Search bioRxiv⌕ Search

Biology subjects

Kohler, B.

Publications and source records attributed to Kohler, B..

4 recordsLinked to original sources

Rapid Detection and Initial Treatment of Life-Threatening Subdural Hematoma in a Sheep Model

Traumatic brain injury (TBI) is the leading cause of death and disability in people under 40 worldwide. There is an unmet need for detection and treatment of life-threatening TBI when computed tomography (CT) scanners and neurosurgeons are unavailable. We developed a new handheld frequency-domain multidetector infrared hemorrhage detection device. Using the new device, military pre-hospital medics required <4 minutes to detect life-threatening subdural hematoma in a sheep model. We developed a second device that allows non-neurosurgeons to safely create a burr hole and partially remove clotted subdural blood. In sheep, the treatment device reduced intracranial pressure within 20 minutes, and improved post-anesthesia blinded neurological outcomes. With human use adaptation, these devices could allow rapid detection and initial treatment of some life-threatening TBIs in challenging situations.

neuroscience↗

B-REAL: A keypoint-less behavior platform for offline classification and real-time detection

Two obstacles limit automated behavior analysis in neuroethology: the burden of first training pose estimation models, and the inability to identify behavior quickly enough for real-time classification that could trigger stimuli, drug delivery, or environmental manipulations. Here we present B-REAL, a pose-free classifier that maps raw video to behavior faster than video frames are recorded, even on a CPU. Given substantially less training data, B-REAL matched or surpassed established methods trained on full benchmark rodent or fly datasets, particularly on rare and even single-frame behaviors. Pretraining on unlabeled video further improves its accuracy without slowing inference or training time. In closed loop, rewarding mice for B-REAL-detected grooming more than doubled their performance of grooming bouts. B-REAL thus makes closed-loop behavioral experiments practical with minimal annotation and standard hardware.

neuroscience↗

Motor Learning and Transfer Are Symmetric Across Hands

Functional asymmetry between the cerebral hemispheres is a defining feature of the sensorimotor system, with the dominant hemisphere playing a central role in motor control. Whether motor learning is similarly lateralized, however, remains unresolved. To tackle this question, we combined a comprehensive meta-analysis (114 datasets) with a series of well-powered, preregistered experiments (N = 526) to test two core behavioral predictions of hemispheric lateralization in sensorimotor adaptation, a canonical form of motor learning: (1) adaptation is preferentially expressed in the dominant hand and (2) transfers asymmetrically between limbs. Across both approaches, we found that adaptation and interlimb transfer were strikingly symmetric. Together, these findings support a fundamental dissociation in the neural organization of skilled behavior: whereas motor control is lateralized to the dominant hemisphere, motor learning is supported by a neural architecture that functions symmetrically.

neuroscience↗

Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer

PURPOSEEstrogen receptor (ER) positive breast cancer is frequently sensitive to endocrine therapy. Multiple mechanisms of endocrine therapy resistance have been identified, including cancer stem-like cell (CSC) activity. Sulforaphane (SFN) has previously been shown to target CSCs but its mechanism of action is unclear. Here we investigate SFX-01, a stabilised formulation of SFN, for its effects on breast CSC activity in ER+ preclinical models and to study its mechanism. EXPERIMENTAL DESIGNCSC activity was measured by mammosphere formation efficiency (MFE), aldehyde dehydrogenase (ALDH) activity, and tumor formation using patient samples and patient-derived xenograft (PDX) tumors treated with SFX-01 alone or in combination with tamoxifen or fulvestrant. Gene expression and SFN target proteins in treated samples were assessed. RESULTSSFX-01 reduced MFE of both ER+ primary and metastatic patient samples. Both tamoxifen and fulvestrant increased MFE and ALDH activity of PDX tumors, which was reversed by combination with SFX-01. SFX-01 significantly reduced tumor initiating cell frequency in secondary transplants at limiting dilution and reduced the formation of spontaneous lung micrometastases by PDX tumors in mice. Mechanistically, we establish that both tamoxifen and fulvestrant induce STAT3 phosphorylation. SFX-01 suppressed phospho-STAT3 and SFN directly bound STAT3 in patient and PDX samples. Analysis of ALDH+ cells from endocrine-resistant patient samples revealed activation of STAT3 target genes MUC1 and OSMR, which were inhibited by SFX-01 in patient samples. Increased expression of these genes after 3 months endocrine treatment of ER+ patients (n=68) predicted poor prognosis. CONCLUSIONSOur data establish the importance of STAT3 signaling in CSC-mediated resistance to endocrine therapy and the potential of SFX-01 for improving clinical outcomes in ER+ breast cancer.

cancer biology↗