A multivariate view of the speciation continuum.

The concept of a "speciation continuum" has gained popularity in recent decades. It emphasizes speciation as a continuous process that may be studied by comparing contemporary population pairs that show differing levels of divergence. In their recent perspective article in Evolution, Stankowski and Ravinet provided a valuable service by formally defining the speciation continuum as a continuum of reproductive isolation, based on opinions gathered from a survey of speciation researchers. While we agree that the speciation continuum has been a useful concept to advance the understanding of the speciation process, some intrinsic limitations exist. Here, we advocate for a multivariate extension, the speciation hypercube, first proposed by Dieckmann et al. in 2004, but rarely used since. We extend the idea of the speciation cube and suggest it has strong conceptual and practical advantages over a one-dimensional model. We illustrate how the speciation hypercube can be used to visualize and compare different speciation trajectories, providing new insights into the processes and mechanisms of speciation. A key strength of the speciation hypercube is that it provides a unifying framework for speciation research, as it allows questions from apparently disparate subfields to be addressed in a single conceptual model.

Evolutionary gain and loss of a pathological immune response to parasitism.

Parasites impose fitness costs on their hosts. Biologists often assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests that selection may sometimes favor loss of resistance, which may result in alternative stable states where some populations are resistant and others are tolerant. Intraspecific variation in immune costs is rarely surveyed in a manner that tests evolutionary patterns, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes, they gained resistance to the freshwater-associated cestode Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation are a commonly observed phenotype that contributes to suppression of cestode growth and viability but also imposes a substantial cost on fecundity. Combining genetic mapping and population genomics, we find that opposing selection generates immune system differences between tolerant and resistant populations, consistent with divergent optimization.

Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.

Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p < 0.001). Protein and gene expression of cleaved caspase-9 were significantly increased after MTX treatment, whereas the expression of Bcl-xL, c-FLIP, NFκBp65, pAkt1 significantly downregulated after MTX treatment. In conclusion, these results showed that intrinsic apoptotic pathway induced by MTX eventually adds the beneficial therapeutic role of MTX in psoriasis by controlling the acanthosis.

Methotrexate regulates Th-1 response by suppressing caspase-1 and cytokines in psoriasis patients.

BACKGROUND: Caspase-1 induces the proinflammatory cytokines which appears to be a promising target in Th1-type inflammatory diseases, like psoriasis. We determined the effect of MTX on caspase-1, TNF-α and IL-18 in psoriasis patients. METHODS: We recruited 45 control subjects and 58 psoriasis patients for this study. The patients were treated with 7.5mg of MTX per week for 12weeks. Folic acid was given at 5mg once daily except on the day of MTX for 12weeks. Blood samples and lesional skin biopsy were taken. Histological examination has been done. IL-18 and TNF-α levels were analyzed by using ELISA. Caspase-1 expression was analyzed by western blot and Real Time PCR. RESULTS: Histological examinations showed MTX decreased acanthosis in psoriasis skin. Plasma IL-18 level and serum TNF-α were increased in psoriasis and deduced significantly (P<0.001) after MTX treatment. Protein and mRNA expression of caspase-1 in skin biopsy were higher in psoriasis and reduced significantly (P<0.001) after MTX treatment. CONCLUSION: Decreasing inflammatory caspase and proinflammatory cytokines by MTX, inhibits the Th1 response in psoriasis. This shows the therapeutic effect of MTX in controlling the immunopathogenesis of psoriasis.

Methotrexate normalized keratinocyte activation cycle by overturning abnormal keratins as well as deregulated inflammatory mediators in psoriatic patients.

BACKGROUND: In psoriatic skin, epidermal keratinocytes undergo deregulated inflammatory response that leads to prolonged expression of inflammatory mediators as well as abnormal keratins. Methotrexate (MTX) is an immunosuppressive agent used as a standard drug to treat severe psoriasis. The aim of the study is to find the pharmacological effect of MTX on abnormal keratin and deregulated inflammatory mediators. METHODS: Fifty-eight psoriasis vulgaris patients were recruited for this study. Skin biopsies of psoriatic patients were collected and analyzed for activation signal such as TNF-α and IFN-γ and deactivation signal such as TGF-ß1. Also, protein and gene expression of normal keratins K14 and K10 and abnormal keratins K16 and K17 were analyzed in skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. RESULTS: Results show a significant decrease in tissue TNF-α and IFN-γ and increase in TGF-ß1 after MTX treatment when compared with before MTX treatment in psoriasis patients (p<0.001). Protein and gene expression of K14, K16 and K17 decreased after MTX treatment, whereas the expression of differentiation marker K10 increased after MTX treatment. CONCLUSION: MTX resolves deregulated inflammatory markers and maintains normal keratin phenotype on hyperproliferating KC, thereby controlling acanthosis in psoriasis patients.

Impact of methotrexate on oxidative stress and apoptosis markers in psoriatic patients.

Methotrexate (MTX), a cytotoxic chemotherapeutic agent, is considered an effective drug in the treatment of psoriasis. The aim of this study was to find out whether the effect of MTX treatment in psoriasis is due to oxidative stress-induced apoptosis. Psoriasis vulgaris patients (58 in number) were recruited for this study. Healthy volunteers (45 in number) served as control. Samples of psoriatic patients were collected and analyzed for total reactive oxygen species (ROS), malondialdehyde (MDA) levels, nitrite, nitrate levels and the activities of antioxidants like superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) and also the protein expression of caspase-3, before (Day 0) and after (at the end of 6 and 12 weeks) MTX treatment. Our results show a significant increase in tissue ROS and plasma MDA after MTX treatment when compared with before MTX treatment in psoriasis patients (p < 0.001). The levels of serum nitrite and nitrate were decreased significantly after MTX treatment (p < 0.001). The activities of plasma SOD, TAS and serum CAT levels were decreased, but not significantly after 12 weeks of treatment. The expression of caspase-3 was increased after MTX treatment. In conclusion, MTX induce apoptosis through oxidative stress by reducing NO and increasing caspase-3 levels. MTX-induced apoptosis may account for the beneficial effect of MTX treatment in psoriasis patients, which is characterized by acanthosis.

Serum interleukin-6 levels in response to methotrexate treatment in psoriatic patients.

BACKGROUND: Psoriasis is a chronic autoimmune hyperproliferative skin disease. In psoriasis, the cutaneous and systemic overexpression of various proinflammatory cytokines, such as interleukin-6 (IL-6) has been demonstrated. Methotrexate (MTX) has been used in the treatment of psoriasis. The aim of this study is to assess the effect of MTX on serum IL-6 levels and also to find the association between PASI score and IL-6 levels in psoriatic patients during MTX therapy. METHODS: We recruited 20 control subjects and 22 Psoriasis vulgaris patients for this study. The patients were treated with 7.5mg of methotrexate per week for 12 weeks. Folic acid was given at 5mg once daily except on the day of MTX for 12 weeks. There were 2 dropouts, because of increased liver enzyme levels. Blood samples were collected at three intervals (i.e., Day 0, 6 weeks, 12 weeks) from psoriatic patients and only once from control subjects. PASI score, biochemical and hematological parameters were assessed. Serum IL-6 level was analyzed by using ELISA. RESULTS: Biochemical and hematological parameters showed no significant changes. Serum IL-6 level and PASI score declined significantly (p<0.001) from Day 0 to 12 weeks of MTX treatment and also showed positive correlation before (r=0.992; p<0.000) and after (r=0.987; p<0.000) treatment with MTX. Out of 4 clinical indices of PASI, only 2 indices namely Infiltration (I) and Desquamation (D) showed positive correlation with IL-6 before and after MTX treatment. CONCLUSION: The treatment response with MTX in psoriatic patients can be seen both at clinical and molecular levels.

Role of sudarshan kriya and pranayam on lipid profile and blood cell parameters during exam stress: A randomized controlled trial.

BACKGROUND: Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis. AIM: Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters. MATERIALS AND METHODS: Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals. RESULTS: ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels. CONCLUSION: Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters.

Clinical efficacy of propylthiouracil and its influence on prolactin in psoriatic patients.

OBJECTIVE: Propylthiouracil (PTU) is an effective drug for psoriasis treatment. Prolactin (PRL) is increased during psoriasis which has hyperproliferative effect on keratinocytes. Hence, the objective is to find the effect of PTU on PRL level in psoriatic patients. DESIGN AND METHODS: 25 psoriatic patients and 10 control subjects were involved in the study. Serum PRL, hematological and biochemical parameters, thyroid profile and histopathological examination were performed. RESULTS: PTU treatment for 6 weeks and 12 weeks cleared psoriatic lesions indicated by decreased PASI score (p<0.001). Patients before treatment showed significantly increased PRL levels (male p<0.01, female p<0.001) when compared to controls, which was found to decrease significantly (male p<0.01, female p<0.001) after 12 weeks. Hematological and biochemical parameters showed no significant change. Histopathology showed reduced thickening of the epidermis and acanthosis after PTU treatment. CONCLUSION: Since PRL is a growth hormone involved in hyperproliferation of keratinocytes, this study reveals the antiproliferative effect of PTU. Furthermore, no major side effects were observed following PTU treatment.

Impact of propylthiouracil on quality of life in psoriasis patients.

BACKGROUND: Psoriasis greatly impacts the quality of life (QOL) of patients including several dermatological conditions that are listed in the Dermatology Life Quality Index (DLQI). Decrease in psoriatic lesion as measured by Psoriasis Area Severity Index (PASI) score is associated with improvement in QOL. Propylthiouracil (PTU) was found to be clinically efficient in clearing psoriatic lesions. Our objective is to find the extent of improvement in QOL in psoriatic patients treated with PTU. MATERIALS AND METHODS: Twenty-three psoriatic patients who were taking 300 mg PTU/day were involved in the study. Clinical improvement was assessed by PASI score and QOL was assessed by DLQI questionnaire at baseline, 6 th and 12 th week of PTU treatment. RESULTS: Psoriatic patients before treatment showed significantly increased DLQI score when compared with 6 and 12 weeks of PTU treatment which was found to be decreased significantly (P < 0.001) after PTU treatment. There was a positive correlation between DLQI and PASI score at all three intervals of treatment period at P < 0.001 (r = 0.793, r = 0.834, r = 0.801), respectively. CONCLUSION: Since PTU was found to improve the QOL of psoriasis patients, this study adds an advantage of using it as treatment option in psoriasis.

Psychological well-being in medical students during exam stress-influence of short-term practice of mind sound technology.

INTRODUCTION: Medical education is perceived as stressful. As excessive stress hampers students' performance, stress management is required for medical students. This study was aimed to assess the effect of Mind Sound Technology (MST), an intelligence enhancing program, on psychological well-being of medical undergraduates during exam stress. MATERIALS AND METHODS: Forty-two medical students were recruited and Dukes Health Profile scoring was done at baseline and during Exam Stress (ES). After pre-intervention measurements, the students were randomized into two groups: non-practitioners and MST practitioners. Post-intervention measurement was done at the end of 6 weeks when the students had examination. RESULTS: Students showed a significant increase (P < 0.001) in negative health scores like perceived health scores, anxiety, and depression and a significant decrease (P < 0.001) in positive health scores like Self-Esteem, Mental Health Score, Social Health Score, and General Health Score during exam when compared with baseline. MST practice increased positive health scores (P < 0.001) and decreased perceived health score (P < 0.01), anxiety, depression, and anxiety-depression scores significantly (P < 0.001) when compared with ES score. Non practitioners did not show any significant change in any of the scores when compared with ES score. Six weeks of MST practice by medical students have improved the academic scores (P < 0.05) when compared with their non-practitioner counterpart. CONCLUSION: Thus, practice of MST has helped in coping up the stress that occurs during examination and improved academic performance in medical undergraduates.