Active Causal Learning for Decoding Chemical Complexities with Targeted Interventions

Predicting and enhancing inherent properties based on molecular structures is paramount to design tasks in medicine, materials science, and environmental management. Most of the current machine learning and deep learning approaches have become standard for predictions, but they face challenges when applied across different datasets due to reliance on correlations between molecular representation and target properties. These approaches typically depend on large datasets to capture the diversity within the chemical space, facilitating a more accurate approximation, interpolation, or extrapolation of the chemical behavior of molecules. In our research, we introduce an active learning approach that discerns underlying cause-effect relationships through strategic sampling with the use of a graph loss function. This method identifies the smallest subset of the dataset capable of encoding the most information representative of a much larger chemical space. The identified causal relations are then leveraged to conduct systematic interventions, optimizing the design task within a chemical space that the models have not encountered previously. While our implementation focused on the QM9 quantum-chemical dataset for a specific design task-finding molecules with a large dipole moment-our active causal learning approach, driven by intelligent sampling and interventions, holds potential for broader applications in molecular, materials design and discovery

Chemogenetic manipulation of astrocyte activity at the synapse- a gateway to manage brain disease

Astrocytes are the major glial cell type in the central nervous system (CNS). Initially regarded as supportive cells, it is now recognized that this highly heterogeneous cell population is an indispensable modulator of brain development and function. Astrocytes secrete neuroactive molecules that regulate synapse formation and maturation. They also express hundreds of G protein-coupled receptors (GPCRs) that, once activated by neurotransmitters, trigger intracellular signalling pathways that can trigger the release of gliotransmitters which, in turn, modulate synaptic transmission and neuroplasticity. Considering this, it is not surprising that astrocytic dysfunction, leading to synaptic impairment, is consistently described as a factor in brain diseases, whether they emerge early or late in life due to genetic or environmental factors. Here, we provide an overview of the literature showing that activation of genetically engineered GPCRs, known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), to specifically modulate astrocyte activity partially mimics endogenous signalling pathways in astrocytes and improves neuronal function and behavior in normal animals and disease models. Therefore, we propose that expressing these genetically engineered GPCRs in astrocytes could be a promising strategy to explore (new) signalling pathways which can be used to manage brain disorders. The precise molecular, functional and behavioral effects of this type of manipulation, however, differ depending on the DREADD receptor used, targeted brain region and timing of the intervention, between healthy and disease conditions. This is likely a reflection of regional and disease/disease progression-associated astrocyte heterogeneity. Therefore, a thorough investigation of the effects of such astrocyte manipulation(s) must be conducted considering the specific cellular and molecular environment characteristic of each disease and disease stage before this has therapeutic applicability.This work was supported by the KU Leuven Research Council (C14/20/071) and the Research Foundation Flanders Belgium (FWO, G080821N) via research project funding. MGH is currently the ERA Chair (NCBio) at i3S Porto funded by the European Commission (H2020-WIDESPREAD-2018-2020-6; NCBio; 951923)

Comparison Of Butterfly Diversity In Natural, Semi-Natural And Human-Modified Ecosystems At Kundamankadavu,Thiruvananthapuaram, Kerala, South India .

Among insects, butterflies are the most taxonomically studied group and play key role in ecosystem as pollinators and bioindicator species. The diversity of butterflies inhabiting at Kundamankadavu, Vilavoorkal Panchayath, Thiruvananthapuram was recorded through a Pollard walk method by traversing slowly and observing within 5m radius of the observer for the period of November 2019 to March 2020. Three different ecosystems such as natural, semi-natural and human-modified ecosystems were evaluated for analysis of the diversities of butterfly species. The maximum diversity was observed in the natural ecosystem. A total of 15 species were observed across the three habitat types during the study period. Maximum number of butterflies were observed in natural ecosystem (6) followed by human-modified (5) and minimum in semi-natural ecosystem (4) respectively. Out of these, members belonging to the family Nymphalidae was the most common with 6 species being recorded accounting for 34% of total species. The study area is rich in butterfly diversity and further research could be conducted to obtain more details and documentation on butterfly diversity for the conservation and butterfly park. As the population of these insects decline rapidly due to human activities, habitat destruction, uses of pesticides and unawareness of people about the importance of butterflies, appropriate measures should be adopted for their protection

EFFECT OF PRE EXAMINATION STRESS ON OLFACTORY SENSITIVITY IN COLLEGE STUDENTS.

 Objective: The present study was undertaken to assess the effect of pre-examination stress on olfactory sensitivity in college students.Methods: A total of 80 apparently healthy males and females were included in the study after obtaining written informed consent. Blast injection method was used to measure the olfactory sensitivity.Result: In the present study, we have observed decrease in the olfactory sensitivity in both males and females during pre-examination stress. However, it is not statistically significant.Conclusion: We recommend further detailed studies for better understanding the links between stress and olfaction.Â

Assessment of rainwater management practices and land use land cover changes in the Meja watershed of Ethiopia

Poor rainwater management (RWM) practices and resultant problems of land degradation and low water productivity are severe problems in the rural highlands of Ethiopia. The current study was undertaken at Meja watershed, which is located in the Jeldu district of Oromia region. The study investigated rainwater management practices and associated socio-economic and biophysical conditions in the watershed. The existing RWM interventions, their extent and the nature of changes in land use and land cover (LULC) conditions were mapped and evaluated. Results indicated that over the two decades between 1990 and 2010 there was an increase in the extent of cultivated land and large expansion in eucalyptus plantation at the expense of natural forest and grazing lands. Results indicate that, with few exceptions of RWM interventions practised, there were mainly poor and inefficient rainwater management practices. The overall effect leads to inadequacy of water for household consumption, livestock and for intensifying agricultural production via small scale irrigation systems. Deforestation and poor resource management resulted in soil degradation, reduction of hydrological regimes and water productivities in the watershed

Urban Termites of Recife, Northeast Brazil (Isoptera)

This study surveyed the termite fauna in urban properties of the city of Recife, state of Pernambuco, northeastern Brazil. Six-hundred properties were inspected in search for termites or signs of their activity, such as abandoned nests, galleries on walls, and fecal pellets. Seven termite species, belonging to seven genera and three families (Kalotermitidae, Rhinotermitidae, and Termtidae) were found causing some type of damage. Nasutitermes corniger and Cryptotermes dudleyi were the most frequent species within buildings (82.4% and 9.5 %, respectively). Such species, along with Coptotermes gestroi, were responsible for the greatest damage recorded. With the exception of Cryptotermes dudleyi and Coptotermes gestroi, all of the species are native and relatively common in northeastern Brazil’s Atlantic forest

Genetic diversity and population structure among sorghum (Sorghum bicolor, L.) germplasm collections from Western Ethiopia

The Western Ethiopian region harbors a unique set of sorghum germplasm adapted to conditions not conventional to sorghums grown in other parts of the world. Accessions from the region possess unique resistance to multiple leaf and grain diseases. This study is aimed at exploring the extent of genetic variation and population structure among accessions of this region. A total of 123 accessions comprising 111 from Western Ethiopia (62 from Asosa and 49 from Pawe) and 12 U.S. adapted lines were genotyped using 30 sorghum simple sequence repeat markers (SSR). Genetic diversity and population structure were analyzed using PowerMarker and STRUCTURE software, respectively, based on 23 polymorphic SSR markers. Principal component analysis (PCA) was performed to view the variability in multi-dimensional space. Population structure analysis revealed considerable admixtures between Pawe and Asosa accessions, while the PowerMarker analysis grouped the accessions into three distinct clusters largely based on collection regions. The PCA did not clearly differentiate Asosa and Pawe accessions, but U.S. adapted lines were clearly separated from the rest. The study indicated the presence of marked genetic variability among accessions from Western Ethiopia and also provided clues on shared genetic events among accessions adapted to the two areas in Western Ethiopia.Keywords: Sorghum, genetic diversity, population structure, SSR, Ethiopi

Autocrine Production of β-Chemokines Protects CMV-Specific CD4+ T Cells from HIV Infection

Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1α and MIP-1β mRNA, resulting in a rapid increase in production of MIP-1α and MIP-1β after cognate antigen stimulation. Production of β-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of β-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1β contained 10 times less Gag DNA than did those which failed to produce MIP-1β. These data suggest that CD4+ T cells which produce MIP-1α and MIP-1β bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection