Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
Aim
After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension‐free anastomosis. Total ...colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans‐mesenteric colorectal anastomosis or inverted right colonic transposition (the so‐called Deloyers procedure) are two possible solutions for creating a tension‐free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans‐mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients.
Method
This was retrospective chart review of laparoscopic colorectal surgery with trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques.
Results
Thirteen consecutive patients underwent either a laparoscopic trans‐mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra‐operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra‐abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2–5).
Conclusions
Trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well‐established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures.
Neuromyelitis optica is an autoimmune inflammatory disorder of the central nervous system that preferentially targets the spinal cord and optic nerve. Following the discovery of circulating ...antibodies against the astrocytic aquaporin 4 (AQP4) water channel protein, recent studies have expanded our knowledge of the unique complexities of the pathogenesis of neuromyelitis optica and its relationship with the immune response. This review describes and summarizes the recent advances in our understanding of the molecular mechanisms underlying neuromyelitis optica disease pathology and examines their potential as therapeutic targets. Additionally, we update the most recent research by proposing major unanswered questions regarding how peripheral AQP4 antibodies are produced and their entry into the central nervous system, the causes of AQP4‐IgG‐seronegative disease, why peripheral AQP4‐expressing organs are spared from damage, and the impact of this disease on pregnancy.
Axillary lymph node (LN) metastasis is the most important predictor of overall recurrence and survival in patients with breast cancer, and accurate assessment of axillary LN involvement is an ...essential component in staging breast cancer. Axillary management in patients with breast cancer has become much less invasive and individualized with the introduction of sentinel LN biopsy (SLNB). Emerging evidence indicates that axillary LN dissection may be avoided in selected patients with node-positive as well as node-negative cancer. Thus, assessment of nodal disease burden to guide multidisciplinary treatment decision making is now considered to be a critical role of axillary imaging and can be achieved with axillary US, MRI, and US-guided biopsy. For the node-positive patients treated with neoadjuvant chemotherapy, restaging of the axilla with US and MRI and targeted axillary dissection in addition to SLNB is highly recommended to minimize the false-negative rate of SLNB. Efforts continue to develop prediction models that incorporate imaging features to predict nodal disease burden and to select proper candidates for SLNB. As methods of axillary nodal evaluation evolve, breast radiologists and surgeons must work closely to maximize the potential role of imaging and to provide the most optimized treatment for patients.
The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We ...show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato (Solanum lycopersicum) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea, MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes.
The material class of rare earth nickelates with high Ni3+ oxidation state is generating continued interest due to the occurrence of a metal-insulator transition with charge order and the appearance ...of non-collinear magnetic phases within this insulating regime. The recent theoretical prediction for superconductivity in LaNiO3 thin films has also triggered intensive research efforts. LaNiO3 seems to be the only rare earth nickelate that stays metallic and paramagnetic down to lowest temperatures. So far, centimeter-sized impurity-free single crystal growth has not been reported for the rare earth nickelates material class since elevated oxygen pressures are required for their synthesis. Here, we report on the successful growth of centimeter-sized LaNiO3 single crystals by the floating zone technique at oxygen pressures of up to 150 bar. Our crystals are essentially free from Ni2+ impurities and exhibit metallic properties together with an unexpected but clear antiferromagnetic transition.
Functional synapses require mitochondria to supply ATP and regulate local Ca2+i for neurotransmission. Mitochondria are thought to be transported to specific cellular regions of increased need such ...as synapses. However, little is known about how this occurs, including the spatiotemporal distribution of mitochondria relative to presynaptic and postsynaptic sites, whether mitochondria are dynamically recruited to synapses, and how synaptic activity affects these trafficking patterns. We used primary cortical neurons in culture that form synaptic connections and show spontaneous synaptic activity under normal conditions. Neurons were cotransfected with a mitochondrially targeted cyan fluorescent protein and an enhanced yellow fluorescent protein-tagged synaptophysin or postsynaptic density-95 plasmid to label presynaptic or postsynaptic structures, respectively. Fluorescence microscopy revealed longer dendritic mitochondria that occupied a greater fraction of neuronal process length than axonal mitochondria. Mitochondria were significantly more likely to be localized at synaptic sites. Although this localization was unchanged by inhibition of synaptic activity by tetrodotoxin, it increased in dendritic synapses and decreased in axonal synapses during overactivity by veratridine. Mitochondrial movement and recruitment to synapses also differed between axons and dendrites under basal conditions and when synaptic activity was altered. Additionally, we show that movement of dendritic mitochondria can be selectively impaired by glutamate and zinc. We conclude that mitochondrial trafficking to synapses is dynamic in neurons and is modulated by changes in synaptic activity. Furthermore, mitochondrial morphology and distribution may be optimized differentially to best serve the synaptic distributions in axons and dendrites. Last, selective cessation of mitochondrial movement in dendrites suggests early postsynaptic dysfunction in neuronal injury and degeneration.
Saliva is a useful biofluid for the early detection of disease, but how distal tumors communicate with the oral cavity and create disease-specific salivary biomarkers remains unclear. Using an in ...vitro breast cancer model, we demonstrated that breast cancer-derived exosome-like microvesicles are capable of interacting with salivary gland cells, altering the composition of their secreted exosome-like microvesicles. We found that the salivary gland cells secreted exosome-like microvesicles encapsulating both protein and mRNA. We also showed that the interaction with breast cancer-derived exosome-like microvesicles communicated and activated the transcriptional machinery of the salivary gland cells. Thus, the interaction altered the composition of the salivary gland cell-derived exosome-like microvesicles on both the transcriptomically and proteomically.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. ...First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs).
Introduction
The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures.
Methods
Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis.
Results
The search yielded 19 observational studies (
n
= 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45–1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11–1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43–2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95–1.83).
Conclusions
FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.
Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would ...attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD + quercetin (HF + Q), or HFD + RO (HF + RO) for 9 weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF + Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF + Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin—but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.