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Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and peptide molecules, which are drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains. This was the beginning of the prebiotic information age. The origin of the genetic code is enigmatic; herein, we propose an evolutionary explanation: the demand for a wide range of protein enzymes over peptides in the prebiotic reactions was the main selective pressure for the origin of information-directed protein synthesis. The molecular basis of the genetic code manifests itself in the interaction of aaRS and their cognate tRNAs. In the beginning, aminoacylated ribozymes used amino acids as a cofactor with the help of bridge peptides as a process for selection between amino acids and their cognate codons/anticodons. This process selects amino acids and RNA species for the next steps. The ribozymes would give rise to pre-tRNA and the bridge peptides to pre-aaRS. Later, variants would appear and evolution would produce different but specific aaRS-tRNA-amino acid combinations. Pre-tRNA designed and built pre-mRNA for the storage of information regarding its cognate amino acid. Each pre-mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within pre-mRNA and mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional with the emergence of the translation and genetic code. The genetic code developed in three stages that are coincident with the refinement of the translation machines: the GNC code that was developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. We suggest the coevolution of translation machines and the genetic code. The emergence of the translation machines was the beginning of the Darwinian evolution, an interplay between information and its supporting structure. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to better understand the prebiotic information system, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software, called CATI (Codon-Amino Acid-Translator-Imitator), to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the genetic code might have evolved in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics, such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. While using AnyLogic software, we were able to simulate and visualize the entire evolution of the translation machines, amino acids, and the genetic code.

Prebiotic information systems exist in three forms: analog, hybrid, and digital. The Analog Information System (AIS), manifested early in abiogenesis, was expressed in the chiral selection, nucleotide formation, self-assembly, polymerization, encapsulation of polymers, and division of protocells. It created noncoding RNAs by polymerizing nucleotides that gave rise to the Hybrid Information System (HIS). The HIS employed different species of noncoding RNAs, such as ribozymes, pre-tRNA and tRNA, ribosomes, and functional enzymes, including bridge peptides, pre-aaRS, and aaRS (aminoacyl-tRNA synthetase). Some of these hybrid components build the translation machinery step-by-step. The HIS ushered in the Digital Information System (DIS), where tRNA molecules become molecular architects for designing mRNAs step-by-step, employing their two distinct genetic codes. First, they created codons of mRNA by the base pair interaction (anticodon–codon mapping). Secondly, each charged tRNA transferred its amino acid information to the corresponding codon (codon–amino acid mapping), facilitated by an aaRS enzyme. With the advent of encoded mRNA molecules, the first genes emerged before DNA. With the genetic memory residing in the digital sequences of mRNA, a mapping mechanism was developed between each codon and its cognate amino acid. As more and more codons ‘remembered’ their respective amino acids, this mapping system developed the genetic code in their memory bank. We compared three kinds of biological information systems with similar types of human-made computer systems.

Birds make sound in the syrinx, a unique vocal organ situated deep in the chest, but little is known about the evolution of this structure; a fossilized Cretaceous age syrinx from Antarctica is described from a species that might have been capable of making a goose-like honking sound. A bird's vocal organ from the Cretaceous From tweets to honks, birds make sounds with the syrinx, an organ derived from a modification of the reinforced rings at the base of the trachea where it divides into bronchi. Apart from fragmentary remains from the Pleistocene and Holocene epochs, and a single find from the Eocene epoch that has not been formally described, the fossil record of the syrinx is blank. Here Julia Clarke et al . describe the first syrinx from the age of dinosaurs. It comes from a new specimen of Vegavis iaai from the Cretaceous period of Antarctica. Vegavis was a bird related to modern ducks and geese, and study of its fossilized syrinx shows that it would have been a 'honker', like its modern relatives. From complex songs to simple honks, birds produce sounds using a unique vocal organ called the syrinx 1 , 2 . Located close to the heart at the tracheobronchial junction, vocal folds or membranes attached to modified mineralized rings vibrate to produce sound 1 , 2 , 3 , 4 , 5 , 6 , 7 . Syringeal components were not thought to commonly enter the fossil record 6 , and the few reported fossilized parts of the syrinx are geologically young 8 , 9 , 10 , 11 (from the Pleistocene and Holocene (approximately 2.5 million years ago to the present)). The only known older syrinx is an Eocene specimen that was not described or illustrated 12 . Data on the relationship between soft tissue structures and syringeal three-dimensional geometry are also exceptionally limited 5 . Here we describe the first remains, to our knowledge, of a fossil syrinx from the Mesozoic Era, which are preserved in three dimensions in a specimen from the Late Cretaceous (approximately 66 to 69 million years ago) of Antarctica. With both cranial and postcranial remains, the new Vegavis iaai specimen is the most complete to be recovered from a part of the radiation of living birds (Aves). Enhanced-contrast X-ray computed tomography (CT) of syrinx structure in twelve extant non-passerine birds, as well as CT imaging of the Vegavis and Eocene syrinxes, informs both the reconstruction of ancestral states in birds and properties of the vocal organ in the extinct species. Fused rings in Vegavis form a well-mineralized pessulus, a derived neognath bird feature, proposed to anchor enlarged vocal folds or labia 5 . Left-right bronchial asymmetry, as seen in Vegavis , is only known in extant birds with two sets of vocal fold sound sources. The new data show the fossilization potential of the avian vocal organ and beg the question why these remains have not been found in other dinosaurs. The lack of other Mesozoic tracheobronchial remains, and the poorly mineralized condition in archosaurian taxa without a syrinx, may indicate that a complex syrinx was a late arising feature in the evolution of birds, well after the origin of flight and respiratory innovations.

Upper Permian rocks of the former supercontinent Gondwana record climax late Paleozoic terrestrial vertebrate faunas that were dominated numerically and ecologically by therapsid synapsids. Older faunal elements of earlier Paleozoic faunas, such as captorhinid reptiles, are rare and scattered components of the first amniote faunas to inhabit high-latitude regions. Here we describe a new genus and species of moradisaurine captorhinid that represents an archaic faunal element of the high-fibre herbivore fauna of the late Permian of what is now peninsular India. The presence of a relatively broad parietal and three rows of conical teeth on the maxilla and the dentary distinguishes Indosauriscus kuttyi gen. et sp. nov. from other moradisaurines. The hypodigm of I. kuttyi comprises skulls that range in length from 39 mm to 54 mm, and high ossification of the braincase elements and well developed skull-roof sutures, indicate that I. kuttyi adults were smaller than those of most moradisaurines. Results of our phylogenetic analyses suggest that moradisaurines, despite appearing first in the paleotropics, dispersed into temperate, high-latitude regions of Pangea early in their evolutionary history. Moradisaurines in dicynodont-dominated faunas, viz. Indosauriscus kuttyi and Gansurhinus naobaogouensis , were the smallest high-fibre herbivores in their respective faunas. This suggests that small body size may have evolved in these moradisaurines as they co-evolved with the more numerous and diverse dicynodont therapsids.

Some of the oldest known dinosaurs and the first faunas numerically dominated by them are documented in the Upper Triassic–Lower Jurassic-aged Gondwana formations exposed in the Pranhita-Godavari Valley of south-central and east-central India. The Upper Maleri Formation of the Pranhita-Godavari Basin preserves an early-middle Norian dinosaur assemblage numerically dominated by sauropodomorph dinosaurs, including at least two nominal species. However, the preliminary report of a herrerasaurian dinosaur specimen indicates that this assemblage of south-central Gondwana was more taxonomically diverse. Here, we describe and compare in detail the anatomy and assess the taxonomy and phylogenetic relationships of the Upper Maleri herrerasaurian specimen. A unique combination of character states present in this specimen allows the erection of the new genus and species Maleriraptor kuttyi . Updated quantitative phylogenetic analyses focused on early dinosauriforms recovered Maleriraptor kuttyi as a member of Herrerasauria outside of the South American clade Herrerasauridae. Maleriraptor kuttyi fills a temporal gap between the Carnian South American herrerasaurids and the younger middle Norian–Rhaetian herrerasaurs of North America. Maleriraptor kuttyi shows the first evidence that herrerasaurs survived also in Gondwana the early Norian tetrapod turnover that resulted in the global extinction of the rhynchosaurs.

Cullin-RING ligases (CRLs) are a significant subset of Ubiquitin E3 ligases that regulate multiple cellular substrates involved in innate immunity, cytoskeleton modeling, and cell cycle. The glutamine deamidase Cycle inhibitory factor (Cif) from enteric bacteria inactivates CRLs to modulate these processes in the host cell. The covalent attachment of a Ubiquitin-like protein NEDD8 catalytically activates CRLs by driving conformational changes in the Cullin C-terminal domain (CTD). NEDDylation results in a shift from a compact to an open CTD conformation through non-covalent interactions between NEDD8 and the WHB subdomain of CTD, eliminating the latter’s inhibitory interactions with the RING E3 ligase-Rbx1/2. It is unknown whether the non-covalent interactions are sufficient to stabilize Cullin CTD’s catalytic conformation. We studied the dynamics of Cullin-CTD in the presence and absence of NEDD8 using atomistic molecular dynamics (MD) simulations. We uncovered that NEDD8 engages in non-covalent interactions with 4HB/αβ subdomains in Cullin-CTD to promote open conformations. Cif deamidates glutamine 40 in NEDD8 to inhibit the conformational change in CRLs by an unknown mechanism. We investigated the effect of glutamine deamidation on NEDD8 and its interaction with the WHB subdomain post-NEDDylation using MD simulations and NMR spectroscopy. Our results suggest that deamidation creates a new intramolecular salt bridge in NEDD8 to destabilize the NEDD8/WHB complex and reduce CRL activity.

Purpose: Crucial requirement of exstrophy bladder repair is to make patients continent as well as to preserve kidney functions. We analyzed our patients' data retrospectively to study their continence and to find out the justification behind continence and preservation of renal functions. Patients and Methods: We selected files of 18 fully continent patients from 52 patients operated. Eleven out of 18 patients were presented from beginning and 7 were referred after around 8 to 14 years, as incontinent bladder following good repair of bladder neck and posterior urethra. Eleven were operated with complete primary repair of exstrophy along with pubic osteotomy minimal and were kept on cystostomy track (CT) till augmentation to vent out vesical pressure. In seven patients, we did reduction of caliber of posterior urethra and bladder neck along with CT followed by augmentation after 6 months. Results: All 18 patients are maintaining dry period for 24 h. Two patients had enuresis but are manageable with partial fluid restriction from evening. Seventeen out of 18 patients are maintaining their renal functions. Conclusion: No tension abdominal wall closure with rectus muscle apposition is essential to preserve repaired bladder exstrophy. Osteotomy prevents lateral drag to overcome failure of whole reconstruction. Increased \"systolic\" vesical pressure from contraction of small bladder might destroy the mechanism of continence and renal functions. Hence, venting of vesical pressure through CT is obligatory till augmentation which is of necessity to be done as early as possible to create a low-pressure continent system.

Microraptor gui, a four-winged dromaeosaur from the Early Cretaceous of China, provides strong evidence for an arboreal-gliding origin of avian flight. It possessed asymmetric flight feathers not only on the manus but also on the pes. A previously published reconstruction shows that the hindwing of Microraptor supported by a laterally extended leg would have formed a second pair of wings in tetrapteryx fashion. However, this wing design conflicts with known theropod limb joints that entail a parasagittal posture of the hindlimb. Here, we offer an alternative planform of the hindwing of Microraptor that is concordant with its feather orientation for producing lift and normal theropod hindlimb posture. In this reconstruction, the wings of Microraptor could have resembled a staggered biplane configuration during flight, where the forewing formed the dorsal wing and the metatarsal wing formed the ventral one. The contour feathers on the tibia were positioned posteriorly, oriented in a vertical plane for streamlining that would reduce the drag considerably. Leg feathers are present in many fossil dromaeosaurs, early birds, and living raptors, and they play an important role in flight during catching and carrying prey. A computer simulation of the flight performance of Microraptor suggests that its biplane wings were adapted for undulatory \"phugoid\" gliding between trees, where the horizontal feathered tail offered additional lift and stability and controlled pitch. Like the Wright 1903 Flyer, Microraptor, a gliding relative of early birds, took to the air with two sets of wings.