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Background: Females with schizophrenia often experience more severe and persistent depressive symptoms than males, in particular during the acute phase of the illness. In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and depression in schizophrenia., Aim: We examined the associations of sex versus gender with visit-wise changes in depressive symptoms over 24 months in patients with first-episode schizophrenia spectrum disorders (FES) (n = 77) compared to matched healthy controls (n = 64)., Methods: The Bem Sex Role Inventory was used to measure feminine gender role endorsement. The Calgary Depression Scale for Schizophrenia was used to measure depressive symptoms at baseline, weeks 2, 4, and 6, and months 3, 6, 9, 12, 15, 18, 21, and 24. We used mixed models for continuous repeated measures to examine the moderating effects of childhood trauma, premorbid adjustment, age of psychosis onset, and cannabis use on the associations of sex and gender with depressive symptoms., Results: Higher feminine gender role endorsement, independent of biological sex, was associated with more severe baseline depression and worse initial treatment trajectories. Childhood trauma exposure was also associated with worse depression outcomes, and mediated the association between gender and pre-treatment depression severities., Conclusions: Gender, but not sex, was associated with depressive symptom trajectories in FES. The consideration of both sex and gender offered a more nuanced insight into depressive symptoms compared to biological sex alone., Competing Interests: Declaration of competing interest Robin Emsley has participated in speakers/advisory boards and received honoraria from Janssen, Lundbeck, Servier and Otsuka. Hilmar Luckhoff, Elisabetta Del Re, Retha Smit, Sanja Kilian, Lebogang Phahladira, and Laila Asmal declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Coral reefs, vital ecosystems supporting diverse marine life, are primarily shaped by the clonal expansion of coral colonies. Although the principles of coral clonal growth, involving polyp division for spatial extension, are well-understood, numerical modelling efforts are notably scarce in the literature. In this article, we present a parsimonious numerical model based on the cloning of polyps, using five key parameters to simulate a range of coral shapes. The model is agent-based, where each polyp represents an individual. The colony's surface expansion is dictated by the growth mode parameter ( s ), guiding the preferred growth direction. Varying s facilitates the emulation of diverse coral shapes, including massive, branching, cauliflower, columnar and tabular colonies. Additionally, we introduce a novel approach for self-regulatory branching, inspired by the intricate mesh-like canal system and internode regularity observed in Acropora species. Through a comprehensive sensitivity analysis, we demonstrate the robustness of our model, paving the way for future applications that incorporate environmental factors, such as light and water flow. Coral colonies are known for their high plasticity, and understanding how individual polyps interact with each other and their surroundings to create the reef structure has been a longstanding question in the field. This model offers a powerful framework for studying these interactions, enabling a future implementation of environmental factors and the possibility of identifying the key mechanisms influencing coral colonies' morphogenesis.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods . Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for International Journal of Clinical and Health Psychology and was not involved in the editorial review or the decision to publish this article., (© 2024 The Author(s).)

We examined the associations of sex (biological distinction) and gender (societal distinction) with psychopathology, depressive symptoms and social and occupational functioning over 24 months. We found that lower masculinity scores were associated with worse psychopathology outcomes, independent of sex and other neurodevelopmental factors. These effects were mediated by poor premorbid adjustment, which also mediated the relationship between childhood trauma and masculinity scores as predictors of disorganized symptom outcomes. Our findings highlight the importance of considering gender as a separate construct and the need for further research to understand the clinical implications of sex and gender differences in schizophrenia., Competing Interests: Declaration of Competing Interest Robin Emsley has participated in speakers/advisory boards and received honoraria from Janssen, Lundbeck, Servier, and Otsuka. Hilmar Luckhoff, Lebogang Phahladira, Laila Asmal, Retha Smit, and Elisabetta del Re declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Automatic identification of human facial expressions has many potential applications in today's connected world, from mental health monitoring to feedback for onscreen content or shop windows and sign-language prosodic identification. In this work we use visual information as input, namely, a dataset of face points delivered by a Kinect device. The most recent work on facial expression recognition uses Machine Learning techniques, to use a modular data-driven path of development instead of using human-invented ad hoc rules. In this paper, we present a Machine-Learning based method for automatic facial expression recognition that leverages information fusion architecture techniques from our previous work and soft voting. Our approach shows an average prediction performance clearly above the best state-of-the-art results for the dataset considered. These results provide further evidence of the usefulness of information fusion architectures rather than adopting the default ML approach of features aggregation.

Multi-sensor fusion intends to boost the general reliability of a decision-making procedure or allow one sensor to compensate for others' shortcomings. This field has been so prominent that authors have proposed many different fusion approaches, or "architectures" as we call them when they are structurally different, so it is now challenging to prescribe which one is better for a specific collection of sensors and a particular application environment, other than by trial and error. We propose an approach capable of predicting the best fusion architecture (from predefined options) for a given dataset. This method involves the construction of a meta-dataset where statistical characteristics from the original dataset are extracted. One challenge is that each dataset has a different number of variables (columns). Previous work took the principal component analysis's first k components to make the meta-dataset columns coherent and trained machine learning classifiers to predict the best fusion architecture. In this paper, we take a new route to build the meta-dataset. We use the Sequential Forward Floating Selection algorithm and a T transform to reduce the features and match them to a given number, respectively. Our findings indicate that our proposed method could improve the accuracy in predicting the best sensor fusion architecture for multiple domains.

The production of top-quark pairs in hadronic collisions is among the most important reactions in modern particle physics phenomenology and constitutes an instrumental avenue to study the properties of the heaviest quark observed in nature. The analysis of this process at the Large Hadron Collider relies heavily on Monte Carlo simulations of the final state events, whose accuracy is challenged by the outstanding precision of experimental measurements. In this Letter we present the first matched computation of top-quark pair production at next-to-next-to-leading order in QCD with all-order radiative corrections as implemented via parton-shower simulations. Besides its intrinsic relevance for LHC phenomenology, this work also establishes an important step towards the simulation of other hadronic processes with color charges in the final state.

Aim: We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at 1-year follow-up in patients with first-episode schizophrenia. P300 reduction as well as intact P1/N1 were also observed in clinical high-risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR., Methods: Visual event-related potentials (ERP) were recorded twice, once at baseline and once at 1-year follow-up in CHR (n = 19) and healthy comparison subjects (HC; n = 28). Participants silently counted infrequent target stimuli ('x') among standard stimuli ('y') presented on the screen while the 64-channel electroencephalogram was recorded., Results: No CHR converted to psychosis from baseline to 1-year follow-up in this study. Visual P300 amplitude was reduced and the latency was delayed significantly in CHR at both time points compared with HC. Furthermore, CHR subjects who had more positive symptoms showed more amplitude reduction at both time points. P1, N1, and N200 did not differ between groups., Conclusion: Visual P300 amplitude was found to be reduced in CHR individuals compared with HC. We note that this finding is in subjects who did not convert to psychosis at 1-year follow-up. The association between visual P300 amplitude and symptoms suggests that for CHR who often experience clinical symptoms and seek medical care, visual P300 may be an important index that reflects the pathophysiological impairment underlying such clinical states., (© 2020 The Authors Psychiatry and Clinical Neurosciences © 2020 Japanese Society of Psychiatry and Neurology.)

Multi-sensor fusion refers to methods used for combining information coming from several sensors (in some cases, different ones) with the aim to make one sensor compensate for the weaknesses of others or to improve the overall accuracy or the reliability of a decision-making process. Indeed, this area has made progress, and the combined use of several sensors has been so successful that many authors proposed variants of fusion methods, to the point that it is now hard to tell which of them is the best for a given set of sensors and a given application context. To address the issue of choosing an adequate fusion method, we recently proposed a machine-learning data-driven approach able to predict the best merging strategy. This approach uses a meta-data set with the Statistical signatures extracted from data sets of a particular domain, from which we train a prediction model. However, the mentioned work is restricted to the recognition of human activities. In this paper, we propose to extend our previous work to other very different contexts, such as gas detection and grammatical face expression identification, in order to test its generality. The extensions of the method are presented in this paper. Our experimental results show that our extended model predicts the best fusion method well for a given data set, making us able to claim a broad generality for our sensor fusion method.

We perform a phenomenological study of Z plus jet, Higgs plus jet and di-jet production at the Large Hadron Collider. We investigate in particular the dependence of the leading jet cross section on the jet radius as a function of the jet transverse momentum. Theoretical predictions are obtained using perturbative QCD calculations at the next-to and next-to-next-to-leading order, using a range of renormalization and factorization scales. The fixed order predictions are compared to results obtained from matching next-to-leading order calculations to parton showers. A study of the scale dependence as a function of the jet radius is used to provide a better estimate of the scale uncertainty for small jet sizes. The non-perturbative corrections as a function of jet radius are estimated from different generators., (© The Author(s) 2020.)

In Ambient Intelligence (AmI), the activity a user is engaged in is an essential part of the context, so its recognition is of paramount importance for applications in areas like sports, medicine, personal safety, and so forth. The concurrent use of multiple sensors for recognition of human activities in AmI is a good practice because the information missed by one sensor can sometimes be provided by the others and many works have shown an accuracy improvement compared to single sensors. However, there are many different ways of integrating the information of each sensor and almost every author reporting sensor fusion for activity recognition uses a different variant or combination of fusion methods, so the need for clear guidelines and generalizations in sensor data integration seems evident. In this survey we review, following a classification, the many fusion methods for information acquired from sensors that have been proposed in the literature for activity recognition; we examine their relative merits, either as they are reported and sometimes even replicated and a comparison of these methods is made, as well as an assessment of the trends in the area.

The early auditory-evoked gamma band response (EAGBR) may serve as an index of the integrity of fast recurrent inhibition or synaptic connectivity in the auditory cortex, where abnormalities in individuals with schizophrenia have been consistently found. The EAGBR has been rarely investigated in first episode schizophrenia patients (FESZ) and individuals at clinical high risk (CHR) for schizophrenia, and never been compared directly between these populations nor evaluated longitudinally. Here we examined the EAGBR in FESZ, CHR, and matched healthy controls (HC) at baseline and 1-year follow-up assessments to determine whether the EAGBR was affected in these clinical groups, and whether any EAGBR abnormalities changed over time. The electroencephalogram was recorded with a dense electrode array while subjects (18 FESZ, 18 CHR, and 40 HC) performed an auditory oddball task. Event-related spectral measures (phase locking factor [PLF] and evoked power) were computed on Morlet-wavelet-transformed single epochs from the standard trials. At baseline, EAGBR PLF and evoked power did not differ between groups. FESZ showed progressive reductions of PLF and evoked power from baseline to follow-up, and deficits in PLF at follow-up compared to HC. EAGBR peak frequency also increased at temporal sites in FESZ from baseline to follow-up. Longitudinal effects on the EAGBR were not found in CHR or HC, nor did these groups differ at follow-up. In conclusion, we detected neurophysiological changes of auditory cortex function in FESZ during a one-year period, which were not observed in CHR. These findings are discussed within the context of neurodevelopmental models of schizophrenia., (Published by Elsevier B.V.)

Sensors are becoming more and more ubiquitous as their price and availability continue to improve, and as they are the source of information for many important tasks. However, the use of sensors has to deal with noise and failures. The lack of reliability in the sensors has led to many forms of redundancy, but simple solutions are not always the best, and the precise way in which several sensors are combined has a big impact on the overall result. In this paper, we discuss how to deal with the combination of information coming from different sensors, acting thus as "virtual sensors", in the context of human activity recognition, in a systematic way, aiming for optimality. To achieve this goal, we construct meta-datasets containing the "signatures" of individual datasets, and apply machine-learning methods in order to distinguish when each possible combination method could be actually the best. We present specific results based on experimentation, supporting our claims of optimality.

We present accurate QCD predictions for the transverse momentum ( p ⊥ ) spectrum of electroweak gauge bosons at the LHC for 13 TeV collisions, based on a consistent combination of a NNLO calculation at large p ⊥ and N 3 LL resummation in the small p ⊥ limit. The inclusion of higher order corrections leads to substantial changes in the shape of the differential distributions, and the residual perturbative uncertainties are reduced to the few percent level across the whole transverse momentum spectrum. We examine the ratio of p ⊥ distributions in charged- and neutral-current Drell-Yan production, and study different prescriptions for the estimate of perturbative uncertainties that rely on different degrees of correlation between these processes. We observe an excellent stability of the ratios with respect to the perturbative order, indicating a strong correlation between the corresponding QCD corrections., (© The Author(s) 2019.)

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal-retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.

We propose a novel strategy to constrain the bottom and charm Yukawa couplings by exploiting Large Hadron Collider (LHC) measurements of transverse momentum distributions in Higgs production. Our method does not rely on the reconstruction of exclusive final states or heavy-flavor tagging. Compared to other proposals, it leads to an enhanced sensitivity to the Yukawa couplings due to distortions of the differential Higgs spectra from emissions which either probe quark loops or are associated with quark-initiated production. We derive constraints using data from LHC run I, and we explore the prospects of our method at future LHC runs. Finally, we comment on the possibility of bounding the strange Yukawa coupling.

Shrimp farm aquaculture causes environmental impacts, notably decreased water quality due to the release of nutrient-rich effluents. Pond wastewater is usually discharged without treatment, and tidal conditions are not taken into account in the management plans. However, natural variability of nutrients makes difficult field evaluation and attribution of impacts. Here we implemented a three-dimensional coupled hydrodynamic-biogeochemical model (spatial resolution=50m×50m, time resolution=4s) in order to evaluate the dispersion conditions under specific tidal conditions of nutrient discharges from a semi-intensive shrimp farm during spring and neap tide. Ammonia was quickly assimilated by plankton and its concentration recovered initial levels 10days after the beginning of the harvest. Due to the higher salinity of the pond effluents, shrimp farm discharges accumulate in waters and sediments of the upper lagoon creeks, mostly affecting the benthos, thus implying a potential risk of shrimp farm self-contamination. Maximum concentrations of most biogeochemical tracers occurred when the harvest ends and the ponds are fully emptied. We show that maximum nutrient concentrations can be reduced by ~10% when the harvest ends during spring tides compared to harvests ending during neap tides. This work may be useful to improve the management of shrimp farm effluents by reducing, easily and at little cost, nutrient impacts on tropical and sub-tropical receiving ecosystems., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA)., Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology., Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed., Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Variability in the phenotypic features and severity of fetal alcohol spectrum disorder (FASD) is not fully linked to alcohol dose. We hypothesize that FASD-type neurodevelopmental abnormalities may be caused by exposures to the tobacco-specific nitrosamine, NNK, since a high percentage of pregnant women who drink also smoke. In vitro experiments using PNET2 human cerebellar neuronal cultures examined ethanol and NNK effects on viability and mitochondrial function. Early postnatal rat cerebellar slice cultures were used to examine effects of ethanol and NNK on cerebellar histology and neuroglial and stress protein expression. Ethanol (50 mM) decreased viability and ATP content and increased mitochondrial mass, while NNK (100 μM or higher) selectively inhibited mitochondrial function. The slice culture studies demonstrated striking adverse effects of ethanol, NNK and ethanol+NNK exposures manifested by architectural disorganization of the cortex with relative reductions of internal granule cells, increases in external granule cells, and loss of Purkinje cells. Ethanol, NNK, and ethanol+NNK inhibited expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and increased levels of 4-hydroxynonenal (HNE). In addition, ethanol increased activated Caspase 3, NNK decreased tau and phospho-tau, and ethanol+NNK inhibited expression of Aspartyl-β-hydroxylase (ASPH), which mediates neuronal migration. In conclusion, ethanol and NNK were shown to exert independent but overlapping adverse effects on cerebellar cortical development, neuronal viability, function, and neuroglial protein expression. These findings support our hypothesis that NNK exposures via tobacco smoking in pregnancy can contribute to FASD-associated neurodevelopmental abnormalities.

We propose a new approach to the resummation of the transverse-momentum distribution of a high-mass color-singlet system in hadronic collisions. The resummation is performed in momentum space and is free of kinematic singularities at small transverse momentum. We derive a formula accurate at the next-to-next-to-leading-logarithmic level, and present the first matched predictions to next-to-next-to-leading order for Higgs-boson production in gluon fusion at the LHC. This method can be adapted to all observables featuring kinematic cancellations in the infrared region.

Light harvesting complex stress-related 3 (LHCSR3) is the protein essential for photoprotective excess energy dissipation (non-photochemical quenching, NPQ) in the model green algaChlamydomonas reinhardtii Activation of NPQ requires low pH in the thylakoid lumen, which is induced in excess light conditions and sensed by lumen-exposed acidic residues. In this work we have used site-specific mutagenesisin vivoandin vitrofor identification of the residues in LHCSR3 that are responsible for sensing lumen pH. Lumen-exposed protonatable residues, aspartate and glutamate, were mutated to asparagine and glutamine, respectively. By expression in a mutant lacking all LHCSR isoforms, residues Asp(117), Glu(221), and Glu(224)were shown to be essential for LHCSR3-dependent NPQ induction inC. reinhardtii Analysis of recombinant proteins carrying the same mutations refoldedin vitrowith pigments showed that the capacity of responding to low pH by decreasing the fluorescence lifetime, present in the wild-type protein, was lost. Consistent with a role in pH sensing, the mutations led to a substantial reduction in binding the NPQ inhibitor dicyclohexylcarbodiimide., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Cerebellar developmental abnormalities in Fetal Alcohol Spectrum Disorder (FASD) are linked to impairments in insulin signaling. However, co-morbid alcohol and tobacco abuses during pregnancy are common. Since smoking leads to tobacco specific Nitrosamine (NNK) exposures which have been shown to cause brain insulin resistance, we hypothesized that neurodevelopmental abnormalities in FASD could be mediated by ethanol and/or NNK., Methods: Long Evans rat pups were intraperitoneal (IP) administered ethanol (2 g/kg) on postnatal days (P) 2, 4, 6 and/or NNK (2 mg/kg) on P3, P5, and P7 to simulate third trimester human exposures. The Cerebellar function, histology, insulin and Insulin-like Growth Factor (IGF) signaling, and neuroglial protein expression were assessed., Results: Ethanol, NNK and ethanol+NNK groups had significant impairments in motor function (rotarod tests), abnormalities in cerebellar structure (Purkinje cell loss, simplification and irregularity of folia, and altered white matter), signaling through the insulin and IGF-1 receptors, IRS-1, Akt and GSK-3β, and reduced expression of several important neuroglial proteins. Despite similar functional effects, the mechanisms and severity of NNK and ethanol+NNK induced alterations in cerebellar protein expression differed from those of ethanol., Conclusions: Ethanol and NNK exert independent but overlapping adverse effects on cerebellar development, function, insulin signaling through cell survival, plasticity, metabolic pathways, and neuroglial protein expression. The results support the hypothesis that tobacco smoke exposure can serve as a co-factor mediating long-term effects on brain structure and function in FASD., Competing Interests: CONFLICTS OF INTEREST: None.

Objective: To understand the underlying dynamic neurophysiological changes over the course of schizophrenia, it is important to study subjects longitudinally from the early stage of the illness. We previously reported that visual P300 was already impaired in patients with first-episode schizophrenia (FESZ). This study demonstrates how the visual P300, as well as earlier components P1, N1, and N200, changed at the 1-year follow-up after their initial measurement., Methods: Visual ERPs were recorded with the same experimental paradigm and acquisition protocol at both time points in FESZ (n = 18) and healthy comparison subjects (n = 24). Participants silently counted infrequent target stimuli ("x") amid standard stimuli ("y") presented on the screen while the 64-channel electroencephalogram was recorded., Results: FESZ showed smaller visual P300, N200, P1 (trend level) amplitude and delayed P300 and N1 latency at both time points; however, only P300 showed progressive amplitude reduction over the course of the illness at 1-year follow-up. P300 latency did not change over time in either group. FESZ showed significantly reduced Spatial Span total score at both time points, and there was a significant negative correlation between P300 peak amplitude and the Brief Psychiatric Rating Scale positive symptom score at baseline., Conclusion: These data show progressive P300 amplitude reduction in response to visual stimuli in the early stage of schizophrenia. These visual P300 findings support the concept of progression of schizophrenia, suggesting the usefulness of the visual P300 as a biological marker of progression., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study used event-related potentials to examine interactions between mood, sentence context, and semantic memory structure in schizophrenia. Seventeen male chronic schizophrenia and 15 healthy control subjects read sentence pairs after positive, negative, or neutral mood induction. Sentences ended with expected words (EW), within-category violations (WCV), or between-category violations (BCV). Across all moods, patients showed sensitivity to context indexed by reduced N400 to EW relative to both WCV and BCV. However, they did not show sensitivity to the semantic memory structure. N400 abnormalities were particularly enhanced under a negative mood in schizophrenia. These findings suggest abnormal interactions between mood, context processing, and connections within semantic memory in schizophrenia, and a specific role of negative mood in modulating semantic processes in this disease., (Copyright © 2014 Society for Psychophysiological Research.)

The photosystem II (PSII) protein PsbS and the enzyme violaxanthin deepoxidase (VDE) are known to influence the dynamics of energy-dependent quenching (qE), the component of nonphotochemical quenching (NPQ) that allows plants to respond to fast fluctuations in light intensity. Although the absence of PsbS and VDE has been shown to change the amount of quenching, there have not been any measurements that can detect whether the presence of these proteins alters the type of quenching that occurs. The chlorophyll fluorescence lifetime probes the excited-state chlorophyll relaxation dynamics and can be used to determine the amount of quenching as well as whether two different genotypes with the same amount of NPQ have similar dynamics of excited-state chlorophyll relaxation. We measured the fluorescence lifetimes on whole leaves of Arabidopsis thaliana throughout the induction and relaxation of NPQ for wild type and the qE mutants, npq4, which lacks PsbS; npq1, which lacks VDE and cannot convert violaxanthin to zeaxanthin; and npq1 npq4, which lacks both VDE and PsbS. These measurements show that although PsbS changes the amount of quenching and the rate at which quenching turns on, it does not affect the relaxation dynamics of excited chlorophyll during quenching. In addition, the data suggest that PsbS responds not only to ΔpH but also to the Δψ across the thylakoid membrane. In contrast, the presence of VDE, which is necessary for the accumulation of zeaxanthin, affects the excited-state chlorophyll relaxation dynamics.

Since the radical changes in Italian mental health law in the 1970s, quality assurance models have gained consensus as the most suitable service assessment tool. In the 1990s, the whole Italian National Health System changed into a corporate model, and an accreditation system was implemented.The Italian Association for Quality and Accreditation in Mental Health (Associazione Italiana per la Qualità e l'Accreditamento in Salute Mentale [QUASM]) was founded in 1984, and since then, it offers consultation and support for Mental Health Departments and Regional Governments to help them to develop psychiatric programs, self-evaluation, educational programs, and professional peer-model accreditation. The QUASM accreditation manual has now gone through several revisions, the last in 2008. Until 2008, QUASM was successful in promoting quality and facilitating both institutional and professional accreditation. However, radical changes triggered by financial crisis have jeopardized quality assurance implementation. Nowadays, the challenge for QUASM is to maintain quality and accreditation geared to excellence against prevailing leveling trends.

Carotenoids play an essential role in photoprotection, interacting with other pigments to safely dissipate excess absorbed energy as heat. In cyanobacteria, the short time scale photoprotective mechanisms involve the photoactive orange carotenoid protein (OCP), which binds a single carbonyl carotenoid. Blue-green light induces the photoswitching of OCP from its ground state form (OCPO) to a metastable photoproduct (OCPR). OCPR can bind to the phycobilisome antenna and induce fluorescence quenching. The photoswitching is accompanied by structural and functional changes at the level of the protein and of the bound carotenoid. Here, we use broadband two-dimensional electronic spectroscopy to study the differences in excited state dynamics of the carotenoid in the two forms of OCP. Our results provide insight into the origin of the pronounced vibrational lineshape and oscillatory dynamics observed in linear absorption and 2D electronic spectroscopy of OCPO and the large inhomogeneous broadening in OCPR, with consequences for the chemical function of the two forms.

Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10(-4)), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10(-5)), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension.

Background: Schizophrenia is characterized by deficits in emotional prosody (EP) perception. However, it is not clear which stages of processing prosody are abnormal and whether the presence of semantic content contributes to the abnormality. This study aimed to examine event-related potential (ERP) correlates of EP processing in 15 chronic schizophrenia individuals and 15 healthy controls., Method: A total of 114 sentences with neutral semantic content [sentences with semantic content (SSC) condition] were generated by a female speaker (38 with happy, 38 with angry, and 38 with neutral intonation). The same sentences were synthesized and presented in the 'pure prosody' sentences (PPS) condition where semantic content was unintelligible., Results: Group differences were observed for N100 and P200 amplitude: patients were characterized by more negative N100 for SSC, and more positive P200 for angry and happy SSC and happy PPS. Correlations were found between delusions and P200 amplitude for happy SSC and PPS. Higher error rates in the recognition of EP were also observed in schizophrenia: higher error rates in neutral SSC were associated with reduced N100, and higher error rates in angry SSC were associated with reduced P200., Conclusions: These results indicate that abnormalities in prosody processing occur at the three stages of EP processing, and are enhanced in SSC. Correlations between P200 amplitude for happy prosody and delusions suggest a role that abnormalities in the processing of emotionally salient acoustic cues may play in schizophrenia symptomatology. Correlations between ERP and behavioral data point to a relationship between early sensory abnormalities and prosody recognition in schizophrenia.

Photosynthetic organisms convert photoenergy to chemical energy with near-unity quantum efficiency. This occurs through charge transfer in the reaction center, which consists of two branches of pigments. In bacteria, both branches are energy-transfer pathways, but only one is also an electron transfer pathway. One barrier to a full understanding of the asymmetry is that the two branches contain excited states close in energy that produce overlapping spectroscopic peaks. We apply polarization-dependent, 2D electronic spectroscopy to the B band of the oxidized bacterial reaction center. The spectra reveal two previously unresolved peaks, corresponding to excited states localized on each of the two branches. Furthermore, a previously unknown interaction between these two states is observed on a time scale of ∼100 fs. This may indicate an alternative pathway to electron transfer for the oxidized reaction center and thus may be a mechanism to prevent energy from becoming trapped in local minima.

In Alzheimer's disease (AD), brain insulin and insulin-like growth factor (IGF) resistance and deficiency begin early, and worsen with severity of disease. The factors mediating progression of brain insulin/IGF resistance in AD are not well understood. We hypothesize that AD progression is mediated via negative cross-talk that promotes toxic ceramide generation and endoplasmic reticulum (ER) stress. The rationale is that insulin resistance dysregulates lipid metabolism and promotes ceramide accumulation, and thereby increases inflammation and stress. Consequences include disruption of cytoskeletal function and AβPP-Aβ secretion. The present study correlates AD stage with activation of pro-ceramide genes, ceramide levels, and molecular indices of ER stress in postmortem human brain tissue. The results demonstrated that in AD, brain insulin/IGF resistance was associated with constitutive activation of multiple pro-ceramide genes, increased ceramide levels, and increased expression of pro-ER stress pathway genes and proteins. Expression of several pro-ceramide and pro-apoptotic ER stress pathway molecules increased with AD severity and brain insulin/IGF resistance. In contrast, ER stress molecules that help maintain homeostasis with respect to unfolded protein responses were mainly upregulated in the intermediate rather than late stage of AD. These findings support our hypothesis that in AD, a triangulated mal-signaling network initiated by brain insulin/IGF resistance is propagated by the dysregulation of ceramide and ER stress homeostasis, which themselves promote insulin resistance. Therefore, once established, this reverberating loop must be targeted using multi-pronged approaches to disrupt the AD neurodegeneration cascade.

We demonstrate an ultrafast manipulation of the Rabi splitting energy Ω(R) in a metal-molecular aggregate hybrid nanostructure. Femtosecond excitation drastically alters the optical properties of a model system formed by coating a gold nanoslit array with a thin J-aggregated dye layer. Controlled and reversible transient switching from strong (Ω(R) ≃ 55 meV) to weak (Ω(R) ≈ 0) coupling on a sub-ps time scale is directly evidenced by mapping the nonequilibrium dispersion relations of the coupled excitations. Such a strong, externally controllable coupling of excitons and surface plasmon polaritons is of considerable interest for ultrafast all-optical switching applications in nanoscale plasmonic circuits.

Currently, the relatively high cost of enzymes such as glycoside hydrolases that catalyze cellulose hydrolysis represents a barrier to commercialization of a biorefinery capable of producing renewable transportable fuels such as ethanol from abundant lignocellulosic biomass. Among the many families of glycoside hydrolases that catalyze cellulose and hemicellulose hydrolysis, few are more enigmatic than family 61 (GH61), originally classified based on measurement of very weak endo-1,4-beta-d-glucanase activity in one family member. Here we show that certain GH61 proteins lack measurable hydrolytic activity by themselves but in the presence of various divalent metal ions can significantly reduce the total protein loading required to hydrolyze lignocellulosic biomass. We also solved the structure of one highly active GH61 protein and find that it is devoid of conserved, closely juxtaposed acidic side chains that could serve as general proton donor and nucleophile/base in a canonical hydrolytic reaction, and we conclude that the GH61 proteins are unlikely to be glycoside hydrolases. Structure-based mutagenesis shows the importance of several conserved residues for GH61 function. By incorporating the gene for one GH61 protein into a commercial Trichoderma reesei strain producing high levels of cellulolytic enzymes, we are able to reduce by 2-fold the total protein loading (and hence the cost) required to hydrolyze lignocellulosic biomass.

We discuss and experimentally demonstrate a scheme to achieve photorefractive solitons of arbitrary linear polarization using the quadratic electro-optic effect and describe the observation of the self-trapping of a set of linear polarized beams in different positions of a paraelectric photorefractive crystal of potassium-lithium-tantalate-niobate (KLTN) biased by the inhomogeneous field produced by two miniaturized top electrodes. The polarization of the single solitons of the set is determined by the local electrostatic configuration and the underlying tunable anisotropy, which is detected through zero-field electro-activation.

The vasopressin type 2 receptor (V2R) is a G protein-coupled receptor that plays a central role in renal water reabsorption. Termination of ligand (vasopressin) stimulation is an important physiological regulatory event, but few proteins that interact with the V2R during downregulation after vasopressin (VP) binding have been identified. Using yeast two-hybrid screening of a human kidney cDNA library, we show that a 100-kDa protein called ALG-2-interacting protein X (Alix) interacts with the last 29 amino acids of the V2R COOH terminus. This was confirmed by pull-down assays using a GST-V2R-COOH-tail fusion protein. Alix was immunolocalized in principal cells of the kidney, which also express the V2R. The function of the Alix-V2R interaction was studied by transfecting Alix into LLC-PK(1) epithelial cells expressing V2R-green fluorescent protein (GFP). Under basal conditions, V2R-GFP localized mainly at the plasma membrane. On VP treatment, V2R-GFP was internalized into perinuclear vesicles in the nontransfected cells. In contrast, V2R-GFP fluorescence was virtually undetectable 2 h after exposure to VP in cells that coexpressed Alix. Western blotting using an anti-GFP antibody showed marked degradation of the V2R after 2 h in the presence of VP and Alix, a time point at which little or no degradation was detected in the absence of Alix. In contrast, little or no degradation of the parathyroid hormone receptor was detectable in the presence or absence of Alix and/or the PTH ligand. The VP-induced disappearance of V2R-GFP was abolished by chloroquine, a lysosomal degradation inhibitor, but not by MG132, a proteosome inhibitor. These data suggest that Alix increases the rate of lysosomal degradation of V2R and may play an important regulatory role in the VP response by modulating V2R downregulation.

Transforming growth factor-beta (TGF-beta) has previously been implicated in the progression of diabetic nephropathy, including the onset of fibrosis and albuminuria. Here we report for the first time the use of a high-affinity TGF-beta1 binding molecule, the soluble human TGF-beta type II receptor (sTbetaRII.Fc), in the treatment of diabetic nephropathy in 12-week streptozotocin-induced diabetic Sprague-Dawley rats. In vitro studies using immortalized rat proximal tubule cells revealed that 50 pmol/l TGF-beta1 disrupted albumin uptake (P < 0.001 vs. control), an inhibition significantly reversed by the use of the sTbetaRII.Fc (1,200 pmol/l). In vivo studies demonstrated that treatment with sTbetaRII.Fc reduced urinary albumin excretion by 36% at 4 weeks, 59% at 8 weeks (P < 0.001), and 45% at 12 weeks (P < 0.01 for diabetic vs. treated). This was correlated with an increase in megalin expression (P < 0.05 for diabetic vs. treated) and a reduction in collagen IV expression following sTbetaRII.Fc treatment (P < 0.001 for diabetic vs. treated). These changes occurred independently of changes in blood glucose levels. This study demonstrates that the sTbetaRII.Fc is a potential new agent for the treatment of fibrosis and albuminuria in diabetic nephropathy and may reduce albuminuria by reducing TGF-beta1-induced disruptions of renal proximal tubule cell uptake of albumin.

Several missions for planetary exploration, including comets and asteroids, are ongoing or planned by the European Space Agencies: Rosetta, Venus Express, Bepi Colombo, Dawn, Aurora and all Mars Programme (in its past and next missions) are good examples. The satisfaction of the scientific request for the mentioned programmes calls for the development of new instruments and facilities devoted to investigate the body (planet, asteroid or comet) both remotely and by in situ measurements. The paper is an overview of some instruments for remote sensing and in situ planetary exploration already developed or under study by Galileo Avionica Space & Electro-Optics B.U. (in the following shortened as Galileo Avionica) for both the Italian Space Agency (ASI) and for the European Space Agency (ESA). Main technologies and specifications are outlined; for more detailed information please refer to Galileo Avionica's web-site at: http://www.galileoavionica.com .

Activins and inhibins compose a heterogeneous subfamily within the transforming growth factor-beta (TGF-beta) superfamily of growth and differentiation factors with critical biological activities in embryos and adults. They signal through a heteromeric complex of type II, type I, and for inhibin, type III receptors. To characterize the affinity, specificity, and activity of these receptors (alone and in combination) for the inhibin/activin subfamily, we developed a cell-free assay system using soluble receptor-Fc fusion proteins. The soluble activin type II receptor (sActRII)-Fc fusion protein had a 7-fold higher affinity for activin A compared with sActRIIB-Fc, whereas both receptors had a marked preference for activin A over activin B. Although inhibin A and B binding was 20-fold lower compared with activin binding to either type II receptor alone, the mixture of either type II receptor with soluble TGF-beta type III receptor (TbetaRIII; betaglycan)-Fc reconstituted a soluble high affinity inhibin receptor. In contrast, mixing either soluble activin type II receptor with soluble activin type I receptors did not substantially enhance activin binding. Our results support a cooperative model of binding for the inhibin receptor (ActRII.sTbetaRIII complex) but not for activin receptors (type II + type I) and demonstrate that a complex composed of activin type II receptors and TbetaRIII is both necessary and sufficient for high affinity inhibin binding. This study also illustrates the utility of this cell-free system for investigating hypotheses of receptor complex mechanisms resulting from crystal structure analyses.

Follistatin (FS) is an important physiological regulator of activin and other TGFbeta superfamily members. The recently discovered follistatin-like 3 (FSTL3; a.k.a. FLRG; FSRP) shares significant structural and functional homology with FS, but also has some interesting differences, including a prominent nuclear localization. The existence of these two related proteins allows detailed molecular and biochemical comparisons of the biologic roles of their individual structural elements. Current studies indicate that the heparin binding sequence is essential for the ability of FS to inhibit autocrine activin but is not sufficient to confer this activity on FSTL3. Preliminary analysis of FSTL3 transgenic mice suggests that FSTL3 regulates gonadal development and function through inhibition of the paracrine activity of activin and/or other related factors. These studies have identified important structural elements necessary for biological activity of FS and FSTL3 and potential roles for FSTL3 in vivo.

Transforming growth factor beta (TGF-beta) ligands exert their biological effects through type II (TbetaRII) and type I receptors (TbetaRI). Unlike TGF-beta1 and -beta3, TGF-beta2 appears to require the co-receptor betaglycan (type III receptor, TbetaRIII) for high affinity binding and signaling. Recently, the TbetaRIII null mouse was generated and revealed significant non-overlapping phenotypes with the TGF-beta2 null mouse, implying the existence of TbetaRIII independent mechanisms for TGF-beta2 signaling. Because a variant of the type II receptor, the type II-B receptor (TbetaRII-B), has been suggested to mediate TGF-beta2 signaling in the absence of TbetaRIII, we directly tested the ability of TbetaRII-B to bind TGF-beta2. Here we show that the soluble extracellular domain of the type II-B receptor (sTbetaRII-B.Fc) bound TGF-beta1 and TGF-beta3 with high affinity (K(d) values = 31.7 +/- 22.8 and 74.6 +/- 15.8 pm, respectively), but TGF-beta2 binding was undetectable at corresponding doses. Similar results were obtained for the soluble type II receptor (sTbetaRII.Fc). However, sTbetaRII.Fc or sTbetaRII-B.Fc in combination with soluble type I receptor (sTbetaRI.Fc) formed a high affinity complex that bound TGF-beta2, and this complex inhibited TGF-beta2 in a biological inhibition assay. These results show that TGF-beta2 has the potential to signal in the absence of TbetaRIII when sufficient TGF-beta2, TbetaRI, and TbetaRII or TbetaRII-B are present. Our data also support a cooperative model for receptor-ligand interactions, as has been suggested by crystallization studies of TGF-beta receptors and ligands. Our cell-free binding assay system will allow for testing of models of receptor-ligand complexes prior to actual solution of crystal structures.

Our analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in colorectal cancers compared to control mucosa (P = 0.003; n = 77). Highest specific activities and cancer/normal ratios (C/N) for activity were measured in Dukes' B and C stage carcinomas, cancers involved in local spread and invasion to lymph nodes. In contrast, cathepsin B and L activities analysed in the same paired extracts had been shown to be most frequently elevated in earlier stage carcinomas (Dukes' A and B), confirming that cathepsin H demonstrates a distinct pattern of expression during colorectal cancer progression. Although cathepsin H activities were most commonly elevated in Dukes' C cancers at all colon sites, both specific activity and C/N ratios were significantly higher for cancers of the left colon compared to other colon locations. A subset of 43 paired extracts analysed on Western blots also revealed consistent changes in cathepsin H protein forms in cancers. Normal mucosa typically showed a strong protein doublet at 31 and 29 kDa while cancers demonstrated decreased expression or total loss of the 31 kDa protein (90% of cases), equal or increased expression of the 29-kDa protein (67% of cases) and the new appearance or up-regulation of a cathepsin H band at 22 kDa (78% of cases). C/N ratios for cathepsin H enzyme activity correlated significantly with C/N ratios for the 29 kDa mature single-chain protein form (P < 0.001), with increased activity most commonly associated with elevated expression of 29-kDa cathepsin H but also with up-regulation of the 22-kDa band, suggesting a shift to more fully processed, mature active cathepsin H protein forms in cancers. Changes in cathepsin H expression were also detected by immunohistochemistry as elevated cathepsin H staining in tumour epithelial cells.

Aims and Background: This report retrospectively analyzes 106 cases of endometrioid carcinoma of the ovary treated at the National Cancer Institute of Milan from 1974 through December 1993. In 12 of the 106 cases (11.3%) a synchronous carcinoma of the uterine body was observed., Methods and Study Design: Only patients who had previously untreated disease were included in the study. Patients with synchronous tumors were staged according to their ovarian cancer and treated according to the stage of that disease., Results: Thirty-nine patients (36.8%) had stage 1, 17 (16.0%) stage 11, 43 (40.6%) stage III, and 7 (6.6%) stage IV disease. Moderately plus poorly differentiated tumors were present in 76 of the 106 cases (71.7%). Considering the 67 patients with advanced disease, residual tumor was absent in 27 cases (40.3%), < or = 2 cm in 17 (25.4%), and > 2 cm in 23 (34.3%) cases. Systematic pelvic and para-aortic lymphadenectomy was performed in 60 patients (56.6%); selective sampling was carried out in 23 cases (21.7%). After surgery, 77 patients underwent various chemotherapy regimens., Conclusion: Using univariate analysis, FIGO stage, tumor grade, residual disease after surgery, lymph node status, and platinum in the chemotherapy regimen significantly influenced 5-year survival. However, when all these variables were included in a multivariate analysis only FIGO stage still had a significant impact on survival. Survival analysis also showed a trend towards longer survival in patients with synchronous tumors.

A retrospective review of the medical records of all ovarian cancer patients admitted to our institution from January 1974 to December 1993 was performed. A total of 58 consecutive patients who underwent systematic pelvic and paraaortic lymphadenectomy during second-look surgery was found. Node metastases were found in 15 of 58 patients (25.8%). No significant correlation was found between the variables of disease (e.g., stage of the disease at diagnosis, histology, grade, residual tumor after the first cytoreductive surgery, and the type of chemotherapy administered) and node status at second-look. Node metastases were found in 8 of 45 (17.7%) patients with absence of intraperitoneal disease, compared with 7 of 11 (63.6%) patients with intraabdominal residual disease (P < 0.02). There was no difference in 5-year survival for patients with absence of residual tumor in the peritoneal cavity as well as in the retroperitoneum (5-year survival 80%) and for patients with retroperitoneal disease only (5-year survival 77%). On the contrary, a highly significant difference in survival (P < 0.001) was observed between these two groups of patients and those who had intraabdominal residual tumor. Twelve of 45 (26.6%) patients have recurred. FIGO stage, grade, and residual disease after primary surgery were determinant in predicting recurrence. Notably, no relation emerged between relapse rate and the node status at second-look., (Copyright 1998 Academic Press.)

Background: In epithelial ovarian cancer, conservative surgery has mainly been adopted for stage Ia disease. The aim of this study is to report on a conservative surgical approach used in selected young patients with ovarian cancer who would usually undergo radical operations., Study Design: From 1980 through 1994, 10 patients with invasive epithelial ovarian cancer and with high-grade or limited extraovarian disease were treated with conservative surgery. The mean age was 22.7 years. The stage was Ia grade 3 in 2 patients, Ic in 2 patients, IIIa in 2 patients, and IIIc in 4 patients. Eight patients were given adjuvant therapy (radiotherapy in 1 and chemotherapy in 7)., Results: All patients were alive and disease-free at a median followup time of 70 months (range 24-138 months). Nine patients were menstruating regularly and three had become pregnant., Conclusions: It seems that in selected patients, conservative operations can be used beyond the worldwide accepted criterion of stage Ia. This concept deserves additional investigation in larger series.

We have examined the amino terminal membrane anchoring domain of Arabidopsis thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmg1p), a key enzyme of the isoprenoid biosynthetic pathway. Using both in vitro and in vivo approaches, we have analyzed a series of recombinant derivatives to identify key structural elements which play a role in defining Hmg1p transmembrane topology. Based on our results, we have proposed a topological model for Hmg1p in which the enzyme spans the lipid bilayer twice. We have shown the two transmembrane segments, designated TMS1 and TMS2, to be structurally and functionally inequivalent in their ability to direct the targeting and orientation of reporter proteins. Furthermore, we provide evidence indicating both the extreme amino terminal end and carboxyl terminal domain of the protein reside in the cytosol. This model therefore provides a key basis for the future examination of the role of the transmembrane domain in the targeting and regulation of Hmg1p in plant cells.

Clinicopathologic staging of colorectal cancers cannot always predict aggressiveness of prognosis for a particular patient. We have used activity assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix metalloproteinases, MMP-2 and MMP-9, to identify several distinctive, reproducible proteolytic profiles in a large set of colorectal carcinomas. We observed that individual proteinases demonstrated specific and distinct levels of activity at different cancer stages, possible reflecting non-random steps in a proteolytic cascade related to tumor development. We also observed that individual colon cancers fell into relatively few categories when characterized for the combined expression of three proteinases: CB, CL and MMP-9. Four proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be used to define almost 80% of the colorectal carcinomas analyzed. Such profiles, based on the expression of several proteinases in a given tumor, provided information independent of clinical stage and may identify crucial variations in tumor behavior.