Altermagnetic lifting of Kramers spin degeneracy.

Lifted Kramers spin degeneracy (LKSD) has been among the central topics of condensed-matter physics since the dawn of the band theory of solids1,2. It underpins established practical applications as well as current frontier research, ranging from magnetic-memory technology3-7 to topological quantum matter8-14. Traditionally, LKSD has been considered to originate from two possible internal symmetry-breaking mechanisms. The first refers to time-reversal symmetry breaking by magnetization of ferromagnets and tends to be strong because of the non-relativistic exchange origin15. The second applies to crystals with broken inversion symmetry and tends to be comparatively weaker, as it originates from the relativistic spin-orbit coupling (SOC)16-19. A recent theory work based on spin-symmetry classification has identified an unconventional magnetic phase, dubbed altermagnetic20,21, that allows for LKSD without net magnetization and inversion-symmetry breaking. Here we provide the confirmation using photoemission spectroscopy and ab initio calculations. We identify two distinct unconventional mechanisms of LKSD generated by the altermagnetic phase of centrosymmetric MnTe with vanishing net magnetization20-23. Our observation of the altermagnetic LKSD can have broad consequences in magnetism. It motivates exploration and exploitation of the unconventional nature of this magnetic phase in an extended family of materials, ranging from insulators and semiconductors to metals and superconductors20,21, that have been either identified recently or perceived for many decades as conventional antiferromagnets21,24,25.

Spin-valve-like magnetoresistance in Mn2NiGa at room temperature.

Spin valves have revolutionized the field of magnetic recording and memory devices. Spin valves are generally realized in thin film heterostructures, where two ferromagnetic (FM) layers are separated by a nonmagnetic conducting layer. Here, we demonstrate spin-valve-like magnetoresistance at room temperature in a bulk ferrimagnetic material that exhibits a magnetic shape memory effect. The origin of this unexpected behavior in Mn(2)NiGa has been investigated by neutron diffraction, magnetization, and ab initio theoretical calculations. The refinement of the neutron diffraction pattern shows the presence of antisite disorder where about 13% of the Ga sites are occupied by Mn atoms. On the basis of the magnetic structure obtained from neutron diffraction and theoretical calculations, we establish that these antisite defects cause the formation of FM nanoclusters with parallel alignment of Mn spin moments in a Mn(2)NiGa bulk lattice that has antiparallel Mn spin moments. The direction of the Mn moments in the soft FM cluster reverses with the external magnetic field. This causes a rotation or tilt in the antiparallel Mn moments at the cluster-lattice interface resulting in the observed asymmetry in magnetoresistance.

Néel Vector Induced Manipulation of Valence States in the Collinear Antiferromagnet Mn2Au.

The coupling of real and momentum space is utilized to tailor electronic properties of the collinear metallic antiferromagnet Mn2Au by aligning the real space Néel vector indicating the direction of the staggered magnetization. Pulsed magnetic fields of 60 T were used to orient the sublattice magnetizations of capped epitaxial Mn2Au(001) thin films perpendicular to the applied field direction by a spin-flop transition. The electronic structure and its corresponding changes were investigated by angular-resolved photoemission spectroscopy with photon energies in the vacuum-ultraviolet, soft, and hard X-ray range. The results reveal an energetic rearrangement of conduction electrons propagating perpendicular to the Néel vector. They confirm previous predictions on the origin of the Néel spin-orbit torque and anisotropic magnetoresistance in Mn2Au and reflect the combined antiferromagnetic and spin-orbit interaction in this compound leading to inversion symmetry breaking.

Fetal congenital anomalies diagnosed by ultrasound in Asian and non-Asian women.

The incidence of congenital heart defects in Asian children is significantly higher than in non-Asian, however little data are available for other anomalies. The Fetal Management Unit at St Mary's Hospital is a tertiary referral centre for prenatal diagnosis in the north-west region. Using data collected after routine prenatal ultrasonography between 1996-2001, we show that in a defined population there was a significant reduction in the incidence of central nervous system (CNS) anomalies over this period but not in other anomalies. Furthermore, fetal congenital anomalies were diagnosed in a higher proportion of Asian than non-Asian women, with CNS, cardiac, bowel, thoracic and facial anomalies and hydrops being statistically significant. Monitoring local trends in a multiethnic community is essential for appropriate counselling, providing parents with an informed choice and in assessing the effectiveness of interventions.

Altered activity of the system A amino acid transporter in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women.

Fetal macrosomia (FM) is a well-recognized complication of diabetic pregnancy but it is not known whether placental transport mechanisms are altered. We therefore studied the activity of the system A amino acid transporter, the system L amino acid transporter, and the Na+/H+ exchanger in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women (FM group), from placentas of appropriately grown babies born to diabetic women (appropriate for gestational age group) and from placentas of appropriately grown babies of normal women (control group). Sodium-dependent uptake of [14C]-methylaminoisobutyric acid at 30 s (initial rate, a measure of system A activity) was 49% lower into FM vesicles than into control vesicles (P < 0.02); this effect was due to a decrease in Vmax of the transporter with no change in Km. There was no significant difference in system A activity between the appropriate for gestational age group and control or FM group. There was also no difference between system L transporter or Na+/H+ exchanger activity between the three groups. We conclude that the number of system A transporters per milligram of membrane protein in the placental microvillous membrane is selectively reduced in diabetic pregnancies associated with FM.

Isolated parenchymal lesions on cranial ultrasound in very preterm infants in the context of maternal infection.

AIM: To explore the associations between a clinical diagnosis of maternal infection (CDMI) and findings on the initial cranial ultrasound scan in very preterm infants. METHODS: Among infants born at less than 32 weeks gestation, cases of CDMI and controls were identified on the basis of routinely available obstetric data. Neonatal cranial ultrasound scans carried out soon after birth were retrospectively reviewed for evidence of parenchymal echodensity (PED), intraventricular haemorrhage (IVH) or PED contiguous with IVH. RESULTS: Any PED was identified in 20/40 (50%) cases of CDMI and 9/30 (30%) of controls. Logistic regression was used to adjust for differences between the two study groups. When compared with normal scans, isolated PED was more likely with CDMI odds ratio, OR (95% confidence interval, CI), 41.8 (2.64, 662) and lower Apgar score at 5 min 2.89 (1.05, 7.98). IVH was more likely with lower gestational age, OR for each completed week of gestation 0.64 (0.46, 0.88) and a protective effect of female sex, OR 0.25 (0.063, 0.98), PED contiguous with IVH was more likely with lower gestational age OR 0.59 (0.336, 1.04). CONCLUSIONS: CDMI may be associated with isolated PED in very preterm infants. We speculate that isolated PED (including "flares") identify infants who have sustained early brain injury because of intrauterine infection. Isolated PED may be a useful intermediate outcome in perinatal cohort studies.

Robust Bain distortion in the premartensite phase of a platinum-substituted Ni2MnGa magnetic shape memory alloy.

The premartensite phase of shape memory and magnetic shape memory alloys (MSMAs) is believed to be a precursor state of the martensite phase with preserved austenite phase symmetry. The thermodynamic stability of the premartensite phase and its relation to the martensitic phase is still an unresolved issue, even though it is critical to the understanding of the functional properties of MSMAs. We present here unambiguous evidence for macroscopic symmetry breaking leading to robust Bain distortion in the premartensite phase of 10% Pt-substituted Ni2MnGa. We show that the robust Bain-distorted premartensite (T2) phase results from another premartensite (T1) phase with preserved cubic-like symmetry through an isostructural phase transition. The T2 phase finally transforms to the martensite phase with additional Bain distortion on further cooling. Our results demonstrate that the premartensite phase should not be considered as a precursor state with the preserved symmetry of the cubic austenite phase.

Room-temperature tetragonal non-collinear Heusler antiferromagnet Pt2MnGa.

Antiferromagnetic spintronics is a rapidly growing field, which actively introduces new principles of magnetic storage. Despite that, most applications have been suggested for collinear antiferromagnets. In this study, we consider an alternative mechanism based on long-range helical order, which allows for direct manipulation of the helicity vector. As the helicity of long-range homogeneous spirals is typically fixed by the Dzyaloshinskii-Moriya interactions, bi-stable spirals (left- and right-handed) are rare. Here, we report a non-collinear room-temperature antiferromagnet in the tetragonal Heusler group. Neutron diffraction reveals a long-period helix propagating along its tetragonal axis. Ab-initio analysis suggests its pure exchange origin and explains its helical character resulting from a large basal plane magnetocrystalline anisotropy. The actual energy barrier between the left- and right-handed spirals is relatively small and might be easily overcome by magnetic pulse, suggesting Pt2MnGa as a potential candidate for non-volatile magnetic memory.

Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells.

We investigated the expression and activity of arginine transporters and endothelial nitric oxide synthase (eNOS) in human placental microvascular endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1, CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light chain dimers were indicated by a shift in molecular mass detected under nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine. The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic analysis supported a two-transporter model attributed to system y+L and system y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h, either as the basal production of nitric oxide (NO) or as the accumulation of intracellular cGMP was not detectable. We conclude that HPMEC transport cationic amino acids by systems y+ and y+L and that basal eNOS expression and activity in these cells is low.

L-arginine transport by the microvillous plasma membrane of the syncytiotrophoblast from human placenta in relation to nitric oxide production: effects of gestation, preeclampsia, and intrauterine growth restriction.

Nitric oxide (NO) is an important regulator of placental perfusion, and its production is dependent on the activity of substrate (L-arginine) transporters. In the light of evidence for altered NO production in the feto-placental unit in preeclampsia and intrauterine growth restriction (IUGR), we investigated gestational changes in human placental L-arginine transport by systems y(+) and y(+)L in purified microvillous plasma membrane vesicles. We also examined the effect of preeclampsia and IUGR on the activity of these transport systems and the relationship between transporter activity and NO production (nitrate/nitrite concentrations) in the feto-placental unit. Between first trimester and term, there was a significant positive correlation between system y(+) activity and gestational age (r = 0.36; P = 0.013; n = 47), but a significant negative correlation between system y(+)L activity and gestational age (r = -0.6; P < 0.0001; n = 47). The activity of these transport systems was not altered in preeclampsia or IUGR. In placentas from normal term pregnancies, there was no correlation between the activity of microvillous plasma membrane L-arginine transporters and nitrate/nitrite concentrations in umbilical venous plasma or placental homogenate.

L-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and preeclamptic pregnancies.

Cord blood levels of nitrate/nitrite, as a measure of nitric oxide (NO), are generally increased in preeclampsia. As L-arginine is the precursor for NO synthesis, we hypothesized that L-arginine transport across the syncytiotrophoblast basal plasma membrane (BM) of placentas from preeclamptic patients is also increased. Glutamine-sensitive and -insensitive [(3)H]L-arginine uptakes into BM vesicles were measured and expressed as femtomoles per milligram of protein per minute. Total L-arginine uptake was 418 +/- 15 (mean +/- SEM; n = 9) in BM from control placentas (CBM) and 495 +/- 27 (n = 7) in BM from preeclamptic placentas (PE BM; P < 0.05, by two-tailed t test). Glutamine insensitive (system y(+)) uptake was 45 +/- 3 (n = 6) in CBM, with a significantly higher uptake of 97 +/- 23 (n = 5) into PE BM (P < 0.05, by two-tailed t test). There was no significant difference in glutamine-sensitive uptake between the two groups. The expression of mRNA for human cationic amino acid transporter (hCAT) 1, 2, and 4 (system y(+) genes) and 4F2hc (heavy chain of system y(+)L) was not different in homogenates of whole placenta from the two groups. Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM. These data suggest increased activity of the BM system y(+) cationic amino acid transporter in preeclampsia. If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS.

Postnatal changes in N-methyl-D-aspartate receptor binding and stimulation by glutamate and glycine of [3H]-MK-801 binding in human temporal cortex.

1. Homogenates of human infant and adult temporal cortex were used to measure [3H]-TCP and [3H]-MK-801 binding to the N-methyl-D-aspartate (NMDA)-coupled ion channel phencyclidine site. 2. Both [3H]-TCP and [3H]-MK-801 binding increased in infant cortex by > 100% between term and 26 weeks suggesting that the numbers of NMDA receptors increase during postnatal brain development. 3. [3H]-MK-801 binding was measured under non-equilibrium conditions in temporal cortex homogenates with the addition of 100 microM of L-glutamate plus a range of concentrations (0.05 microM-100 microM) of glycine. Glutamate and glycine increased [3H]-MK-801 binding by stimulating NMDA receptors and improving [3H]-MK-801 access to ion channel binding sites; maximum stimulation in adult and infant temporal cortex was achieved with 100 microM glutamate plus 5 microM glycine; a higher concentration of glycine (50 microM) reduced [3H]-MK-801 binding to below maximum. 4. The stimulation by 100 microM glutamate plus 5 microM glycine of [3H]-MK-801 binding in infant temporal cortex was affected by postnatal age. For example, although the stimulation of [3H]-MK-801 binding in 5-6 week infant cortex (236% of basal) was similar to adult cortex (230% of basal), in samples taken from infants aged 5-6 months glycine (plus glutamate) stimulation of [3H]-MK-801 binding (392% of basal) was substantially greater than that measured in adult temporal cortex. 5. The binding of [3H]-glycine to the glycine modulatory site associated with the NMDA receptor in infant cortex also increased with postnatal age by > 100% between term and 26 weeks. 6. It is concluded that NMDA receptors in infant cortex increase to levels greater than those in adult cortex during postnatal development. The results do not exclude the possibility that the transiently increased NMDA receptor-ion channel complex in infant cortex shows enhanced responses to agonists and modulators.

Epidermal growth factor receptors in rat placenta, amnion and yolk sac: characteristics of specific binding are dependent on gestational age.

Studies of [125I]-EGF binding to the rat placenta, amnion and yolk sac were carried out on days 14, 17 and 20 of gestation. In the placenta EGF binding was detectable on all 3 days; in the amnion EGF binding was undetectably low on day 14 but was present on days 17 and 20, while in the yolk sac EGF binding was undetectably low on all 3 days. Although Scatchard analysis of EGF binding to placental tissue raised the possibility of high and low affinity receptors, a statistical analysis of the ligand binding data was consistent with the presence of only one type of EGF receptor. The overall affinity of the receptors did not change with stage of gestation. However, the concentration of EGF receptors was lower in placental tissue on day 17 than on days 14 or 20 of gestation; the receptor concentrations were similar on days 14 and 20. It is suggested that EGF binding to the placenta, amnion, and yolk sac may reflect the levels of cell proliferation in those tissues in the latter part of gestation.

Fetal and maternal blood volumes in shed human placentae: discrepant results comparing morphometry to haemoglobin content.

The maternal blood volume (MBV) and fetal blood volume (FBV) of shed human placentae delivered by caesarean section at term were measured using a morphometric technique and from the placental content of adult and fetal haemoglobin. MBV was 35.3 +/- 1.5 (s.e.m.) per cent by the former and 11.0 +/- 1.5 per cent by the latter technique. FBV was 11.0 +/- 0.7 and 9.0 +/- 0.6 per cent respectively (n = 6). Measurement of the dimensions of individual villi initially photomicrographed in 0.9 per cent NaCl and subsequently re-photographed in fixative suggested that individual villi shrank to 0.7 of their initial volume during fixation. It is suggested that morphometric measurement of MBV may lead to approximately a threefold overestimate because of relative MBV expansion and villous tissue shrinkage during the process of fixation without alteration in overall placental volume.

Placental water content and distribution.

The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations.

Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta.

We investigated the polarization of l-lactate transport in human syncytiotrophoblast by measuring uptake of [(14)C] l-lactate by both microvillous (maternal-facing; MVM) and basal (fetal-facing; BM) plasma membranes. [(14)C] l-lactate uptake by MVM and BM was stimulated in the presence of an inwardly directed H(+)gradient, with a significantly higher uptake in MVM than in BM at initial rate (15.4+/-2.3 vs 5.6+/-0.6 pmol/mg protein/20 sec). Stereospecific inhibition was observed in MVM, with a higher affinity for l-lactate compared with d-lactate. In BM, there was no difference in the inhibition by these two stereoisomers. Inhibition of lactate uptake in both MVM and BM by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of monocarboxylate transporter (MCT) activity, indicated MCT-mediated mechanisms across both membranes. Kinetic modelling supported a two-transporter model as the best fit for both MVM and BM, the K(m)of the major component being 6.21 mm and 25.01 mm in MVM and BM respectively. Western blotting and immunolocalization examining the distribution of MCT1 and MCT4, showed that MCT expression was polarized, MCT1 being predominantly localized to BM and MCT4 showing greater abundance on MVM. CD147, a chaperone protein for MCT1 and MCT4, was equally expressed by both membranes. These studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both MCT activity and expression.

Monoclonal antibodies to CD18 and CD11A (LFA-1) distinguish Down's syndrome (trisomy 21) from normal lymphoblastoid cells.

To evaluate the potential of using fluorescence flow cytometry (FFC) in the diagnosis of Down's syndrome we analysed a series of Trisomy 21 lymphoid cell-lines (LCL) with a panel of monoclonal antibodies (MoAb) to the CD11a and CD18 subunits of lymphocyte function associated antigen 1 (LFA-1). In pairwise analysis of Trisomy 21 (T21) and normal LCL with 6 CD18 and 10 CD11a MoAb we found that T21 LCL could be distinguished from normal LCL with both types of MoAb, even though only the CD18 gene is duplicated in Down's syndrome. Experiments in which CD18 or CD11a were capped showed that the two subunits co-migrate on T21 and normal LCL, probably as heterodimers. This appears to explain the increased expression of CD11a on Trisomy 21 LCL. There was no evidence that T21 LCL express the other two leucocyte integrin subunits CD11b and CD11c, indicating that Trisomy 21 has little affect on tissue specific control of these molecules. In contrast, there appears to be reduced expression of an unrelated adhesion molecule LFA-3 on Trisomy 21 LCL. We discuss the relevance of these results in the diagnosis of Down's syndrome.

Age-related changes in binding to excitatory amino acid uptake sites in human cerebellum.

In vitro autoradiography and test-tube assay of the sodium-dependent binding of D-[3H]aspartate were used to localize and quantify the uptake site for the excitatory amino acid neurotransmitters glutamate and aspartate in the cerebellar cortex of human cerebellar hemispheres. Autoradiograms revealed a pronounced heterogeneity in the distribution of D-[3H]aspartate binding in cortex from adult brains, with the highest binding density corresponding to the Purkinje cell layer, high binding in molecular layer and low binding in granule cell layer. In contrast, cerebellar cortex from infants at term (40 weeks gestation) had only low binding of the ligand in both the molecular and the Purkinje cell layers. Both methods employed for measuring D-[3H]aspartate binding showed that the number of binding sites in Purkinje and molecular layers increased rapidly from term to 20 weeks postnatal age and achieved levels higher than those found in adult cerebellum. It is concluded that a substantial increase in the numbers of glutamate/aspartate uptake sites takes place in the human cerebellum during the early postnatal period. It is deduced that the excess uptake sites are eliminated as the cerebellum matures.

A polyamine binding site labelled with [3H]spermidine in developing human cerebellum.

Polyamines regulate cell division in developing brain. Neuronal membranes and the NMDA receptor have polyamine binding or functional sites. We have visualized [3H]spermidine binding in human cerebellum sections. Autoradiographs showed high specific [3H]spermidine binding in granule cell layer and low binding in molecular layer in neonate, infant and adult cerebellum which qualitatively resembled NMDA binding. Cerebellum from neonates and infants below 6 months had a further zone of dense [3H]spermidine binding in the external granule layer of migratory cells. This second zone may show a polyamine regulatory site for cerebellar development from fetal life to early infancy.

Age-related changes in binding to excitatory amino acid uptake site in temporal cortex of human brain.

The binding of D-[3H]aspartate to the specific uptake site for the excitatory amino acids glutamate and aspartate was measured in homogenates of temporal lobe cortex taken at postmortem from 76 human infant and adult brains. Binding levels were very low in brains of preterm and term infants but increased rapidly during the first 20 postnatal weeks to reach levels which exceeded those in adult brains. Linear regression analysis which compared the amount of D-[3H]aspartate binding with the age of the infant, showed a positive correlation up to 25 postnatal weeks. Saturation analysis showed that the maximum number of D-[3H]aspartate binding sites (Bmax) in temporal cortex from infants aged 20 postnatal weeks was 3 times greater than the number of sites in adult brain. The findings show that the number of excitatory amino acid uptake sites, which may be associated in part with presynaptic terminals, increase in number rapidly after birth. Furthermore, the data may indicate that a slow regression of excitatory amino acid terminals occurs during the later stages of brain development.