Glycaemic control mediates the relationships of employment status and self-stigma with self-care behaviours in young adults with type 2 diabetes.

AIMS AND OBJECTIVES: To investigate the relationships of sociodemographic factors, self-stigma, glycaemic control (measured by glycated haemoglobin (A1C)) and self-care behaviours in young adults with type 2 diabetes. BACKGROUND: Young adults aged 25-44 years are in their most productive period. Once diagnosed with diabetes, this population tends to experience poor glycaemic control and perform poorly in self-care activities. Such patterns may raise perceptions of self-stigma and further decrease motivations to engage in self-care behaviours in patients with diabetes. DESIGN: A cross-sectional, correlational research design. METHODS: The STROBE guidelines for cross-sectional studies were followed. A convenience sample of 115 participants was recruited from a medical centre in southern Taiwan. Instruments included the Self-Stigma Scale-Chinese version and the Diabetes Self-Care Behaviours Scale. Data were analysed using a three-step hierarchical regression analysis and the Sobel test. RESULTS: The average age of the participants was 36.7 years. Marital status, employment status, self-stigma and A1C were significantly associated with self-care behaviours, and these four variables explained 43.6% of the variance in self-care behaviours. However, A1C (ß = -.58, p < .001) was found to be the only determinant of self-care behaviours in the last regression model. The Sobel test showed that A1C had mediating effects on self-stigma and self-care behaviours as well as employment status and self-care behaviours. CONCLUSION: This study supports the interactive relationship among self-stigma, employment status, glycaemic control and self-care behaviours in young adults with type 2 diabetes. Strategies aimed at optimising glycaemic control can help reduce the effects of self-stigma perceptions and employment status on the self-care behaviours of such patients. RELEVANCE TO CLINICAL PRACTICE: More effective educational programmes should be designed to improve glycaemic control, lower the effects of employment and decrease perceptions of self-stigma to further motivate young adults to engage in better diabetes self-care behaviours.

Nanolipoprotein Particles as a Delivery Platform for Fab Based Therapeutics.

Nanolipoprotein particles (NLPs), a lipid bilayer-based nanoparticle platform, have recently been developed for in vivo delivery of a variety of molecules of therapeutic interest, but their potential to deliver Fabs with valencies that exceed those of current multivalent formats has not yet been evaluated. Here we describe the development, optimization, and characterization of Fab-NLP conjugates. NLPs were generated with maleimide reactive lipids for conjugation to a Fab with a C-terminal cysteine. Of note, maleimide reactive lipids were shown to conjugate to the apolipoprotein when the NLPs were assembled at pH 7.4. However, this undesirable reaction was not observed when assembled at pH 6. Site-specific Fab conjugation conditions were then optimized, and conjugation of up to 30 Fab per NLP was demonstrated. Interestingly, although conjugation of higher numbers of Fabs had a significant impact on NLP molecular weight, only a minimal impact on NLP hydrodynamic radius was observed, indicating that particle size is largely dictated by the discoidal shape of the NLP. Fab-NLP viscosity and its stability upon lyophilization were also evaluated as an assessment of the manufacturability of the Fab-NLP. Significantly higher Fab concentrations were achieved with the Fab-NLP conjugates relative to another multivalent format (Fab-PEG conjugates). Fab conjugation to the NLP was also not found to have an impact on Fab activity in both an inhibitory and agonist setting. Finally, the stability of the Fab-NLP conjugates was evaluated in 50% serum and Fab-NLPs demonstrated increased stability, with >63% of Fab-NLP remaining intact after 24 h at Fab per particle ratios of 7 or greater. Our findings suggest Fab-NLPs are a promising platform for the targeted delivery of Fabs in a multivalent format and are compatible with established manufacturing processes.

AviTrap: A novel solution to achieve complete biotinylation.

Site specific biotinylation of AviTagged recombinant proteins using BirA enzyme is a widely used protein labeling technology. However, due to the incomplete biotinylation reactions and the lack of a purification method specific for the biotinylated proteins, it is challenging to purify the biotinylated sample when mixed with the non-biotinylated byproduct. Here, we have developed a monoclonal antibody that specifically recognizes the non-biotinylated AviTag but not the biotinylated sequence. After a ten-minute incubation with the resin that is conjugated with the antibody, the non-biotinylated AviTagged protein is trapped on the resin while the fully biotinylated material freely passes through. Therefore, our AviTrap (anti-AviTag antibody conjugated resin) provides an efficient solution for enriching biotinylated AviTagged proteins via a simple one-step purification.

i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.

The ability to leverage antibodies to agonize disease relevant biological pathways has tremendous potential for clinical investigation. Yet while antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biology of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Here, we describe an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. iAb engineering provides a tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

Double- and monofunctional CD4⁺ and CD8⁺ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals.

More than 2 billion individuals are latently infected with Mycobacterium tuberculosis (Mtb). Knowledge of the key Mtb antigens and responding T-cell subsets mediating protection against Mtb is critical for developing improved tuberculosis (TB) vaccines. We previously reported that Mtb DosR-regulon-encoded antigens are recognized well by human T cells in association with control of Mtb infection. The characteristics of the responding T-cell subsets, however, remained unidentified. We have therefore studied the cytokine production and memory phenotypes of Mtb DosR-regulon-encoded antigen-specific T cells from individuals who had been infected with Mtb decades ago, yet never developed TB (long-term latent Mtb-infected individuals). Using multi-parameter flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α and IL-2, we found double and single cytokine-producing CD4(+) as well as CD8(+) T cells to be the most prominent subsets, particularly IFN-γ(+) TNF-α(+) CD8(+) T cells. The majority of these T cells comprised effector memory and effector T cells. Furthermore, CFSE labeling revealed strong CD4(+) and CD8(+) T-cell proliferative responses induced by several "immunodominant" Mtb DosR antigens and their specific peptide epitopes. These findings demonstrate the prominent presence of double- and monofunctional CD4(+) and CD8(+) T-cell responses in naturally protected individuals and support the possibility of designing Mtb DosR antigen-based TB vaccines.

Khmer Girls in Action and healing justice: Expanding understandings of anti-Asian racism and public health solutions.

This community case study highlights how Khmer Girls in Action (KGA), a Southeast Asian young women-led organizing group in Long Beach, California, enacts healing justice. Healing justice is a framework for both transforming structures at the crux of health inequities and healing emotional, spiritual, and psychological wounds inflicted by structural violence. KGA also anchors the cross-racial and intersectional Invest in Youth (IIY-LB) coalition. IIY-LB youth leaders have successfully fought to increase the city's investments in the social determinants of health, especially young people's well-being. Meanwhile, the coalition has critiqued over-investments in criminalization and policing as devastating Black, Brown, queer, low-income, immigrant, and refugee youth and communities. This case study highlights how KGA's work expands understandings of both anti-Asian racism and public health solutions in the following ways: First, KGA cultivates youth leaders' critical analyses to define root causes of health inequities impacting Southeast Asian refugees as rooted in imperialism, disinvestment, and increased criminalization. Furthermore, youth leaders come to understand how their communities' struggles and liberation necessitate intersectional and cross-racial coalitions. Second, youth leaders forge public health solutions that involve divesting from criminalization and institutionalizing an Office of Youth Development, as co-created with young people. Third, KGA and other IIY-LB organizations cultivate youth's leadership skills and community's political power to move hearts and minds of decision-makers and community members. For example, youth leaders have passed a ballot measure funding youth, climate, and health programs in addition to the city-based Office of Youth Development. Fourth, KGA engages in a wide range of "inward" healing practices to salve wounds caused by intergenerational trauma. This case study contributes to Asian American health equity by highlighting the specific importance of organizing, while illuminating abolitionist perspectives on public health solutions- both of which are under-discussed in discourse about anti-Asian racism. KGA's work thus illustrates the importance of centering critical analyses and leadership of communities most impacted by structural violence in forging transformative public health solutions to anti-Asian racism.

Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration.

The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs.

Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration.

In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38α and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-π stacking interaction. Compound 38 ameliorates neurotoxicity induced by amyloid-ß in human cortical neurons. Lastly, we demonstrate how to install propitious in vitro CNS-like properties into these selective inhibitors.

Cordycepin inhibits the proliferation of malignant peripheral nerve sheath tumor cells through the p53/Sp1/tubulin pathway.

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. In addition to skin pigmentation and cutaneous neurofibroma, some patients developed the plexiform neurofibroma since birth. Plexiform neurofibroma has abundant Schwann cells, fibroblasts, mast cells, blood vessels, and connective tissues, which increases the risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNST is a highly invasive cancer with no effective therapeutic agent. Cordycepin or 3'-deoxyadenosine is an extract from cordyceps militaris, which has been reported as an anti-inflammation and anti-tumor agent. Herein, we evaluated cordycepin's anti-proliferative effect on MPNST cell lines both in vitro and in vivo. Cordycepin inhibited the MPNST cell growth with an arrest of cell cycle at G2/M and S phases. The administration of naringin and pentostatin, inhibitors for adenosine deaminase (ADA), enzyme responsible for cordycepin degradation, did not show a synergistic effect in MPNST cells treated with cordycepin. However, the combined treatment enhanced the decrease of tumors in xenograft mouse model. Immunoblotting showed a decreased level of p53 protein in all MPNST cell lines, but S462TY cells. After cordycepin treatment, the levels of ERK, survivin, pAKT, and Sp1 proteins also decreased. The level of tubulin, but not actin or GAPDH, decreased in a dose-dependent manner. The microtubule network which is composed of tubulins was markedly decomposed in those treated MPNST cells. To elucidate the epigenetic control of transcription, ChIP-qPCR assay of the Sp1 and tubulin promoter regions revealed decreased Sp1 binding. The incorporation of 3'-doexyadenosine is detrimental for the process of poly(A) tail elongation. The poly(A) tail length assay showed the tail length in Sp1 and tubulin transcripts decreased in the treated cells. Nevertheless, the administration of SP1 protein to the treated cells could not rescue them completely. Furthermore, the p53-knocked-down cells (S462TY) where the expression of both p53 and Sp1 was suppressed, were vulnerable to cordycepin. The p53 protein could ameliorate the effect. In summary, cordycepin is effective to inhibit the growth of MPNST, probably through the pathway of p53/Sp1/tubulin.

Nanolipoprotein particles for co-delivery of cystine-knot peptides and Fab-based therapeutics.

Nanolipoprotein particles (NLPs) have been evaluated as an in vivo delivery vehicle for a variety of molecules of therapeutic interest. However, delivery of peptide-like drugs in combination with therapeutic Fabs has not yet been evaluated. In this study, we describe the development and characterization of cystine-knot peptide (CKP)-containing NLPs and Fab-CKP-NLP conjugates. CKPs were incorporated into NLPs using a self-assembly strategy. The trypsin inhibitor EETI-II, a model CKP, was produced with a C16 fatty acyl chain to enable incorporation of the CKP into the lipid bilayer core during NLP assembly. The CKP-NLP retained trypsin inhibitory function although the overall activity was reduced by ∼5 fold compared to free CKP, which was presumably due to steric hindrance. The NLP platform was also shown to accommodate up to ∼60 CKP molecules. Moreover, the stability of the CKP-NLP was comparable to the NLP control, displaying a relatively short half-life (∼1 h) in 50% serum at 37 °C. Therapeutic Fabs were also loaded onto the CKP-NLP by introducing thiol-reactive lipids that would undergo a covalent reaction with the Fab. Using this strategy, Fab loading could be reliably controlled from 1-50 Fabs per CKP-NLP and was found to be independent of CKP density. Surprisingly, Fab incorporation into CKP-NLPs led to a substantial improvement in NLP stability (half-life > 24 h) at 37 °C; also, there was no reduction in CKP activity in the Fab-CKP-NLP conjugates compared to CKP-NLPs. Altogether, our data demonstrate the potential of NLPs as a promising platform for the targeted or multidrug delivery of peptide-based drug candidates in combination with Fabs.

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region.

The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.

Cross-reactive immunity to Mycobacterium tuberculosis DosR regulon-encoded antigens in individuals infected with environmental, nontuberculous mycobacteria.

Mycobacterium tuberculosis DosR regulon-encoded antigens are highly immunogenic in M. tuberculosis-infected humans and are associated with latent tuberculosis infection. We have investigated the hypothesis that infection with or exposure to nontuberculous mycobacteria (NTM) can induce cross-reactive immunity to M. tuberculosis DosR regulon-encoded antigens since responsiveness has been observed in non-M. tuberculosis-exposed but purified protein derivative-responsive individuals. M. tuberculosis DosR regulon-encoded antigen-specific T-cell responses were studied in peripheral blood mononuclear cells (PBMCs) of NTM-infected/exposed individuals. BLASTP was used to determine the presence of M. tuberculosis DosR regulon-encoded protein orthologs among environmental mycobacteria and nonmycobacteria. Significant gamma interferon production was observed in PBMCs from NTM-infected/exposed individuals in response to M. tuberculosis DosR regulon-encoded antigens. DosR regulon-encoded protein orthologs were prominently present in tuberculous and environmental mycobacteria and surprisingly also in nonmycobacteria. The ubiquitous presence of the highly conserved DosR master regulator protein Rv3133c suggests that this is a general adaptive bacterial response regulator. We report a first series of M. tuberculosis antigens to which cross-reactive immunity is induced by NTM infection/exposure. The high conservation of M. tuberculosis DosR regulon-encoded antigens most likely enables them to induce cross-reactive T-cell responses.

Calebin-A induced death of malignant peripheral nerve sheath tumor cells by activation of histone acetyltransferase.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. The malignant peripheral nerve sheath tumor (MPNST), transformed from NF1 related plexiform neurofibroma, is a rapidly growing and highly invasive tumor. No effective chemotherapeutic agent is currently available. Calebin-A is a derivative from turmeric Curcuma longa. Given the anti-inflammatory and anticancer potentials of curcumin, whether Calebin-A also had the tumoricidal effect upon MPNST cells is still elusive. PURPOSE: To determine whether Calebin-A has the potential for anti-MPNST effect. METHODS: The MTT and FACS analysis of normal Schwann (HSC) and MPNST cells have been employed to determine the tumoricidal effect of Calebin-A. The expression of the signal pathway molecules was assessed by Western blotting. The CHIP with quantitative PCR assay was performed to quantify the promoter DNA binding to acetylated histone 3 (acetyl H3). The enzyme activities of histone acetyltransferase (HAT) and deacetylase (HDAC) have been evaluated by commercial kits. The measurements of tumor size of the xenograft mouse model were also performed. RESULTS: Calebin-A inhibited the proliferation of MPNST and primary neurofibroma cells in a dose-dependent manner. The flow cytometry analysis of the MPNST cells after treatment of 25 µm of Calebin-A demonstrated an increase of population in the G0/G1 phase but decrease in G2/M phase. Before treatment, the expression of Axl, Tyro3, and acetyl H3 was significantly higher in MPNST cells when compared to HSC. The expression of phosphorylated-AKT, -ERK1/2, survivin, hTERT, and acetyl H3 proteins were reduced after treatment. The CHIP assay shows the promoter DNA copies of survivin (BRIC5) and hTERT genes are significantly reduced post-treatment. The enzyme activity of HAT was significantly reduced, but not that of HDAC. Two HAT inhibitors, epigallocatechin-3-gallate (EGCG) and anacardic acid (AA) have also demonstrated a significant inhibitory effect on MPNST cells. Finally, the measurements of tumor size showed a significant reduction of the xenograft tumors after treatment of Calebin-A. CONCLUSION: Both in vitro and in vivo studies showed Calebin-A could inhibit the proliferation of MPNST with suppression of survivin and hTERT. The reduced expression of these two factors might be through the epigenetic histone modification resulting from the decreased activity of HAT.

Corrigendum to "Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children".

[This corrects the article DOI: 10.1155/2019/5948379.].

Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children.

There are no national data available of the oral health in Myanmar. In this study, we examined dental caries status of 187 school children located in the suburban area of Naypyidaw, capital of Myanmar, at the age of five and six and analyzed by the individual level and tooth level. Maxillary D and B were sensitive for dental caries almost at the same level. They were less sensitive than maxillary A. Mandibular A and B were tolerant for dental caries. Prevalence of dental caries in Myanmar children was still high. By applying item response theory and multilevel modeling, tooth level analysis can be implemented to confirm the tendency for sensitivity or tolerance for dental caries by the tooth level.

Adaptive adipose tissue stromal plasticity in response to cold stress and antibody-based metabolic therapy.

In response to environmental and nutrient stress, adipose tissues must establish a new homeostatic state. Here we show that cold exposure of obese mice triggers an adaptive tissue remodeling in visceral adipose tissue (VAT) that involves extracellular matrix deposition, angiogenesis, sympathetic innervation, and adipose tissue browning. Obese VAT is predominated by pro-inflammatory M1 macrophages; cold exposure induces an M1-to-M2 shift in macrophage composition and dramatic changes in macrophage gene expression in both M1 and M2 macrophages. Antibody-mediated CSF1R blocking prevented the cold-induced recruitment of adipose tissue M2 macrophages, suggesting the role of CSF1R signaling in the process. These cold-induced effects in obese VAT are phenocopied by an administration of the FGF21-mimetic antibody, consistent with its action to stimulate sympathetic nerves. Collectively, these studies illuminate adaptive visceral adipose tissue plasticity in obese mice in response to cold stress and antibody-based metabolic therapy.

How Community Organizing Promotes Health Equity, And How Health Equity Affects Organizing.

Public health scholarship increasingly recognizes community organizing as a vehicle for unleashing the collective power necessary to uproot socioeconomic inequities at the core of health disparities. In this article we reverse the analytical focus from how organizing can affect health equity, and we consider how the frame of health equity has shaped grassroots organizing. Using evidence from a range of cases in California, we suggest that the health equity frame can guide and justify grassroots groups' efforts to improve the health outcomes of marginalized populations; connect issues such as housing and school discipline to health; and provide a rationale for community organizing groups to directly address the trauma experienced by their own members and staff, who often come from communities at risk for poor health outcomes.

Malaria Case Detection Among Mobile Populations and Migrant Workers in Myanmar: Comparison of 3 Service Delivery Approaches.

BACKGROUND: Mobile populations and migrant workers are a key population to containing the spread of artemisinin-resistant malaria found in the border areas between Cambodia, Myanmar, and Thailand. Migrants often have limited knowledge of public health, including malaria, services in the area, and many seek care from unregulated, private vendors. METHODS: Between October 2012 and August 2016, we implemented malaria case finding and treatment in Tanintharyi Region, Kayin State, and Rakhine State of Myanmar through 3 entry points: village malaria workers (VMWs), mobile malaria clinics, and screening points. A total of 1,000 VMWs provided passive case detection and treatment services to residents in malaria-endemic villages. Active case finding through mobile malaria clinics was conducted by staff in 354 remote villages and work sites, where regular monitoring and supervision of VMWs would be difficult to maintain. Malaria screening points were a hybrid combination of active and passive case finding in which screening points were set up at fixed locations in Tanintharyi Region and Kayin State, such as bus stops, ferry docks, or informal border crossing points, and migrants entering into or departing from endemic areas could voluntarily receive malaria testing and treatment. Using routine monitoring data, we assessed and compared the malaria positive rate-the number of positive malaria cases out of those tested-across the 3 approaches as an indication of the programmatic effectiveness in identifying malaria cases in the population. Most testing was conducted with rapid diagnostic tests. RESULTS: Mobile teams (169,859) and VMWs (157,048) tested a higher number of community members than screening points (3,676) as they covered a wider geographical area. However, the malaria positive rate was higher among VMWs (7.29%) and screening points (7.10%) than mobile teams (2.64%). VMWs were located in hard-to-access areas that have higher malaria prevalence and are difficult to reach by vehicle while screening points specifically targeted mobile populations and migrant workers. Mobile teams also screened non-fever patients during their visits, which may explain their lower malaria positive rate. CONCLUSIONS: A combination of malaria testing approaches helps achieve both maximum reach and high case finding as it allows access to a range of migrant communities and provides an opportunity for continuity of service delivery as the migrants travel to their destinations.

Primary trabeculectomy surgery performed by residents at a county hospital.

PURPOSE: To evaluate the safety and efficacy of trabeculectomies performed by ophthalmology residents at a metropolitan county hospital, under the supervision of attending physicians. METHODS: A retrospective analysis of resident-performed trabeculectomies at the San Francisco General Hospital from the period of 1994 to 2004 was performed. The preoperative and postoperative ocular data of 50 eyes in 35 patients were evaluated. Of the 50 cases, 47 procedures were performed as primary trabeculectomies and 3 were revisions of trabeculectomies. RESULTS: The average follow-up period was 28.9+/-17.6 months with an intraocular pressure (IOP) decrease from 23.2+/-9.4 mm Hg preoperatively to 11.3+/-4.4 mm Hg at last follow-up, for a mean reduction of 11.9+/-10.5 mm Hg (51.6%) (P<0.0001). Follow-up periods ranged from 3 months to over 6 years. The number of medications required decreased from 3.2+/-1.1 to 0.6+/-0.1 (P<0.0001). Success, defined by a postoperative IOP < or =21 mm Hg or a decreased postoperative IOP of at least 25% from preoperative pressure if the preoperative IOP was already < or =21 mm Hg, was observed in 42 eyes (84%) at last follow-up. Best-corrected visual acuity was stable or improved in 22 eyes (44%) and was noted to decrease 2 or more Snellen lines in 28 eyes (56%). Notable complications included 3 cases (6%) of persistent hypotony (IOP<5), 1 case (2%) of late endophthalmitis, and 1 case (2%) of phthisis. Seven eyes (14%) required subsequent penetrating glaucoma procedures due to bleb failure. CONCLUSIONS: Results of this study suggest that the outcomes of trabeculectomies performed by residents at a county hospital can have a high success rate, comparable with previous studies in the literature. Rates of complications are overall similar to those found in the published literature.

Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis.

The dormancy (DosR) regulon of Mycobacterium tuberculosis is expressed in vitro during hypoxia and low-dose nitric oxide stimulation. Tubercle bacilli are thought to encounter these conditions in humans during latent infection. In this study, immune responses were evaluated to 25 most strongly induced DosR-regulon-encoded proteins, referred to as latency antigens. Proliferation assays were performed using M. tuberculosis-specific T-cell lines and peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients, tuberculin skin test positive (TST+) individuals and uninfected controls. All 25 latency antigens were able to induce production of interferon-gamma (IFN-gamma) by T-cell lines. Eighteen latency antigens were also recognized by PBMC of M. tuberculosis-infected individuals, which indicates expression of the DosR-regulon during natural infection. Differential analysis showed that TST+ individuals recognized more latency antigens and with a stronger cumulative IFN-gamma response than TB patients, while the opposite profile was found for culture filtrate protein-10. In particular Rv1733c, Rv2029c, Rv2627c and Rv2628 induced strong IFN-gamma responses in TST+ individuals, with 61%, 61%, 52% and 35% responders, respectively. In conclusion, several new M. tuberculosis antigens were identified within the DosR-regulon. Particularly strong IFN-gamma responses to latency antigens were observed in latently infected individuals, suggesting that immune responses against these antigens may contribute to controlling latent M. tuberculosis infection.