A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges

Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-59

A Femtosecond Neutron Source

The possibility to use the ultrashort ion bunches produced by circularly polarized laser pulses to drive a source of fusion neutrons with sub-optical cycle duration is discussed. A two-side irradiation of a thin foil deuterated target produces two countermoving ion bunches, whose collision leads to an ultrashort neutron burst. Using particle-in-cell simulations and analytical modeling, it is evaluated that, for intensities of a few $10^{19} W cm^{-2}$, more than $10^3$ neutrons per Joule may be produced within a time shorter than one femtosecond. Another scheme based on a layered deuterium-tritium target is outlined.Comment: 15 pages, 3 figure

Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD-derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in the abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression of a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β, and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy

Global Networks of Trade and Bits

Considerable efforts have been made in recent years to produce detailed topologies of the Internet. Although Internet topology data have been brought to the attention of a wide and somewhat diverse audience of scholars, so far they have been overlooked by economists. In this paper, we suggest that such data could be effectively treated as a proxy to characterize the size of the "digital economy" at country level and outsourcing: thus, we analyse the topological structure of the network of trade in digital services (trade in bits) and compare it with that of the more traditional flow of manufactured goods across countries. To perform meaningful comparisons across networks with different characteristics, we define a stochastic benchmark for the number of connections among each country-pair, based on hypergeometric distribution. Original data are thus filtered by means of different thresholds, so that we only focus on the strongest links, i.e., statistically significant links. We find that trade in bits displays a sparser and less hierarchical network structure, which is more similar to trade in high-skill manufactured goods than total trade. Lastly, distance plays a more prominent role in shaping the network of international trade in physical goods than trade in digital services.Comment: 25 pages, 6 figure

The impacts of Information and Communications Technology (ICT) and E-commerce on bilateral trade flows

This study examines the impact of Internet and e-commerce adoption on bilateral trade flows using a panel of 21 developing- and least-developed countries and 30 OECD countries. Given the commitment of East African Community (EAC) to become the frontrunner in export-led economy across the African continent, special attention is dedicated to analyse the role of ICT and e-commerce on EAC’s export performance. The empirical results indicate that better access to the modern ICT and adoption of e-commerce applications stimulate bilateral trade flows at various levels. The study notes that the efficient use of ICT equipped with high speed internet and secured servers is a crucial milestone for unlocking the e-trade potentials for developing- and least-developed counties

An unusual presentation of anetoderma: a case report

BACKGROUND: Anetoderma is a benign condition with focal loss of dermal elastic tissue resulting in localized areas of flaccid or herniated saclike skin. Currently, anetoderma is classified as either primary (idiopathic), or secondary anetoderma (which is associated with a variety of skin conditions, penicillamine use, or neonatal prematurity). Lesions appear on the upper arms, trunk, and thighs. CASE PRESENTATION: We report a 14-year-old boy, which was noticed to have had multiple, white, non-pruritic areas on the acral sites of upper and lower extremities for two years. In physical examination, the patient had normal mental development. Skin lesions consisted of scattered, white to skin-colored papules, less than 1 cm in diameter, and with central protrusion, with distribution on dorsal part of the index finger, forearms, distal portion of thighs and calves. Lesions were detected neither on the trunk nor the proximal areas of extremities. There are no sensory changes associated with the lesions. Otherwise, his general health was good. He did not have any medication consumption history. Family history was negative. Laboratory examinations were within normal limits. Skin biopsy from one of his lesions was done, that confirmed the diagnosis of anetoderma. CONCLUSIONS: In summary, we report a case of anetoderma on unusual sites of the skin. We could not find similar reports of anetoderma developing on distal extremities without involvement of the upper trunk and proximal arms, in the medical literature