Foreword

The immigration laws in our country have been influenced by population growth and distribution, as well as economic and political conditions both in the United States and foreign nations. Such influences have caused significant variations in patterns of immigration throughout our nation\u27s history. It is important for us to remember our distinguished immigrant heritage when commenting upon past immigration policy and projecting as to the future of our immigration laws

Editorial

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Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency following AAV5 Gene Transfer

The dysferlinopathies comprise a group of untreatable muscle disorders including limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment syndrome, and rigid spine syndrome. As with other forms of muscular dystrophy, adeno-associated virus (AAV) gene transfer is a particularly auspicious treatment strategy, however the size of the DYSF cDNA (6.5 kb) negates packaging into traditional AAV serotypes known to express well in muscle (i.e. rAAV1, 2, 6, 8, 9). Potential advantages of a full cDNA versus a mini-gene include: maintaining structural-functional protein domains, evading protein misfolding, and avoiding novel epitopes that could be immunogenic. AAV5 has demonstrated unique plasticity with regards to packaging capacity and recombination of virions containing homologous regions of cDNA inserts has been implicated in the generation of full-length transcripts. Herein we show for the first time in vivo that homologous recombination following AAV5.DYSF gene transfer leads to the production of full length transcript and protein. Moreover, gene transfer of full-length dysferlin protein in dysferlin deficient mice resulted in expression levels sufficient to correct functional deficits in the diaphragm and importantly in skeletal muscle membrane repair. Intravascular regional gene transfer through the femoral artery produced high levels of transduction and enabled targeting of specific muscle groups affected by the dysferlinopathies setting the stage for potential translation to clinical trials. We provide proof of principle that AAV5 mediated delivery of dysferlin is a highly promising strategy for treatment of dysferlinopathies and has far-reaching implications for the therapeutic delivery of other large genes

Nodular diagnosis for ecological engineering of the symbiotic nitrogen fixation with legumes

As a major contributor to the reduced nitrogen pool in the biosphere, symbiotic nitrogen fixation by legumes plays a critical role in a sustainable production system. However this legume contribution varies with the physico-chemical and biological conditions of the nodulated-root rhizosphere. In order to assess the abiotic and biotic constrains that might limit this symbiosis at the agroecosystem level, a nodular diagnosis is proposed with common bean as a model grain-legume, and a major source of plant proteins for world human nutrition. The engineering of the legume symbiosis is addressed by participatory assessment of bean recombinant inbred lines contrasting for their efficiency in use of phosphorous for symbiotic nitrogen fixation. With this methodology, in field-sites chosen with farmers of an area of cereal-cropping in the Mediterranean basin, a large spatial and temporal variation in the legume nodulation was found. Soil P availability was a major limiting factor of the rhizobial symbiosis. In order to relate the field measurements with progress in functional genomics of the symbiosis, in situ RT-PCR on nodule sections has been implemented showing that the phytase gene is expressed in the cortex with significantly higher number of transcripts in P-efficient RILs. It is concluded that various tools and indicators are available for developing the ecological engineering of the rhizobial symbiosis, in particular for its beneficial contribution to the bio-geochemical cycle of N, and also P and C

Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities