Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

Facial width-to-height ratio is associated with agonistic and affiliative dominance in bonobos (Pan paniscus).

Facial width-to-height ratio (fWHR) is associated with social dominance in human and non-human primates, which may reflect the effects of testosterone on facial morphology and behaviour. Given that testosterone facilitates status-seeking motivation, the association between fWHR and behaviour should be contingent on the relative costs and benefits of particular dominance strategies across species and socioecological contexts. We tested this hypothesis in bonobos (Pan paniscus), who exhibit female dominance and rely on both affiliation and aggression to achieve status. We measured fWHR from facial photographs, affiliative dominance with Assertiveness personality scores and agonistic dominance with behavioural data. Consistent with our hypothesis, agonistic and affiliative dominance predicted fWHR in both sexes independent of age and body weight, supporting the role of status-seeking motivation in producing the link between fWHR and socioecologically relevant dominance behaviour across primates.

Aging and sex affect soluble alpha klotho levels in bonobos and chimpanzees.

BACKGROUND: Throughout life, physiological homeostasis is challenged and the capacity to cope with such challenges declines with increasing age. In many species, sex differences exist in life expectancy. Sex-specific differences have been related to extrinsic factors like mate competition and/or intrinsic proximate mechanisms such as hormonal changes. In humans, an intrinsic factor related to aging is soluble alpha klotho (α-Kl). Both sexes show an age-related decline in α-Kl, but throughout life women have higher levels than men of the same age. Sex differences in α-Kl have been linked to a shorter lifespan, as well as to specific morbidity factors such as atherosclerosis and arteries calcifications. In non-human animals, information on α-Kl levels is rare and restricted to experimental work. Our cross-sectional study is the first on α-Kl levels in two long-lived species: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). As in most mammals, female bonobos and chimpanzees have longer life expectancy than males. METHODS: We measured serum α-Kl levels of 140 subjects from 16 zoos with an ELISA to examine if α-Kl levels reflect this difference in life expectancy. RESULTS: In both species and in both sexes, α-Kl levels declined with age suggesting that this marker has potential for aging studies beyond humans. We also found species-specific differences. Adult female bonobos had higher α-Kl levels than males, a difference that corresponds to the pattern found in humans. In chimpanzees, we found the opposite: males had higher α-Kl levels than females. CONCLUSION: We suggest that contrasting sex differences in adult α-Kl levels mirror the dominance relations between females and males of the two Pan species; and that this might be related to corresponding sex differences in their exposure to stress. In humans, higher cortisol levels were found to be related to lower α-Kl levels. We conclude that there is great potential for studying aging processes in hominoids, and perhaps also in other non-human primates, by measuring α-Kl levels. To better understand the causes for sex differences in this aging marker, consideration of behavioural parameters such as competition and stress exposure will be required as well as other physiological markers.

Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees.

Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in female chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees.

Embryos whose polar bodies contain isolated reciprocal chromosome aneuploidy are almost always euploid.

STUDY QUESTION: When a chromosome aneuploidy is detected in the first polar body and a reciprocal loss or gain of the same chromosome is detected in the second polar body, is the resulting embryo usually aneuploid for that chromosome? SUMMARY ANSWER: When reciprocal aneuploidy occurs in polar bodies, the resulting embryo is usually normal for that chromosome, indicating that premature separation of sister chromatids (PSSC)-not non-disjunction-likely occurred in meiosis I. WHAT IS KNOWN ALREADY: Single-nucleotide polymorphism-based microarray analysis can be used to accurately determine the chromosomal status of polar bodies and embryos. Sometimes, the only abnormality found is a reciprocal gain or loss of one or two chromosomes in the two polar bodies. Prediction of the status of the resulting embryo in these cases is problematic. STUDY DESIGN, SIZE, DURATION: Blinded microarray analysis of previously diagnosed aneuploid embryos that had reciprocal polar body aneuploidy. MATERIALS, SETTING, METHODS: IVF cycles were performed between 2008 and 2011 in patients aged 40 ± 3 years (range 35-47 years) with an indication for polar body-based aneuploidy screening. Thirty-five aneuploid vitrified Day 3 embryos were warmed, cultured to Day 5 and biopsied for microarray analysis. Predictions were made for the ploidy status of the embryo if PSSC or non-disjunction had occurred. The signal intensity for the aneuploid chromosome in the first polar body was compared between those that resulted in euploid and aneuploid embryos. MAIN RESULTS AND THE ROLE OF CHANCE: Among 34 embryos with evaluable results, 31 were euploid on re-analysis. Of 43 chromosomes that had reciprocal aneuploidy in the polar bodies, 41 were disomic in the embryo, indicating that PSSC was likely to have occurred 95% (95% confidence interval 85-99%) of the time. The log 2 ratio signal intensity from the chromosomes that underwent non-disjunction, resulting in unbalanced embryos, were outliers when compared with those that underwent PSSC. LIMITATIONS, REASONS FOR CAUTION: Although most embryos with reciprocal aneuploid polar bodies were euploid, it is unknown whether they maintain equivalent reproductive potential when transferred. Further study is needed to determine whether these embryos should be re-biopsied and considered for transfer. WIDER IMPLICATIONS OF THE FINDINGS: This study is consistent with increasing evidence that PSSC is the primary cause of meiosis I errors in embryos from women of advanced reproductive age. Clinicians should be cautious in interpreting results from polar body aneuploidy screening, especially when only the first polar body is tested.

PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.

PAX6 is widely expressed in the central nervous system. Heterozygous PAX6 mutations in human aniridia cause defects that would seem to be confined to the eye. Magnetic resonance imaging (MRI) and smell testing reveal the absence or hypoplasia of the anterior commissure and reduced olfaction in a large proportion of aniridia cases, which shows that PAX6 haploinsuffiency causes more widespread human neuro developmental anomalies.

Mapping the contact area of the patellofemoral joint: the relationship between stability and joint congruence.

AIMS: The aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ. PATIENTS AND METHODS: A prospective case-control MRI imaging study of patients with a history of PFJ instability and a control group of volunteers without knee symptoms was performed. The PFJs were imaged with the use of an MRI scan during both passive and active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. In all, 40 patients were studied. The case group included 31 patients with symptomatic patellofemoral instability and the control group of nine asymptomatic volunteers. The ages were well matched between the case and control groups. The mean age was 25 years (16 to 42; sd 6.9) in the case group and 26 years (19 to 32; sd 5.1) in the control group. There were 19 female and 12 male patients in the case group. RESULTS: The unstable PFJs were demonstrably less congruent than the stable PFJs throughout the range of knee movement. The greatest mean differences in congruency between unstable and stable PFJ's were observed between 11° and 20° flexion (1.73 cm2vs 4.00 cm2; p < 0.005). CONCLUSION: The unstable PFJ is less congruent than the stable PFJ throughout the range of knee movement studied. This approach to mapping PFJ congruency produces a measurable outcome and will allow the assessment of pre- and postoperative results following surgical intervention. This may facilitate the design of new procedures for patients with PFJ instability. If a single axial series is to be obtained on MRI scan, the authors recommend 11° to 20° of tibiofemoral flexion, as this was shown to have the greatest difference in contact surface area between the case and control groups. Cite this article: Bone Joint J 2019;101-B:552-558.

Marine spatial planning makes room for offshore aquaculture in crowded coastal waters.

Marine spatial planning (MSP) seeks to reduce conflicts and environmental impacts, and promote sustainable use of marine ecosystems. Existing MSP approaches have successfully determined how to achieve target levels of ocean area for particular uses while minimizing costs and impacts, but they do not provide a framework that derives analytical solutions in order to co-ordinate siting of multiple uses while balancing the effects of planning on each sector in the system. We develop such a framework for guiding offshore aquaculture (bivalve, finfish, and kelp farming) development in relation to existing sectors and environmental concerns (wild-capture fisheries, viewshed quality, benthic pollution, and disease spread) in California, USA. We identify > 250,000 MSP solutions that generate significant seafood supply and billions of dollars in revenue with minimal impacts (often < 1%) on existing sectors and the environment. We filter solutions to identify candidate locations for high-value, low-impact aquaculture development. Finally, we confirm the expectation of substantial value of our framework over conventional planning focused on maximizing individual objectives.

Reproducibility of computer-quantified carotid plaque echogenicity: can we overcome the subjectivity?

BACKGROUND AND PURPOSE: We sought to assess the reproducibility, interobserver variability, and application to clinical studies of a new method for the quantitative assessment of carotid plaque echogenicity. METHODS: Carotid plaques were scanned with the use of ultrasound, and their images were stored in a computer. They were normalized by assigning certain gray values to blood and adventitia, and the gray scale median (GSM) was used to quantify their echogenicity. The variability between storage media, between degrees of magnification, and between probes was assessed. The method was applied to 232 asymptomatic carotid plaques causing 60% to 99% stenosis in relation to the presence of ipsilateral CT-demonstrated brain infarcts. In all parts of the study the plaque GSM was measured before and after normalization to evaluate its effect. Interobserver agreement for the scanning process was assessed. RESULTS: The GSM mean difference before and after normalization for variability studies of storage media, degrees of magnification, and probes was -14.5 and -0.12, 2.24 and 1.68, and -8.3 and -0.7, respectively. The median GSM of plaques associated with ipsilateral nonlacunar silent CT-demonstrated brain infarcts was 14, and that of plaques that were not so associated was 30 (P:=0.003). The interobserver GSM difference was -0.05 (95% CI, -1.7 to 1.6). CONCLUSIONS: Our method decreases the variability between storage media and between probes but not the variability between degrees of magnification. It separates echomorphologically the carotid plaques associated with silent nonlacunar CT-demonstrated brain infarcts from plaques that are not so associated.

The demonstration of gyral abnormalities in patients with cryptogenic partial epilepsy using three-dimensional MRI.

BACKGROUND: Despite the use of high-resolution magnetic resonance imaging (MRI) in the demonstration of structural abnormalities underlying chronic partial epilepsy, a significant proportion of MRI scans in such cases still appear normal when viewed conventionally as two-dimensional images, especially in extratemporal epilepsies. OBJECTIVES: To increase the yield of MRI in patients with extratemporal epilepsies. To examine specific regions of three-dimensional surface renderings of the cerebral hemispheres. DESIGN: Postprocessing of volumetric MRI data was used to detect abnormalities of gyration that may not be seen otherwise. SETTING: Scans were obtained at a hospital clinical imaging facility. PARTICIPANTS: Sixty-four subjects were studied: 33 controls, 15 patients with hippocampal sclerosis (as disease controls), and 16 patients with cryptogenic partial epilepsy that on clinical grounds was extratemporal. MAIN OUTCOME MEASURES: Gyral patterns were evaluated for abnormality by visual comparison between subjects. RESULTS: Inspection of the routine two-dimensional images had failed to demonstrate relevant underlying neocortical abnormality in any of the patients' scans. Three-dimensional reconstruction revealed abnormal gyral patterns in the frontal lobe convexity in seven of the 16 cryptogenic clinically extratemporal cases. Macrogyria was revealed in one case and increased gyral complexity with altered disposition was seen in six cases. Similar gyral patterns were not seen in any subjects from the other groups. CONCLUSION: Three-dimensional analysis of volumetric MRI data can reveal structural abnormality that is not visible when the data are viewed as two-dimensional images only.

Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutation.

BACKGROUND: Three affected individuals are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene. METHODS: Clinical information on the pedigree was collected directly from family members and from hospital records. Samples of DNA were screened by means of direct sequencing of all coding exons of PSEN1. One patient underwent neuropathological examination. RESULTS: Mean age at onset of symptoms was 35.3 years (95% confidence interval [CI], 34.6-36.0 years); at death, 44.0 years (95% CI, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% CI, 4.7-11.9 years). Myoclonus was a late feature in 1 patient; seizures were not reported in any subjects. Spastic paraparesis and extrapyramidal signs were absent. The neuropsychometric profile of 1 patient showed relatively preserved naming skills in the setting of global cognitive deficits. Results of neuropathological examination demonstrated the signature lesions of Alzheimer disease and the presence of occasional cortical Lewy bodies. CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees.

Etiology and early prognosis of newly diagnosed partial seizures in adults: a quantitative hippocampal MRI study.

Sixty-three adult patients with newly diagnosed partial seizures underwent MRI of the brain including hippocampal quantitation. Seventy-six percent of patients had normal MRI findings, 10% had hippocampal sclerosis (HS), and 14% had MRI abnormalities other than HS. Patients with HS had a worse early prognosis than patients with other MRI findings with respect to seizures. The extent of hippocampal damage appeared to be an important mediating factor in frequency of seizures, secondary generalization, and resistance to antiepileptic drug treatment. Because MRI provides prognostic information and can alter management for the individual patient, high-resolution MRI should be performed in all patients with newly diagnosed partial seizures.

Cortical dysplasia with angiodysgenesis and chronic inflammation in multifocal partial epilepsy.

A 25-year-old man with a long history of temporal lobe epilepsy developed right occipital lobe seizures and a progressive right homonymous hemianopia. MRI showed diffuse enhancement of the left temporoparieto-occipital white matter and cortical thickening of the left medial temporal lobe. The resected temporal lobe revealed cortical dysplasia and angiodysplasia with foci of more recent ischemic necrosis and chronic inflammation as an explanation for the clinical deterioration.

Anterior commissure absence without callosal agenesis: a new brain malformation.

The authors report a novel human brain malformation characterized by the absence of the anterior commissure without callosal agenesis, but associated with gross unilateral panhemispheric malformation incorporating subependymal heterotopia, subcortical heterotopia, and gyral abnormalities including temporal malformation and polymicrogyria. In contrast, a normal anterior commissure was found in 125 control subjects and in 113 other subjects with a range of brain malformations.

Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy.

The possible dual occurrence of hippocampal sclerosis (HS) and other structural lesions (especially cortical dysgenesis [CD]) is well established in patients with chronic partial epilepsy. We describe the frequency of additional CD in a series of 100 patients with evidence of HS, using volumetric MRI. Additional, often subtle, CD was present in 15 patients: subependymal heterotopia (six), forme fruste of tuberous sclerosis (two), focal macrogyria (two), focal cortical dysplasia (one), laminar heterotopia (one), bilateral schizencephaly (one), and simplified gyral patterns (two). In contrast, in 46 healthy volunteers, only one had possible CD (p < 0.05). Only 2 of 15 patients had a history of childhood febrile convulsions. HS is a heterogeneous condition; patients being evaluated for temporal lobe surgery should be carefully screened for additional CD using appropriate MR techniques.

Three cases of craniopharyngioma showing optic tract hypersignal on MRI.

Three patients presenting with visual failure had MRIs with hypersignal extending from the region of the optic chiasm along both optic tracts in 2 cases, and along 1 optic tract in the 3rd. In all patients intrinsic tumor of the chiasm was the most likely diagnosis based on MRI appearances, but all 3 had craniopharyngioma.

Disproportion in the distribution of gray and white matter: neuropsychological correlates.

OBJECTIVE: To examine the relationship between measures of disproportion in the regional distribution of gray and white matter and preoperative neuropsychological function in temporal lobe epilepsy patients with proved hippocampal sclerosis (HS). BACKGROUND: Subtle cerebral structural disruption, not evident on routine inspection of high-resolution MRI, is associated with poor surgical outcome in patients with histologically proved HS. Preoperative global memory dysfunction is also associated with poor postoperative seizure control. The authors hypothesize that patients with HS and abnormal regional distributions of gray and white matter would show more diffuse neuropsychological deficits preoperatively than patients with isolated HS alone. METHODS: A total of 28 adults with lateralized temporal lobe epilepsy and hippocampal volume loss measured on MRI were assessed preoperatively on neuropsychological tests of general intellect and the learning and recall of both verbal and nonverbal material. Quantitative MRI analysis of the regional distribution of gray and white matter was performed. Chi-square analyses were used to examine the relation between the presence or absence of cerebral abnormalities and preoperative performance on the neuropsychological tests. RESULTS: A total of 15 of 28 patients had extrahippocampal abnormalities on quantitative MRI analysis. Thirteen patients had global memory impairment. Bilateral memory deficits were significantly associated with both the presence of cerebral abnormalities (p < 0.02) and poor postoperative seizure control (p < 0.05). CONCLUSIONS: Disproportion in the regional distribution of gray and white matter in patients with HS may form the structural basis of global memory disturbance in a distinct group of patients with temporal lobe epilepsy.

The regulation of integrin-linked kinase in human platelets: evidence for involvement in the regulation of integrin alpha 2 beta 1.

BACKGROUND: Activation of the platelet integrin alpha 2 beta 1 is closely regulated due to the high thrombogenicity of its ligand. As a beta 1 interacting kinase, ILK represents a candidate intracellular regulator of alpha 2 beta 1 in human platelets. OBJECTIVES: We investigated the regulation of ILK in human platelets and the role of ILK in regulating alpha 2 beta 1 activation in HEL cells, a megakaryocytic cell line. METHODS: An in-vitro kinase assay was used to determine the effect of platelet agonists on ILK kinase activity together with the contribution of PI3K and PKC on ILK activation. Interaction of ILK with beta 1-integrin subunits was investigated by coimmunoprecipitation and the role of ILK in regulating alpha 2 beta 1 function assessed by overexpression studies in HEL cells. RESULTS: We report that collagen and thrombin modulate ILK kinase activity in human platelets in an aggregation-independent manner. Furthermore, ILK activity is dually regulated by PI3K and PKC in thrombin-stimulated platelets and regulated by PI3K in collagen-stimulated cells. ILK associates with the beta 1-integrin subunits immunoprecipitated from platelet cell lysates, an association which increased upon collagen stimulation. Overexpression of ILK in HEL cells enhanced alpha 2 beta 1-mediated adhesion whereas overexpression of kinase-dead ILK reduced adhesion, indicating a role for this kinase in the positive regulation of alpha 2 beta 1. CONCLUSIONS: Our findings that ILK regulates alpha 2 beta 1 in HEL cells, is activated in platelets and associates with beta 1-integrins, raise the possibility that it may play a key role in adhesion events upon agonist stimulation of platelets.

Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway.

BACKGROUND: The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. OBJECTIVES: In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. METHODS: The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. RESULTS: We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and phospholipase Cgamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. CONCLUSIONS: The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake.

Structure--activity relationships of n-substituted dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene analogues: behavioral effects in lesioned and reserpinized mice.

N,N-Disubstituted dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) analogues were synthesized and tested intraperitoneally in mice for dopamine agonism. Compounds inducing asymmetric postures in unilaterally caudectomized mice were further tested in mice treated with reserpine and alpha-methyl-p-tyrosine methyl ester. ED50 values determined for reversal of reserpine-induced catalepsy were used to rank drug potency and correlated with molecular structure. N-n-Propyl N-substituted compounds were more effective than other N,N-dialkyl homologues. Of these, analogues with one alkyl group larger than propyl became inactive or their dopaminomimetic effect was reduced when the propyl was replaced with a larger group. N-Monosubstituted analogues were inactive as dopamine agonists. N-n-P-r-N-n-Bu-6,7-ADTN was six times more potent than N-n-propyl-N-n-pentyl- and N-n-propyl-N-phenethyldopamine but ten times less potent than apomorphine. The availability of an array of structurally related dopamine analogues with dopaminomimetic properties may make it possible to test the hypothesis that there are more than one type of dopamine receptor and that stereotypy and locomotor activity may have different central nervous system loci. Moreover, they may be of potential use in the treatment of parkinsonism and other extrapyramidal disorders.