Crystal Structures of the ATPase Domains of Four Human Hsp70 Isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78

The 70-kDa heat shock proteins (Hsp70) are chaperones with central roles in processes that involve polypeptide remodeling events. Hsp70 proteins consist of two major functional domains: an N-terminal nucleotide binding domain (NBD) with ATPase activity, and a C-terminal substrate binding domain (SBD). We present the first crystal structures of four human Hsp70 isoforms, those of the NBDs of HSPA1L, HSPA2, HSPA5 and HSPA6. As previously with Hsp70 family members, all four proteins crystallized in a closed cleft conformation, although a slight cleft opening through rotation of subdomain IIB was observed for the HSPA5-ADP complex. The structures presented here support the view that the NBDs of human Hsp70 function by conserved mechanisms and contribute little to isoform specificity, which instead is brought about by the SBDs and by accessory proteins.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

The use of dual-tracer PET/CT in selection of HCC patients based on Milan criteria before liver transplant

General Clinical Specialties: GastroenterologyObjectives: Selection of HCC patients for liver transplant (LT) is crucial for prognosis and survival. The conventional tool for assessment is contrast CT but its accuracy is suboptimal for detection of early HCC in cirrhotic livers and for metastatic survey. We evaluated the accuracy of dual-tracer (11C-acetate: ACT and 18F-FDG: FDG) PET/CT in selecting candidates for LT based on Milan criteria. Methods: HCC patients status post LT or partial hepatectomy (HCC lesion<7 cm) with both preoperative dual-tracer PET/CT and contrast CT within 1 month were recruited into this study. Dual-tracer PET/CT and contrast CT were reviewed independently based on the parameters specified by Milan criteria: HCC lesion size and number, presence/absence of vascular invasion and extrahepatic metastasis, with postoperative pathology as the gold standard. Statistical analysis was performed using Chi-square test. Results: Forty three HCC patients (M: 34, F: 9, mean: 57±10.1 years) were included. Postoperative pathology confirmed 31 patients satisfying and 12 not satisfying Milan criteria. ACT (29/31: 93.5%) and dual-tracer (30/31: 96.8%) PET/CT were significantly more accurate in patient selection for LT than FDG (8/31: 25.8%) or contrast CT (13/31: 41.9%; all p<0.05). ACT (11/12: 91.7%) and dual-tracer (11/12: 91.7%) PET/CT were also more concordant with pathology in patient exclusion for LT than FDG (6/12: 50.0%) or contrast CT (4/12: 33.3%; all p<0.05). The discordance between contrast CT and pathology was due to: false negative diagnosis (n=17), HCC lesion size (n=6) and number (n=1), and overstaging by false positive diagnosis of vascular (n=2) and extrahepatic metastases (n=2). The discordance between dual-tracer PET/CT and pathology was found in 2 false negative cases with post-treatment necrosis. Conclusions: Dual-tracer PET/CT is significantly more accurate in preoperative assessment and selection of HCC patients for LT. Implementation of this imaging for transplant work-up may be considere

Dual-tracer PET/CT for the differential diagnosis of small liver nodules (1-2 cm) in cirrhosis: Early HCC or dysplastic nodule?

Oncology: Clinical Diagnosis: GI-Colorectal & LiverObjectives: Contrast CT was less accurate in the differentiation of small liver nodules (1-2 cm), particularly in severe cirrhosis. We evaluated the accuracy of dual-tracer (11C-acetate: ACT and 18F-FDG: FDG) PET/CT for the differentiation between small HCC and dysplastic nodules in cirrhotic liver as compared to contrast CT. Methods: Patients with cirrhosis and HCC 1-2 cm confirmed by postoperative pathology after liver transplant or hepatectomy were included if they had both preoperative dual-tracer PET/CT and contrast CT within 1 month. For the diagnosis of HCC, dual-tracer PET/CT was reviewed qualitatively by 3 nuclear medicine physicians in consensus, supported by lesion-to-liver SUV>1.20 (either tracer). Diagnosis by CT was made by 2 radiologists based on the triple-phase pattern of arterial contrast enhancement and washout during portal venous or delayed phase. Each lesion was compared with pathology in terms of diagnosis, size and location. Statistics were analysed by Chi-square and student t tests. Results: 20 patients (M: 15, F: 5, mean: 54±9.2y) with 23 small HCC lesions and 12 dysplastic nodules were identified by postoperative pathology. The mean size of small HCC was 1.6±0.35 cm, dysplastic nodules 1.5±0.34 cm (p>0.05). ACT PET identified 20/23 (87.0%) small HCC lesions while FDG detected 4/23 (17.4%) with dual-tracer sensitivity of 91.3% (21/23). ACT and dual-tracer PET were significantly more sensitive for the diagnosis of early HCC than contrast CT (10/23: 43.5%), with both p<0.05. Of the 23 small HCC lesions, 15 (65.2%) were well and 8 (34.8%) were moderately differentiated. Both FDG and ACT were true negative for all dysplastic nodules (specificity: 100%); while contrast CT misdiagnosed 4 dysplastic nodules as early HCC (specificity: 66.7%). Conclusions: Dual-tracer PET/CT was superior to contrast CT for differentiating small HCC from dysplastic nodules (1-2 cm) in cirrhotic livers. ACT was the PET tracer essential for early HCC detectio

Fish diversity and discharge rates in Bornean rainforest streams

TFE Field course 2020 group project. Recorded the fish communities and discharge rates along 100m transects on 7 rainforest streams in and around the SAFE project site in Sabah, Borneo. - Stream discharge: this was estimated using gulp-injection dilution gauging using table salt as the tracer. An Omega CDH-SD conductivity logger was used to record stream conductivity at 1 second intervals. The conductivity meter was set up at 0m on the stream's transect, it was left to stabilise and then 50m upstream 200g of salt was injected. Conductivity was monitored for a peak followed by a return to original levels. - Electrofishing: For each stream fishes were caught and released using three-pass electrofishing (model EFGI 650 electrofisher). The fishing occurred along a 100m transect with fish net blockades set up at each end to prevent immigration and emigration of fish during the sampling period. Electrofishing occurred in 3 phases, the same transect line was repeated with different voltages. Voltage varied per stream based on its conductivity and the recommended guidelines provided by SAFE. Fishes caught were identified to species level following the fish identification guide provided by SAFE and length of fishes was measured using a ruler. The data collected was used to estimate fish biodiversity and stream discharge rates in R.TFE Field course 2020 group project. Recorded the fish communities and discharge rates along 100m transects on 7 rainforest streams in and around the SAFE project site in Sabah, Borneo. - Stream discharge: this was estimated using gulp-injection dilution gauging using table salt as the tracer. An Omega CDH-SD conductivity logger was used to record stream conductivity at 1 second intervals. The conductivity meter was set up at 0m on the stream's transect, it was left to stabilise and then 50m upstream 200g of salt was injected. Conductivity was monitored for a peak followed by a return to original levels. - Electrofishing: For each stream fishes were caught and released using three-pass electrofishing (model EFGI 650 electrofisher). The fishing occurred along a 100m transect with fish net blockades set up at each end to prevent immigration and emigration of fish during the sampling period. Electrofishing occurred in 3 phases, the same transect line was repeated with different voltages. Voltage varied per stream based on its conductivity and the recommended guidelines provided by SAFE. Fishes caught were identified to species level following the fish identification guide provided by SAFE and length of fishes was measured using a ruler. The data collected was used to estimate fish biodiversity and stream discharge rates in R.

Relationships between physical and social behavioural changes and the mental status of homebound residents in hong kong during the covid-19 pandemic

202101 bcrcVersion of RecordPublishe

Investigating the relationship between tree stem respiration and growth rate

This study was conducted at the Maliau Basin Conservation area (4.747°, 116.970°) in an old-growth forest, the Belian plot. The sample consisted of ten trees of variety of species and a range of growth rates. Sampling took place over 3 consecutive days (18/02/2020 - 20/02/2020) to compile a 24-hour cycle due to logistical constrains impeding continuous measurement. Stem Respiration was measured hourly using a closed chamber EGM-4 Infrared Gas Analyser. Each tree has a 5cm long PVC collar with a 10.6cm internal diameter sealed with glue at 1.1m height. For each measurement, the chamber was flushed and collar fanned to remove stagnant air. The chamber was then sealed onto the PVC collar and Rs measured for 120 seconds. The raw measurements provides CO2 concentration (ppm), the results were then downloaded and filtered to remove initial stabilisation period and outliers using the R package "egm_r_tools" (see https://github.com/davidorme/egm_r_tools), with the ideal measurement being a linear slope with minimal residuals. The filtered efflux slope for each tree was then scaled to hourly and summed to give a daily total per tree. Out of the 24-hour period, two hour slots were missing (14:00 and 04:00) due to logistical constraints .This study was conducted at the Maliau Basin Conservation area (4.747°, 116.970°) in an old-growth forest, the Belian plot. The sample consisted of ten trees of variety of species and a range of growth rates. Sampling took place over 3 consecutive days (18/02/2020 - 20/02/2020) to compile a 24-hour cycle due to logistical constrains impeding continuous measurement. Stem Respiration was measured hourly using a closed chamber EGM-4 Infrared Gas Analyser. Each tree has a 5cm long PVC collar with a 10.6cm internal diameter sealed with glue at 1.1m height. For each measurement, the chamber was flushed and collar fanned to remove stagnant air. The chamber was then sealed onto the PVC collar and Rs measured for 120 seconds. The raw measurements provides CO2 concentration (ppm), the results were then downloaded and filtered to remove initial stabilisation period and outliers using the R package "egm_r_tools" (see https://github.com/davidorme/egm_r_tools), with the ideal measurement being a linear slope with minimal residuals. The filtered efflux slope for each tree was then scaled to hourly and summed to give a daily total per tree. Out of the 24-hour period, two hour slots were missing (14:00 and 04:00) due to logistical constraints .

Capecitabine but not 5-FU worsened hepatosplenomegaly and liver function when used with oxaliplatin and cetuximab as first-line treatment in K-ras wild-type metastatic colorectal cancer

Theme: Building Bridges to Conquer CancerThis abstract will not be presented at the 2013 ASCO Annual Meeting but has been published in conjunction with the meeting - http://meetinglibrary.asco.org/content/113435-132BACKGROUND: MRC COIN study showed that OXA and CAP (CAPOX) have greater toxicities compared with OXA and 5-FU (FOLFOX) when cetuximab (C225) was added for mCRC. Meanwhile, OXA was associated with splenomegaly and hepatic sinusoidal injury. We investigated if CAPOX+C225 worsened hepatosplenomegaly and liver function compared with FOLFOX+C225 in K-rasWT mCRC. METHODS: 97 patients with K-ras WT mCRC received either FOLFOX or CAPOX ...link_to_OA_fulltex