Structures of Get3d reveal a distinct architecture associated with the emergence of photosynthesis.

Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.

Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.

AIM: This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. METHODS: In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention. RESULTS: By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. CONCLUSIONS: In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced ß-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.

Enhanced critical current density in optimized high-temperature superconducting bilayer thin films.

The superconducting and structural properties of bilayer thin films based on YBa2Cu3O7-x / YBa2Cu3O7-x+6%BaZrO3heterstructures have been studied. In a broad range of magnetic field strengths and temperatures, the optimal bilayer film comprises 30% YBCO at the substrate interface and 70% YBCO+6%BZO on the top. The critical current density measured for the optimal bilayer structure is shown to outperform the corresponding single layer films up to almost 60%. The obtained results are comprehensively discussed in the light of our previously published theoretical framework (Rivastoet al2023J. Phys.: Condens. Matter35075701:1-10). We conclude that the bilayering provides an efficient and easily applicable way to further increase the performance and applicability of high-temperature superconductors in various applications. Consequently, the bilayer films should be seriously considered as candidates for the upcoming generation of coated conductors.

Defining optimal thickness for maximal self-fieldJcin YBCO/CeO2multilayers grown on buffered metal.

The effect of multilayering YBa2Cu3O6+x(YBCO) thin films with sequentially deposited CeO2layers between YBCO layers grown on buffered metallic template is investigated to optimize the self-field critical current densityJc(0). We have obtained that the improvement inJc(0)clearly depends on the YBCO layer thickness and temperature, where at high temperatureJc(0)can be increased even 50% when compared with the single layer YBCO films. Based on our experimental results and theoretical approach to the growth mechanism during multilayer deposition, we have defined a critical thickness for the YBCO layer, where the maximal self-fieldJc(0)is strongly related to the competing issues between the uniform and nonuniform strain relaxation and the formation of dislocations and other defects during the film growth. Our results can be directly utilized in the future coated conductor technology, when maximizing the overall in-fieldJc(B)by combining both the optimal crystalline quality and flux pinning properties typically in bilayer film structures.

Jejunal diverticulosis: case report of a rare cause of mechanical intestinal obstruction.

Jejunal diverticulosis is a rare condition and usually discovered incidentally at laparotomy for an unrelated pathology. When inflamed or perforated, jejunal diverticulosis may present with paralytic ileus. In contrast, mechanical bowel obstruction is an unusual presentation. This paper reports the first local case of jejunal diverticulosis presenting with mechanical bowel obstruction due to impaction at the terminal ileum by an enterolith originating from a diverticulum, and reviews the recent literature on the subject.

Ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after bilateral vagotomy.

This study describes the ultrastructural changes in the sinu-atrial (SA) and atrio-ventricular (AV) nodes of the monkey (Macaca fascicularis) after bilateral mid-cervical vagotomy at 1, 3, 5, 7 and 14 days post-operations. The changes were similar in both types of nodal cells. The most obvious feature of the degenerating nodal cells was the swollen mitochondria with disrupted cristae. Other changes include increased granular sarcoplasmic reticulum, increased glycogen particles, vacuolation of mitochondria and increased lysosomal activity. Axonal profiles in the vicinity of the nodal cells showed swelling and vacuolation. Cardiac neurons also showed some changes such as distended granular endoplasmic reticulum, increased accumulation of glycogen particles and increased lipofuscin granules. Macrophages and Schwann cells were the main scavengers in removing the degenerated nodal cells and axonal profiles. In the case of affected cardiac neurons, satellite cells seemed to act as main scavenger cells. It is postulated that the nodal cells are dependent on the incoming fibres of the vagus nerve for their survival. By an understanding of the ultrastructural changes in the nodal cells after bilateral vagotomy, it may help in developing new strategies to explore in depth of the conducting system of the heart.

Ultrastructural study of the effects of 6-hydroxydopamine on the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis).

The present study examined the ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after 6-hydroxydopamine (6-OHDA) at survival times of 1, 3, 5, 7 and 14 days. Changes ranged from dissolution of the cytoplasm to amorphous appearance and darkening of the nodal cells. Initially, the ultrastructural changes were quite similar in both sinuatrial (SA) and atrioventricular (AV) nodal cells but in the later stage, especially at fourteen days, affected SA nodal cells showed empty-looking appearance while affected AV nodal cells displayed a darkened appearance. The cardiac neurons also showed ultrastructural changes such as diffuse accumulation of glycogen particles, distended cisternae of the rough endoplasmic reticulum and increased lipofuscin granules. Some of the vacuolated axonal profiles containing large dense-cored vesicles were in close association with the somata of the cardiac neurons. There were also changes in the non-neuronal cells such as darkening and vacuolation of the cells capping the neurons. Macrophages and Schwann cells were activated to engulf the degenerating nodal cells and axonal profiles. The ultrastructural changes in the nodal cells and the cardiac neurons reflect a disturbance in the cell metabolism presumably brought about by the impairment of the sympathetic nervous system.

Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system.

Although brain lesions have been described in some cases with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the nature of brain lesion and its relation to the spinal cord lesion. In the present study, we performed histopathological analysis of the brain and the spinal cord of four autopsied cases with HAM/TSP to clarify the relationship between the brain and the spinal cord lesions. In two cases with active-chronic inflammation in the spinal cord, perivascular inflammatory infiltration was also seen in the brain, and the composition of cell subsets was similar both in the spinal cord and in the brain. No active inflammatory change was seen in the brain in two cases with inactive-chronic spinal cord lesions. Inflamed vessels were distributed mainly in the deep white matter and in the area between cerebral cortex and white matter of the brain. In the spinal cord inflamed vessels were mainly seen in the bilateral lateral and the ventral posterior columns. Parenchymal infiltration was diffused in the spinal cord but very sparse in the brain, suggesting the importance of parenchymal infiltration in the destruction of tissues. These results suggest that inflammatory changes occurred simultaneously in the spinal cord and in the brain, and that distribution of inflamed vessels closely correlated with the characteristics of vascular architecture of the brain and the spinal cord, which lead to a slow blood flow. This study may help promote a better understanding of the pathogenesis of HAM/TSP.

Histopathological and ultrastructural features of feline hereditary cerebellar cortical atrophy: a novel animal model of human spinocerebellar degeneration.

Human spinocerebellar degeneration is one of the intractable diseases. We studied the detailed neuropathology of cats with hereditary cerebellar degeneration obtained from the experimental breeding. The findings included almost total loss of Purkinje cells with an increase in Bergmann's glia in the cerebellar hemisphere, preservation of some Purkinje cells in the vermis and moderate neuronal depletion of the olive nucleus. Cerebellar and pontine nuclei were normal. The cerebrum and spinal cord as well as the peripheral nervous system appeared normal. Electron microscopic examination revealed swelling of the distal dendrites of Purkinje cells in the less-affected nodule of the vermis, and clusters of presynaptic boutons without any synaptic contact in the severely affected folia where Purkinje cell bodies and dendrites disappeared. Prolonged existence of presynapses in the molecular and Purkinje cell layers was confirmed by positive immunoreactivity to anti-synaptophysin. Quantitative analysis using electron microscopy demonstrated an apparent increase in the density and mean size of presynapses in the molecular layer of the severely affected folia. These findings indicate that degeneration of Purkinje cells started at the most distal part of the dendrite in this animal model of cerebellar degeneration, and that presynapses, axon terminals of the granular cells and basket cells can exist for a long time even after complete degeneration of the Purkinje cells. Further investigation of this novel animal model may promote a better understanding of pathogenesis of human hereditary cerebellar degeneration.