Polarized thermal emission from dust in a galaxy at redshift 2.6.

Magnetic fields are fundamental to the evolution of galaxies, playing a key role in the astrophysics of the interstellar medium and star formation. Large-scale ordered magnetic fields have been mapped in the Milky Way and nearby galaxies1,2, but it is not known how early in the Universe such structures formed3. Here we report the detection of linearly polarized thermal emission from dust grains in a strongly lensed, intrinsically luminous galaxy that is forming stars at a rate more than 1,000 times that of the Milky Way at redshift 2.6, within 2.5 Gyr of the Big Bang4,5. The polarized emission arises from the alignment of dust grains with the local magnetic field6,7. The median polarization fraction is of the order of 1%, similar to nearby spiral galaxies8. Our observations support the presence of a 5-kiloparsec-scale ordered magnetic field with a strength of around 500 µG or lower, oriented parallel to the molecular gas disk. This confirms that such structures can be rapidly formed in galaxies, early in cosmic history.

AGM2015: Antineutrino Global Map 2015.

Every second greater than 10(25) antineutrinos radiate to space from Earth, shining like a faint antineutrino star. Underground antineutrino detectors have revealed the rapidly decaying fission products inside nuclear reactors, verified the long-lived radioactivity inside our planet, and informed sensitive experiments for probing fundamental physics. Mapping the anisotropic antineutrino flux and energy spectrum advance geoscience by defining the amount and distribution of radioactive power within Earth while critically evaluating competing compositional models of the planet. We present the Antineutrino Global Map 2015 (AGM2015), an experimentally informed model of Earth's surface antineutrino flux over the 0 to 11 MeV energy spectrum, along with an assessment of systematic errors. The open source AGM2015 provides fundamental predictions for experiments, assists in strategic detector placement to determine neutrino mass hierarchy, and aids in identifying undeclared nuclear reactors. We use cosmochemically and seismologically informed models of the radiogenic lithosphere/mantle combined with the estimated antineutrino flux, as measured by KamLAND and Borexino, to determine the Earth's total antineutrino luminosity at . We find a dominant flux of geo-neutrinos, predict sub-equal crust and mantle contributions, with ~1% of the total flux from man-made nuclear reactors.

Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) exerts neurotrophic and neuroprotective effects on substantia nigra (SN) dopamine neurons and has great therapeutic potential for Parkinson's disease (PD). Hindering this potential is the fact that GDNF cannot cross the blood-brain barrier. The aim of this study was to assess the effects of GDNF administered by the intranasal route in normal rats, and in the unilateral 6-hydroxydopamine (6-OHDA) model of PD. In the first study, rats received single intranasal doses of 50-µg GDNF in phosphate-buffered saline (PBS) or cationic liposomes, but no 6-OHDA. In the second study, rats were nasally administered 10, 50 or 150 µg of GDNF in PBS or cationic liposomes 1h before injection of 6-OHDA. All groups were sacrificed 3-4 weeks later. Both intranasal GDNF treatments induced a neurotrophic effect in the SN insofar as the number of tyrosine hydroxylase (TH)-positive neurons was significantly higher than in controls given intranasal PBS liposomes. Dopamine cell counts were also higher in the intact SN of 6-OHDA-lesioned rats compared to controls given PBS liposomes. Most importantly, intranasal GDNF provided significant neuroprotective efficacy indicated by greater TH immunostaining density in the lesioned versus intact SN of rats given single 50-µg doses of GDNF in PBS, or 150-µg doses of liposomal GDNF, compared to lesioned rats given PBS liposomes. Three 50-µg doses given at daily intervals (1 day before, 1h before, and 1 day after 6-OHDA) provided even greater protection than single 150-µg doses. Multiple doses at short intervals may therefore provide greater neuroprotection than single bolus doses. These results demonstrate both a neurotrophic effect of intranasal GDNF in the intact SN as well as neuroprotective efficacy in the unilateral 6-OHDA model, supporting pursuit of this approach as a potential treatment for PD.

The suppression of star formation by powerful active galactic nuclei.

The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.

The detection of a population of submillimeter-bright, strongly lensed galaxies.

Gravitational lensing is a powerful astrophysical and cosmological probe and is particularly valuable at submillimeter wavelengths for the study of the statistical and individual properties of dusty star-forming galaxies. However, the identification of gravitational lenses is often time-intensive, involving the sifting of large volumes of imaging or spectroscopic data to find few candidates. We used early data from the Herschel Astrophysical Terahertz Large Area Survey to demonstrate that wide-area submillimeter surveys can simply and easily detect strong gravitational lensing events, with close to 100% efficiency.

Preliminary study using an indirect ELISA for the detection of serum antibodies to Alternaria in domestic cats.

Alternaria is a saprophytic fungus that is widespread in the environment; it is an opportunistic pathogen and causes disease in human beings and domestic animals. Fungal spores gain entry to the host through skin lesions and cause slow-growing, soft to firm, subcutaneous swellings, either with or without ulcers. An indirect ELISA was developed for the detection of anti-Alternaria immunoglobulin G (IgG) antibodies in serum to determine the prevalence of Alternaria exposure in domestic cats. Fifty-two of 63 cats had detectable levels of anti-Alternaria IgG antibody. There were no correlations between the concentration of antibody and the sex, breed or living environment of the cats, but cats less than two years of age had significantly lower concentrations than older cats. The cats with disease caused by culture-confirmed Alternaria infections did not have significantly higher concentrations of antibody than the healthy cats or cats with other diseases.

A cross-system comparison of bacterial and fungal biomass in detritus pools of headwater streams.

The absolute amount of microbial biomass and relative contribution of fungi and bacteria are expected to vary among types of organic matter (OM) within a stream and will vary among streams because of differences in organic matter quality and quantity. Common types of benthic detritus [leaves, small wood, and fine benthic organic matter (FBOM)] were sampled in 9 small (1st-3rd order) streams selected to represent a range of important controlling factors such as surrounding vegetation, detritus standing stocks, and water chemistry. Direct counts of bacteria and measurements of ergosterol (a fungal sterol) were used to describe variation in bacterial and fungal biomass. There were significant differences in bacterial abundance among types of organic matter with higher densities per unit mass of organic matter on fine particles relative to either leaves or wood surfaces. In contrast, ergosterol concentrations were significantly greater on leaves and wood, confirming the predominance of fungal biomass in these larger size classes. In general, bacterial abundance per unit organic matter was less variable than fungal biomass, suggesting bacteria will be a more predictable component of stream microbial communities. For 7 of the 9 streams, the standing stock of fine benthic organic matter was large enough that habitat-weighted reach-scale bacterial biomass was equal to or greater than fungal biomass. The quantities of leaves and small wood varied among streams such that the relative contribution of reach-scale fungal biomass ranged from 10% to as much as 90% of microbial biomass. Ergosterol concentrations were positively associated with substrate C:N ratio while bacterial abundance was negatively correlated with C:N. Both these relationships are confounded by particle size, i.e., leaves and wood had higher C:N than fine benthic organic matter. There was a weak positive relationship between bacterial abundance and streamwater soluble reactive phosphorus concentration, but no apparent pattern between either bacteria or fungi and streamwater dissolved inorganic nitrogen. The variation in microbial biomass per unit organic matter and the relative abundance of different types of organic matter contributed equally to driving differences in total microbial biomass at the reach scale.

Role of endogenous opioid peptides in mediating progesterone-induced disruption of the activation and transmission stages of the GnRH surge induction process.

How progesterone blocks the E2-induced GnRH surge in females is not known. In this study we assessed whether the endogenous opioid peptides (EOPs) that mediate progesterone negative feedback on pulsatile GnRH secretion also mediate the blockade of the GnRH surge. We treated ovariectomized ewes with physiological levels of E2 and progesterone to stimulate and block the GnRH surge, respectively, using LH secretion as an index of GnRH release. A pilot study confirmed that blocking opioidergic neurotransmission with the opioid receptor antagonist, naloxone (NAL; 1 mg/kg.h, i.v.), could prevent the suppression of pulsatile LH secretion by progesterone in our model. By contrast, antagonizing EOP receptors with NAL did not restore LH surges in ewes in which the E2-induced GnRH surge was blocked by progesterone treatment during the E2-dependent activation stage (Exp 1) of the GnRH surge induction process. However, in ewes treated with progesterone during the E2-independent transmission stage (Exp 2), NAL partially restored blocked LH surges, as indicated by increased fluctuations in LH that, in some cases, resembled LH surges. We conclude, therefore, that the EOPs that mediate progesterone negative feedback on pulsatile GnRH secretion are not involved in blockade of activation of the E2-induced GnRH surge by progesterone, but do appear to be part of the mechanism by which progesterone disrupts the transmission stage.

Progesterone can block transmission of the estradiol-induced signal for luteinizing hormone surge generation during a specific period of time immediately after activation of the gonadotropin-releasing hormone surge-generating system.

The preovulatory GnRH/LH surge in the ewe is stimulated by a rise in the circulating estradiol concentration that occurs in conjunction with preovulatory ovarian follicle development. In the presence of high levels of progesterone, such as during the luteal phase of the estrous/menstrual cycle, the stimulatory effects of elevated estradiol on GnRH/LH secretion are blocked. Recent work in the ewe has shown that a relatively short period of estradiol exposure can stimulate a GnRH/LH surge that begins after estrogenic support has been removed. This result suggests that surge generation is characterized by an estradiol-dependent period (during which the signal is read) and an estradiol-independent period (during which a cascade of neuronal events transmits the stimulatory signal to the GnRH neurosecretory system, which releases a surge of GnRH). In this series of studies, we addressed the hypothesis that progesterone can block transmission of the stimulatory estradiol signal after it has been read. Nine ovariectomized ewes were run through repeated artificial estrous cycles by sequential addition and removal of exogenous steroids. In study one, ewes received three treatments in a randomized cross-over design. Exposure to a follicular phase estradiol concentration for 10 h (positive control treatment) stimulated an LH surge in all ewes, as determined in hourly jugular blood samples. Maintenance of luteal phase progesterone concentrations throughout the artificial follicular phase (2 x CIDR-G devices, negative control) blocked the stimulatory effects of a 10-h estradiol signal, and no ewes that received this treatment expressed an LH surge. In the experimental group, exposure to luteal phase levels of progesterone, during the period after the surge generating system had been activated by estradiol, blocked the LH surge in six of nine ewes. This result demonstrates that progesterone can block the surge, even when applied after the surge-generating system has been activated and, therefore, that it inhibits either the transmission of the estradiol signal and/or the release of the GnRH/LH surge. In study 2, we assessed whether sensitivity to the inhibitory effects of progesterone was confined to a specific stage of the transmission of the estradiol signal. Eight ewes were exposed to four treatments, over successive artificial estrous cycles. Positive and negative controls were similar to those described in Study 1, except the duration of the stimulatory estradiol signal was reduced to 8 h. The two experimental groups consisted of an EARLY P (progesterone) treatment, in which progesterone was given from hours 8-13 after estradiol insertion (immediately after estradiol removal), and a LATE P treatment, in which progesterone was given from hours 13-18 (immediately before LH surge secretion). As expected, LH surges were stimulated and blocked, in response to the positive and negative controls, respectively. Whereas the EARLY P treatment blocked the LH surge in seven of eight ewes, the LATE P treatment was only successful in inhibiting a surge in one of eight animals. This result demonstrates that progesterone can block the estradiol-induced surge-generating signal soon after the onset of signal transmission (immediately after estradiol removal) but not during the later stages of signal transmission (at the time of GnRH/LH surge onset).

No evidence for left superior temporal dysfunction in asymptomatic schizophrenia and bipolar disorder. PET study of verbal fluency.

BACKGROUND: Positron emission tomography (PET) studies have revealed functional left superior temporal gyrus (STG) abnormalities in symptomatic schizophrenia during word generation. AIMS: To discover if this dysfunction is present in asymptomatic schizophrenia. To determine whether, without concurrent symptomatology, schizophrenia and bipolar affective disorder (BPD) are distinguishable by differing regional cerebral blood flow (rCBF) patterns during word generation. METHOD: A PET verbal fluency protocol was applied to six patients with BPD in remission and six patients with asymptomatic schizophrenia. Analysis included 10 control subjects from a contemporaneous study. RESULTS: All groups showed relative reduction of rCBF in both superior temporal cortices. There were no quantitative differences in any group comparison. All groups exhibited negative covariation between rCBF in left prefrontal and right (but not left) temporal regions. CONCLUSIONS: Abnormal patterns of left STG function cannot be regarded as a trait marker for schizophrenia. Functional abnormalities may reflect aspects of mental state.

Conscious neurosensory mapping of the internal structures of the human knee without intraarticular anesthesia.

The conscious neurosensory characteristics of the internal components of the human knee were documented by instrumented arthroscopic palpation without intraarticular anesthesia. With only local anesthesia injected at the portal sites, the first author (SFD) had both knees inspected arthroscopically. Subjectively, he graded the sensation from no sensation (0) to severe pain (4), with a modifier of either accurate spatial localization (A) or poor spatial localization (B). The nature of the intraarticular sensation was variable, ranging from 0 on the patellar articular cartilage to 4A on the anterior synovium, fat pad, and joint capsule. The sensation arising from the cruciate ligaments ranged from 1 to 2B in the midportion, and from 3 to 4B at the insertion sites. The sensation from the meniscal cartilages ranged from 1B on the inner rim to 3B near the capsular margin. Innervation of most intraarticular components of the knee is probably crucial for tissue homeostasis. Failure of current intraarticular soft tissue reconstructions of the knee may be due, in part, to the lack of neurosensory restoration. Research studies of the knee designed to delineate factors that restore neurosensory characteristics of the musculoskeletal system may lead to techniques that result in true restoration of joint homeostasis and function.

Actions of an IGF-I-enhancing antibody on IGF-I pharmacokinetics and tissue distribution: increased IGF-I bioavailability.

We have previously demonstrated that a specific anti-IGF-I antibody will enhance the growth-promoting activity of IGF-I in vivo (Stewart et al. 1993). Since the antibody had a modest affinity for IGF-I we suggested that the antiserum might protect IGF-I from degradation whilst maintaining it in a bioavailable form. The aim of this investigation was to test that hypothesis by determining the plasma clearance and tissue distribution of tracer IGF-I in the presence of the enhancing anti-IGF-I immunoglobulin (anti-IGF-I Ig) or non-immune immunoglobulin (NI Ig). Dwarf rats were treated with saline, NI Ig or anti-IGF-I Ig for 4 days. On day 4, 125I-IGF-I (1.6 x 10(7) c.p.m.) was injected into the jugular vein and blood sampled over the next 330 min when the rats were killed: samples of liver, kidney and skeletal muscle were quickly dissected out. Mean plasma trichloroacetic acid (TCA)-precipitable 125I-IGF-I was always significantly greater (P < 0.001 for each time point) from anti-IGF-I Ig rats versus the NI Ig or saline groups (which exhibited practically identical decay curves), implying increased binding capacity for IGF-I in the anti-IGF-I Ig rats. Pharmacokinetic parameters were calculated by resolution of the decay curves using a two-phase model. The total clearance rate of 125I-IGF-I was significantly decreased (P < 0.001) by almost twofold in the anti-IGF-I versus the two control groups, consistent with the increased binding capacity in the anti-IGF Ig rats. The half-lives of the faster-decaying phase were not significantly different between treatment groups but, surprisingly, that for the slower-decaying phase was significantly decreased (P < 0.001) in the anti-IGF-I Ig rats versus the two control groups; this may reflect the low affinity of the anti-IGF-I Ig for IGF-I and its enhancing properties. The degradation of 125I-IGF-I was significantly decreased in animals receiving the anti-IGF-I Ig. In support of this, kidney TCA-precipitable radioactivity (c.p.m.) was seven-fold less (P < 0.001) in the anti-IGF-I Ig groups versus the controls, indicative of reduced excretion. Liver TCA-precipitable radioactivity was increased (P < 0.001) in the anti-IGF-I Ig rats, probably due to reticuloendothelial clearance of non-self antibodies: skeletal muscle TCA-precipitable radioactivity tended to increase in the anti-IGF-I Ig group versus the controls which might indicate increased targeting of IGF-I to muscle. Size exclusion chromatography of plasma 15 and 120 min after administration of 125I-IGF-I demonstrated a broad peak of radioactivity with a molecular mass of 150-300 kDa in the anti-IGF-I Ig-treated rats, which was responsible for more than 90% of the eluted radioactivity. This suggests that: (1) 125I-IGF-I was bound to the anti-IGF-I Ig and might also be able to associate with IGFBPs or (2) the polyclonal antibody might recognise more than one antigenic site on IGF-I. These data indicate that the anti-IGF-I Ig was protecting IGF-I from degradation, leading to a large plasma pool of IGF-I but that IGF-I could be transferred readily from the plasma pool to tissues. We suggest that administration of IGF-I in conjunction with a binding molecule similar to the antibody described here could provide the basis for effective IGF-I treatment strategy.

Kappa-opioid restraint of oxytocin secretion: plasticity through pregnancy.

Oxytocin neurone terminals display a powerful opioid-mediated auto-inhibitory mechanism which restrains secretory activity. In pregnancy, upregulation of this mechanism may underlie the accumulation of large stores of oxytocin in the pituitary. In the present study, conscious pregnant rats were cannulated to allow blood samples to be taken for measurement of oxytocin secretion in response to intravenous administration of cholecystokinin (CCK). In each rat, we measured the secretory response to CCK before and after administration of norbinaltorphine (norBNI), a selective kappa-opioid antagonist, or of naloxone, a relatively mu-selective antagonist. Throughout pregnancy, the stimulatory effect of CCK was enhanced by prior administration of norBNI. In pregnant rats norBNI also consistently increased basal oxytocin secretion, while naloxone had no effect, suggesting that in pregnancy there is active restraint of oxytocin secretion by endogenous opioids acting at kappa-receptors. However, in late pregnancy, between days 17 and 20, there was a significant reduction in the efficacy of norBNI in potentiating the oxytocin release in response to CCK, compared to its efficacy either in non-pregnant rats or in rats between days 8 and 13 of pregnancy. This suggests that in late pregnancy, endogenous kappa-opioid restraint is downregulated. In addition, the present results demonstrate an attenuation in the potency with which CCK evoked oxytocin release in late pregnancy. The attenuation was unrelated to opioid restraint at the level of the pituitary since it coincided with apparent desensitization of this auto-inhibitory mechanism.

Guidelines for prevention and control of hepatitis A in American Indian and Alaska Native communities.

The Aberdeen Area Indian Health Service, South Dakota Department of Health, and the Centers for Disease Control and Prevention have collaborated since 1985 to investigate hepatitis A in Indian communities in the Northern Plains and to implement clinical trials of hepatitis A vaccine. After licensure of the hepatitis A vaccine in February 1995, community wide immunization programs have been implemented effectively in several communities experiencing hepatitis A outbreaks. The state health department, tribal health departments, Indian Health Service facilities, Head Start programs and schools have provided hepatitis A immunizations to children aged 2-12 years in each of these communities after obtaining parental consent. Culturally-specific educational materials were developed and extensive health education efforts were provided by IHS and tribal programs. Hepatitis A contacts age 2-12 were offered the hepatitis A vaccine at the same time they were offered passive immunization with immune globulin. To date over 70% of parents contacted by letter or in person have returned consent forms to have their children immunized. Higher response rates were obtained in communities where home visits were made to explain this program in more detail. The outbreaks appear to have stopped after 70% or more of the children aged 2-12 years were immunized. Immunization programs are being implemented in all Northern Plains Indian communities utilizing hepatitis. A vaccine from the Vaccine For Children Program. These efforts will likely eliminate hepatitis A as a health problem for Indian communities.

Induction of members of the Fos/Jun family of immediate-early genes in identified hypothalamic neurons: in vivo evidence for differential regulation.

In situ hybridization was used to measure the expression of members of the Fos/Jun family of immediate-early genes in hypothalamic neurons in vivo following defined stimuli that utilize different afferent pathways. Only c-jun messenger RNA was expressed in the hypothalamic supraoptic and paraventricular nuclei of control animals. Intravenous infusions of sodium chloride solutions of different tonicity produced a range of plasma osmolalities within physiological limits. While the induction of c-fos and jun B messenger RNAs followed the stimulus intensity, the expression of c-jun was repressed at low levels of stimulation. A higher level of osmotic stimulation was able to co-induce c-jun with the c-fos, jun B and fos B genes, suggesting that other signalling pathways may then be activated. Parturition or systemic administration of cholecystokinin, that activate supraoptic and paraventricular neurons via ascending afferent pathways from the brainstem, both induced c-fos, but not the other genes, in the magnocellular nuclei. Use of double in situ hybridization confirmed that, unlike with osmotic stimulation, induction of c-fos only occurred in oxytocin neurons. These two stimuli did not cause a concomitant repression of c-jun messenger RNA expression in magnocellular oxytocin neurons. These patterns of induction provide evidence for the differential regulation of members of this family of genes in a physiological context.

The future of anterior cruciate ligament restoration.

Advancements in the understanding of anatomy, kinematics, and physiology should improve future treatment of anterior cruciate ligament injured knees. The ultimate goal of full restoration of an anterior cruciate ligament injured knee to preinjury status, may be possible in the distant future through genetic manipulation inducing regeneration of tissues. In the midterm future, resorbable stents with incorporated bioactive growth factors have the potential of inducing normal anterior cruciate ligament anatomy without the need for detrimental harvesting of the patient's tissues, or risk of microbial transmission with the use of an allograft. In the near future, the development of more benign autografts and allografts is possible along with methods of resorbable fixation of the graft to bone. Future development of 3-dimensional arthroscopic visualization and robotic surgical techniques have the potential for improvement in graft placement. Advancements in treatment of anterior cruciate ligament deficient knees also can be expected from nonsurgical areas, such as control of muscle atrophy, enhancing cerebellar-proprioceptive rehabilitation, and better bracing techniques. The basic principle of therapy should be to maximize the functional load acceptance and transference capacity of the knee with the least degree of risk to the patient.

The knee as a biologic transmission with an envelope of function: a theory.

The knee can be characterized as a complex set of asymmetrical moving parts acting together as a living biologic transmission. The purpose of this system is to accept, transfer, and dissipate loads generated at the ends of the long mechanical lever arms of the femur and tibia. In this analogy, the various ligaments represent sensate adaptive linkages, the articular cartilages represent bearings, and the menisci, mobile sensate bearings within the transmission. The muscles represent both living engines providing motive forces, and brakes and dampening systems under complex neurologic control mechanisms. The range of load that can be applied across an individual joint in a given period without supraphysiologic overload or structural failure can be termed the envelope of function. This range of homeostatic loading can be graphed with increasing applied loads on the vertical axis and the frequency of loading on the horizontal axis. At least 4 categories of factors together determine the envelope of function for a given joint including anatomic, kinematic, physiologic, and treatment factors. This theory of joint function can result in a more rational clinical approach to treating patients with knee injuries and other orthopaedic conditions. Orthopaedic therapy should be designed to maximize the envelope of function of musculoskeletal systems with the least degree of risk.