Miracle-dz/UniFAR-FTUs huggingface dataset:
Inherited lipodystrophies and hypertriglyceridemia

Purpose of review Inherited lipodystrophies are rare autosomal recessive and dominant disorders characterized by selective, but variable, loss of adipose tissue. Marked hypertriglyceridemia is a common feature of these disorders and highlights the role of adipose tissue in lipid homeostasis. In the last decade, advances have been made in elucidating the molecular basis of many inherited lipodystrophies. We review the new insights in the pathophysiology and treatment of these disorders based on the current understanding of the biologic role of these lipodystrophy genes. Recent findings Eight different genetic loci, including 1-acylglycerol-3-phosphate-O-acyltransferase 2, Berardinelli–Seip congenital lipodystrophy 2, caveolin 1, lamin A/C, peroxisome proliferator-activated receptor gamma, v-AKT murine thymoma oncogene homolog 2, zinc metalloprotease and lipase maturation factor 1 have been described linked to different lipodystrophy syndromes. Mutations in these genes may cause fat loss and dyslipidemia through multiple mechanisms, which remain fully elucidated; however, they may involve defects in development and differentiation of adipocytes, and premature death and apoptosis of adipocytes. Hypertriglyceridemia is a consequence of increased VLDL synthesis from the liver, which is also loaded by ectopic triglyceride deposition, reduced clearance of triglyceride-rich lipoproteins or both. A recent study in mice with Agpat2 deficiency reports marked reduction in serum triglyceride upon feeding a fat-free diet, which suggests that low-fat diets are likely to be beneficial in lipodystrophic patients. Leptin replacement therapy is also a promising therapeutic option for lipodystrophic patients with hypoleptinemia. Summary Inherited lipodystrophies are an important cause for monogenic hypertriglyceridemia and serve to highlight the role of adipocytes in maintaining normolipidemia.
Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route.

A murine model based on infection by the respiratory route has been used to study the pathogenesis of recombinant vaccinia viruses. The neurovirulent Western Reserve (WR) strain and the Wyeth smallpox vaccine strain were used as vectors. Recombinant viruses were constructed by insertion of the Epstein-Barr virus membrane glycoprotein 340 gene into the thymidine kinase (TK) gene of each vaccinia virus. Intranasal inoculation of DBA/2 mice with 10(6) pock-forming units (pk.f.u.) of the WR strain was lethal but mice survived similar infection with the WR recombinant virus. Each virus was recovered from lung, blood and brain but, unlike wild-type virus, the recombinant virus was subsequently cleared. No deaths occurred after similar infection with the Wyeth strain or the Wyeth recombinant virus. There was limited growth of the Wyeth strain in the respiratory tract, low levels of virus in the blood and only sporadic recovery in brain extracts. The Wyeth recombinant virus was cleared rapidly with little viraemia or detectable infection of the central nervous system. No phenotypic character determined in vitro could be related consistently to the virulence of wild-type and recombinant viruses. Although the lethal character of the WR strain was affected by its TK+ phenotype, mice survived infection by intranasal inoculation with 10(6) pk.f. u. of WR TK+ recombinant viruses which either expressed the human interleukin 2 gene or had a deficient vaccinia virus growth factor gene.
Growth, Unemployment and Wage Inertia

We introduce wage setting via efficiency wages in the neoclassical one-sector growth model to study the growth effects of wage inertia. We compare the dynamic equilibrium of an economy with wage inertia with the equilibrium of an economy without it. We show that wage inertia affects the long run employment rate and that the transitional dynamics of the main economic variables will be different because wages are a state variable when wage inertia is introduced. In particular, we show that the model with wage inertia can explain some growth patterns that cannot be explained when wages are flexible. We also study the growth effects of permanent technological and fiscal policy shocks in these two economies. During the transition, the growth effects of technological shocks obtained when wages exhibit inertia may be the opposite of those obtained when wages are flexible. These technological shocks may have long run effects if there is wage inertia.
Production of cloned pigs expressing human thrombomodulin in endothelial cells

Yazaki S, Iwamoto M, Onishi A, Miwa Y, Hashimoto M, Oishi T, Suzuki S, Fuchimoto D‐I, Sembon S, Furusawa T, Liu DG, Nagasaka T, Kuzuya T, Ogawa H, Yamamoto K, Iwasaki K, Haneda M, Maruyama S, Kobayashi T. Production of cloned pigs expressing human thrombomodulin in endothelial cells. Xenotransplantation 2012; 19: 82–91. © 2012 John Wiley & Sons A/S.
Biomechanical Analysis and Review of Lateral Lumbar Fusion Constructs

Study Design. Biomechanical study and the review of literature on lumbar interbody fusion constructs. Objective. To demonstrate the comparative stabilizing effects of lateral interbody fusion with various supplemental internal fixation options. Summary of Background Data. Lumbar interbody fusion procedures are regularly performed using anterior, posterior, and more recently, lateral approaches. The biomechanical profile of each is determined by the extent of resection of local supportive structures, implant size and orientation, and the type of supplemental internal fixation used. Methods. Pure moment flexibility testing was performed using a custom-built 6 degree-of-freedom system to apply a moment of ±7.5 Nm in each motion plane, while motion segment kinematics were evaluated using an optoelectronic motion system. Constructs tested included the intact spine, stand-alone extreme lateral interbody implant, interbody implant with lateral plate, unilateral and bilateral pedicle screw fixation. These results were evaluated against those from literature-reported biomechanical studies of other lumbar interbody constructs. Results. All conditions demonstrated a statistically significant reduction in range of motion (ROM) as a percentage of intact. In flexion-extension, ROM was 31.6% stand-alone, 32.5% lateral fixation, and 20.4% and 13.0% unilateral and bilateral pedicle screw fixation, respectively. In lateral bending, the trend was similar with greater reduction with lateral fixation than in flexion-extension; ROM was 32.5% stand-alone, 15.9% lateral fixation, and 21.6% and 14.4% unilateral and bilateral pedicle screw fixation. ROM was greatest in axial rotation; 69.4% stand-alone, 53.4% lateral fixation, and 51.3% and 41.7% unilateral and bilateral pedicle screw fixation, respectively. Conclusion. The extreme lateral interbody construct provided the largest stand-alone reduction in ROM compared with literature-reported ALIF and TLIF constructs. Supplemental bilateral pedicle screw-based fixation provided the overall greatest reduction in ROM, similar among all interbody approach techniques. Lateral fixation and unilateral pedicle screw fixation provided intermediate reductions in ROM. Clinically, surgeons may evaluate these comparative results to choose fixation options commensurate with the stability requirements of individual patients.
Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men*

The capacity for conversion of α-linolenic acid (ALNA) to n−3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U−13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n−3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALNA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.
Andrology: Natural spermatoceles in irreversible obstructive azoospermia—reservoirs of viable spermatozoa for assisted conception

: Fine needle aspiration of asymptomatic spermatoceles detected in five men with obstructive azoospermia was evaluated as a minimally invasive method of sperm retrieval for assisted conception. Sperm preparations adequate for in-vitro fertilization were initially obtained from three men, but there was failure of fertilization in all three cycles. However, intracytoplasmic sperm injection (ICSI) in three couples resulted in fertilization of 58% of metaphase II oocytes, with embryo transfers in five of six cycles. A successful pregnancy and delivery resulted from spermatozoa from a man with an irreversible vasectomy, for whom previous epididymal microaspiration and ICSI had been unsuccessful. Spermatoceles were found in 4% of men with irreversible obstructive azoospermia referred for assisted conception. These patients should therefore be examined very carefully for small cysts near the epididymis, because fine needle aspiration, usually without anaesthesia, can instantly locate a ready source of viable spermatozoa for ICSI. This is less invasive than the alternative sperm retrieval procedures, which are more traumatic and require local or general anaesthesia.
A histological study of local anesthetic‐induced muscle degeneration and regeneration in the monkey

Small amounts (1–2 ml) of local anesthetics (bupivacaine, lidocaine, and mepivacaine) were injected into the abductor pollicis brevis muscles of 35 monkeys. Control muscles were injected with saline. The muscles were preserved for histology from 4.5 h to 48 days after the injection. Histological damage to muscle fibers was evident from the time of the first sampling. Invasion of damaged muscle fibers by phagocytic cells was prominent by 2–3 days postinjection. At 4 to 5 days, areas of muscle fiber damage were characterized by dense concentrations of phagocytes and mononuclear myoblastic cells. At 6 days, fields of early myotubes were evident. Maturation of myotubes into immature cross‐striated muscle fibers occurred over the next week. Occasional myotubes or immature regenerating muscle fibers were seen as late as 28 days. The topographical pattern of muscle fiber degeneration and regeneration showed a concentration along the surfaces of muscle fascicles or, if intrafascicular, around the presumed site of injection.
Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins

ABSTRACT The primate TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. The TRIM5 proteins act early after virion entry and prevent viral reverse transcription products from accumulating. We recently found that proteasome inhibitors altered the rhesus monkey TRIM5α restriction of human immunodeficiency virus type 1 (HIV-1), allowing reverse transcription products to accumulate even though viral infection remained blocked. To assess whether sensitivity to proteasome inhibitors was a common feature of primate TRIM5 proteins, we conducted a similar analysis of restriction mediated by owl monkey TRIM-cyclophilin A (CypA) or human TRIM5α. Similar to rhesus monkey TRIM5α restriction, proteasome inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse transcription, even though HIV-1 infection and the output of 2-LTR circles remained impaired. Likewise, proteasome inhibition alleviated human TRIM5α restriction of N-tropic murine leukemia virus reverse transcription. Finally, HIV-1 reverse transcription products escaping rhesus TRIM5α restriction by proteasome inhibition were fully competent for integration in vitro, demonstrating that TRIM5α likely prevents the viral cDNA from accessing chromosomal target DNA. Collectively, these data indicate that the diverse TRIM5 proteins inhibit retroviral infection in multiple ways and that inhibition of reverse transcription products is not necessary for TRIM5-mediated restriction of retroviral infection.
FutureCrafting: Speculation, Design and the Nonhuman, or how to live with digital uncertainty

How can design craft potential futures in a scenario shaped by planetary computation? Unlike 4th revolution narratives that frame the future of human-machine interaction as techno-dystopias, a future of human-machine coevolution can be imagined by speculating on digital uncertainty: the potential for unpredictability in computation, manifest in the autonomy of algorithmic agency. Human-machine interaction is then reframed in terms of human-nonhuman ecologies that are emergent, cohabiting and highly contingent. Speculation via design is proposed as a mode of strategic, metic intelligence, able to capture and to capitalise on this systemic unpredictability, enabling the proposition of what ‘may be’: future-crafting in action. Invited Talk. Presented at the Symposium: Agents in the Anthropocene: Trans/disciplinary Practices in Art and Design Education Today.
Arginine synthesis by hepatomas in vitro. I. The requirements for cell growth in medium containing ornithine in place of arginine and the isolation and characterization of variant hepatomas auxotrophic for arginine.

Cell growth in 'ornithine-medium' requires the expression of two liver-specific genes, those for ornithine transcarbamoylase (OTC) and carbamoyl phosphate synthetase I (CPS-I). CPS-II appears unable to replace CPS-I in this system. The need for N-acetylglutamate (to activate CPS-I) can be met, at least in part, by providing it in the medium. The other gene products involved in arginine biosynthesis are probably all ubiquitous (i.e. not tissue-specific). In an attempt to study the factors responsible for the expression of liver-specific genes, variant hepatomas are isolated that have lost the ability to grow in ornithine-medium. Two classes of 'orn-' variants are identified: unstable variants that require dexamethasone for adequate CPS-I production, and 'stable' variants that have lost many liver-specific traits. Studies on one stable variant show that it can revert (though rarely), and that it regains its various liver-specific traits in a non-coordinate fashion.
Mutants in flaI and flaJ of the archaeon Methanococcus voltae are deficient in flagellum assembly

The fla gene locus of Methanococcus voltae encodes the major structural components of the flagellum as well as other flagellar‐related proteins. The flaHIJ genes have been found in all flagellated archaea, suggesting a central role in flagella biogenesis. FlaI shares similarity with the type II and type IV secretion NTPases (such as PilB, VirB11 and TadA), and FlaJ exhibits similarity to putative bacterial integral membrane proteins involved in type IV pilus biogenesis such as TadB. In this study, reverse transcription polymerase chain reaction (RT‐PCR) and Northern blotting data revealed that flaHIJ are co‐transcribed with the upstream structural flagellin genes, thus demonstrating the expression of the entire fla gene cluster in vivo. Non‐polar mutants in flaI and flaJ of M. voltae were isolated using insertional inactivation via a novel mutagenic vector. These mutants were non‐motile and non‐flagellated by microscopy, demonstrating the involvement of FlaI and FlaJ in flagella biogenesis. Interestingly, all the mutants maintained the ability to produce and localize flagellins to the cytoplasmic membrane. Amino‐terminal sequencing of flagellins produced by the flaJ mutant strain revealed that the flagellins did not have their cognate leader peptides, thus indicating that preflagellin processing had occurred in vivo. This result was confirmed using an in vitro processing assay. The fla− phenotype and protein secretion characteristics of the flaI and flaJ mutants therefore implicate these respective genes in archaeal flagellin secretion and assembly. These findings further support a model describing the archaeal flagellum as a novel prokaryotic motility structure.
The Mechanisms of Pain-Induced Pulmonary Vasoconstriction: An Experimental Study in Fetal Lambs

BACKGROUND:Nociceptive stimulation induces pulmonary vasoconstriction in fetuses and newborns. The mechanism of this response is not fully understood. As the systemic hemodynamic response to pain is mainly mediated by sympathetic stimulation, we hypothesized that pain-induced pulmonary vasoconstriction results from the activation of catecholaminergic receptors. To test this hypothesis, we studied the pulmonary vascular response to nociceptive stimuli in fetal lambs before and after &agr;-adrenoceptor blockade. METHODS:Surgery was performed in fetal lambs. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery, and subcutaneous catheters were placed in the limb. The hemodynamic responses to (1) subcutaneous injection of formalin (which is used as nociceptive stimulus in experimental studies), (2) prazosin (specific &agr;1-adrenoceptor antagonist), and (3) formalin during prazosin infusion were evaluated. Plasma cortisol and catecholamine concentrations were measured. RESULTS:Pulmonary vascular resistance (PVR) increased by 50% (P < 0.01) after the formalin test. PVR did not change after the formalin test during prazosin infusion or during prazosin infusion alone. Catecholamine and cortisol levels did not change during any of the protocols. DISCUSSION:Our results indicate that the fetal pulmonary vasoconstrictive response to pain involves &agr;1-adrenoceptors activation. As plasma catecholamine concentrations did not change after the formalin test, we speculate that the pulmonary vascular response to nociceptive stimuli could be triggered by a local release of catecholamine induced by sympathetic stimulation.
Multiple myeloma in Northern Israel, 1970–1979

From 1970 to 1979, multiple myeloma was diagnosed in 184 residents of Northern Israel. The data were analyzed for variations by demographic factors, ethnicity, country of origin, and urban/rural residence areas. The average annual age‐adjusted incidence rate per 100,000 residents was 1.78. The rates for males and females were 2.1 and 1.46/105 person‐years, respectively. The male to female incidence ratio was 1.44:1.0. The average incidence rate was significantly higher for Jews than for Arabs and was higher for European Jews than for Afro‐Asians or native Israelis. Urban areas had significantly higher rates than rural areas. A statistically significant increase in the incidence rates was demonstrated for the years 1975 to 1979 compared to the period 1970 to 1974. The increase was evident in all population categories, but was particularly prominent in females, the Jewish population, urban areas, and in the oldest age group. The results of the current study suggest that both culturally derived factors and industrial environment may play a role in the etiology of multiple myeloma. Cancer 58:206–209, 1986.
Administration of the potent PPARα agonist, Wy‐14,643, reverses nutritional fibrosis and steatohepatitis in mice

Administration of a methionine and choline deficient (MCD) diet to rodents causes progressive fibrosing steatohepatitis pathologically similar to human metabolic steatohepatitis. We have previously shown that the peroxisome proliferator‐activated receptor‐α (PPARα) agonist, Wy‐14,643, prevented the development of MCD diet‐induced steatohepatitis. We have now tested whether Wy‐14,643 ameliorates established steatohepatitis and fibrosis. Male C57BL6 mice were fed the MCD diet for 51 days to induce severe steatohepatitis. They were then treated with Wy‐14,643 together with the MCD diet for 5 or 12 days; positive controls continued on the MCD diet for 5 or 12 days. After 5 days of Wy‐14,643 treatment, alanine aminotransferase (ALT) levels were significantly decreased, steatohepatitis less severe, and hepatic lipoperoxides significantly reduced. After 12 days, hepatic triglycerides were normalized and there was near resolution of histological changes. MCD dietary feeding was associated with increased expression of vascular cell adhesion molecule (VCAM)‐1, and increased numbers of activated macrophages in the liver. Treatment with Wy‐14,643 reduced VCAM‐1 expression and macrophage numbers. MCD diet‐fed mice developed hepatic fibrosis with increased hepatic collagen α1(I), tissue inhibitor of metalloproteinases (TIMP)‐1, TIMP‐2, and matrix metalloproteinase (MMP)‐13 mRNA levels. After treatment with Wy‐14,643, expression of these genes was reduced in a manner that paralleled the reduction in activated hepatic stellate cells and near resolution of liver fibrosis. In conclusion, the present study shows that MCD diet‐induced fibrosing steatohepatitis can be reversed by treatment with Wy‐14,643. It is likely that activation of PPARα reverses fibrosis indirectly by reducing stimuli, such as lipid peroxides, and activation of cells responsible for promoting hepatic fibrosis. (HEPATOLOGY 2004;39:1286–1296.)
Statin therapy and stroke prevention: what was known, what is new and what is next?

Purpose of review Randomized trials have shown that statins may reduce the risk of primary stroke. There is no evidence however that statins can reduce recurrent stroke incidence. Recent findings In the SPARCL trial, patients with a recent stroke or transient ischemic attack randomized to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke, and a 35% reduction in major coronary events compared with placebo. This was obtained despite 25% of the placebo arm patients receiving a commercially-available statin outside of the trial. Post-hoc analysis used blinded LDL-cholesterol measurements as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-cholesterol (the group adherent to placebo or not taking a statin), the group with over 50% reduction in LDL-cholesterol had a significant 31% reduction in stroke. The next step is to define whether achieving LDL-cholesterol below 70 mg/dl is better than a standard dose of statin (LDL around 100–110 mg/dl) in the secondary prevention of stroke. Summary Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-cholesterol lowering.