Differential functions of Interleukin-10 derived from different cell types in the regulation of immune responses

Interleukin-10 (IL-10) is an important regulator of immune responses secreted by different cell types. Previous results from our group suggested that the biological effects of this cytokine critically depend on its cellular source. Recent studies reported IL-10 dependent immunosuppressive functions of a specialized subset of regulatory B cells and mast cells. These results relied on adoptive cell transfers, a technique which can potentially introduce artifacts. Therefore, we aimed to readdress these questions in independent models using IL-10 transcriptional reporter mice and various conditional IL-10 mutant mice. Findings in IL-10 reporter system suggested prominent IL-10 transcription in regulatory B cells upon LPS administration. Exposure of mice to contact allergen revealed robust reporter expression in CD8 T cells, moderate to mild reporter expression in CD4 T cells and dendritic cells (DC) respectively, and lack of reporter expression in B cells, mast cells and NK cells in allergen challenged ears. We generated cell-type specific IL-10 mutants by Cre/LoxP-mediated conditional gene inactivation. Efficiency and specificity of Cre-mediated recombination was demonstrated by Southern blot and PCR methods. Various immunogenic challenges in conditional IL-10 mutants did not reveal a role for B cell-derived IL-10 in restraining innate TLR or T cell-dependent inflammatory responses. Likewise, mice with selective inactivation of the il10 gene in mast cells exhibited normal CHS responses and unaltered immune response to CpG oligodeoxynucleotides. On the other hand, DC-specific IL-10 mutants developed excessive inflammatory responses to contact allergens, while innate responses to TLR ligands were not altered. This indicates a non-redundant role for DC-derived IL-10 in contact allergy. Thus, the conditional IL-10 ‘‘knockout’’ mice combined with the novel transcriptional IL-10 reporter system can serve as ideal tools to understand the cell-type specific contributions to IL-10-mediated immune regulation

Accidental Entry of Fish into Throat While Bathing in a Pond

While fish bones are common foreign bodies in the throat, a whole live fish in the pharynx is very rare. We report a case where a whole fish accidentally entered the throat of a 52-year-old male, where it became lodged causing throat pain and dysphagia. The fish was removed as an emergency procedure

Anonymity-Preserving Space Partitions

We consider a multidimensional space partitioning problem, which we call Anonymity-Preserving Partition. Given a set P of n points in ?^d and a collection H of m axis-parallel hyperplanes, the hyperplanes of H partition the space into an arrangement A(H) of rectangular cells. Given an integer parameter t > 0, we call a cell C in this arrangement deficient if 0 < |C ? P| < t; that is, the cell contains at least one but fewer than t data points of P. Our problem is to remove the minimum number of hyperplanes from H so that there are no deficient cells. We show that the problem is NP-complete for all dimensions d ? 2. We present a polynomial-time d-approximation algorithm, for any fixed d, and we also show that the problem can be solved exactly in time (2d-0.924)^k m^O(1) + O(n), where k is the solution size. The one-dimensional case of the problem, where all hyperplanes are parallel, can be solved optimally in polynomial time, but we show that a related Interval Anonymity problem is NP-complete even in one dimension

Parameterized Complexity of Fair Bisection: FPT-Approximation meets Unbreakability

In the Minimum Bisection problem, input is a graph $G$ and the goal is to partition the vertex set into two parts $A$ and $B$, such that $||A|-|B|| \le 1$ and the number $k$ of edges between $A$ and $B$ is minimized. This problem can be viewed as a clustering problem where edges represent similarity, and the task is to partition the vertices into two equally sized clusters, while minimizing the number of pairs of similar objects that end up in different clusters. In this paper, we initiate the study of a fair version of Minimum Bisection. In this problem, the vertices of the graph are colored using one of $c \ge 1$ colors. The goal is to find a bisection $(A, B)$ with at most $k$ edges between the parts, such that for each color $i\in [c]$, $A$ has exactly $r_i$ vertices of color $i$. We first show that Fair Bisection is $W$[1]-hard parameterized by $c$ even when $k = 0$. On the other hand, our main technical contribution shows that is that this hardness result is simply a consequence of the very strict requirement that each color class $i$ has {\em exactly} $r_i$ vertices in $A$. In particular, we give an $f(k,c,\epsilon)n^{O(1)}$ time algorithm that finds a balanced partition $(A, B)$ with at most $k$ edges between them, such that for each color $i\in [c]$, there are at most $(1\pm \epsilon)r_i$ vertices of color $i$ in $A$. Our approximation algorithm is best viewed as a proof of concept that the technique introduced by [Lampis, ICALP '18] for obtaining FPT-approximation algorithms for problems of bounded tree-width or clique-width can be efficiently exploited even on graphs of unbounded width. The key insight is that the technique of Lampis is applicable on tree decompositions with unbreakable bags (as introduced in [Cygan et al., SIAM Journal on Computing '14]). Along the way, we also derive a combinatorial result regarding tree decompositions of graphs.Comment: Full version of ESA 2023 paper. Abstract shortened to meet the character limi

Inoperable Renal Malignant Glomus Tumor, the answers for all the “W’s”?

Glomus tumor, arising from glomus bodies (specialized neurovascular structures involved in thermoregulation), commonly occurs in extremities and rarely in viscera. The spectrum of glomus tumors range from benign tumors to tumors with uncertain malignant potential to tumors of the malignant subtype. A vast majority of visceral glomus tumors are benign. Most common visceral tumors arise in the gastrointestinal tract. Glomus tumors of the kidney are a rare entity of which malignant glomus tumors are exceedingly rare. The index patients in the existing case reports were middle-aged males. We report our experience with malignant glomus tumor of the left kidney in a 60-year-old female, with computed tomography (CT) showing involvement of renal vein and inferior vena cava (IVC). Percutaneous biopsy was performed as imaging did not conform to the appearance of a conventional renal tumor and was reported as malignant glomus tumor after immunohistochemistry. After informed decision, the patient and family elected to proceed with surgery. However, intraoperatively, the left renal mass was found to infiltrate the pancreas, duodenum, aorta, and root of the colonic mesentery due to which surgery was aborted. Biopsy obtained intraoperatively again confirmed diagnosis of left renal malignant glomus tumor. She had an uneventful postoperative recovery. Options of treatment were reviewed by a multidisciplinary board. In light of no proven benefit for systemic therapy, she was referred for supportive care. She was under follow-up and she expired after 7 months due to progressive disease. Our literature review focuses on the clinicopathologic features and the current standard of management of malignant renal glomus tumors