A rare case of bilateral distal segmental absence of fallopian tubes in a patient presenting with hydrosalpinx.

Isolated fallopian tube anomalies are a rare group of disorders, usually observed in otherwise asymptomatic patients. If symptomatic, the patients may present with infertility or unspecified abdominal pains. Various aetiologies have been proposed to explain this phenomenon, ranging from congenital to vascular events. Diagnosis is very challenging because in most cases those abnormalities are not easily seen on ultrasound, computed tomography, or even magnetic resonance imaging. The most objective and certain diagnosis, however, can be obtained through laparoscopy with an associated histopathological examination performed if necessary. Management of this rare group of disorders remains unclear - because the number of cases is relatively small, there is no consensus on treatment. We present a case of a 22-year-old woman with no relevant clinical history and no sexual activity with large bilateral hydrosalpinx that developed as a result of bilateral distal fallopian tube segmental absence with associated occlusion and concomitant endometriotic implants in the vicinity of the left ovarian fossa and the peritoneum of the rectouterine pouch. To our best knowledge, only a few similar cases have been described in the literature. We summarise the available descriptions of this group of pathologies, present theories that have been proposed to explain this phenomenon, and provide various classifications of those disorders.

Evaluation of serum levels of soluble (s)L- and (s)P-selectins in endometrial cancer.

OBJECTIVES: A number of reports on the role of selectin in the process of carcinogenesis, at the stage of proliferation and metastasis, have been available. The aim of the study was to analyze (s)P- and (s)L-selectin serum concentrations in women with EC and to compare these concentrations to clinical/pathological parameters and disease progression using surgical-pathological staging data. MATERIAL AND METHODS: A total of 46 patients with EC and 50 healthy controls were included in the study. Serum concentrations of sL- and sP-selectins were measured in all participants. The oncologic protocol was implemented in all women from the study group. RESULTS: Significantly higher serum concentrations were found in EC women as compared to controls. No statistically significant differences were found between the concentrations of the soluble forms of selectins and the following parameters: histologic type of EC, histologic tumor differentiation, depth of myometrial infiltration, cervical involvement, distant metastases, vascular space invasion, and disease advancement. Slightly higher (s)P-selectin concentrations were observed in serous carcinoma, in women with cervical involvement, in the sera of women with vascular space invasion and with advanced stages of the disease. Slightly higher mean (s)P-selectin concentrations correlated with lower differentiation of the tumor. Slightly higher mean (s)P-selectin concentration was detected in the sera of women with lymph node metastases and with the serosal and/or adnexal involvement. The results were statistically insignificant, but they almost reached statistical significance. CONCLUSIONS: L- and P-selectins play a role in the biology of EC. The absence of an unambiguous relationship between differences in (s)L- and (s)P-selectin levels and disease advancement suggests that they do not play a vital role in tumor progression in endometrial cancer.

Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

Is torpor a water conservation strategy? Heterothermic responses to acute water and food deprivation are repeatable among individuals of Phodopus sungorus.

Energy conservation is a clear function of torpor. Although many studies imply that torpor is also a water-saving strategy, the experimental evidence linking water availability with torpor is inconclusive. We tested the relative roles of water and energy shortages in driving torpor, using the Siberian hamster Phodopus sungorus as a model species. To account for the seasonal development of spontaneous heterothermy, we used male hamsters acclimated to short (8L:16D, SP; n = 40) and long (16L:8D, LP; n = 36) photoperiods. We continuously measured body temperature (Tb) during consecutive 32 h of complete removal of water, food, or both, separated by 7.5 d recovery periods. We predicted that all deprivation types would increase the frequency of spontaneous torpor in SP, and induce torpor in LP-acclimated hamsters. Individuals underwent each deprivation type twice in random orders. Food and water deprivation did not induce torpor in LP-acclimated P. sungorus. Patterns of torpor expression varied among deprivation types in SP individuals. Torpor frequency was significantly lower, but bouts were ∼2 h longer and 2.5 °C deeper, during water deprivation compared to food and food-and-water deprivation. Heterothermic responses to all deprivation types were repeatable among individuals. Different torpor patterns during water and food deprivation suggest that water and energy shortages are distinct physiological challenges. Deeper and longer bouts during water deprivation likely led to higher energy and water savings, while shorter and shallower bouts during fasting may reflect a trade-off between energy conservation and food-seeking activity. The lack of a difference between food- and food-and-water-deprived hamsters suggests a higher sensitivity to food than water shortage. This supports the traditional view that energy conservation is the major function of torpor, but suggests that water shortages may also modulate torpor use. The high repeatability of thermoregulatory responses to resource deprivation suggests that these may be heritable traits subject to natural selection.

Polymorphism of winter phenotype in Siberian hamster: consecutive litters do not differ in photoresponsiveness but prolonged acclimation to long photoperiod inhibits winter molt.

BACKGROUND: The theory of delayed life history effects assumes that phenotype of adult individual results from environmental conditions experienced at birth and as juvenile. In seasonal environments, being born late in the reproductive season affects timing of puberty, body condition, longevity, and fitness. We hypothesized that late-born individuals are more prone to respond to short photoperiod (SP) than early born ones. We used Siberian hamsters Phodopus sungorus, a model species characterized by high polymorphism of winter phenotype. We experimentally distinguished the effect of litter order (first or third) from the effect of exposure to long photoperiod (LP) before winter (3 months or 5 months) by manipulating the duration of LP acclimation in both litters. We predicted that, irrespective of the litter order, individuals exposed to long photoperiod for a short time have less time to gather energy resources and consequently are more prone to developing energy-conserving phenotypes. To assess effect of litter order, duration of acclimation to long days, and phenotype on basal cost of living we measured basal metabolic rate (BMR) of hamsters. RESULTS: Individuals born in third litters had faster growth rates and were bigger than individuals from first litters, but these differences vanished before transfer to SP. Litter order or duration of LP acclimation had no effects on torpor use or seasonal body mass changes, but prolonged acclimation to LP inhibited winter molting both in first and third litters. Moreover, individuals that did not molt had significantly higher BMR in SP than those which molted to white fur. Although one phenotype usually predominated within a litter, littermates were often heterogeneous. We also found that over 10% of individuals presented late response to short photoperiod. CONCLUSIONS: Our data indicate that duration of postnatal exposure to LP may define propensity to photoresponsiveness, regardless of the litter in which animal was born. Existence of littermates presenting different phenotypes suggests a prudent reproductive strategy of investing into offspring of varied phenotypes, that might be favored depending on environmental conditions. This strategy could have evolved in response to living in stochastic environment.

Cohesin-dockerin code in cellulosomal dual binding modes and its allosteric regulation by proline isomerization.

Cellulose is the most abundant organic molecule on Earth and represents a renewable and practically everlasting feedstock for the production of biofuels and chemicals. Self-assembled owing to the high-affinity cohesin-dockerin interaction, cellulosomes are huge multi-enzyme complexes with unmatched efficiency in the degradation of recalcitrant lignocellulosic substrates. The recruitment of diverse dockerin-borne enzymes into a multicohesin protein scaffold dictates the three-dimensional layout of the complex, and interestingly two alternative binding modes have been proposed. Using single-molecule fluorescence resonance energy transfer and molecular simulations on a range of cohesin-dockerin pairs, we directly detect varying distributions between these binding modes that follow a built-in cohesin-dockerin code. Surprisingly, we uncover a prolyl isomerase-modulated allosteric control mechanism, mediated by the isomerization state of a single proline residue, which regulates the distribution and kinetics of binding modes. Overall, our data provide a novel mechanistic understanding of the structural plasticity and dynamics of cellulosomes.

Phenotypic flexibility in heat production and heat loss in response to thermal and hydric acclimation in the zebra finch, a small arid-zone passerine.

To maintain constant body temperature (Tb) over a wide range of ambient temperatures (Ta) endothermic animals require large amounts of energy and water. In hot environments, the main threat to endothermic homeotherms is insufficient water to supply that necessary for thermoregulation. We investigated flexible adjustment of traits related to thermoregulation and water conservation during acclimation to hot conditions or restricted water availability, or both, in the zebra finch, Taeniopygia guttata a small arid-zone passerine. Using indirect calorimetry, we measured changes in whole animal metabolic rate (MR), evaporative heat loss (EHL) and Tb before and after acclimation to 23 or 40 °C, with different availability of water. Additionally, we quantified changes in partitioning of EHL into respiratory and cutaneous avenues in birds exposed to 25 and 40 °C. In response to heat and water restriction zebra finches decreased MR, which together with unchanged EHL resulted in increased efficiency of evaporative heat loss. This facilitated more precise Tb regulation in heat-acclimated birds. Acclimation temperature and water availability had no effect on the partitioning of EHL into cutaneous or respiratory avenues. At 25 °C, cutaneous EHL accounted for ~ 60% of total EHL, while at 40 °C, its contribution decreased to ~ 20%. Consistent among-individual differences in MR and EHL suggest that these traits, provided that they are heritable, may be a subject to natural selection. We conclude that phenotypic flexibility in metabolic heat production associated with acclimation to hot, water-scarce conditions is crucial in response to changing environmental conditions, especially in the face of current and predicted climate change.

Predictive and reactive changes in antioxidant defence system in a heterothermic rodent.

Living in a seasonal environment requires periodic changes in animal physiology, morphology and behaviour. Winter phenotype of small mammals living in Temperate and Boreal Zones may differ considerably from summer one in multiple traits that enhance energy conservation or diminish energy loss. However, there is a considerable variation in the development of winter phenotype among individuals in a population and some, representing the non-responding phenotype (non-responders), are insensitive to shortening days and maintain summer phenotype throughout a year. Differences in energy management associated with the development of different winter phenotypes should be accompanied by changes in antioxidant defence capacity, leading to effective protection against oxidative stress resulting from increased heat production in winter. To test it, we analysed correlation of winter phenotypes of Siberian hamsters (Phodopus sungorus) with facultative non-shivering thermogenesis capacity (NST) and oxidative status. We found that in both phenotypes acclimation to winter-like conditions increased NST capacity and improved antioxidant defence resulting in lower oxidative stress (OS) than in summer, and females had always lower OS than males. Although NST capacity did not correlate with the intensity of OS, shortly after NST induction responders had lower OS than non-responders suggesting more effective mechanisms protecting from detrimental effects of reactive oxygen metabolites generated during rewarming from torpor. We suggest that seasonal increase in antioxidant defence is programmed endogenously to predictively prevent oxidative stress in winter. At the same time reactive upregulation of antioxidant defence protects against reactive oxygen species generated during NST itself. It suggests that evolution of winter phenotype with potentially harmful characteristics was counterbalanced by the development of protective mechanisms allowing for the maintenance of phenotypic adjustments to seasonally changing environment.

An oversimplification of physiological principles leads to flawed macroecological analyses.

Macrophysiological analyses are useful to predict current and future range limits and improve our understanding of endotherm macroecology, but such analyses too often rely on oversimplifications of endothermic thermoregulatory and energetic physiology, which lessens their applicability. We detail some of the major issues with macrophysiological analyses based on the classic Scholander-Irving model of endotherm energetics in the hope that it will encourage other research teams to more appropriately integrate physiology into macroecological analyses.

Photoresponsiveness affects life history traits but not oxidative status in a seasonal rodent.

BACKGROUND: Shortening photoperiod triggers seasonal adjustments like cessation of reproduction, molting and heterothermy. However there is a considerable among-individual variation in photoresponsiveness within one population. Although seasonal adjustments are considered beneficial to winter survival, and natural selection should favor the individuals responding to changes in photoperiod (responders), the phenotype non-responding to changes in day length is maintained in population. Assuming the same resource availability for both phenotypes which differ in strategy of winter survival, we hypothesized that they should differ in life history traits. To test this we compared reproductive traits of two extreme phenotypes of Siberian hamster Phodopus sungorus - responding and non-responding to seasonal changes in photoperiod. We bred individuals of the same phenotype and measured time to first parturition, time interval between litters, offspring body mass 3, 10 and 18 days after birth and their growth rate. We also analyzed nest-building behavior. Additionally, we estimated the correlation between reproduction, and basal metabolic rate (BMR) and oxidative status in both phenotypes to infer about the effect of reproductive output on future investments in somatic maintenance. RESULTS: Prior to reproduction responding individuals were smaller than non-responding ones, but this difference disappeared after reproduction. Responding pairs commenced breeding later than non-responding ones but there was no difference in time interval between consecutive litters. Responders delivered smaller offspring than non-responders and more out of responding individuals built the nest during winter than non-responding ones. Reproduction did not affect future investments in somatic maintenance. Phenotypes did not differ in BMR and oxidative status after reproduction. However, concentration of reactive oxygen metabolites (ROM) was highest in responding males, and biological antioxidant potential (BAP) was higher in males of both phenotypes than in females. CONCLUSIONS: Delayed breeding in responding Siberian hamsters and high ROM concentration in male responders support our hypothesis that differences in adjustment to winter result in different life history characteristics which may explain coexistence of both phenotypes in a population. We propose that polymorphism in photoresponsiveness may be beneficial in stochastic environment, where environmental conditions differ between winters. We suggest that non-responding phenotype may be particularly beneficial during mild winter, whereas responders would be favored under harsh conditions. Therefore, none of the phenotypes is impaired when compared to the other.

Dual binding in cohesin-dockerin complexes: the energy landscape and the role of short, terminal segments of the dockerin module.

The assembly of the polysaccharide degradating cellulosome machinery is mediated by tight binding between cohesin and dockerin domains. We have used an empirical model known as FoldX as well as molecular mechanics methods to determine the free energy of binding between a cohesin and a dockerin from Clostridium thermocellum in two possible modes that differ by an approximately 180° rotation. Our studies suggest that the full-length wild-type complex exhibits dual binding at room temperature, i.e., the two modes of binding have comparable probabilities at equilibrium. The ability to bind in the two modes persists at elevated temperatures. However, single-point mutations or truncations of terminal segments in the dockerin result in shifting the equilibrium towards one of the binding modes. Our molecular dynamics simulations of mechanical stretching of the full-length wild-type cohesin-dockerin complex indicate that each mode of binding leads to two kinds of stretching pathways, which may be mistakenly taken as evidence of dual binding.

Melatonin attenuates phenotypic flexibility of energy metabolism in a photoresponsive mammal, the Siberian hamster.

The duration of melatonin (MEL) secretion conveys information about day length and initiates a cascade of seasonal phenotypic adjustments in photoresponsive mammals. With shortening days, animals cease reproduction, minimize energy expenditure, enhance thermoregulatory capacity and adjust functioning of the hypothalamic-pituitary-adrenal (HPA) axis to match the winter increase in energy demands. Within each season, stress plays an important role in the flexible adjustments of a phenotype to environmental perturbations. Recent studies have shown that thermal reaction norms of energy metabolism were narrower in winter-acclimated Siberian hamsters, Phodopus sungorus We tested the hypothesis that physiological changes occurring in response to prolonged MEL signals, including changes in the secretion of stress hormones, are responsible for the seasonal decrease in phenotypic flexibility of energy metabolism in photoresponsive mammals. To quantify reaction norms for basal metabolic rate (BMR) and cortisol (CORT) secretion, male Siberian hamsters maintained at a long (16 h:8 h light:dark) photoperiod were acclimated repeatedly for 12 days to 10 and 28°C. As predicted, the phenotypic flexibility of BMR decreased when animals were supplemented with MEL. However, at the same time, mean CORT concentration and the reaction norm for its secretion in response to changes in acclimation temperature increased. These results suggest that decreased sensitivity of HPA axis to CORT signal, rather than changes in CORT level itself, is responsible for the decreased phenotypic flexibility in photoresponsive species. Our results suggest that decreased phenotypic flexibility in winter, together with increased stress hormone secretion, make photosensitive species more vulnerable to climate change.

Specialist-generalist model of body temperature regulation can be applied at the intraspecific level.

According to theoretical predictions, endothermic homeotherms can be classified as either thermal specialists or thermal generalists. In high cost environments, thermal specialists are supposed to be more prone to using facultative heterothermy than generalists. We tested this hypothesis at the intraspecific level using male laboratory mice (C57BL/cmdb) fasted under different thermal conditions (20 and 10°C) and for different time periods (12-48 h). We predicted that variability of body temperature (Tb) and time spent with Tb below normothermy would increase with the increase of environmental demands (duration of fasting and cold). To verify the above prediction, we measured Tb and energy expenditure of fasted mice. We did not record torpor bouts but we found that variations in Tb and time spent in hypothermia increased with environmental demands. In response to fasting, mice also decreased their energy expenditure. Moreover, animals that showed more precise thermoregulation when fed had more variable Tb when fasted. We postulate that the prediction of the thermoregulatory generalist-specialist trade-off can be applied at the intraspecific level, offering a valid tool for identifying mechanistic explanations of the differences in animal responses to variations in energy supply.

Individual Differences in the Phenotypic Flexibility of Basal Metabolic Rate in Siberian Hamsters Are Consistent on Short- and Long-Term Timescales.

Basal metabolic rate (BMR) correlates with the cost of life in endothermic animals. It usually differs consistently among individuals in a population, but it may be adjusted in response to predictable or unpredictable changes in the environment. The phenotypic flexibility of BMR is considered an adaptation to living in a stochastic environment; however, whether it is also repeatable it is still unexplored. Assuming that variations in phenotypic flexibility are evolutionarily important, we hypothesized that they are consistently different among individuals. We predicted that not only BMR but also its flexibility in response to changes in ambient temperature (Ta) are repeatable on short- and long-term timescales. To examine this, we acclimated Siberian hamsters (Phodopus sungorus) for 100 d to winterlike and then to summerlike conditions, and after each acclimation we exposed them interchangeably to 10° and 28°C for 14 d. The difference in BMR measured after each exposure defined an individual's phenotypic flexibility (ΔBMR). BMR was repeatable within and among seasons. It was also flexible in both seasons, but in winter this flexibility was lower in individuals responding to seasonal changes than in nonresponding ones. When we accounted for individual responsiveness, the repeatability of ΔBMR was significant in winter (τ = 0.48, P = 0.01) and in summer (τ = 0.55, P = 0.005). Finally, the flexibility of BMR in response to changes in Ta was also repeatable on a long-term timescale, that is, among seasons (τ = 0.31, P = 0.008). Our results indicate the evolutionary importance of the phenotypic flexibility of energy metabolism and suggest that it may be subject to selection.

The sL1CAM in sera of patients with endometrial and ovarian cancers.

PURPOSE: L1CAM is a cell adhesion molecule suspected to play an important role in carcinogenesis. The objective of the study was to evaluate the level of soluble L1CAM in the sera of patients with endometrial and ovarian carcinomas and verify the feasibility of the sL1CAM as a marker of these carcinomas. METHODS: 35 endometrial and 18 ovarian cancer patients were enrolled in the study. 43 patients with benign gynecological conditions constituted a control group. The sL1CAM serum level was measured with ELISA test in each patient and it was referred to the data from the surgical staging of the cancers. RESULTS: The sL1CAM serum level was significantly lower in patients with endometrial cancer than in healthy women and slightly lower in the ovarian cancer group than in the control group. In the endometrial cancer group there was no correlation between sL1CAM concentration and cancer histopathology, stage or grade. sL1CAM concentration positively correlated with ovarian cancer stage and (not significantly) with grade. CONCLUSIONS: Despite the increasing data about the possible role of L1CAM as a strong prognostic factor of poor outcome in many cancers, we did not find evidence supporting the use of sL1CAM as a marker of endometrial or ovarian cancers.

Is M235T polymorphism of the angiotensinogen gene involved in the development of endometriosis?

OBJECTIVES: The aim of the study was to analyze the M235T polymorphism of the angiotensinogen (AGT) gene in women with endometriosis and to identify correlations between identified genotypes and the disease progression, its stage and clinical course as well as to evaluate the prognostic value of the investigated polymorphism in patients with endometriosis treated for infertility. MATERIAL AND METHODS: The study group consisted of 241 women with minimal to severe stage of endometriosis, the control group (without endometriosis) - 127. The molecular analysis was performed by PCR-RFLP technique. RESULTS: The analysis of the frequency of genotypes and alleles of M235T polymorphism showed no significant differences between the study and the control groups and between the severity grades of the disease (p > 0.05). No such differences were reported in the case of different localizations of the disease lesions, either. Evaluation of the correlations related to pain accompanying endometriosis did not demonstrate association with any genotypes of the analyzed AGT gene poly-morphism. Comparison of the results obtained in the group in which infertility treatment was successful (n = 54) and in those who failed to conceive (n = 73) did not show the correlation between the investigated polymorphism and the effect of infertility treatment. CONCLUSIONS: M235T polymorphism of the AGT gene seems unrelated to the development or the clinical course of en-dometriosis. No prognostic value has been found of the investigated polymorphism in predicting the effects of infertility treatment in women with endometriosis.

Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

Dual binding mode in cohesin-dockerin complexes as assessed through stretching studies.

A recent experimental study by Jobst et al. of stretching of a wild-type (WT) cohesin-dockerin complex has identified two kinds of the force-displacement patterns, with a single or double-peaked final rupture, which are termed "short" and "long" here. This duality has been interpreted as arising from the existence of two kinds of binding. Here, we analyze the separation of two cohesin-dockerin complexes of C. thermocellum theoretically. We use a coarse-grained structure-based model and the values of the pulling speeds are nearly experimental. In their native states, the two systems differ in the mutual binding orientations of the molecules in the complex. We demonstrate that the WT complex (PDB:1OHZ) unravels along two possible pathways that are qualitatively consistent with the presence of the short and long patterns observed experimentally. On the other hand, the mutated complex (PDB:2CCL) leads only to short trajectories. The short and long stretching pathways also appear in the cohesin-dockerin-Xmodule complex (PDB:4IU3, WT) of R. flavefaciens. Thus the duality in the stretching patterns need not be necessarily due to the duality in binding.

Structural fluctuations and thermal stability of proteins in crowded environments: effects of the excluded volume.

We perform molecular dynamics simulations for a simple coarse-grained model of a protein placed inside of a softly repulsive sphere of radius R. The protein is surrounded either by a number of same molecules or a number of spherical crowding particles that immitate other biomolecules such as the osmolytes. The two descriptions are shown to lead to distinct results when testing thermal stability as assessed by studying the unfolding times as a function of temperature. We consider three examples of proteins and show that crowding increases the thermal stability provided the inter-protein or protein-crowder interactions are repulsive. On the other hand, an introduction of attraction between the proteins is found to destabilize the proteins. Crowding by repulsive crowder particles is seen to enhance the RMSF in certain exposed regions. The effect grows on decreasing the size of the crowding particles. In the absence of crowding the RMSF anticorrelates with the coordination number related to the residue-residue interaction.