scholarly journals Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins

2021 ◽  
Vol 118 (49) ◽  
pp. e2108163118
Author(s):  
Hubert Wyszkowski ◽  
Anna Janta ◽  
Wiktoria Sztangierska ◽  
Igor Obuchowski ◽  
Tomasz Chamera ◽  
...  

Protein homeostasis is constantly being challenged with protein misfolding that leads to aggregation. Hsp70 is one of the versatile chaperones that interact with misfolded proteins and actively support their folding. Multifunctional Hsp70s are harnessed to specific roles by J-domain proteins (JDPs, also known as Hsp40s). Interaction with the J-domain of these cochaperones stimulates ATP hydrolysis in Hsp70, which stabilizes substrate binding. In eukaryotes, two classes of JDPs, Class A and Class B, engage Hsp70 in the reactivation of aggregated proteins. In most species, excluding metazoans, protein recovery also relies on an Hsp100 disaggregase. Although intensely studied, many mechanistic details of how the two JDP classes regulate protein disaggregation are still unknown. Here, we explore functional differences between the yeast Class A (Ydj1) and Class B (Sis1) JDPs at the individual stages of protein disaggregation. With real-time biochemical tools, we show that Ydj1 alone is superior to Sis1 in aggregate binding, yet it is Sis1 that recruits more Ssa1 molecules to the substrate. This advantage of Sis1 depends on its ability to bind to the EEVD motif of Hsp70, a quality specific to most of Class B JDPs. This second interaction also conditions the Hsp70-induced aggregate modification that boosts its subsequent dissolution by the Hsp104 disaggregase. Our results suggest that the Sis1-mediated chaperone assembly at the aggregate surface potentiates the entropic pulling, driven polypeptide disentanglement, while Ydj1 binding favors the refolding of the solubilized proteins. Such subspecialization of the JDPs across protein reactivation improves the robustness and efficiency of the disaggregation machinery.

1931 ◽  
Vol 5 (2) ◽  
pp. 208-218 ◽  
Author(s):  
J. B. Harrington

The relationship between the degree of plumpness of F2 seeds and the type of the resulting F2 plants was studied in the cross Vernal (T. dicoccum) × Marquis (T. vulgare). A random sample of F2 seeds was divided into three classes based upon kernel plumpness, viz. plump (Class A), slightly shrunken (Class B), and shrunken (Class C). In these there were by number 55.5, 41.0 and 3.5% of seeds respectively. Emergence of F2 plants in the field was 64, 58 and 36% for Classes A, B and C. The F2 plants were studied for 13 morphological characters. Comparing the populations for all characters combined, Class A was more dicoccum-like than Class B, and Class B much more dicoccum-like than Class C. The proportion of vulgare-like character was 16, 20 and 32% for Classes A, B and C, respectively. Considering the character of the individual plants, the ratios of dicoccum-like to vulgare-like were 12.1:1, 5.3:1, and 2.2:1 for classes A, B and C, respectively. Furthermore, the vulgare-like plants of classes A and B were less vulgare-like than those of Class C. There were present, however, in Classes A and B some plants that were fully as vulgare-like as any in Class C. These results indicate that, in an interspecific wheat cross, the breeder should give special attention to the shrunken F2 seeds if he has very limited nursery space and a large amount of seed; whereas if he has plenty of space for a large population, special care of shrunken F2 seeds does not seem warranted.


Author(s):  
Suharmon Suharmon

This research aims to obtain infomation about Arabic learning especially speaking skill in Arabic Language Education Department at IAIN Batusangkar. The research uses a quantitative approach. The instruments to collect the data are test and questionnaire. The data were analyzed using descriptive statistics. The results of the research state that the students’ speaking ability at class “ A “ are 28% low, 36% moderate, and 36% high. While, at class “B”, students’ speaking abilities are 36.4% low, 40,9% moderate, and 22.7% high. The cause of students’ low ability is the unappropriateness of teachers’ strategy in teaching speaking. There are about 96% students at class “A” agreed and 86.4% students at class “B” had similar answer. Another cause is students’ low motivation in learning. Class “A” students agreed for about 76% of them and 77% of class “B” students answered the same. From the finding, it can be concluded that the inability of students to speak Arabic can be overcomed by improving teaching strategies and encouraging maximum motivation  to learn Arabic.


2020 ◽  
Vol 20 (26) ◽  
pp. 2380-2390 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Abdullah Al Mamun ◽  
Md. Ataur Rahman ◽  
Tapan Behl ◽  
Asma Perveen ◽  
...  

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.


2020 ◽  
Vol 29 (1) ◽  
pp. 81-88
Author(s):  
Virendra Kumar Verma ◽  
Nishant Mittal ◽  
Ramesh Chandra

AbstractWe present an investigation of halo coronal mass ejections (HCMEs) kinematics and other facts about the HCMEs. The study of HCMEs is very important because HCMEs are regarded as the main causes of heliospheric and geomagnetic disturbances. In this study, we have investigated 313 HCMEs observed during 1996-2012 by LASCO, coronal holes, and solar flares. We find that HCMEs are of two types: accelerated HCMEs and decelerated HCMEs. The mean space speed of HCMEs is 1283 km/s while the mean speed of decelerated HCMEs and accelerated HCMEs is 1349 km/s and 1174 km/s, respectively. The investigation shows that 1 (0.3%) HCME was associated with class A SXR, 14 (4.7%) HCMEs were associated with class B SXR-flares, 87 (29.4%) HCMEs were associated with class C SXR-flares, 125 (42.2%) HCMEs were associated with class M SXR-flares and 69 (23.3%) HCMEs were associated with class X SXR-flares. The speed of HCMEs increases with the importance of solar SXR-flares. The various results obtained in the present analysis are discussed in the light of the existing scenario of heliospheric physics.


2021 ◽  
Vol 11 (4) ◽  
pp. 1964
Author(s):  
Daniele Colarossi ◽  
Eleonora Tagliolini ◽  
Paolo Principi ◽  
Roberto Fioretti

This work presents an adjustable large-scale solar simulator based on metal halide lamps. The design procedure is described with regards to the construction and spatial arrangement of the lamps and the designed optical system. Rotation and translation of the lamp array allow setting the direction and the intensity of the luminous flux on the horizontal plane. To validate the built model, irradiance nonuniformity and temporal instability tests were carried out assigning Class A, B, or C for each test, according to the International Electrotechnical Commission (IEC) standards requirements. The simulator meets the Class C standards on a 200 × 90 cm test plane, Class B on 170 × 80 cm, and Class A on 80 × 40 cm. The temporal instability returns Class A results for all the measured points. Lastly, a PV panel is characterized by tracing the I–V curve under simulated radiation, under outdoor natural sunlight, and with a numerical method. The results show a good approximation.


2011 ◽  
Vol 22 (No. 4) ◽  
pp. 133-142 ◽  
Author(s):  
I. Švec ◽  
M. Hrušková

Abstract: Baking quality of flour from six wheat cultivars (harvest 2002 and 2003), belonging to the quality classes A and B, was evaluated using the fermented dough test. Analytical traits of kernel and flour showed differences between the classes which were confirmed by the baking test with the full-bread-formula according to Czech method. In addition to standard methods of the bread parameters description (specific bread volume and bread shape measurements) rheological measurements of penetrometer and image analysis were used in effort to differentiate wheat samples into the quality classes. The results of the baking test proved significant differences in specific bread volumes – the highest volume in class A was obtained with the cultivar Vinjet and in class B with SG-S1098 – approx. 410 and 420 ml/100 g. Although significant correlations among image analysis data and specific bread volume having been proved, any image analysis parameter did not distinguish the quality classes. Only the penetronetric measurements made with bread crumb were suitable for such purpose (r = 0.9083; for  = 0.01). Among image analysis data the total cell area of the crumb had the strongest correlation with specific bread volume (r = 0.7840; for α = 0.01).    


2011 ◽  
Vol 114 (3) ◽  
pp. 842-849 ◽  
Author(s):  
Robert F. Spetzler ◽  
Francisco A. Ponce

Object The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. Methods Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. Results Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). Conclusions Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.


2017 ◽  
Vol 7 (2) ◽  
pp. 182-199 ◽  
Author(s):  
Rebecca D. Folkerth ◽  
Jacqueline Nunez ◽  
Zhanna Georgievskaya ◽  
Declan McGuone

In infants and toddlers (less than four years of age), determination of cause and manner of death often requires a complete autopsy. Few evidence-based guidelines exist regarding optimum nervous system sectioning in this population. Over a six-month interval and using a comprehensive section protocol, we categorized cases having neuropathological findings that were critical (Class A), contributory (Class B), or noncontributory (Class C) to the final cause and manner of death. We further evaluated which sections helped make this determination. Among 53 cases (44 infants, 9 toddlers; 26 girls, 27 boys), Class A neuropathology was noted in nine (16.9%). Seven infants had meningoencephalitis (2/7, 28.6%), craniospinal trauma (3/7, 42.8%), brainstem necrosis suggesting Leigh Disease (1/7, 14.3%), and hydrocephalus in Dandy-Walker malformation (1/7, 14.3%); two toddlers had inflicted craniospinal trauma (2/2, 100%). Class B factors were identified in 11/53 (20.8%), including recent hypoxic-ischemic lesions (2/11, 18.2%), meningitis or dural venous sinus thrombosis in systemic sepsis (2/11, 18.2%), multicystic encephalopathy following peripartum asphyxia (2/11, 18.2%), and microcephaly and delayed myelination (Cri-du-Chat Syndrome) (1/11, 9.09%). Class B also included three toddlers (3/11, 27.2%) with features of hippocampal dysgenesis, two in the setting of febrile seizures. Class C comprised normal brains (3/53, 5.7%), and those with findings of uncertain significance, such as white matter and brainstem gliosis (30/53, 56.6%). The sections most valuable for detection of relevant pathology, and thus recommended for routine sampling, were: 1) bilateral hippocampus; 2) cerebral cortex and leptomeninges; and 3) pons or medulla.


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