Structural Basis for the Calmodulin-Mediated Activation of eEF-2K

Translation is a highly energy consumptive process tightly regulated for optimal protein quality and adaptation to energy and nutrient availability. A key facilitator of this process is the α-kinase eEF-2K that specifically phosphorylates the GTP-dependent translocase eEF-2, thereby reducing its affinity for the ribosome and suppressing the elongation phase of protein synthesis. eEF-2K activation requires calmodulin binding and auto-phosphorylation at the primary stimulatory site, T348. Biochemical studies have predicted that calmodulin activates eEF-2K through a unique allosteric process mechanistically distinct from other calmodulin-dependent kinases. Here we resolve the atomic details of this mechanism through a 2.3 Å crystal structure of the heterodimeric complex of calmodulin with the functional core of eEF-2K (eEF-2KTR). This structure, which represents the activated T348-phosphorylated state of eEF-2KTR, highlights how through an intimate association with the calmodulin C-lobe, the kinase creates a spine that extends from its N-terminal calmodulin-targeting motif through a conserved regulatory element to its active site. Modification of key spine residues has deleterious functional consequences.

Do Microbiota in the Soil Affect Embryonic Development and Immunocompetence in Hatchling Reptiles?

Reptile eggs develop in intimate association with microbiota in the soil, raising the possibility that embryogenesis may be affected by shifts in soil microbiota caused by anthropogenic disturbance, translocation of eggs for conservation purposes, or laboratory incubation in sterile media. To test this idea we incubated eggs of keelback snakes (Tropidonophis mairii, Colubridae) in untreated versus autoclaved soil, and injected lipopolysaccharide (LPS) into the egg to induce an immune response in the embryo. Neither treatment modified hatching success, water uptake, incubation period, or white-blood-cell profiles, but both treatments affected hatchling size. Eggs incubated on autoclaved soil produced smaller hatchlings than did eggs on untreated soil, suggesting that heat and/or pressure treatment decrease the soil’s suitability for incubation. Injection of LPS reduced hatchling size, suggesting that the presence of pathogen cues disrupts embryogenesis, possibly by initiating immune reactions unassociated with white-blood-cell profiles. Smaller neonates had higher ratios of heterophils to leucocytes, consistent with higher stress in smaller snakes, or body-size effects on investment into different types of immune cells. Microbiota in the incubation medium thus can affect viability-relevant phenotypic traits of hatchling reptiles. We need further studies to explore the complex mechanisms and impacts of environmental conditions on reptilian embryogenesis.

Intact rDNA arrays of Potentilla-origin detected in Erythronium nucleus suggest recent eudicot-to-monocot horizontal transfer

The occurrence of horizontal gene transfer (HGT) in Eukarya is increasingly gaining recognition. Nuclear-to-nuclear jump of DNA between plant species at high phylogenetic distance and devoid of intimate association (e.g., parasitism) is still scarcely reported. Within eukaryotes, components of ribosomal DNA (rDNA) multigene family have been found to be horizontally transferred in protists, fungi and grasses. However, in neither case HGT occurred between phylogenetic families, nor the transferred rDNA remained tandemly arrayed and transcriptionally active in the recipient organism. This study aimed to characterize an alien eudicot-type of 45S nuclear rDNA, assumingly transferred horizontally to the genome of monocot European Erythronium (Liliaceae). Genome skimming coupled by PacBio HiFi sequencing of a BAC clone were applied to determine DNA sequence of the alien rDNA. A clear phylogenetic signal traced the origin of the alien rDNA of Erythronium back to the Argentea clade of Potentilla (Rosaceae) and deemed the transfer to have occurred in the common ancestor of E. dens-canis and E. caucasicum. Though being discontinuous, transferred rDNA preserved its general tandemly arrayed feature in the host organism. Southern blotting, molecular cytogenetics, and sequencing of a BAC clone derived from flow-sorted nuclei indicated integration of the alien rDNA into the recipient's nuclear genome. Unprecedently, dicot-type alien rDNA was found to be transcribed in the monocot Erythronium albeit much less efficiently than the native counterpart. This study adds a new example to the growing list of naturally transgenic plants while holding the scientific community continually in suspense about the mode of DNA transfer.

Omental cyst: a case report and review of the literature

Background Omental cysts are rare, predominantly occur in children, and often initially present with symptoms masquerading as other more common intra-abdominal pathologies. In this case report, we present the case of a child with an omental cyst that originated from the lesser sac. Due to the location of this cyst, resection presented unique technical challenges that have not been described in existing literature. Case presentation A 4-year-old male patient presented with symptoms initially concerning for appendicitis. Ultrasound showed a normal appendix but a large volume of complex intraperitoneal fluid. Computed tomography subsequently demonstrated a large cystic structure spanning from the stomach to the bladder. The patient was taken to the operating room where a large omental cyst was found to originate from the lesser sac. The resection was difficult due to the thin wall of the cyst and the intimate association of the superior-most aspect of the cyst with the tail of the pancreas, but was ultimately successful. Conclusions Omental cysts are rarely suspected before detection on abdominal imaging. Surgical resection is the treatment of choice, and complete resection can result in a recurrence-free postoperative course. Laparoscopic resection has been reported, but laparotomy is reasonable when a minimally invasive approach may not allow for a safe resection without rupture of the cyst. Anatomical characteristics of the cyst, as demonstrated in our case, can present challenges in the treatment of this otherwise benign entity.

Mitochondrial genomes of two parasitic Cuscuta species lack clear evidence of horizontal gene transfer and retain unusually fragmented ccmFC genes

Background The intimate association between parasitic plants and their hosts favours the exchange of genetic material, potentially leading to horizontal gene transfer (HGT) between plants. With the recent publication of several parasitic plant nuclear genomes, there has been considerable focus on such non-sexual exchange of genes. To enhance the picture on HGT events in a widely distributed parasitic genus, Cuscuta (dodders), we assembled and analyzed the organellar genomes of two recently sequenced species, C. australis and C. campestris, making this the first account of complete mitochondrial genomes (mitogenomes) for this genus. Results The mitogenomes are 265,696 and 275,898 bp in length and contain a typical set of mitochondrial genes, with 10 missing or pseudogenized genes often lost from angiosperm mitogenomes. Each mitogenome also possesses a structurally unusual ccmFC gene, which exhibits splitting of one exon and a shift to trans-splicing of its intron. Based on phylogenetic analysis of mitochondrial genes from across angiosperms and similarity-based searches, there is little to no indication of HGT into the Cuscuta mitogenomes. A few candidate regions for plastome-to-mitogenome transfer were identified, with one suggestive of possible HGT. Conclusions The lack of HGT is surprising given examples from the nuclear genomes, and may be due in part to the relatively small size of the Cuscuta mitogenomes, limiting the capacity to integrate foreign sequences.

Adipose MDM2 regulates systemic insulin sensitivity

The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.

Terrestrial-type nitrogen-fixing symbiosis between seagrass and a marine bacterium

Symbiotic N2-fixing microorganisms have a crucial role in the assimilation of nitrogen by eukaryotes in nitrogen-limited environments1–3. Particularly among land plants, N2-fixing symbionts occur in a variety of distantly related plant lineages and often involve an intimate association between host and symbiont2,4. Descriptions of such intimate symbioses are lacking for seagrasses, which evolved around 100 million years ago from terrestrial flowering plants that migrated back to the sea5. Here we describe an N2-fixing symbiont, ‘Candidatus Celerinatantimonas neptuna’, that lives inside seagrass root tissue, where it provides ammonia and amino acids to its host in exchange for sugars. As such, this symbiosis is reminiscent of terrestrial N2-fixing plant symbioses. The symbiosis between Ca. C. neptuna and its host Posidonia oceanica enables highly productive seagrass meadows to thrive in the nitrogen-limited Mediterranean Sea. Relatives of Ca. C. neptuna occur worldwide in coastal ecosystems, in which they may form similar symbioses with other seagrasses and saltmarsh plants. Just like N2-fixing microorganisms might have aided the colonization of nitrogen-poor soils by early land plants6, the ancestors of Ca. C. neptuna and its relatives probably enabled flowering plants to invade nitrogen-poor marine habitats, where they formed extremely efficient blue carbon ecosystems7.

Derivation and Clinical Validation of a Redox-Driven Prognostic Signature for Colorectal Cancer

Colorectal cancer (CRC), a seriously threat that endangers public health, has a striking tendency to relapse and metastasize. Redox-related signaling pathways have recently been extensively studied in cancers. However, the study and potential role of redox in CRC remain unelucidated. We developed and validated a risk model for prognosis and recurrence prediction in CRC patients via identifying gene signatures driven by redox-related signaling pathways. The redox-driven prognostic signature (RDPS) was demonstrated to be an independent risk factor for patient survival (including OS and RFS) in four public cohorts and one clinical in-house cohort. Additionally, there was an intimate association between the risk score and tumor immune infiltration, with higher risk score accompanied with less immune cell infiltration. In this study, we used redox-related factors as an entry point, which may provide a broader perspective for prognosis prediction in CRC and have the potential to provide more promising evidence for immunotherapy.

Satellite glia are essential modulators of sympathetic neuron survival, activity, and autonomic function

Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, how satellite glia contribute to sympathetic functions remain unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via extracellular K+ buffering. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.

Plants of Temples and Religious Places in Khandesh Region (Maharashtra): An Ethnobotanical Perspective

Plants have been, since time immemorial, the focus of religious purposes for many human societies worldwide. Because of efficacious use in religious aspects, some plant species are said to be important. Certain plants are held sacred due to their intimate association with special locations like temple courtyards. These locations are easily overlooked for scientific investigations. People are closely associated with the plant-wealth in such places as well although on religious ground. These need to be tapped for indigenous wisdom for human welfare. The present authors inventorised three districts of Khandesh region (Maharashtra) to divulge plantlore. Total 28 species belonging to 27 genera and 21 angiospermic families are presently focussed touching four aspects viz., sacredness, miscellaneous uses, cosmetics and medicinal utilities. The worshippers, trustees and people intimately associated with temples and religious places have been interviewed to tap down traditional ethnobotanical information. This work provides an account of religious and cultural ways of conserving biodiversity. At the same, these places help improve local environment. Further studies in a country like India are desired to unearth the potentials of religious locations.