Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors

Scalable Transport Models for Non-Evaporating and Evaporting Sessile Droplets within Porous Substrates

To create a system that can greatly enhance the ability to predict the outcome of a chemical attack event in terms of the existing level of an agent’s concentratio

Infiltration Time and Imprint Shape of a Sessile Droplet Imbibing Porous Medium

The infiltration of a sessile droplet into a homogeneous porous medium for a constant droplet base radius case is solved numerically, where the porous medium is represented as a capillary network consisting of pores and throats. For a homogeneous medium, the network is built of the spherical pores of constant radius, and the cylindrical throats of constant radius and height. Having such defined network, the droplet imbibes porous medium in a single-phase flow for which the free interface in porous medium is smooth, and the liquid phase permeability and the capillary pressure are constant. Using the numerical solution we carry out the parametric study in which: (i) liquid viscosity and surface tension, (ii) droplet volume and base radius, and (iii) porous medium porosity and permeability are varied. The droplet infiltration time, and the imprint shape that is given with two spheroid half-axes are calculated. The dimensionless analysis is utilized to correlate the droplet infiltration parameters from which master curves for the droplet infiltration time and the droplet imprint shape are obtained. Using the infiltration time correlation, both numerical and experimental results show a linear behavior

Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients

A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta 1 (TGF-beta 1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta 1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta 1 levels when compared to plasma TGF-beta 1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors status had no plasma TGF-beta 1 values overlapping with patients having positive receptors status. The TGF-beta 1 cut-off value was defined as the highest plasma TGF-beta 1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta 1 cut-off value defined low-risk subgroup of 19 patients (! 3.28 ng/ml) and high-risk subgroup of 10 patients ( GT 3.28 ng/ml) (P=0.047). Plasma TGF-beta 1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta 1 levels may be suggested