Syndromic congenital myelofibrosis associated with a loss-of-function variant in RBSN

The human proteins rabenosyn-5 and VPS45 form a complex that plays a key role in early endocytosis. Pathogenic variants in VPS45 cause severe congenital neutropenia (SCN) with impaired neutrophil function, reticulin fibrosis of the bone marrow, and extramedullary hematopoiesis (OMIM: 615285). Patients with a specific VPS45 variant (p.Glu238Lys) also have intellectual disability and bilateral optic nerve hypoplasia. To date, the only evidence of a potential role for RBSN in human disease is the report of a homozygous missense variant (p.Gly425Arg) in a patient with intellectual disability, seizures, microcephaly, osteopenia, mild reticulin fibrosis of the bone marrow, and transient neutropenia

Innate Immune Activation and Subversion of Mammalian Functions by Leishmania Lipophosphoglycan

Leishmania promastigotes express several prominent glycoconjugates, either secreted or anchored to the parasite surface. Of these lipophosphoglycan (LPG) is the most abundant, and along with other phosphoglycan-bearing molecules, plays important roles in parasite infectivity and pathogenesis in both the sand fly and the mammalian host. Besides its contribution for parasite survival in the sand fly vector, LPG is important for modulation the host immune responses to favor the establishment of mammalian infection. This review will summarize the current knowledge regarding the role of LPG in Leishmania infectivity, focusing on the interaction of LPG and innate immune cells and in the subversion of mammalian functions by this molecule

Influence of feeding on the circadian rhythm of digestive enzymes in cultivated juveniles of the freshwater crayfish Cherax quadricarinatus (Parastacidae)

Se analiza en juveniles en etapa de engorde (7 g) de Cherax quadricarinatus, el ritmo circadiano de los niveles de proteínas totales, la actividad de las proteasas, lipasas y amilasas, y su posible modificación en función del momento de alimentación matutino (8 h) y vespertino (17 h). En general, la actividad de las enzimas digestivas de los juveniles de C. quadricarinatus no mostró un patrón circadiano de secreción, a excepción de las lipasas, donde se observó un incremento de actividad hacia la tarde-noche y disminución hacia las primeras horas de la mañana. Los niveles de proteína total, la actividad de proteinasas y amilasas registradas en la glándula digestiva, permanecieron prácticamente inalterados en todos los experimentos. A pesar de ello, se observó tendencia a que los niveles de actividad de proteinasas disminuyan luego del pulso de alimentación, recuperando los niveles anteriores 3 h después, independientemente del horario de alimentación. En cambio la actividad de amilasa no mostró ninguna tendencia por efecto del horario de alimentación. El estudio de los patrones de secreción de las enzimas digestivas y sus posibles modificaciones, podría ser utilizado como una herramienta para establecer los momentos del día más propicios para la alimentación de los juveniles en cultivo.ABSTRACT. We analyze in juvenile Cherax quadricarinatus fattening stage, the circadian rhythm of total protein levels, activity of proteases, lipases and amylases, and their possible change as a function of morning (8 h) and evening (17 h) feeding. In general, the activity of digestive enzymes of juvenile C. quadricarinatus showed no circadian pattern of secretion of lipases except where there was an increase towards the evening-night and a decrease towards the early hours of the morning. The total protein levels, the activity of proteinases and amylases of juveniles of C. quadricarinatus registered in the midgut gland remained virtually unchanged in all experiments. However, a non-significant tendency to diminish the proteinase activity levels after the feeding pulse was observed, with a return to previous enzymatic levels after 3 h. In contrast, the amylase activity did not show an observable effect by the feeding schedule. The study of the patterns of the digestive enzyme secretion and their possible changes, could be used as a tool to establish the most favorable times of the day for juveniles feeding.Fil: Sacristán, Hernán Javier. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; Argentina; Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biologia Experimental y Aplicada; Argentina;Fil: Franco-Tadic, Luis M.. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental. Laboratorio de Fisiologia de Crustáceos; Argentina;Fil: Lopez, Laura Susana. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Biodiversidad y Biologia Experimental; Argentina; Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biologia Experimental y Aplicada; Argentina

Explosive Disintegration of a Massive Young Stellar System in Orion

Young massive stars in the center of crowded star clusters are expected to undergo close dynamical encounters that could lead to energetic, explosive events. However, there has so far never been clear observational evidence of such a remarkable phenomenon. We here report new interferometric observations made with the Submillimeter Array (SMA) that indicate the well known enigmatic wide-angle outflow located in the Orion BN/KL star-forming region to have been produced by such a violent explosion during the disruption of a massive young stellar system, and that this was caused by a close dynamical interaction about 500 years ago. This outflow thus belongs to a totally different family of molecular flows which is not related to the classical bipolar flows that are generated by stars during their formation process. Our molecular data allow us to create a 3D view of the debris flow and to link this directly to the well known Orion H$_2$ "fingers" farther outComment: Accepted by ApJ Letters The 3D movie can be found in: ftp://ftp.mpifr-bonn.mpg.de/outgoing/lzapata/movie.gi

A Multiple System of Radio Sources at the Core of the L723 Multipolar Outflow

We present high angular resolution Very Large Array multi-epoch continuum observations at 3.6 cm and 7 mm towards the core of the L723 multipolar outflow revealing a multiple system of four radio sources suspected to be YSOs in a region of only ~4 arcsecs (1200 AU) in extent. The 3.6 cm observations show that the previously detected source VLA 2 contains a close (separation ~0.29 arcsecs or ~90 AU) radio binary, with components (A and B) along a position angle of ~150 degrees. The northern component (VLA 2A) of this binary system is also detected in the 7 mm observations, with a positive spectral index between 3.6 cm and 7 mm. In addition, the source VLA 2A is associated with extended emission along a position angle of ~115 degrees, that we interpret as outflowing shock-ionized gas that is exciting a system of HH objects with the same position angle. A third, weak 3.6 cm source, VLA 2C, that is detected also at 7 mm, is located ~0.7 arcsecs northeast of VLA 2A, and is possibly associated with the water maser emission in the region. The 7 mm observations reveal the presence of an additional source, VLA 2D, located ~3.5 arcsecs southeast of VLA 2A, and with a 1.35 mm counterpart. All these radio continuum sources have a positive spectral index, compatible with them being YSOs. We also propose that the high velocity CO emission observed in the region could be the superposition of multiple outflows (at least three independent bipolar outflows) excited by the YSOs located at the core, instead of the previous interpretations in terms of only one or two outflows.Comment: Accepted for publication in The Astrophysical Journal (2007 December 6

Effect of Caffeine on Heart Rate and Calories Burned During Exercise

Four active collegiate level students were asked to participate in a 3 day study, conducted in a strict environment. These students were required to perform the same exact exercise each day at the same time upon waking on an empty stomach following a fasted sleep. All individuals performed the exercise at 7:00 AM. On day one, the participant was to perform the exercise with no caffeine consumption. The following day, the participant was to drink one cup of coffee and perform the required exercise. On the last day of the experiment, each participant drank two cups of coffee before the exercise was performed. The exercise was one mile of walking on a flat treadmill at a speed of 3.5mph. These individuals were wearing a Garmin fitness watch and the heart rate strap that was included in the packaging. Immediately following exercise, these individuals took note of both their heart rate and calories burned. The basis of this study is to show the effects of caffeine on calorie burn and heart rate fluctuation. Following this study, it is important to note that all four participants showed a slight increase in both calories burned and heart rate following the required exercise on each day. The average calories burned with no caffeine was 109.25 and a heart rate of 103 beats per minute. When one cup of coffee was consumed by each individual, the average readings were 118.5 calories burned and a heart rate of 110.25 beats per minute. On the third and final day, the averages were 123.75 calories burned and a heart rate of 120 beats per minute. Thus, proving that caffeine consumption before exercise can help increase heart rate and in return burn more calories. This information can be especially helpful to all individuals trying to lose weight

Monitoring the Large Proper Motions of Radio Sources in the Orion BN/KL Region

We present absolute astrometry of four radio sources in the Becklin-Neugebauer/Kleinman-Low (BN/KL) region, derived from archival data (taken in 1991, 1995, and 2000) as well as from new observations (taken in 2006). All data consist of 3.6 cm continuum emission and were taken with the Very Large Array in its highest angular resolution A configuration. We confirm the large proper motions of the BN object, the radio source I (GMR I) and the radio counterpart of the infrared source n (Orion-n), with values from 15 to 26 km/s. The three sources are receding from a point between them from where they seem to have been ejected about 500 years ago, probably via the disintegration of a multiple stellar system. We present simulations of very compact stellar groups that provide a plausible dynamical scenario for the observations. The radio source Orion-n appeared as a double in the first three epochs, but as single in 2006. We discuss this morphological change. The fourth source in the region, GMR D, shows no statistically significant proper motions. We also present new, accurate relative astrometry between BN and radio source I that restrict possible dynamical scenarios for the region. During the 2006 observations, the radio source GMR A, located about 1' to the NW of the BN/KL region, exhibited an increase in its flux density of a factor of ~3.5 over a timescale of one hour. This rapid variability at cm wavelengths is similar to that previously found during a flare at millimeter wavelengths that took place in 2003.Comment: Accepted for publication in Ap

Phase behaviour of hard cylinders

Using isobaric Monte Carlo simulations, we map out the entire phase diagram of a system of hard cylindrical particles of length $L$ and diameter $D$, using an improved algorithm to identify the overlap condition between two cylinders. Both the prolate $L/D>1$ and the oblate $L/D<1$ phase diagrams are reported with no solution of continuity. In the prolate $L/D>1$ case, we find intermediate nematic \textrm{N} and smectic \textrm{SmA} phases in addition to a low density isotropic \textrm{I} and a high density crystal \textrm{X} phase, with \textrm{I-N-SmA} and \textrm{I-SmA-X} triple points. An apparent columnar phase \textrm{C} is shown to be metastable as in the case of spherocylinders. In the oblate $L/D<1$ case, we find stable intermediate cubatic \textrm{Cub}, nematic \textrm{N}, and columnar \textrm{C} phases with \textrm{I-N-Cub}, \textrm{N-Cub-C}, and \textrm{I-Cub-C} triple points. Comparison with previous numerical and analytical studies is discussed. The present study, accounting for the explicit cylindrical shape, paves the way to more sophisticated models with important biological applications, such as viruses and nucleosomes.Comment: 16 pages, 16 figures, JCP in press. Supplementary material has been included as Appendix