Similar to LOO, hyperleptinemic DIO mice showed no c-Fos

Similar to LOO, hyperleptinemic DIO mice showed no c-Fos

response after fasting, while ob/ob mice showed a stronger response than lean control mice. Mimicking hyperleptinemia by repeated leptin injections in lean mice during fasting attenuated the fasting-induced c-Fos expression. Our findings indicate that high leptin levels prevent the fasting-induced activation of ARC neurons in mice. Moreover, leptin sensitivity is dynamic in obese subjects and depends on the feeding status. During short-term increases in leptin sensitivity, PD98059 purchase e. g., during fasting, leptin signaling appears to be effective, even in hyperleptinemic obesity. As reflected by the blockade of the fasting-induced ARC activation, fasting seems to interfere with the responsiveness of the ARC to signals related to the status of energy intake.”
“Hirai DM, Copp SW, Holdsworth CT, Ferguson SK, Musch TI, Poole DC. Effects of neuronal nitric oxide synthase inhibition on microvascular and contractile function in skeletal muscle of aged rats. Am J Physiol Heart Circ Physiol 303: H1076-H1084, 2012. First published August 24, 2012; doi:10.1152/ajpheart.00477.2012.-Advanced age is associated with derangements in skeletal muscle microvascular function during

the transition from rest to contractions. We tested the hypothesis that, contrary to what was reported previously in young rats, selective neuronal nitric oxide (NO) synthase (nNOS) inhibition would result in attenuated buy Dinaciclib or absent alterations in skeletal muscle microvascular oxygenation (PO2mv), which reflects the matching between muscle O-2 delivery and utilization, following the onset of contractions in old rats. Spinotrapezius muscle blood flow (radiolabeled microspheres), PO2mv (phosphorescence quenching), O-2 utilization ((V)over dot(O2); Fick calculation), and submaximal force production were measured at rest and following the onset of contractions in anesthetized old male Fischer 344 x Brown Norway rats (27 to 28 mo) pre-

and postselective nNOS inhibition (2.1 mu mol/kg S-methyl-L-thiocitrulline; SMTC). At rest, SMTC had no effects on muscle blood flow (P > 0.05) but reduced (V)over dot(O2) by similar to 23% (P < 0.05), which elevated basal Anlotinib order PO2mv by similar to 18% (P < 0.05). During contractions, steady-state muscle blood flow, (V)over dot(O2), PO2mv, and force production were not altered after SMTC (P > 0.05 for all). The overall PO2mv dynamics following onset of contractions was also unaffected by SMTC (mean response time: pre, 19.7 +/- 1.5; and post, 20.0 +/- 2.0 s; P > 0.05). These results indicate that the locus of nNOS-derived NO control in skeletal muscle depends on age and metabolic rate (i.e., rest vs. contractions). Alterations in nNOS-mediated regulation of contracting skeletal muscle microvascular function with aging may contribute to poor exercise capacity in this population.

“The National Health and Hospitals Reform Commission (NHHR

“The National Health and Hospitals Reform Commission (NHHRC) has recommended that Australia develop a “single health system”, governed

by the federal government. Steps to achieving this include: a “Healthy Australia Accord” to agree on the reform framework; the progressive takeover of funding of public hospitals by the federal government; and the possible implementation selleck of a consumer-choice health funding model, called “Medicare Select”.\n\nThese proposals face significant implementation issues, and the final solution needs to deal with both financial and political sustainability.\n\nIf the federal and state governments cannot agree on a reform plan, the Prime Minister may need to go to the electorate for a mandate, which may be shaped by other economic issues such as tax reform and intergenerational challenges.”
“Background: Patellofemoral osteoarthritis (PFOA) is a common form of knee OA in middle and older age, but its relation to PF disorders and symptoms earlier in life is unclear. Our aim was to conduct a systematic review

to investigate the strength of evidence for an association between anterior knee pain (AKP) in younger adults and subsequent PFOA.\n\nMethods: The search strategy included electronic databases (Pubmed, EMBASE, AMED, CINAHL, Cochrane, PEDro, SportDiscus: inception to December 2009), reference lists of potentially eligible studies and selected reviews. Full text articles in any language, -identified via English titles and abstracts, were included if Pevonedistat ic50 they were retrospective or prospective in design and contained quantitative data regarding structural changes indicative of PFOA, incident to original idiopathic selleck kinase inhibitor AKP. Eligibility criteria were applied to titles, abstracts and full-texts by two independent reviewers. Data extraction included study location, design, date,

sampling procedure, sample characteristics, AKP/PFOA definitions, follow-up duration and rate, and main findings. Foreign language articles were translated into English prior to examination.\n\nResults: Seven articles satisfied eligibility (5 English, 2 German). Only one case-control study directly investigated a link between PFOA and prior AKP, providing level 3b evidence in favour of an association (OR 4.4; 95%Cl 1.8, 10.6). Rough estimates of the annual risk of PFOA from the remaining six small, uncontrolled, observational studies (mean follow-up range: 5.7 to 23 years) ranged from 0% to 3.4%. This was not the primary aim of these studies, and limitations in design and methodology mean this data should be interpreted with caution.\n\nConclusions: There is a paucity of high-quality evidence reporting a link between AKP and PFOA. Further, well-designed cohort studies may be able to fill this evidence gap.

“This study evaluated

the pharmacodynamics of the

“This study evaluated

the pharmacodynamics of the lantibiotic MU1140 and the ability of selected organisms to develop resistance to this antibiotic. MU1140 demonstrated activity against all Gram-positive organisms tested, including oxacillin-and vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VREF). No activity was observed against Gram-negative bacteria or yeast. Time -kill studies revealed that MU1140 was rapidly bactericidal against Streptococcus pneumoniae and multidrug-resistant S. aureus, whilst it was bacteriostatic against VREF. In vitro resistance development to MU1140, tested by sequential subculturing in subinhibitory concentrations of MU1140, revealed a stable threefold increase in the minimum inhibitory concentration (MIC) for S. aureus and S. pneumoniae. Subsequent subculturing of the strains with PF-6463922 elevated MICs in antibiotic-free media for 7 days did not result in a reduction of their MIC values for MU1140. Collectively, our findings illustrate the therapeutic potential of MU1140 BI 2536 solubility dmso for management of Gram-positive infections. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.”
“Reactive peroxides in povidone often lead to degradation of oxidation-labile drugs. To reduce peroxide concentration in povidone, the roles of storage conditions, antioxidants, and silicates were investigated. Povidone alone and its physical mixtures with ascorbic acid, propyl

gallate, sodium sulfite, butylated hydroxyanisole (BHA), or butylated hydroxytoluene (BHT) were stored at 25 degrees C and 40 degrees C, at 11%, 32%, and 50% relative humidity. In addition, povidone solution in methanol was equilibrated with silicates (silica gel and molecular sieves), followed by solvent evaporation

to recover povidone powder. Peroxide concentrations in povidone were measured. The concentration of peroxides in povidone increased under very-low-humidity storage conditions. Among the antioxidants, ascorbic acid, propyl gallate, and sodium sulfite reduced the peroxide concentration in povidone, whereas BHA and BHT did not. Water solubility find more appeared to determine the effectiveness of antioxidants. Also, some silicates significantly reduced peroxide concentration in povidone without affecting its functionality as a tablet binder. Porosity of silicates was critical to their ability to reduce the peroxide concentration in povidone. A combination of these approaches can reduce the initial peroxide concentration in povidone and minimize peroxide growth under routine storage conditions. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:127139, 2012″
“Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment.


Ex vivo, in vitro whole organ culture o


Ex vivo, in vitro whole organ culture of subglottises grown with and without the presence of an MMP inhibitor.\n\nSETTING: Tertiary care facility.\n\nSUBJECTS AND METHODS: Subglottises from 20 neonatal mice were divided into 10 grown with an MMP inhibitor, GM6001, and 10 grown in basic medium alone. The luminal cross-sectional area, apoptosis levels, cell proliferation rates, and presence or absence of cleaved aggrecan fragments were determined.\n\nRESULTS: Subglottises that were exposed to the MMP inhibitor displayed statistically significant luminal narrowing, accompanied by apparent circumferential thickening of the cricoid ring, relatively decreased apoptosis, increased chondrocyte proliferation,

and decreased amounts of aggrecan cleavage fragments in the extracellular matrix.\n\nCONCLUSION: Matrix metalloproteinases likely play a significant role in growth of the cricoid cartilage such that their Vorinostat mouse inhibition leads to marked changes in the shape of the ring. (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved.”
“We compared lipids, lipid peroxidation product malondialdehyde (MDA), the acute phase reactant high-sensitivity C-reactive protein (hsCRP), interleukin 1 beta (IL-1 beta), and platelet selectin (P-selectin) between healthy controls, type 2 diabetes mellitus (DM) participants without myocardial LY3039478 clinical trial infarction (MI), as well as type 2 DM participants with MI. Malondialdehyde, IL-1 beta, and P-selectin

levels were significantly higher in the diabetic participants with MI than in either healthy controls or diabetic participants without MI. In the diabetic groups, fasting blood glucose (FBG) level, glycated hemoglobin (HbA(1c)), MDA, hsCRP, and P-selectin were all significantly positively correlated with each other. This study suggests that increased levels of oxidative stress markers, Fer-1 ic50 proinflammatory markers, and adhesion molecules contribute to the atherosclerotic process that eventually leads to coronary artery disease in diabetic patients.”
“The present study was carried out to assess the culturable actinomycetes diversity of near-shore sediments of Algoa Bay collected at depths ranging from 5.91 to 7.51 m and approximately 500 m distance from shore. Counts of the actinomycetes ranged in the orders 10(1) to 10(2) cfu/g using CSPY-ME agar and 10(2) to 10(3) cfu/g using M1 agar. A total of 326 actinomycetes isolates belonging to sixteen (16) genera were isolated from sediment samples and includes Actinoplane spp. (4.9%); Actinopolyspora spp. (3.68%); Amycolata spp. (0.92%), Actinosynema spp. (1.53%); Ampularia spp. (3.37%); Amycolaptosis spp. (2.45%); Catellospora spp. (6.14%); Intrasporangium spp. (3.37%); Kibdellosporium spp. (2.45%); Kitasatospora spp. (2.15%); Micromonospora spp. (7.98%); Norcadia spp. (2.45%); Salinispora spp. (2.15%); Saccharopolyspora spp. (0.92%); Streptoverticillium spp.

Despite their frequency, the overlapping mechanisms that repair t

Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1

or APE1 GANT61 cell line depletion alone. Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased Ulixertinib MAPK inhibitor sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge.

Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide.”
“The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and death by modulating gene expression. We previously examined this pathway in the myocardium via manipulation of the unique E2F repressor, E2F6, which is believed to repress gene activity independently of Rb. Mice with targeted expression of E2F6 in postnatal myocardium developed dilated cardiomyopathy (DCM) without hypertrophic growth. We assessed the mechanisms of the apparent failure of compensatory hypertrophic growth as well as their response to the beta-adrenergic agonist isoproterenol. As early as 2 weeks, E2F6 transgenic (Tg) mice present with dilated thinner left GM6001 solubility dmso ventricles and significantly reduced ejection fraction and fractional shortening which persists at 6 weeks of age, but with no apparent increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated with isoproterenol (6.1 mg/kg/day) show double

the increase in LVW:BW than their Wt counterparts (32% vs 16%, p-value: 0.007). Western blot analysis revealed the activation of the adrenergic pathway in Tg heart tissue under basal conditions with similar to 2-fold increase in the level of beta(2)-adrenergic receptors (p-value: 8.9E-05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c-Src tyrosine-protein kinase (p-value: 0.0002), extracellular receptor kinase 2 (ERK2) (p-value: 0.0005), and induction of the anti-apoptotic protein Bcl2 (p-value 0.0.00001). In contrast, a similar to 60% decrease in the cardiac growth regulator: AKT1 (p-value 0.0001) and a similar to four fold increase in cyclic AMP dependent phosphodiesterase 4D (PDE4D), the negative regulator of PICA activity, were evident in the myocardium of E2F6-Tg mice.

The method was successfully applied to quantify urapidil concentr

The method was successfully applied to quantify urapidil concentrations in a preclinical pharmacokinetic study after a single oral administration of urapidil at 3 mg/kg HM781-36B order to rats. Following oral administration

the maximum mean concentration in plasma (C(max); 616 +/- 73 ng/mL) was achieved at 0.5 h (T(max)) and area under curve (AUC(0-24)) was 1841 +/- 308 ng h/mL. The half-life (t(1/2)) and clearance (Cl) were 2.47 +/- 0.4 h and 1660 +/- 276 mL/h/kg, respectively. Moreover, it is plausible that the assay method in rat plasma would facilitate the adaptability of urapidil quantification in human plasma for clinical trials. Copyright (C) 2011 John Wiley & Sons, Ltd.”
“A subset of CD4(+) Cilengitide T cells, the CD4(+) CD25(+) regulatory T (T(reg)) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such ‘natural regulatory (T(reg)) cells’ and for activation of the effector function of CD4+ CD25+ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes,

the B-1 cells, primarily localized to coelomic cavities, Peyer’s patches, tonsils and spleen. CD5 acts as a negative regulator of T cell and B cell signaling via recruitment Selleck Screening Library of SHP-1. Here, we demonstrate that T(reg) cells obtained from CD5(-/-) mice are more potent than those from wild type mice in suppressing the in vitro cell proliferation of anti-CD3 stimulated CD4(+) CD25(-) responder T cells. This phenomenon was cell contact and GITR dependent. Lack of CD5 expression on T(reg) cells (from spleen, lymph node and thymus) did not affect the intracellular levels of Foxp3. However, CD5(-/-) Treg thymocytes were able to elicit a higher Ca(2+) response

to TCR + co-stimulatory signals than the wild type cells. CD5(-/-) mice expressed more Foxp3 mRNA in the colon than wild type mice, and additionally, the severity of the dextran sulfate sodium (DSS)-induced colitis in CD5(-/-) mice was less than the wild type strain. We suggest that manipulation of CD5 expression or the downstream signaling components of CD4(+) CD25(+) T(reg) cells as a potential strategy for therapeutic intervention in cases of auto-immune disorders. (C) 2008 Elsevier B.V. All rights reserved.”
“The NF-kappa B/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-kappa B consists of a heterodimer which is complexed with its inhibitor, I kappa B.

In total, 248 eligible replies were received resulting in a usabl

In total, 248 eligible replies were received resulting in a usable response rate of 25%. The majority of respondents (91%) had experienced or

click here witnessed some form of violence in community pharmacy within the preceding 12 months. Of all respondents, approximately one-third (33%) had been subjected to verbal abuse on at least a once-monthly basis. One-fifth of all respondents experienced or witnessed incidents of bullying/intimidation at least monthly, while one-tenth of all respondents had been exposed to sexual harassment/assault at least once-monthly. The impact of violent incidents was significant, with approximately one in ten respondents who had experienced violent incidents having changed employment as a direct result of these violent incidents; the majority of these pharmacists changed to a different community pharmacy (95%). A large proportion of respondents

claimed that they either ‘sometimes’ or ‘never’ reported violent incidents. Over half of all respondents claimed that they received no post-incident support regardless of the type of violence experienced. Conclusion Recognising the likelihood of selection bias in responding to the survey, the results nevertheless indicate that violence appears a real and common problem in Australian community pharmacies. The under-utilisation of violence preventative strategies, LCL161 the lack of violence management by employers, under-reporting of violence JIB-04 mouse and the lack of post-violence support need to be addressed.”
“Plant disease resistance genes are a key component of defending plants from a range of pathogens. The majority of these resistance genes belong to the super-family that harbors a Nucleotide-binding site (NBS). A number of studies have focused on NBS-encoding genes in disease resistant breeding programs for diverse plants. However, little information has been reported with an emphasis on systematic analysis and comparison of NBS-encoding

genes in cotton. To fill this gap of knowledge, in this study, we identified and investigated the NBS-encoding resistance genes in cotton using the whole genome sequence information of Gossypium raimondii. Totally, 355 NBS-encoding resistance genes were identified. Analyses of the conserved motifs and structural diversity showed that the most two distinct features for these genes are the high proportion of non-regular NBS genes and the high diversity of N-termini domains. Analyses of the physical locations and duplications of NBS-encoding genes showed that gene duplication of disease resistance genes could play an important role in cotton by leading to an increase in the functional diversity of the cotton NBS-encoding genes.

In contrast to CD8(+) T cells, we show that CD4(+) T cells expres

In contrast to CD8(+) T cells, we show that CD4(+) T cells expressing m33 survived for months in vivo. Furthermore, the m33-transduced CD4(+) T cells were able to mediate

antigen-specific rejection of 6-day-old tumors. Together, we show that CD8(+) T cell expressing a MHC class I-restricted high-affinity TCR were rapidly deleted whereas CD4(+) T cells expressing the same TCR survived and provided function while being directed against a class I-restricted antigen. Received 27 June 2011; accepted 1 December 2011; published online 10 January 2012. doi:10.1038/mt.2011.286″
“P>fwa is a late flowering epi-mutant in Arabidopsis thaliana. FWA is silenced by DNA methylation in vegetative tissue but is demethylated in the central cell of the female GSK1120212 ovule and continues to be expressed in the endosperm from the maternal copy. FWA is stably silenced in A. thaliana, but check details in related Arabidopsis species, FWA expression and DNA methylation levels vary in vegetative tissue. In this study, we show that variation in FWA expression in field isolates having identical DNA sequences is associated with changes in DNA methylation

and may change over time. Vegetative FWA expression is correlated with decreased methylation at non-CG sites in the region upstream of the transcription start site in species related to A. thaliana and we conclude that methylation of this region is critical for FWA silencing in these species. In A. thaliana, FWA expression is affected by methylation in regions both upstream and downstream of the transcription start site. Ectopic A. thaliana FWA expression causes a late flowering phenotype,

but over-expression of Arabidopsis lyrata FWA does not. In A. thaliana, stable silencing of FWA to prevent late flowering may have evolved through the selection of large tandem repeats and spread of the critical methylated Metabolism inhibitor region to include these repeats.”
“A computer program has been developed to exploit the multimedia capabilities of a personal computer for a new design of sodar (sonic detection and ranging) data acquisition and control system with minimized hardware elements. Advantages include trouble-free, cost-effective and user-friendly sodar data acquisition using any standard computer. The new design overcomes limitations due to using an add-on data acquisition card with conventional computer-controlled sodar. The data can be processed to produce online display of the dynamics of prevailing atmospheric boundary layer thermal structures and inversion/mixing depth for environmental applications.”
“The present feasibility study evaluated the chorioallantoic membrane (CAM) assay established in cancer and angiogenesis research as a tool for the study of vascular anomalies (VAs) in the head and neck area, since the lack of appropriate model systems poses a major obstacle in VA research.

Results: Eight hTERT-specific SECs (SEC-1-8) were successfully co

Results: Eight hTERT-specific SECs (SEC-1-8) were successfully constructed. In comparison to that of the negative control SEC, the hTERT-specific SECs, especially, SEC-4, SEC-5, SEC-7 and SEC-8 significantly reduced the activity of hTERT in HepG2 cells at 48 hours after transfection. Moreover, the mRNA and protein expression levels of hTERT as well as the cell viability were significantly reduced by SECs. Knockdown of hTERT by SECs in HepG2 cells led to cell apoptosis. Conclusions: Our developed simple SEC was a powerful strategy for screening highly effective RNAi-targeted sequences and showed promise for gene therapy of HCC.”

and research on detained girls has mainly been problem oriented, overlooking these minors’ own perspective on and find more satisfaction with life. The aim of this study was to examine how girls evaluate multiple domains of quality of life (QoL) and how each domain is affected by psychiatric (co)morbidity, trauma, and socioeconomic status (SES). An abbreviated version of the World Health Organization (WHO) QoL Instrument was used to assess the girls’ (N = 121; Selleckchem LY2606368 M (age) = 16.28) QoL prior to detention. This self-report questionnaire

consists of two benchmark items referring to their overall QoL and health, and 24 remaining items measuring their QoL regarding four domains (physical health, psychological health, social relationships, and environment). The Diagnostic Interview Schedule for Children-IV was used to assess the past-year prevalence of psychiatric disorders and life-time trauma exposure. Detained girls perceived their QoL almost as good as the 12- to 20-year-olds from the WHO’s international field trial on all but one domain (i.e., psychological health). They were most satisfied with their social relationships and least satisfied with their

psychological health. Psychiatric disorders, trauma, and low SES were distinctively and negatively related to various domains of QoL. The girls’ psychological health was most adversely affected by psychosocial and socioeconomic problems, while these variables had an almost negligible impact on their satisfaction with their social relationships. The particularity of each domain of QoL supports a multidimensional conceptualization of QoL. Regarding treatment, psychological health appears as a domain of major concern, while social relationships might serve as a source of resilience.”
“A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear.

However, it is not well understood how selection on the phenotype

However, it is not well understood how selection on the phenotype determines fitness. In accordance with Fisher’s fundamental theorem, fitness should have no or very little genetic variance, whereas empirical data suggest that is not the case. To bridge these knowledge gaps, we follow Fisher’s geometrical model and assume that fitness is determined by multivariate stabilizing selection toward an optimum that may vary among generations. We assume random mating, free recombination, additive genes, and uncorrelated stabilizing selection and mutational effects on traits. In a constant environment, we find that genetic variance in fitness under

mutation-selection balance is a U-shaped function of the number of traits (i.e., AZD8186 of the so-called organismal complexity). Because the variance can be high if the organism is of either low or high complexity, this suggests that complexity has little direct costs. Under a temporally varying

optimum, genetic variance increases relative to a constant optimum BYL719 in vitro and increasingly so when the mutation rate is small. Therefore, mutation and changing environment together can maintain high genetic variance. These results therefore lend support to Fisher’s geometric model of a fitness landscape.”
“Two unusual cases of anterior urethral valves (AUV) without diverticulae are presented. The first case is a male child born with prenatal diagnosis of bilateral hydronephrosis. On cystoscopy, iris-like diaphragm valves were encountered about 3mm distal to the skeletal sphincter. In the second case, an 18-month-old male child was investigated for recurrent febrile urinary tract infections and obstructed urinary symptoms. Cystoscopy confirmed the presence of slit-like valves 5mm distal to the PFTα inhibitor skeletal sphincter. Fulguration of the AUVs was performed in both cases. It may be worthwhile to review all cases of anterior urethral obstruction collectively and re-categorize them appropriately

to include the unusual AUVs without diverticulum in that classification.”
“Bacterial infections are a common and serious complication of type 2 diabetes (T2D). The prevalence of melioidosis, an emerging tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is increased in people with T2D. This is the first study to compare murine models of T2D and melioidosis. Susceptibility and disease progression following infection with B. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic model of T2D. The metabolic profile of mice with diet-induced diabetes, including body weight, blood glucose, cholesterol, triglycerides, insulin resistance, and baseline levels of inflammation, closely resembled that of clinical T2D. Following subcutaneous infection with B.