Optimising nucleic acid recovery from rapid antigen tests for whole genome sequencing of respiratory viruses.

BACKGROUND: Whole genome sequencing (WGS) of respiratory viruses from rapid antigen tests (RAT-WGS) is a novel approach to expanding genomic surveillance of respiratory infections. To date however, there are limited data on the genomic stability of these viruses on RATs. In this study, we investigated the effect of storage conditions and nucleic acid preservatives on the ability to enhance stability and improve recovery of respiratory virus genomes from RATs. METHODS: A mixture of common respiratory viruses was used to inoculate RATs at different environmental temperatures (4°C, 20°C and 36°C), with two preservative reagents (RNALater and DNA/RNA shield) Nucleic acid was extracted from RATs at two different timepoints (72 h and seven days) and subject to real-time multiplex respiratory PCR to detect a range of respiratory viruses. WGS was performed using target-enrichment with the TWIST Comprehensive Viral Research Panel. Defined metrics from an automated in-house bioinformatic pipeline were used to assess and compare viral genome recovery under different conditions. RESULTS: Nucleic acid degradation (indicated by relative change in PCR cycle threshold and WGS-based metrics) was most notable at 20 °C and 36 °C. Storage in either RNALater or DNA / RNA shield improved genome recovery for respiratory viruses across all temperature conditions, although this was most pronounced for RNALater. Subtyping of Influenza viruses demonstrated the applicability of RAT-WGS in downstream genomic epidemiological surveillance. CONCLUSIONS: Under simulated conditions, RAT-WGS demonstrated that (i) viral genomes were generally stable at 4°C at 72 h and 1 week, (ii) RNALater has a more significant preservation of nucleic acids compared to DNA/RNA Shield and (iii) genome recovery can be achieved using a sequencing depth of 500,000 reads per sample in RNALater, across all respiratory viruses and conditions.

Observation of photo-induced plasmon-phonon coupling in PbTe via ultrafast x-ray scattering.

We report the observation of photo-induced plasmon-phonon coupled modes in the group IV-VI semiconductor PbTe using ultrafast x-ray diffuse scattering at the Linac Coherent Light Source. We measure the near-zone-center excited-state dispersion of the heavily screened longitudinal optical (LO) phonon branch as extracted from differential changes in x-ray diffuse scattering intensity following above bandgap photoexcitation. We suggest that upon photoexcitation, the LO phonon-plasmon coupled (LOPC) modes themselves become coupled to longitudinal acoustic modes that drive electron band shifts via acoustic deformation potentials and possibly to low-energy single-particle excitations within the plasma and that these couplings give rise to displacement-correlations that oscillate in time with a period given effectively by the heavily screened LOPC frequency.

Possible Neurobiological Underpinnings of Homosexuality and Gender Dysphoria.

Although frequently discussed in terms of sex dimorphism, the neurobiology of sexual orientation and identity is unknown. We report multimodal magnetic resonance imaging data, including cortical thickness (Cth), subcortical volumes, and resting state functional magnetic resonance imaging, from 27 transgender women (TrW), 40 transgender men (TrM), and 80 heterosexual (40 men) and 60 homosexual cisgender controls (30 men). These data show that whereas homosexuality is linked to cerebral sex dimorphism, gender dysphoria primarily involves cerebral networks mediating self-body perception. Among the homosexual cisgender controls, weaker sex dimorphism was found in white matter connections and a partly reversed sex dimorphism in Cth. Similar patterns were detected in transgender persons compared with heterosexual cisgender controls, but the significant clusters disappeared when adding homosexual controls, and correcting for sexual orientation. Instead, both TrW and TrM displayed singular features, showing greater Cth as well as weaker structural and functional connections in the anterior cingulate-precuneus and right occipito-parietal cortex, regions known to process own body perception in the context of self.

MRI Shows that Exhaustion Syndrome Due to Chronic Occupational Stress is Associated with Partially Reversible Cerebral Changes.

The present study investigates the cerebral effects of chronic occupational stress and its possible reversibility. Forty-eight patients with occupational exhaustion syndrome (29 women) and 80 controls (47 women) underwent structural magnetic resonance imaging (MRI) and neuropsychological testing. Forty-four participants (25 patients, 19 controls) also completed a second MRI scan after 1-2 years. Only patients received cognitive therapy. The stressed group at intake had reduced thickness in the right prefrontal cortex (PFC) and left superior temporal gyrus (STG), enlarged amygdala volumes, and reduced caudate volumes. Except for the caudate volume, these abnormalities were more pronounced in females. They were all related to perceived stress, which was similar for both genders. Thickness of the PFC also correlated with an impaired ability to down-modulate negative emotions. Thinning of PFC and reduction of caudate volume normalized in the follow-up. The amygdala enlargement and the left STG thinning remained. Longitudinal changes were not detected among controls. Chronic occupational stress was associated with partially reversible structural abnormalities in key regions for stress processing. These changes were dynamically correlated with the degree of perceived stress, highlighting a possible causal link. They seem more pronounced in women, and could be a substrate for an increased cerebral vulnerability to stress-related psychiatric disorders.

Anatomical and Functional Findings in Female-to-Male Transsexuals: Testing a New Hypothesis.

Gender dysphoria (GD) is characterized by incongruence between onés gender assigned at birth and the gender that one identifies with. The biological mechanisms of GD are unclear, especially in female-to-male transsexuals (FtM-TR). Here, we investigate whether distinct structural and functional patterns along cerebral midline networks processing own-body perception may constitute a biological correlate. METHOD: MRI of functional connectivity, cortical thickness, surface area, and gray matter volume was carried out in 28 female-to-male transsexuals (FtM-TR) and 68 cis-sexual controls (34 male). FtM-TR displayed thicker mid-frontal, precuneal-parietal, and lingual cortex than both male and female controls, whereas, in regions with reported anatomical sex differences among the controls, FtM-TR followed patterns of the gender assigned at their birth. FtM-TR also displayed weaker functional connections from the pregenual anterior cingulate to the insular cortex, and the temporo parietal junction compared with both control groups. Distinct structural and functional pattern in the own-body image network may represent biological markers for the dysphoric own-body perception in transgender individuals.

The origin of incipient ferroelectricity in lead telluride.

The interactions between electrons and lattice vibrations are fundamental to materials behaviour. In the case of group IV-VI, V and related materials, these interactions are strong, and the materials exist near electronic and structural phase transitions. The prototypical example is PbTe whose incipient ferroelectric behaviour has been recently associated with large phonon anharmonicity and thermoelectricity. Here we show that it is primarily electron-phonon coupling involving electron states near the band edges that leads to the ferroelectric instability in PbTe. Using a combination of nonequilibrium lattice dynamics measurements and first principles calculations, we find that photoexcitation reduces the Peierls-like electronic instability and reinforces the paraelectric state. This weakens the long-range forces along the cubic direction tied to resonant bonding and low lattice thermal conductivity. Our results demonstrate how free-electron-laser-based ultrafast X-ray scattering can be utilized to shed light on the microscopic mechanisms that determine materials properties.

Conduct disorder in females is associated with reduced corpus callosum structural integrity independent of comorbid disorders and exposure to maltreatment.

The behavioral phenotype and genotype of conduct disorder (CD) differ in males and females. Abnormalities of white matter integrity have been reported among males with CD and antisocial personality disorder (ASPD). Little is known about white matter integrity in females with CD. The present study aimed to determine whether abnormalities of white matter are present among young women who presented CD before the age of 15, and whether abnormalities are independent of the multiple comorbid disorders and experiences of maltreatment characterizing females with CD that may each in themselves be associated with alterations of the white matter. Three groups of women, aged on average 24 years, were scanned using diffusion tensor imaging and compared: 28 with prior CD, three of whom presented ASPD; a clinical comparison (CC) group of 15 women with no history of CD but with similar proportions who presented alcohol dependence, drug dependence, anxiety disorders, depression disorders and physical and sexual abuse as the CD group; and 24 healthy women. Whole-brain, tract-based spatial statistics were computed to investigate differences in fractional anisotropy, axial diffusivity and radial diffusivity. Compared with healthy women, women with prior CD showed widespread reductions in axial diffusivity primarily in frontotemporal regions. After statistically adjusting for comorbid disorders and maltreatment, group differences in the corpus callosum body and genu (including forceps minor) remained significant. Compared with the CC group, women with CD showed reduced fractional anisotropy in the body and genu of the corpus callosum. No differences were detected between the CD and healthy women in the uncinate fasciculus.

[ETIOLOGY OF PROSTATE CANCER].

Prostate cancer is now recognized as one of the most important medical problems in male population. Epigenetic regulation of gene expression by promoter methylation and histone acetylation, proinflammatory enzyme cyclooxygenase-2 and somatic mutations in a variety of genes with diverse biological functions has been implicated in prostate cancer development and progression.

Penile metastases of rectal adenocarcinoma.

INTRODUCTION: Penile metastases are very rare and arise most frequently from genitourinary cancers. Penile metastases from rectal adenocarcinoma are less common and only 50 or so cases have been reported. CASE PRESENTATION: We present a 43-year-old man with penile metastases from a rectal adenocarcinoma. Two years before admittance to our department, abdomino-perineal resection of the rectum (Miles operation) was performed for a Dukes B (T3N0M0) rectal adenocarcinoma; the surgical resection margins wee negative. Adjuvant chemotherapy and radiotherapy treatment were administered. One year after initial management, excision of a local recurrence was performed followed by further chemotherapy. The patient subsequently noticed lesions of the penis measuring up to 1.2 cm in diameter. Biopsy revealed metastatic adenocarcinoma. Computed tomography showed normal structure of penis with subcutaneous nodular thickening. Soon thereafter, the entire shaft of the penis becomes indurated and the patient developed urinary obstruction. A suprapubic cystostomy was performed. The patient died within 6 months. DISCUSSION: Penile metastases arise most frequently from genitourinary cancers, primarily from the bladder and the prostate gland. Metastasis to the penis from a rectal adenocarcinoma occurs much less commonly. Other reported primary origins of penile metastases include malignancies of the lung, nasopharynx and melanoma. The major symptoms are penile nodular mass, malignant priapism, penile pain and tenderness, difficulty in micturition, and urinary retention. Possible routes of metastasis are arterial, retrograde venous spread, retrograde lymphatic spread, but direct tumor infiltration/extension is also possible. Penile metastases from rectal adenocarcinoma usually occur within 2 years after diagnosis of the primary tumor. The prognosis is very poor regardless of treatment modality. Treatment is more often palliative than curative. Survival usually varies from 7 months to 2 years. Long-term survival (9 years) has been seen after aggressive surgical treatment (penile amputation) with best results for patients when penile metastasis was the only evident region of recurrence. CONCLUSION: The prognosis of metastasis to the penis is very poor; the best results have been achieved with surgery but only for lesions where metastasis is limited to the penis.

Allopregnanolone and mood disorders.

UNLABELLED: Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. CONCLUSION: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

Sex differences in cortical thickness and their possible genetic and sex hormonal underpinnings.

Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing as XXY males have 1 extra X chromosome, we investigated the possible effects of X- and sex-chromosome dosage on Cth by comparing data from 31 XXY males with 39 XY and 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parietal and occipital Cth was greater in XX females than XY males. In these regions Cth was inversely correlated with z-normalized testosterone. In the motor strip, the cortex was thinner in XY males compared with both XX females and XXY males, indicating the possibility of an X-chromosome gene-dosage effect. XXY males had thinner right superior temporal and left middle temporal cortex, and a thicker right orbitofrontal cortex and lingual cortex than both control groups. Based on these data and previous reports from women with XO monosomy, it is hypothesized that programming of the motor cortex is influenced by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of the superior temporal cortex is mediated by X-chromosome escapee genes with Y-homologs.

Sex differences in the human brain and the impact of sex chromosomes and sex hormones.

While there has been increasing support for the existence of cerebral sex differences, the mechanisms underlying these differences are unclear. Based on animal data, it has long been believed that sexual differentiation of the brain is primarily linked to organizational effects of fetal testosterone. This view is, however, in question as more recent data show the presence of sex differences before the onset of testosterone production. The present study focuses on the impact that sex chromosomes might have on these differences. Utilizing the inherent differences in sex and X-chromosome dosage among XXY males, XY males, and XX females, comparative voxel-based morphometry was conducted using sex hormones and sex chromosomes as covariates. Sex differences in the cerebellar and precentral gray matter volumes (GMV) were found to be related to X-chromosome dosage, whereas sex differences in the amygdala, the parahippocamus, and the occipital cortex were linked to testosterone levels. An increased number of sex chromosomes was associated with reduced GMV in the amygdala, caudate, and the temporal and insular cortices, with increased parietal GMV and reduced frontotemporal white matter volume. No selective, testosterone independent, effect of the Y-chromosome was detected. Based on these observations, it was hypothesized that programming of the motor cortex and parts of cerebellum is mediated by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of certain limbic structures involves testosterone and X-chromosome escapee genes with Y-homologs.

Chronic stress is linked to 5-HT(1A) receptor changes and functional disintegration of the limbic networks.

There are increasing reports about stress related cognitive and psychic declines in subjects who have no psychiatric premorbidity, depression, or major life trauma. Yet, little is known about the underlying neurobiology. Based on the typical symptomatology, fMRI data suggesting that stress activates the limbic circuits, and animal data showing a major involvement of the 5-HT(1A) receptor in stress regulation, we hypothesized that enduring daily stress causes widespread limbic dysfunctions, and specific changes of the 5-HT(1A) receptor. To test these hypotheses combined PET studies were carried out in 16 chronically stressed, and 16 non-stressed subjects. Limbic function was tested by measuring cerebral blood flow during rest, and when using an odor activation paradigm. 5-HT(1A) receptor binding potential (BP) was assessed with [(11)C]WAY100635. All subjects went through a battery of neuropsychological tests. Stressed subjects showed a functional disconnection between the amygdala and ACC/medial prefrontal cortex (mPFC), and an impaired odor activation of the ACC. They also displayed a reduced 5-HT(1A) receptor BP in the anterior cingulate (ACC), the insular-cortex, and the hippocampus. Their performance in attention-, odor discrimination-, and semantic memory tasks was impaired, and correlated with the BP-values in the respective region. The degree of reported stress was inversely correlated with activation of ACC, and the 5-HT(1A) receptor BP in the amygdala and hippocampus. Enduring every day psychosocial stress seems to be associated with a limbic reduction of 5-HT(1A) receptor binding and functional disintegration of ACC/mPFC. These changes support the notion of an impaired top-down regulation of stress stimuli, and identify potential targets for early treatment.

Precise control of thermal conductivity at the nanoscale through individual phonon-scattering barriers.

The ability to precisely control the thermal conductivity (kappa) of a material is fundamental in the development of on-chip heat management or energy conversion applications. Nanostructuring permits a marked reduction of kappa of single-crystalline materials, as recently demonstrated for silicon nanowires. However, silicon-based nanostructured materials with extremely low kappa are not limited to nanowires. By engineering a set of individual phonon-scattering nanodot barriers we have accurately tailored the thermal conductivity of a single-crystalline SiGe material in spatially defined regions as short as approximately 15 nm. Single-barrier thermal resistances between 2 and 4 x 10(-9) m(2) K W(-1) were attained, resulting in a room-temperature kappa down to about 0.9 W m(-1) K(-1), in multilayered structures with as little as five barriers. Such low thermal conductivity is compatible with a totally diffuse mismatch model for the barriers, and it is well below the amorphous limit. The results are in agreement with atomistic Green's function simulations.

High fetal testosterone and sexually dimorphic cerebral networks in females.

Active masculinization by fetal testosterone is believed to be a major factor behind sex differentiation of the brain. We tested this hypothesis in a 15O-H2O positron emission tomography study of 11 women with congenital adrenal hyperplasia (CAH), a condition with high fetal testosterone, and 26 controls. Two indices of cerebral dimorphism were measured--functional connectivity and cerebral activation by 2 putative pheromones (androstadienone [AND] and estratetraenol [EST]), previously reported to activate the hypothalamic networks in a sex-differentiated manner. Smelling of unscented air was the baseline condition, also used for measurements of functional connectivity from the amygdala. In CAH women and control women AND activated the anterior hypothalamus, and EST the amygdala, piriform, and anterior insular cortex. The pattern was reciprocal in the male controls. Also the functional connections were similar in CAH women and control women, but different in control men. Women displayed connections with the contralateral amygdala, cingulate, and the hypothalamus, men with the basal ganglia, the insular and the sensorimotor cortex. Furthermore, the connections were in CAH and control women more widespread from the left amygdala, in men from the right amygdala. Thus, we find no evidence for masculinization of the limbic circuits in women with high fetal testosterone.

Oxygen isotope effects on the superconducting transition and magnetic states within the phase diagram of Y1-xPrxBa2Cu3O7-delta.

The various phases observed in all cuprate superconductors [superconducting (SC), spin-glass (SG), and antiferromagnetic (AFM)] were investigated with respect to oxygen-isotope (16O/18O) effects, using here as a prototype system of cuprates Y1-xPrxBa2Cu3O7-delta. All phases exhibit an isotope effect which is strongest where the respective phase terminates. In addition, the isotope effects on the magnetic phases (SG and AFM) are sign reversed as compared to the one on the superconducting phase. In the coexistence regime of the SG and SC phase a two-component behavior is observed where the isotope induced decrease of the superfluid density leads to a corresponding enhancement in the SG related density.

Reduced dopamine transporter binding in patients with juvenile myoclonic epilepsy.

BACKGROUND: Behavioral and cognitive problems are frequently encountered in juvenile myoclonic epilepsy (JME). The underlying mechanisms are unknown. Based on previous data showing that the dopamine system is involved in motor as well as cognitive functions, we tested whether JME may be associated with changes in this system, and if such changes are linked to interictal dysfunctions in these patients. METHOD: PET and [(11)C]PE2I was used to investigate the regional binding potential to the dopamine transporter (DAT) in 12 patients with JME and 12 healthy controls. Binding potential was calculated in the midbrain, substantia nigra, caudate, and putamen. We also tested possible correlations between the respective measures and performance in several neuropsychological tests. RESULTS: Patients had a reduced binding potential in the substantia nigra and midbrain (p = 0.009 and 0.007), and normal values in the caudate and putamen. They also exhibited impaired psychomotor speed and motor function, which in some tests correlated with DAT binding potential in the midbrain. CONCLUSION: Dopamine signaling seems impaired in the target regions for dopaminergic neurons (the striatum and frontal lobe), and related to several interictal dysfunctions in JME. The findings add a new aspect to the pathophysiology of JME.

Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids.

One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.