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The vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell-type specific neuroproteomes is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteomes in the mouse brain, confirmed by imaging, electron microscopy, and mass spectrometry. We virally express subcellular-localized APEX2 to map the proteome of direct and indirect pathway spiny projection neurons in the striatum. The workflow provides sufficient depth to uncover changes in the proteome of striatal neurons following chemogenetic activation of Gαq-coupled signaling cascades. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome snapshots in the mouse brain.

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The study of childhood diet, including breastfeeding and weaning, has important implications for our understanding of infant mortality and fertility in past societies1. Stable isotope analyses of nitrogen from bone collagen and dentine samples of infants have provided information on the timing of weaning2; however, little is known about which foods were consumed by infants in prehistory. The earliest known clay vessels that were possibly used for feeding infants appear in Neolithic Europe, and become more common throughout the Bronze and Iron Ages. However, these vessels-which include a spout through which liquid could be poured-have also been suggested to be feeding vessels for the sick or infirm3,4. Here we report evidence for the foods that were contained in such vessels, based on analyses of the lipid 'fingerprints' and the compound-specific δ13C and Δ13C values of the major fatty acids of residues from three small, spouted vessels that were found in Bronze and Iron Age graves of infants in Bavaria. The results suggest that the vessels were used to feed infants with milk products derived from ruminants. This evidence of the foodstuffs that were used to either feed or wean prehistoric infants confirms the importance of milk from domesticated animals for these early communities, and provides information on the infant-feeding behaviours that were practised by prehistoric human groups.

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Current understanding of knee meniscus pathology and the known consequences of meniscal loss dictate preservation of tissues wherever feasible. Surgical approaches to meniscal repair include open and combined arthroscopic-open or arthroscopic-percutaneous procedures. A variety of needles, guides, sutures, and retractors have been marketed. Over a 2 year period, we used these techniques in the repair of 19 medial and 5 lateral meniscus tears, with no known retears and no complications. We used an 18-gauge, 6-inch spinal needle and a strand of number one nonabsorbable suture.

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Fifty-one knees in 32 ambulatory patients with rheumatoid arthritis were examined arthroscopically, enabling direct observation of the pattern of gross degeneration at the joint line and synovial chondral junction. Four distinct stages of pannus ingrowth and meniscal degeneration were observed, which correlated with the extent of articular destruction. Significant direct pannus invasion of articular cartilage was not observed in any stage in the ambulatory mobile rheumatoid knee. Stage I is comprised of synovial hypertrophy. Stage II shows invasive pannus affecting meniscal surfaces. Stage III exhibits meniscal tearing and production of abrasive debris. Stage IV is end-stage loss of meniscus and denudation of articular surfaces. Articular cartilage destruction was not observed in patients without visible meniscal degeneration or pannus ingrowth but was observed in knees without roentgenographic erosion or joint space narrowing. A new evaluation of articular degeneration in the ambulatory mobile rheumatoid knee is based on mechanical destruction by torn menisci and free debris observed by arthroscopy.

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Fifty-two patients with severe degenerative joint disease of the knees were treated by arthroscopic debridement. The results of arthroscopic debridement on normally aligned degenerative knees are encouraging. A combination of arthroscopic debridement and high tibial osteotomy could be an appealing alternative to total knee arthroplasty in the young patients. Patients with varus angular deformity in the degenerative knee had a poor result and should be excluded from consideration for arthroscopic debridement.

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Thirty patients with proximal third femur fractures were treated with pins-in-thigh plaster. Patients were divided into two groups: (1) acute (pins-in-plaster applied within one month after injury); and (2) late (pins-in-plaster applied later than one month ater injury). Patients in the acute group had application of pins-in-plaster inserted at an average of nine days after injury, and were treated in plaster for 9.4 weeks with union occurring at 10.7 weeks. Patients in the late group had application of pins-in-plaster an average of 13.3 weeks after injury, treatment in plaster for 7.7 weeks, and union at 21 weeks. Subtrochanteric fractures healed as rapidly as other areas of the femur when braced early. Twenty-five fractures demonstrated less than 2 cm of shortening and less than 10 degrees of varus. There were no nonunions. One patient developed a deep wound infection. Antibiotics were required in seven patients because of pin tract drainage, which ceased once the pins were removed. This method is indicated in active patients with comminuted or open fractures but neither in the elderly or senile patients, or in intertrochanteric-subtrochanteric fractures.

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