaling. Solution to these tasks requires methods allowing to predict the efficacy of ongoing differentiation at early differentiation stages. Here, we evaluated whether iPSC hematopoietic/myeloid differentiation can be monitored by means of flow cytometry. Human iPSCs were differentiated into hematopoietic/myeloid cells using two protocols previously suggested for the generation of macrophages from iPSCs. The protocols differed by methods used to induce early and late stages of cell differentiation. At early differentiation stages, the protocols differed by approaches used to induce the generation of mesoderm and hemogenic endothelium, i.e., 2D differentiation in the presence of exogenous factors known to promote mesoderm and hemogenic endothelium development (“factor-dependent” protocol) or 3D differentiation in the absence of exogenous cytokines and growth factors (“spontaneous” protocol). At late differentiation stages, the protocols differed by factors added to the cultures to promote hematopoietic/myeloid specification (i.e., SCF, FGF2, IL-6, IL-3 and M-CSF or only IL-3 and M-CSF). At different stages of differentiation, the expressions of antigens known to be expressed by mesoderm, hemogenic endothelium and hematopoietic cells (i.e., CD309, CD34, CD31, CD43 and CD45) were evaluated. At early differentiation stages, the main phenotypic changes observed in cell cultures were an upregulation of the expression of CD309 (a receptor for vascular endothelial growth factor), the appearance of the expression of sialophorin CD43 and the expression of CD34 antigen. In cells cultured in 2D factor-dependent conditions, these changes appeared earlier and were more pronounced as compared with cells cultured in 3D “spontaneous” conditions. The results suggest that CD309 and/or CD43 are valuable markers for an early prediction of the effectiveness of iPSC differentiation into hematopoietic/ myeloid progeny.

Differential Effect of Omega-3 Fatty Acids on Platelet Inhibition by Antiplatelet Drugs In Vitro.

The omega-3 polyunsaturated fatty acids (PUFAs) Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) exert multiple cardioprotective effects, influencing inflammation, platelet activation, endothelial function and lipid metabolism, besides their well-established triglyceride lowering properties. It is not uncommon for omega-3 PUFAs to be prescribed for hypertriglyceridemia, alongside antiplatelet therapy in cardiovascular disease (CVD) patients. In this regard, we studied the effect of EPA and DHA, in combination with antiplatelet drugs, in platelet aggregation and P-selectin and αIIbβ3 membrane expression. The antiplatelet drugs aspirin and triflusal, inhibitors of cyclooxygenase-1 (COX-1); ticagrelor, an inhibitor of the receptor P2Y12; vorapaxar, an inhibitor of the PAR-1 receptor, were combined with DHA or EPA and evaluated against in vitro platelet aggregation induced by agonists arachidonic acid (AA), adenosine diphosphate (ADP) and TRAP-6. We further investigated procaspase-activating compound 1 (PAC-1) binding and P-selectin membrane expression in platelets stimulated with ADP and TRAP-6. Both DHA and EPA displayed a dose-dependent inhibitory effect on platelet aggregation induced by AA, ADP and TRAP-6. In platelet aggregation induced by AA, DHA significantly improved acetylsalicylic acid (ASA) and triflusal's inhibitory activity, while EPA enhanced the inhibitory effect of ASA. In combination with EPA, ASA and ticagrelor expressed an increased inhibitory effect towards ADP-induced platelet activation. Both fatty acids could not improve the inhibitory effect of vorapaxar on AA- and ADP-induced platelet aggregation. In the presence of EPA, all antiplatelet drugs displayed a stronger inhibitory effect towards TRAP-6-induced platelet activation. Both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though they had no effect on P-selectin expression induced by ADP or TRAP-6. The antiplatelet drugs exhibited heterogeneity regarding their effect on P-selectin and αIIbβ3 membrane expression, while both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though had no effect on P-selectin expression induced by ADP or TRAP-6. The combinatory effect of DHA and EPA with the antiplatelet drugs did not result in enhanced inhibitory activity compared to the sum of the individual effects of each component.

Influence of nationality on the trajectories of pain, disability and health related quality of life in neck and back patients – The Norwegian Neck and Back Registry

PurposeThe aim of the current study was to examine differences in trajectories of pain, disability, and health related quality of life (HRQOL) between non-Norwegian and Norwegian patients with neck and back pain over 12 months. MethodsThe study is based on data from the Norwegian Neck and Back Registry (NNRR). The data include demographics and patient-reported outcome measures such as pain rating, the Oswestry Disability Index and HRQOL. Data were collected at baseline, 6 and 12 months after consultation for neck and back pain in specialist health care. ResultsA total of 5012 patients were included. We found a significant main effect of nationality. Non-Norwegian patients showed higher levels of pain and disability and lower HRQOL than Norwegian patients. Both patient groups exhibited an improvement in all three outcomes at 6- and 12-month follow-ups. The improvement was similar for pain with the greatest improvement taking place during the first 6 months and then slightly flattening out. For disability and HRQOL, we observed a differential effect over time as a function of nationality. Both groups reported an improvement the first 6 months, however, while the Norwegian patients continued their improvement to 12 months, non-Norwegian patients had increasing disability and lower HRQOL at 12 months. ConclusionBoth patient groups improved over the 12-month period. Non-Norwegian patients showed an overall higher level of pain, disability and lower HRQOL compared to Norwegian patients, with a differential effect over time as a function of nationality for disability and HRQOL. Suggesting that future studies should focus on potential systemic barriers that may affect the recovery of neck and back patients based on nationality.

I Bond, I Engage, I Visit: Investigating the Effects of Vloggers Tourist Engagement and Its Outcome on Tourist Attitudes

The present study investigates the effectiveness of tourism vlogs (video blogs), the parasocial bonding between the vloggers and the tourist/prospect and the wishful identification of the tourist/prospect on the different components of engagement namely, affective, cognitive and behavioral. The study also inspects the subsequent effect of the components of engagement on visit intentions and electronic word of mouth. We adopted a mixed method approach involving two focus group discussions followed by a sample survey of 541 respondents from India to construct and validate the study hypotheses using structural equation modeling. The findings indicate a differential effect of parasocial bonding and wishful identification on the components of consumer engagement. Likewise, engagement components are observed to have differential effects on visit intentions and electronic word of mouth. This study extends the application of social learning theory to tourism by offering a novel perspective on how interactions with travel vlogs collectively shape customer decisions and travel intentions. Tourism marketers can capitalize on the impact of parasocial interactions and wishful identification with travel vloggers to enhance engagement and boost the dissemination of electronic word-of-mouth.

Cumulative risk predicting differential effectiveness of the incredible years parent-training

The evidence on whether socioeconomic status moderates the effectiveness of parent-training programs for disruptive child behaviors is inconclusive. These varied results may stem from differences in the programs or the studies themselves. We applied an equivalence test paradigm to test the hypothesis of equal benefit from the Incredible Years Parent-Training (IYPT) across family risk on disruptive child behaviors. During the Danish roll-out of the IYPT, 1203 families were recruited across 20 different municipalities. The isolated and cumulative effect of five markers of low socioeconomic status, specifically single parent household, parental unemployment, low family income, low parental educational level, and teen parenthood, were analyzed as predictors of pre-to-post treatment response. Results showed equal benefit among families experiencing from zero to four accumulated socioeconomic risks (99 % of our sample). Our findings suggest that the IYPT brings equal benefit across socioeconomic backgrounds and risk levels in Danish community settings.

Differential biological effect of low doses of ionizing radiation depending on the radiosensitivity in a cell line model

Purpose Exposure to low doses (LD) of ionizing radiation (IR), such as the ones employed in computed tomography (CT) examination, can be associated with cancer risk. However, cancer development could depend on individual radiosensitivity. In the present study, we evaluated the differences in the response to a CT-scan radiation dose of 20 mGy in two lymphoblastoid cell lines with different radiosensitivity. Materials and Methods Several parameters were studied: gene expression, DNA damage, and its repair, as well as cell viability, proliferation, and death. Results were compared with those after a medium dose of 500 mGy. Results After 20 mGy of IR, the radiosensitive (RS) cell line showed an increase in DNA damage, and higher cell proliferation and apoptosis, whereas the radioresistant (RR) cell line was insensitive to this LD. Interestingly, the RR cell line showed a higher expression of an antioxidant gene, which could be used by the cells as a protective mechanism. After a dose of 500 mGy, both cell lines were affected by IR but with significant differences. The RS cells presented an increase in DNA damage and apoptosis, but a decrease in cell proliferation and cell viability, as well as less antioxidant response. Conclusions A differential biological effect was observed between two cell lines with different radiosensitivity, and these differences are especially interesting after a CT scan dose. If this is confirmed by further studies, one could think that individuals with radiosensitivity-related genetic variants may be more vulnerable to long-term effects of IR, potentially increasing cancer risk after LD exposure.

Differential Effect of Simulated Microgravity on the Cellular Uptake of Small Molecules.

The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours. We assessed the cellular accumulation of compounds representing substrates of uptake and efflux transporters, and of compounds not shown to be transported by membrane carriers. Exposure to SMG led to an increase of up to 60% (p < 0.01) in the cellular uptake of efflux transporter substrates, whereas a glucose transporter substrate showed a decrease of 20% (p < 0.05). The uptake of the cathepsin activity-based probe GB123 (MW, 1198 g/mol) was also enhanced (1.3-fold, p < 0.05). Cellular emission of molecules larger than ~3000 g/mol was reduced by up to 50% in SMG (p < 0.05). Our findings suggest that short-term exposure to SMG could differentially affect drug distribution across membranes. Longer exposure to microgravity, e.g., during spaceflight, may have distinct effects on the cellular uptake of small molecules.

Differential Efficacy of Weight Loss Interventions in Patients with Versus Without Diabetes.

Obesity is both a major risk factor for diabetes and a serious comorbidity of the condition. The twin epidemics of obesity and diabetes have spread globally over the past few decades. Treatment of obesity in patients with diabetes provides a host of clinical benefits that encompass virtually all body systems. Despite this, multiple lines of evidence suggest that the efficacy of most therapies for weight loss is significantly reduced among patients with diabetes. With this background, we summarize the evidence of a differential effect of lifestyle, pharmacological, and surgical treatments for obesity in patients with existing diabetes, and explore the potential mechanisms involved in this phenomenon. This information is then used to formulate strategies to improve weight loss outcomes for patients with diabetes.