Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.

Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other

Dysregulation of of phospholipid-specific phagocytosis by B1 B cells in diet-induced obese mice

B1 B cells have received increasing attention recently due to their newly discovered phagocytic and microbicidal capabilities. Several studies have demonstrated that B1 cells can phagocytize polystyrene fluorescent particles, bacteria (Staphylococcus aureus, Escherichia coli), and even apoptotic cells. Nevertheless, little is known about the biological significance of this seemingly redundant function of B1 B cells as compared to that of conventional phagocytes. Here we investigate the unique phosphotidylcholine (PtC)-specific B1 B cell phagocytosis. PtC is a major phospholipid in the biological membrane and a classical antigen recognized by B1 B cell-derived natural antibodies. These antibodies play important roles in immune defense as well as tissue homeostasis. Here we report that B1 cells preferentially phagocytose PtC-coated beads, differing from that of conventional macrophages. We further attest that these beads were truly internalized and subsequently fused with hydrolytic lysosomes indicated by increasing fluorescent intensity of a pH-sensitive dye. Despite the differences in antigen specificity, phagocytosis of both B1 cells and macrophages can be inhibited by the microtubule-inhibitor, Colchicine, in a dose-dependent manner. Most intriguingly, upon chronic high-fat diet (HFD) consumption by the host, B1 cell phagocytosis starts to lose antigen-specificity for PtC. Morphologically, some of these B1 B cells in DIO mice show enlarged cytosol and engulfed more beads, indicating a transition to macrophage-like cells. Our study suggests for the first time that B1 B cells have unique phospholipid-specific phagocytosis capacity, which is affected by diet-induced obesity

Modulation of Negative Work Output from a Steering Muscle of the Blowfly Calliphora Vicina

Of the 17 muscles responsible for flight control in flies, only the first basalar muscle (b1) is known to fire an action potential each and every wing beat at a precise phase of the wing-beat period. The phase of action potentials in the b1 is shifted during turns, implicating the b1 in the control of aerodynamic yaw torque. We used the work loop technique to quantify the effects of phase modulation on the mechanical output of the b1 of the blowfly Calliphora vicina. During cyclic length oscillations at 10 and 50 Hz, the magnitude of positive work output by the b1 was similar to that measured previously from other insect muscles. However, when tested at wing-beat frequency (150 Hz), the net work performed in each cycle was negative. The twitch kinetics of the b1 suggest that negative work output reflects intrinsic specializations of the b1 muscle. Our results suggest that, in addition to a possible role as a passive elastic element, the phase-sensitivity of its mechanical properties may endow the b1 with the capacity to modulate wing-beat kinematics during turning maneuvers

<i>Herschel</i> observations of B1-bS and B1-bN: two first hydrostatic core candidates in the Perseus star-forming cloud

We report far-infrared Herschel observations obtained between 70 μm and 500 μm of two star-forming dusty condensations, [HKM99] B1-bS and [HKM99] B1-bN, in the B1 region of the Perseus star-forming cloud. In the western part of the Perseus cloud, B1-bS is the only source detected in all six PACS and SPIRE photometric bands, but it is not visible in the Spitzer map at 24 μm. B1-bN is clearly detected between 100 μm and 250 μm. We have fitted the spectral energy distributions of these sources to derive their physical properties, and find that a simple greybody model fails to reproduce the observed spectral energy distributions. At least a two-component model is required, consisting of a central source surrounded by a dusty envelope. The properties derived from the fit, however, suggest that the central source is not a Class 0 object. We then conclude that while B1-bS and B1-bN appear to be more evolved than a pre-stellar core, the best-fit models suggest that their central objects are younger than a Class 0 source. Hence, they may be good candidates to be examples of the first hydrostatic core phase. The projected distance between B1-bS and B1-bN is a few Jeans lengths. If their physical separation is close to this value, this pair would allow studying the mutual interactions between two forming stars at a very early stage of their evolution

High fat diet deviates PtC-specific B1 B cell phagocytosis in obese mice

Phagocytosis had been attributed predominantly to "professional" phagocytes such as macrophages, which play critical roles in adipose tissue inflammation. However, recently, macrophage-like phagocytic activity has been reported in B1 B lymphocytes. Intrigued by the long-established correlation between high fat diet (HFD)-induced obesity and immune dysfunction, we investigated how HFD affects B1 B cell phagocytosis. A significant number of B1 B cells recognize phosphatidylcholine (PtC), a common phospholipid component of cell membrane. We report here that unlike macrophages, B1 B cells have a unique PtC-specific phagocytic function. In the presence of both PtC-coated and non-PtC control fluorescent nano-particles, B1 B cells from healthy lean mice selectively engulfed PtC-coated beads, whereas B1 B cells from HFD-fed obese mice non-discriminately phagocytosed both PtC-coated and control beads. Morphologically, B1 B cells from obese mice resembled macrophages, displaying enlarged cytosol and engulfed more beads. Our study suggests for the first time that HFD can affect B1 B cell phagocytosis, substantiating the link of HFD-induced obesity and immune deviation.R21 AR063387 - NIAMS NIH HHS; R25 CA153955 - NCI NIH HHS; UL1 TR000157 - NCATS NIH HH

Experiments on the carboxylase of pea roots

It is known that vitamin B1 is a growth factor for numerous bacteria and fungi including the yeasts (see the summary in Koser and Saunders (1938)). It has also been demonstrated that vitamin B1 is essential for the growth of the isolated roots of higher plants (Bonner, 1937; Robbins and Bartley, 1937). Because of this general vitamin B1 requirement of living organisms, it would seem a priori probable that the vitamin plays a role in some basic cellular process. That this is indeed the case was shown conclusively by the work of Peters and coworkers (see Peters and O’Brien (1938)) and of Lohmann and Schuster (1937). The latter workers found that the prosthetic group of yeast carboxylase is vitamin B1 pyrophosphate. In the case of yeast, vitamin B1 is, then, a constituent of a respiratory enzyme and vitamin B1 pyrophosphate is hence commonly referred to as “cocarboxylase,” a terminology used throughout this paper. Although considerable information is available concerning the rôle of vitamin B1 as a growth factor for roots, there is little known about the carboxylase of such roots. The present work was undertaken with the hope of elucidating possible relationships between vitamin B1 and the carboxylase of pea roots