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Many species, including humans exhibit a wide range of social behaviors that are crucial for the adaptation and survival of most species. Brain organization and function are shaped by genetic and environmental factors, although their precise contributions have been relatively understudied in the context of artificial selection. We used divergent lines of quail selected on their high versus low level of motivation to approach a group of conspecifics (S + and S-, respectively) to investigate the influence of genetic selection and early social environment on sociability. We observed distinct sex- and brain-region-specific expression patterns of three neuronal markers: mesotocin, and vasotocin, the avian homologues of mammalian oxytocin and vasopressin, as well as aromatase, the enzyme that converts androgens into estrogens. These markers displayed pronounced and neuroanatomically specific differences between S + and S- quail. Additionally, in a second experiment, we assessed the influence of early social environment on social skills in juvenile birds. Mixing S + and S- resulted in more S- males approaching the group without affecting the sociability of S + or other behaviors, suggesting that the early social environment may influence the results of genetic selection. In conclusion, the divergent quail lines offer a valuable model for unraveling the neuronal and behavioral mechanisms underlying social behaviors., (© 2024. The Author(s).)

Cardiorespiratory coordination (CRC) probes the interaction between cardiac and respiratory oscillators in which cardiac and respiratory activity are synchronized, with individual heartbeats occurring at approximately the same temporal positions during several breathing cycles. An increase of CRC has previously been related to pathological stressful states. We studied CRC employing coordigrams computed from non-contact photoplethysmography imaging (PPGI) and respiratory data using the optical flow method. In a blocked study design, we applied the cold pressure test (CPT), water at ambient temperature (AWT), and intermittent resting conditions. In controls (no intervention), CRC remained on initial low levels throughout measurements. In the experimental group (AWT and CPT intervention), CRC decreased during AWT and CPT. Following both interventions, CRC increased significantly, with a rebound effect following AWT. In controls, HR increased steadily over time. CPT evoked a significant HR increase which correlated with subjective stress/pain ratings. The CRC increase following AWT correlated significantly with subjective pain (r = .79) and stress (r = .63) ratings. Furthermore, we observed a significant correlation (r = - .80) between mean RMSSD and mean duration of CRC, which further supports an association between autonomic state and CRC level. CRC analysis obtained from cutaneous tissue perfusion data therefore appears to be a sensitive and useful method for the study of CRC and ANS activity. Future studies need to investigate the physiological principles and clinical significance of these findings., (© 2023. Springer Nature Limited.)

Recurring heat and drought episodes present challenges to the sustainability of grape production worldwide. We investigated the impacts of heat and drought stress on transcriptomic and metabolic responses of berries from two wine grape varieties. Cabernet Sauvignon and Riesling grapevines were subjected to one of four treatments during early fruit ripening: (1) drought stress only, (2) heat stress only, (3) simultaneous drought and heat stress, (4) no drought or heat stress (control). Berry metabolites, especially organic acids, were analyzed, and time-course transcriptome analysis was performed on samples before, during, and after the stress episode. Both alone and in conjunction with water stress, heat stress had a much more significant impact on berry organic acid content, pH, and titratable acidity than water stress. This observation contrasts with previous reports for leaves, which responded more strongly to water stress, indicating that grape berries display a distinct, organ-specific response to environmental stresses. Consistent with the metabolic changes, the global transcriptomic analysis revealed that heat stress had a more significant impact on gene expression in grape berries than water stress in both varieties. The differentially expressed genes were those associated with the tricarboxylic acid cycle and glyoxylate cycle, mitochondrial electron transport and alternative respiration, glycolysis and gluconeogenesis, carbohydrate allocation, ascorbate metabolism, and abiotic stress signaling pathways. Knowledge regarding how environmental stresses, alone and in combination, impact the berry metabolism of different grape varieties will form the basis for developing recommendations for climate change mitigation strategies and genetic improvement., (© 2023. The Author(s).)

Intermediate (IM) band physiology in skin blood flow exhibits parallels with the primary respiratory mechanism (PRM) or cranial rhythmic impulse (CRI), controversial concepts of osteopathy in the cranial field (OCF). Owing to inconsistent manual palpation results, validity of evidence of PRM/CRI activity has been questionable. We therefore tried to validate manual palpation combining instrumented tracking and algorithmic objectivation of frequencies, amplitudes, and phases. Using a standard OCF intervention, cranial vault hold (CVH), two OCF experts palpated and digitally marked CRI frequencies in 25 healthy adults. Autonomic nervous system (ANS) activity in low frequency (LF) and IM band in photoplethysmographic (PPG) forehead skin recordings was probed with momentary frequency of highest amplitude (MFHA) and wavelet amplitude spectra (WAS) in examiners and participants. Palpation errors and frequency expectation bias during CVH were analyzed for phases of MFHA and CRI. Palpated CRI frequencies (0.05-0.08 Hz) correlated highly with mean MFHA frequencies with 1:1 ratio in 77% of participants (LF-responders; 0.072 Hz) and with 2:1 ratio in 23% of participants (IM-responders; 0.147 Hz). WAS analysis in both groups revealed integer number (harmonic) waves in (very) low and IM bands in > 98% of palpated intervals. Phase analyses in participants and examiners suggested synchronization between MFHA and CRI in a subset of LF-responders. IM band physiology in forehead PPG may offer a sensible physiological correlate of palpated CRI activity. Possible coordination or synchronization effects with additional physiological signals and between examiners and participants should be investigated in future studies., (© 2023. The Author(s).)

Animals are widely believed to sense human emotions through smell. Chemoreception is the most primitive and ubiquitous sense, and brain regions responsible for processing smells are among the oldest structures in mammalian evolution. Thus, chemosignals might be involved in interspecies communication. The communication of emotions is essential for social interactions, but very few studies have clearly shown that animals can sense human emotions through smell. We used a habituation-discrimination protocol to test whether horses can discriminate between human odors produced while feeling fear vs. joy. Horses were presented with sweat odors of humans who reported feeling fear or joy while watching a horror movie or a comedy, respectively. A first odor was presented twice in successive trials (habituation), and then, the same odor and a novel odor were presented simultaneously (discrimination). The two odors were from the same human in the fear or joy condition; the experimenter and the observer were blinded to the condition. Horses sniffed the novel odor longer than the repeated odor, indicating they discriminated between human odors produced in fear and joy contexts. Moreover, differences in habituation speed and asymmetric nostril use according to odor suggest differences in the emotional processing of the two odors., (© 2023. The Author(s).)

Numerous functional factors may interactively contribute to the course of self-report functional abilities after anterior cruciate ligament  (ACL)-reconstruction. This study purposes to identify these predictors using exploratory moderation-mediation models in a cohort study design. Adults with post unilateral ACL reconstruction (hamstring graft) status and who were aiming to return to their pre-injury type and level of sport were included. Our dependent variables were self-reported function, as assessed by the the KOOS subscales sport (SPORT), and activities of daily living (ADL). The independent variables assessed were the KOOS subscale pain and the time since reconstruction [days]. All other variables (sociodemographic, injury-, surgery-, rehabilitation-specific, kinesiophobia (Tampa Scale of Kinesiophobia), and the presence or absence of COVID-19-associated restrictions) were further considered as moderators, mediators, or co-variates. Data from 203 participants (mean 26 years, SD 5 years) were finally modelled. Total variance explanation was 59% (KOOS-SPORT) and 47% (KOOS-ADL). In the initial rehabilitation phase (< 2 weeks after reconstruction), pain was the strongest contributor to self-report function (KOOS-SPORT: coefficient: 0.89; 95%-confidence-interval: 0.51 to 1.2 / KOOS-ADL: 1.1; 0.95 to 1.3). In the early phase (2-6 weeks after reconstruction), time since reconstruction [days] was the major contributor (KOOS-SPORT: 1.1; 0.14 to 2.1 / KOOS-ADL: 1.2; 0.43 to 2.0). Starting with the mid-phases of the rehabilitation, self-report function was no longer explicitly impacted by one or more contributors. The amount of rehabilitation [minutes] is affected by COVID-19-associated restrictions (pre-versus-post: - 672; - 1264 to - 80 for SPORT / - 633; - 1222 to - 45 for ADL) and by the pre-injury activity scale (280; 103 to 455 / 264; 90 to 438). Other hypothesised contributors such as sex/gender or age were not found to mediate the time or pain, rehabilitation dose and self-report function triangle. When self-report function is rated after an ACL reconstruction, the rehabilitation phases (early, mid, late), the potentially COVID-19-associated rehabilitation limitations, and pain intensity should also be considered. As, for example, pain is the strongest contributor to function in the early rehabilitation phase, focussing on the value of the self-report function only may, consequently, not be sufficient to rate bias-free function., (© 2023. The Author(s).)

The mechanisms underlying the photoperiodic control of reproduction in mammals and birds have been recently clarified. In contrast, the potential impact of photoperiod on more complex, integrative processes, such as cognitive behaviors, remains poorly characterized. Here, we investigated the impact of contrasted long and short photoperiods (LP, 16 h light/day and SP, 8 h light/day, respectively) on learning, spatial orientation abilities, and emotional reactivity in male Japanese quail. In addition, we quantified cell proliferation and young cell maturation/migration within the hippocampus, a brain region involved in spatial orientation. Our study reveals that, in male quail, SP increases emotional responses and spatial orientation abilities, compared to LP. Behaviorally, SP birds were found to be more fearful than LP birds, exhibiting more freezing in the open field and taking longer to exit the dark compartment in the emergence test. Furthermore, SP birds were significantly less aggressive than LP birds in a mirror test. Cognitively, SP birds were slower to habituate and learn a spatial orientation task compared to LP birds. However, during a recall test, SP birds performed better than LP birds. From a neuroanatomical standpoint, SP birds had a significantly lower density of young neurons, and also tended to have a lower density of mature neurons within the hippocampus, compared to LP birds. In conclusion, our data reveal that, beyond breeding control, photoperiod also exerts a profound influence on behavior, cognition, and brain plasticity, which comprise the seasonal program of this species., (© 2023. The Author(s).)

Trapped ions are a promising platform for the deployment of quantum technologies. However, traditional ion trap experiments tend to be bulky and environment-sensitive due to the use of free-space optics. Here we present a single-ion trap with integrated optical fibers directly embedded within the trap structure, to deliver laser light as well as to collect the ion's fluorescence. This eliminates the need for optical windows. We characterise the system's performance and measure the ion's fluorescence with signal-to-background ratios on the order of 50, which allows us to perform internal state readout measurements with a fidelity over 99% in 600 [Formula: see text]s. We test the system's resilience to thermal variations in the range between 22 and 53 [Formula: see text]C, and the system's vibration resilience at 34 Hz and 300 Hz and find no effect on its performance. The combination of compactness and robustness of our fiber-coupled trap makes it well suited for applications in, as well as outside, research laboratory environments, and in particular for highly compact portable quantum technologies, such as portable optical atomic clocks. While our system is designed for trapping 40 Ca + ions the fundamental design principles can be applied to other ion species., (© 2023. The Author(s).)

Golden Syrian hamsters (Mesocricetus auratus) are used as a research model for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Millions of Golden Syrian hamsters are also kept as pets in close contact to humans. To determine the minimum infective dose (MID) for assessing the zoonotic transmission risk, and to define the optimal infection dose for experimental studies, we orotracheally inoculated hamsters with SARS-CoV-2 doses from 1 * 10 5 to 1 * 10 -4 tissue culture infectious dose 50 (TCID 50 ). Body weight and virus shedding were monitored daily. 1 * 10 -3 TCID 50 was defined as the MID, and this was still sufficient to induce virus shedding at levels up to 10 2.75 TCID 50 /ml, equaling the estimated MID for humans. Virological and histological data revealed 1 * 10 2 TCID 50 as the optimal dose for experimental infections. This compelling high susceptibility leading to productive infections in Golden Syrian hamsters must be considered as a potential source of SARS-CoV-2 infection for humans that come into close contact with pet hamsters., (© 2022. The Author(s).)

Since neurotensin (NT) receptors of subtype-1 (NTS1) are expressed by different types of malignant tumors, such as pancreatic adenocarcinoma, colorectal and prostate carcinoma, they represent an interesting target for tumor imaging by positron emission tomography (PET) and endoradiotherapy. Previously reported neurotensin-derived NTS1 ligands for PET were radiolabeled by modification and prelongation of the N-terminus of NT(8-13) peptide analogs. In this study, we demonstrate that modifying Arg 8 or Arg 9 by N ω -carbamoylation and subsequent fluoroglycosylation provides a suitable approach for the development of NT(8-13) analogs as PET imaging agents. The N ω -carbamoylated and fluoroglycosylated NT(8-13) analogs retained high NTS1 affinity in the one-digit nanomolar range as well as high metabolic stability in vitro. In vivo, the radioligand [ 18 F]21 demonstrated favorable biokinetics in HT-29 tumor-bearing mice with high tumor uptake and high retention, predominantly renal clearance, and fast wash-out from blood and other non-target tissues. Therefore, [ 18 F]21 has the potential to be used as molecular probe for the imaging of NTS1-expressing tumors by PET., (© 2022. The Author(s).)

Glioblastoma is a highly aggressive brain tumor with poor patient prognosis. Treatment outcomes remain limited, partly due to intratumoral heterogeneity and the invasive nature of the tumors. Glioblastoma cells invade and spread into the surrounding brain tissue, and even between hemispheres, thus hampering complete surgical resection. This invasive motility can arise through altered properties of the cytoskeleton. We hypothesize that cytoskeletal organization and dynamics can provide important clues to the different malignant states of glioblastoma. In this study, we investigated cytoskeletal organization in glioblastoma cells with different subtype expression profiles, and cytoskeletal dynamics upon subtype transitions. Analysis of the morphological, migratory, and invasive properties of glioblastoma cells identified cytoskeletal components as phenotypic markers that can serve as diagnostic or prognostic tools. We also show that the cytoskeletal function and malignant properties of glioblastoma cells shift during subtype transitions induced by altered expression of the neurodevelopmental transcription factor SOX2. The potential of SOX2 re-expression to reverse the mesenchymal subtype into a more proneural subtype might open up strategies for novel glioblastoma treatments., (© 2022. The Author(s).)

Distributed cutaneous tissue blood volume oscillations contain information on autonomic nervous system (ANS) regulation of cardiorespiratory activity as well as dominating thermoregulation. ANS associated with low-frequency oscillations can be quantified in terms of frequencies, amplitudes, and phase shifts. The relative order between these faculties may be disturbed by conditions colloquially termed 'stress'. Photoplethysmography imaging, an optical non-invasive diagnostic technique provides information on cutaneous tissue perfusion in the temporal and spatial domains. Using the cold pressure test (CPT) in thirteen healthy volunteers as a well-studied experimental intervention, we present a method for evaluating phase shifts in low- and intermediate frequency bands in forehead cutaneous perfusion mapping. Phase shift changes were analysed in low- and intermediate frequency ranges from 0.05 Hz to 0.18 Hz. We observed that time waveforms increasingly desynchronised in various areas of the scanned area throughout measurements. An increase of IM band phase desynchronization observed throughout measurements was comparable in experimental and control group, suggesting a time effect possibly due to overshooting the optimal relaxation duration. CPT triggered an increase in the number of points phase-shifted to the reference that was specific to the low frequency range for phase-shift thresholds defined as π/4, 3π/8, and π/2 rad, respectively. Phase shifts in forehead blood oscillations may infer changes of vascular tone due to activity of various neural systems. We present an innovative method for the phase shift analysis of cutaneous tissue perfusion that appears promising to assess ANS change processes related to physical or psychological stress. More comprehensive studies are needed to further investigate the reliability and physiological significance of findings., (© 2022. The Author(s).)

The neurophysiological mechanisms underlying the behavioural improvements usually associated with an external (EF) compared with an internal focus of attention (IF) remain poorly investigated. Surround inhibition in the primary cortex has been shown to be more pronounced with an EF, indicating a more spatial restriction of the motor command. However, the influence of different foci on the temporal aspect of the motor command, such as the modulation of fast versus slow(er) motor pathways, remains unknown and was therefore investigated in this study. Fourteen participants were asked to press on a pedal with the right foot to match its position with a target line displayed on a screen. The deviation of the pedal from the target line was used as a behavioural parameter and compared between both foci (EF vs IF). Additionally, conditioned H-reflexes were evoked during the motor task to assess the excitability of fast (direct) and slower (more indirect) motor pathways when adopting an EF or IF. With an EF compared to an IF, the motor performance was enhanced (P = .001; + 24%) and the activation of slow(er) motor pathways was reduced (P < 0.001, - 11.73%). These findings demonstrate for the first time that using different attentional strategies (EF and IF) has an influence on the excitability of slow(er) motor pathways. Together with the increased intracortical inhibition and surround inhibition known from previous studies, the diminished activation in the slow(er) motor pathways further explains why using an EF is a more economic strategy., (© 2021. The Author(s).)

Trapped molecular ions in pure rovibronic states are desirable in experiments ranging from cold chemistry to searches for physics beyond the Standard Model. Resonance-enhanced multiphoton ionisation (REMPI) can be used to prepare molecular ions in specific internal states with high fidelities. However, in the presence of electric fields, ionisation spectra exhibit frequency shifts and the ionisation thresholds are broadened. For this reason, REMPI studies are normally conducted in low and highly homogeneous electric fields, whereas the operating principle of rf ion traps requires electric fields that vary in space and time. In order to investigate the impact of this on the state-selectivity of REMPI in ion traps, we have simulated the expected broadening of the ionisation threshold under various operating conditions of a typical linear Paul trap. In many cases, the width of the ionisation threshold exceeds the separation between rotational energy levels, preventing state-selective ionisation. Careful choice of the trapping and laser parameters during loading can reduce this broadening, enabling state-selective ionisation in some instances. Where this strategy is not sufficient, the broadening can be reduced further by rapidly switching the trapping voltages off and on again during loading. This has been demonstrated experimentally for a Coulomb crystal of [Formula: see text] ions without descrystallising it.

Incorporating optical cavities in ion traps is becoming increasingly important in the development of photonic quantum networks. However, the presence of the cavity can hamper efficient laser cooling of ions because of geometric constraints that the cavity imposes and an unfavourable Purcell effect that can modify the cooling dynamics substantially. On the other hand the coupling of the ion to the cavity can also be exploited to provide a mechanism to efficiently cool the ion. In this paper we demonstrate experimentally how cavity cooling can be implemented to improve the localisation of the ion and thus its coupling to the cavity. By using cavity cooling we obtain an enhanced ion-cavity coupling of [Formula: see text] MHz, compared with [Formula: see text] MHz when using only Doppler cooling.

Cellular transitions during development and stress response depend on coordinated transcriptomic and proteomic alterations. Pollen is particular because its development is a complex process that includes meiotic and mitotic divisions which causes a high heat sensitivity of these cells. Development and stress response are accompanied by a reprogramming of the transcriptome, e.g. by post-transcriptional regulation via miRNAs. We identified known and potentially novel miRNAs in the transcriptome of developing and heat-stressed pollen of Solanum lycopersicum (tomato). The prediction of target mRNAs yielded an equal number of predicted target-sites in CDS and 3'UTR regions of target mRNAs. The result enabled the postulation of a possible link between miRNAs and a fine-tuning of transcription factor abundance during pollen development. miRNAs seem to play a role in the pollen heat stress response as well. We identified several heat stress transcription factors and heat shock proteins as putative targets of miRNAs in response to heat stress, thereby placing these miRNAs as important elements of thermotolerance. Moreover, for members of the AP2, SBP and ARF family members we could predict a miRNA-mediated regulation during development via the miR172, mir156 and mir160-family strengthening the current concept of a cross-connection between development and stress response in plants.

The water vole Arvicola terrestris is endemic to Europe where its outbreak generates severe economic losses for farmers. Our project aimed at characterising putative chemical signals used by this species, to develop new sustainable methods for population control that could also be used for this species protection in Great Britain. The water vole, as well as other rodents, uses specific urination sites as territorial and sex pheromone markers, still unidentified. Lateral scent glands and urine samples were collected from wild males and females caught in the field, at different periods of the year. Their volatile composition was analysed for each individual and not on pooled samples, revealing a specific profile of flank glands in October and a specific profile of urinary volatiles in July. The urinary protein content appeared more contrasted as males secrete higher levels of a lipocalin than females, whenever the trapping period. We named this protein arvicolin. Male and female liver transcript sequencing did not identify any expression of other odorant-binding protein sequence. This work demonstrates that even in absence of genome, identification of chemical signals from wild animals is possible and could be helpful in strategies of species control and protection.

Neuropeptide Y Y 1 receptors (Y 1 R) have been found to be overexpressed in a number of different tumours, such as breast, ovarian or renal cell cancer. In mammary carcinoma the high Y 1 R density together with its high incidence of 85% in primary human breast cancers and 100% in breast cancer derived lymph node metastases attracted special attention. Therefore, the aim of this study was the development of radioligands for Y 1 R imaging by positron emission tomography (PET) with a special emphasis on imaging agents with reduced lipophilicity to provide a PET ligand with improved biodistribution in comparison with previously published tracers targeting the Y 1 R. Three new radioligands based on BIBP3226, bearing an 18 F-fluoroethoxy linker (12), an 18 F-PEG-linker (13) or an 18 F-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayed Y 1 R affinities of 2.8 nM (12), 29 nM (13) and 208 nM (11) and were characterised in vitro regarding binding to human breast cancer MCF-7-Y1 cells and slices of tumour xenografts. In vivo, small animal PET studies were conducted in nude mice bearing MCF-7-Y1 tumours. The binding to tumours, solid tumour slices and tumour cells correlated well with the Y 1 R affinities. Although 12 and 13 showed displaceable and specific binding to Y 1 R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios for Y 1 R imaging by PET. Yet the present study is another step towards an optimized PET radioligand for imaging of Y 1 R in vivo.

In this paper we investigate the 2 + 1' resonance enhanced multi-photon ionisation (REMPI) of molecular nitrogen via the a 1 Π g (v = 6) intermediate state and analyse its feasibility to generate molecular nitrogen ions in a well defined ro-vibrational state. This is an important tool for high precision experiments based on trapped molecular ions, and is crucial for studying the time variation of the fundamental constant m p /m e using [Formula: see text]. The transition is not reported in the literature and detailed spectral analysis has been conducted to extract the molecular constants of the intermediate state. By carefully choosing the intermediate ro-vibrational state, the ionisation laser wavelength and controlling the excitation laser pulse energy, unwanted formation of rotationally excited molecular ions can be suppressed and ro-vibrational ground state ions can be generated with high purity.

The neural circuitry processing male sexual behavior is tightly regulated by testosterone and its neural metabolite estradiol. The present study evaluated the effects of adult exposure to low doses of nonylphenol (NP), a widespread environmental contaminant, on the neuroendocrine regulation of testosterone and expression of sexual behavior. Oral exposure of C57BL/6J males to NP (0.5, 5 or 50 μg/kg/day) for 4 weeks did not affect circulating levels of testosterone or the kisspeptin system, a key regulator of the gonadotropic axis. In contrast, mice exposed to NP at 5 μg/kg/day emitted an increased number and duration of ultrasonic vocalizations, took longer to reach ejaculation and showed increased number of mounts, intromissions and thrusts. This was associated with normal olfactory preference and locomotor activity, and increased anxiety level. Analysis of the neural circuitry that underlies sexual behavior showed changes in the number of cells expressing androgen and estrogen receptors in males exposed to NP at 5 μg/kg/day. The neural circuitry underlying sexual behavior is thus highly sensitive to adult exposure to NP. Furthermore, almost all the observed effects were induced at 5 μg/kg/day of NP, indicating that this endocrine disrupter triggers a non-monotonic response in the adult male mouse brain.

To further investigate the mechanism of surround inhibition (SI) and to determine whether adopting different attentional strategies might have an impact on the modulation of SI, the effects of adopting an external (EF) or internal focus of attention (IF) on SI and motor performance were investigated. While performing an index flexion with either an EF or IF, transcranial magnetic stimulation was applied at various time points in 14 healthy subjects. When adopting an EF compared to an IF, the results show an improved motor performance (+14.7% in MVC) and a reduced bEMG in the adjacent APB (-22.3%) during maximal index flexion. This was accompanied by an increased SI in the APB with an EF (+26.4%). Additionally, the decrease in bEMG correlated with the magnitude of SI in APB. The current results demonstrate an efficient way to modulate SI by changing the attentional focus in healthy subjects and might, at least in part, explain the better motor performance being associated with an EF. The present findings help to better understand the positive mechanisms of an EF on SI in the healthy motor system and may also points towards a treatment strategy in pathologies with disturbed SI such as focal hand dystonia.

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10 -6 ), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT and SAT methylation correlated negatively with IRS1 gene expression in obese subjects (N = 16, P = 0.007 and P = 0.010). The major T-allele is related to increased DNA methylation in OVAT (N = 146, P = 0.019). Finally, DNA methylation and gene expression in OVAT correlated with anthropometric traits (waist- circumference waist-to-hip ratio) and parameters of glucose metabolism in obese individuals. Our data suggest that the association between rs2943650 near the IRS1 gene locus with clinically relevant variables may at least be modulated by changes in DNA methylation that translates into altered IRS1 gene expression.

In fiber based Fabry-Pérot Cavities (FFPCs), limited spatial mode matching between the cavity mode and input/output modes has been the main hindrance for many applications. We have demonstrated a versatile mode matching method for FFPCs. Our novel design employs an assembly of a graded-index and large core multimode fiber directly spliced to a single mode fiber. This all-fiber assembly transforms the propagating mode of the single mode fiber to match with the mode of a FFPC. As a result, we have measured a mode matching of 90% for a cavity length of ~400 μm. This is a significant improvement compared to conventional FFPCs coupled with just a single mode fiber, especially at long cavity lengths. Adjusting the parameters of the assembly, the fundamental cavity mode can be matched with the mode of almost any single mode fiber, making this approach highly versatile and integrable.

Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to altered expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation of p97/VCP expression, which is an IFN-γ-independent component of the UPS and part of the ER-dependent protein degradation pathway (ERAD), was found to be essentially involved in the observed immune escape. In support, our data demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant melanoma cells completely restored immune recognition by Melan-A/MART-126-35 CTL. In conclusion, our experiments show that impaired expression of IFN-γ-independent components of the UPS can exert rapid immune evasion of tumor cells and suggest that tumor antigens processed by distinct UPS degradation pathways should be simultaneously targeted in T cell therapies to restrict the likelihood of immune evasion due to impaired antigen processing.

Reproductive behavior and physiology in adulthood are controlled by hypothalamic sexually dimorphic neuronal networks which are organized under hormonal control during development. These organizing effects may be disturbed by endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to Ethinylestradiol (EE2) may alter reproductive parameters in adult male mice and their progeny, Swiss mice (F1 generation) were exposed from prenatal to peripubertal periods to EE2 (0.1-1 μg/kg/d). Sexual behavior and reproductive physiology were evaluated on F1 males and their F2, F3 and F4 progeny. EE2-exposed F1 males and their F2 to F4 progeny exhibited EE2 dose-dependent increased sexual behavior, with reduced latencies of first mount and intromission, and higher frequencies of intromissions with a receptive female. The EE2 1 μg/kg/d exposed animals and their progeny had more calbindin immunoreactive cells in the medial preoptic area, known to be involved in the control of male sexual behavior in rodents. Despite neuroanatomical modifications in the Gonadotropin-Releasing Hormone neuron population of F1 males exposed to both doses of EE2, no major deleterious effects on reproductive physiology were detected. Therefore EE2 exposure during development may induce a hypermasculinization of the brain, illustrating how widespread exposure of animals and humans to EDCs can impact health and behaviors.

Direct catalytic conversion of ethanol to hydrocarbon blend-stock can increase biofuels use in current vehicles beyond the ethanol blend-wall of 10-15%. Literature reports describe quantitative conversion of ethanol over zeolite catalysts but high C2 hydrocarbon formation renders this approach unsuitable for commercialization. Furthermore, the prior mechanistic studies suggested that ethanol conversion involves endothermic dehydration step. Here, we report the complete conversion of ethanol to hydrocarbons over InV-ZSM-5 without added hydrogen and which produces lower C2 (<13%) as compared to that over H-ZSM-5. Experiments with C2H5OD and in situ DRIFT suggest that most of the products come from the hydrocarbon pool type mechanism and dehydration step is not necessary. Thus, our method of direct conversion of ethanol offers a pathway to produce suitable hydrocarbon blend-stock that may be blended at a refinery to produce fuels such as gasoline, diesel, JP-8, and jet fuel, or produce commodity chemicals such as BTX.