Impact of Structure, Coupling Scheme, and State of Interest on the Energy Transfer in CP29.

The Qy and Bx excitation energy transfer (EET) in the minor light-harvesting complex CP29 (LHCII B4.1) antenna complex of Pisum sativum was characterized using a computational approach. We applied Förster resonance energy transfer (FRET) and the transition density cube (TDC) method to estimate the Coulombic coupling, based on a combination of classical molecular dynamics and quantum mechanics/molecular mechanics calculations. Employing TDC instead of FRET mostly affects the EET between chlorophylls (Chls) and carotenoids (Crts), as expected due to the Crts being spatially more challenging for FRET. Only between Chls, effects are found to be small (about only 0.1 EET efficiency change when introducing TDC instead of FRET). Effects of structural sampling were found to be small, illustrated by a small average standard deviation for the Qy state coupling elements (FRET/TDC: 0.97/0.94 cm-1). Due to the higher flexibility of the Bx state, the corresponding deviations are larger (FRET/TDC between Chl-Chl pairs: 17.58/22.67 cm-1, between Crt-Chl pairs: 62.58/31.63 cm-1). In summary, it was found for the Q band that the coupling between Chls varies only slightly depending on FRET or TDC, resulting in a minute effect on EET acceptor preference. In contrast, the coupling in the B band spectral region is found to be more affected. Here, the S2 (1Bu) states of the spatially challenging Crts may act as acceptors in addition to the B states of the Chls. Depending on FRET or TDC, several Chls show different Chl-to-Crt couplings. Interestingly, the EET between Chls or Crts in the B band is found to often outcompete the corresponding decay processes. The individual efficiencies for B band EET to Crts vary however strongly with the chosen coupling scheme (e.g., up to 0.29/0.99 FRET/TDC efficiency for the Chl a604/neoxanthin pair). Thus, the choice of the coupling scheme must involve a consideration of the state of interest.

Diastolic Blood Pressure and Cognitive Functioning: Differences by Systolic Blood Pressure Among US Adults.

BACKGROUND: The role of diastolic blood pressure (DBP) with cognitive functioning is under-explored in relation to levels of systolic blood pressure (SBP). METHODS: We studied 5466 participants from the National Health and Nutrition Examination Survey. Blood pressure was measured 3 times manually with a standardized sphygmomanometer and averaged. Cognitive functioning was measured using the digit symbol substitution test (DSST). RESULTS: Participants were 60 years or older, 55% female, and 81% non-Hispanic White. Most participants had a DBP between 70 to <80 mmHg (33.7%), between 60 to <70 mmHg (29.3%), or <60 mmHg (18.8%). From multivariable linear regression analyses, each 5 mmHg increment of DBP was associated with significantly higher DSST scores among individuals with SBP <120 only (ß: 0.56, 95% CI: 0.09, 1.03). CONCLUSIONS: Among older US adults, at non-elevated levels of SBP, higher DBP is associated with better cognitive performance.

Integrative couple treatment for pathological gamblers with an emphasis on forgiveness processes: A case study with three couples.

Gambling's impact on a couple's relationship is an essential element in the gambling disorder (GD). Gamblers tend to lie to their partner to conceal the extent of their gambling problems and debts, which can lead to a serious relational transgression for the couple. One promising avenue is a couple treatment focusing on forgiveness processes. The objective of this study was to determine whether the Integrative Couple Treatment for Pathological Gamblers (ICT-PG) with an emphasis on forgiveness processes helped couples to enhance these processes. A Single-Case Research Design (SCRD) was used with three couples in which one of the members had a GD. The results highlight the importance of jointly analyzing the forgiveness processes between the gamblers and their partner, which constantly influenced each other. These promising results illustrate the relevance of integrating forgiveness processes in treatment for couples where one of the members has a GD.

Acute effects of exercise on cerebrovascular response and cognitive performance in individuals with stable coronary heart disease.

BACKGROUND: Individuals with coronary heart disease (CHD) exhibit cognitive deficits and cerebrovascular dysfunctions, and are at higher risk of developing dementia. Cognitive function in individuals with CHD has never been studied during acute aerobic exercise. Given the increasing popularity of training at high peak power output (PPO), its impact on cerebrovascular and cognitive functions in individuals with CHD should be further studied. METHOD: Thirty-eight individuals with CHD and 16 healthy controls completed two exercise bouts at 30% and 70% of their individualized PPO on an ergocycle while performing a cognitive task including non-executive and executive conditions. Variations of oxy- deoxy-hemoglobin, and total hemoglobin concentrations were measured on left prefrontal cortex at both PPO using near-infrared spectroscopy. RESULTS: Cognitive task performances were equivalent between groups at all intensity levels. Individuals with CHD exhibited larger variation of deoxyhemoglobin in the executive condition and larger variation in total hemoglobin concentration in all task conditions compared to healthy controls at 70% of PPO. CONCLUSION: Exercising at high intensity seems to have a larger impact on cerebral blood volume in CHD patients compared to healthy age-matched controls. Higher exercise intensity has negative impacts on cerebral blood volume variations during a cognitive task in CHD patients and could potentially lead to other neurocognitive dysfunctions. Other studies are needed to determine if a cognitive task administered during an exercise test could help identify individuals with CHD at higher risk of developing cognitive decline.

Plant Compartments and Developmental Stages Modulate the Balance between Niche-Based and Neutral Processes in Soybean Microbiome.

Understanding the dynamics of plant-associated microbial communities within agriculture is well documented. However, the ecological processes that assemble the plant microbiome are not well understood. This study elucidates the relative dominance of assembly processes across plant compartments (root, stem, and leaves) and developmental stages (emergence, growth, flowering, and maturation). Bacterial community composition and assembly processes were assessed using 16S rRNA gene amplicon sequencing. Null models that couple phylogenetic community composition and species distribution models were used to evaluate ecological assembly processes of bacterial communities. All models highlighted that the balance between the assembly process was modulated by compartments and developmental stages. Dispersal limitation dominated amongst the epiphytic communities and at the maturation stage. Homogeneous selection dominated assembly across plant compartments and development stages. Overall, both sets of models were mostly in agreement in predicting the prevailing assembly processes. Our results show, for the first time, that even though niche-based processes dominate in the plant environment, the relative influence of dispersal limitation in community assembly is important.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.

Is it really possible to control aromaticity of benzene with light?

Recent theoretical investigations claim that tailored laser pulses may selectively steer benzene's aromatic ground state to localized non-aromatic excited states. For instance, it has been shown that electronic wavepackets, involving the two lowest electronic eigenstates, exhibit subfemtosecond charge oscillation between equivalent Kekulé resonance structures. In this contribution, we show that such dynamical electron-localization in the molecule-fixed frame contravenes the principle of the indistinguishability of identical particles. This breach stems from a total omission of the nuclear degrees of freedom, giving rise to nonsymmetric electronic wavepackets under nuclear permutations. Enforcement of the latter leads to entanglement between the electronic and nuclear states. To obey quantum statistics, the entangled molecular states should involve compensating nuclear-permutation symmetries. This in turn engenders complete quenching of dynamical electron-localization in the molecule-fixed frame. Indeed, for the (six-fold) equilibrium geometry of benzene, group-theoretic analysis reveals that any electronic wavepacket exhibits a (D6h) totally symmetric electronic density, at all times. Thus, our results clearly show that the six carbon atoms, and the six C-C bonds, always have equal Mulliken charges, and equal bond orders, respectively. However, electronic wavepackets may display dynamical localization of the electronic density in the space-fixed frame, whenever they involve both even and odd space-inversion (parity) or permutation-inversion symmetry. Dynamical spatial-localization can be probed experimentally in the laboratory frame, but it should not be deemed equivalent to charge oscillation between benzene's identical electronic substructures, such as Kekulé resonance structures.

Stochastic wave packet approach to nonadiabatic scattering of diatomic molecules from metals.

In this contribution, we present a quantum dynamical approach to study inelastic scattering of diatomic molecules from metal surfaces at normal incidence. The dissipative dynamics obeys a stochastic Schrödinger equation describing the time-evolution of the system as a piecewise deterministic process. Energy exchange between the molecular vibrational degrees of freedom and the metal electrons is represented using operators in tensor product form, which are coupled via anharmonic transition rates calculated from first-order perturbation theory. Full dimensional observables are obtained by averaging over simulations in 4D-including the internal stretch, the distance to the surface, and the orientation angles-at different surface sites. The method is applied to the state-resolved scattering of vibrationally excited NO from Au(111), revealing important channels for quantized energy relaxation.

Ultrafast Transient Dynamics of Adsorbates on Surfaces Deciphered: The Case of CO on Cu(100).

Time-resolved vibrational spectroscopy constitutes an invaluable experimental tool for monitoring hot-carrier-induced surface reactions. However, the absence of a full understanding of the precise microscopic mechanisms causing the transient spectral changes has limited its applicability. Here we introduce a robust first-principles theoretical framework that successfully explains both the nonthermal frequency and linewidth changes of the CO internal stretch mode on Cu(100) induced by femtosecond laser pulses. Two distinct processes engender the changes: electron-hole pair excitations underlie the nonthermal frequency shifts, while electron-mediated vibrational mode coupling gives rise to linewidth changes. Furthermore, the origin and precise sequence of coupling events are finally identified.

Phosphorylation of GATA4 serine 105 but not serine 261 is required for testosterone production in the male mouse.

BACKGROUND: GATA4 is a transcription factor essential for male sex determination, testicular differentiation during fetal development, and male fertility in the adult. GATA4 exerts part of its function by regulating multiple genes in the steroidogenic enzyme pathway. In spite of these crucial roles, how the activity of this factor is regulated remains unclear. OBJECTIVES: Studies in gonadal cell lines have shown that GATA4 is phosphorylated on at least two serine residues-serine 105 (S105) and serine 261 (S261)-and that this phosphorylation is important for GATA4 activity. The objective of the present study is to characterize the endogenous role of GATA4 S105 and S261 phosphorylation in the mouse testis. MATERIALS AND METHODS: We examined both previously described GATA4 S105A mice and a novel GATA4 S261A knock-in mouse that we generated by CRISPR/Cas9 gene editing. The male phenotype of the mutants was characterized by assessing androgen-dependent organ weights, hormonal profiles, and expression of multiple testicular target genes using standard biochemical and molecular biology techniques. RESULTS: The fecundity of crosses between GATA4 S105A mice was reduced but without a change in sex ratio. The weight of androgen-dependent organs was smaller when compared to wild-type controls. Plasma testosterone levels showed a 70% decrease in adult GATA4 S105A males. This decrease was associated with a reduction in Cyp11a1, Cyp17a1, and Hsd17b3 expression. GATA4 S261A mice were viable and testis morphology appeared normal. Testosterone production and steroidogenic enzyme expression were not altered in GATA4 S261A males. DISCUSSION AND CONCLUSION: Our analysis showed that blocking GATA4 S105 phosphorylation is associated with decreased androgen production in males. In contrast, S261 phosphorylation by itself is dispensable for GATA4 function. These results confirm that endogenous GATA4 action is essential for normal steroid production in males and that this activity requires phosphorylation on at least one serine residue.

The subpolar gyre regulates silicate concentrations in the North Atlantic.

The North Atlantic is characterized by diatom-dominated spring blooms that results in significant transfer of carbon to higher trophic levels and the deep ocean. These blooms are terminated by limiting silicate concentrations in summer. Numerous regional studies have demonstrated phytoplankton community shifts to lightly-silicified diatoms and non-silicifying plankton at the onset of silicate limitation. However, to understand basin-scale patterns in ecosystem and climate dynamics, nutrient inventories must be examined over sufficient temporal and spatial scales. Here we show, from a new comprehensive compilation of data from the subpolar Atlantic Ocean, clear evidence of a marked pre-bloom silicate decline of 1.5-2 µM throughout the winter mixed layer during the last 25 years. This silicate decrease is primarily attributed to natural multi-decadal variability through decreased winter convection depths since the mid-1990s, a weakening and retraction of the subpolar gyre and an associated increased influence of nutrient-poor water of subtropical origin. Reduced Arctic silicate import and the projected hemispheric-scale climate change-induced weakening of vertical mixing may have acted to amplify the recent decline. These marked fluctuations in pre-bloom silicate inventories will likely have important consequences for the spatial and temporal extent of diatom blooms, thus impacting ecosystem productivity and ocean-atmosphere climate dynamics.

Reconstruction after ureteral resection during HIPEC surgery: Re-implantation with uretero-neocystostomy seems safer than end-to-end anastomosis.

INTRODUCTION: Resection of the pelvic ureter may be necessary in cytoreductive surgery for peritoneal carcinomatosis in combination with hyperthermic intraperitoneal chemotherapy (HIPEC). As the morbidity for cytoreductive surgery with HIPEC has decreased, expert teams have begun to perform increasingly complex surgical procedures associated with HIPEC, including pelvic reconstructions. After ureteral resection, two types of reconstruction are possible: uretero-ureteral end-to-end anastomosis and uretero-vesical re-implantation or uretero-neocystostomy (the so-called psoas hitch technique). By compiling the experience of three surgical teams that perform HIPEC surgeries, we have tried to compare the effectiveness of these two techniques. METHODOLOGY: A retrospective comparative case-matched multicenter study was conducted for patients undergoing operation between 2005 and 2014. Patients included had undergone resection of the pelvic ureter during cytoreductive surgery with HIPEC for peritoneal carcinomatomosis; ureteral reconstruction was by either end-to-end anastomosis (EEA group) or re-implantation uretero-neocystostomy (RUC group). The primary endpoint was the occurrence of urinary fistula in postoperative follow-up. RESULTS: There were 14 patients in the EEA group and 14 in the RUC group. The groups were comparable for age, extent of carcinomatosis (PCI index) and operative duration. Four urinary fistulas occurred in the EEA group (28.5%) versus zero fistulas in the RUC group (0%) (P=0.0308). CONCLUSION: Re-implantation with uretero-neocystostomy during cytoreductive surgery with HIPEC is the preferred technique for reconstruction after ureteral resection in case of renal conservation.

Deletion of the GAA repeats from the human frataxin gene using the CRISPR-Cas9 system in YG8R-derived cells and mouse models of Friedreich ataxia.

The Friedreich ataxia is a monogenic disease due to a hyperexpanded GAA triplet located within the first intron of the frataxin gene that causes transcriptional issues. The resulting frataxin protein deficiency leads to a Fe-S cluster biosynthesis dysfunction in the mitochondria and to oxidative stress and cell death. Here we use the CRISPR-Cas9 system to remove the mutated GAA expansion and restore the frataxin gene transcriptional activity and protein level. Both YG8R and YG8sR mouse models and cell lines derived from these mice were used to CRISPR-edited successfully the GAA expansion in vitro and in vivo. Nevertheless, our results suggest the YG8sR as a better and more suitable model for the study of the CRISPR-Cas9 edition of the mutated frataxin gene.

Ultrafast photoelectron migration in dye-sensitized solar cells: Influence of the binding mode and many-body interactions.

In the present contribution, the ultrafast photoinduced electron migration dynamics at the interface between an alizarin dye and an anatase TiO2 thin film is investigated from first principles. Comparison between a time-dependent many-electron configuration interaction ansatz and a single active electron approach sheds light on the importance of many-body effects, stemming from uniquely defined initial conditions prior to photoexcitation. Particular emphasis is put on understanding the influence of the binding mode on the migration process. The dynamics is analyzed on the basis of a recently introduced toolset in the form of electron yields, electronic fluxes, and flux densities, to reveal microscopic details of the electron migration mechanism. From the many-body perspective, insight into the nature of electron-electron and hole-hole interactions during the charge transfer process is obtained. The present results reveal that the single active electron approach yields quantitatively and phenomenologically similar results as the many-electron ansatz. Furthermore, the charge migration processes in the dye-TiO2 model clusters with different binding modes exhibit similar mechanistic pathways but on largely different time scales.

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice.

Artificially designed transcription activator-like effector (TALE) proteins fused to a transcription activation domain (TAD), such as VP64, are able to activate specific eukaryotic promoters. They thus provide a good tool for targeted gene regulation as a therapy. However, the efficacy of such an agent in vivo remains to be demonstrated as the majority of studies have been carried out in cell culture. We produced an adeno-associated virus 9 (AAV9) coding for a TALEfrat#8 containing 13 repeat variable diresidues able to bind to the proximal promoter of human frataxin (FXN) gene. This TALEfrat#8 was fused with a 3XFLAG at its N terminal and a VP64 TAD at its C terminal, and driven by a CAG promoter. This AAV9_3XFLAG-TALEfrat#8-VP64 was injected intraperitoneally to 9-day-old and 4-month-old YG8R mice. After 1 month, the heart, muscle and liver were removed and their FXN mRNA and FXN protein were analyzed. The results show that the AAV9_3XFLAG-TALEfrat#8-VP64 increased the FXN mRNA and FXN protein in the three organs studied. These results corroborate our previous in vitro studies in the FRDA human fibroblasts. Our study indicates that an AAV coding for a TALE protein coupled with a TAD may be used to increase gene expression in vivo as a possible treatment not only for FRDA but also for other haploinsufficiency diseases.

MEF2 and NR2F2 cooperate to regulate Akr1c14 gene expression in mouse MA-10 Leydig cells.

Leydig cells are essential for male reproductive development and health throughout life. Production of androgens [testosterone, dihydrotestosterone (DHT)] as well as intermediate steroids [progesterone, dihydroprogesterone (DHP)] is tightly regulated. In the mouse, the 3α-hydroxysteroid dehydrogenase enzyme (3α-HSD, AKR1C14) catalyses the interconversion of DHP and DHT into less potent steroids. Despite its importance, nothing is currently known regarding the regulation of Akr1c14 expression in Leydig cells. Recently, the transcription factors MEF2 and NR2F2 were identified in the mouse testis including in Leydig cells where they were found to regulate expression of genes involved in steroidogenesis. Analyses of transcriptomic data from MEF2- or NR2F2-deficient MA-10 Leydig cells revealed a significant decrease in Akr1c14 mRNA levels. Using qPCR, we confirmed that Akr1c14 mRNA levels were decreased in MEF2- and in NR2F2-deficient conditions. Conversely, overexpression of MEF2A or/and NR2F2 in MA-10 Leydig cells led to an increase in endogenous Akr1c14 mRNA levels. Recruitment of MEF2 and NR2F2 to the Akr1c14 promoter was confirmed by ChIP while DNA precipitation assays revealed direct binding of MEF2 but not NR2F2 to this region. In functional promoter studies, NR2F2 was found to activate the Akr1c14 promoter while MEF2A on its own had no effect. Combination of both NR2F2 and MEF2A led to a cooperative activation of the Akr1c14 promoter and this required intact MEF2 and NR2F2 elements. Finally, co-immunoprecipitation experiments showed that MEF2 and NR2F2 are present in the same protein complex. In conclusion, our results identify a novel cooperation between MEF2 factors and NR2F2 in the expression of the Akr1c14 gene involved in the regulation of DHP/DHT levels.

Patient-specific compensation for Co-60 TBI treatments based on Monte Carlo design: A feasibility study.

PURPOSE: To develop an AP-PA treatment technique for the delivery of total body irradiation (TBI) at extended SSD using a modified Co-60 unit equipped with flattening filter and patient-specific compensators supported by Monte Carlo (MC) simulations and measurements. METHODS: An existing Eldorado-78 Co-60 teletherapy unit was stripped of its original collimator and equipped with two beam-defining cerrobend blocks. An acrylic flattening filter was numerically designed based on detailed mapping of the dose distribution of the large open field at a 10 cm depth in water using a primary radiation attenuation calculation. An EGSnrc/BEAMnrc MC model of the resulting unit was developed and experimentally validated and was used to calculate MC dose distributions in whole-body supine and prone CT images of a patient. AP-PA patient-specific compensators were designed based on the supine and prone mid-plane dose distributions. RESULTS: The designed flattening filter flattens the beam to within ±2% over a 200 cm × 70 cm area at 10 cm depth in water. Experimental validation of the calculated dose profiles in the open and flattened beams shows agreement of better than 2% and 1%, respectively. Patient MC dose calculations in the flattened, uncompensated beam showed dose deviations from prescription dose most notably in lung, neck and extremities ranging from -5% to +25%. The use of patient-specific compensators reduced inhomogeneities to within -5% to +10%. CONCLUSIONS: This work demonstrates that a Co-60 TBI setup upgraded with patient-specific compensators, numerically designed using MC patient dose calculations, is feasible and considerably improves the dose homogeneity.

fMRI brain response during sentence reading comprehension in children with benign epilepsy with centro-temporal spikes.

INTRODUCTION: Children with benign epilepsy with centro-temporal spikes (BECTS) often have language problems. Abnormal epileptic activity is found in central and temporal brain regions, which are involved in reading and semantic and syntactic comprehension. Using functional magnetic resonance imaging (fMRI), we examined reading networks in BECTS children with a new sentence reading comprehension task involving semantic and syntactic processing. METHOD: Fifteen children with BECTS (age=11y 1m ± 16 m; 12 boys) and 18 healthy controls (age=11 y 8m ± 20 m; 11 boys) performed an fMRI reading comprehension task in which they read a pair of syntactically complex sentences and decided whether the target sentence (the second sentence in the pair) was true or false with respect to the first sentence. All children also underwent an exhaustive neuropsychological assessment. RESULTS: We demonstrated weaknesses in several cognitive domains in BECTS children. During the sentence reading fMRI task, left inferior frontal regions and bilateral temporal areas were activated in BECTS children and healthy controls. However, additional brain regions such as the left hippocampus and precuneus were activated in BECTS children. Moreover, specific activation was found in the left caudate and putamen in BECTS children but not in healthy controls. Cognitive results and accuracy during the fMRI task were associated with specific brain activation patterns. CONCLUSION: BECTS children recruited a wider network to perform the fMRI sentence reading comprehension task, with specific activation in the left dorsal striatum. BECTS cognitive performance differently predicted functional activation in frontal and temporal regions compared to controls, suggesting differences in brain network organisation that contribute to reading comprehension.