Search Results (91)

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection. Methods: Pregnant mares (n = 12 per group) were immunized either at months 8 and 10 of gestation with the VP8* mRNA or at months 8, 9, and 10 of gestation with the KV. Serum samples were collected from mares before and after immunization and from their foals at ages 1, 35, and 49 days. Serum samples were tested by indirect ELISA for VP8*-specific relative antibody concentrations and relative concentrations were compared for effects of study group and sample-time using linear mixed-effects regression. To detect functional antibodies against ERVA, a virus neutralization titer assay was performed to compare titers between mares vaccinated with the mRNA vaccine (and their foals) and unvaccinated control mares (and their foals). Results: Mares vaccinated with VP8* mRNA had significantly (p < 0.05) higher antibody concentrations after foaling than mares in the KV group, and foals of VP8* mRNA-vaccinated mares had significantly (p < 0.05) higher concentrations through age 49 days than foals in the KV group. In addition, the VP8* mRNA vaccine elicited higher titers of ERVA-neutralizing antibodies against both G3 and G14 strains. Conclusions: Longer-lasting, higher concentrations of virus-neutralizing antibodies might provide superior duration of immunity to ERVA in foals from mares vaccinated with VP8* mRNA. Full article

Background: Physiological and psychological factors are important for determining static breath-hold duration. Preconditioning, such as preparatory apneas at functional residual capacity, is a potentially valuable method for prolonging breath-hold duration at total lung capacity. We investigated the physiological influence of preparatory apneas to determine the possible association with maximal apnea duration via diaphragmatic pressure and electromyographic measurements. Methods: Fourteen male breath-hold divers (39 ± 10 years; body mass, 87.2 ± 8.5 kg; body fat, 14.4 ± 3.8%; body height, 186.6 ± 3.9 cm; training experience, 14.2 ± 9.6 years) were included. We measured diaphragm activity during breath-holds via transdiaphragmatic pressure (Pdia) using balloon-tipped catheters in the stomach and esophagus and electromyographic (EMG) activity. From these, ∆EMG and ∆Pdia for every involuntary breathing movement (IBM) during all apneas were quantified. Furthermore, a pressure difference (difference between the first and last IBM Pdia value) and the respiratory neuromuscular output index (RNMI) (∆Pdia/∆EMG) were included as indirect parameters of the pressure perceived. These variables were measured during three preparatory breath-holds (average duration = 185 ± 69 s and range = 62–309 s, separated by 2.5 min) and three maximal breath-holds (average duration = 308 s and range = 179–733 s, separated by 5 min). Results: The preparatory apnea performed at FRC elicited significantly higher Pdia activity (p < 0.00) and a significantly lower RNMI (p = 0.00–0.01) compared to the maximal apneas. Furthermore, a higher and more pronounced increase in Pdia during the preparatory apnea at FRC was related to longer maximal apneas (Max 1, r = 0.65, p = 0.01; Max 2, r = 0.65, p = 0.02; Max 3, r = 0.66, p = 0.01). Conclusions: The results suggest an acute preconditioning effect of primarily the preparatory apnea at FRC on the duration of the subsequent maximal apneas. The implementation of preparatory apneas preceding maximal apneas during training sessions may elicit a longer breath-hold duration in trained divers. Full article

Background: Toxoplasma gondii is a globally distributed apicomplexan parasite capable of causing congenital infections and spontaneous abortions in humans. While the parasite-secreted effector proteins TgGRA28 and TgGRA83 are known to mediate virulence or immune modulation, their potential as vaccine targets remains unexplored. Despite its immunomodulatory properties, the role of IL-28B (a type III interferon) in enhancing DNA vaccine efficacy against T. gondii infection remains unclear. Methods: In this study, we constructed eukaryotic expression plasmids pVAX-GRA28, pVAX- GRA83 and pVAX-IL-28B. After transfection into -293-T cell, protein expression encoding TgGRA28 and TgGRA83 was confirmed via indirect immunofluorescence assay (IFA), while IL-28B expression was analyzed by ELISA. Subsequently, C57BL/6J or IFNαR1 knockout mice were immunized with single or dual-antigen DNA vaccines, with or without the molecular adjuvant pVAX-IL-28B. Immune responses were assessed through Toxoplasma-specific antibody levels, cytotoxic T lymphocyte (CTL) activity, cytokine profiling (IFN-γ, IL-2, IL-12p40, IL-12p70), and flow cytometric analysis of lymphocyte subsets and dendritic cells (DCs). Protective efficacy was determined by survival rates and brain cyst burden following challenge with 100 or 10 ME49 T. gondii cysts, respectively. Results: Vaccination with pVAX-GRA28 and pVAX-GRA83 elicited robust humoral immune responses with increased T. gondii-specific IgG levels and also Th1-polarized immunity, characterized by elevated IgG2a/IgG1 ratio, IFN-γ-dominant cytokine responses, and enhanced DCs, CD4+ and CD8+ T-cell activation. The cocktail vaccine conferred superior protection compared to single-antigen formulations, significantly improving survival and reducing cyst formation. Co-administration of pVAX-IL-28B further augmented vaccine-induced immunity, enhancing both cellular and humoral responses. Moreover, these DNA immunization with pVAX-GRA28 and pVAX-GRA83 plus pVAX-IL-28B induced robust protective immunity that was largely independent of type I IFN signaling, consistent with type III IFN biology. Conclusions: Our findings demonstrate that TgGRA28 and TgGRA83 are promising vaccine candidates against toxoplasmosis, capable of inducing protective immunity against acute and chronic infection. Moreover, IL-28B serves as a potent genetic adjuvant, warranting further investigation for its broader application in vaccines targeting apicomplexan parasites. Full article

Plant growth-promoting bacteria (PGPB) associated with Coffea arabica L. and Coffea canephora Pierre ex Froehner offer a viable strategy to reduce synthetic inputs and enhance resilience in coffee agroecosystems. This review synthesizes evidence from the past decade on rhizosphere-associated and endophytic taxa, their plant growth-promotion and biocontrol mechanisms and the resulting agronomic outcomes. A compartment-specific core microbiome is reported, in the rhizosphere of both hosts, in which Bacillus and Pseudomonas consistently dominate. Within endophytic communities, Bacillus predominates across tissues (roots, leaves and seeds), whereas accompanying genera are host- and tissue-specific. In C. arabica, endophytes frequently include Pseudomonas in roots and leaves. In C. canephora, root endophytes recurrently include Burkholderia, Kitasatospora and Rahnella, while seed endophytes are enriched for Curtobacterium. Functionally, coffee-associated PGPB solubilize phosphate; fix atmospheric nitrogen via biological nitrogen fixation; produce auxins; synthesize siderophores; and express 1-aminocyclopropane-1-carboxylate deaminase. Indirect benefits include the production of antifungal and nematicidal metabolites, secretion of hydrolytic enzymes and elicitation of induced systemic resistance. Under greenhouse conditions, inoculation with PGPB commonly improves germination, shoot and root biomass, nutrient uptake and tolerance to drought or nutrient limitation. Notable biocontrol activity against fungal phytopathogens and plant-parasitic nematodes has also been documented. Key priorities for translation to practice should include (i) multi-site, multi-season field trials to quantify performance, persistence and economic returns; (ii) strain-resolved omics to link taxa to functions expressed within the plant host; (iii) improved bioformulations compatible with farm management and (iv) rationally designed consortia aligned with production goals and biosafety frameworks. Full article

Maritime ferries increasingly operate under non-stationary hydro–meteorological conditions that complicate cost planning. This study investigates how short-term weather variability affects expenditures for a ferry on the Gdynia–Karlskrona route. We combine a state-based operational framework (18 discrete states) with a subsystem-level cost model covering navigation, propulsion/steering, loading/unloading, stability control, and mooring/anchoring. Direct and indirect costs are linked to subsystem activity and state duration, while weather is incorporated through hazard categories that scale hourly costs. Expert-elicited rates and observed monthly state durations provide the basis for baseline estimates and hazard scenario simulations. Results reveal a disproportionate cost structure: two open-sea states constitute over 97% of the baseline monthly cost (19,490.19 PLN). Weather hazards further amplify costs, with moderate (1st-degree) and severe (2nd-degree) scenarios producing increases of ~8% and ~20%, respectively, compared to normal conditions. By embedding weather as an endogenous factor in a probabilistic cost model based on a semi-Markov process, the approach enhances predictive fidelity and supports decision-making for climate-resilient planning. These findings suggest that adaptive routing, speed management, and targeted maintenance of the propulsion and steering subsystems during open-sea navigation offer the highest potential for cost resilience. The study provides operators and policymakers with a transparent framework for climate-resilient planning and investment in semi-enclosed maritime corridors. Full article

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, Candida albicans and C. albicans-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific C. albicans antigens that activate Th17 cells during this disease are unknown. The C. albicans 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of C. albicans, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; R = 0.33, p = 0.0092), alanine aminotransferase (ALT; R = 0.27, p = 0.037), gamma-glutamyl transferase (GGT; R = 0.35, p = 0.0055) and alkaline phosphatase (R = 0.36, p = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; R = 0.51, p = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (p = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2–F4 as compared with patients with no or minimal fibrosis F0–F1 (p = 0.0082). The area under the curve (AUC) for detecting F2–F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder. Full article

Plant viruses can significantly influence the behavior and performance of their insect vectors, with profound implications for viral epidemiology. However, studies on the effects of co-infection with multiple plant viruses on vector feeding behavior remain scarce, despite its frequent occurrence in nature and potential for altered transmission outcomes. Bemisia tabaci MED, a key vector insect, is closely linked to the rapid spread of tomato chlorosis virus (ToCV) and tomato yellow leaf curl virus (TYLCV) in China. In this study, the electrical penetration graph (EPG) technique was employed to investigate and compare the indirect (via infected plants) and direct (via viruliferous insects) effects of ToCV alone and ToCV and TYLCV co-infection on the feeding behaviors of B. tabaci MED. The results revealed that whiteflies on ToCV-infected or ToCV&TYLCV co-infected plants exhibited significantly longer non-probing durations compared to those on un-infected plants. The intracellular puncture activity of whiteflies was markedly reduced on virus-infected plants, and ToCV infection particularly shortened the duration of phloem sap ingestion. Moreover, viruliferous whiteflies (carrying ToCV or both viruses) spent less time in the intercellular pathway phase. Specifically, ToCV-viruliferous whiteflies had a shorter first-probe duration than non-viruliferous ones. The time from the first probe to the first E phase was also shorter in viruliferous whiteflies, especially in those carrying both ToCV and TYLCV. Furthermore, a significant difference was observed in the total duration of phloem sap ingestion between ToCV-viruliferous and ToCV&TYLCV-viruliferous whiteflies. These findings indicate that both ToCV infection and ToCV&TYLCV co-infection can modulate whitefly feeding behaviors through indirect and direct manners, with co-infection eliciting unique behavioral changes. These insights are valuable for elucidating the negative impact of ToCV-infected and ToCV&TYLCV co-infected tomato plants on whitefly performance, and for uncovering the mechanisms underlying the epidemics of these viruses. Full article

Despite its central role in fostering effective social support, support-seeking behavior has received limited empirical attention—particularly among older adults, who have heightened needs for support due to age-related cognitive and physical decline. This study identified and examined key predictors of four types of support-seeking behaviors—direct and indirect instrumental and emotional support-seeking. Long-term married couples, with at least one partner aged 65 or older, participated in a laboratory-based discussion about a personal life stressor, during which support-seeking behaviors were coded. We examined both the support-seeker’s and support-provider’s attachment orientation, as well as the support-seeker’s stress level and relationship quality (e.g., satisfaction, commitment, and trust), as predictors of observed support-seeking behaviors. Results indicated that greater stress and higher relationship quality were associated with more direct instrumental support-seeking, while lower relationship quality and greater attachment insecurity in both partners predicted more indirect instrumental and emotional support-seeking. However, support-seekers also showed more direct emotional support-seeking with avoidantly attached partners, possibly as a compensatory effort to elicit needed support. This study contributes to the limited literature focusing on support-seeking behaviors, particularly in older adulthood, and has implications for interventions aimed at promoting effective communication and support-seeking. Full article

Maternal behavior encompasses a range of biologically driven responses whose expression and duration vary across species. Maternal responses rely on robust adaptive changes in the female brain, enabling mothers to engage in caregiving, nourishing, and offspring protection. Morphological and functional changes in the maternal brain enhance sensitivity to offspring cues, eliciting maternal behaviors, rewarding responses, and social processing stimuli essential for parenting. Maternal behavior comprises a range of biological responses that extend beyond basic actions, reflecting a complex, evolutionarily shaped neurobiological adaptation. These behaviors can be broadly categorized into direct behaviors, which are explicitly aimed at the care of the offspring, and indirect behaviors that, overall, ensure the protection, nourishment, and survival of the newborn. The secretion of main neuropeptide hormones, such as oxytocin (OT), prolactin (PRL), and placental lactogens (PLs), during the peripartum period, is relevant for inducing and regulating maternal responses to offspring cues, including suckling behavior. Although PRL is primarily associated with reproductive and parental functions in vertebrates, it also modulates distinct neural functions during pregnancy that extend from lactogenesis to adult neurogenesis, neuroprotection, and neuroplasticity, all of which contribute to preparing the maternal brain for motherhood and parenting interactions. Parvocellular OT-containing neurons in the paraventricular nucleus (PVN) and in the anterior hypothalamic nucleus (AHN) project axon collaterals to the medial preoptic area, which, in turn, projects to the nucleus accumbens (NACC) and lateral habenula (lHb) via the retrorubral field (RRF) and the ventral tegmental area (VTA), which mediate the motivational aspects of maternal responses to offspring cues. The reshaping process of the brain and neural networks implicated in motherhood depends on several factors, such as up- and downregulation of neuronal gene expression of bioactive peptide hormones (i.e., OT, PRL, TIP-39, galanin, spexin, pituitary adenylate cyclase-activating polypeptide (PACAP), corticotropin-releasing hormone (CRH), peptide receptors, and transcription factors (i.e., c-fos and pSTAT)) in target neurons in hypothalamic nuclei, mesolimbic areas, the hippocampus, and the brainstem, which, overall, regulate the expression of maternal behavior to offspring cues, as shown in postpartum female rodents. In this review, we describe the modulatory neuropeptides, the neural networks underlying peptide transmission systems, and cell signaling involved in parenthood. We highlight the dysregulation of neuropeptide hormones and their receptors in the central nervous system in relation to psychiatric disorders. Full article

Lumpy skin disease (LSD) is a contagious animal disease caused by the lumpy skin disease virus (LSDV). LSD can be transmitted through direct, indirect and insect vectors, severely impacting global cattle production. To evaluate difference in immune response and gut microbiota of 30 healthy 16–18 months old Angus cattle, treated with live attenuated or inactivated goatpox vaccine virus strains. The cattle were randomly divided into three groups (10 animals per group): Group A—goatpox live attenuated vaccine; Group B—goatpox inactivated vaccine; Group C—control (saline). Blood samples were collected on days 14, 28, 42, and 56 post-vaccination to assess hematological parameters, serum biochemical indices, and antibody levels; rectal feces were collected on day 28 for 16S rRNA analysis of gut microbiota. Results showed that, on day 28, both Group A and Group B reached their peak antibody levels (the log₁₀ value of Group A was 2.6, and that of Group B was 2.7), with about 90% of the cattle in each vaccinated group testing antibody-positive. On day 42, Group B retained 90% seropositivity, whereas Group A declined to 80%. Significantly altered in vaccinated Groups (A and B) compared to controls on days 14 and 28 (p < 0.05). Hematological parameters (PLT, NEUT, and LYM) and serum biochemical indices (AST, TP, and GGT) were elevated early after vaccination but returned to baseline by days 42 and 56.Which returned to control levels by days 42 and 56. On day 28 post-vaccination, Vaccinated cattle showed significantly higher gut microbiome richness and diversity than unvaccinated controls (p < 0.05). At the phylum level, the dominance was observed in Firmicutes and Bacteroidetes: the relative abundances were 62.90% and 29.65% in Group A, 60.84% and 30.13% in Group B, and 49.99% and 39.73% in Group C, respectively. These findings indicate that the inactivated goatpox vaccine elicits a more durable and stable antibody response, maintaining higher specific antibody titers, and induces more pronounced shifts in the gut microbiota community structure at the phylum level compared with the live attenuated vaccine. Full article

SSB proteins play essential roles in DNA replication, recombination, and repair in bacteria, archaea, and eukarya. This study investigates the transcript levels, identification, expression and purification, subcellular localization, and immune protective potential of the SSB-like proteins of Eimeria necatrix (EnSSB), exploring its role in the development of E. necatrix and its potential as a candidate antigen for a subunit vaccine against avian coccidiosis. The level of EnSSB gene transcription was highest in unsporulated oocysts (UO), followed by gametocytes (GAM) (p < 0.05). The gene consisted of an open reading frame of 1488 nucleotides encoding a protein of 495 amino acid residues with a predicted molecular weight of 53.31 kDa. EnSSB contained a SSB domain with a conserved OB (oligonucleotide/oligosaccharide binding) fold. The molecular mass of the native protein, as determined by Western blot analysis, was ~58 kDa in second-generation merozoites (MZ-2) and UO. In addition to the 58 kDa band, four other bands (~98 kDa, ~82 kDa, ~36 kDa and ~28 kDa) were detected in GAM. No bands were detected in MZ-3. Indirect immunofluorescence and immuno-electron microscopy localized EnSSB in the cytoplasm of macrogametocytes but not in wall-forming bodies and oocyst wall. Animal challenge experiments demonstrated that rEnSSB elicited robust IgY responses, increased splenic T lymphocytes and body weight gain, reduced intestinal lesion scores and oocyst shedding, and presented anticoccidial index (ACI) more than 160. These findings not only offer a foundation for understanding the role of EnSSB protein in regulating the development of E. necatrix, but also present a potential protective antigen of E. necatrix for the development of a subunit vaccine against avian coccidiosis. Full article

Among the numerous compounds released as a result of human activities, endocrine-disrupting chemicals (EDCs) have attracted particular attention due to their widespread detection in human biological samples and their accumulation across various ecosystems. While early research primarily focused on their effects on reproductive health, it is now evident that EDCs may impact neurodevelopment, altering the integrity of neural circuits essential for cognitive abilities, emotional regulation, and social behaviors. These compounds may elicit epigenetic modifications, such as DNA methylation and histone acetylation, that result in altered expression patterns, potentially affecting multiple generations and contribute to long-term behavioral phenotypes. The effects of EDCs may occur though both direct and indirect mechanisms, ultimately converging on neurodevelopmental vulnerability. In particular, the gut–brain axis has emerged as a critical interface targeted by EDCs. This bidirectional communication network integrates the nervous, immune, and endocrine systems. By altering the microbiota composition, modulating immune responses, and triggering epigenetic mechanisms, EDCs can act on multiple and interconnected pathways. In this context, elucidating the impact of EDCs on neurodevelopmental processes is crucial for advancing our understanding of their contribution to neurological and behavioral health risks. Full article

Background/Objectives: Beak and feather disease virus (BFDV) is the causative agent of psittacine beak and feather disease (PBFD), affecting psittacine birds. There is currently no commercial vaccine or treatment for this disease. This study developed a novel BFDV coat protein mRNA vaccine encapsidated by TMV coat protein to form pseudovirions (PsVs) and tested its immunogenicity alongside BFDV coat protein (CP) subunit and DNA vaccine candidates. Methods: mRNA and BFDV CP subunit vaccine candidates were produced in Nicotiana benthamiana and subsequently purified using PEG precipitation and gradient ultracentrifugation, respectively. The DNA vaccine candidate was produced in E. coli cells harbouring a plasmid with a BFDV1.1mer pseudogenome. Immunogenicity of the vaccine candidates was evaluated in African grey parrot chicks. Results: Successful purification of TMV PsVs harbouring the mRNA vaccine, and of the BFDV-CP subunit vaccine, was confirmed by SDS-PAGE and western blot analysis. TEM analyses confirmed formation of TMV PsVs, while RT-PCR and RT-qPCR cDNA amplification confirmed encapsidation of the mRNA vaccine candidate within TMV particles. Restriction digests verified presence of the BFDV1.1mer genome in the plasmid. Four groups of 5 ten-week-old African grey parrot (Psittacus erithacus) chicks were vaccinated and received two boost vaccinations 2 weeks apart. Blood samples were collected from all four groups on day 14, 28 and 42, and sera were analysed using indirect ELISA, which showed that all vaccine candidates successfully elicited specific anti-BFDV-CP immune responses. The subunit vaccine candidate showed the strongest immune response, indicated by higher binding titres (>6400), followed by the mRNA and DNA vaccine candidates. Conclusions: The candidate vaccines present an important milestone in the search for a protective vaccine against PBFD, and their inexpensive manufacture could considerably aid commercial vaccine development. Full article

This study examined the pragmatic competence and awareness of L2 learners of English, with a focus on their request strategies in L2 English, levels of (in)directness, request perspective, internal and external modifications, and the impact of tasks. The participants comprised 80 Cypriot Greek (CG) undergraduate students. The pragmatic tests were designed based on Speech Act Theory and included discourse completion tasks (DCTs) and multiple-choice questionnaires (MCQs). Additionally, a role-play and an interview task were employed to assess L2 learners’ pragmatic competence in oral discourse. The tasks featured four conditions related to power and social distance: [+social distance, status equals], [−social distance, status equals], [+social distance, hearer dominance], and [−social distance, hearer dominance]. Overall, the results indicated that L2 learners of English tended to prefer conventionally indirect requests, suggesting that L1 linguistic and cultural backgrounds influence expressions of politeness. Face-threatening situations with a high degree of imposition elicited more conventionally indirect requests. Data analysis revealed contextual variation but not a clear task effect. Factors such as social distance, hearer dominance, power, familiarity, and imposition impacted the degree of (in)directness, request perspective, and both internal and external modifications. Full article

We recently reported that a chimeric peptide (GEP44) targeting the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2- receptors decreased body weight (BW), energy intake, and core temperature in diet-induced obese (DIO) male and female mice. In the current study, we tested the hypothesis that the strong reduction in body weight in response to GEP44 is partially related to the stimulation of energy expenditure (EE). To test this, rats were maintained on a high fat diet (HFD) for at least 4 months to elicit DIO prior to undergoing a sequential 2-day vehicle period, 2-day GEP44 (50 nmol/kg) period, and a minimum 2-day washout period, and detailed measures of energy homeostasis. GEP44 (50 nmol/kg) reduced EE (indirect calorimetry), respiratory exchange ratio (RER), core temperature, activity, energy intake, and BW in male and female rats. As in our previous study in mice, GEP44 reduced BW in male and female HFD-fed rats by 3.8 ± 0.2% and 2.3 ± 0.4%, respectively. These effects appear to be mediated by increased lipid oxidation and reductions in energy intake as GEP44 reduced RER and cumulative energy intake in male and female HFD-fed rats. The strong reduction in body weight in response to GEP44 is related to a robust reduction in energy intake, but not to the stimulation of EE. The paradoxical finding that GEP44 reduced EE might be secondary to a reduction in diet-induced thermogenesis or might indicate an important mechanism to limit the overall efficacy of GEP44 to prevent further weight loss. Full article