Startle is a fast response to sudden, intense stimuli and probably protects the organism from injury by a predator or by a blow. The acoustic startle response (ASR) of mammals is mediated by a ...relatively simple neuronal circuit located in the lower brainstem. Neurons of the caudal pontine reticular nucleus (PnC) are key elements of this primary ASR pathway. The ASR in humans and animals has a non-zero baseline, that is, the response magnitude can be increased or decreased by a variety of pathological conditions and experimental manipulations. Therefore, the ASR has been used as a behavioral tool to assess the neuronal basis of behavioral plasticity and to model neuropathological dysfunctions of sensorimotor information processing. Cross-species examples for the increase of the ASR magnitude are sensitization, fear-potentiation and drug-induced enhancement. Examples for the reduction of the ASR magnitude are habituation, prepulse inhibition, drug-induced inhibition and the attenuation by positive affect. This review describes the neuronal basis underlying the mediation of the ASR, as well as the neuronal and neurochemical substrates of different phenomena of enhancement and attenuation of the ASR. It also attempts to elucidate the biological background of these forms of behavioral plasticity. Special emphasis is put on the potential relevance of ASR modulations for the understanding of human psychiatric and neurological diseases.
Human body burdens of chemicals used in plastic manufacture Koch, Holger M.; Calafat, Antonia M.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
07/2009, Letnik:
364, Številka:
1526
Journal Article
Recenzirano
Odprti dostop
In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. ...biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information.
There is an ongoing probing of the role of chemicals in the indoor environment. The majority of potential target substances are so‐called very volatile, volatile, and semi‐volatile organic compounds ...(VVOCs, VOCs, and SVOCs). Depending on their physical properties and the mass transfer conditions, they are distributed in or between the gas phase, particle phase, settled house dust, surface films, clothing, and other fabrics as well as the exposed skin and hair of the occupants themselves. Therefore, inhalation, ingestion, and dermal uptake all must be considered as relevant pathways for exposure assessment in human habitats. Exposure to VVOCs, VOCs, and SVOCs can be estimated by measuring their concentrations in relevant indoor compartments or by determining the amounts of the target compounds and/or their metabolites in urine and blood. Assessing the various routes of exposure often requires a combination of sophisticated and interdisciplinary theoretical background and experimental techniques. Consequently, close communication and collaboration between chemical and exposure scientists are needed to achieve a better understanding of human exposure to chemical substances in various indoor environments. Embedded in the toxicological context, this is the basis for assessing the corresponding health risks and for determining control strategies or approaches to limit such risks.
Body burdens of exogeneous organic chemicals can be assessed from the outside in (estimating inhalation, ingestion, and dermal absorption) or the inside out (biomonitoring of chemicals or metabolites in blood and urine). When these approaches are combined, they synergistically improve our knowledge of how organic chemicals get into our bodies as well as their effects on us.
Disruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impairs vocal development in humans and songbirds. The basal ganglia are important for the selection and ...sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalizations are unknown. Here, we show that expression of FoxP2 in the basal ganglia is vital for the fluent initiation and termination of birdsong, as well as the maintenance of song syllable sequencing in adulthood. Knockdown of FoxP2 imbalances dopamine receptor expression across striatal direct-like and indirect-like pathways, suggesting a role of dopaminergic signaling in regulating vocal motor sequencing. Confirming this prediction, we show that phasic dopamine activation, and not inhibition, during singing drives repetition of song syllables, thus also impairing fluent initiation and termination of birdsong. These findings demonstrate discrete circuit origins for the dysfluent repetition of vocal elements in songbirds, with implications for speech disorders.
Although arbuscular mycorrhizal (AM) fungi are obligate symbionts that can influence plant growth, the magnitude and direction of these effects are highly variable within fungal genera and even among ...isolates within species, as well as among plant taxa.
To determine whether variability in AM fungal morphology and growth is correlated with AM fungal effects on plant growth, we established a common garden experiment with 56 AM fungal isolates comprising 17 genera and six families growing with three plant host species.
Arbuscular mycorrhizal fungal morphology and growth was highly conserved among isolates of the same species and among species within a family. By contrast, plant growth response to fungal inoculation was highly variable, with the majority of variation occurring among different isolates of the same AM fungal species.
Our findings show that host performance cannot be predicted from AM fungal morphology and growth traits. Divergent effects on plant growth among isolates within an AM fungal species may be caused by coevolution between co-occurring fungal and plant populations.
Cell invasion through a dense three-dimensional (3D) matrix is believed to depend on the ability of cells to generate traction forces. To quantify the role of cell tractions during invasion in 3D, we ...present a technique to measure the elastic strain energy stored in the matrix due to traction-induced deformations. The matrix deformations around a cell were measured by tracking the 3D positions of fluorescent beads tightly embedded in the matrix. The bead positions served as nodes for a finite element tessellation. From the strain in each element and the known matrix elasticity, we computed the local strain energy in the matrix surrounding the cell. We applied the technique to measure the strain energy of highly invasive MDA-MB-231 breast carcinoma and A-125 lung carcinoma cells in collagen gels. The results were compared to the strain energy generated by non-invasive MCF-7 breast and A-549 lung carcinoma cells. In all cases, cells locally contracted the matrix. Invasive breast and lung carcinoma cells showed a significantly higher contractility compared to non-invasive cells. Higher contractility, however, was not universally associated with higher invasiveness. For instance, non-invasive A-431 vulva carcinoma cells were the most contractile cells among all cell lines tested. As a universal feature, however, we found that invasive cells assumed an elongated spindle-like morphology as opposed to a more spherical shape of non-invasive cells. Accordingly, the distribution of strain energy density around invasive cells followed patterns of increased complexity and anisotropy. These results suggest that not so much the magnitude of traction generation but their directionality is important for cancer cell invasion.
For solid-state spin qubits, single-gate rf readout can minimize the number of gates required for scale-up since the readout sensor can integrate into the existing gates used to manipulate the ...qubits. However, state-of-the-art topological error correction codes benefit from the ability to resolve the qubit state within a single shot, that is, without repeated measurements. Here, we demonstrate single-gate, single-shot readout of a singlet-triplet spin state in silicon, with an average readout fidelity of 82.9% at 3.3 kHz measurement bandwidth. We use this technique to measure a tripletT−to singletS0relaxation time of 0.62 ms in precision donor quantum dots in silicon. We also show that the use of rf readout does not impact the spin lifetimes (S0toT−decay remained approximately 2 ms at zero detuning). This establishes single-gate sensing as a viable readout method for spin qubits.
Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we ...studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC.
E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index.
Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented.
Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.
Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.
We performed ...a hospital-based, case-control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case-control comparisons.
A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval CI, 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16.
Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.
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