The cost of mutualism in a fly-fungus interaction

The movement ability of individuals has become increasingly important to a variety of ecological questions. In this study, I investigate how plant structure and changes in body size through development affect the movement ability of a predaceous stinkbug, Podisus maculiventris, on three species of goldenrod (Solidago spp.) representing a wide range of surface complexities. I adapt existing techniques for quantifying movement in two dimensions to the study of movement on natural plant structures in three dimensions. These experiments indicate that plant structure and insect size are significant factors affecting the movement ability of P. maculiventris. Changes in movement ability due to factors of ontogeny and different habitat structures suggest that the scale of an individual’s ambit or ecological sphere of influence may vary within its lifespan. Considering the influence of ontogeny and habitat structure on movement ability may be useful to investigations of population dynamics, foraging behavior, and pest management. Received: 14 July 1999 / Accepted: 23 March 2000     

Calreticulin enhances the secretory trafficking of a misfolded α-1-antitrypsin

α1-antitrypsin (AAT) regulates the activity of multiple proteases in the lungs and liver. A mutant of AAT (E342K) called ATZ forms polymers that are present at only low levels in the serum and induce intracellular protein inclusions, causing lung emphysema and liver cirrhosis. An understanding of factors that can reduce the intracellular accumulation of ATZ is of great interest. We now show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media:cell ratio. This effect is more pronounced for ATZ than with AAT and is only partially dependent on the glycan-binding site of CRT, which is generally relevant to substrate recruitment and folding by CRT. The CRT-related chaperone calnexin does not enhance ATZ secretory trafficking, despite the higher cellular abundance of calnexin-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions with components required for ER-Golgi trafficking, coincident with reduced levels of the protein transport protein Sec31A in CRT-deficient cells. These findings indicate a novel role for CRT in promoting the secretory trafficking of a protein that forms polymers and large intracellular inclusions. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ inclusion bodies. Further understanding of the factors that control the secretory trafficking of ATZ and their regulation by CRT could lead to new therapies for lung and liver diseases linked to AAT deficiency.     

Acid-induced aggregation propensity of nivolumab is dependent on the Fc

Nivolumab, an anti-programmed death (PD)1 IgG₄ antibody, has shown notable success as a cancer treatment. Here, we report that nivolumab was susceptible to aggregation during manufacturing, particularly in routine purification steps. Our experimental results showed that exposure to low pH caused aggregation of nivolumab, and the Fc was primarily responsible for an acid-induced unfolding phenomenon. To compare the intrinsic propensity of acid-induced aggregation for other IgGs subclasses, tocilizumab (IgG₁), panitumumab (IgG₂) and atezolizumab (aglyco-IgG₁) were also investigated. The accurate pH threshold of acid-induced aggregation for individual IgG Fc subclasses was identified and ranked as: IgG₁?1?2?4. This result was cross-validated by thermostability and conformation analysis. We also assessed the effect of several protein stabilizers on nivolumab, and found mannitol ameliorated the acid-induced aggregation of the molecule. Our results provide valuable insight into downstream manufacturing process development, especially for immune checkpoint modulating molecules with a human IgG₄ backbone.     

Chronic restraint stress disturbs meiotic resumption through APC/C-mediated cyclin B1 excessive degradation in mouse oocytes

Psychological stress, which exerts detrimental effects on human reproduction, may compromise the meiotic competence of oocytes. Meiotic resumption, germinal vesicle breakdown (GVBD), is the first milestone to confer meiotic competence to oocytes. In the practice of assisted reproductive technology (ART), the timing for GVBD is associated with the rates of cleavage and blastocyst formation. However, whether chronic stress compromises oocyte competence by influencing GVBD and the underlying mechanisms are unclear. In the present study, a chronic restraint stress (CRS) mouse model was used to investigate the effects of stress on oocyte meiotic resumption, as well as the mechanisms. Following a 4-week chronic restraint stress in female mice, the percentage of abnormal bipolar spindles increased and indicated compromised oocyte competence in the CRS group. Furthermore, we identified a decreased percentage of GVBD and prolonged time of GVBD in the CRS mouse oocytes compared with the control group. CRS simultaneously reduced the expression of cyclin B1 (CCNB1), which represents a regulatory subunit of M-phase/mature promoting factor (MPF). However, MG132, an inhibitor of anaphase-promoting complex/cyclosome (APC/C), could rescue the prolonged time of GVBD and increase the expression level of CCNB1 of oocytes from the CRS mice. Collectively, our results demonstrated that stress disturbed meiotic resumption through APC/C-mediated CCNB1 degradation, thus providing a novel understanding for stress-related oocyte quality decline; moreover, it may provide a non-invasive approach to select high-quality gametes and novel targets for molecular therapy to treat stress-related female infertility.     

Cortical vein thrombosis in adult patients of cerebral venous sinus thrombosis correlates with poor outcome and brain lesions: a retrospective study

Background

Cortical vein thrombosis (CVT) receives little attention in adult patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the clinical and radiological features of adult CVST patients with concomitant CVT.

Methods

From May 2009 to May 2016, we recruited 44 adult CVST patients (diagnosed within 1 month of onset; 33.8?±?14.0 years of age, 28 males). CVT was primarily confirmed using computed tomography venography and magnetic resonance imaging sequence of contrast enhanced three dimensions magnetization prepared rapid acquisition with gradient echo. Patients with concomitant CVT were divided into the CVT group; otherwise, the patients were placed into the non-CVT group. The clinico-radiological characteristics were compared between the two groups.

Results

The CVT group included 27 patients (61.4%), and the non-CVT group included 17 patients (38.6%). Seizure (63.0% versus 11.8%), focal neurological deficits (44.4% versus 5.9%), and consciousness disorders (33.3% versus 0) occurred more frequently in the patients in the CVT group than in those of the non-CVT group (P?<?0.05). The modified Rankin Scale (mRS) score at discharge was higher for the CVT group patients (median 2, range 1–4) than for the non-CVT group patients (median 0, range 0–4) (P?<?0.001). Venous infarction (63.0% versus 11.8%), parenchymal hemorrhage (40.7% versus 5.9%), and subarachnoid hemorrhage (22.2% versus 0) were identified more frequently in the CVT group than in the non-CVT group (P?<?0.05).

Conclusions

This study demonstrates that concomitant CVT is a common finding in adult patients with CVST and is associated with severe clinical manifestations, poor short-term outcomes, and brain lesions.

     

Blood osmolality in vitro: dependence on base addition, buffer value, and temperature

Blood osmolality (Osm) increases with PCO2 because of CO2 absorption. The influences of NaOH addition, equilibration temperature, and hemoglobin concentration on these respiratory changes of Osm were measured by freezing-point determination in true plasma. Addition of NaOH increases Osm by 2 mosmol X kg H2O-1 X mmol base-1 X l at constant PCO2 due to the osmotic effects of Na+ and produced bicarbonate. Respiratory compensation of the pH change further increases Osm. This contrasts to the respiratory compensation of the osmolar disturbance caused by fixed acid. Raising the equilibration temperature reduces Osm by 0.5 mosmol X kg H2O-1 X degrees C-1 at constant pH mainly caused by a lower absorption coefficient for CO2 and changed pK value for H2CO3. The slope of the linear regression lines between Osm and pH during CO2 equilibration increases with hemoglobin; the value of the quotient delta Osm/delta pH depends directly on the nonbicarbonate buffer value. The use of this quotient for the estimation of the mean nonbicarbonate buffer value of the whole body is suggested. The osmotic effects of therapeutic base infusion should be regarded with caution.