Dormant Phase Research Articles

Stressful Conditions Affect Seed Quality in Glyphosate Resistant Conyza bonariensis (L.)

Conyza bonariensis (L.) Cronquist is one of the main glyphosate-resistant weeds in no-till fields in Brazil. Here, the seed quality of glyphosate-resistant (R) and -susceptible (S) C. bonariensis biotypes, collected from different sites, was evaluated under stressful conditions by different seed tests. Glyphosate resistance was confirmed by dose-response and shikimate accumulation assays. The resistance factors were 6.9 (R1/S1), 4.5 (R2/S2), and 5.8 (R3/S3). Biotypes S1, S2, and S3 accumulated 2.7, 2.4, and 2.8 times more shikimic acid than biotypes R1, R2, and R3, respectively. Stress-free seed viability and germination potential ranged from 39% to 57% and from 37% to 57%, respectively, with no difference between R and S biotypes within each collection site. Seed incubation at 8 °C over 7 days (cold test) promoted greater germination in S biotypes (54% to 79%) compared to R ones (28% to 39%). In the accelerated aging tests (incubation at 42 °C over 48 hours), the germination decreased in both S (11% to 27%) and R (6% to 16%) biotypes. In the high-temperature stress tests, there were no differences in germination within biotypes at 35 and 45 °C; however, at 60 °C, the germination of the S1, R1, S2, R2, S3, and R3 biotypes was reduced by approximately 51%, 54%, 63%, 59%, 40%, and 30%, respectively. Under non-stressful conditions, germination potential and seed viability were similar in R and S biotypes; however, under cold or heat stress conditions, R biotypes reduced their germination rates, revealing that glyphosate resistance causes a fitness penalty in C. bonariensis at the seed level. However, because seed viability was not determined after experiments, it cannot be stated that such reduction in germination was due to the death or only a dormant phase of the seeds.

Effect of autologous growth factors on apoptosis and thickness of the outer nuclear layer in an experimental retinal degeneration model

Retinal pigment epithelium and photoreceptor cells are a microenvironment where 90 different peptides are synthesized for transduction, visual cycle, intracellular electron transport chain, and removal of metabolic wastes. Depending on the inheritance pattern, either mutant proteins accumulate inside the cells or the energy cycle is disrupted. Disruption of homeostasis causes the cells to switch to the dormant phase; if the improper conditions last longer, then apoptosis eventually develops resulting in a loss of visual function. In neural tissues, growth factors such as neural growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor are regulatory peptides for intracellular energy cycle and intracellular digestion. In this study, it has been shown histopathologically that autologous growth factors can prevent apoptosis and prevent loss of outer retinal thickness in the retinal degeneration model created with sodium iodate.

Metformin and Rifampicin combination augments active to latent tuberculosis conversion: A computational study

Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR-DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.

Autogenous and drying shrinkage of mortars based on Portland and calcium sulfoaluminate cements

Calcium sulfoaluminate (CSA) cement can be used as an alternative binder in concrete, partially or fully replacing ordinary Portland cement. While CSA cement considerably accelerates the mechanical properties development, the rapid evolution of the microstructure together with the high water demand cause rapid and large volume changes at early ages. As volume changes may lead to early-age cracking, measures to reduce them may be required In this paper, autogenous and drying shrinkage are studied in mortars prepared with Portland cement, CSA cement or a 50/50 blend as binder. Very fast self-desiccation and high autogenous shrinkage of the CSA-based mortar were observed compared to the mortar made with Portland cement. On the other hand, the early-age volume changes can be limited if a blend of the two cements is used. The blended system revealed a bi-modal trend in the evolution of self-desiccation and autogenous shrinkage, in which the initial fast self-desiccation and shrinkage enter the dormant phase after the first couple of days and again start after about 28 days.

Agronomic performance of the lignocellulosic feedstock crop energy cane in the Texas Rolling Plains

AbstractFeedstock genetics and environment are important factors determining biomass yield of biofuel crops. Field studies were conducted to evaluate agronomic performance of four energy cane (Saccharum spp. hybrid) genotypes (TUS11‐62, TUS11‐58, TCP10‐4928, and Ho 02‐113) in the Texas Rolling Plains. In the first study, cane billets were planted in 2015 and data were collected from first (2016) and second (2017) ratoons. A second study was planted in 2016 and data were collected the same year from plant cane. Data collected include biomass, stalk height, stalk population, leaf area index (LAI), and normalized difference vegetation index (NDVI). Biomass yield of ratoons was not significantly different (p > .05) among genotypes. However, TUS11‐58 had the highest plant cane yield. The average biomass yield of plant cane, first, and second ratoons were 20.2, 40.4, and 26.4 t ha−1 respectively. Longer growing period of ratoon (∼8 mo) compared to plant cane (∼5.5 mo) increased biomass. However, low temperatures (−14 to −16 °C) during the dormant phase resulted in lower yield of the second ratoon. Among genotypes, TUS11‐62 had taller stalks, but was cold sensitive. Genotype TCP10‐4928 had higher stalk population and LAI. An exponential relationship was observed between LAI and NDVI (R2 = .67). Overall, there were differences in growth characteristics of energy cane genotypes, however biomass yield was similar in the ratoon phase. The results of this study showed that low temperature tolerance and growing season duration are key factors in determining biomass yield in higher latitude regions such as the Texas Rolling Plains.

Implications of immune-mediated metastatic growth on metastatic dormancy, blow-up, early detection, and treatment.

Metastatic seeding of distant organs can occur in the very early stages of primary tumor development. Once seeded, these micrometastases may enter a dormant phase that can last decades. Curiously, the surgical removal of the primary tumor can stimulate the accelerated growth of distant metastases, a phenomenon known as metastatic blow-up. Recent clinical evidence has shown that the immune response can have strong tumor promoting effects. In this work, we investigate if the pro-tumor effects of the immune response can have a significant contribution to metastatic dormancy and metastatic blow-up. We develop an ordinary differential equation model of the immune-mediated theory of metastasis. We include both anti- and pro-tumor immune effects, in addition to the experimentally observed phenomenon of tumor-induced immune cell phenotypic plasticity. Using geometric singular perturbation analysis, we derive a rather simple model that captures the main processes and, at the same time, can be fully analyzed. Literature-derived parameter estimates are obtained, and model robustness is demonstrated through a time dependent sensitivity analysis. We determine conditions under which the parameterized model can successfully explain both metastatic dormancy and blow-up. The results confirm the significant active role of the immune system in the metastatic process. Numerical simulations suggest a novel measure to predict the occurrence of future metastatic blow-up in addition to new potential avenues for treatment of clinically undetectable micrometastases.

Area estimation of saffron cultivation using satellite images and time difference method (case study: Fazl Village in Nishabur County of Iran)

Estimating crop area is a key factor for crop monitoring and agricultural management. Having annual information on crop acreage and production change is necessary for agricultural decision-makers and planners. In recent years, the cultivation of saffron in Nishabur has received more attention by farmers due to low water requirements and its good income. Planning for the marketing of this strategic product and the provision of agricultural inputs for saffron requires that the information of the area under its cultivation be estimated accurately. The aim of this study was to monitor changes in cultivated areas and to estimate the saffron area using satellite imagery with different spatial resolutions and time series normalized different vegetation indexes (NDVITs). Using Landsat 8 satellite images and time difference methods based on plant phenology estimate the areas under cultivation of saffron was estimated in Fazl Village of Nishabur County. A satellite image of June 17, 2016, related to the plant's dormant phase and another on January 11, 2017, for the vegetative growth stage of saffron was prepared. Using different vegetation indices, saffron cultivation was distinguished from other agricultural products and estimated at 497 hectares with an overall accuracy of 72% and a kappa value of 71%. Also, the results indicated that the accuracy of this method depended on the patch area of agricultural lands, such that in areas less than 2000 square meters, the user's accuracy was 44 percent, in lands with an area between 2000 and 5000 square meters, the accuracy was 66 percent, while in farms between half to one-hectare, the accuracy reached 80% and in lands more than one hectare, the accuracy was 89%. The results of this research indicated that the use method is suitable for estimating the area under the cultivation of saffron and we suggest its examination in other parts of the country.

Variation and Dynamics of Soil Nematode Communities in Greenhouses with Different Continuous Cropping Periods

Continuous cropping in greenhouses can result in root-knot nematode outbreaks resulting from imbalances in the soil nematode community. However, the changes in soil nematode communities in greenhouses with continuous crop production are unclear. We compared soil nematode communities in greenhouses after 2 years (2-yr) and 10 years (10-yr) of continuous crop production by 18S rDNA high-throughput sequencing. Compared with the 2-yr greenhouse, soil in the 10-yr greenhouse showed acidification, nutrient accumulation and salinization. Bacterial-feeding nematodes (BF) were dominant in the 2-yr greenhouse over the whole growing season, but plant-parasitic nematodes (PP) were the dominant group in the 10-yr greenhouse during the late growing season. Meloidogyne gradually became the dominant group and had a relative abundance of 70.9% (maximum) in the 10-yr greenhouse. Rhabditidae, with relative abundance ranging from 99.8% to 26.8%, was the predominant group in the 2-year greenhouse. For β-diversity, hierarchical clustering analysis, unweighted UniFrac principal component analysis (PCA) and principal co-ordinates analysis (PCoA) all revealed that soil nematode communities in the two types of greenhouses were significantly different. Redundancy analysis (RDA) showed that soil nematode communities in the 10-yr greenhouse were related to high soil organic material, total nitrogen, electrical conductivity and disease index of root-knot nematodes. Fisher's exact test and Pearson's correlation coefficients revealed that Meloidogyne contributed to the main differences in soil nematode communities between the two types of greenhouses. Population dynamics of Meloidogyne were divided into dormant phase, low-level increasing phase and exponential phase during the whole season. The soil nematode communities within the 2-yr and 10-yr greenhouses had significant variation and different dynamics. This work contributes to a deeper understanding of changes in the soil nematode community in greenhouses with different continuous cropping duration.

Hypoxia-mediated changes in bone marrow microenvironment in breast cancer dormancy.

Breast cancer (BC) remains a clinical challenge despite improved treatments and public awareness to ensure early diagnosis. A major issue is the ability of BC cells (BCCs) to survive as dormant cancer cells in the bone marrow (BM), resulting in the cancer surviving for decades with the potential to resurge as metastatic cancer. The experimental evidence indicates similarity between dormant BCCs and other stem cells, resulting in the preponderance of data to show dormant BCCs being cancer stem cells (CSCs). The BM niche and their secretome support BCC dormancy. Lacking in the literature is a comprehensive research to describe how the hypoxic environment within the BM may influence the behavior of BCCs. This information is relevant to understand the prognosis of BC in young and aged individuals whose oxygen levels differ in BM. This review discusses the changing information on vascularity in different regions of the BM and the impact on endogenous hematopoietic stem cells (HSCs). This review highlights the necessary information to provide insights on vascularity of different BM regions on the behavior of BCCs, in particular a dormant phase. For instance, how the transcription factor HIF1-α (hypoxia-inducible factor 1 alpha), functioning as first responder under hypoxic conditions, affects the expression of specific gene networks involved in energy metabolism, cell survival, tumor invasion and angiogenesis. This enables cell fate transition and facilitates tumor heterogeneity, which in turn favors tumor progression and resistance to anticancer treatments Thus, HIF1-α could be a potential target for cancer treatment. This review describes epigenetic mechanisms involved in hypoxic responses during cancer dormancy in the bone marrow. The varied hypoxic environment in the BM is relevant to understand the complex process of the aging bone marrow for insights on breast cancer outcome between the young and aged.

Male meiosis in sweet cherry is constrained by the chilling and forcing phases of dormancy.

Male meiosis in temperate fruit trees occurs in the anthers once a year, synchronized with the seasons. The alternation of dormant and growth cycles determines the optimum moment for the male gametophyte formation, a process sensitive to both cold and warm temperatures. This ensures pollen viability and subsequent reproduction success that guarantee fruit production. In this work, we explore how male meiosis is framed by seasonality in sweet cherry. For this purpose, the dormant phases, male meiosis and blooming dates were established in four cultivars with different flowering dates and chilling requirements over 7 years. The chilling and heat requirements for each cultivar were empirically estimated, and chilling and heat temperatures were quantified according to the Dynamic and Growing Degree Hours (GDH) models, respectively. Endodormancy was overcome approximately a fortnight earlier during the colder winters than during the milder winters. Against our initial hypothesis, these differences were not clearly reflected in the time of male meiosis. The period between chilling fulfillment and meiosis lasted several weeks, during which a high amount of GDH accumulated. Results showed that male meiosis is conditioned by endodormancy but especially by warm temperatures, during the forcing period. This differs from what has been described in other related species and creates a framework for further studies to understand the strategies of synchronizing dormancy with seasons.

Anti-angiogenesis Potential of Phytochemicals for the Therapeutic Management of Tumors.

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models. The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

One-Year Old Dormant, "Non-culturable" Mycobacterium tuberculosis Preserves Significantly Diverse Protein Profile.

For adaptation to stressful conditions, Mycobacterium tuberculosis (Mtb) is prone to transit to a dormant, non-replicative state, which is believed to be the basis of the latent form of tuberculosis infection. Dormant bacteria persist in the host for a long period without multiplication, cannot be detected from biological samples by microbiological methods, however, their “non-culturable” state is reversible. Mechanisms supporting very long capacity of mycobacteria for resuscitation and further multiplication after prolonged survival in a dormant phase remain unclear. Using methods of 2D electrophoresis and MALDI-TOF analysis, in this study we characterized changes in the proteomic profile of Mtb stored for more than a year as dormant, non-replicating cells with a negligible metabolic activity, full resistance to antibiotics, and altered morphology (ovoid forms). Despite some protein degradation, the proteome of 1-year-old dormant mycobacteria retained numerous intact proteins. Their protein profile differed profoundly from that of metabolically active cells, but was similar to the proteome of the 4-month-old dormant bacteria. Such protein stability is likely to be due to the presence of a significant number of enzymes involved in the protection from oxidative stress (katG/Rv1908, sodA/Rv3846, sodC/Rv0432, bpoC/Rv0554), as well as chaperones (dnaJ1/Rv0352, htpG/Rv2299, groEL2/Rv0440, dnaK/Rv0350, groES/Rv3418, groEL1/Rv3417, HtpG/Rv2299c, hspX/Rv2031), and DNA-stabilizing proteins. In addition, dormant cells proteome contains enzymes involved in specific metabolic pathways (glycolytic reactions, shortened TCA cycle, degradative processes) potentially providing a low-level metabolism, or these proteins could be “frozen” for usage in the reactivation process before biosynthetic processes start. The observed stability of proteins in a dormant state could be a basis for the long-term preservation of Mtb cell vitality and hence for latent tuberculosis.

Anatomical and biochemical studies on tuber growth and development in Gloriosa superba L.

The present investigation was carried out at the Botanical Garden, Department of Medicinal and Aromatic Crops, Tamil Nadu Agricultural University, Coimbatore during 2018-19. Cultivated type and Andhra wild ecotypes of glory lily in two different growth phases viz. 1) actively sprouting period and 2) dormant period were used for anatomical and biochemical studies. Observations were made on internal structure of tubers using SEM analyzer with EDAX instrument. Further biochemical analyses were made on starch, soluble protein, peroxidase and catalase activities of the tubers in both phases. The results indicated that, there was no difference found in internal structure of the tubers between the two ecotypes (Andhra wild and cultivated type) of glory lily but, the number and size of starch granules increased in dormant phase compared to sprouting phase. In dormant phase, Mn, Fe, Cu and Zn elements were absent while those elements are present in sprouting phase. The starch content was recorded highest in Andhra wild tubers in dormant phase (43.65 mg/g) while the cultivated type tubers in sprouting phase recorded lowest content (17.25 mg/g). Highest catalase activity (7.85 μg of H2O2 g−1 min−1) and peroxidase activity (1.84 min−1 g−1) was registered in sprouting phase of cultivated type. The total soluble protein content was highest in Andhra wild tuber with dormant phase (7.81 mg/g), while cultivated type in sprouting phase recorded lowest soluble protein content (3.46 mg/g).

Absence of convection in solid tumors caused by raised interstitial fluid pressure severely limits success of chemotherapy-a numerical study in cancers.

In comparison with lymphomas and leukemias, chemotherapy of solid neoplasms, i.e., cancer, has much more limited success in curing the patient. This lack of efficacy of chemotherapy has been attributed to increased interstitial fluid pressure within cancers, which obstructs convection and only permits diffusion of oxygen and nutrients about 100 μm from blood vessels. As diffusion is limited to this distance, hypoxic and necrotic fractions within the tumor are observed beyond this region. The comparably small number of cancer cells that can be targeted with drugs inevitably leads to an ineffective treatment response. This study presents an analysis of the influence of interstitial fluid pressure on the chemotherapeutic effect in an HT29 human colon cancer xenograft mouse tumor model. To investigate the limited distribution of drugs into primary tumor and metastases, we developed a mathematical model describing tumor growth dynamics of oxygenated, hypoxic, and necrotic fractions, combined with a pharmacokinetic-pharmacodynamic model describing the behavior and effectivity of the chemotherapeutic agent. According to the numerical simulations, the age of the tumor at treatment was the decisive factor in the reduction in size of the primary tumor. This effect is mediated by the rapid decrease in the percentage of oxygenated cells within the tumor, which reduces the fraction of cells that can be affected by the drug. As in the primary tumor, interstitial fluid pressure builds up in metastases when they reach a specific size, leading to the formation of tumor fractions. This behavior is absent if the metastasis enters a dormant phase before the threshold for the development of interstitial fluid pressure has been reached. The small size of these metastases maximizes therapeutic success since they consist only of oxygenated cells, and the drug therefore affects all the cells.

Ovarian Hemangioma Presented as an Incidental Ovarian Mass: A Rare Case Report along with Literature Review

Vascular malformation tumors in the female genital tract, especially those arising in the ovary are uncommon with low morbidity. Ovarian hemangioma (OH) featured as a benign rare tumor occurs among adults and children with the age ranging from infancy till octogenarian. Moreover, it presents as an obscured landscape in the backdrop of other gynecologic issues, making hard accuracy perceiving an isolated diagnosis. Usually asymptomatic cases amid patients are being investigated, remaining in dormant phase for a long time and until simultaneously cohabiting with another primary pathology. Metrorrhagia, a dysfunction uterine bleeding, might be a unique sign or association with suprapubic abdominal pain may suggest a vascular ovarian hemangioma.

Latent Tuberculosis Infection (LTBI) and Its Potential Targets: An Investigation into Dormant Phase Pathogens

One-third of the world's population harbours the latent tuberculosis infection (LTBI) with a lifetime risk of reactivation. Although, the treatment of LTBI relies significantly on the first-line therapy, identification of novel drug targets and therapies are the emerging focus for researchers across the globe. The current review provides an insight into the infection, diagnostic methods and epigrammatic explanations of potential molecular targets of dormant phase bacilli. This study also includes current preclinical and clinical aspects of tubercular infections and new approaches in antitubercular drug discovery.

CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression.

The first results of tephrochronological investigations of the late pleistocene-holocene volcanic explosions in the valley of the Zhom-Bolok River (Eastern Sayan)

This article presents first tephrochronological data on the volcanic activity in the valley of the Jom-Bolok River (East Sayan Mountains, Siberia), which is the largest manifestation of the Holocene eruptions in Central Asia. The data results from our study of the proglacial Kaskadnoe-1 Lake situated near the Jom-Bolok basalt field. The lake sediments include a series of tephra-rich layers. Radiocarbon dating of the lake sediments provided a robust age model which allowed us to build timing of eruptions formed the Jom-Bolok volcanic field. We recognize two large phases of volcanism separated by almost 5 thousand years dormant phase. The first phase is traced back to ca. 14.3 cal ka BP and lasted until 6.3 cal ka BP. Ten clusters of microtephra layers in the sediments of the first phase show 300-800 years recurrence of the volcanic events weakening upward. The event of 14.3-13.3 cal ka BP probably represents the strongest eruptions of the Jom-Bolok. The second phase started ca. 1.6 cal ka BP and highly likely continues in our days. Its strongest eruptions occurred between 1.6 and 0.8 cal ka BP with periodicity of 200 years. This tephrostratigraphy shows a multiplicity of the Jom-Bolok volcanic events and amplifies the earlier built scheme resulted from investigations of the stratified basalts, pyroclasts and lake damming events.

Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection.

One‐third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single‐center prospective observational study, we analyzed IgG‐antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA‐binding protein 1 (MDP1) and alpha‐crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18‐month follow‐up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy.

Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis.

Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures. However, looking into the multifactorial nature of AD and the overlapping pathology with other forms of dementia, it is important to integrate the core CSF biomarkers with a broader panel of other biomarkers reflecting different aspects of pathology. The review is focused upon a panel of biomarkers that relate to different aspects of AD pathology, as well as various studies that have evaluated their diagnostic potential. The panel includes markers of neurodegeneration: neurofilament light chain and visinin-like protein (VILIP-1); markers of amyloidogenesis and brain amyloidosis: apolipoproteins; markers of inflammation: YKL-40 and monocyte chemoattractant protein 1; marker of synaptic dysfunction: neurogranin. These markers can highlight on the state and stage-associated changes that occur in AD brain with disease progression. A combination of these biomarkers would not only aid in preclinical diagnosis, but would also help in identifying early brain changes during the onset of disease. Successful treatment strategies can be devised by understanding the contribution of these markers in different aspects of disease pathogenesis.