Peripheral nerve injury results in persistent motor deficits, even after the nerve regenerates and muscles are reinnervated. This lack of functional recovery is partly explained by brain and spinal ...cord circuit alterations triggered by the injury, but the mechanisms are generally unknown. One example of this plasticity is the die-back in the spinal cord ventral horn of the projections of proprioceptive axons mediating the stretch reflex (Ia afferents). Consequently, Ia information about muscle length and dynamics is lost from ventral spinal circuits, degrading motor performance after nerve regeneration. Simultaneously, there is activation of microglia around the central projections of peripherally injured Ia afferents, suggesting a possible causal relationship between neuroinflammation and Ia axon removal. Therefore, we used mice (both sexes) that allow visualization of microglia (CX3CR1-GFP) and infiltrating peripheral myeloid cells (CCR2-RFP) and related changes in these cells to Ia synaptic losses (identified by VGLUT1 content) on retrogradely labeled motoneurons. Microgliosis around axotomized motoneurons starts and peaks within 2 weeks after nerve transection. Thereafter, this region becomes infiltrated by CCR2 cells, and VGLUT1 synapses are lost in parallel. Immunohistochemistry, flow cytometry, and genetic lineage tracing showed that infiltrating CCR2 cells include T cells, dendritic cells, and monocytes, the latter differentiating into tissue macrophages. VGLUT1 synapses were rescued after attenuating the ventral microglial reaction by removal of colony stimulating factor 1 from motoneurons or in CCR2 global KOs. Thus, both activation of ventral microglia and a CCR2-dependent mechanism are necessary for removal of VGLUT1 synapses and alterations in Ia-circuit function following nerve injuries.
Synaptic plasticity and reorganization of essential motor circuits after a peripheral nerve injury can result in permanent motor deficits due to the removal of sensory Ia afferent synapses from the spinal cord ventral horn. Our data link this major circuit change with the neuroinflammatory reaction that occurs inside the spinal cord following injury to peripheral nerves. We describe that both activation of microglia and recruitment into the spinal cord of blood-derived myeloid cells are necessary for motor circuit synaptic plasticity. This study sheds new light into mechanisms that trigger major network plasticity in CNS regions removed from injury sites and that might prevent full recovery of function, even after successful regeneration.
Phosphorylcholine is known to repel the absorption of proteins onto surfaces, which can prevent the formation of a protein corona on the surface of nanoparticles. This can influence the fate of ...nanoparticles used for drug delivery. This material could therefore serve as an alternative to poly(ethylene glycol) (PEG). Herein, the synthesis of different particles prepared by polymerization-induced self-assembly (PISA) coated with either poly(ethylene glycol) (PEG) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and 4-(
-(
-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was reported. The anticancer drug 4-(
-(
-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was conjugated to the shell-forming block. Interactions of the different coated nanoparticles, which present comparable sizes and size distributions (76-85 nm, PDI = 0.067-0.094), with two-dimensional (2D) and three-dimensional (3D) cultured cells were studied, and their cytotoxicities, cellular uptakes, spheroid penetration, and cell localization profiles were analyzed. While only a minimal difference in behaviour was observed for nanoparticles assessed using in vitro experiment (with PEG-
- PENAO-coated micelles showing slightly higher cytotoxicity and better spheroid penetration and cell localization ability), the effect of the different physicochemical properties between nanoparticles had a more dramatic effect on in vivo biodistribution. After 1 h of injection, the majority of the MPC-
-PENAO-coated nanoparticles were found to accumulate in the liver, making this particle system unfeasible for future biological studies.
Gestational hemodynamic adaptations, including lowered blood pressure (BP) until mid-gestation, might benefit placental function. We hypothesized that elevated BP from early to mid-gestation ...increases risks of preeclampsia and small-for-gestational-age birth (SGA), especially in women who also deliver preterm (< 37 weeks).
In 64,490 healthy primiparous women, the change in systolic and diastolic BP from early to mid-gestation was categorized into lowered (≥ 0 mmHg decreased), and elevated (≥ 1 mmHg increase). Women with chronic hypertension, chronic renal disease, pre-gestational diabetes and systemic lupus erythematosus were excluded. Risks of preeclampsia and SGA birth were estimated by logistic regression, presented with adjusted odds ratio (aOR) and 95% confidence intervals (CI). Further, the effect of BP change in combination with stage 1 hypertension (systolic BP 130-139 mmHg or diastolic BP 80-89 mmHg) in early gestation was estimated.
Compared to women with lowered diastolic BP from early to mid-gestation, those with elevated diastolic BP had increased risks of preeclampsia (aOR: 1.8 1.6-2.0) and SGA birth (aOR: 1.3 1.2-1.5). The risk estimates were higher for preeclampsia and SGA when combined with preterm birth (aORs: 2.2 1.8-2.8 and 2.3 1.8-3.0, respectively). The highest rate of preeclampsia (9.9%) was seen in women with stage 1 hypertension in early gestation and a diastolic BP that was elevated until mid-gestation. This was three times the risk, compared to women with normal BP in early gestation and a diastolic BP that was decreased until mid-gestation. The association between elevated systolic BP from early to mid-gestation and preeclampsia was weak, and no significant association was found between changes in systolic BP and SGA births.
Elevated diastolic BP from early to mid-gestation was associated with increased risks of preeclampsia and SGA, especially for women also delivering preterm. The results may imply that the diastolic BP starts to increase around mid-gestation in women later developing placental dysfunction disorders.
Motoneurons axotomized by peripheral nerve injuries experience profound changes in their synaptic inputs that are associated with a neuroinflammatory response that includes local microglia and ...astrocytes. This reaction is conserved across different types of motoneurons, injuries, and species, but also displays many unique features in each particular case. These reactions have been amply studied, but there is still a lack of knowledge on their functional significance and mechanisms. In this review article, we compiled data from many different fields to generate a comprehensive conceptual framework to best interpret past data and spawn new hypotheses and research. We propose that synaptic plasticity around axotomized motoneurons should be divided into two distinct processes. First, a rapid cell-autonomous, microglia-independent shedding of synapses from motoneuron cell bodies and proximal dendrites that is reversible after muscle reinnervation. Second, a slower mechanism that is microglia-dependent and permanently alters spinal cord circuitry by fully eliminating from the ventral horn the axon collaterals of peripherally injured and regenerating sensory Ia afferent proprioceptors. This removes this input from cell bodies and throughout the dendritic tree of axotomized motoneurons as well as from many other spinal neurons, thus reconfiguring ventral horn motor circuitries to function after regeneration without direct sensory feedback from muscle. This process is modulated by injury severity, suggesting a correlation with poor regeneration specificity due to sensory and motor axons targeting errors in the periphery that likely render Ia afferent connectivity in the ventral horn nonadaptive. In contrast, reversible synaptic changes on the cell bodies occur only while motoneurons are regenerating. This cell-autonomous process displays unique features according to motoneuron type and modulation by local microglia and astrocytes and generally results in a transient reduction of fast synaptic activity that is probably replaced by embryonic-like slow GABA depolarizations, proposed to relate to regenerative mechanisms.
The present experiment was conducted in a rectangular aquarium for three months to evaluate the growth performance of common carp (Cyprinus carpio). Growth performance of Common Carp were studied ...under four different feed supplements i.e. Feed contained Rice and Wheat bran (CG), Fish meal (T1), Poultry meal (T2) and waste proteins (T3). These four different supplementary feed were supplied to fish which were kept in four different tanks at Aquarium (Fisheries Lab) in Zoology department UAJ and K Muzaffarabad, at the rate of 0.25 gm/per day. Initially, at the time of stocking, the morphometric characteristics, viz, average body weight and average body length was measured. After initiation of experiment, these morphometric characteristics as well as physico-chemical parameters (pH and water temperature) of the water were recorded on daily basis throughout the study period. Average Body weight of Common Carp was recorded as, 13.91±1.592, 10.88±0.617, 11.96±0.967, 10.841±0.725 gm under treatment T1, T2 and T3 and Control group respectively. The final body weight of fish in Control group and treatment groups showed that fish kept in T1 (P-Value=0.003) have gained the maximum body weight, while other treatment groups showed no significant statistical difference. Final Body Length of Common Carp was recorded as 7.44±0.169, 11.28±1.407, 8.031±0.473, 9.293±1.490cm under Control group, T1, T2 and T3, respectively. The final body length of fish in Control group and treatment groups showed that fish kept in T1 (P-Value = 0.001) gained more length followed by T3 (P-Value = 0.007). There is no significant statistical difference in Control group and T2. These results suggest that T1 containing the 30% wheat and rice bran supplementary diets can increase the fish maximum body weight and body length.
Preeclampsia is a severe obstetric complication affecting 2–8% of pregnancies.
There is a common belief that women with preeclampsia experience a shorter duration of labor, where it is thought that ...increased inflammation that occurs with the disease facilitates labor. However, little evidence exists to support or refute this. Thus, we undertook a register-based cohort study investigating the association between hypertensive disorders of pregnancy and labor duration.
This was a Swedish register-based cohort study of nulliparous women with spontaneous or induced onset of labor at >34 weeks of gestation with a singleton fetus in cephalic presentation. Information of duration of labor was retrieved from electronic birth records and compared between women with hypertensive disorders and normotensives pregnancies. Data was represented as mean adjusted difference in hours (adjusted for pre-gestational disorders, maternal characteristics and mode of delivery) and adjusted hazard ratios (aHR), with an event defined as vaginal birth and women with intrapartum caesarean section censored. An aHR >1 indicated shorter duration of labor.
Among 101,531 women, 5548 (5.5%) developed a hypertensive disorder of pregnancy. The overall mean duration of labor was 9.43 (SD 5.32) hours. Women with hypertensive disorders experienced a shorter duration of labor compared to normotensive women, with an adjusted mean difference of -0.68 h (95% CI −0.90, −0.47) for gestational hypertension and -1.53 h (95% CI −1.72, −1.35) for preeclampsia. This corresponded to an aHR of 1.05 (95% CI 1.01, 1.10) and 1.12 (95% CI 1.08, 1.17), respectively. However, when we confined the analysis to those who labored spontaneously, the presence of hypertensive disorders did not alter duration of labor (aHR 0.98, 95% CI 0.95,1.01). Only women who were induced and also had hypertensive disorders experienced a shorter duration of labor (aHR 1.07, 95% CI 1.04,1.09).
Hypertensive disorders did not alter labor duration among women with spontaneous onset of labor, however an association was observed among women who were induced.
Cylindrical and spherical （nonplanar） solitary waves （SWs） and double layers （DLs） in a multi-ion plasma system （containing inertial positively as well as negatively charged ions, non-inertial ...degenerate electrons, and negatively charged static dust） are studied by employing the standard reductive perturbation method. The modified Gardner （MG） equation describing the nonlinear propagation of the dust ion-acoustic （DIA） waves is derived, and its nonplanar SWs and DLs solutions are numerically analyzed. The parametric regimes for the existence of SWs, which are associated with both positive and negative potential, and DLs which are associated with negative potential, are obtained. The basic features of nonplanar DIA SWs, and DLs, which are found to be different from planar ones, are also identified.
A numerical investigation on the spatiotemporal evolution of an electron beam, externally injected in a plasma in the presence of a plasma wake field, is carried out. The latter is driven by an ...ultra-short relativistic axially-symmetric femtosecond electron bunch. We first derive a novel Poisson-like equation for the wake potential where the driving term is the ultra-short bunch density, taking suitably into account the interplay between the sharpness and high energy of the bunch. Then, we show that a channel is formed longitudinally, through the externally injected beam while experiencing the effects of the bunch-driven plasma wake field, within the context of thermal wave model. The formation of the channel seems to be a final stage of the 3D evolution of the beam. This involves the appearance of small filaments and bubbles around the longitudinal axis. The bubbles coalesce forming a relatively stable axially-symmetric hollow beam structure.
•A novel Poisson-like equation for the wake potential driven by the ultra-short bunch density is derived in the context of PWF theory.•The spatiotemporal evolution of another externally injected electron beam in the presence plasma wake field is numerically investigated.•A channel is formed longitudinally, through the externally injected beam while experiencing the effects of the bunch-driven plasma wake field.•A relatively stable axially symmetric hollow beam structure is formed through the evolution.
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