The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) defines a group of genetic disorders characterized by brain iron deposition and associated with neuronal death. The known causes of NBIA include pantothenate kinase-associated neurodegeneration (PKAN), neuroferritinopathy, infantile neuroaxonal dystrophy (INAD), and aceruloplasminemia. OBJECTIVE: To define the radiologic features of each NBIA subtype. METHODS: Brain MRIs from patients with molecularly confirmed PKAN (26 cases), neuroferritinopathy (21 cases), INAD (four cases), and aceruloplasminemia (10 cases) were analyzed blindly to delineate patterns of iron deposition and neurodegeneration. RESULTS: In most cases of PKAN, abnormalities were restricted to globus pallidus and substantia nigra, with 100% having an eye of the tiger sign. In a minority of PKAN cases there was hypointensity of the dentate nuclei (1/5 on T2* sequences, 2/26 on fast spin echo [FSE]). In INAD, globus pallidus and substantia nigra were involved on T2* and FSE scans, with dentate involvement only seen on T2*. By contrast, neuroferritinopathy had consistent involvement of the dentate nuclei, globus pallidus, and putamen, with confluent areas of hyperintensity due to probable cavitation, involving the pallida and putamen in 52%, and a subset having lesions in caudate nuclei and thalami. More uniform involvement of all basal ganglia and the thalami was typical in aceruloplasminemia, but without cavitation. CONCLUSIONS: In the majority of cases, different subtypes of neurodegeneration associated with brain iron accumulation can be reliably distinguished with T2* and T2 fast spin echo brain MRI, leading to accurate clinical and subsequent molecular diagnosis.

Predicting the rate of cognitive decline in aging and early Alzheimer disease.

OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer disease (AD) and to determine the role of region-specific brain volumes as predictors of cognitive decline. METHODS: Longitudinal data from 166 normal elderly individuals and 59 early AD patients were analyzed. Brain volumes were extracted from MRI scans using semiautomated recursive segmentation methods. Prognostic factors were considered significant if they had a significant effect on the rate of cognitive decline. RESULTS: In multivariate analysis, higher Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic factor for an increased rate of cognitive decline. Significant prognostic factors within the baseline CDR = 0 group were base rate of progression and percent total high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base rate of progression, family history, and percent ventricular volume were significant prognostic factors within the CDR = 0.5 group and APOE had a marginally significant effect on the rate of cognitive decline in the CDR = 1 group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures can independently predict the rate of cognitive decline and improve the predictive power of statistical models that use only clinical data. Brain volumetric measures from MRI can be used to estimate the rate of cognitive decline even among normal elderly individuals and thus may aid in the prediction of time of onset of disease.

Remarkable improvement in adult Leigh syndrome with partial cytochrome c oxidase deficiency.

Leigh syndrome (LS) is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Typically, signs and symptoms commence in infancy or childhood, although rare cases of adult onset have been described. Progressive deterioration is the norm. The authors describe a 22-year-old woman with partial cytochrome c oxidase deficiency who developed fulminant LS following an acute febrile illness and who subsequently showed dramatic clinical and neuroradiologic improvement.

Biobehavioral basis of coronary-prone behavior in middle-aged men. Part I: Evidence for chronic SNS activation in Type As.

In previous research using young male subjects, the Type A behavior pattern was linked with cardiovascular and neurohormonal hyperresponsivity to laboratory stressors. The main objective of the present study was to determine whether the positive association between the Type A pattern and such physiological hyperreactivity is also present among healthy middle-aged men. Subjects were 28 middle-aged (35-50 years) white males who were classified as Type A (n = 16) or Type B (n = 12) on both the Structured Interview and the Jenkins Activity Survey. In two laboratory sessions, one week apart, subjects participated in either a mental arithmetic task or a sensory intake task. Twenty-four-hour urine collection was completed on a third day. Results showed that while no A/B differences in reactivity to either task were found, Type A subjects exhibited chronic elevation of plasma neurohormones on both laboratory days. The catecholamine elevations found across experimental periods on two laboratory days among Type A men generalized to more naturalistic settings, as indexed by 24-hr urinary excretion rates. The chronic elevations in both sympathetic nervous system and hypothalamic-pituitary-adrenal axis function we observed in middle-aged Type A men could account for epidemiological findings of increased coronary risk in this group.

Immunological studies with a monoclonal antibody suggest a different conformation of neurophysin in parvicellular neurons of rat hypothalamus.

A monoclonal antibody (mAb L6) to a carcinoma surface antigen has previously been shown to recognize neurophysins (NP), proteins associated with oxytocin and vasopressin. L6-reactivity in rat hypothalamus was confined to magnocellular neuronal systems. No staining was detected in parvicellular suprachiasmatic or paraventricular systems. mAb L6 immunoprecipitated vasopressin-neurophysin only under reducing conditions, and detected it in Western blots only after gel-renaturation and electroblotting in basic buffer. These findings suggest L6-reactivity to NP is conformation-sensitive, and imply NP expression in a unique configurational form in hypothalamic parvicellular systems.

The effect of borderline personality disorder on the hospital course of affective illness.

Two groups of patients with affective disorders, one group with a coexistent axis II diagnosis of borderline personality disorder and one group without, were compared to determine if the presence of borderline personality disorder affects the hospital course of patients with affective illness. Response to hospital treatment was assessed using standard psychiatric rating scales administered at admission, after one week of hospitalization, and before discharge. Although the patients with borderline personality disorder were more severely impaired than the comparison group, they were as likely as patients without the disorder to improve over the course of hospitalization.

An antiserum to atrial natriuretic factor (ANF) cross-reacts with neurophysins in the hypothalamo-neurohypophysial system of rat brain.

The distribution of atrial natriuretic factor (ANF)-like reactivity was examined in rat brain and heart by immunohistochemistry. Immunostaining in heart was confined to atrial myocytes. In the hypothalamus, ANF-absorbable immunoreactivity was observed in magnocellular perikarya of the paraventricular and supraoptic nuclei, and in their projections to the neural lobe of the pituitary gland. No staining was seen in the preoptic or arcuate hypothalamic nuclei or in brain stem nuclei as previously reported by other investigators. The patterns of reactivity for ANF reported here is similar to that observed for neurophysins (NPs). Comparison of sequence data between rat ANF-28 and bovine NPs revealed three regions of 3 amino acid homology between these hypothalamic peptides. Preabsorption of the ANF antiserum with Affigel-coupled bovine NP I also resulted in complete elimination of all "ANF-immunoreactivity" in both atrium and hypothalamus. Cross-reactivity of the ANF antiserum with bovine NP I and II was further confirmed by Western blot analysis. Our findings suggest that ANF antisera can cross-react with NPs if they are directed against the shared antigenic epitopes; complete elimination of staining by preabsorption of the antibody with the immunogen, therefore, does not guarantee authenticity of localization. These observations may have relevance to an earlier study which reported on the existence of ANF-immunoreactivity in oxytocin neurons of the hypothalamus.

Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fuscata).

The regional distribution of the three opioid peptide neuronal systems--proopiomelanocortin (POMC), proenkephalin A, and proenkephalin B--was investigated in the lower brainstem of Japanese monkeys (Macaca fuscata) by immunocytochemical techniques. Antiserum to beta-endorphin/beta-lipotropin, [Met]-enkephalin-Arg6-Gly7-Leu8, and human leumorphin were used to identify the POMC and the proenkephalin A and B systems, respectively. POMC-related immunoreactive material was not found in the neuronal perikarya in the lower brainstem; reactive fibers and apparent terminals were distributed in the substantia nigra, lemniscus lateralis, midbrain central gray, the nucleus raphes, nucleus parabrachialis lateralis, ventral area of the spinal trigeminal nerve, nucleus tractus solitarii, and in the reticular formation throughout the lower brainstem. Proenkephalin A-related immunoreactive neuronal perikarya were detected in the central gray, reticular formation, nucleus raphes, trapezoid body, nucleus parabrachialis lateralis and medialis, nucleus spinalis nervi trigemini, nucleus dorsalis nervi vagi, and in the nucleus tractus solitarii. Densely packed immunoreactive fibers were widely distributed in the substantia nigra, nucleus interpeduncularis, nucleus raphes, superior colliculus, periaqueductal central gray, nucleus parabrachialis lateralis and medialis, locus coeruleus, trapezoid body, nuclei cochleares, nucleus spinalis nervi trigemini, tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus gracilis, nucleus cuneatus, nucleus cuneatus accessorius, and in the reticular formation throughout the lower brainstem. Neuronal perikarya containing immunoreactive material related to proenkephalin B were found in the periaqueductal central gray, nucleus parabrachialis lateralis and medialis, nucleus tractus solitarii, and nucleus spinalis nervi trigemini. In addition, immunoreactive fibers were detected in the ventral tegmental area, substantia nigra, nucleus parabrachialis lateralis and medialis, nucleus vestibularis lateralis and medialis, and in some areas of the reticular formation. These anatomical findings demonstrate that these three opioid peptide neuronal systems are widely but uniquely distributed in the lower brainstem of the monkey.

Infants of depressed mothers show "depressed" behavior even with nondepressed adults.

To determine whether the "depressed" behavior (e.g., less positive affect and lower activity level) of infants noted during interactions with their "depressed" mothers generalizes to their interactions with nondepressed adults, 74 3-6-month-old infants of "depressed" and nondepressed mothers were videotaped in face-to-face interactions with their mothers and with nondepressed female strangers. "Depressed" mothers and their infants received lower ratings on all behaviors than nondepressed mothers and infants. Although the infants of "depressed" versus nondepressed mothers also received lower ratings with the stranger adult, very few differences were noted between those infants' ratings when interacting with their mother versus the stranger, suggesting that their "depressed" style of interacting is not specific to their interactions with depressed mothers but generalizes to their interactions with nondepressed adults as early as 3 months of age.

Characterization of complementary deoxyribonucleic acid for precursor of porcine motilin.

Cloned cDNAs encoding the precursor protein for motilin and a novel peptide, motilin-associated peptide, were isolated from a library derived from porcine intestinal mucosa mRNA. Nucleotide sequence analysis predicts a precursor protein of 119 amino acids including a signal peptide in direct linkage with the 22 amino acid sequence for motilin, and a 70 amino acid peptide of unknown function. The putative bioactive moieties are separated by Lys-Lys, dibasic residues that serve as substrates for cleavage by proteolytic maturation enzymes in many polyprotein precursors. While there is an abundant literature detailing a spectrum of tissues and cell types which express motilin like immunoreactivity, analysis of mRNA derived from many of these tissues suggests that the mRNA for the mucosal motilin precursor is only transcribed in this tissue. The nature of the immunoreactive material in the central nervous system and other peripheral tissues remains to be determined.

Implantation of fetal preoptic area into the lateral ventricle of adult hypogonadal mutant mice: the pattern of gonadotropin-releasing hormone axonal outgrowth into the host brain.

Transplantation of fetal preoptic area tissue containing gonadotropin-releasing hormone neurons into the third ventricle of male hypogonadal mice resulted in an elevation of pituitary gonadotropin levels and correction of hypogonadism. This reversal of the neuroendocrine deficit was correlated with innervation of the median eminence by gonadotropin-releasing hormone axons. The specificity of fiber outgrowth suggested that local neuromodulatory factors might guide these axons to the nearby median eminence. To test this hypothesis, 14 adult hypogonadal males received unilateral fetal preoptic area grafts into the lateral ventricle, a site distant from the median eminence. After four months, healthy grafts containing numerous gonadotropin-releasing hormone neurons were seen in 9 hosts. However, none of these grafts corrected the hypogonadism of the host and there was no gonadotropin-releasing hormone innervation of the median eminence in any of these animals, thus demonstrating that the presence of gonadotropin-releasing hormone neurons in the ventricular space is itself not sufficient to stimulate the pituitary-gonadal axis. Instead, gonadotropin-releasing hormone axons coursed in the host fimbria, fornix, corpus callosum, and stria terminalis. These fibers could be traced into the anterior hippocampal area, medial and lateral septum, and the anterior hypothalamus. The distribution of these fibers included a number of regions which receive gonadotropin-releasing hormone fiber input in the normal mouse. These findings show that gonadotropin-releasing hormone neurons transplanted into the lateral ventricle can survive and extend processes into the host brain, often projecting to sites of normal gonadotropin-releasing hormone innervation. Their success in contacting these sites suggests that gonadotropin-releasing hormone fiber outgrowth may be influenced by regionally specified trophic and/or guidance factors.

Accessory olfactory bulb transplants correct hypogonadism in mutant mice.

Transplantation of normal fetal gonadotropin-releasing hormone (GnRH) neurons from the accessory olfactory bulb (AOB) to the third ventricle of GnRH-deficient adult mutant mice reverses the genetically determined reduction in pituitary hormones and poorly developed gonads. The transplanted heterotopic AOB neurons adapt their morphology and secretory functions to what is observed with preoptic GnRH neurons when transplanted into deficient mice and in the normal intact mature animal. This suggests the presence of median eminence trophic factors affecting the growth, terminal sprouting, and functional behavior of the transplanted neurons.

The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice.

Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion.

Chronic syndrome of inappropriate antidiuretic hormone secretion and hypertension in a patient with olfactory neuroblastoma. Evidence of ectopic production of arginine vasopressin by the tumor.

A 28-year-old man with the chronic syndrome of Inappropriate antidiuretic hormone secretion and hypertension was found to have an olfactory neuroblastoma. We demonstrated evidence of elevated circulating arginine vasopressin levels, significantly elevated arginine vasopressin and vasopressin neurophysin levels in the tumor extract, and immunohistochemical staining for arginine vasopressin and vasopressin neurophysin in the tumor cells. The patient's clinical syndrome, including hypertension, resolved following subtotal removal of the tumor and radiation therapy. This study identified olfactory neuroblastoma as a definite cause of ectopic arginine vasopressin secretion causing the syndrome of inappropriate antidiuretic hormone secretion.

Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.

Ultrastructure of gonadotropin-releasing hormone neuronal structures derived from normal fetal preoptic area and transplanted into hypogonadal mutant (hpg) mice.

The hpg mutant mouse lacks the neurohormone gonadotropin-releasing hormone (GnRH) and hence has a reproductive deficit. This deficit can be corrected by placement of normal fetal preoptic area into the third ventricle (see Krieger et al., 1985). We have now used ultrastructural immunocytochemistry to investigate the morphology of GnRH neurons in such intraventricular grafts, the routes that their axons take as they exit into the host, and the neurosecretory terminations that they make in the host median eminence. The GnRH cells in the transplant were similar in morphology to that reported for such cells in the preoptic area of other rodents. There was a large central nucleus, frequently indented and containing 1 or 2 nucleoli. The thin rim of cytoplasm was filled with rough endoplasmic reticulum, Golgi stacks, and mitochondria. Both dendritic and axonal profiles were identified, and a modest synaptic input to the former was found. Between the host and the implant a complex multilayered ependymal zone developed, and it was through this region that GnRH axons exited into the host arcuate nucleus and median eminence, usually surrounded by ependymal or glial elements. Within the median eminence, GnRH terminals were in close association with fenestrated blood vessels forming a normal neurosecretory terminus.