Out-of-equilibrium interactions and collective locomotion of colloidal spheres with squirming of nematoelastic multipoles.

Many living and artificial systems show similar emergent behavior and collective motions on different scales, starting from swarms of bacteria to synthetic active particles, herds of mammals, and crowds of people. What all these systems often have in common is that new collective properties like flocking emerge from interactions between individual self-propelled or driven units. Such systems are naturally out-of-equilibrium and propel at the expense of consumed energy. Mimicking nature by making self-propelled or externally driven particles and studying their individual and collective motility may allow for deeper understanding of physical underpinnings behind collective motion of large groups of interacting objects or beings. Here, using a soft matter system of colloids immersed into a liquid crystal, we show that resulting so-called nematoelastic multipoles can be set into a bidirectional locomotion by external oscillating electric fields. Out-of-equilibrium elastic interactions between such colloidal objects lead to collective flock-like behaviors emerging from time-varying elasticity-mediated interactions between externally driven propelling particles. Repulsive elastic interactions in the equilibrium state can be turned into attractive interactions in the out-of-equilibrium state under applied external electric fields. We probe this behavior at different number densities of colloidal particles and show that particles in dense dispersions collectively select the same direction of a coherent motion due to elastic interactions between near neighbors. In our experimentally implemented design, their motion is highly ordered and without clustering or jamming often present in other colloidal transport systems, which is promising for technological and fundamental-science applications, like nano-cargo transport, out-of-equilibrium assembly, and microrobotics.

Field-controlled dynamics of skyrmions and monopoles.

Magnetic monopoles, despite their ongoing experimental search as elementary particles, have inspired the discovery of analogous excitations in condensed matter systems. In chiral condensed matter systems, emergent monopoles are responsible for the onset of transitions between topologically distinct states and phases, such as in the case of transitions from helical and conical phase to A-phase comprising periodic arrays of skyrmions. By combining numerical modeling and optical characterizations, we describe how different geometrical configurations of skyrmions terminating at monopoles can be realized in liquid crystals and liquid crystal ferromagnets. We demonstrate how these complex structures can be effectively manipulated by external magnetic and electric fields. Furthermore, we discuss how our findings may hint at similar dynamics in other physical systems and their potential applications.

Topological steering of light by nematic vortices and analogy to cosmic strings.

Liquid crystals are widely known for their technological uses in displays, electro-optics, photonics and nonlinear optics, but these applications typically rely on defining and switching non-topological spatial patterns of the optical axis. Here, we demonstrate how a liquid crystal's optical axis patterns with singular vortex lines can robustly steer beams of light. External stimuli, including an electric field and light itself, allow us to reconfigure these unusual light-matter interactions. Periodic arrays of vortices obtained by photo-patterning enable the vortex-mediated fission of optical solitons, yielding their lightning-like propagation patterns. Predesigned patterns and spatial trajectories of vortex lines in high-birefringence liquid crystals can steer light into closed loops or even knots. Our vortex lattices might find technological uses in beam steering, telecommunications, virtual reality implementations and anticounterfeiting, as well as possibly offering a model system for probing the interaction of light with defects, including the theoretically predicted, imagination-capturing light-steering action of cosmic strings, elusive defects in cosmology.

Geometric transformation and three-dimensional hopping of Hopf solitons.

Arising in many branches of physics, Hopf solitons are three-dimensional particle-like field distortions with nontrivial topology described by the Hopf map. Despite their recent discovery in colloids and liquid crystals, the requirement of applied fields or confinement for stability impedes their utility in technological applications. Here we demonstrate stable Hopf solitons in a liquid crystal material without these requirements as a result of enhanced stability by tuning anisotropy of parameters that describe energetic costs of different gradient components in the molecular alignment field. Nevertheless, electric fields allow for inter-transformation of Hopf solitons between different geometric embodiments, as well as for their three-dimensional hopping-like dynamics in response to electric pulses. Numerical modelling reproduces both the equilibrium structure and topology-preserving out-of-equilibrium evolution of the soliton during switching and motions. Our findings may enable myriads of solitonic condensed matter phases and active matter systems, as well as their technological applications.

UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Thermally reconfigurable monoclinic nematic colloidal fluids.

Fundamental relationships are believed to exist between the symmetries of building blocks and the condensed matter phases that they form1. For example, constituent molecular and colloidal rods and disks impart their uniaxial symmetry onto nematic liquid crystals, such as those used in displays1,2. Low-symmetry organizations could form in mixtures of rods and disks3-5, but entropy tends to phase-separate them at the molecular and colloidal scales, whereas strong elasticity-mediated interactions drive the formation of chains and crystals in nematic colloids6-11. To have a structure with few or no symmetry operations apart from trivial ones has so far been demonstrated to be a property of solids alone1, but not of their fully fluid condensed matter counterparts, even though such symmetries have been considered theoretically12-15 and observed in magnetic colloids16. Here we show that dispersing highly anisotropic charged colloidal disks in a nematic host composed of molecular rods provides a platform for observing many low-symmetry phases. Depending on the temperature, concentration and surface charge of the disks, we find nematic, smectic and columnar organizations with symmetries ranging from uniaxial1,2 to orthorhombic17-21 and monoclinic12-15. With increasing temperature, we observe unusual transitions from less- to more-ordered states and re-entrant22 phases. Most importantly, we demonstrate the presence of reconfigurable monoclinic colloidal nematic order, as well as the possibility of thermal and magnetic control of low-symmetry self-assembly2,23,24. Our experimental findings are supported by theoretical modelling of the colloidal interactions between disks in the nematic host and may provide a route towards realizing many low-symmetry condensed matter phases in systems with building blocks of dissimilar shapes and sizes, as well as their technological applications.

Effect of saracatinib on pulmonary metastases from hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Src is involved in multiple processes of cancer metastasis; however, its significance in HCC is not well defined. In the present study, overexpression of Src phosphorylation (Y416) was observed in the highly metastatic MHCC97H cell line; additionally, through inhibition of Src kinase activation, HCC cell proliferation, migration, invasion and colony formation were significantly reduced in vitro. Tumour growth was not affected in the orthotopic xenograft HCC model, but the metastasic potential was inhibited as revealed by reduced lung metastasic foci after administration of saracatinib. Phosphorylation level of Src pathway signalling molecules, such as Src, FAK and Stat3, were also reduced in vitro and in vivo, as a result of the anti-metastasic effects caused by saracatinib treatment. In conclusion, we demonstrated the pro-metastasic role of Src in HCC, and further experiments suggest the use of the Src inhibitor in combination with cytotoxic agents and other anticancer treatments to improve HCC prognosis.

Complementary interactions between command-like interneurons that function to activate and specify motor programs.

Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.

Giant chylous cyst and ileal duplication in a young adult.

Alimentary tract duplications are rare congenital anomalies that usually present in childhood and occasionally in adults. They are most common in the ileum, but can occur anywhere along the alimentary tract from the mouth to the anus. We report a 24-year-old woman who presented with a giant chylous ileum cyst duplication. To our knowledge, there is only one other report of a patient with a giant chylous cyst in the literature.

Composite modulatory feedforward loop contributes to the establishment of a network state.

Feedforward loops (FFLs) are one of many network motifs identified in a variety of complex networks, but their functional role in neural networks is not well understood. We provide evidence that combinatorial actions of multiple modulators may be organized as FFLs to promote a specific network state in the Aplysia feeding motor network. The Aplysia feeding central pattern generator (CPG) receives two distinct inputs-a higher-order interneuron cerebral-buccal interneuron-2 (CBI-2) and the esophageal nerve (EN)-that promote ingestive and egestive motor programs, respectively. EN stimulation elicits a persistent egestive network state, which enables the network to temporarily express egestive programs following a switch of input from the EN to CBI-2. Previous work showed that a modulatory CPG element, B65, is specifically activated by the EN and participates in establishing the egestive state by enhancing activity of egestion-promoting B20 interneurons while suppressing activity and synaptic outputs of ingestion-promoting B40 interneurons. Here a peptidergic contribution is mediated by small cardioactive peptide (SCP). Immunostaining and mass spectrometry show that SCP is present in the EN and is released on EN stimulation. Importantly, SCP directly enhances activity and synaptic outputs of B20 and suppresses activity and synaptic outputs of B40. Moreover, SCP promotes B65 activity. Thus the direct and indirect (through B65) pathways to B20 and B40 from SCPergic neurons constitute two FFLs with one functioning to promote egestive output and the other to suppress ingestive output. This composite FFL consisting of the two combined FFLs appears to be an effective means to co-regulate activity of two competing elements that do not inhibit each other, thereby contributing to establish specific network states.

[Laparoscopic adjustable gastric banding in the treatment of obesity: analysis of 172 cases].

OBJECTIVE: To evaluate the outcome of weight loss by laparoscopic adjustable gastric banding (LAGB) on obesity patients and the improvement of comorbidity. METHODS: From June 2003 to June 2009, the data 172 obesity patients(119 women, 53 men, mean age 28.5 years, mean body mass index 38.5 kg/m(2)) were analyzed. Comorbidities included 28 cases with diabetes, 36 with hypertension, 85 with dyslipidemia, 56 with sleep apnea and 138 with fatty liver. RESULTS: Mean body mass index(BMI) at 1,3,6,12, 24, 36 and 48 months was 37.2 kg/m(2),35.9 kg/m(2), 34.5 kg/m(2), 32.9 kg/m(2), 30.7 kg/m(2), 29.2 kg/m(2) and 28.1 kg/m(2), respectively. The percentage of excess weight loss(% EWL) at 1, 3, 6, 12, 24, 36, and 48 months was 10.1%, 16.2%, 25.1%, 37.4%, 51.3%, 59.0% and 62.1%, respectively. At 24, 36 and 48 months, respectively, 50.7%, 63.6% and 70.0% of patients had more than 50% excess weight loss. Complications included 6 cases of port infection, 3 of other port problem, 7 of gastric pouch dilatations, 4 of slippage and 1 of chronic intestinal obstruction. Bands of 5 patients were explanted. No death occurred. Blood glucose of 60.7% patients with diabetes was controlled well without any drug. The blood pressure of 22 hypertensive patients became normal. The blood fat of 49 hyperlipidemia cases returned to normal. The symptom of 29 patients with sleep apnea disappeared. All the patients with fatty liver were improved in different degree. CONCLUSION: Gastric banding provides good weight loss and significant reduction in comorbidities with few and minor complications.

[Efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation: an animal experimental study].

OBJECTIVE: To investigate the efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation in SD rat model. METHODS: Sleeve gastrectomy plus gastric remnant banding was performed in 20 male SD rats as the study group; sleeve gastrectomy was performed in 20 SD male rats as the control group, and laparotomy was performed in 10 SD male rats as the blank control group. Body weight was measured before the experiment, at day 1 and at 2-week intervals within 16 weeks after operation. RESULTS: The number of survival rats was 15 in the study group (15/20), 13 in the control group (13/20), and 10 in the blank control group (10/10). Postoperative body weight increased markedly in the blank control group, returned to the pre-operative level two weeks after operation in the control group, and four weeks after operation in the study group. Weight increase of the study group was significantly slower than that of the other two groups (P<0.01). Postoperative gastric dilation of the control group was more obvious as compared to the study group. CONCLUSION: Sleeve gastrectomy plus gastric remnant banding is safe and effective because of the restriction of postoperative gastric dilation.

State dependence of spike timing and neuronal function in a motor pattern generating network.

When sustained firing of a neuron is similar in different types of motor programs, its role in the generation of these programs is often similar. We investigated whether this is also the case for neurons involved in phase transition. In the Aplysia feeding central pattern generator (CPG), identified interneuron B64 starts firing at the transition between the protraction and the retraction phases of all types of motor programs, and its firing is sustained during the retraction phase. It was thought that B64 functions as a protraction terminator as it provides strong inhibitory input to protraction interneurons and motoneurons. Furthermore, premature activation of B64 can lead to premature termination of the protraction phase. Indeed, as we show here, B64 can terminate the protraction phase regardless of the type of motor program. However, B64 actually only functions as a protraction terminator in ingestive-like but not in egestive-like programs. This differential role of B64 results from a differential timing of the initiation of B64 spiking in the two types of programs. In turn, this differential timing of the initiation of B64 firing is determined by the internal state of the CPG. Thus, this study indicates the importance of the timing of initiation of firing in determining the functional role of a neuron and demonstrates that this role depends on the activity-dependent state of the network.

[Effects of vasectomy on prostatic histomorphology and cell apoptosis in rats].

OBJECTIVE: To detect the effects of vasectomy on the growth and apoptosis of prostatic tissue cells. METHODS: Forty-five SD rats were divided at random into three groups of fifteen each. Vasectomy (Vsm) model was established by ligating the bilateral vas deferens of the rats in Group A and testosterone propionate and normal saline were subcutaneously injected in those of Groups B and C, respectively. The area percentage of each part in the prostatic tissue was measured with computer-assisted image analysis system. The apoptotic rate was examined with TUNEL. RESULTS: The ratio of stromal area to epithelial plus lumen area in the prostatic tissues in Groups A, B and C were (29.20 +/- 6.85), (39.77 +/- 7.58) and (48.90 +/- 6.49), respectively, and the differences were significant statistically (P all < 0.05). The apoptosis rates in Groups A, B and C were (6.39 +/- 0.84)%, (2.62 +/- 0.57)% and (4.58 +/- 0.93)%, respectively, significantly higher in Group A than in Groups B and C (P all < 0.05). CONCLUSION: Vasectomy may induce interstitium reduction and cell apoptosis in the prostatic tissues of rats, which may help prevent benign prostatic hyperplasia.

Repetition rates of specific interval patterns in single spike train reflect excitation level of specific receptor types, shown by high-speed favored-pattern detection method.

UNLABELLED: Interval patterns in single spike train, e.g. "favored patterns (FPs, the FP is a sequence of successive intervals of action potentials that occur more often than what is reasonably expected at random.)", may represent neural codes containing information. The present study developed a "high-speed FP-detection method" which could qualitatively and quantitatively analyze FPs. By using this method, single spike trains of nucleus paraventricularis (NPV) and rostral ventrolateral medulla (RVL) having different firing patterns, being involved in regulation of arterial pressure, and controlled by different transmitters, were chosen for analysis. RESULTS: (1) Corticotropin releasing factor, substance P and agonists of alpha-, beta- and M-receptor microinjected into these brain areas, respectively, induced dominant change of specific FP. Repetition rates of specific FPs reflect excitation level of specific receptor types. It shows that chemical codes (different transmitters with their receptor types or subtypes) are transformed into electrical codes (different FPs). (2) When alpha-, beta- and M-receptors of RVL neurons were activated simultaneously by intrinsic excitatory transmitters released due to activation of input pathway, only repetition rate of the specific FP that represented the predominant activity of the receptor type (alpha-adrenergic receptor) markedly increased. The activities of other receptor types (beta- and M-receptors) were masked. (3) Intrinsic inhibitory transmitters (GABA, beta-endorphin) in the RVL all decreased specific FP repetition rate of dominant receptor type. These results may provide a new way to further explore how information in the CNS is conveyed and processed.

Concerted GABAergic actions of Aplysia feeding interneurons in motor program specification.

GABAergic inhibitory interneurons regulate the activity of diverse types of neural networks, but the specific roles of these interneurons in motor control are poorly understood. In the Aplysia feeding motor network, three interneurons, cerebral-buccal interneuron-3 (CBI-3) and buccal interneurons B40 and B34, are GABA-immunoreactive and evoke fast IPSPs in their postsynaptic followers. Using a combination of pharmacological experiments with GABA antagonists, agonists, and uptake inhibitors, we found that these fast IPSPs are likely mediated by GABA. Functionally, these fast IPSPs specify two parameters for ingestive motor programs elicited by the command-like interneuron CBI-2: (1) the appropriate phasing of activity of the radula closer motor neuron B8 relative to protraction-retraction, and (2) protraction duration. First, in ingestive programs, B8 activity is phased such that it fires minimally during protraction. CBI-3 and B40 exert fast inhibition to minimize B8 activity during protraction, by either acting directly on B8 (B40) or indirectly on B8 (CBI-3). Second, these ingestive programs are characterized by long protraction duration, which is promoted by B40 and B34 because hyperpolarization of either cell shortens protraction. Such effects of B40 and B34 are attributable, at least partly, to their inhibitory effects on the retraction-phase interneuron B64 whose activation terminates protraction. Consistent with a GABAergic contribution to both B8 phasing and protraction duration, blockade of GABAergic inhibition by picrotoxin increases B8 activity during protraction and shortens protraction, without disrupting the integrity of motor programs. Thus, the concerted actions of GABAergic inhibition from three Aplysia feeding interneurons contribute to the specification of multiple features that define the motor program as an ingestive one.

Identification of a GABA-containing cerebral-buccal interneuron-11 in Aplysia californica.

The cerebral-buccal interneurons (CBIs) in Aplysia are a group of inter-ganglionic projection neurons that regulate feeding motor programs. In this study, electrophysiological and immunocytological methods were used to identify a previously uncharacterized CBI, designated CBI-11. CBI-11 is a gamma-aminobutyric acid (GABA)-immunoreactive neuron located in the G cluster of the cerebral ganglion. Firing CBI-11 produced fast picrotoxin-sensitive inhibitory postsynaptic potentials (IPSPs) in buccal motor neuron B3. Local application of GABA to B3 produced a picrotoxin-sensitive hyperpolarization that reversed at the same membrane potential as the IPSPs elicited by stimulation of CBI-11. Together, these observations indicate that CBI-11 utilizes GABA as its transmitter. Finally, stimulation of CBI-11 elicited rhythmic motor programs in quiescent buccal ganglia. Thus, CBI-11 is a GABAergic CBI that can function as a motor program initiator.