Computed structures of core eukaryotic protein complexes Humphreys, Ian R; Pei, Jimin; Baek, Minkyung ...
Science (American Association for the Advancement of Science),
2021-Dec-10, 2021-12-10, 20211210, Letnik:
374, Številka:
6573
Journal Article
Recenzirano
Odprti dostop
Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take ...advantage of advances in proteome-wide amino acid coevolution analysis and deep-learning–based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes within the
proteome. We use a combination of RoseTTAFold and AlphaFold to screen through paired multiple sequence alignments for 8.3 million pairs of yeast proteins, identify 1505 likely to interact, and build structure models for 106 previously unidentified assemblies and 806 that have not been structurally characterized. These complexes, which have as many as five subunits, play roles in almost all key processes in eukaryotic cells and provide broad insights into biological function.
The COVID-19 pandemic and sudden lockdown have severely hampered the country’s economic growth and socio-cultural activities while imparting a positive effect on the overall fitness of the ...environment especially air and water resources. Increased urbanization and rapid industrialization have led to rising pollution and deterioration of rivers and associated sectors such as agriculture, domestic and commercial needs. However, various available studies in different parts of the country indicate that the COVID-19 pandemic has changed the entire ecosystem. But it is noted that studies are lacking in the southern Western Ghats region of India. Therefore, the present study attempts to investigate how the continuous lockdowns affect the River Water Quality (RWQ) during lockdown (October 2020) and post-lockdown (January 2021) periods in the lower catchments (Eloor-Edayar industrialized belt) of Periyar river, Kerala state, South India. A total of thirty samples (15 samples each) were analyzed based on drinking water quality, irrigational suitability, and multivariate statistical methods to evaluate the physical and chemical status of RWQ. The results of the Water Quality Index (WQI) for assessing the drinking water suitability showed a total of 93% of samples in the excellent and good category during the lockdown, while only 47% of samples were found fit for drinking during the post-lockdown period. Irrigational suitability indices like Mg hazard, KR, PI, SAR, and Wilcox diagram revealed lockdown period samples as more suitable for irrigational activities compared to post-lockdown samples with site-specific changes. Spearman rank correlation analysis indicated EC and TDS with a strong positive correlation to Ca
2+
, Mg
2+
, Na
+
, K
+
, TH, SO
4
2−
, and Cl
−
during both periods as well as strong positive correlations within the alkaline earth elements (Ca
2+
and Mg
2+
) and alkalis (Na
+
and K
+
). Three significant components were extracted from principal component analysis (PCA), explaining 88.89% and 96.03% of the total variance for lockdown and post-lockdown periods, respectively. Variables like DO, BOD, Ca
2+
, NO
3
−
, and Cl
−
remained in the same component loading during both periods elucidating their natural origin in the basin. The results of health risk assessment based on US EPA represented hazard quotient and hazard index values below the acceptable limit signifying no potential noncarcinogenic risk via oral exposure except As, suggesting children as more vulnerable to the negative effects than adults. Furthermore, this study also shows rejuvenation of river health during lockdown offers ample scope to policymakers, administrators and environmentalists for deriving appropriate plans for the restoration of river health from anthropogenic stress.
Owing to the consequences of Anthropocene climate changes, extremes of weather and climate disasters such as heavy precipitation, tropical cyclones, and floods, have strengthened in every region ...across the globe and are badly affecting the earth system processes. The climate change has a tremendous impact in the Western Ghats, the UNESCO heritage site in India, and has to be studied in detail. Floods are the most common (and among the most deadly) natural disasters bringing heavy destruction in the Western Ghat river basins of India, and the Periyar basin is one among them. The low-lying areas of Periyar river basin (RPLB) is one of the worst affected river basins in the 2018 Kerala floods. Since the basin was continuously monitoring, the groundwater quality has been assessed in Periyar basin during three periods (pre-flood, flood, and post-flood—April, August, and October 2018 respectively) and is described in this paper. Since the water table is shallow in RPLB, floodwaters quickly reach the groundwater table, thus influencing the groundwater quality. So, the groundwater samples were collected from 26 sites in RPLB, and analyzed for quality determining parameters. Parameters like pH, TDS, EC, TH, NH
3
−
, NO
2
−
, HCO
3
−
, SO
4
2−
, SiO
4
4−
, Mg
2+
, and K
+
decreased during flood compared to pre-flood times. On the other hand, Ca
2+
, Na, and Cl
−
, turbidity values were increased during flood times. The values of pH, TDS, EC, turbidity, NH
3
−
, HCO
3
−
, SO
4
2−
, SiO
4
4−
, Mg
2+
, Na
+
, and K
+
were slightly increased in post-flood period compared to flood period. When compared to the pre-flood values, turbidity, NH
3
−
, SO
4
2−
, Na
+
, and K
+
were slightly increased in post-flood period. It was also observed that pH, TDS, EC, TH, NO
2
−
, Cl
−
, HCO
3
−
, SiO
4
4−
, PO
4
3−
, Ca
2+
, Mg
2+
, and
E. coli
values were higher in pre-flood periods compared to the post-flood scenario. Except pH, turbidity, and
E. coli
, the averages of all other parameters are falling under the recommended drinking quality values of WHO. The pH belongs to acidic nature throughout the study period. The Piper plot indicates the dominance of Ca–Mg–HCO
3
type in pre-flood, and mixing of Ca–Mg–HCO
3
type in both flood and post-flood periods. The Gibbs plot reveals that the concentration of elements is mainly depending on rock weathering and sub-surface water flow. The USSL plot depicted that the 92–96% of samples are noted as lower salinity and low sodium hazard at the source of C2S1 and C1S1; however, the 4–11% of samples are noted as high salinity but low sodium hazard at a source of C4S1 and C3S1. The Wilcox diagram indicates that the 88–96% of groundwater was found as higher suitability for irrigation during the study periods. Based on GIS based WQI model, out of the 26 samples studied, 69% of wells showed improvement in water quality after flood; meanwhile, 19% well water samples in flood were observed for lower quality compared to pre-flood times and 12% of samples remain unchanged during flood. Though floods are having positive and negative impacts, from this study, it is clear that quality of the groundwater in the RPLB is not severely affected, but they became diluted to permissible limits during flood and post-flood periods except some locations. Since the flood impact studies on groundwater systems are meager, this data from Periyar basin can be used as baseline groundwater reference data for all future flood-related river basin studies and will be very beneficial for the policy and planning needs in the context of climate change. It is high time to establish the baseline data of all river basins of Western Ghats since the normal earth system processes are worse affected by the recurrence of floods which are reporting every year.
Well-developed mouse models are important for understanding the pathogenesis and progression of immunological response to viral infections in humans. Moreover, to test vaccines, anti-viral drugs and ...therapeutic agents, mouse models are fundamental for preclinical investigations. Human viruses, however, seldom infect mice due to differences in the cellular receptors used by the viruses for entry, as well as in the innate immune responses in mice and humans. In other words, a species barrier exists when using mouse models for investigating human viral infections. Developing transgenic (Tg) mice models expressing the human genes coding for viral entry receptors and knock-out (KO) mice models devoid of components involved in the innate immune response have, to some extent, overcome this barrier. Humanized mouse models are a third approach, developed by engrafting functional human cells and tissues into immunodeficient mice. They are becoming indispensable for analyzing human viral diseases since they nearly recapitulate the human disease. These mouse models also serve to test the efficacy of vaccines and antiviral agents. This review provides an update on the Tg, KO, and humanized mouse models that are used in studies investigating the pathogenesis of three important human-specific viruses, namely human immunodeficiency (HIV) virus 1, influenza, and dengue.
Dissociative electron attachment (DEA) cross sections for simple organic molecules, namely, acetic acid, propanoic acid, methanol, ethanol, and n-propyl amine are measured in a crossed beam ...experiment. We find that the H(-) ion formation is the dominant channel of DEA for these molecules and takes place at relatively higher energies (>4 eV) through the core excited resonances. Comparison of the cross sections of the H(-) channel from these molecules with those from NH(3), H(2)O, and CH(4) shows the presence of functional group dependence in the DEA process. We analyze this new phenomenon in the context of the results reported on other organic molecules. This discovery of functional group dependence has important implications such as control in electron induced chemistry and understanding radiation induced damage in biological systems.
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with ...poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment’s (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints.
The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion.
The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic.
The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.
•Healthcare challenges during the pandemic are linked to resource constraints including shortage of PPE, laboratory tests and medications•A group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19•The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions•This will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.
Purpose: To report the clinicopathological correlation of absent crystalline lens in an eye with retinoblastoma. Methods: A 1-year-old female child was brought to our patient services for pain and ...swelling in the right eye since the past few months. The child was diagnosed to have bilateral retinoblastoma and was suspected to have absence of crystalline lens in the right eye on the basis of clinical findings and ocular imaging. After 3 cycles of chemotherapy for suspected extraocular extension of tumor, she underwent enucleation. Absence of crystalline lens was confirmed on both gross and microscopic pathology. Results: We present a child with retinoblastoma, suspected to have absence of crystalline lens clinically and on ocular imaging (ultrasound and MRI), which was finally confirmed on ocular pathology examination post enucleation. Conclusion: We report for the first time clinicopathologically proven absence of crystalline lens in an eye with retinoblastoma.