Distal Region Research Articles

An Acute Transition from Rearfoot to Forefoot Strike does not Induce Major Changes in Plantarflexor Muscles Activation for Habitual Rearfoot Strike Runners.

Footstrike pattern has received increased attention within the running community because there is a common belief that forefoot strike running (FFS) is more advantageous (i.e., improve performance and reduce running injuries) than rearfoot strike running (RFS) in distance running. Literature reports suggest greater knee joint flexion magnitude and initial knee angle during stance in FFS compared with RFS running We examined the EMG activation of the triceps surae muscles during an acute transition from RFS to FFS strike. We tested the hypothesis that due to larger knee flexion in FFS the gastrocnemius muscles possibly decrease their EMG activity because muscle fascicles operate under unfavorable conditions. Fourteen competitive healthy middle- and long-distance runners who were habitual RFS runners ran on a treadmill at three speeds: 12, 14, and 16 km·h-1. Each running speed was performed with both FFS and RFS patterns. Lower limb kinematics in the sagittal plane and normalized electromyography (EMG) activity of medial gastrocnemius proximal, middle and distal regions, lateral gastrocnemius and soleus muscles were compared between footstrike patterns and running speeds across the stride cycle. Contrary to our expectations, the knee joint range of motion was similar in FFS and RFS running. However, the sagittal plane ankle joint motion was greater (p < 0.01) while running with FFS, resulting in a significantly greater muscle-tendon unit lengthening (p < 0.01) in FFS compared with RFS running. In addition, medial and lateral gastrocnemius showed higher EMG activity in FFS compared with RFS running in the late swing and early stance but only for a small percentage of the stride cycle. However, strike patterns and running speed failed to induce region-specific activation differences within the medial gastrocnemius muscle. Overall, well-trained RFS runners are able to change to FFS running by altering only the ankle joint kinematics without remarkably changing the EMG activity pattern.

An Acute Transition from Rearfoot to Forefoot Strike does not Induce Major Changes in Plantarflexor Muscles Activation for Habitual Rearfoot Strike Runners

Footstrike pattern has received increased attention within the running community because there is a common belief that forefoot strike running (FFS) is more advantageous (i.e., improve performance and reduce running injuries) than rearfoot strike running (RFS) in distance running. Literature reports suggest greater knee joint flexion magnitude and initial knee angle during stance in FFS compared with RFS running We examined the EMG activation of the triceps surae muscles during an acute transition from RFS to FFS strike. We tested the hypothesis that due to larger knee flexion in FFS the gastrocnemius muscles possibly decrease their EMG activity because muscle fascicles operate under unfavorable conditions. Fourteen competitive healthy middle- and long-distance runners who were habitual RFS runners ran on a treadmill at three speeds: 12, 14, and 16 km·h-1. Each running speed was performed with both FFS and RFS patterns. Lower limb kinematics in the sagittal plane and normalized electromyography (EMG) activity of medial gastrocnemius proximal, middle and distal regions, lateral gastrocnemius and soleus muscles were compared between footstrike patterns and running speeds across the stride cycle. Contrary to our expectations, the knee joint range of motion was similar in FFS and RFS running. However, the sagittal plane ankle joint motion was greater (p &lt; 0.01) while running with FFS, resulting in a significantly greater muscle-tendon unit lengthening (p &lt; 0.01) in FFS compared with RFS running. In addition, medial and lateral gastrocnemius showed higher EMG activity in FFS compared with RFS running in the late swing and early stance but only for a small percentage of the stride cycle. However, strike patterns and running speed failed to induce region-specific activation differences within the medial gastrocnemius muscle. Overall, well-trained RFS runners are able to change to FFS running by altering only the ankle joint kinematics without remarkably changing the EMG activity pattern.

Eomes restricts Brachyury functions at the onset of mouse gastrulation.

Mammalian specification of mesoderm and definitive endoderm (DE) is instructed by the two related Tbx transcription factors (TFs) Eomesodermin (Eomes) and Brachyury sharing partially redundant functions. Gross differences in mutant embryonic phenotypes suggest specific functions of each TF. To date, the molecular details of separated lineage-specific gene regulation by Eomes and Brachyury remain poorly understood. Here, we combine mouse embryonic and stem-cell-based analyses to delineate the non-overlapping, lineage-specific transcriptional activities. On a genome-wide scale, binding of both TFs overlaps at promoters of target genes but shows specificity for distal enhancer regions that is conferred by differences in Tbx DNA-binding motifs. The unique binding to enhancer sites instructs the specification of anterior mesoderm (AM) and DE by Eomes and caudal mesoderm by Brachyury. Remarkably, EOMES antagonizes BRACHYURY gene regulatory functions in coexpressing cells during early gastrulation to ensure the proper sequence of early AM and DE lineage specification followed by posterior mesoderm derivatives.

ARID4B loss leads to activated STAT1-dependent interferon pathway in mouse embryonic stem cells and during meso/endodermal differentiation.

Proper deactivation of the pluripotency network and activation of a lineage-specific gene expression program are critical for mouse embryonic stem cell (mESC) differentiation. This is achieved by the coordinated action of transcription and chromatin factors. Our previous work identified ARID4B as a critical chromatin factor for mesoderm and endoderm differentiation. As part of a histone deacetylase complex, ARID4B plays a role in transcriptional suppression of its direct targets. Here, we investigated the mechanism of ARID4B function in mESC differentiation by focusing on genes and pathways that are upregulated in its absence. We analyzed transcriptomic results of wild-type and arid4bΔ endoderm or mesoderm differentiated cells through integrative genomics viewer and ingenuity pathway analysis. We performed real-time quantitative polymerase chain reaction for selected genes. To understand pathway activation, we performed Western blot for candidate proteins during the time-course of differentiation. We also analyzed H3K4me3, H3K27me3 and H3K27Ac ChIP-seq results to understand changes in the chromatin environment. Interferon-related genes were activated in arid4bΔ mESCs and endoderm or mesoderm directed cells. Consistent with this, higher phosphorylated STAT1 levels were found in arid4bΔ mESCs while a related phosphorylated STAT3 was unchanged. Finally, we observed a significant increase in H3K4me3 around interferon-related distal gene regulatory regions with a combination of either upregulation of H3K27Ac level or downregulation of H3K27me3 level. These results provide evidence that ARID4B is involved in the suppression of interferon-related genes in mESCs and during meso/endoderm differentiation through modulation, mainly of H3K4me3. This regulation might be important for successful mESC differentiation.

Wheat (Triticum aestivum) chromosome 6D harbours the broad spectrum common bunt resistance gene Bt11

Key messageA major QTL on chromosome 6DL corresponding to bunt resistance gene Bt11 was identified in four mapping populations generated through crosses with Bt11-carriers PI 166910 and M822123.Common bunt in wheat has witnessed a renaissance with the rise of organic agriculture that began in the 1980s. The abandonment of systemic fungicides in organic farming, together with a lack of resistant cultivars, has led to wide-spread problems due to common bunt infections. Knowledge about genetic sources for resistance is still scarce and only few of the known bunt resistance factors are currently used in breeding. We therefore aimed to map the resistance factor harboured by the Turkish landrace PI 166910, which is the resistance donor for the Bt11 bunt differential line. Four mapping populations (MPs) with 96–132 recombinant inbred lines (RILs) were phenotyped for common bunt resistance over 2, 3 or 4 years with one or two local bunt populations and genotyped with the 25K SNP array. A major bunt resistance locus on the distal end of chromosome 6D designated QBt.ifa-6DL was identified in all MPs and experiments. Additional QTL contributing to resistance were detected on chromosomes 4B, 1A, 1B, 2A and 7B. QBt.ifa-6DL mapped to a region overlapping with the Bt9-locus identified in previous studies, but results indicate that QBt.ifa-6DL is different from Bt9 and convincing evidence from haplotype comparisons suggests that it represents the Bt11 resistance allele. Markers for the distal region of chromosome 6D between 492.6 and 495.2 Mbp can be used to select for QBt.ifa-6DL. This resistance factor confers high and stable resistance against common bunt and should be integrated into organic and low-input wheat breeding programs.

Moisture sources and climatic effects controlling precipitation stable isotope composition in a western Mediterranean island (Pianosa, Italy)

The Mediterranean basin is indicated as a hot spot of climate change, which is an area whose climate is especially responsive to variations. The insular environment is one of the most threatened by the current climate change, especially in terms of drought events, with serious consequences for water scarcity and water stress. This issue is even enhanced in small islands, whose ecosystems are among more sensitive to climatic changes and water availability. The stable isotope composition of hydrogen (δ2H) and oxygen (δ18O) in precipitation is globally recognized as a powerful natural tracer in the water cycle and represents the starting point to investigate hydrological processes. The understanding of the prevailing factors that drive the isotopic variability of precipitation in the Mediterranean is therefore essential to unravel the hydrological processes and to ensure proper and sustainable management of potentially vulnerable resources to climate change. Here, we discuss the results of multi-year isotopic monitoring in the period 2014–2021 of monthly precipitation collected on Pianosa Island (Italy), a small island located in the northern Tyrrhenian (western Mediterranean). The lower slope and intercept of the Local Meteoric Water Line of the island compared to the Global Meteoric Water Line indicated warmer and drier climatic conditions, suggesting the existence of sub-cloud evaporation processes of raindrops during precipitation, especially in summer. The mean δ18O of precipitation was lower with respect to other sites placed at higher elevation in this Mediterranean region, due to the lack of summer precipitation which were generally enriched in heavy isotopes. Temperature and amount effects may explain part of the δ18O variability observed at the monthly and seasonal scale. An HYSPLIT-based moisture uptake analysis indicated the area between the western Mediterranean basin, Italy, and the Adriatic Sea as the region that supplied most of the humidity associated with monthly precipitation samples on Pianosa Island. Less moisture was picked from the northwestern areas of Europe, the North Atlantic Ocean, the proximal Atlantic Ocean, the Iberian Peninsula and North Africa. Consistently with the rainout effect, the higher the moisture fraction picked from the more proximal regions, the more positive the δ18O of precipitation occurring on Pianosa Island; conversely, the higher the percentage of moisture sourced from more distal regions, the more negative the δ18O. A multiple linear model was proposed to predict the δ18O of monthly precipitation from temperature, precipitation amount and moisture origin data, which explained 45% of the δ18O variability. The deuterium excess variability on the island was partly controlled by the local climatic variables, whose effect potentially modifies the original d-excess signature imprinted at the moisture source. No relationship was found between the precipitation deuterium excess and moisture sources, suggesting that more attention should be paid when using the deuterium excess as a tracer of moisture origin, especially in the Mediterranean.

Histological Comparison of Porcine Small Intestine Submucosa and Bovine Type-I Collagen Conduit for Nerve Repair in a Rat Model

After nerve injury, macrophages and Schwann cells remove axon and myelin debris. We hypothesized that nerves repaired with different conduit materials will result in varying levels of these cell populations, which impacts Wallerian degeneration and axonal regeneration. We performed a unilateral sciatic nerve transection in 18 rats. The nerves were repaired with small intestine submucosa (SIS, n= 9) or isolated type-I collagen (CLC, n= 9) conduits. Rats were monitored for 4 weeks. Histology samples were obtained from the proximal nerve, mid-implant, and distal nerve regions. Samples were stained for total macrophages, M2 macrophages, foamy phagocytes, Schwann cells, vascular components, axon components, and collagen density. Distal nerve analyses showed higher populations of total macrophages and M2 macrophages in SIS-repaired nerves and higher density of foamy phagocytes in CLC-repaired nerves. Proximal nerve, mid-implant, and distal nerve analyses showed higher Schwann cell and vascular component densities in SIS-repaired nerves. Axon density was higher in the mid-implant region of SIS-repaired nerves. Collagen staining in the mid-implant was scant, but less collagen density was observed in SIS-repaired versus CLC-repaired nerves. In the distal nerve, the following were observed: (1) lower total macrophages in CLC-repaired nerves, suggesting lower overall inflammation versus SIS-repaired nerves; (2) higher M2 macrophages in SIS-repaired versus CLC-repaired nerves, a driving factor for higher total macrophages and indicative of an inflammation resolution response in SIS-repaired nerves; and (3) a lower foamy phagocyte density in SIS-repaired nerves, suggesting earlier resolution of Wallerian degeneration versus CLC-repaired nerves. In the proximal nerve, mid-implant, and distal nerve, higher Schwann cell and vascular component densities were noted in SIS-repaired nerves. In the mid-implant, a higher axon component density and a lower collagen density of the SIS-repaired nerves versus CLC-repaired nerves were noted. These results indicate more robust nerve regeneration with less collagen deposition. This invivo study evaluated two common conduit materials that are used in peripheral nerve repair. Clinical outcomes of nerves repaired with conduits may be impacted by the response to different conduit materials. These nerve repair responses include Wallerian degeneration, nerve regeneration, and nerve scarring. This study evaluated Wallerian degeneration using total macrophages, M2 macrophages, and foamy phagocytes. Nerve regeneration was evaluated using Schwann cells and axons. Nerve scarring was evaluated using vascular and collagen density.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

Islet amyloid deposition and reduced β-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional β-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of β-cell area, α-cell area and amyloid deposits. Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

Regulation of Osteoimmune Microenvironment and Osteogenesis by 3D-Printed PLAG/black Phosphorus Scaffolds for Bone Regeneration.

The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKTsignaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

Areal roughness of the dorsal nail plate

Objective: Beau’s lines, onychorrhexis, and psoriatic lesions of the dorsal nail plate may be missed by photographic methods, indicating a need for surface texture measurement methods that are more quantitative, sensitive, and repeatable than visual inspection or imaging. We conducted this study to evaluate the utility of surface texture measurements of cadaveric nails that can be associated with histopathological studies in the future. Materials: The nail plates of four cadaveric right pollices and halluces were cleaned and molded, cast in clear epoxy, and scanned with a Sensofar S Neox optical profilometer. A one-way analysis of variance (ANOVA) was performed to determine statistical significance of findings. Results: Almost no differences were observed between the pollex and hallux scans, and between the distal and proximal regions. The greatest differences were found between individuals. Although lower magnification (5×) is less sensitive than higher magnification (20×), the lower magnification represented and characterized more of the dorsal nail plate. Conclusions: The dorsal nail plate areal roughness has a measurable range of values that may serve as a starting point for evaluating pathological findings, particularly Beau’s lines and psoriatic lesions. The sensitivity of these techniques may be especially valuable in the recognition of less severe states of these diseases that may enable the diagnosis of earlier stages of growth disruptions (Beau’s lines) or psoriasis. Such applications could be especially useful in investigations of the health of wildlife populations or vulnerable human populations with incomplete treatment records.

Z-Form Extracellular DNA in Pediatric CRS May Provide a Mechanism for Recalcitrance to Treatment.

We examined sinus mucosal samples recovered from pediatric chronic rhinosinusitis (CRS) patients for the presence of Z-form extracellular DNA (eDNA) due to its recently elucidated role in pathogenesis of disease. Further, we immunolabeled these specimens for the presence of both members of the bacterial DNA-binding DNABII protein family, integration host factor (IHF) and histone-like protein (HU), due to their known role in converting common B-DNA to the rare Z-form. Sinus mucosa samples recovered from 20 patients during functional endoscopic sinus surgery (FESS) were immunolabelled for B- and Z-DNA, as well as for both bacterial DNABII proteins. Nineteen of 20 samples (95%) included areas rich in eDNA, with the majority in the Z-form. Areas positive for B-DNA were restricted to the most distal regions of the mucosal specimen. Labeling for both DNABII proteins was observed on B- and Z-DNA, which aligned with the role of these proteins in the B-to-Z DNA conversion. Abundant Z-form eDNA in culture-positive pediatric CRS samples suggested that bacterial DNABII proteins were responsible for the conversion of eukaryotic B-DNA that had been released into the luminal space by PMNs during NETosis, to the Z-form. The presence of both DNABII proteins on B-DNA and Z-DNA supported the known role of these bacterial proteins in the B-to-Z DNA conversion. Given that Z-form DNA both stabilizes the bacterial biofilm and inactivates PMN NET-mediated killing of trapped bacteria, we hypothesize that this conversion may be contributing to the chronicity and recalcitrance of CRS to treatment. NA Laryngoscope, 134:1564-1571, 2024.

Delineating Structural Propensities of the 4E-BP2 Protein via Integrative Modeling and Clustering.

The intrinsically disordered 4E-BP2 protein regulates mRNA cap-dependent translation through interaction with the predominantly folded eukaryotic initiation factor 4E (eIF4E). Phosphorylation of 4E-BP2 dramatically reduces the level of eIF4E binding, in part by stabilizing a binding-incompatible folded domain. Here, we used a Rosetta-based sampling algorithm optimized for IDRs to generate initial ensembles for two phospho forms of 4E-BP2, non- and 5-fold phosphorylated (NP and 5P, respectively), with the 5P folded domain flanked by N- and C-terminal IDRs (N-IDR and C-IDR, respectively). We then applied an integrative Bayesian approach to obtain NP and 5P conformational ensembles that agree with experimental data from nuclear magnetic resonance, small-angle X-ray scattering, and single-molecule Förster resonance energy transfer (smFRET). For the NP state, inter-residue distance scaling and 2D maps revealed the role of charge segregation and pi interactions in driving contacts between distal regions of the chain (∼70 residues apart). The 5P ensemble shows prominent contacts of the N-IDR region with the two phosphosites in the folded domain, pT37 and pT46, and, to a lesser extent, delocalized interactions with the C-IDR region. Agglomerative hierarchical clustering led to partitioning of each of the two ensembles into four clusters with different global dimensions and contact maps. This helped delineate an NP cluster that, based on our smFRET data, is compatible with the eIF4E-bound state. 5P clusters were differentiated by interactions of C-IDR with the folded domain and of the N-IDR with the two phosphosites in the folded domain. Our study provides both a better visualization of fundamental structural poses of 4E-BP2 and a set of falsifiable insights on intrachain interactions that bias folding and binding of this protein.

Progression of reactive gliosis and astroglial phenotypic changes following stab wound-induced traumatic brain injury in mice.

Astrocytes are the main homeostatic cells in the central nervous system (CNS) and they have an essential role in preserving neuronal physiology. After brain injury, astrocytes become reactive, and that involves a profound change in the astroglial gene expression program as well as intense cytoskeleton remodeling that has been classically shown by the up-regulation of glial fibrillary acidic protein (GFAP), a pan-reactive gene over-expressed in reactive astrocytes, independently of the type of injury. Using the stab wound rodent model of penetrating traumatic injury in the cortex, we here studied the reactive astroglial morphology and reactive microgliosis in detail at 1, 3, 7, 14, and 28 days post-injury (dpi). By combining immunohistochemistry, morphometrical parameters, and Sholl analysis, we segmented the astroglial cell population into clusters of reactive astrocytes that were localized in the core, penumbra, and distal regions of the stab wound. Specifically, highly reactive clusters with more complex morphology, increased C3, decreased aquaporin-4 (AQP4), and glutamine synthetase (GS) expression, were enriched at 7 dpi when behavioral alterations, microgliosis, and neuronal alterations in injured mice were most significant. While pro-inflammatory gain of function with peripheral lipopolysaccharide (LPS) administration immediately after a stab wound expanded these highly reactive astroglial clusters, the treatment with the NF-κB inhibitor sulfasalazine reduced the abundance of this highly reactive cluster. Increased neuronal loss and exacerbated reactive microgliosis at 7 dpi were associated with the expansion of the highly reactive astroglial cluster. We conclude that highly reactive astrocytes found in stab wound injury, but expanded in pro-inflammatory conditions, are a population of astrocytes that become engaged in pathological remodeling with a pro-inflammatory gain of function and loss of homeostatic capacity. Controlling this astroglial population may be a tempting strategy to reduce neuronal loss and neuroinflammation in the injured brain.

LncRNA MACC1-AS1 associates with DDX5 to modulate MACC1 transcription in breast cancer cells

MACC1 is a master oncogene involved in multiple aspects of cancer metastasis in a broad variety of tumors. However, the molecular mechanism by which MACC1 transcription is regulated remains unclear. Here, we show that in breast cancer cells, lncRNA MACC1-AS1 serves as a cis-factor to up-regulate MACC1 transcription and this regulation increases the cell proliferation potential. Mechanistically, MACC1-AS1 forms a complex with DEAD-Box helicase 5 (DDX5) and simultaneously interacts with the distal region of the MACC1 promoter. The interaction allows its associated DDX5 to spatially contact the MACC1 core promoter and shift from MACC1-AS1 to the core promoter. Moreover, binding of DDX5 to the core promoter results in local recruitment of the transcription factor SP-1, thus enhancing MACC1 transcription. Our findings reveal a molecular mechanism by which MACC1-AS1 cis-regulates MACC1 transcription by interacting with the distal promoter region and delivering DDX5 to the core-promoter of the gene.

Distal Endovascular Occlusion for Incomplete Occlusion of Cavernous Carotid Aneurysms after High-flow Bypass and Cervical Internal Carotid Artery Ligation.

Internal carotid artery (ICA) ligation for placing a high-flow extracranial-intracranial (EC-IC) bypass is used in patients with aneurysms on the cavernous portion of the ICA. Recanalization and rupture after proximal ICA ligation can occur. We present four patients who underwent endovascular distal ICA occlusion and report our surgical technique and treatment results. We ligated the ICA to place an EC-IC bypass using a radial artery (RA) graft. Failure to obtain spontaneous occlusion in the distal region required endovascular treatment an average of 219 days later. A guide catheter was placed in the common carotid artery, a guide or distal access catheter was introduced in the RA graft from the external carotid artery, and a microcatheter was navigated into the cavernous aneurysm through the RA graft. Using detachable coils, endovascular ICA occlusion was from just distal to the aneurysmal neck to a site proximal to the origin of the ophthalmic artery. Aneurysmal occlusion was completed by endovascular occlusion of the distal ICA. Complications were RA graft stenosis and transient consciousness disturbance due to local subarachnoid hemorrhage. Outpatient follow-up for a mean of 109.5 months revealed no recurrences. Distal occlusion of the ICA through the implanted RA graft is simple and presents a low risk for cerebral infarction due to thrombus formation during the procedure. To treat cavernous carotid aneurysms that do not disappear after placing the EC-IC bypass after ICA ligation at the aneurysmal neck, we offer our procedure as a treatment option.

A single dominant locus restricts retrovirus replication in YBR/Ei mice.

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the anti-virus response in susceptible mice. Virus control is unrelated to virus-neutralizing antibodies, cytotoxic CD8+ T cells, NK cells, and NK T cells, which are the best characterized mechanisms of resistance to retroviruses. We identified a single, dominant locus that controls the resistance mechanism, which we provisionally named attenuation of virus titers (Avt) and mapped to the distal region of chromosome 18. IMPORTANCE Elucidation of the mechanism that mediates resistance to retroviruses is of fundamental importance to human health, as it will ultimately lead to knowledge of the genetic differences among individuals in susceptibility to microbial infections.

Neurohypophysial and paracrine vasopressinergic signaling regulates aquaporin trafficking to hydrate marine teleost oocytes.

The dual aquaporin (Aqp1ab1/Aqp1ab2)-mediated hydration of marine teleost eggs, which occurs during oocyte meiosis resumption (maturation), is considered a key adaptation underpinning their evolutionary success in the oceans. However, the endocrine signals controlling this mechanism are almost unknown. Here, we investigated whether the nonapeptides arginine vasopressin (Avp, formerly vasotocin) and oxytocin (Oxt, formerly isotocin) are involved in marine teleost oocyte hydration using the gilthead seabream (Sparus aurata) as a model. We show that concomitant with an increased systemic production of Avp and Oxt, the nonapeptides are also produced and accumulated locally in the ovarian follicles during oocyte maturation and hydration. Functional characterization of representative Avp and Oxt receptor subtypes indicates that Avpr1aa and Oxtrb, expressed in the postvitellogenic oocyte, activate phospholipase C and protein kinase C pathways, while Avpr2aa, which is highly expressed in the oocyte and in the follicular theca and granulosa cells, activates the cAMP-protein kinase A (PKA) cascade. Using ex vivo, in vitro and mutagenesis approaches, we determined that Avpr2aa plays a major role in the PKA-mediated phosphorylation of the aquaporin subdomains driving membrane insertion of Aqp1ab2 in the theca and granulosa cells, and of Aqp1ab1 and Aqp1ab2 in the distal and proximal regions of the oocyte microvilli, respectively. The data further indicate that luteinizing hormone, which surges during oocyte maturation, induces the synthesis of Avp in the granulosa cells via progestin production and the nuclear progestin receptor. Collectively, our data suggest that both the neurohypophysial and paracrine vasopressinergic systems integrate to differentially regulate the trafficking of the Aqp1ab-type paralogs via a common Avp-Avpr2aa-PKA pathway to avoid competitive occupancy of the same plasma membrane space and maximize water influx during oocyte hydration.

Functional and structural brain reorganization in patients with ischemic stroke: a multimodality MRI fusion study.

Understanding how structural and functional reorganization occurs is crucial for stroke diagnosis and prognosis. Previous magnetic resonance imaging (MRI) studies focused on the analyses of a single modality and demonstrated abnormalities in both lesion regions and their associated distal regions. However, the relationships of multimodality alterations and their associations with poststroke motor deficits are still unclear. In this study, 71 hemiplegia patients and 41 matched healthy controls (HCs) were recruited and underwent MRI examination at baseline and at 2-week follow-up sessions. A multimodal fusion approach (multimodal canonical correlation analysis + joint independent component analysis), with amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) as features, was used to extract the co-altered patterns of brain structure and function. Then compared the changes in patients' brain structure and function between baseline and follow-up sessions. Compared with HCs, the brain structure and function of stroke patients decreased synchronously in the local lesions and their associated distal regions. Damage to structure and function in the local lesion regions was associated with motor function. After 2 weeks, ALFF in the local lesion regions was increased, while GMV did not improve. Taken together, the brain structure and function in the local lesions and their associated distal regions were damaged synchronously after ischemic stroke, while during motor recovery, the 2 modalities were changed separately.

Multimodal imaging and surgical repair of a dorsal‐oblique plane, proximal third metacarpal fracture and the diagnostic challenge of radiographic visualisation

SummaryA 10‐year‐old Connemara mare presented with persistent 3/5 (AAEP) right forelimb lameness following a traumatic incident whilst hunting, which was localised to the proximal metacarpal and distal carpal regions with diagnostic anaesthesia. Radiography revealed non‐specific moderately increased mineral opacity at the proximomedial margin of the third metacarpus, dorsal to the enthesis of the proximal suspensory ligament. However, subsequent computed tomography (CT) performed under general anaesthesia, identified an incomplete, dorsal ‐ obliquely orientated third metacarpal fracture arising from the interosseous space between the third and second metacarpi, also involving the carpometacarpal joint. Using CT guidance, internal surgical fixation was performed under the same anaesthetic episode and resulted in a shortened post‐operative recovery period with a successful return to previous athletic function. Surgical fixation can be performed using cross‐sectional imaging guidance to optimise recovery and facilitate a positive outcome.

Factors Affecting Neurological Deficits in Thoracic Tuberculous Spondylodiscitis.

Thoracic spinal tuberculosis (TB) causes destruction of the spine and compression of the adjacent spinal cord. This study aimed to identify the risk factors for neurological deterioration in patients with thoracic spinal TB to guide decision-making regarding immediate surgery before the onset of weakness. Demographic, clinical, laboratory, and radiologic (x-ray and magnetic resonance imaging) data of 115 patients with active thoracic spinal TB were retrospectively analyzed. Patients with neurological status categorized as Frankel grades A, B, or C (n = 71) were classified as the neurological deficit group, while those with neurological status categorized as Frankel grades D and E (n = 44) constituted the control group. Univariate and multivariate logistic regression analyses were used to predict the risk factors for neurological deficits. The mean patient age was 57.2 years. The most common lesion location was the distal thoracic region (T9-L1; 62.6%). Paradiscal involvement was the most common form of involvement (73%). In the univariate analysis, the significant risk factors associated with neurological worsening were overweight (body mass index [BMI] >25), C-reactive protein level > 20 mg/L, panvertebral involvement, loss of cerebrospinal fluid posterior to the cord, cord signal changes, and canal compromise. The multivariate analysis revealed that only BMI >25 (adjusted OR = 16.18; 95% CI 1.60-163.64; P = 0.018), cord signal changes (adjusted OR = 7.42; 95% CI 1.85-29.74; P = 0.005), and canal encroachment >50% ( adjusted OR = 51.86; 95% CI 5.53-486.24; P = 0.001) were independent risk factors for predicting the risk of neurological deficits. Overweight (BMI >25), cord signal changes, and canal compromise >50% significantly predicted neurological deficits in patients with thoracic spinal TB. Prompt spinal surgery should be considered before progressive worsening of the neurological condition in patients with all of these risk factors. Predictive factors for neurological deficits in thoracic spinal TB were determined. Overweight, cord signal changes, and canal compromise >50% showed predictive value. These factors can help identify patients who require early surgical intervention.