Simultaneous determination of six penicillins in cows'' raw milk by a multiresidue high-performance liquid chromatographic method

A high-performance liquid chromatographic method based on C₁₈ solid-phase extraction and ultraviolet detection at 323 nm of analytes derivatized with benzoic anhydride and 1,2,4-triazole mercuric chloride solution was developed for the simultaneous determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin and dicloxacillin residues in raw milk. The detection limit of the method was 1.3 μg/l for penicillin G; 1.4 μg/l for amoxicillin, oxacillin and cloxacillin, 1.5 μg/l for ampicillin and 2.7 μg/l for dicloxacillin. The mean recovery was 95–102% for amoxicillin, penicillin G and ampicillin, 92–98% for oxacillin and cloxacillin and 87–94% for dicloxacillin, measured by using an internal standard. The relative repeatability standard deviation was 4–9% on level 4–15 μg/l, respectively, 2–7% on level 30–40 μg/l.     

Cryptorchidism and Infertility in Rats with Targeted Disruption of the Adamts16 Locus

A Disintegrin And Metalloproteinase with ThromboSpondin motifs16 (ADAMTS-16) is a member of a family of metalloproteinases. Using a novel zinc-finger nuclease based gene-edited rat model harboring a targeted mutation of the Adamts16 locus, we previously reported this gene to be linked to blood pressure regulation. Here we document our observation with this model that Adamts16 is essential for normal development of the testis. Absence of Adamts16 in the homozygous Adamts16^mutant males resulted in cryptorchidism and male sterility. Heterozygous Adamts16^mutant males were normal, indicating that this is a recessive trait. Testes of homozygous Adamts16^mutant males were significantly smaller with significant histological changes associated with the lack of sperm production. Temporal histological assessments of the testis demonstrated that the seminiferous tubules did not support active spermatogenesis, but progressively lost germ cells, accumulated vacuoles and did not have any sperm. These observations, taken together with our previous report of renal abnormalities observed with the same Adamts16^mutant rats, suggest an important mechanistic link between Adamts16 and the functioning of the male genitourinary system.     

Mitochondrial morphodynamics alteration induced by influenza virus infection as a new antiviral strategy

Influenza virus infections are major public health threats due to their high rates of morbidity and mortality. Upon influenza virus entry, host cells experience modifications of endomembranes, including those used for virus trafficking and replication. Here we report that influenza virus infection modifies mitochondrial morphodynamics by promoting mitochondria elongation and altering endoplasmic reticulum-mitochondria tethering in host cells. Expression of the viral RNA recapitulates these modifications inside cells. Virus induced mitochondria hyper-elongation was promoted by fission associated protein DRP1 relocalization to the cytosol, enhancing a pro-fusion status. We show that altering mitochondrial hyper-fusion with Mito-C, a novel pro-fission compound, not only restores mitochondrial morphodynamics and endoplasmic reticulum-mitochondria contact sites but also dramatically reduces influenza replication. Finally, we demonstrate that the observed Mito-C antiviral property is directly connected with the innate immunity signaling RIG-I complex at mitochondria. Our data highlight the importance of a functional interchange between mitochondrial morphodynamics and innate immunity machineries in the context of influenza viral infection.     

Apoptosis repressor with caspase recruitment domain is dramatically reduced in cardiac, skeletal, and vascular smooth muscle during hypertension

Apoptosis repressor with caspase recruitment domain (ARC) is a unique anti-apoptotic protein with a distinct tissue distribution. In addition, unlike most anti-apoptotic proteins which act on one pathway, ARC can inhibit apoptosis mediated by both the death-receptor and mitochondrial signaling pathways. In this study, we confirm previous reports showing high levels of ARC protein in rat heart and skeletal muscle, but demonstrate for the first time that ARC is also expressed in rat aorta. Immunoblot analysis on endothelium-denuded aorta as well as immunohistochemical analysis on intact aorta demonstrated that ARC was highly expressed in smooth muscle. Immunoblot analysis also found that ARC protein was severely downregulated in skeletal muscle (−82%; P < 0.001), heart (−80%; P < 0.001), and aorta (−71%; P < 0.001) of spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. Decreased ARC levels were also confirmed in tissues of hypertensive animals by immunohistochemical analysis. Collectively, this data suggests that ARC protein is expressed in vascular smooth muscle and is significantly reduced in several target tissues during hypertension.     

An integrated framework for discovery and genotyping of genomic variants from high-throughput sequencing experiments

Recent advances in high-throughput sequencing (HTS) technologies and computing capacity have produced unprecedented amounts of genomic data that have unraveled the genetics of phenotypic variability in several species. However, operating and integrating current software tools for data analysis still require important investments in highly skilled personnel. Developing accurate, efficient and user-friendly software packages for HTS data analysis will lead to a more rapid discovery of genomic elements relevant to medical, agricultural and industrial applications. We therefore developed Next-Generation Sequencing Eclipse Plug-in (NGSEP), a new software tool for integrated, efficient and user-friendly detection of single nucleotide variants (SNVs), indels and copy number variants (CNVs). NGSEP includes modules for read alignment, sorting, merging, functional annotation of variants, filtering and quality statistics. Analysis of sequencing experiments in yeast, rice and human samples shows that NGSEP has superior accuracy and efficiency, compared with currently available packages for variants detection. We also show that only a comprehensive and accurate identification of repeat regions and CNVs allows researchers to properly separate SNVs from differences between copies of repeat elements. We expect that NGSEP will become a strong support tool to empower the analysis of sequencing data in a wide range of research projects on different species.     

Isolation and characterization of superoxide dismutase: A personal history and tribute to Joe McCord and Irwin Fridovich

The discovery of superoxide dismutase twenty years ago gave new meaning to work on erythrocuprein. This tribute to the achievement of Joe McCord and Irwin Fridovich is an account of experience of superoxide dismutase from old obscure copper protein of red blood cells to new exciting enzyme of oxygen free-radical metabolism, and an affirmation of the superoxide theory of oxygen toxicity.     

Abnormalities of human sex chromosomes

Summary The cytogenetic study of a pair of identical, mentally-retarded twins with the chromosome complement 48,XXXY is reported, along with extensive clinical and endocrinological studies of one twin.The genetic and clinical features of 30 reported 48,XXXY individuals were summarized and compared to those of 47,XXY and 49,XXXXY individuals. For 47,XXY the mean maternal age clearly is increased; for 48,XXXY it appears definitely but only slightly increased; and for 49,XXXXY it may not be increased at all. Developmental defects, similar in type, appear to be progressively more marked when an additional 1, 2, or 3 X chromosomes are added to the normal male chromosome complement. 47,XXY individuals may be either normal in intelligence or mentally retarded, whereas severe mental retardation has been present in all those with the complements 48,XXXY and 49,XXXXY.The interesting suggestion of increased twining associated with poly-X male complements is noted.

---

Zusammenfassung Die cytogenetische Untersuchung eines Paares eineiiger, geistig zurückgebliebener Zwillinge mit dem Chromosomenstatus 48,XXXY wird dargestellt; bei dem einen Paarling konnten außerdem ausgedehnte klinische und endokrinologische Studien durchgeführt werden.Außerdem wurden die genetischen und klinischen Merkmale der 30 bekannten Fälle mit 48,XXXY dargestellt und mit denen von Patienten mit 47,XXY und mit 49,XXXXY verglichen. Bei Fällen mit 47,XXY ist das mütterliche Alter deutlich erhöht; bei 48,XXXY ist es eindeutig, aber nur leicht erhöht; es sieht so aus, als ob es für 49,XXXXY überhaupt nicht erhöht wäre. Defekte der Entwicklung, die dem Typ nach ähnlich sind, scheinen dem Ausmaß nach desto mehr ausgeprägt zu sein, je mehr X-Chromosomen zusätzlich bei dem normalen männlichen Chromosomensatz vorhanden sind. 47,XXY Individuen können entweder schwachsinnig sein oder eine normale Intelligenz haben; dagegen zeigten alle Fälle mit 48,XXXY und 49,XXXXY einen schweren Schwachsinn.Es wird die interessante Frage aufgeworfen, ob die Zwillingshäufigkeit bei Poly X-Männern erhöht ist.

---

---

Research supported by grants HD 04134, HL 09011, RR-47, AM-11105, and TIAM 53950-11 from the National Institutes of Health.